how we are hungry

FoxP2 in the News

2011-11-19T14:25:00.001-08:00

I wrote on Monday last week about Svante Pääbo's work with hominin lineage, and his recent findings with FoxP2 transgenic mice. This morning, this article was printed in Nature News on FoxP2's spotlight moment. The author highlights the work presented at SfN last week by Christiane Schreiweis, a colleague of Dr. Pääbo.

SfN Wednesday 2011: Second Wind

2011-11-19T08:04:00.000-08:00

By the end of the conference, my eating schedule has not adapted to being on the east coast, but my body has. Exhaustion kicks in like a toddler, and come Wednesday morning I feel like slithering through the grasping arms of Science and collapsing to the floor. Of course, my poster is this morning.

In contrast to the anticipated slow puttering of folk on the final day of the meeting, area L10 boasted anywhere between 3-10 participants for the entire 4-hr block. <thrillz> In addition, several of teh femus peepl made appearances. One hung out in the back of the crowd and chimed in when I referenced his work's influence on ours. Another offered excellent discussion and announced that he had begun using the model that we developed last year (also employed in this year's work) <chillz>. A third made offer of collaboration and (either partly or entirely in jest) a post doc position for five years from now when I potentially actually have a doctorate. And a renowned woman for whom there is a special place in my heart offered suggestions for follow-up studies, collaboration, and an awkward scientist hug as she left. <second wind>

Also notably, there is good Phở in DC. Following the rush of the poster session, Boss Man treated me to my second dose of Phở for the week, and it was grand. The Super Shuttle that was then scheduled to escort me to my next 11 hours of travel failed to appear, and the taxi that rescued me from certain doom naturally forgot to tell me that his apparatus was broken and that he couldn't take my card, and naturally didn't have any change to break the $20 of which he only should have taken $14, and naturally had no means by which to provide me with a receipt for reimbursement. This was not the first such incident during my week in DC. <billz>

See you next year in New Orleans!

SfN Tuesday 2011: Winding

2011-11-18T20:01:00.001-08:00

Tuesday morning: a slew of great posters and conversations. I prefer poster sessions with fewer and more impactful scans, and was very impressed with the elegance of several presentations in this session. I was also fascinated to see that several of the bigwigs whose work I have followed over the last four years are transitioning into more genetic/molecular and less neurotoxin-centric modeling systems. This is a direction in which I may continue if planted in Dr. PDstemcell's lab next year, and wouldn't it be grand to already have some acquaintances in that new arena?

Sally Temple, the current director of the Neural Stem Cell Institute, gave an excellent talk later in the morning and into the afternoon. Although my lunch rendezvous prevented my attending the full symposium, I was able to digest her historical overview. Some key points of interest are below. **If anyone was able to attend this full talk, please comment!**

In 1887, Wilhelm His identified 2 cell types: germinal cells as rounded cells nearest the lumen (neuronal precursors), and columnar spongioblasts (radial glia).
In 1987, Jack Price and colleagues were the first to monitor cellular development using retroviral lineage tracing with β-galactosidase. The paper in PNAS is beautiful and succinct, and I highly recommend reviewing it for as an introduction to neural lineages. Arnold Kreigstein's lab has also played a pivotal role in describing neural lineages, which Dr. Temple referred to briefly but I believe warrant more obvious credit in the evolution of this field.
The last piece I caught was in reference to recent software developed by Andy Cohen's lab: a program for tagging and following cell division in vitro via time-lapse microscopy, and easily translating these divisions into lineage trees. To appreciate this fully, consider the giant leaps forward that technological development have allowed in the evolution of scientific industry. The polymerase chain reaction (PCR) is so simple, and used so ubiquitously now that one has to imagine the grueling hours of restriction enzyme assays and semi-quantitative analyses that were necessary before its development in order to realize its gigantic contribution to throughput. Andy Cohen's software is another such landmark in the progress of scientific industry.

I attended the Protein Synthesis and Axon Pathfinding in Regeneration minisymposia later in the afternoon. Of note to your humble narrator was some research from Samie Jaffery's lab at Cornell U. Dr. Jaffrey proposed a mechanism of axon guidance through nonsense-mediated decay (NMD), a process wherein mRNA is degraded following a "pioneer round" of transcription.

Commissural neurons grow toward the midline and netrin-1 in the floor plate, then are repelled from the floor plate post-crossing. A family of receptor proteins called Robos are key players in this mechanism. Jaffrey's research indicates compartmental expression of Robo3.1 and Robo3.2 receptors in commissural neurons. Robo3.1 suppresses other Robos so that the axon can grow toward the midline, after which point Robo3.2 expression enhances repulsion from the floor plate. If ther eis no Robo3.1, axons don't cross the midline. If there is no Robo3.2, axons cross and then turn backward and grow aberrantly.
Jaffrey's lab asked if the switch between Robo3.1 and Robo3.2 was temporally dependent, or in the determined in the floor plate. They made open book explants of spinal cord with no floor plate, and observed protein expression at E10. Although Robo3.2 expression was expected by this time point, only Robo3.1 was expressed. When the floor plate was reintroduced, Robo3.2 expression was observed. This indicated a floor plate mechanism as opposed to a temporal switch within the commissural neurons.
To confirm this suspicion, the spinal cord floor plate was cultured alone, and the resulting conditioned media was applied to the tips of axons in spinal cord explants without a floor plate. With the floor plate media, the commissural axon tips expressed Robo3.2.
The next obvious question was what mediated this switch. The group predicted a NMD switch based on indicative NMD sequence in the Robo3.2 gene not observe in the Robo3.1 gene. When they expressed the dominant-negative form of NMD proteins, axons crossed the midline but then grew aberrantly. If the NMD mechanism was blocked, more Robo3.2 was produced and there was increased repulsion to both the floor plate and midline. Therefore, an NMD-dependent mechanism of axon guidance in developing commissural neurons was speculated, although the proteins involved in NMD activity in the floor plate is yet to be determined.

Tuesday evening was spent having a somewhat awkward but fun dinner with my former PI, and acting like a child with my fascinating and inspiring last-minute conference roommate. The ideal way to wrap up a grueling SfN day as the conference approaches its final hours and inflicts an inescapable exhaustion/delirium.

SfN Monday 2011: Almost Femus

2011-11-14T13:01:00.001-08:00

Saturday and Sunday were gargantuan days whose events were not ideal blog fodder (read: 5,000,203 posters). Today's events, in contrast, are worth reporting.

This morning's poster session began with a very brief reunion with my most admired undergraduate professor, and ended with the development of a potential future collaboration to take place in the lab in which I have not yet even rotated (lolz...).

In the late morning I attended the David Kopf Lecture on Neuroethics, given by Svante Pääbo of the Max Plank Institute of Evolutionary Anthropology in Germany (yes, I just Wiki-linked him). The man's career is packed with astounding work, only a glimpse of which we were given today. In brief, Dr. Pääbo's talk came down to three parts:

Although evolution has seen total replacement of mitochondrial DNA in modern humans such that none of us share mitochondrial DNA with Neadertals, 2.5% of our nuclear genome derives from Neandertal lineage.
Analysis of a newly unearthed finger tip fossil reveals a hitherto unknown line of hominin that Pääbo's group called Denisovans, who share Neandertal DNA back to 650,000 years, and with modern humans back to 800,000 years. From genome comparisons, Pääbo elucidated the geographical interbreeding patterns of these three lines. Matching between modern humans and Denisovans was 90K in a French subject, 70K in an African subject, and 86K in a New Guinean subject (*approximations). Which... if you've ever read [and loved] Richard Dawkins' The Ancestor's Tale, Pääbo's work will blow your mind.
Finally (and my favorite part, as a basal ganglia fanatic), Pääbo et al have utilized the divergence of Neandertal, Denisovan and modern human to identify genomic regions positively selected in human evolution. He elaborates on one such candidate, the FoxP2 gene, which is involved in speech and language development. In a transgenic mouse, the expression of human FoxP2 produces 323 phenotypes. One of these phenotypes is elongation of dendritic trees in the striatum. Another is an overall decrease in whole brain dopamine levels, and finally altered vocalization patterns. I'll reiterate: a human gene positively selected by evolution to help humans develop language is capable of altering the morphology of a mouse brain region involved in spatial learning and attention, and altering the way mice "speak". (scencegasm)

Elated by Pääbo's lecture, which has nothing to do with what I'm researching currently (or in the forseeable future), I re-entered the massive dungeon hall of posters and ran into my current rotation PI as well as a crew of several of his past students and post docs. What fantastic people they were, and how enamored they were of Dr. Spinal Cord Repairman, and how encouraging they were that I continue in his lab! At what a time, too, when I am frustrated by my lack of productivity this term and the general disorganization of the lab atmosphere. Perhaps these are things which are worth taking with a grain of salt after all. I was even more encouraged when I happened upon [read: hunted down] a collaborator of Dr. Spinal Cord Repairman's who is mucho femus. This is a man with whom I have exchanged all of two emails discussing the direction of the project I'm currently working on which happens to be a collaborative one, and who remembered my name. (flutter)

Tonight: tour of the sites, BANTER.

SfN Sunday 2011: Ms. Raga goes to Washington

2011-11-13T19:00:00.000-08:00

The great and consuming thing about the Society for Neuroscience meeting is that even veterans can be noobs.

Last year, I approached SfN as somewhat of an expert in my niche of the Parkinson's field, seeking out renowned folks whose work had inspired my own and carrying meaningful scientific conversations with poster and talk presenters as if it were casual chatter.

This year, I find myself engaging in so many unfamiliar arenas that I have retired a whole 2 hours early to the comfort of my snazzy hotel room to put my feet up and compile/further research the whirlwind of fascinating information gleaned today.

Today was poster intensive, to put it lightly, so tomorrow will include some symposia. Just to mix it up.

Second lesson learned: Neurotypical? is as fantastic IRL as in the blogosphere.

SfN Survival Guide 2011

2011-11-08T20:30:00.000-08:00

This is my second year attending SfN. Last year, I managed to pull off a pretty successful run. However, SfN is such a vast meeting that the experience you have there is redefined every year you go, depending on where you are in your career.

This year, I am a first year grad student and will be scoping out roughly 3x the content (catering to rotations) as when I was a research assistant last year. This means that burn-out is 3x as likely, but I have planned my schedule with two things in mind:

1) I will not get to everything that I have put on my itinerary.
2) The goal is to get an introduction to the most exciting recent activity in the 3 areas encompassing my rotation projects, and not to get bogged down by exciting developments in these entire fields. I have some people to meet, some "old" acquaintances to schmooze, and some free mugs to acquire. Should be baller.

I was going to write a First Year Graduate Student's Survival Guide to SfN, but found that Dr Becca has beaten me to it: SfN Survival 101. Check out her stellar overview of things to keep in mind while planning your SfN experience. Seriously, she hits everything.

As for yours truly, although I am not an official Neuroblogger this year, I will be reporting regularly. And I will be seeing some of y'all at BANTER...

are exosomes the Priuses of RNAi transport?

2011-04-15T11:03:00.000-07:00

Knocking out insidious genes using RNA-interference (RNAi) has been massively pursued as a therapeutic technique since its discovery. Specifically, methods of delivering RNAi through the blood stream to target tissues have been of great interest. Scientists have successfully packaged and delivered RNAi in lentiviruses, micelles and other nanoparticles. However, the search for cost-effectiveness, efficiency and target accuracy never sleeps (insert wise crack about the tendency of their funding to hibernate).

In a study recently published in Nature Biotechnology, exosomes are suggested to be a significant improvement over other vehicles. The scientists used dendritic cells -- derived from bone marrow progenitor cells, and not to be confused with neural somas -- and proceeded to test the efficiency and accuracy of their RNAi packaging and delivery. They purified the exosomes, tagged them with muscle or brain targeting peptides, loaded them with exogenous cargo (siRNA for GADPH, a housekeeping gene), and tested their delivery both in vitro and in vivo.

Alvarez-Erviti and colleagues achieved a marked knockdown of GADPH in vitro, and an even more impressive knockdown in several peripheral organ and brain region tissues in vivo, suggesting an improved blood brain barrier-transcending capacity compared to other methods. The exosome delivery method was accurate, and achieved a 60% knockdown of mRNA and a 62% knockdown of protein expression using, allegedly, 10% of the siRNA cargo that other methods have used.

62% efficiency is generally accepted as a pretty high yield in the biomedical sciences. Whether this exosomal packing and delivery system can be optimized to better penetrate the blood brain barrier remains to be seen. However, with its cost-effective, accurate and non-invasive methods, the exosome may be the Prius of siRNA delivery.

Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, & Wood MJ (2011). Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nature biotechnology, 29 (4), 341-5 PMID: 21423189

Saccharomyces boulardii improves migration of new epithelial cells

2011-04-14T10:14:00.000-07:00

The lifespan of healthy intestinal epithelia is generally accepted to be about 5 days. These cells, once departed and sloughed off into the fecal stream, are replaced by newer, younger, healthier cells which proceed through the same life-cycle. In the case of inflammatory bowel diseases (IBDs), in addition to inflammation/ulceration/tissue injury, the migration process of these new epithelial cells is stunted. Since the replacement cells have trouble reaching their destination, damage to the intestinal lining is exacerbated.

A recent study -- published in PLoS ONE and open access if anyone wants to take a peek -- investigated the capacity of a nonpathogenic yeast to alleviate this stunted migration of new epithelial cells to the tips of intestinal villi (the fingers of tissue that protrude from the intestinal wall to create surface area for absorption). Saccharomyces boulardii (Sb) is typically used to treat issues such as diarrhea, the idea being that it stimulates growth factors that help restore homeostasis to the gut.

This nigh-rockstar study strikes me because it is targeting a curative mechanism as opposed to a squelching of symptoms. To achieve actual remission in IBDs, one has to pwn both inflammatory and repair dysfunctions. The inflammatory component is predominantly targeted by the entourage of immuno-suppressants with which Crohns are so familiar. Repair is seldom highlighted as it should be -- excepting methods of balancing gut flora.

The team of scientists in France, lead by one Frederic Andre, looked at the beneficial effects of Sb in both mice and an in vitro wound model (this is a strain of cultured epithelial cells which are attacked gently with a toothpick... rather cute).

The first major finding was that mice who were fed Sb for one week doubled new epithelial cell migration. Only one downer for me in this study was that the mice were all healthy, with no in vivo IBD model for comparison. Nonetheless quite encouraging, no?

The second conclusion was that the wounded cell line closed its wound (or, repaired its injury) by roughly 70%. Their video supplement to this end is quite something.

The scientists conclude that Sb improves new epithelial migration both in vivo and in vitro. Interestingly, the study suggests that increased migration is due to increased motility of cells and not to increased proliferation (the generation of new cells). Sb may be stimulating this activity by secreting factors that stimulate a target signaling pathway FAX/paxillin, which leads to several physiological changes in the intestinal epithelial lining that enable motility of new epithelial cells.

The thing about supplement studies such as this one is that they make me want to stop by the grocery and pick some up on my way home...

Canonici A, Siret C, Pellegrino E, Pontier-Bres R, Pouyet L, Montero MP, Colin C, Czerucka D, Rigot V, & André F (2011). Saccharomyces boulardii Improves Intestinal Cell Restitution through Activation of the α2β1 Integrin Collagen Receptor. PloS one, 6 (3) PMID: 21483797

increasing women in neuroscience

2011-01-12T10:03:00.000-08:00

The Department Chair Training to Increase Women in Neuroscience (IWiN) is scheduled to meetin in Tucson, at the University of Arizona this April. The workshop, funded by the National Science Foundation's ADVANCE program, is a three-year program aiming to increase the number of women on neurosciences faculty. The participants of these workshops expect to leave them with tools to implement recruitment and advancement plans for women within their universities, and to disseminate the information they have gained in "echo" workshops at their institutions.

The IWiN workshops will be hosted in 2011 and 2012 at two of the graduate schools at which I may be a [woman] student at the time... depending on how interviews go at the end of this month. Three of my four choice graduate schools are already participants of the ADVANCE program, which is not too shabby except that the missing institution has a ratio of approximately 1:3 women to men and does not facilitate an equity program in research.

I mention the IWiN workshops in response to a recent article in the New York Times discussing a nice array of statistics about the paucity of tenured female faculty, and women in the upper administrative echelons of science in general. This was summarizing a study based out of UC Berkley. The statistic that I thought was deserving of further attention in the New York Times report was this one:

"Tenured male scientists are considerably more likely to be married with children than tenured female scientists — 73 percent for men versus 53 percent for women. The report noted that among tenured science professors, women are nearly three times more likely to be single without children than men — 25 percent to 9 percent."

The Berkeley article itself furthers this discussion beautifully, and as a woman weighing the possibilities of children and eventual faculty tenure (albeit, we're talking about ten years down the line), I highly recommend a read and consideration of the original research article:

Mary Ann Mason, Marc Goulden, Karie Frasch (2010). Keeping Women in the Science Pipeline Focus on Workplace Flexibility

in indirect support of the hygiene hypothesis

2011-01-11T09:43:00.000-08:00

A recent study out of the University of Michigan Medical School suggests that the stomach bacterium Helicobacter pylori protects against inflammation caused by Salmonella in a mouse model of Inflammatory Bowel Disease (IBD).

This is surprising for two reasons: 1) IBDs occur primarily in the colon while H. pylori is active in the stomach, and 2) the H. pylori bacterium is regarded as dangerous gut flora and typically treated with antibiotics to avoid the development of stomach ulcers.

The findings of Higgins et al are equally unsurprising given the light that has been shed on helpful bacterial/parasitic gut balance by the Hygiene Hypothesis. The Hygiene Hypothesis suggests that a modest intestinal hookworm population may stave off the excessive inflammatory response inherent to Crohn's disease, Lyme disease, asthma, rheumatoid arthritis and other conditions. If this parasite whose reputation is built from its roles in epidemic illnesses in countries where sanitation is poor can, in small doses, help defend inflammatory diseases, then why couldn't the H. pylori bacterium as well?

There are currently no reports of an additive or destructive effect of both H. pylori and hookworm on gastrointestinal inflammation in humans, although it would be quite telling to see the results of their coincidence. Patients from many H. pylori studies have been excluded from reports because they also shown signs of hookworm-related anemia (Vijayan et al 2007, as an example). But this scientists wonders, because humans evolved almost symbiotically with both of these flora, if all of our immune systems would be better balanced were we not to wipe them both out completely.

A few thoughts from Dr. Higgins, one of the Salmonella study's researchers, can be found in an interview here.

Higgins PD, Johnson LA, Luther J, Zhang M, Sauder KL, Blanco LP, & Kao JY (2010). Prior Helicobacter pylori infection ameliorates Salmonella typhimurium-induced colitis: Mucosal crosstalk between stomach and distal intestine. Inflammatory bowel diseases PMID: 20976712

in which more evidence accumulates for utility of calcium channel blockers in treating Parkinson's disease

2010-12-24T11:26:00.000-08:00

Neurodegeneration in Parkinson's disease is known to be specific to a group of dopamine neurons originating in the substantia nigra pars compacta (SNpc). In nearby region, the ventral tegmental area (VTA), dopamine neurons are all but unaffected by disease progression. This selectivity has generated great interest from the PD research community. In a study out of Dr. D. James Surmeier's lab at Northwestern University, this selectivity was suggested to be related to calcium channel activity.

Neural pacemaking, or the rhythmic signalling common to neurons in the motor circuit, involves the influx of calcium into the cell. Pacemaking in juvenile SNpc dopamine neurons is similar to neurons in the VTA. However, in mature SNpc neurons pacemaker firing opens many more L-type calcium channels than in VTA neurons. This allows for greater influx of calcium to the cell, and puts a greater burden on the mitochondrial system in order to pump it out, fostering oxidative stress. Therefore, basal oxidative stress is thought to be significantly higher in SNpc compared to VTA dopamine neurons.

The Surmeier team wanted to confirm the importance of the L-type calcium channel in producing the differences in oxidative stress levels between SNpc and VTA neurons. In order to do this, they used a genetic knockout model of DJ-1 (or Park7), the popular gene linked to occurance of familiar Parkinson's disease.

In a beautiful study, they recorded intracellular calcium oscillations and oxidation of mitochondrial matrix proteins from SNpc dopamine neurons in mice with or without the DJ-1 gene, and found that oxidative stress was greater in SNpc neurons in DJ-1 knockouts compared to wild type. They also showed that pretreatment with isradipine, an L-type calcium channel agonist, kept DJ-1 knockout oxidative stress levels near wild type levels.

The study also suggests that mitochondrial uncoupling protein (UCP) expression is greater in SNpc dopamine neurons compared to VTA, resulting in more frequent mitochondrial 'flickering', or transient depolarization. In DJ-1 knockout mice, UCP expression was lower, suggesting that UCP expression in SNpc dopamine neurons contributes to oxidative stress.

Collectively, the restuls of the study indicate that high calcium entry to SNpc dopamine neurons through L-type channels during pacemaking activity leads to selectively elevated oxidative stress. In turn, these SNpc dopamine neurons are made more susceptible to toxins, aging and the degenerative effects of DJ-1 mutations. Several calcium blockers are currently used to treat conditions like cardiomyopathy and kidney disease, btu the current study suggests their use in Parkinson's disease in order to protect against oxidative stress to which these mature neurons are so vulnerable.

Guzman JN, Sanchez-Padilla J, Wokosin D, Kondapalli J, Ilijic E, Schumacker PT, & Surmeier DJ (2010). Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature, 468 (7324), 696-700 PMID: 21068725

an instance of misconstrued media reporting: placebos

2010-12-23T20:54:00.000-08:00

A most recent example of the media mis-representing scientific findings is the recent NPR report on placebos being equally effective in IBS patients as "the strongest prescription drugs", even when the patients knew that they were being given the placebo. This coverage was a translation of a study out of Harvard Medical, and published in PLoS ONE.

The study, termed "honest placebo", didn't actually eliminate the deception for which placebo studies are renowned. In the methodology, the researchers report telling the patients who received placebo treatment that “placebo pills, something like sugar pills, have been shown in rigorous clinical testing to produce significant mind-body self-healing processes.” By this design, the patients may have received a similar benefit to what they would have experienced if they had expected that they were being given a strong prescription drug. The patients were given the impression that the placebo would help them. What would have contributed even greater meaning to this study is an additional group who were told that they were receiving a placebo drug, but not told that it was expected to help them.

As many of the comments on the NPR report echo, a strong component in placebo studies is the idea of holism and self-healing. Dr. Ted Kaptchuk, a co-investigator in the Harvard study, states in his interview that the healing factor was assumed to be the "self-healing ritual" of dosing oneself twice daily, even with a placebo. This scientist would suggest that self-healing is as likely to take place due to the belief that a placebo had been reported helpful as it is to be due to the ritual of pill-taking.

The great value of this study's conclusions is lost in the media translation: there is healing potential in having the expectation that your therapy will work.
NPR does the courtesy of acknowledging that "placebos don't shrink tumors or stop multiple sclerosis in its tracks". However, particularly for conditions such as IBS, which have consistently shown to be negatively effected by stress and proactive treatment, this study's findings are important to treatment development.

Ted J. Kaptchuk, Elizabeth Friedlander, John M. Kelley, M. Norma Sanchez, Efi Kokkotou, Joyce P. Singer, Magda Kowalczykowski, Franklin G. Miller, Irving Kirsch, Anthony J. Lembo (2010). Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome PLoS

VEGF-B as a therapeutic intervention for Parkinson's disease

2010-12-02T15:17:00.000-08:00

Since it was discovered that the brain had tremendous neuroregenerative potential, growth factors have been highly speculated as therapeutic tools. The vascular endothilial growth factor (VEGF) family, and particularly VEGF-B, has recently been distinguished as having a neuroprotective role in the Parkinsonian brain.

Carolina Hagberg et al. published the findings in Nature Letters earlier this year that VEGF-B was tightly co-expressed with several mitochondrial genes, suggesting a role for this growth factor in metabolism. VEGF-B was specifically found to regulate endothilial fatty acid transport (uptake) proteins, and thus, the uptake of fatty acids into peripheral and heart muscle, and brown adipose tissue. The co-expression of VEGF-B and mitochondrial proteins suggests a coordination of endothilial lipid uptake and mitochondrial lipid use, which is why it is an attractive intervention for PD, wherein it is thought that dopaminergic neurons die by dysfunction of mitochondrial metabolism.

This mechanistic information provides support for work lead by Torsten Falk at the University of Arizona suggesting a role for VEGF-B in the Parkinsonian brain. In a 2009 study, a midbrain cell culture showed upregulation of the VEGF-B gene following treatment with rotenone (a pesticide specifically toxic to dopaminergic neurons, and commonly used in non-primate animal models of PD). Additionally, application of exogenous VEGF-B to cell cultures resulted in neuroprotection from rotenone toxicity.

More recently, Falk et al. have shown exogenous VEGF-B to be neuroprotective in vivo. From a 2006 study by Sun et al., intraventricularly administered VEGF-B restored neurogenesis to wild-type levels in VEGF-B knockout mice.

In corroboration with the Hagberg study, there is a strong suggestion that VEGF-B may be neuroregenerative via direct effect on mitochondrial function. Correlative studies associating VEGF-B expression with midbrain mitochondrial un-coupling proteins, Complex I, or apoptotic cascades remain to be seen. Additionally, there are no reports of VEGF-B's capacity to be neurorestorative, or slow dopaminergic neurodegeneration in a progressive PD model.

Hagberg, C., Falkevall, A., Wang, X., Larsson, E., Huusko, J., Nilsson, I., van Meeteren, L., Samen, E., Lu, L., Vanwildemeersch, M., Klar, J., Genove, G., Pietras, K., Stone-Elander, S., Claesson-Welsh, L., Ylä-Herttuala, S., Lindahl, P., & Eriksson, U. (2010). Vascular endothelial growth factor B controls endothelial fatty acid uptake Nature, 464 (7290), 917-921 DOI: 10.1038/nature08945

T. A. FALK, X. YUE, S. ZHANG, S. J. SHERMAN (2010). Evidence for neuroprotection after treatment with Vascular Endothelial Growth Factor-B in vivo in the 6-hydroxydopamine rat model of Parkinson’s disease Society for Neuroscience 2010 Abst.

Sun, Y., Jin, K., Childs, J., Xie, L., Mao, X., & Greenberg, D. (2006). Vascular endothelial growth factor-B (VEGFB) stimulates neurogenesis: Evidence from knockout mice and growth factor administration Developmental Biology, 289 (2), 329-335 DOI: 10.1016/j.ydbio.2005.10.016

SfN 2010 Take-aways

2010-11-21T11:34:00.000-08:00

Things that I learned from posters, presentations and lectures at SfN this year will play themselves out in my research and career direction, but there were other notables which were not so directly translatable. Here are my not-necessarily-scientific take-aways from SfN 2010:

1. Had anyone told me growing up that learning multiple languages with any degree of volubility would be very important in my communication with other scientists, I would have put more effort into Spanish, German and French. Four years of Latin does me worlds of good in reading, but in deciphering various accents and breaking language barriers... repetition and speaking loudly were my only saving tools last week. It is very humbling that all of these wonderful minds, to whom English is a second language, have learned it so fluently.

2. Although it was immense fun to spend a week on a yacht in a nearby harbor, I think that I would have gotten more out of staying closer to the convention center. By the time 7pm approached and I had mosied back to my boat, had a bite to eat (on those nights when we did not go out to eat) and relaxed, another twenty minute drive back to the convention center area for any of the satellite events was less appealing. ... and I do regret missing out on some of those -- thank goodness for Neuroblogger reports!

3. Limiting my content was certainly helpful, and the best approach for me. What happened was that I made sure that I got to everything on my list, and then ventured out into other subfields (olfaction, methodologies, learning and memory). Next year, I think I will venture even further, as I still limited this extended content to its relation to my methodologies, or my circuits, or my disease.

4. Taking two afternoons to explore the city was essential.

SfN 2010: Tuesday

2010-11-17T06:56:00.000-08:00

Tuesday was the biggest day of the conference, for me. While I maintained my initial pace during poster sessions, I soon discovered that on days when those posters were scattered throughout the convention hall, my body was substantially more taxed by the end of the day. Tuesday was no exception, as the morning encompassed introducing myself via poster speculation to three potential mentors, each in a different subtopic of the session.

I succeeded in making a fool of myself in introduction to one such PI, by attempting to hide behind other poster surveyors until I was equipped with intelligent questions about his research. My scheme unraveled when he recognized the name on my badge and made the introduction himself. I spun a subterfuge of embarrassed chatter until recovering my intellect. Fortunately, he stopped by my poster in the afternoon and was enthusiastic and impressed. Score.

A dear late post doc of our neighboring lab, now working in industry as a medical liaison, imparted some wisdom regarding the giant that is SfN. "What is unique about this conference," she said, "is that what your experience here changes each year as your career changes." When you are a graduate student, your mission is to soak up any and all information about other research that may help design your own. When you are a post doc, you are sponging in addition to networking. When you are a PI, you are peppering your collaborative learning with reunions and lunch dates. In industry, she says, you are honing in on studies where drug intervention studies may be beneficial for your company, as well as attending committee meetings. SfN is consistently a whole 'nother world defined by where you are outside of it.

And, I suppose, as a pre-pre-doc, my mission this year was to get my feet wet, to network, to get some face time with potential mentors and, of course, benefit from poster feedback on my own research. In all of these regards, I believe I was successful.

Tuesday afternoon was my poster session, and though I initially planned on holding the fort for two of the four hours, both my boss and myself were present for almost the entire session breaking away for no more than half an hour each to visit other posters. Thank goodness for my wonderful colleague who fielded questions in our brief absences even though she works with a different model! By half an hour into the session, the traffic in front of our poster was boggling. My boss and I ended up tag-teaming presentation/question rounds for different handfuls of people. The feedback was spectacular, with several unique directions offered, several potential collaborations resulting and a few friends made.

What's more, I was totally starstruck by the flow of big names in front of our poster whose badges I recognized from manuscripts that had jump-started my career or helped to define my work, but whose faces were met for the first time. At one point I remember surreptitiously asking my boss, "is that the Mike Salvatore?" What a rush to present and discuss your work with minds whose contributions to neuroscience have shaped your own, and what an even greater honor to be commended by them for your ideas. These folks are all friends of my boss -- you come to know or at least meet most of your field at some point -- and he got a kick out of my agog state.

SfN 2010: Monday

2010-11-15T22:47:00.000-08:00

Monday morning's highlight was the Experience-Dependent Synaptic Plasticity and Neurogenesis in the Degenerating and Injured Brain nanosymposia session.

Carl Cotman, professor of neurology at UC Irvine and a potential mentor, spoke about the effects of exercise in mice, canines and humans. Dr. Cotman specializes in Alzheimer's (AD) research, and presented a collection of studies highlighting the effect of exercise on blood flow, amyloid aggregation and instance of BDNF. In transgenic mouse models of AD (Tg2576), Cotman discussed reduced amyloid and increased BDNF with exercise. In humans with AD, increased vessel volume and blood flow was observed with fast walking, corroborative with decreased amyloid reported by Liang et al in the Annals of Neurology this year.

Most notably, Dr. Cotman proposed that the brain "has a memory for exercise." Exemplifying this statement was his study from 2005 where AD rats exercised on a treadmill for one week, resulting in increased BDNF in the hippocampus. Some of these rats proceeded without exercise in the following week which resulted in decreased BDNF levels. These levels increased rapidly when the animals were exercised for an additional week to levels beyond those revealed due to the initial exposure, a phenomenon that typically takes weeks to induce in naive rats. This "memory for exercise" may prove to be key in designing rehabilitative exercise programs.

Mike Jakowec and Giselle Petzinger, respectively professor and clinician-researcher at USC, represented the recent work of their labs as well as the strong collaborative efforts within USC's Neuroscience labs. Advocate of exercise in rodent models of Parkinson's disease, Dr. Petzinger presented evidence that exercise may be working through the indirect dopamine pathway (D2) to aide motor recovery. Mot strikingly to me, their lab has reported that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) results in dopamine neuron spine loss specific to the D2 pathway via [F]Fallypride radiotracing (PET scan). Exercise in their MPTP mouse model results in a 98% increase in the striatal D2 receptor. This research suggests some very interesting targets for intervention.

The David Kopf lecture on Neuroethics was given this year by Hank Greely, professor of law at Stanford, and a professor by courtesy of genetics at the School of Medicine. Beyond delivering a lecture as eloquently as one will ever hear, the poignant stars of Dr. Greely's talk were copious.

Dr. Greely opened by saying that the "ethical issues of neuroscience are 10 years behind those in genetics," referring to the paradigm sweeps that genetic discoveries have prompted (i.e. eugenics). He elaborated that the implications of neuroscientific discovery were "more important than [those of] genetics, made so by immediacy and power." Namely, neurological dysfunction has very present consequences, whereas genetic abnormalities must emerge on the physiological level before they can be acted upon. For instance, if you were to find yourself predisposed to Alzheimer's through genetic testing, you would be protected from discrimination by the Genetic Information Non-discrimination Act of 2008. However, there exists no such protection if you are diagnosed via MRI.

Humans as mind-readers, MRI's distinguishing between conscious and unconscious vegetative states, and the responsibility of humanity to discern what is an adverse disease and what is just a condition that makes "us" (the indirectly affected "us") uncomfortable: these are some of many issues with which neuroscientists can become dangerously dissociated, but the bench does not separate us from the issues produced by our discoveries. The mindfulness of scientists guides social consequences.

I refer readers to Stanford's Neuroblog and The Neuro Dilettante for more adequate coverage of Greely's lecture.

Liang KY, Mintun MA, Fagan AM, Goate AM, Bugg JM, Holtzman DM, Morris JC, & Head D (2010). Exercise and Alzheimer's disease biomarkers in cognitively normal older adults. Annals of neurology, 68 (3), 311-8 PMID: 20818789

Adlard, P. (2005). Voluntary Exercise Decreases Amyloid Load in a Transgenic Model of Alzheimer's Disease Journal of Neuroscience, 25 (17), 4217-4221 DOI: 10.1523/JNEUROSCI.0496-05.2005

SfN 2010: Sunday

2010-11-14T21:30:00.000-08:00

Before I extrapolate on neuroscientific happenings, I must take this opportunity to reflect on how stellar it is that I am staying on a docked yacht, and drinking margaritas at sunset on the deck of said yacht with two extraordinary people.

Onward.

Sunday was booked with two four-hour poster sessions and one afternoon symposium. The morning was filled with Spinal Cord Injury and Parkinson's Therapies sessions, with a not-so-quick diversion to the triple-letter aisles where one of my prospective graduate program PIs sported sixteen -- count 'em, sixteen -- posters on expression of the immediate early gene Arc in various brain regions associated with cognition in models of aging and environmental stimulation (Session 204. Learning and Memory: Genes and Aging).

The afternoon's symposium of choice was Silvia Arber's talk on Motor Circuits, which was excellent but for a somewhat misleading in title. This particular neuroscientist sees "Connecting Motor Circuits" and expects a comprehensive discussion of relationships of both central and peripheral nervous system motor circuits. Instead, Dr. Arber focused on her research, which is entirely peripheral and has become famous for classifying the proprioceptive identity of the spinal cord; specifically, the innervation of the dorsal and ventral horns, and during what movements their respective peripheral pathways are activated. Numerous beautifully conducted studies were exemplified during her talk.

An afternoon of inducing, protecting against and ameliorating dyskinesias brought me back to my element, but my brain was re-tuned once more with a quick tour through the vendor exhibits. The vendors first open shop on Sunday, and traffic through their booths was daunting. Free widgets, pens and t-shirts galore spanned the entire length of the convention center; I am told that there were significantly more vendors this year than ever before.

Adorned with newly acquired tote bags full of free scincey goodies, off we went to the The Fish Market on Harbor Drive to pick up some prawns to accompany our margaritas -- peeled, cooked and devoured on our boat.

SfN 2010: Saturday

2010-11-13T17:27:00.000-08:00

Glenn Close has been a heroine of mine since 1991, when I saw her in Sarah Plain and Tall. Today, I met her... almost.

Glenn Close, her sister Jessie Close and nephew Calen Pick were the introduction to my first SfN. Their stories of battling bipolar disorder and schizoaffective disorder were strong, and deeply touching. Bringchange2mind.org has done a fantastic job of reaching out to people with or touched by mental illness; and communicating to the world that mental illness is a physical ailment like any other of the body, not to be isolated as demonic or self-inflicted. Calen spoke of the self-hatred coincident with not being able to control your own stream of consciousness or emotion, and the effort that bringchange2mind puts toward erasing this attitude from Consumers, survivors and loved ones whose lives are impacted. One in four families is touched by mental illness, Glenn reminded us.

Jessie and Calen gave very personal insight into their struggles to find and hold on to reality, and opened a week-long convention of cutting edge research by suggesting that neuroscientists like those present were responsible for their current states of health. It is so infrequently in science that people look at your work and say, "this is so beautiful, what you've done." And it was profoundly impactful to me to hear Calen Pick thank the present body of researchers for their work. From an artist, that is an especially beautiful complement.

The afternoon's first poster session was overwhelming only in that I did not expect to be pumping so much adrenaline. Twenty-six posters interrupted by a nanosymposium was a good pace. However, my session frequency was all over the place, and I spanned the length of the convention center from the single to the triple letter aisles more than once. The following days were much more focused.

Nearing 5pm, as I walked out of the center I passed Glenn and Jessie Close and Calen Pick in the company of their entourage. In the ten seconds during which I approached and then passed them by, I made eye contact, smiled and nodded respectfully, chickened out of approaching and asking to shake the hand of my emotive activist childhood heroine, and regretted it. Thus began the epicness of my first SfN.

Society for Neuroscience, 2010: An Introduction

2010-11-10T15:02:00.000-08:00

The next several posts will be SfN-centric, as it is my first year of both attending and presenting and I am teeming with fledgling excitement. So that I am not undone by the insidious and unrealistic lure to see and do everything, I have been following the guidance of a few Neurobloggers and of my boss.

After going through the almost innumerable legions of posters and symposia in the Meeting Planner by session, then doing separate name and keyword searches, I realized that getting the most out of every one of the many hundreds of titles I had ear marked was just not realistic. Though I have not slimmed down my itinerary, I have taken the sage advice of The Neuro Dilettante, and acknowledged that even if I visit all the posters on my itinerary, I will have only seen a minute fraction of what this mass international gathering has to offer, and that is fine.

I am told that many first-timers (mostly grad students) burn out within the first two days attempting to see and learn about everything. In the interest of surviving the entire week, I will not be rushing about with my laptop or busily scratching volumes of notes. Instead, the most key research conclusions or methodology along with contact information will be incorporated into my notepad. And if I happen to spend a little extra time at the posters presented by the PI's with whom I'm interested in doing my PhD work (in two years, universe willing)... so be it.

And I intend to exploit the free give-aways of the vendors who have taken the time to email me with specific requests for demonstration and face time. Can one have too many key chain laser pointers or letter openers?

I will also be equipped with thumb tacks, mini-poster hand-outs, sharpies, bottled water, a sweater (yes, though San Diego will be between 70-80 degrees the convention center is kept at a chill), and convention center floor plans.

Following the high of seeing Glen Close, heroine of my childhood, on Saturday afternoon, the Navigating the Meeting seminar may be just the thing to settle me into conference mode -- I highly recommend this tool, especially for those who do not yet have plans of attack. I intend to be a SfN Ninja by the end of this.

On Choosing a Publishing Name: Part Deux

2010-11-07T13:16:00.000-08:00

When the proofs of my first publication were forthcoming and reaching decision became pressing, choosing my publishing name was not nearly so convoluted as I had built it up to be.

Though my maiden name is as unique as they come, my husband is a huge part of my work and why I am able to create what I do. His last name is the one with which I have decided to publish, and my maiden name will be assembled in an unmistakable set of initials. This representation, I have decided, adequately honors all in my family while keeping my title reasonably concise and fairly recognizable while avoiding the logistical nightmare of separating legal and publishing names.

On Choosing a Publishing Name

2010-06-26T11:13:00.000-07:00

I decided in high school, after finally getting my signature to a state of calligraphic excellence, that it was a sign this name was truly mine and I would never lose my last name.

However, as a huge fan of historical record keeping and genealogical efficiency, and out of solidarity with my very-soon-to-be husband, I would like to have his last name as well.

I am now faced with imminent marriage and the simultaneous publishing of my first science journal article, and must decide how I will define myself professionally. This decision has seen weeks of emotional turmoil though the obvious solution, simple and logical, took a while to sit right.

As a research scientist, I want to be identifiable and easily associated with my work. My maiden name is so Ellis Island-unique that there is not another soul on earth who has it to whom I am not related. I would like to continue being affiliated with my clan (read: my clan is notoriously and hazardously crazy, and it is not so much the affiliation to them as to my father, and to honor my parents, that is a strong need). My fiance's last name is strong, but ever-so-common.

This is the obvious and logical decision:

Legally: Maiden HisLast
Socially: HisLast
Professionally: Maiden

My point of contention has been whether or not to use both of our names in publications. If my pen name is solely my maiden name, I am ignoring his profound role in my accomplishments (read: without such support and enthusiasm for my own ambition and ardor, my productivity would certainly be less colorful). However, if I use both of our names professionally, the uniqueness of my maiden name is countered by the addition of his common one.

Does it make a name less strong to have two parts? In terms of identity, I don't think so. But in terms of a pen name, it does help them to compliment one another: our last names do not compliment one another. This clash is the caveat. Perhaps it is mostly because I am new to the idea, or perhaps it is because (as an amateur script editor for a film maker) I know that a character's name is strongest and most memorable when it does not trail on being degraded by mumbling as a telomere by replication.

Ultimately, the name is mine and if at least part of it is memorable in publication, then I am satisfied. And if we have children along the line, they will take his name, because history has enough obstacles to accuracy without having to negotiate when names were anagramed, traded or ultra-hyphenated. Therefore:

Legally: Maiden HisLast
Socially: HisLast
Professionally: Maiden HisLast

However!

At this point in the rationale, the fiance himself finally feels it appropriate to chime in again. His original wish was that I take his name. However, his evolved stance is that anyone who knows me well enough on a social/personal level for me to care will know me as Mrs HisLast or Dr Maiden. Therefore, rather than have my pen name be Maiden HisLast, he votes for the original scenario of a solitary, solid last professional name. Therefore, the final consensus is:

Legally: Maiden HisLast
Socially: HisLast
Professionally: Maiden

Journal Club Follow-Up: Coenzyme Q10

2010-03-01T19:53:00.000-08:00

Many Parkinson's patients take Coenzyme Q10 supplements. As mentioned in the previous post, CoQ10 is part of the Electron Transport Chain -- a very important part, in fact, as it alleviates pressure on our precarious and susceptible-to-aging Complex I.

While many theorize that Complex I is shut down or is deficient in PD (1, 2, 3, 4), others believe that deficient activity of the CoQ10 pool beside Complex I is more to blame (5, 6). The CoQ10 theory claims that PD causes a deficiency in the CoQ10 pool that carries electrons from Complex I to their next destination without producing ROS. As a result of low CoQ10, electrons build up in Complex I and get released from the entrance because they cannot leave through the exit.

Some PD patients are able to take CoQ10 supplements and improve their condition (7).

It is my opinion that CoQ10 is a palliative treatment and not a long-term solution. The Ndi1gene therapy discussed in the previous post is a better option if it makes it to, and proves robust in clinical trials. My reasoning is that a genetic replacement for Complex I is a more stable therapy than a persistent aid to CoQ10: it is more permanent and a more widespread solution; a large portion of PD patients do not have CoQ10 deficiencies. Ndi1 would also contribute to the sustaining of the proton gradient in the mitochondria, also vital to creating energy in the ETC.

Greenamyre, J. (2001). Response: Parkinson's disease, pesticides and mitochondrial dysfunction Trends in Neurosciences, 24 (5) DOI: 10.1016/S0166-2236(00)01788-4

Schapira AH (1994). Evidence for mitochondrial dysfunction in Parkinson's disease--a critical appraisal. Movement disorders : official journal of the Movement Disorder Society, 9 (2), 125-38 PMID: 8196673

Morais, V., Verstreken, P., Roethig, A., Smet, J., Snellinx, A., Vanbrabant, M., Haddad, D., Frezza, C., Mandemakers, W., Vogt-Weisenhorn, D., Van Coster, R., Wurst, W., Scorrano, L., & De Strooper, B. (2009). Parkinson's disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function EMBO Molecular Medicine, 1 (2), 99-111 DOI: 10.1002/emmm.200900006

Storch, A., Jost, W., Vieregge, P., Spiegel, J., Greulich, W., Durner, J., Muller, T., Kupsch, A., Henningsen, H., Oertel, W., Fuchs, G., Kuhn, W., Niklowitz, P., Koch, R., Herting, B., Reichmann, H., & , . (2007). Randomized, Double-blind, Placebo-Controlled Trial on Symptomatic Effects of Coenzyme Q10 in Parkinson Disease Archives of Neurology, 64 (7), 938-944 DOI: 10.1001/archneur.64.7.nct60005

Journal Club: Neuroprotection by NGI1 Gene in a Parkinson's Disease Model

2010-02-27T16:39:00.000-08:00

One of the most popular mechanisms of pathology in Parkinson's disease (PD) research is cell death through Complex I inhibition in the mitochondria.

Mitochondria -- affectionately known as the power houses of all cells -- are where energy is produced. There is a series of protein complexes forming the Electron Transport Chain (ETC) which, as their acronym exposes, steal electrons from contributing molecules and convert them into energy and water.

The fully reduced H2O form of oxygen is non-toxic. The various single-electron intermediates between O2 and H2O are ALL toxic free radicals, the so-called Reactive Oxygen Species (ROS). Complex IV (cytochrome oxidase complex) has a gate that transfers electrons directly to O2, reducing it to water without generating ROS. Complexes I and III, however, occasionally allow electrons to escape from the ETC to form ROS.

In Parkinson's disease, Complex I is dysfunctional, and it is thought that much higher concentrations of ROS are produced in the ETC. These attack multiple systems in the mitochondria which eventually lead to the breakdown of cellular DNA, and the cell itself.

Many cases of PD are characterized post mortem by a selective loss of dopamine cells via this mechanism.

The study by Marella et al has used the variant of Complex 1 found in yeast to attempt to quell this rampant ROS formation. Using the rotenone rat model, the group injected the Ndi1 gene via biodegradable microspheres (classy...), and monitored recovery in the substantia nigra pars compacta (SNpc; the primary region of dopamine cell loss) and in behavior.

After 60 days, tissue analysis of Ndi1-injected rotenone rats showed increased staining for viable dopamine cells in the SNpc. Those lesioned rats who did not receive the Ndi1 gene showed significantly fewer stained dopamine cells, and extensive staining with antibody against 8-oxo-dG (indicating oxidative damage to DNA).

My gripe with the study -- in addition to its not being tremendously written -- is that it is lacking in relevant behavioral assessment. The study monitored speed of movement, and the number of rotations in a widely used apomorphine test. The rotations test is normally used in unilaterally lesioned animals (which these were) to indicate preference to rotate in one direction. However, the direction of rotation induced by apomorphine in this study was determined by more factors than the unilateral lesion, which caused the animals to rotate in both directions. Therefore, behavioral data was reported as the "number of animals exhibiting 100% lateralized rotation irrespective of the direction." In my opinion, the behavioral test was severely weakened by this caveat and the group should have employed a quick additional test... like the Whisker test or lateralized grip strength.

This suggests that the Ndi1 gene -- the yeast version of Complex 1 -- was able to compensate for inhibition of Complex 1 by rotenone, decrease ROS activity by serving as an electron transporter, and lessen cell death. If this could be replicated in higher animals, it may prove a viable candidate for clinical trials.

Aside from deficits in writing and behavioral analysis, the story told by this article was fascinating with very intriguing implications. They did their homework, publishing several studies on in vitro activity of the Ndi1 gene and subsequent protein (1, 2) as well as confirming benign effects of introducing a yeast gene in vivo (1, 2) .

Marella M, Seo BB, Nakamaru-Ogiso E, Greenamyre JT, Matsuno-Yagi A, & Yagi T (2008). Protection by the NDI1 gene against neurodegeneration in a rotenone rat model of Parkinson's disease. PloS one, 3 (1) PMID: 18197244

Journal Club: RBD and Parkinson's Disease

2010-01-24T16:47:00.000-08:00

There is a great deal of research being done regarding the mechanisms of Parkinson's disease (PD) and possible targets for therapeutic cures. Yet, it is one of many conditions that remains incredibly hard to diagnose. PD patients are not typically diagnosed until the disease has progressed to 70-90% dopamine cell depletion when symptoms become observable in movement behaviors (Jankovic 2008).

By the time cell loss has progressed this far, it is very difficult to achieve a successful long-term treatment plan. Pharmaceuticals such as L-Dopa (Jubalt et al 2009) and rasagiline (Olanow et al 2009) are generally effective, but can lose their effect or cause dangerous side effects over time. Deep brain stimulation has been shown to be very effective behaviorally, but there it is an intense procedure which has occasionally been correlated with subsequent cognitive impairments (York et al 2008). Exercise therapies have also shown promise in recovery therapy, but have seemed more lasting in the peripheral nervous system than the dopamine system of the CNS (Goodwin et al 2009; Petzinger et al 2007; Muhlack et al 2007).

When it is so important to try to identify markers of PD before it progresses beyond our current ability to treat it in a lasting way, Dr. Ronald Postuma and colleagues out of Montreal, Quebec, Canada have identified REM sleep behavior disorder (RBD) as a possible indication of developing PD. RBD is the loss of muscle atonia that normally occurs during REM sleep, causing a person to thrash unconsciously.

Their study is a beautiful longitudinal representation of several patients diagnosed with RBD in the 1980s who developed either PD or dementia by 2004. Of their 17 final RBD patients, 6 (5m/1f) had developed PD and 11 (10m/1f) developed dementia.

The Postuma group suggests that there might be a discrete pathological condition specific to "RBD-then-neurodegeneration"which has different early manifestations than PD alone. A very interesting concept as RBD, dementia and PD are all distinctive in their Lewy body and ß-amyloid
deposition. If further study of the evolution of RBD into PD shows a strong correlation, this could be a giant leap forward in terms of PD diagnosis and early treatment. There may indeed be a distinct pathology to this progression or there may not be. In any case, this is a very important study in the field of neurodegenerative disorders, and I believe it is expecially important to get longitudinal studies like this one funded.

The staging model of PD developmnt proposed by Braak et al in 2003 proposes that the effects of PD begin in the olfactory area of the brain, spreading to autonomic and sleep-involved regions, and finally to dopamine loss in the nigrostriatal pathway and several downstream cortical pathways (Braak et al 2003). The Braak model, in conjunction with this new proposal from Postuma et al, leaves me wondering about Restless Leg Syndrome (RLS) as another possible indicator of PD.

The connection between RLS and PD is in dopaminergic transmission, as suggested by Dr. David Rye in 2004. A study by Tan et al in 2002 found that prevalence of RLS in PD patients was not significantly different from incidence in their healthy population, roughly 15%. The Tan study was not looking at progression of RLS into PD, however, so it is possible, as suggested in the Postuma study, that RLS-PD may have its own unique pathology.

To date, I have not found any longitudinal studies of RLS progressing into RBD or PD.

gene patenting

2009-12-13T21:53:00.000-08:00

This week's Science Friday focused on gene patenting. Specifically, a case that has been in court since May of 2009: the American Civil Liberties Union (ACLU) -- along with several cancer patients and organizations of pathologists -- has raised a lawsuit against Myriad Genetics' patenting of the two genes BRCA1 and BRCA2. Mutations of these genes are indicative of increased risk of breast and ovarian cancer.

The ACLU claims that Myriad's 1994 patent on the genes is illegal, unconstitutional and should be thrown out. The issue of importance to the cancer patients involved is that Myriad's monopoly on the tests for mutated BRCA1 and 2 prevents patients from getting a second opinion on the results of their tests, and from obtaining a more affordable version of the test.

In my mind, patenting genes is like patenting anything else in medicine. By invoking a 20-year period of exclusive rights, development of the patented technology or drug is inhibited. This is the way it has worked with pharmaceuticals for eons: drugs remain produced, distributed and exorbitantly priced by the pharmaceutical companies who patent them, and become eligible for other companies to optimize and distribute generically when that 20-year period is up.

The opposition to this argument is that patenting genes causes more stunting to medical innovation -- and, by default, medical cures -- than does patenting of drugs and other medical technology. By patenting genes and the single test that has been developed to identify them, patients interested in the risk those genes may pose to them are forced to rely on the interpretation of the patenting company. In the case of BRCA1 and 2, patients cannot get a second opinion outside of Myriad Genetics; they are forced to rely on the results obtained from Myriad's test and on the interpretation of Myriad's doctors.

My response to this opposition is as follows:

Genes are only a single indication of disease. It has been reported that "inherited BRCA1 and BRCA2 mutations account for 5 to 10 percent of breast cancers and 10 to 15 percent of ovarian cancers among white women in the United States" (Campeau et al 2008) -- having the mutations is not a definitive diagnosis of cancer. It has also been reported that this percentage is even smaller: "[a]pproximately 5-10% of breast carcinomas and 10% of ovarian carcinomas are ascribable to a genetic susceptibility. Of these, about 40% are related to genetic mutations in the genes BRCA1 and BRCA2" (Palma et al 2006). Take from that statistical discrepancy what you will -- I guarantee there was not a new census taken between 2006 and 2008.

If patenting of genes inhibits patients from getting a second opinion on their genetic tests, it seems that seeking a verification through other diagnostic methods is not only an acceptable option, but a preferable one. Treatment of breast/ovarian cancers in particular are radically invasive and life-altering; until the BRCA gene identification tests are available "generically", mammograms, MRI and screenings for other genetic markers of breast/ovarian cancers are not only options but -- in my very humble opinion -- an incredibly good idea before making decisions about radical mastectomy and chemo:

"Clinical testing options for BRCA1 and BRCA2 are limited in the United States. In contrast to genetic testing for BRCA1 and BRCA2, genetic testing for other cancer susceptibility genes (MSH2, MLH1, PTEN, TP53, etc) is available from numerous profit and notfor- profit laboratories, with a range of testing options and prices."

"In addition to DNA sequencing of BRCA1 and BRCA2, genetic testing for other major breast cancer susceptibility genes including CHEK2, PTEN, and TP53 is clinically available in the United States." (Walsh et al 2008)

Patients at risk for cancer should not limit their diagnosis to the outcome of a single kind of test when there are several out there, and certainly not to a single genetic test which measures only susceptibility. I do not argue against the legitimacy of a patient's concern, I just don't think that this particular argument is reasonable ground to make illegal the patenting of genes by their discoverers.

I am not sure I agree with the ACLU's argument either:

“What they have really patented,” says Chris Hansen of the ACLU to the New York Times, “is knowledge.”

Really? If that is a legitimate statement, then every biomedical patent in the world is a blockade against knowledge, and they should all be overturned. Patenting is a measure taken to protect and honor the discoveries of researchers. It gives them the opportunity to make advancements on their own discoveries before the whole world is allowed to take a crack at them.

"Genes are informational. [By] allowing a company to have a patent on the actual sequence you are restricting the free flow of information," Tania Simoncelli, ACLU's science advisor, told Pharmacogenomics Reporter back in May. Simoncelli's colorful expatiation of this comment can be found here.

THE POINT OF PATENTS IS TO TEMPORARILY RESTRICT THE FLOW OF INFORMATION. IF YOU WANT TO BRING THE FIRST AMENDMENT INTO THIS, YOU HAVE TO FIGHT ALL PATENTING OF ALL DISCOVERIES EVER.

BIOMEDICAL RESEARCH HAS BEEN PATENTING GENES SINCE THE 1980's AND DOCTORS HAVE BEEN PISSED OFF ABOUT IT SINCE THE 1980's. IF THE PATENT OFFICE WAS WORRIED ABOUT GENE PATENTING BEING CONTRARY TO THE PUBLIC INTEREST, THEY WOULD NOT ISSUE THEM.

In short, I have yet to find a legitimate argument made by the ACLU against patenting the BRCA1 and 2 genes, much less any gene. I'm not saying that genes should or should not be patentable; what I'm saying is that the ACLU is making a poor argument, and needs to approach this from more of a patient access angle.

Maybe what needs to happen here is for gene patenting to selectively be restricted to 5 years instead of 20. Five years is nothing from a scientific standpoint, and wouldn't actually allow researchers the opportunity to make significant headway before the rest of the world chimed in, but it would at least give them a head start without making prospective patients wait an inordinate amount of time for reasonable diagnosis or treatment. And five years of profit from over-priced tests certainly ain't bad.

in vitro meat and the de-evolution of homo sapiens

2009-12-02T16:26:00.000-08:00

Homo sapiens is Latin for wise or knowing man. I would like to strike "sapiens" from our evolutionary title and replace it with "homo follis", which is Latin for windbag or foolish man. Can I do that?

Normally, I love technology and am all for its advancement as long as there is an antidote should it prove to be physically or ethically harmful. There is a line, however, over which technological advancement frequently crosses into the world of promulgating sheer gluttonous sloth. The antedote in the case of modern animal farming is to change human behavior. If we consume less meat, farmers aren't pressured to over-produce massive qunatities in order to stay economically competitive. Less pressure to over-produce means less incentive to abuse farmed animals with antibiotics, hormones, extremely unhealthy food and other revolting living conditions.

But is the American populous ready to make that sacrifice for the sake of being humane? You bet your ass we're not. Instead, commercial science has discovered a much more attractive antidote to modern animal farming -- one that requires significantly less effort on the part of the consumer than reducing meat consumption. For the last decade or so, scientists have been learning how to culture "meat" in a petri dish (Datar & Betti 2009; Edelman et al 2005). We (the people) are so lazy and so addicted to meat that scientists and economists have fleshed out an analysis of the viability of in vitro meat culturing as a "replacement" for meat farming (In Vitro Meat Consortium 2008).

Is it less of a personal burden to adjust to the taste of stem cell meat than to eat less meat and/or eat more local/grassfed/humanely farmed meat? The In Vitro Meat Consortium seems to think so, as does PETA:

"As far as we’re concerned, if meat is no longer a piece of a dead animal there’s no ethical objection."

Really? Because I'm pretty sure that teaching humanity survival through relying on technology to save us from having to make proactive changes in our behavior has negative ethical implications. For instance, the backward evolution of our species.

"Lab-grown meat isn't an easy sell, but there could be benefits. Designer meat would theoretically be free of hormones, antibiotics, and the threat of mad cow disease or bird flu. Omega-3 fatty acids and vitamins could be blasted into the mixture ", says Ian Christe in his article in Popular Mechanics on the subject.

Yes, Ian, you are absolutely correct. However, HUMANELY FARMED ANIMALS WOULD ALSO BE THEORETICALLY FREE OF HORMONES, ANTIBIOTICS AND THE THREAT OF MAD COW DISEASE OR BIRD FLU. Additionally, OMEGA-3 FATTY ACIDS AND VITAMINS ARE PRESENT IN FREE-ROAMING UNGULATES WHO ARE NOT PUMPED FULL OF GRAIN-BASED SLOP TO FATTEN THEM UP ALL YEAR ROUND. And further, WHAT ABOUT ALL THE OTHER SUBSTANCES THAT ARE USED IN THE CULTURING OF THE MEAT; MUST WE ASSUME (like idiots) THEY WILL BE TOTALLY HARMLESS?

So, I must pose the final question: will humanity prefer the financial burden of commercial in vitro meat production, or the burden of changing their consumptive behavior in order to promote humane animal farming? Unfortunately, I fear the former may win out.

Lastly, a warm thank you to PETA for supporting the de-evolution of humanity (not that I'm surprised), as well as an alternative to industrially farmed meat that wont actually stop anyone who wants to taste real meat from doing so (tofu dogs have already made this attempt).

phthalates and ADHD

2009-11-26T00:25:00.000-08:00

The outstanding debate on whether the benefits of soft plastics outweigh their potential harms continues.

The group of esters called phthalates are used in an array of products ranging from pill capsules to children's toys to shower curtains. A research group in Korea has found a strong positive correlation between ADHD behavioral characteristics and phthalate metabolites in the urine of Korean school children. This is a particularly important study for two reasons: 1) a correlation between ADHD and phthalate exposure during critical periods of development has never been shown, and 2) the metabolite levels found in these children indicates the amount of exposure that can now be replicated in animal models.

"Previous animal studies (6,15,16) have shown that phthalate related metabolites induce hyperactivity in rats. These studies reported that pups treated with phthalate demonstrated 1.4 times the level of hyperactivity at night compared with control subjects. Such hyperactivity was dose-dependent, which is consistent with the results of our study."

"It is possible that the toxicity of phthalates is attributable to degeneration of dopaminergic neurons, leading to the hyperkinetics observed in rats in cases of 6-hydroxydopamine (OHDA) procedures (27). Well-known animal models of ADHD like the OHDA rat model suggest that the dopamine neuronal damage can provoke hyperactivity and impulsivity. Many structural magnetic resonance imaging studies showed striatal volume loss suggesting the dopamine neuronal loss in ADHD patients (28)."

"With DNA macroarray data, researchers have found that phthalate metabolites change
the expression patterns of various genes, including both the dopamine receptor D4 (DRD4) and the dopamine transporter in the midbrain (6). The dopamine receptor D4 and dopamine transporter gene expression modulation can induce changes in extracellular dopamine and neuronal dopamine sensitivity, resulting in hyperactivity and impulsivity in rats."

Here is something particularly interesting: if excessive exposure to phthalates is linked causally to ADHD phenotypes -- which has yet to be explored -- perhaps the time-release medications used to treat ADHD such as Wellbutrin and Ritalin should cease to use phthalates in the enteric coating of their medications. It seems odd that they are so widely used in films of pharmaceutical capsules if for no other reason than their heavy reputation as endocrine disruptors. Capsules can contain in the range of 3600 ug phthalates, while most studies estimate that the "safe" exposure range is near 20 ug per kilogram body weight. That means the "safe" range for most young children is about 750 ug. Note that phthalates do not bioaccumulate, so exposure levels are dailies.

"The bupropion (Wellbutrin® SR) release rate has been improved by the introduction of two types of film coated active pellets that release the drug at different pH resulting in novel dissolution profiles. Inert spheres are initially coated with bupropion and hydroxypropyl methylcellulose. The active pellets containing bupropion comprise 70-75 weight % of the dosage form. An enteric coating, applied to about one third of the active drug pellets, is comprised of a film insoluble at low pH, such as hydroxypropyl methylcellulose phthalate. The second coating applied to the other two thirds of active drug pellets is comprised of a combination of a hydrophobic coating agent and methyl acrylic acid copolymer. The two pellet types are then combined in a capsule."

"The novel dosage forms are used to administer methylphenidate (Ritalin) in a pulsatile release manner... Suitable membrane coating materials for effecting delayed release include, but are not limited to: cellulosic polymers such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, cellulose acetate, cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropylmethyl cellulose phthalate, cellulose ester-ether phthalate, hydroxypropylcellulose phthalate, alkali salts of cellulose acetate phthalate, alkaline earth salts of cellulose acetate phthalate, hydroxypropylmethyl cellulose hexahydrophthalate, cellulose acetate hexahydrophthalate..."

Journal Club: on the selective degeneration of dopamine neurons in Parkinson's disease

2009-11-16T13:10:00.000-08:00

http://www.ncbi.nlm.nih.gov/pubmed/16299504

The therapeutic application of potassium gated ATP channels (K-ATP) in Parkinson's disease arises from their ubiquitous expression in the basal ganglia. Regulation of these channels evokes cell hyperpolarization in order to prevent cell excitability. In the mitrochondria, they play a role in translating the metabolic state of the neuron. This week's journal club discussed an article suggesting that K-ATP channels are necessary for the selective vulnerability of dopamine neurons in the substantia nigra pars compacta (SNpc) relative to the ventral tegmental area (VTA). Liss et al demonstrate this theory using mitrochondrial complex I inhibitors rotenone and MPP+, both neurotoxins commonly used in developing Parkinson's disease models in rodents.

Rotenone and MPP+ are known to selectively degenerate dopamine neurons of the SNpc, leaving the VTA dopamine neurons primarily in tact. Liss et al suggest that this phenomenon is due to differential mitochondrial uncoupling (or, disruption of metabolism). Extensive uncoupling with the application of FCCP resulted in activation of K-ATP channels in both the SNpc and VTA. Mild uncoupling with FCCP did not activate K-ATP channels in either region.

"Notably, however, mild uncoupling inverted the response of K-ATP channels to complex I inhibition: in this case, VTA DA neurons, but not SN DA neurons, were hyperpolarized and functionally silenced due to K-ATP channel activation. In the presence of 50 nM FCCP, none of the SN DA neurons was significantly affected by 100 nM rotenone (Fig. 5a,b, left; perforatedpatch recording in 50 nM FCCP: 2.33 ± 0.29 Hz; FCCP + rotenone: 1.92 ± 0.36, n ¼ 6; P ¼ 0.40) or 10 mM MPP+ (data not shown). In contrast, the presence of 50 nM FCCP sensitized K-ATP channels of VTA DA neurons to complex I inhibition (Fig. 5a,b, right; 50 nM FCCP: 2.4 ± 0.55 Hz; FCCP + rotenone: 0 ± 0 Hz, n ¼ 6; P ¼ 0.0075)."

"Stereological analysis of all SN pars compacta neurons in hematoxylin-eosin counterstained sections demonstrated genuineMPTP-induced neuronal death in wildtype mice and confirmed the complete rescue of SN neurons in the Kir6.2-/- mice (Fig. 6d, middle panel; Kir6.2+/+ SN: control, 11,882 ± 222; post MPTP, 8,061 ± 632, P ¼ 0.029; Kir6.2 -/- SN: control, 12,288 ± 231; post-MPTP, 12,619 ± 223; P ¼ 0.36; n ¼ 3 each)." ** Kir6.2 -/- mice are a genetic strain not expressing a unit of the K-ATP channel necessary for activation. This means that blocking the channel's activity prevented SN DA neurons from being lost.

I want to see some apoptosis markers in these SNpc DA neurons due to K-ATP activity. The comaprison of SNpc and VTA DA neurons is an invaluable resource for identifying mechanisms of the selective degeneration that marks Parkinson's disease. Because the VTA DA neuron population is so identifiably unaffected by most neurotoxins from which Parkinson's models are developed, the selectivity of the models and the degree of neural degeneration is not only measurable but comparable to many cellular mechanisms of the disease itself. Uncoupling of the mitochondria speaks to selective metabolic toxicity, and a new target for neuroprotective therapies.

** This was a very complex article using six different mouse strains/treatment groups and analyzing the cell viability using electrophysiology, histology and RT-PCR -- I am reciting only the briefest summary which does not to justice to the extensive work done (although my critique is long-winded, I was impressed with these studies).

on the stifling of creativity

2009-11-16T11:39:00.000-08:00

An experiment was conducted by Desmond Morris in 1962 comparing the artistic creativity of young children and chimpanzees. Remarkably, both chimp and human child became so engrossed in their painting that they showed very little interest in food, sex or other activities that would be expected to divert their interest. The major revelation of this study was that creativity was, perhaps, a natural potential; yet, for many of us, the urge to create diminishes significantly as we grow older, revealing itself only in the sciences, music, art... and on a more modern note, advertising [trash].

A follow-up study to Morris' added a reward system to the chimps' sessions of abstract expressionism. The results was that with each reward, the creativity and depth of the painints degenerated until producing only the minimal product necessary to obtain reward from the experimenter (The Biology of Art, Methuen London, 1962).

David Bohm has described this phenomenon as follows:

"In order to do something for a reward, the whole order of the activity, and the energy required for it, are determined by arbitrary requirements that are extraneous to the creative activity itself. This activity then turns into soemthing mechanical and repititious, or else it mechanically seeks change for its own sake. The state of intense passion and vibrant tension that goes with creative perception... then dies away. The whole thing becomes boring and uninteresting so that the kind of energy needed for creative perception and action is lacking. As a result, even greater rewards or punishments are needed to keep the activity going" (Science, order and creativity; 2000).

I've written about ADHD before, but was inspired to revisit the topic by a seminar forwarded to me:

http://www.ted.com/talks/lang/eng/ken_robinson_says_schools_kill_creativity.html

So my question is this: to what extent is the reward system of education -- any kind of education -- destructive to the development of the self? Is not the self-consciousness, dissatisfaction and boredom resulting from intervention by directed creativity dangerous to development? Some of what were considered the greatest creative minds of history thwarted standardized education. From the science realm alone (with which I am most familiar), Copernicus meandered through universities for seven years without bothering to fulfill a degree. Da Vinci was educated by the royal Medici family, but education in the Italian Renaissance was its own matter entirely. Tesla boycotted academia at the age of ten. Thomas Edison never went.

On the other hand, in more recent history it has become nearly impossible to achieve recognizable creativity without eons of academic vigor. How is that demand defining the way we structure the reward system of education? We pump in the sedatives to get this "most troubled" generation through the hoops. In so doing, we are pummeling creativity from both ends: reward and sedation. What will become of our next generation of scientists and artists?

autism spectrum disorders, part deux

2009-11-11T09:25:00.000-08:00

Another instance where the question begs to be asked: are handwriting patterns differentiated between autistic and Asperger children?

This study found quality of letter formation in the handwriting of children with ASD to be lower than in normally developing children. The subject hasn't really been addressed since 2001, when Beversdorf et al identified the significant instance of macrographia in patients with ASD, as compared to age- and IQ-matched control subjects. Both studies have subsumed autism and Asperger into the ASD umbrella -- just as likely for the purposes of procuring a larger test subject sample as for making their results widely applicable:

"Whereas all subjects with autism spectrum disorder met the diagnostic criteria for autism through their reported behavior during childhood, most subjects had demonstrated significant improvement in function over time, such that the distinction between the various forms of autism spectrum disorder was not as clear. Therefore the more general term autism spectrum disorder is used to describe these patients." (Beversdorf)

The original description of Asperger syndrome in 1944 noted difficulties in motor coordination, specifically in handwriting (Frith; translated 1991). One year before, Leo Kanner published his first paper asserting that some autistic children were quite agile, performing "hair-raising feats of balancing," while others were clumsy "despite dextrous manipulation of objects" (Frith pg. 95).

I would love to see a study comparing the different aspects of handwriting using both the Revised Physical and Neurological Examination for Subtle Sign (from the Kennedy Krieger Institute study), and the Autism Spectrum Quotient and Empathy Quotient tests used by Baron-Cohen's group to differentiate autism and Asperger syndrome. Any cerebellar distinctions between autism and Asperger could be very illuminating...

autism spectrum disorders and dsm-v politics

2009-11-10T18:46:00.000-08:00

An article in the New York Times this morning by Simon Baron-Cohen addressed the debate in the DSM committee over subsuming the conditions of Autism and Aspergers in the fifth edition of the "psychiatric bible"(promised in 2012). The committee is deliberating whether or not to eliminate Asperger from the diagnostic manual and characterize its discrete symptoms as a degree of autism in the spectrum (perhaps "intermediate functioning autism").

Autism and Asperger syndrome are both characterized by impaired communication skills, a desire for keenly focused stimuli and strong inclination toward repetition. They are distinguished only by a slower onset of language skills and latency of intelligence in autism, says Baron-Cohen. He further suggests that this distinction is proving not to be concrete enough, and that the DSM-V committee's struggle with the controversy can be attributed to the lack of physiological distinction of these psychiatric conditions.

I would agree with Baron-Cohen that there is not currently enough genetic distinction between autism and Asperger syndrome to warrant their being entirely separate conditions outside the spectrum disorders umbrella in the DSM-V. However, I think that defining Asperger syndrome idiosyncratically is important to preserve in the new manual. Here is why:

1) Baron-Cohen mentions his own group's recent identification of 14 Asperger-specific genes,19 genes specific to autism and 7 shared (Chakrabarti et al 2009). They measured 68 candidate genes in two experiments: the first measured autistic traits in an undiagnosed sample population using the Autism Spectrum Quotient; the second, using the Empathy Quotient. These two experiments were designed to identify autistic and Asperger cases among the sample:

"We searched for common genetic variants (single nucleotide polymorphisms (SNPs)) on the assumption that autistic traits are continuously distributed in the general population [Constantino & Todd, 2005; Sung et al., 2005]."

"In Experiment 1, autistic traits (measured on AQ and/or EQ) were nominally associated at P<0.05 with SNPs from 19 genes. In Experiment 2, SNPs from 14 genes were nominally associated at P<0.05 with AS."

Six genes were nominally significant in both experiments. This study alone suggests that Asperger syndrome deserves a distinction as a sub-group in the Autism Spectrum Disorders (ASD) category that the DSM-V committee is considering, as opposed to eliminating it entirely, as is also being considered.

The Charkrabarti study is impressive, and the first step in the important attempt to identify the genetic and epigenetic correlates of autism and Asperger separately. However, there is still an extensive amount of correlative research to be done. A good amount of this is ongoing through the AutDB Project.

2) If for no other reason than to preserve the honor of the venerable Hans Asperger.

3) To keep company the solitary other recognized ASD, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS).* Perhaps these could both become sub-groups in the ASD category.

It is noteworthy that a great deal of genetic research already refer to their studies as ASD interactions/links/correlations (PubMed or Google Scholar this). I am terribly eager to find out whether or not this plays a strong role in the decision of the DSM-V committee.

*High- and Low-functioning autism are not classified as spectrum disorder subgroups, although they should be... and perhaps, one day, will be, provided there is a physiological distinction to be drawn between them, Asperger and PDD-NOS.

Journal Club: on Vitamin D and Parkinson's disease

2009-11-07T09:01:00.000-08:00

Preface: After a long hiatus during which I have been doing so much research on Crohn's disease that I haven't written a damn thing about neuroscience, I've decided that it's time to return. I have officially submitted my graduate school applications, and now need to get myself back into regular science-writing mode.

This week's Movement Disorders Journal Club held some lively discussion on the roles that vitamin D might play in the balance deficits of Parkinson's disease patients. This was based on data presented for a grant application, so the following will have little to do with Dr. P's actual pilot study.

Vitamin D deficiency appears to be prominent in elderly people who frequently experience falls (Bischoff-Ferrari et al 2004). The mechanisms by which vitamin D is involved with balance, however, are largely unknown. Dr. P's studies propose to look at how vitamin D levels correlate with falls and posturography in patients with Parkinson's disease (PD) because post-mortem immunolabeling studies have shown that vitamin D receptors are particularly dense in the substantia nigra pars compacta (SNpc)(Eyles et al 2005).

The SNpc is an area of primary pathology in PD; specifically, it is the beginning of the primary dopamine pathway that extends to the basal ganglia and motor cortex, which ultimately make commands of the muscles. When this pathway is depleted, as in PD, the lack of dopamine signaling from SNpc cells has ramifications through several terminal brain regions which lead to the rigidity, tremor and poor balance that characterize the disease.

One of the important questions to ask, given the high vitamin D receptor density in the SNpc, is what role vitamin D might play in that region of the brain: Is there a central nervous system mechanism by which vitamin D is involved in alleviating behavioral deficits of PD, or is vitamin D helping patients with more general balance deficits through its effect on muscles?

Dr. P is proposing to address this question on both clinical and basic science levels. Her clinical studies will address the attenuation of several behavioral and motor impairments as correlated with various vitamin D levels. Her complementary basic science component proposes to speculate vitamin D's activity in the SNpc of a rodent model. Naturally, this is super exciting to yours truly, so I have offered my services (as an MD, Dr. P needs a collaborative basic science lab in which to conduct the non-human animal component of her studies). It stunned me, in fact, to learn how little has been studied regarding the role of vitamin D in the SNpc and nigrostriatal pathway, given the clear indication that its receptors are prevalent.

Although this will not begin for several more months, at least, there will be more to come as the publishable results unfurl. In the meantime, expose yourself to the sunshine! -- you supposedly benefit more from 15min/day sun exposure than from dietary means (Hall et al 2009; Wolpowitz & Gilchrest 2006). Fanatic Cook elaborates on this beautifully.

empty thoughts X

2009-10-16T20:54:00.000-07:00

I perceive evolution of knowledge not as continually growing and expanding, but as serially destroyed and recreated.

Expansion is a popular chimera of growth. We think of the universe in terms of ever-orbiting away from those centers that we have identified. We think of political change as manifestation of new direction. We think of steps forward in technology as bursting revelations. But are all of these things not brought about by reconfiguring previous conceptions?

Matter is never either created or destroyed, but recycled. On a quantum level, that's almost always true. On a grossly observable level - the level of content - it is created and destroyed all the time. Not a thing has been brought to my attention that would suggest the growth of knowledge proceeding any differently.

why neuroscience?

2009-08-31T18:40:00.000-07:00

In preparation for meeting with the future of my academic career next week, I set about answering some silly interview questions. The first of these was, naturally, "why do you want to do research in neuroscience?" So I thought I'd share it, as this is the first time I think I've even put it coherently to myself...

Behavioral evolution. The field of neuroscience contains the tools that most interest me in terms of searching for patterns in the evolution of behavior. The nervous system – central and peripheral – guides all the other systems of the body through interaction with the world. From the primitive neural web of the cnidarian to the ganglia of the higher animal, it is interaction with the world that makes us what we are. I love neuroscience for attempting to associate corporeal and ethereal phenomena. I love seeking out the physiological correlates of consciousness, and the pathological correlates of behavioral dysfunction. I crave the abstraction of physiology into a medium for mind and consciousness. My own autonomic system excites when connections are made between the evolution of that medium and the evolution of the intelligence it propagates.

on the changing face of science

2009-08-28T12:48:00.000-07:00

I was inspired to pursue academic science by Santiago Ramon y Cajal, the man who discovered neuroplasticity. He was an academic, but first, a scientist and artist. At the end of the first book I read of him was his epitaph, which became the source of my conviction that real science, unfettered by the politics of academia, still exists.

"Scientists should be adventuresome people, restless and imaginative. They should be generous souls - poets at times, but always romantics - and they have two essential qualities. They scorn material gain and high academic rank, and their noble minds are captivated by lofty ideals."

In this process of bolstering my curriculum vitae to attract graduate schools, I am inundated with the mean face of academic politics. It demands that I be recognizable within the scientific community before I am even part of it. Academia must be able to identify me as unique before they accept the burden of my education, but this uniqueness is rightfully represented only by my publications.

While I am the first author of several abstracts, I have not yet published any articles. And while being a first author before having a PhD is impressive, it is significantly less so than being a co-author on a published article. I have a qualm with this particular rule of hierarchy - and with Academia's perspective on publication in general. To be published as a co-author in a scientific paper, you need be involved as little as collecting a key piece of data without having any clue as to its importance to the paper itself. To be a first author, you are either the primary investigator (head of the lab) or you have performed/analyzed/written a substantial portion of the piece. The latter is my case.

I recently mined a book on this subject by Thomas Bender, Intellect and Public Life: Essays on the Social History of Academic Intellectuals in the United States. Among other discussions is that of Academia's role in determining the evolution of science by publication, and how scientists are evolving to become defined by the magnitude - quality and quantity -of their publications instead of their contributions to scientific stride through their careers.

In Cajal's day (the late 18- and early 1900s), publication was a serious achievement, like Galileo's 550 printed copies of The Starry Messenger. Today, it is not unusual to expect an undergraduate student to have their name planted among a list of authors on a paper or two. This is a blessing and a curse. The circulation of scientific discovery has skyrocketed to a point where many articles are freely accessible to the public. However, credit for scientific discovery has become such a bilious diatribe that publications include up to ten co-authors, and the tiniest inkling of participation in the tiniest piece of the article gets your name on the list. Students are recruited to graduate schools based on their publications. Academic scholars are recruited to run labs based on quantity of publication alone, which may or may not sound absurd only to me. The physicist Richard Feynman was asked to head an engineering lab at Princeton because his name was on an unapplied patent that came out of Los Alamos. During the war, Los Alamos was flooded with some of the brightest minds in physics, and the opportunity was taken to exploit any random idea that popped into their heads. A lot of cool shit went down at Los Alamos.

I can't fairly condemn the evolution of publication's importance to Academia, nor Academia's reliance on publication to determine the worth of a scientist. My hope, however, is that quality does not become lost in quantity. I hope that my curriculum vitae communicates that my lack of publication does not represent my throughput or ingenuity...

I have spent over two years with my boss developing a huge project which has evolved from my own undergraduate thesis. The process has involved a scrupulous amount of project design, methodology, animal model development, endless amounts of research and, as goes without saying, an infinite amount of experimentation. As we have been too busy writing grant proposals and collecting alternative data, we have not yet published anything on the many results of this project. Fortunately, my boss has offered me the opportunity to co-author on a textbook chapter and set aside time to write an article on the novel mouse model I have developed before I submit my graduate applications. My boss reminds me of Cajal.

I maintain, sanguinely, that many graduate institutions still have the integrity to investigate the entire portfolio of a scientist before deeming woth investment. That ideal, however, may prove to be too lofty...

ADHD News

2009-08-24T06:25:00.000-07:00

Alright. I adore the Huffington Post. Truly. But this is the most ass-backwards half-written piece I think I've ever seen come out of there: ADHD Meds Abuse.

To paraphrase... "This non-profit study says this (kind of), but this big-pharma study says that (almost) - oh noes!... ... ..."

As a scientist, I take personal offense to this kind of writing. As a human being, I take umbrage to the lack of integrity in an article addressing an epidemic controversy such as ADHD. It's empty. There's not even an argument for or against the methodology of one study or another. There are no details as to how the study was conducted, no questioning the legitimacy of any of it, and the conclusion is that "the study lacks information on whether abusers were teens with ADHD, but anecdotal evidence suggests many are not."

... what? Really? Your conclusion is something that you left until the penultimate sentence to even bring up? And you're not going to expand on it? How the hell did Lindsay Tanner get the frontline with this thing? I'm almost more impressed with the public commentary... <shudders>

In effect, I think this article trammels the purpose of science writing, which is to translate primary literature into layman language. It is NOT to transliterate scientific discovery into utterances of empty and useless dribble. What is the purpose of this article? It can't possibly have had any other intent than to create hysteria, and that is the worst possible use of the media in general. First rule of translating: do not imply or directly suggest things that are completely irrelevant; please use intelligence.

I now firmly believe that if this Remicade business does not send me into remission and I am rejected from graduate school based on medical biases - yes, that is a legitimate possibility - I will have to go into science writing and do my utmost to revolutionize its currently upsetting condition.

on the roles of science

2009-08-23T19:57:00.000-07:00

I've been thinking about how the role of scientific endeavor has morphed since the Scientific Revolution. What it's value has been, and what it has become.

One of our current controversial quests is to take advantage of what opportunity stem cells hold. Is the aspect of reality at stake here as great as that of Copernicus' heliocentric system or Giordano Bruno's infinite universe? Sciences battle with the church exists in the stem cell revolution, but is it as prevalent and restrictive as was the Roman Inquisition? The obvious answer is that no, it is not. Science has an easier time evolving in modern society because our paradigm since the Scientific Revolution has been to encourage the pursuit of knowledge. Since the breakdown and reconfiguration of the Church, theory has become a more friendly phenomenon. Theory then evolves into science much more naturally and with less turbulence. Scientific discovery glides into public gaze with less suspicion.

There are more scientists and, as such, more reason for the public to accept that what the scientific community promulgates. This is something that Thomas Kuhn does not talk about, and I wish he would have. He considers the role of individuals within the scientific community who are more bold than others, and who stimulate acts of revolutionary science. The roles of the other community members, however, are somehow uninteresting to Kuhns concepts.

The role of the scientific community, I think, is to speed up the process of insight. The scientific body gravitates toward one emerging framework or its opponent with the same outcome as the battle of superseding geniuses against the Roman Inquisition. Internal discordance now slows the progress of science instead of the fear of a shift in reality or religious allegiance. It's no less turbid than pre-Revolution, but certainly more urbane... there is no sabotage or torture in modern Science. I actually think that by handing the beast to itself, the Church has simply backed away from the recidivism of the tyrannical father and become the comforting grandmother to those who can't handle theoretical threats posed to reality.

So has it become easier for science to thrive since the Revolution? Yes. Has new knowledge become globally welcome instead of globally feared? To those territories who experienced a Scientific Revolution, yes. Has the quelling of that global fear opened new doors for the free emergence of scientific revolution? Perhaps.

Does revolutionary scientific discovery hold the same earth-shattering importance that it once did? Not really.

Does an individual scientist suggest as much importance to the growth and sustenance of the world as they did during the Renaissance? Well...

I like to hope that we do. But I will need more convincing as my career proceeds.

on the emergence and immersion of geniuses

2009-08-20T11:09:00.000-07:00

R. Buckminster Fuller is an American architect who is known for patenting the geodesic dome design, and for the discovery of the carbon allotrope which is his namesake. He is - probably more accurately - known for the saying; "everyone is born a genius. Society de-geniuses them."

I think that Fuller's own history is a perfect example of his claim. I also agree strongly with this particular statement. For instance, the C60 allotrope known as the Buckyball or Buckminsterfullerene was actually discovered by Robert Kurl, Sir Harold Koto and Richard Smalley in 1985 . Their 1996 Nobel Prize gives these men their due credit, but in the limpid word of chemistry, the R. Buckminster Fuller is wrongly assumed to be a chemist, and the discoverer of Buckminsterfullerene. The point I aim to make here is that Fuller was incontestably a genius, but he is not known as such for the correct reasons.

Socioeconomic evolution has imbued the term "genius" with melange of defining characteristics with which I don't agree. Before I get in too deep with this assertion, I should clarify that I define genius as one whose unique curiosities become manifest. That's it. Psychometrics has tried admirably to find a way to assess intelligence on a relative scale, allowing the siting of geniuses and savants as they arise. In as much as these tests do have some value to designing our current educational system (with which I also have major discordance), they also serve as a societal breech to the acceptance of the creativity from which genius comes.

I am inclined toward the idea that genius emerges from reaching outside of paradigms, and happens independently of academic guidance. Fuller's genius is identifiable in his childhood endeavors into original architecture, tool design and novel propulsion methods; he was twice expelled from Harvard. Nikola Tesla invented the first paddle-less water wheel at the age of 4; he spent 1 term at the Charles-Ferdinand University in Prague. Francisco Goya; the last of the Old Masters and the first of the Modern. Mozart and Galileo... all geniuses oppressed or quelled by economic demand, marketing and immersion into societal constructs.

I supposed this is my way of letting out some steam from the pneumatic build up of my anxiety and ambivalent contention for graduate school.

I prefer to hope that I have something unique to offer the world of intellect and scientific discovery. While I was never a prodigal child, and have most definitely been the product of academia-induced ADD-promulgated study, there is still a chance that some modicum of genius might arise in the later stages of my own evolution.

In short, it is my profound hope that I am playing out Fuller's apothegm in reverse - that I have first been de-geniused by society, and am now in the midst of my journey toward emergence.

chris kelly + the constitution

2009-08-06T14:14:00.000-07:00

On August 4th, the day before President Obama's birthday, Chris Kelly, a writer for the Bill Maher show, wrote a piece on the authenticity of our president as determined by our Constitution, and on the practicality of our Constitution. (that was a commariffic sentence!)

http://www.huffingtonpost.com/chris-kelly/the-constitution-says-oba_b_249730.html

I love the Huffington Post, and I love its impressive array of contributors.

When interpretation is called into question, I almost immediately become bored, feeling that the inherent flaws in relying on interpretation as truth is fragmenting and destructive in itself. There is no direct or obvious interpretation of anything, and so the subject of flawed interpretation is spoiled and dull.

However. I was inspired to propose a response to Kelly's article (to be interpreted as one would perceive Kelly's article). I think that the United States Constitution should be rewritten on a quarterly basis. And by quarterly, I of course mean every 25 years. Additionally, if nobody wants obfuscated avenues of potential conclusion, shouldn't the Constitution be written as a series of premises? "This, That, Therefore such and such at such and such a time, place and intensity." Eh?

I say 25 years because really, how much social evolution can take place in less than that time? The emergence of each new generation seems like the appropriate time to reevaluate norms. The kind of growth that requires a reformation of the nature of the rules is really of a greater ilk than what happens on an annual scale. For instance, the results of great legal cases (which are the brunt of what determine amendments to our current Constitution) should be considered every 25 years, and a consensus should be taken as to which should be implemented in the the Constitution and contribute to the growth of National Law.

How much easier this would be. The clarity - the insane acceptibility. The absence of religious tongue-tying and the degree of misrepresentation and misconstrued allusion! I think the Constitution should be written for toddlers. Clearly, this is the only way the United States will be able to agree with itself as to "what the fathers wanted". Come, now... WE are now the fathers. We beget the carriers of the next stage of humanity's evolution. We are building for posterity. Let us build on foundations that will uphold our direction and progress, not the rickety and wizened inspirations that allowed our nation to become what we have.

This being said, there is a reason I never went into politics. Call me an elitist - I prefer for the decisions to be made my people who actually understand what is going on, what is implied and what is realistic. The populous should be responsible for finding someone trustworthy, and for communicating concerns at a State level. Beyond that, please oh please let the politicians decide whether Obama is trying to kill our grandmothers or not. I hate town halls. If you're going to lobby (and don't be mistaken - I certainly have done my share), please do so in a polite and intelligent fashion. Picketing is for children and hippies.

penrose + consciousness

2009-08-05T18:11:00.000-07:00

Sir Roger Penrose is one of my favorite fellows. He's a mathematician who uses his intelligence to design obscure puzzle patterns simultaneously denying the emergence of consciousness from a pattern for god's sake - what more could you want in a man?

He uses an entire book - Shadows of the Mind (the "sequel" to The Emperor's New Mind) - to discuss how consciousness can't arise from a consistent mathematical system. He begins, essentially, with E=mc2: a number of superposed quantum states in the brain "work" until there is a gravitational difference between their energy and mass. The gravitational significance of this difference causes the states to collapse - or unfold - into one. This single conglomerate state then becomes one observable in the gross physical world - as an action potential in a neuron, perhaps.

At this point, Penrose would seem to agree with David Bohm's implicate order: actuality is the result of probabilistic collapses/unfolding of quantum and subquantum states. We observe light similarly. When medium of a laser absorbs particular wavelenths of light, the electrons of its atoms elevate to their highest state of energy. When so many electrons are excited to this high energy state (population inversion), they collapse together to a lower energy level which results in the emission of light, an observable condition created from a quantum conglomeration.

I have always been somewhat fearful of humanity's discovering the substrate of consciousness and applying it to artificial intelligence. It is comforting that Penrose agrees with me (!) that we will not be able to design A.I. with consciousness in the foreseeable future because it's something we are not nearly close enough to understaning, not to mention being able to coalesce and manipulate.

It is possible to suggest, then, that the connect between consciousness and brain is a physiological exploitation of the vast magnitude of activity in collapsed quantum states. This "non-algorithmic ingredient", as Penrose coins it, also jives with Bohm's suggestions of probability's role in the playing-out of the quantum universe in the gross or actual universe. Could we give our fatty brains such credit as to be the medium by which quantum states become consciousness? This is a question Penrose explores in The Emperor's New Mind, and which I will not dare attempt to disect.

Not at the moment, anyway.

More to come, then.

piaget + bohm

2009-07-30T21:53:00.000-07:00

When we are infantile, we perceive the world in terms of transformations and continuity. When someone's head disappears behind the playpen wall, it no longer exists. And when someone's arms extend from behind a tree trunk, they are part of that tree trunk. And when that tree appears fairy-sized beside our hand, it is not because the tree is far away, but because you have discovered its untouchable miniature right in our presence. A thing happens to us between this time and adulthood that morphs that cononical perception into an interspersed mass of objects and interactions. Language.

Particularly Indo-European languages (English, French, German, etc.) are primarily based on nouns. We think, communicate and perceive based on what language has done to our interaction with the world. We fragment its natural cohesion just by the way we behold it.

Language was once verb-based... transformation-based. Native American languages, Bengali and other endangered linguistics. These were also peoples who interacted with reality as if it were all actualized in the same condition, and from the same piece of cloth and ultimately still cohesive.

inexhaustible matter

2009-07-25T19:56:00.000-07:00

descartes. the man. cogito ergo sum, etc... the dualist.

the nature of matter, he thought, is to expand itself to occupy space and thus be susceptible to physical examination. the nature of the mind is to think. the defining characteristics of these actualities being so isolated, he surmised, they must function entirely individually. and hence consecrated was the mind-body problem.

and if matter and mind are monistic content of the larger whole?

if matter is infinite such that on many levels it is strongly influenced by consciousness, does it not follow that matter and mind may be more highly interactive than our intellectual paradigm allows?

alright. so i blogged eons ago about what it might mean if microtubules were the carriers of consciousness, and communicated by replicative and epigenetic phenomena with DNA. this remains a feasible possibility to me, but i no longer have reason to believe that microtubules and DNA would be the only instance of this mind-matter causality.

if we one day exhume that matter is inexhaustible, then it becomes plausible that mind intervenes its manifestation and directs it. which is not to say that a cup of jello might appear in the hand of a mind that desires it, or that any massive physicality would arise instantaneously. rather, i think it stands to reason that such a relationship would suggest dialectical movement's role in evolution. of everything.

of electromagnetic fields, of life, of geological shifts, of societal constructions and destructions.

societal thought invades a level of materialism that begets a communal EM field which allows the society to move harmoniously while maintaining the presence of its individuals. like plasma.

universal thought invades a level of materialism that commands a shift in organelle function in a species that causes its evolution and simultaneously the subtle evolution of everything with which it interacts.

humanity builds itself on the "shoulders of giants", or rather, their mistakes. have we not always done so at the command of collective consciousness? do inventors not materialize thoughts in response to communal misgivings? do physicists not seek to explain the existence of the world based on the way that our societies now function (or flounder, rather)? and the problems we seek to eliminate in finding the rational answer to the biggest question of them all? if we one day understand the rational of matter, will we not also comprehend our own existence and, in so doing, realize the key to our own harmonious existence?

here is my confound. i do not believe in god, and i do not believe that the universe exists at the will of humanity or its delusioned elitism. without human directive, what is universal thought explained by if not god? where does it come from? the collective minds of every eletron in existence? the Higgs boson?

the only way i can fix this dissonance is by imagining that mind and consciousness it itself something infinite that we as of yet have no means to address. and by that i am comforted enough to sleep at night. killer.

plasma + marxism

2009-07-17T12:07:00.000-07:00

A cyclotron accelerator strips atoms of their outer electrons, leaving them with a positive charge. The resulting melange of free electrons and positively charges atoms is called plasma.

Plasma functions in a collective way, oscillating as a whole, yet its components move freely and individually. When two electrons are completely isolated, they maintain an interaction over a long distance. But in a plasma, this long-range interaction is shielded by the presence of an astronomical number of additional particles. Because this demands that all particle interactions become short range, electrons move freely within the collective, with individual movements.

The long-range interaction, however, has not completely vanished. Rather, its shadowed impetus is what allows the plasma to behave coherently.

If a society could behave like a plasma, an ideal balance between serving oneself and one's community would emerge. Capitalism brags that it achieves this balance of perfect individual freedom experienced while serving the common good. Pragmatically speaking, however, capitalism exists only in the hope that service to the common good might somehow be fomented from claustrophobic nests of self-committed individuals.

Limitation is a creation of the mind.

2009-05-31T21:32:00.000-07:00

Explain the meaning of the statement above. Describe a specific situation in which limitation may, in fact, be quite realistic. Discuss what you think determines when limitation is real and when it is an illusion created by ones psyche.

There is a sturdy platform bridged between the concept of motivation and the achievements it fosters. In the spirit of optimism, there is a school of thought where the only obstacles between oneself and said achievements are the illusions self-created out of doubt and fear. Painting achievement in this light, it is certain that once confidence reigns anything is possible. Unfortunately, there are circumstances in which limitation is quite real, and emerges in a physical form independent of human confidence.

We will examine the case of a young prospective medical student determined to embark on the ravaging adventure of an MSTP dual degree. Wide eyed, and naive of the particular tolls this endeavor will take on her body and mind, she allows herself to be swept into a realm of fantasy in which all the agonizing training is over. She is the proud and excited principle investigator of a neurodegenerative diseases laboratory where multiple studies are undertaken based on the peculiarities she sees in her diagnostically impossible patients. It was all very well worth it, she thinks - now being in her mid-thirties and about to spring a small family into operation, Boxer puppy and all. The limitations were nowhere to be seen; simple incorrigible self-motivation drove her through eight years of MSTP and three more of residency with but a few bouts of fatigue and scratches to her otherwise-intact ego. She got through it all believing that her only limitations were those she imposed on herself through doubt, self-degradation and fear of incompetence. All of these were easily over-ridden by stepping aside to remind herself of her dreams and her ability to see their fruition. ...right?

Well, sadly there are several real limitations to ones ability to succeed in such endeavors. It is not always the case that young prospectives like our optimistic case study can nullify the limitations of their minds with pep-talks and meditation. There are cases where limitation is not illusion, but reality. Our young prospective MSTP student neglected to inform you that she suffers from Crohn's disease and IBS, two conditions which render her indisposed for up to two days at a time at unpredictable frequency. She did not mention that the numbers by which she was to be assessed in qualification for the MSTP dual degree were unformidable, and by no means set her application aglow. She refused to admit to herself that her intelligence was an obstacle, and she refused to resign to her health as a legitimate hole in her stairway to paradise. These, however, were real limitations. It was, in fact, their neglect that was the self-imposed illusion. And so, the young prospective MSTP student was forced to re-enter the present time and condition in order to assess on a more grounded level whether her limitations were real or surmountable.

She remains in limbo, ruminating over and over the possible outcomes of strength of spirit versus strength of body and intellect. It is here where limitation becomes real and must be faced with the understanding that a different stairway may need to be built in order to ascend to that golden future amongst glowing MD-PhDs and their radiating achievements.

Writing Sample #1
00:28:32

something has to skew nature to choose the ones that work

2009-03-10T20:35:00.000-07:00

the argument from Intelligent Design is that the perfection that is life on Earth cannot have possibly arisen from undirected material causes. there has to be an information source. okay, so there's an information source. DNA is an information source. the modern theory of particle physics is an information source. what's the problem?

why is this information source obviously the intelligence of an omniscient version of what has become the human mind? of course there is a directive force behind the interaction of particles that fosters their becoming something more complex which can harness its own energy fields -- even chaos behaves in an orderly fashion -- but it is silly to default to the idea that that force must be a god-like (human-like) intelligence that wished to put a bunch of tiny blocks together and make the organic lego organism that is the Cosmos. this is the problem with calling it "Intelligent Design"; of course it's intelligent design, but there is a surfeit of different kinds of intelligence.

biological intelligence, for one, refers to the ability of organic matter to recognize and interact with other matter: an amoeba, for instance, learning by trial and error to escape the terminal of a capillary tube.

chemical intelligence; the particular bonding interactions of atomic and molecular electron orbitals that result in spike or mechanistic function.

quantum intelligence; the collective formation of fields which become either rays of concentrated energy or building blocks of matter.

lower-animal intelligence; communication by means that humans are barely beginning to understand, and for reasons about which we have know way to assert an concrete understanding.

human intelligence is an evolved speculative tool like any other tool which arose from any other type of intelligence. there is absolutely no reason to think that Darwinian evolution is made null by the possibility of a god-like directive in the form of a human-like intellect. come on. of course Darwin's was a harrowingly rudimentary explanation - it was the first to make the suggestions that it did, what do you want from a less-than-omniscient creator?

Newtonianism was replaced by Relativity was replaced by Quantum Mechanics to explain increasing levels of what we are now accepting might be indefinite complexity innate to existence. God was pseudo-replaced by Linneaus/Lamarck were pseudo-replaced by Darwinism is being replaced by so many other theories of complex evolution. the ID controversy is no different than any other; it's not entirely devoid of merit, but like any other theory, if interpreted and marketed by extremists it loses what logic there is to the basic idea... which is that "nature" (defined as the gross systems perception of life) behaves more like an pallet, and something has to skew it to choose which particles or atoms or bacterial colonies or animals to drive into interaction.

i would be more swayed were it called Intelligent Particle Design... or Intelligent Boson Design... or fuck "intelligence" which is the component that is giving the argument its extremist ammunition and call it Boson Design. or Field Intelligence...

even in chaos, collision begets evolution.

of course... i'm still invested in the omnipotent command of DNA and microtubules, anyway.

the aquarian conspiracy

2008-10-12T15:54:00.000-07:00

"in our need to cope with everyday concerns, we forfeit awareness of the miracle of awareness"
-Marylin Ferguson

[disclaimer: everything i think about this is based on gatherings from Huxley's biography and Ferguson's A.C. theory. please, please please, you guys... hook me up with the rest of it.]

the Aquarian Conspiracy, so dubbed by Marylin Ferguson, is generally misconstrued as yet another mysterious and frightening undertaking by the CIA to flood the U.S. with psychedelics, and control subliminal brainwashing. being called a "conspiracy" doesn't really do much to battle this assumption. in actuality, the word "conspiracy" is used in a much less menacing regard, namely, its literal sense; to conspire means to breathe together. this was a movement of social synthesis in the "consciousness revolution" of the 1960-70's. "aquarian" refers to the aquarian age - following the current (violent Piscean) into one of love, light and liberation of mind [sidenote: this is the most flower-childesque thing you will ever catch me saying - please note that these are not my words and i say them with a healthy ( or unhealthy) degree of cynicism toward blind love and spiritual enlightenment]. in other words, the aquarian conspiracy is not a governmental heist. rather, it's a social paradigm shift resulting from the slow exposure of individual awareness. it just so happens that conspirators, being everywhere, were also staked in the CIA and could bring in Aldous Huxley and Humphrey Osmond to spike the revolution with psychedelics. it's just too bad that the drug was given to the blind and dumb (yes, Hippies) who brought the revolution into the open carelessly and flippantly.

there was, of course, a CIA operation involved under Allen Dulles (a Rockafeller cousin, go figure). in the late 50's, an investigation began into the utility of LSD (developed by Swiss chemist, Albert Hoffman) as a military weapon. oddly enough, Aldous Huxley's personal physician was recruited by Dulles to lead these investigations. as a side project, Humphrey Osmond (the physician), Huxley and some other dude with funding connections began investigating LSD as a therapeutic tool for mental disorders under the guise that mescaline (a similar alkaloid to LSD) produced a Schizophrenic model. this West Coast project resulted in Huxley recruiting his own cult of experimenters; one of these spiked the Zen Buddhism cult, another, the Hippie cult.

having jump-started the West Coast movement, Huxley went back to Boston to teach at MIT and birthed a similar team on the East Coast. during this time, he started another project with Sandoz Pharmaceuticals (Albert Hoffman's company in Switzerland) to contract the mass production of LSD under the CIA's chemical warfare investigation. and by the 60's, Dulles had made the purchase orders.

the reason for the bad rep of the Aquarian Conspiracy is that it emerged at the same time as the anti-war movement, the "flower child" cult of San Francisco and the manifested inundation of LSD, which was introduced by Huxley in his MIT courses as the window to consciousness.

i think we're on the verge of its second wave.

glycyrrhetinic acid

2008-10-11T22:32:00.000-07:00

glycyrrhetinic acid (the potent sweetener of the licorice root) is an expectorant (a mucous thinner) that inhibits the activity of prostaglandin-metabolizing enzymes (causing lots of prostaglandin activity in the digestive system).

prostaglandins (the bitchinest of all hormones) work in concert with the immune system. their badass reputation comes from regulating classic core body fever. endogenous pyrogenic cytokines (interleukins, interferons, etc.), which are produced in excess in response to an invasive toxin or bacteria, stimulate the hypothalamus to synthesize prostaglandins that modulate the body's core temperature to enable activity of immune mechanisms which fight the pathogen (the reason you take Asprin to break a fever is because it inhibits the production of prostaglandins).

(and) the reason that prostaglandins are the bitchinest of all hormones is because they have such an extensive array of physiological activity through the body.

in the digestive system, the all-star fatty acid derivatives instigate mucous secretion from the stomach lining, both protecting and prolonging the lifespan of the columnar epithelium that so graciously allow for the digestion of food. ergo, tea from boiled licorice root, being concentrated in glycyrrhetinic acid which stimulates prostaglandin secretion in the stomach, is protectice against ulcers, inflammation and general rotting of the digestive tract. incomparably, my favorite medicine.

empty thoughts IX

2008-10-10T15:59:00.000-07:00

incidentally, all this time that i've been drooling over the products of the gods of neurophilosophy, i've never really condoned or disputed any of their arguments. rather, i more or less take them in stride and create something new out of them. sometimes, arguments are that badass, what can you do? at the moment, however, i say "incidentally" because i happen to have come upon a precarious internal consensus about individuality.

i like the way Lewis Thomas puts it: multiple personalities is not a pathology - it's when they all clamor for conscious attention at once that they become a problematic condition.

nice, right? here's where it gets tricky for me. it is conceivable to me to believe in the capacity of a body to merge multiple selves, but i also favor the holism in collective consciousness of the universe. so what is it? are we all of the same energy using not only various bodies differently, but various circuits of each body differently? or are we denying the strength of fragmentation in assuming holism is the healthier, safer and more sane alternative?

the altruism consortia

2008-10-09T09:45:00.001-07:00

"...to have no restraint from, no regard to others in our behaviour is the speculative absurdity of considering ourselves as single and independent, as having nothing in our nature which has respect to our fellow-creatures, reduced to action and practice. and this is the same absurdity, as to suppose a hand, or any part to have no natural respect to any other, or to the whole body."

-- i have a huge crush on Joseph Butler

*disclaimer: all chronology is flippant and estimated because i am slothful and have not thought about any of this since theory of knowledge class in high school.

the altruism debacle is ageless, with one of the more sinusoidal flux patterns of any of the philosophical redundancies. this seems a reflection of what generational mascot sits chair of the committee on altruistic behavior.

in the beginning - the 1850's - altruism was introduced as the diametric of egoism... by some dude whose name escapes me, probably because he's French. the conception of the word provided wind for the Hobbesian argument of self-interest as the evolutionary drive of all beings (which came at least a century before), at which time Hobbes was the committee chair, proclaiming from the grave that altruism itself was a demonstration of supreme egoism. sure, he had critics in Hume and Butler, but their projections of altruistic behavior as innate to both the individual and collective self did not rise to power until the Church adopted the altruism consortia in the late 19th/early 20th century.

under Popes Pius VIII-X (yes, i most definitley had to fact-check this one), altruism became the act of love for the sake of being one with God. from here, the Behavioralists took over not only the chair, but the committee majority. reverting to the era of Hobbes' reign, they effectively obliterated the remote connection between altruism and love (on which it was originally based, go ask Compte [huh, apparently i recall his name after all]) and redefined the act as "reckless curiosity." this was, in my harrowed opinion, in reference to the experimental foray into exactly how much tit one could get for tat. a Machiavellian endeavor, if you will.

giving credit where due, the Hippie movement did actually achieve something. tangential as it was (and I consider almost every lasting effect of their stint to be so), they monopolized the altruism consortia and brought back Christian altruism, replacing "God" with "self" and "love" with "collective consciousness" (or, psychadelics, if you prefer to be technical).

however, the reign was short-lived and power was redistributed to the Atheists (i may or may not be accurate in posting Dawkins at the stern, here, but i'm gonna anyway; its done out of reluctant respect). so here we are, withthe committee on altruism manned by those who have given up on surprised continuity of souls and, instead, mellowed Hobbes' altruism to a more gentle tool of survival; taking responsibility for all associated behaviors out of the hands of conscious creatures and placing it in their genes.

i don't necessarily disagree with the current consortia (see post on Microtubules and Intelligence), but my personal philosophy on altruism is a little more toward the end of irrational benevolence... which, i suppose, places me in the neo-Kantian vein. Nagel is our most prominent hope for the next phase shift in the altruism consortia, riding on the back of the forgotten and forlorn Empathetical movement (shudder).

we are not independent organisms; having a more developed intelligence than other species does not now make us exceptions to the evolutionary tactics that propagated that intelligence in the first place. we need our mothers, we learn by imitation, we thrive on continuity of selves. altruism is a mechanism to foster that continuity.

LHC and the God Particle

2008-09-09T15:52:00.000-07:00

First of all, I am way, way too excited for Wednesday.

Murray Gell-Mann simplified the zoo of fundamental physical particles in the 1960's by identifying their similarities in their symmetries. All 80 (or something) types were made up of three quarks. In the late 60's, the first electron micrographs of protons were taken, finding within this fundamental particle three smaller particles of the correct charges, but of indiscernible structure. These quarks, together with the electron and electron neutrino are capable of explaining everything in the actual world. Among the things that remain unexplained is why there are three families of each of the aforementioned, which are identical in every respect except that they are of three different masses. How is it possible that there are, in perceivable existence, three versions of the exact same fundamental particle which perform the exact same function and have what appears to be the exact same structure?

There is another particle, called a Higgs boson, which - should it actually exist - answers the profound question of why and how things acquire different masses, why so many distinct fundamental particles can arise from the same three quarks, why unique particle interactions occur in particular fashions, and exactly which roles those forces play in our universe.

Particles gain different masses because of the different ways in which they interact with Higgs bosons. Essentially (and I'm not going to try to tackle the actual equations because my mind is feabile and my brain is exhausted), Higgs particles are dark matter. They fill every "empty" space in the universe, and as fundamental particles stream through the universe, those that are said to acquire mass are bombarded with Higgs bosons which slow down their streamline. Those particles which do not acquire mass (photons, etc.) are not impeded by Higgs particles... hence, nothing travels faster than the speed of light :)

The Large Hadron Collider at CERN has been designed (and under construction and legal debate since 2003) to see if the Higgs boson can be revealed. The problem with the Higgs boson theory right now is that it is just mathematical theory - there is no physical observation. The idea behind the LHC is that, as it is a particle accelerator, the collision of protons accelerated within it can result in the creation of a new particle. The energy created by the collision is proportional to a mass (this is the real meaning of E=mc^2), and so a new particle with a new mass can result.

This is why tomorrow is so fucking sweet. Tomorrow... Sept. 10, 2008... and more importantly, Wednesday... the LHC will be "turned on," and the first proton beam will be circulated through the tunnel. The Tevatron particle collider in the Fermi Lab outside Chicago is almost as powerful as CERN's LHC, and may have already shown the existence of the Higgs boson, but have not produced any data, as such. The idea of the LHC is to recreate the conditions up to milli-seconds following the Big Bang, and hopefully make strong suggestions about the nature of this minor event in history.

The identification of the Higgs boson would mean remarkable things for the entire world of physics, beginning with the completion of the Standard Model of particle physics. Specifically, the Higgs boson would give a distinct variable to the differences between massive and massless particles, thus making possible concrete suggestions (as opposed to theoretical) about the nature of the relationship between the four fundamental forces (electromagnetism, gravitation, weak and strong nuclear forces).

Ergo... more redefinition and tweaked theory of the Big Bang.

Boom.

REM and memory consolidation

2008-09-06T17:19:00.001-07:00

consolidation of memories - being the enhancement and stabilization following encoding of information - primarily occurs during sleep. there are, as to be expected, several propositions as to the manner in which this takes place.

the medial temporal lobe, including the hippocampal system, is said to mediate consolidation through enhancing innervation to the neocortex. it is proposed that this occurs in several possible mechanisms:

1) the MTL system consolidates by signaling the neocortex to form a new representation of information, and the neocortex subsequently imprints and stores

2) the MTL is the rehearsal mechanism, strengthening connections with the particular cortical regions so they are all activated when the experience responsible for the information input repeats in the future

3) the MTL encodes AND imprints memories into the neocortex. this final option suggests that once enhanced, the neocortex is the final repository for memories. long-term memory is then distributed by coactivation through the higher neocortices specialized for analysis, each contributing differently to the storage of the complete memory. in this way, the neocortex is primed to reconstruct the representation of the information from partial cues.

regardless of which of these mechanisms is more correct than the other, their common function depends on adequate sleep cycles. it has been shown that not only does consolidation occur primarily during slow-wave and REM sleep (Kandel 2001, Sei et al 2000), but also that MTL activity during the information encoding process decreases dramatically in sleep deprived subjects (Drummond et al 2000). both of these observations correlate with decreased cortical metabolism and reproducible memory deficit.

disruption of encoding and deficit of retention in sleep-deprived subjects map onto particular physiological correlates that pronounce REM sleep as crucial for the memory consolidation process. REM deprivation reduces excitability of hippocampal neurons responsible for imprinting information into the neocortex (Kandel). this, as you might imagine, directly impairs long-term potentiation (LTP), or decays any LTP that does occur [ aka, early-LTP is vulnerable to decay within 90 min if not pushed into late-LTP by excited hippocampal neurons which facilitate the genetic transcription of proteins which are biochemically responsible for the actual "long term"]. in addition to LTP, acetylcholine (ACh) accompanying slow-wave sleep just prior to REM mediates consolidation (Power 2004, see neato pic).

the other important gesture sustained by REM sleep is the production of several nerve growth factors, primarily NGF and BDNF. these are both key regulators of LTP (again referring to the strengthening of neural circuit connections in learning and memory formation). this means that their reduction in REM sleep-deprived subjects probably causes the impairment in memory consolidation - supported by the most drastic deficits occurring in the hippocampus.

apparently, episodic memory is most profoundly affected by REM sleep-deprivation... but we don't know why (Rauchs et al 2004). although it wouldn't surprise me in the least if it had something to do with consolidation involving the prefrontal cortex (which has been suggested by almost everyone in the field to be the primary region of activation and most distinguishable candidate during episodic memory retrieval, and also during MTL mediated consolidation (see entry on "episodic memory and autonoetic awareness")). both the hippocampus and pfc are main players in episodic memory encoding and retrieval (id est, emotional memory depicting information in the context which it was learned). the other half of declarative memory, semantic, seems to involve a much different array of hippocampal efferent circuits. and although i don't actually know what the profiles of ACh, NGF or BDNF are in those circuits... i would imagine that they're also different from the activity seen in the circuits associated with episodic consolidation.

ergo, REM sleep: fighting amnesia since the evolution of the higher limbic system.

P.S.

do dreams arise from the stochastic hippocampal inputs to the neocortex?

did dreams evolve from the prolonged quiescent state in reptiles to promote calcium-dependent memory consolidation?

o.O

everything i love enlivens me to a nostalgia for some piece of life i never knew

2008-08-23T15:15:00.000-07:00

... and yet, the nostalgia does not become ruinous when the thing that inspired it disappears or becomes a relic.

Georgia: I think I've reached a place where I can be happy enough with someone's existence to accept their disappearance from my life when the time comes

Wade: Are you referring to someone or something specific? Give me more.

Georgia: I mean in general - I was thinking about how some of my most treasured have drifted in a way that you would expect from casual acquaintances, and some come back intermittently and some don't - I don't have that aching feeling that accompanies heavy loss like I once did

Wade: You are getting used to people fading, that's a sad event

Georgia: Yes, but it's a nice feeling that I can be happy enough with periods of real love no matter their brevity and appreciate that I've been able to reciprocate them without being possessive of them

Wade: True, but it requires a lack of long term expectation, and people too often fall into that regard toward the nature of friendship

Georgia: I'm not worried about that happening. I don't enter into relationships with people with any expectation of their lasting forever, but I maintain the prospect of their becoming something important and treasurable

Wade: Have you always been this way?

Georgia: No, I spent my life being incredibly possessive and emotionally dependent on any love I could get my hands on.

Wade: ...and now, you are adapting to loss by learned helplessness. What will happen to you if you further develop this lackadaisical expectation of connectedness? You will become cold and sad. We are social creatures, and we crumble without connectedness.

Georgia: Don't call it helplessness, because sad and cold is the opposite of my apparent direction which is why I accept it at all. The connectedness does not disappear with the person or thing, is my point... which is why the love remains, made more fervent by weak nostalgia but also made pleasant by the absence of possessive defeat.

... maybe because those i love most are so grandiose - their own worlds - that i can conceive of our collision as being just emphatic and long enough to have made an impressionable entanglement of selves before ricocheting away - worlds gained and only grossly lost.

aspirin and parkinson's

2008-08-21T21:41:00.001-07:00

arachidonic acid is one of the reasons that a high meat diet contributes to early neurodegeneration - it's not just about caloric intake, it's about the amino acids you accumulate. arachidonic acid is a fatty acid precursor to prostaglandins, which are made in excess when neurons die and release arach. acid into the extracellular system, or when introduced in excess through extensive meat intake.

Aspirin inhibits prostaglandin production. inhibited prostaglandin production releases less arachidonic acid to oxidize other cells. less arach. acid allowed to do damage over time decreases the chances of developing Parkinson's disease.

take Aspririn (or any NSAID, really) to avoid PD when you're eighty. but also, eat less fatty meat.

empty thoughts VIII

2008-08-11T17:01:00.000-07:00

1. handedness in mice seems to correlate with a lateralized dominance of dopamine expression; a mouse who prefers to use the left paw has a lower level of dopamine in the right hemisphere (Berneoud et al 1990) [which screws with my mind because in Parkinson's a mouse who has impairment of left paw control has lower levels of dopamine in the right hemisphere... fucking dopamine].

2. human fetuses suck their thumb beginning at the 15th week of gestation. of 75 fetuses who suck their thumbs, the 60 who suck their right thumb all become right handed teenagers. of the 15 who suck their left thumb, 5 become right handed and 10 become left handed (Cabib et al 1995) [so handedness is a developmental thing, not a consciousness thing?... in the vicinity of week 15 the brain is primarily ventricles, aka stem cell pockets, so what, are we talking about dimorphic differentiation as dictated by the notochord?].

3. whether early brain asymmetries contribute more to language development or handedness remains a challenging question (Corballis 2003) [which is damn sweet... that handedness might correlate with language centers, particularly Broca and Wernike's areas localized in the left hemisphere].

4. fibroblast growth factor 8 (FGF8) is secreted from the anterior cortex during development which might be distributed unevenly to the left and right cortical hemispheres, leading to asymetrical topography (Sun et al 2005) [i can't find any studies on whether or not this secretion occurs anywhere near gestation week 15 where striatum and cortex develop from the ventricle cells... and it is driving me mad].

5. normal brain asymmetry is disrupted in individuals with schizophrenia, autism, dyslexia, etc. (Herbert et al 2005; Hugdahl 1998; Falkai 1992) [does molecular regulation conjugate brain asymmetry and handedness?... do schizophrenics etc. demonstrate tendancies toward ambidexterity?!... do all these conditions correlate to oxygen deprivation during critical periods of gestation?!...].

6. 90% of the human population is right-hand dominant. of that population, 95% are also language skill dominant in the left hemisphere. of the remaining 10% who are left-handed, only 70% are language dominant in the left hemisphere (Sun and Walsh 2006).

Then... does handedness actually indicate a significant specialization in unilateral hemispheric function? The hand manipulates the environment, and the contralateral brain maps the sensory information into a model... but is the correlation between left-handedness and holistic, intuitive and musical function of the right brain as robust as it is imperfect? And for that matter, is 90% of the human population right handed in correlation with evolutionary utility of the left brain as a linear, language manipulating analytical tool?

green sulphate umbrella

2008-08-09T08:22:00.000-07:00

there is a problem with the climate change sector of energy policy with which i'm particularly irritated... which is that people are either concerned with greenhouse gas emissions, or chemical pollutants, and no one seems to be considering the implications of both. namely... that they complement one another, they are both causing severe problems and they need to be decreased together, not separately. and this segregation of focus is all well and good except for that it completely destroys the ability of policy makers to address the current climate crises in a comprehensive manner. in the particular instance of these two issues, if one is given more weight than the other, or one is addressed without the other, we could all die anyway via the acceleration of the geophysical phenomena that greenhouse and pollutant gases are currently holding at bay.

namely... "global warming" versus "global dimming." very brief summary before i rant: in the 60's, particle pollution began to noticeably reflect a great deal of the sun's rays which had a cooling effect on the globe. this effect continued as pollution continued, the phenomenon being explained by the increased particles polluting clouds giving water a greater surface area on which to collect, and water molecules take much longer to collect enough to outweigh the particle and cause it to fall in a raindrop. while the water takes longer to collect, it stays in the clouds, reflecting a substantial amount of sunlight and preventing it from reaching the earth's surface. so from the 60's to the 80's, global dimming has protected us against the full assault of global warming, which would have otherwise been roughly two-fold. so yes, while pollution has been the cause of something like 135,000 premature deaths a year, it has warded off the 1,000,000 that would have been caused by the effects of accelerated global warming. but then, in the 80's when Congress adopted the EPA's Clean Air Act, pollutants decreased in the clouds and global warming revealed itself more drastically. and voila, in the 00's, if we want to live, we have to address both, and here is my rant...

this whole business of chemtrailing a sulfur umbrella into the stratosphere, if i'm being honest, doesn't seem like such a bad idea. because the world is having so much trouble - fuck it, because the United States is having so much trouble - deciding whether or not we want to assume this problem is real much less address it, it's going to take a few years to get policy implemented effectively. in the meantime, sulfate has a half life of roughly ten years, so it is in actuality one of the more innocuous short-term plans. shoot up the sky with more crap that doesn't belong in it while we, down on the ground, figure out how to decrease both ghg and particle pollutants from the atmosphere in concert.

reducing ghg requires technological implementation. reducing soot requires tighter regulation. the latter is easily done, while the former seems to be... the cause of increased rate of aneurysm and heart attack in our political leaders... for whatever reason... likely because (like so many socioeconomic crises that are incorporated into its implications) ghg emission is an exceedingy comprehensive nexus.

my point being this: if you deal with ghg emissions alone, we'll experience global cooling complete with drought, famine, disease, loss of populations, loss of species and loss of existence. if you deal with particle pollutants alone, we'll experience accelerated global heating complete with drought, famine, disease, loss of populations, loss of species and loss of existence. ergo... work simultaneously on decreasing them both [and if you're one of those people who thinks increased snowfall in certain areas of the globe this year is a clear sign that global warming doesn't exist, i have some words for your denial]. yes yes, i understand it's going to be oh so very difficult an endeavor... after all, particle pollutants have a shorter half life than do ghg's, and there's math involved, and oh for fuck's sake get over it and alter your nation's productive and consumptive behaviour so that ghg production are decreased more exponentially and particle pollutants more linearly. and then, oh no!, how do we know how much of atmospheric ghg and particle pollutants are from us and how many are natural? what if we accidentally take too much out of the sky and as a result lose oxygen and gravitational pull? [i'm exercising restraint not to comment on the rapture at this point...] after all, there's no way to tell if any of this is actually our fault! so let's continue to mutate our livestock and crops and make sure we adequately feed our greedily unbalanced economic and consumptive habits [i also think that it should be the govt's responsibility to pay farmers for feeding their nation so that we can ween off of this terrible seething monster of supply and demand]... but as per norm, i digress...

if we are indeed going to continue to restrict funding for and forebearance of green technology, then put a sulphate umbrella over our shallow little heads for a few decades while we figure out how to get over ourselves. and no more of this carbon scrubbing shit that cleans primarily sulfur out of industrial burners - if we're going to scrub, scrub both carbon and sulfur; why trap the more benign gas and give the more-difficult-and-expensive-to-remove-from-the-atmosphere gas VIP entrance? clean coal is actually not a bad baby step... since it seems we are going to need some dirt in our clouds for a while longer before the environmental consequences of Bushee's regime wear off and green technology begins to be taken seriously.

physical component of social pain

2008-08-07T21:26:00.000-07:00

on the potentially incapacitating noxious pain of social exclusion, rejection or loss.

leave it to life to knock me upside the head for meandering through a thought like yesterday's...

when Nicole and Anne's moms were lost to breast cancer, when Robin's father was lost to metastatic brain tumors and her mother Diane was then taken by breast cancer a few years later, yesterday when John didn't come in to work because his dad was waiting on the results of a cancer diagnosis (on Friday i had initiated a conversation with him about health and predisposition, self and family, brilliant timing natalie). and then tonight when Cookie went through the ordeal of diagnosing her three-month old kitten with a neural bacterial infection and had to put him down... i suppose i recall the weight that comes down on my heart when people i love suffer.

"it is conceivable that brain circuits for separation distress represent an evolutionary elaboration of an endorphin-based pain network" -Panksepp

sure, it is sensible to propose that noxious pain accompanying an emotional event would serve to focus attention to that event to promote correction and future avoidance. such an adaptation would promote inclusive fitness: death of genetic kin, sexual jealousy, rap and childlessness as noxiously painful stimuli, recognized as aversive would be avoided.

social and physical pain have been shown to share the opioid and oxytocin neuroendocrine systems that work through the cingulate gyrus and periaquaductal gray [as a side note, the PAG is also a sexually dimorphic region specializing in aggressive behavior... larger and more active in males...].

social integration used to mean survival to us. now, we're so hell-bent on independence and establishing self sufficiency that we seemingly strive to eliminate this integration - this is just one example of modern social exclusion, but the first that comes to mind. if we look at our closest cousins, they form strong relationships within their social network because connections to certain individuals mean connectedness to tools of protection, reproduction and food. the most strongly integrated animals are the most likely to survive... this is because we are one of many many species who learn through imitation.

okay. so connectedness is important, and social exclusion can be equivalent to death. therefore, social animals needed physiological mechanisms to help them react to threats of social exclusion, and avoid them. interdependence.

evolutionary theory would suggest something like... as more complex social networks arose, complex response systems within physiological correlates of behaviour probably became associated with already existing mechanisms of threat defense... drumroll... the nociceptive system. [as another side note i loooooove this system. mm.]

if you throw a lobster into a pot of boiling water, it will flap its tail and appear to be trying to climb out. this is actually a nociceptive reflex wherein pain nerves are activated by the heat and recruit a network of other nerves to move the tail in such a way as to quickly escape the threat. this is the same system on which social pain would supervene... but lobsters don't have an emotional correlate to pain [i've written about this before... don't remember when...].

noxious pain gives information about tissue damage to the dorsal horn of the spinal cord and the periaquaductal gray (PAG). the affective experience of pain depicted by activity in the anterior cingulate gyrus that signals an aversive state and motivates behaviour to escape the noxious stimulus. and it is this affective component whose circuit social pain might directly utilize. hot.

these two circuits - physical and social pain circuits - could become associated through very early-on sensory experiences... with physical pain and separation. for instance, when an infant experiences physical discomfort, it is alleviated by physical contact with the maternal figure - what Bowlby calls the attachment figure (1970's). however, this simultaneously teaches the infant that isolation and physical pain go together.

on a more physiological level, it has been demonstrated that the opiates released in infants when physical pain is alleviated during attachment are stimulated to do so by the PAG. this same pain inhibition in the dorsal horn by opiate stimulation from the PAG occurs when adults experiencing social exclusion related pain - death, sexual jealousy, etc. - are able to alleviate it through social attachment. and when they are isolated or cannot otherwise inhibit the affective component of pain, endogenous opioid production does not occur.

freaking cool that social pain to promote survival in social animals may have developed by mapping onto the more primitive mechanism of noxious pain.

so in other words, fuck you, modern independence epidemic. every social or affective pain i have ever experience - death, social exclusion, medical or financial crisis - has been ameliorated by a hug.

electron tunneling

2008-08-03T23:04:00.000-07:00

In case you were wondering what gets me off...

" By comparison of the measured IETS (*inelastic electron tunneling spectroscopy) spectrum of this molecule with the computed one, it is possible to examine the relative intensities of the different vibrational normal modes, thereby to deduce the pathway for transport. We find that the electrons are injected through the terminal methyl group, tunnel through the sigma bridge to the etheric linkage, mix with the pi electrons, pi tunnel through the aromatic, and switch back to the sigma tunneling, through the thiol and out onto the counter electrode (Galperin and Ratner)."

Bit of background... this was a studying looking at molecular transport junctions wherein a molecule is placed between two electrodes and subjected to applied voltage. This kind of analysis shows particular modes of transport pathways for electrons across the molecule by way of interpreting the molecular junction geometry. This is hot shit because delocalization of electrons across molecules - and in particular, proteins - has the potential to give a great deal of information about protein folding mechanisms...

Protein folding is a fairly simple concept: when DNA copies, it translates its code into a sequence of amino acids. The aa sequence comprises what is called the primary protein structure. AA then fold, through several types of electromagnetic interaction, into secondary structure which begins to take on 3D characteristics. Secondary structure can then fold into several different types of final form, depending on the protein's destined function. But for the purpose of where I'm going with this, I'm going to refer only to primary and secondary structure.

there's a reason that computer modeling has trouble accurately replicating the speed in which proteins fold into their final conformation. that reason is electron tunneling.

in proteins there have been found to exist very significant long-distance tunneling currents of superposed paths over which electrons can delocalize across an entire structure - not just between neighboring atoms which was the conventional assumption.

what this means is that an electron localized to... atom A... can enter into a more delocalized, higher energy superposition between atoms A and B. when it yields back this high energy state, the electron can then relocalize to B rather than back to A, if this is energetically favorable. sound familiar? this is basic electron transfer. now imagine the same mechanism occurring between amino acids of primary and secondary protein structures. because the distance between aa is so much greater than between individual atoms, electron coupling falls away and electrons must delocalize via tunneling currents, connected by "bridges" which enhance tunneling along multiple superposed paths within the molecule.

for instance, in the tubulin protein alpha and beta dimers that make of microtubules (previous post) contain a somewhat patterned arrangement of tryptophan amino acids, arranged all within 2 nanometers of each other. because tryptophan aa contain not only an aromatic ring, but a double aromatic ring (an indole), they provide a tremendously stable delocalization site for electron density, and are thought to be key players in the tunneling current in and between tubulin dimers [this is the tunneling that causes the conformational change in alpha and beta monomers that result in the propagation of an electrical signal down their lattice in the microtubule].

the signal is not just propagated by means of the tryptophan current network; there is also a lattice composes of the aromatic substituents of histidine and phenylalanine amino acids, which correspond to an additional three tunneling possible tunneling patterns. this current-strengthening effect is responsible for the nature of the electromagnetic signal as it is transfered down a microtubule, and from one microtubule to another.

it works as such: the transfer of an electron from one space in a primary structure to another space causes a conformational shift which directs the primary structure to take on secondary characteristics. cysteine amino acids will be reoriented such that they are within few enough angstroms of one another to be reduced to form disulfide bridges... hydrogen bonding will cause proline rings to the outer surface of the molecule such that a helix is left handed as opposed to right, etc. the reason protein folding can occur so rapidly is that this works the other way as well: conformational change of the protein as it folds influences changes in the tunneling current pattern so that the tunneling options electrons have are altered (Balabin and Onuchic 1998).

the remaining question, then, is what controls the dynamics of tunneling electrons? something to do with phonons (vibrational degrees of freedom) as produced by tunneling effects, which then enhance feedback between tunneling current and conformational changes. my understanding of electron-phonon interaction, however, is excruciatingly limited.

i must find someone to educate me on this one... quite frankly, i'm tired of staring at primary literature trying to navigate my way around equations for this shit. where is my on hand physicist?... i can't fit this into my theory of conscious DNA until phonon emission finds its place! gr. grumble. pass out.

selective attention vs psychokinesis

2008-08-03T19:39:00.000-07:00

do we see red coats worn everywhere because, coincidentally, an epidemic of red coats was brought to explicit consciousness by selective attention? or do we see them everywhere, psychokinetically, to prove to our inner thinker that they are truly everywhere?

and what's more, which is evolutionarily beneficial?

reproduction used to be the name of the game; now, those of us who have developed higher intelligence are interrupting the expression of our survival traits with a panoply of stimuli over which to ruminate. numerous strains of fly - mayfly, cattle grub, Bembix - have only one objective upon maturity: propagation. they have no mouth. when you live for sex alone you do not need to be attentive to anything else, and, as such, there is no call for your mind to be selective. this works for such creatures, evolutionarily speaking. they fertilize, lay parasitic nests and call it good. there's no hierarchical categorization of voluntary or involuntary attention, and there's certainly no psychokenesis... right?

here's what i think is interesting about the concept of mind over matter: there is no trace of the more basic mechanism from which it evolved that is given any regard in evolutionary biology. whyyy?! because it doesn't appeal to congenital impulses? that's complete crap. psychokenesis is just as relevant to survival as inhibition of return (a cohort of attention which keeps a creature from re-attending to an object), it's just shoved into the corner there is no observable suggestive behavior in lower animals. personally (and also, reluctantly), i think it's a concept just as observable in the morphogenetic fields of an amoeba as in the wannabe-telekinetic demonstrations of humans who think that bending a spoon by exerting more force than you convince yourself to be necessary is proof of internal electromagnetic command (no, not Sheldrake's concept of MF, the Gurwitsch original).

selective attention. psychokenesis.

i'm chewing.

speech, autism and collective consciousness

2008-08-02T12:15:00.000-07:00

“…a creature cannot have thoughts unless it is the interpreter of the speech of another.” -Donald Davidson (1975, p. 9)

Initial response: ...what?!

Secondary response:

The man is suggesting that communication through speech is the only means by which a creature is able to generate thought, implying that language is the primary vehicle of thought, rather than vice versa. I think that's dumb. The primary vehicle of thought need not be speech; it could more than conceivably be entirely driven by behaviour.

Follow me for a minute here.

A thought can be a belief. A belief is based on the way things are in the actual world. The way things are in the actual world can be interpreted through the behaviour of creatures in the world. Even if it were true that belief emerged only in those organisms capable of interpreting the behaviour of others, it doesn’t follow that that interpretation need be of speech. Thought could be generated merely on the basis of interpretation of behaviour for which speech is not necessary.

[note: the necessity of internal language is an entirely separate issue...]

Translating this into an example - as my philosophy professors would demand is crucial to my train of thought - say two primitive children witness an avalanche of boulders cascading down a nearby mountain. They may be standing close enough to the avalanche to feel the ground shake, and that a small stone may ricochet from it’s main course and hit one child in the arm. The child, having felt the sting of the stone, generates a thought correlating bounding stones with pain, and that if such a small stone inflicts pain then standing beneath the whole cascade will deliver far worse. The child can then infer that it is a good idea to avoid being in close proximity to avalanches. And... run. The second child, having witnessed the discomfort expressed by and the fleeing of the first, may infer from his behaviour that it is wise to avoid avalanches. The first child generated a thought about avalanches based on the behaviour of the cascading boulders, and the second child generated the same thought based on the behaviour of the first child... with speech being a component of neither scenario.

Yes, it can also be provoked by speech alone if a creature were to be told by another that an approaching avalanche was potentially very harmful. However, provocation of thought about the avalanche through the latter scenario would require that the creature, in order to recognize the implication of an avalanche from only the speech of another creature, must have seen it inflict harm before in the content of the phrase “approaching avalanche” could have any meaning. This doesn't make it less likely that the creature could have a belief about the avalanche as solely regarded through speech. Rather, it suggests that witnessing an avalanche harming someone does not require speech to communicate that one might want to avoid cascading boulders...

The other confound of the "no thought without speech" theory is that it can be used to argue against thought in higher animal organisms, as people actually do make the argument that non-human animals can't communicate through speech [this is another assumption with which I have extensive arguments]. And while I'm a proponent of learning and memory being entirely biochemically and anatomically structured in some processes, there is also a component of consciousness that becomes necessary to explain the acquisition of the kind of behaviour learned in higher animals. There's a communication that occurs between human and animal in instances of learning that are not classical conditioning, which suggests thought in the mind of the animal as it interprets the behaviour of its trainer or owner, or what have you.

And then we have the instance of Davidson's awkward collision with cases of Autism. Since he purports that to be a thinker you must be a speaker interpreting other speakers, it then follows that Davidson must believe that Autistic people - who have monstrous trouble interpreting the minds of others but who can put together their own coherent thoughts (Baron-Cohen 1995; Harris 1991)- are not capable of thought. Which, as you might imagine, perplexes me. Thought, as I categorize its nature, can exist irrespective of lingual communication, and as such, does exist in the minds of autistic beings despite their inability to interpret the mental states of others through their speech. Since Davidson's original argument was way back in 1975, it's a struggle to get my hands on - but am still trying to locate - his response to this more recent confound to speech being the primary vehicle of thought, and thought being nonexistent without interpretation of speech. I imagine him saying something to the like of, "autistic beings do indeed interpret speech, they simply do so incorrectly and so they are able to have thought, but only based on fallacious interpretation." [and yes, he would use the word, fallacious]. Then again, responding as such negates Davidson's other stipulation which is that to be translated into a thought, the speech of another person must be interpreted as the speaker intended.

What I maintain is that when Davidson originally proposed this theory, it was meant to be applied to a confined arena of communication and interpretation... in that one might not be able to have correctly designed thought unless in response to the speech of others.

Here is where I skid off the rail, but where my train gets interesting.

In terms of collective consciousness... it would seem that interpretation of speech were completely devoid of purpose, and that Davidson's theory would be completely null. If we are all linked by consciousness (and that includes non-human animals on the level at which they exhibit it) then interpretation of speech is a useless tool except to distance us from being aware that collective consciousness might exist. So there we have the collective conscious arguing against the utility of speech. Then again, if collective consciousness were a fully functional medium, we would never misinterpret one another's speech... or letters... or online chatter... would we. But by the same token, would autistic beings - under the condition that they might even be able to participate in collective consciousness - cease to have this symptom of not quite being able to grasp the mental states of others as portrayed by their speech or any other means?

So perhaps, if we were, as a species - or as a kingdom of organisms, for that matter - to become aware of our collective conscious, would our interpretation of one another improve? Would we disable the function of war? Wouldn't we have a more comprehensive understanding of the international economic dynamics such that "globalization" and recession could be side-stepped entirely? Would sociology even be necessary?

And there you have it. Thought as independent of interpreting speech. Davidson, I like you. Don't say dumb shit.

microtubules and intelligence

2008-07-15T21:13:00.001-07:00

beginning with a personal aside, i love microtubules. remember in elementary school when we learned how to draw a little ovoid bubble with various organelles scattered haphazardly inside? my teacher pulled me aside to ask why in the world my bubble's organelles were surrounded and overwhelmed with what looked to her like chicken scribbles. and i said, those are the microtubules. she looked at me as if i were retarded, but i knew i was accurate enough in my depiction and she just didn't know what to make of it. i knew they were important... i just didn't bother to explore how important they were until neurochemistry class last year. you don't notice at the time when you're taught about basic cell structure and mitosis that microtubules, which compose the cytoskeleton and radiate from the centrioles, are really performing the most exquisite of tasks. this is my mental escapade into microtubules as they might pertain to that most elusive phenomenon, intelligence.

...

microtubules (MT) are constructed of thousands of tubulin proteins, which are dimeric proteins which orient into helical tubes held together at the seems by MT-associated proteins (MAPs). the MT of any system - amoeba or neuron - make up a network which is generally acknowledged as being the skeleton of the cell, and is, in my opinion, extraordinarily underrated in that role.

in the 1980's, Stuart Hameroff proposed that MT also compute. this was based on both the predisposition of MT to self-assemble and disassemble via the aid of MAPs, and collective network oscillation based solely on nearest neighbor interactions (these being the swapping of a free electron between alpha and beta subunits of the tubulin dimers). Hameroff's theory is primarily dependent on nearest neighbor interaction. to be brief, this interaction refers to the electric dipole created between the alpha and beta monomers of each tubulin protein: this is created by the 18 calcium ions bound to the beta subunit, creating a slightly negative orientation toward the alpha monomer. namely, as an energetic wave passes through a given MT region it would excite the free electron on the beta subunit and shift it toward the alpha, thereby changing the molecular conformation of the dimer. this change in conformation would subsequently excite all its neighbor tubulins to exercise the same behavior, resulting in an electric wave being propagated down the length of the MT. and they did some badass computational modeling of this theory which showed that by said rules, MT could indeed be stable, signal-perpetuating structures...

one of the immediate problems with the Hameroff model is that it was designed at a temperature of zero... such that signal propagation was an artifact of design, and not explicitly reminiscent of those rules governing biological signals. [to note, this actually doesn't seem problematic to me because it just implies even a the level of the zero point field this mechanism is probable, but...] because physiological conditions are what they are, and due to the patterns governing tubulin subunit interaction as well as the helical nature of the MT themselves, a new theory of signal propagation potential was proposed by Jack Tuszynski (Canada gets a brownie for that one). the stipulation was that MT could be electromechanical signal transmitters only helically about their circumference... in the manner of a spin glass.

the spin glass behavior, put simply means that because of its geometrical orientation a system can't minimize interaction energies across its area simultaneously (a.k.a. magnetic frustration). so for MT, that means propagating a signal in somewhat of a spiral manner along its length which yields a similarly patterned signal transmission between neighboring MT. because they are hexagonal sheets rolled into tubes, MT have a seam - this is where magnetic frustration occurs as the propagating signal tries to navigate the tubule circumference. despite this obstacle, the tubule length allows for propagation. the equations for this type of system are exceedingly complex and just glancing at them makes my heart sink in defeat... but i trust Dmitri Nanopoulos (who is my superhero of the day) and the modeling enough to be profoundly inspired by the idea that my poor neglected, favorite organelle might have such a role in intelligence (i'll get there...)...

so what does this model mean to the microtubule network as a transmitter of signals?

this is bitchin - hang onto your pants. the spin glass model allows MT networks the capacity to adapt to the demands of neuronal signaling.

if MT are in and of themselves an adaptive network, as suggested by Nanopoulos' and the nature of spin glass perpetuation, that potentially translates to every individual neuron being an adaptive network. during the process of neuronal plasticity, such as learning and memory, this is a conceivable explanation of how particular proteins are recruited to synapses to strengthen them after a particular pattern of neurotransmitter activity (an otherwise mechanistically elusive characteristic of long term potentiation).

let's take a step back and see if i can do this anywhere near coherently... i know i'm verbose as hell, bear with me.

i think... that when Daniel Dennet and David Chalmers look for physical structures on which consciousness and intelligence might supervene, they are not looking small enough. namely, the structures they are looking for (as well as Francis Crick with the claustrum and everyone else with the pineal gland) are neural pathways and specific brain regions. it makes little to no sense to me to suspect that such a comprehensive force as consciousness would supervene on a single structure or originate from a single neural circuit. i like the notion that said phenomena arise from the translation of electromagnetic wave collapse by microtubules... which are everywhere.

in addition to all the computer modeling and quantum computational theory, there are the correlational studies. colchicine, a tubulin binding inhibitor, causes retrograde amnesia in goldfish. tubulin production skyrockets as soon as baby rats first open their eyes to EM radiation, and correlates with peak learning and memory in chicks. on the human level, there is Alzheimer's disease, in which the most prominent biochemical and physiological markers are amyloid plaques and neurofibrillary tangles - the latter being comprised of MT stripped of MAPs and left to aggregate into useless clumps. so here we have examples of the effects of dysfunctional MT on multiple levels of evolutionary development and cognitive function.

this organelle, to my thinking, is the most beautiful candidate for housing intelligence. it is the beginning and the end of life, from mitosis to decay - defining nucleation of a cell by aligning and separating chromosomes, propagating EM signals, responding to IR light and dissociating upon cell death. they are intrinsic and critical to the very existence of every cell.

okay. if you've made it this far, prepare to be rewarded by my coming around to making a fucking point.

take, for instance, a paramecium - a single cell with no nervous system, only MT networks. a paramecium, if sucked into a capillary tube, will find an escape route... and when sucked up again, will find its way out quicker and quicker with each subsequent trial. this study, lead by Joseph Huber in the 1970's describes a mechanism for learning and memory in this single cell system with no neurons. intelligence without a brain [or... the brain of single cell systems is represented by the centrosome! but we won't go there yet...]

if learning can be achieved in a paramecium, what sense is there in attributing intelligence in more complex organisms to solely the strengthening of synapses?

what is to say that intelligence doesn't supervene on MT networks and that consciousness is a separate beast emerging from the larger complication of neural networks?

[on which note, this is why i don't think computers will achieve consciousness in the near future - or i hope not, rather - because neurons are so very much more complex than on-and-off switches, or binary decoders, or all-or-noners as implied by the direction of A.I. research]

to wrap this up... and in the interest of circulating back to not only intelligence and possibly consciousness but the evolution of these phenomena (as well as others), i think of this: microtubules bind to DNA - regardless of chromatin and histone orientation, which has profound implications for the quantum processes of epigenetics - through MT associated proteins, and affects its synthesis by facilitation or inhibition.

whaa?!

through MT perpetuation of EM signaling, or whatever the hell wave collapse results in, DNA may have an intelligence of its own. screw morphogenetic fields... evolutionary process may very well be directed by the very biophysical matter that also genetically codes for it all. what if it's really all in the DNA?

it's entirely conceivable to me that DNA contains the code and the energetic blueprint - that its interaction with microtubules allows it to translate this into initial interaction with the explicate world - that this explicate interaction subsequently feeds back through the nervous system into MT networks which then propagate new signals from which intelligence and consciousness emerge.

i love microtubules.

dimethyltryptamine

2008-07-11T02:21:00.000-07:00

this is a drug synthesized by the pineal gland during REM stages of sleep. it's said to have something to do with the vivid and sometimes euphoric contents of dreams, which also occur during REM. due to its otherwise elusive function in the brain/body and association with the oddball region (pineal) it has, therefore, been postulated as the chemical substance of consciousness.

"Hallucinogenic effects were seen after 0.2 and 0.4 mg/kg of dimethyltryptamine fumarate, and included a rapidly moving, brightly colored visual display of images. Auditory effects were less common. "Loss of control," associated with a brief, but overwhelming "rush," led to a dissociated state, where euphoria alternated or coexisted with anxiety. These effects completely replaced subjects' previously ongoing mental experience and were more vivid and compelling than dreams or waking awareness." (Strassman et al. 2003)

Strassman, a psychopharmacologist at U. New Mexico is one of the first to postulate that DMT is in fact synthesized in the pineal gland. although it seems to be produced in other regions of the body as well, as it has been found in urine, blood and cerebrospinal fluid (Jacob and Presti 2004), although thought to be an insignificant metabolic byproduct. i guess because DMT is synthesized from a serotonin intermediate it followed, for Strassman, that this particular tryptamine could be produced by and secreted from the pineal gland. but nobody really knows where endogenous DMT comes from, suffice if to say, the body uses a pretty wide array of tryptamines (these are primarily monoamine neurotransmitters and hallucinogens), including the melatonin and serotonin produced in the pineal.

serotonin is supposedly converted into DMT by the pineal during REM sleep, playing a role in dream activation (Callaway 1988). Strassman thinks that when these levels get too high persons experience "mystical/spiritual consciousness." he thinks - and as of yet he has no chromatographic/spectrophotometric data to suggest this - that DMT over-synthesis occurs during birth, before death, near-death experiences and deep meditation. in the 1970's, it was speculated that DMT levels might have something to do with Schizophrenia... but the results of these studies were inconclusive (Angrist et al. 1975, and others which escape me...). what i would like to see is a correlational study comparing systemic and cerebrospinal DMT in healthy control subjects to those exercising deep meditation.

in the Strassman study cited above (2003), it becomes suggested that endogenous DMT may function as did trace amounts of DMT; namely, the chemical would be a non-hallucinogenic. returning to the Calloway proposal that DMT participates in dream activation, it would seem like the job of endogenous DMT would be to do activate hallucination, not suppress it. but that's only if you're of the opinion that dreams are hallucinations...

okay, so we have an idea of how DMT acts in the brain... sort of. both DMT and it's precursor, tryptamine act through a recently identified trace amine receptor (TA, localization unidentified but interacting with the dopamine reward pathway). but since i'm mostly curious about it's production in the brain as relevant to the pineal gland and consciousness, we're going to move in that direction instead...

as noted in the Schizophrenic studies, DMT can also be found in the peripheral nervous system and systemically. this would imply that it can be synthesized outside of the brain, and this idea is supported by the systemic localization of indolethylamine-N-transferase (IMNT). IMNT is the enzyme that tryptophan to make methyltryptamine, which is methylated again to yield dimethyltryptamine. this implies two things:

1) DMT can be synthesized in peripheral tissue, and subsequently cross the blood brain barrier... which is uncharacteristic of most neurotransmitters.
2) since during the stress response the body produces excessive amounts of tryptophan, DMT has implications as a non-hallucinogenic, as proposed by Calloway...

so why does Strassman insist that endogenous DMT is produced in the pineal gland, and is a propagator of the hallucinations that deem it worth of sustaining the weight of consciousness? let's explore...

well... so aside from IMNT being part of the peripheral system, the pineal gland is home to quite a few other methyltransferases.

...that's it.

there's also the theory that DMT must be produced in the pineal because it has something to do with calcification of the gland, but that is not Strassman's theory, and even if DMT does play a role in calcification, that isn't sufficient to conclude that the tryptamine is produced there.

so you've got your aging pathology studies that note pineal calcification in response to abnormal secretion of melatonin (Sandyk and Awerbuch 1992), and your pineal calcification in response to excessive calcium influx and significantly decreased metabolic activity that would otherwise regulate calcium levels - characteristic of aging and essentially all aging pathologies (Krstic 1986).

link between calcification and melatonin? fine, i'll take it. link to dimethyltryptamine.................... come on, really? there's nothing? there gots to be something...

evolution

2008-07-08T20:57:00.000-07:00

what is encoded within DNA is the same for every cell in your body; every cell is encoded to have the same molecular and biochemical capacity. and yet, cells differentiate to express this coding in particular ways. dopamine cells express different segments of the genetic code than do spleen cells, for instance. chemically, these different cells are very similar, but from them emerge larger cytological shapes (organs) with entirely different gross function.

the architectural differences between organisms are not in the building materials, nor the energy involved in their design, but in the underlying blueprint. geneticists and embryologists once called these morphogenic fields: a cluster of cells able to respond to local biochemical signals so as to differentiate as a group. this original morphogenetic field hypothesis of Alexander Gurwitsch's means that a region of cells could be directed to become partiular tissues, organs and forms, and it explained how an embryo could be cut in half, and still the whole final form would develop. the modern appreciation of morphogenetic fields, though, has been modified by botanist Rupert Sheldrake, who has redefined the morphogenetic field to encompass an energy field surrounding these cellular clusters. Sheldrake's fields, then, contain virtual future forms which attract the developing organism toward them.

...

the principle of superposition states that the world can exist in any of many possible configurations of wave-particles and fields. what David Bohm, then, calls the explicate world is the result of the observer "choosing" between various patterns of constructive and destructive wave interference. from this "choice" emerges an individual field from the many possible fields contained in the implicate world. when an observation is made the wave function derived from Schrodinger's equation, which represents one of the possibilities, collapses and then corresponds to one said possible outcome.

superposition is also the basis for Fourier's laws suggesting infinite complexity in th universe. this infinite complexity is complementary to the implicate order in that it defines it as infinite potential from which the finite explicate order is derived.

this infinite complexity provided by superposition of wave-particles gives substance to the idea of an ever-expanding universe, as, with time, more and more of the infinite possibilities are "chosen" to emerge as explicate fields. said expansion, in turn, supports evolution as more potential complexity is incorporated from implicate to explicate. it also supports regression of some complexities as explicate forms both feed back and revert to implicate forms. and the notion of the implicate order fits in quite nicely here, i think, because it is at the plane where possibility crosses over into actuality that quantum mechanics fails, and it does so because quantum physical equations don't describe anything actual, but merely probability of the collapse distinguished by the observer... "chooser."

[my opinion for the moment is that the observer does indeed have complete control over the actuality of things on a quantum level. however, i don't believe that observation of more gross physicalities (animate and inanimate) has an effect on their overall condition. put more clearly, i don't believe in the power of modern humans to harness telekinesis, or change the final form of rocks with their eyes... i merely acknowledge that the activity of individual or clusters of smaller particles (electrons, fluid behavior, chemical interaction) may be subject to manipulation. and i think Sheldrake is a little obtuse in his rationale of morphogenetic fields explaining telepathy.]

so who is this "chooser?" whose observation directs evolution at the level of the wave-particle by collapsing infinite possibility into finite actuality? is it in the hands of the mind, or the zpf?

i'm intrigued by the idea of answering addressing these thoughts using the morphogenetic field hypothesis... as a combination of Gurwitsch and Sheldrake's notions (because Sheldrake takes the abstraction a bit too far and Gurwitsch not far enough). Gurwitsch goes no further than explaining that a whole embryo, when cut in half, continues to generate as a whole due to communication between cell clusters (biological MF's). why? because as in the case of magnets, the whole field is contained in every part such that if you chop a magnet in half, each chunk still has a full magnetic field with north and south poles complete with field lines. it is this phenomenon through which Sheldrake later jumps to evolution of the universe being directed by morphogenetic fields as magnetic fields as opposed to clusters of cells responding in like to biochemical signals. Sheldrake's MF's (physical MF's), then, would be the directors of those biochemical signals.

where i am skeptical is concerning the point at which DNA and G-S morphogenetic fields would interact. certainly it's possible that transcription and translation of DNA into differentiated final forms could be guided by an electromagnetic field; if a field is holographic and can differentiate potential complexities into finite actualities, why not, right? but what is it that would make this interaction a necessary explanation of evolution?

[to clarify, Sheldrake is somewhat of a leech hippie who is overstepping the smaller inconsistencies of morphogenetic fields in order to explain telepathy. what he's suggesting is cool; the idea that the mere existence of a form is sufficiently helpful to allow the same form to come into existence somewhere else. and yes, evolution could be based on an idea like this. HOWEVER. Gurwitsch's morphogenetic fields were proposed in the 1930's, long before Rupert the fagele...]

...

genes. genes code for proteins. but they don't explain the final destination of cells, tissues, etc.; they're necessary but not sufficient for the final form of an organism, as such. so morphogenetic fields would supposedly direct the hierarchical organization, and the evolution of genes and the products of their encoding.

neat. how?

they have memory, says hippie Sheldrake. morphic resonance. that's right. morphic resonance refers to the communiction between individual morphogenetic fields. MF's which contain only information - no energy or architectural materials - hold memory of forms which they have directed in the past. which actually reminds me of Jaques Benveniste's studies that demonstrated water retaining memory of IgE antibodies that weren't actually in solution any longer (via antigen immunoreactivity). the MF explanation of his findings would be that water retained memory of the antibody because the morphogenetic resonance of fields in the liquid retained the memory. but this was years and years ago and i'm getting off track...

...morphogenetic fields. evolution. memory contained within morphic resonance. and while i approach this theory with scalpel in hand, i will remind, too, that there was a time at which DNA was no less abstract and metaphysical an idea than morphogenetic fields are currently. okay, back...

Sheldrake suggests that the blueprint memory in morphic resonance is supervened on the inference patterns of waveform activity. lovely. how does this resonance among MF's direct alterations in gene expression so as to dictate evolution? it ends up being very similar to the idea of acquired characteristics... a phrase which makes biologists cringe. grossly, acquired characteristics refers to Lamarck's principle that adaptations of individual organisms could be passed to the next generation. based on Mendelian genetics and observations of inheritance, Lamarck's theory was abandoned. now, with morphogenetic resonance, it is somewhat resurfacing, if only at a quantum level. a change in the environment of a population of an organismic species can supposedly trigger a tuning-in to new ranges of the possible outcomes described by superposition, resulting in a new sequence of genetic changes. which is to say, the MF would respond to changes in the environment, morphic resonance would retain memory of said MF adaptation, and the field would then alter transcription of DNA within the cluster of cells under dictation of that particular MF.

while this is a badass theory and a neato explanation of evolution as controlled by magnetism... it gets a little too magical for me here. i like the idea of electromagnetic fields creating condensed and localized fields from which matter and mind emerge, but i'm also hugely skeptical of the degree of realism that... seems to be missing. the realism, then, returns to my original question: as "choosers" of actuality from infinite possibility, how would morphogenetic fields interact with DNA to direct trascription?

it is because there is no algorithmic explanation for why genes are translated in the manner that they are that morphic resonance and morphogenic fields are so appealing. they allow for responsibility to be supervened on a substance (or physical force, as it were), which is more attractive than responsibility arising out of nowhere. however, without algorithmic definition or non-circular logic, MFs also seem to arise out of nowhere...

it seems like the cluster of cells under the dictation of a given morphogenetic field would be aggregated by said field. then again, it's a question of who came first, the chicken or the egg.

but.

were it the case that morphogenetic fields arose... out of some essence described by a combination of quantum mechanics and relativity... that they could effectively gather un-programmed cells, and direct the biochemical pathways which determine the genetic sequences that are transcribed for that particular group. magic.

then again, there's the issue of the role of consciousness as the observer. how can these collapses of genetic possibility into actuality occur when a meaningful combination of genes already exists to be translated? does the collapse occur before the genes are in place? but this gets into concepts of spontaneous DNA formation which i'm not ready to flush out.

my brain has no idea where to go from here.

...

when think about evolution, i do so in the context of evolution of the universe... none of this "earthly organisms evolve but the universe is quintessential and eternal" crap.

the big bang... from the percept of morphogenetic fields... would go something like... the emergence of form being made possible by a progressive cooling process that began with the sun spitting out electrons at 2500 degrees C, which cooled enough to coagulate into atoms which cooled enough to aggregate into molecules, etc. and this progression occurred as novelty with endurance such that persistent novelty didn't result in complete chaos. i like it. i'll develop it later...

meat machines

2008-07-06T11:00:00.000-07:00

"we are automata entirely controlled by the forces of the medium, being tossed about like corks on the surface of the water, but mistaking the resultant of the impulses from the outside for free will" - Nikola Tesla

i'm about to disagree with my hero - my high school english teacher would shit himself in exaltation right now.

i agree that we are - because we are meat machines built of subatomic wave-particles - automata in the mechanical sense, our medium being the zero point field, i will also agree that we are tossed around on it like corks. however. i will firmly stand that this does not eradicate free will.

so here's why this works. and it only works under the pretenses of a monist world - one in which there is only one substance that makes up reality, which is to say, mind substance and matter substance are really both one energy substance [and yes, in terms of being corks, monism requires Bohm's gnosis: in order to bobble on the surface of the implicate zero point field, our meat machines need be explicate... elsewise, gamush] . this eliminates the fragmented and confused amalgam of the Western worldview. which is fine with me, because on the quantum level the monist view is the only one that really makes sense anyway. matter is wavelike; it is waves of possibility which can be in two or more places at once as it emerges from the superposition of quantum possibilities.

quantum objects, then, exist as the superposition of these possibilities until our observation collapses them into an actuality, or a single localized event. this is to say that observation alone transforms existent possibility into an actual event - causation. this is how the mind exercises free will.

Newtonianly speaking (muddled laugh...), the theory of causation is an upward theory: causal interaction moves from the micro-level quantum particles up to the macro-level brain and consciousness. this ordains causal power to none other than interaction between quantum waves. the problem here [keeping in mind the monist idea that matter and consciousness are both comprised of wavelike possibilities] is that if there were only upward causation in the world, our persons, as nothing more than material possibility, would not feasibly be able to cause the collapse of other waves of possibility into actuality.

ergo, downward causation gives consciousness the power to choose between material waves of possibility provided by quantum objects.

there is, of course, a paradox here. downward causation is discontinuous... mostly in the sense that it is circular: the observer is essential for the collapse of possibility into actuality, however, the observer in itself is merely a possibility before the collapse has taken place. so... there's something that needs to be algorithmically defined in the distinction of a monist world...

nonetheless, monism is how i've rationalized free will. sorry Tesla.

we are all of he same electromagnetic field energy (which arises from zero point). it is the fuel on which everything physical - animate and inanimate - runs. in the body, the field moves through subatomic processes, molecular reactivity, tissue function and organ cooperation. as it moves... as it interacts with the meat machine, two things occur (obviously more than two things occur, but for the sake of coherency...). first, the matter itself is altered with each interaction - this is upward causation. as in the brain, when you learn something new the biochemical feedback cascade mechanisms in the synapses at work are changed such that the next time the learned issue is encountered, the brain responds with increased sensitivity, or biochemical familiarity. second, as the field moves through the meat machine, the wavelengths produced in the zero point field interact with each other to produce interference patterns which (along with Gibbs free energy which i haven't fully reasoned yet but have insisted is involved) produce consciousness. mind is, then, a byproduct.

this is why free will still works. if mind is an emergent property, then we can all be explicately run by the same electromagnetic field, but as it interacts differently over space/time with our differently sensitive meat machines, different minds are produced. and because mind then has some control over the guiding of subsequent energy through the machine - downward causation - there develops a level of free control over the ultimate behavior.

i'm still working this out... it's entirely fractured thought at this point.

survival

2008-07-05T09:12:00.000-07:00

“Relation-R, unlike identity, is a relation we can bear to more than one person. If this is what is important, what matters to me in my survival is not whether “I” survive, but whether someone who is sufficiently R-related to me does. …Although others will not directly remember events because they happened to me, they may certainly know of events because they happened to me. To the extent that such connectedness, and not identity, is what matters to us in our survival, the second kind of connection may be nearly as good as the first.” – C. Korsgaard

Onely, relation-R is the Parfitian term for psychological connectedness and continuity... which is to say, cross-person connectedness of memory and character. Twoly, Korsgaard is suggesting that if the psychological continuity and connectedness between persons is what constitutes survival, then one person’s mere knowledge of an event happening to another person is enough to conclude that the second person is surviving within the first. When I wrote a paper on this a few years ago, my stance was to disagree with this notion of sharing relation-R in parallel because I decided that it was the nature of survival to occur in a chronological fashion. I argued that relation-R could not be shared in parallel because continuity between a person’s psychological state at one instant could only be continuous if it is shared with another person at a later instant.

My thought process at the time was this: my neighbor may know a great deal about me, but it cannot be said that I survive within my neighbor simply because they know a great deal about the nature of my present perceptions and decisions. There is no descendant association between us, therefore there is no continuity. If there is no continuity, then relation-R cannot be said to be shared between us because relation-R is dependent on both connectedness and continuity. Therefore, I cannot be said to survive in my neighbor because we cannot be sufficiently R-related. In this way, contrary to Korsgaard’s statement, knowing of the events that happen to someone is not sufficient to conclude the survival of the first person within the second; two persons must be both psychologically connected and continuous.

For example, something along the lines of... my neighbor may know a great deal about me, but it cannot be said that I survive within my neighbor simply because they know a great deal about my present perceptions and decisions. There is no descendant association between us, therefore there is no continuity of person because the nature of my person must be passed directly from my body to another through replication of the meat machine. Following then, that if there is no continuity relation-R cannot be said to be shared between us because relation-R is dependent on both connectedness and continuity. Therefore, I cannot be said to survive in my neighbor because we cannot be sufficiently R-related. In this way, contrary to Korsgaard’s statement, knowing of the events that happen to someone is not sufficient to conclude the survival of the first person within the second; two persons must be both psychologically connected and continuous.

Why I was convinced that psychological survival was a chronological endeavor... I don't remember. It's entirely possible that it was pulled straight out of the ass crack of neverland. Because of late, I'm almost convinced that any person can survive within any other. Perhaps the biologist in me... sees survival implicitly containing the notion of passing on pieces in the manner of replication. Survival is all about the nature of the replicator. Survival of a person seemed like it would have the same type of rule... but if all persons emerge from the filtering of energy through differently sensitive meat machines, that rule disappears. If our persons - our minds - are superimposed on zero point energy, this novel form of energy spread out over the entire concept of space/time then overlaps with the energy fields of all other persons.

This overlap would seem to have some level of implication for continuity in the Parfitian sense...

Parfit describes survival based on the continuity between being A and beings B1 and B2 (the products of, for example, the fission of being A's brain... or asexual reproduction if you prefer so think of persons as amoebas). That is to say, when being A splits into beings B1 and B2, being A ceases to exist because even though being A survives in both B1 and B2, it does not survive in whole and thus cannot maintain an identity. And if all persons are connected on the level of the zero point field, and the nature of the universe is to function under the laws of the holomovement (or something like it) it stands to reason that survival of being A within both B1 and B2 would be conceivable. If every element and waveform carries within it information about every other element and waveform, then the transfer of these from one omega 6 machine (yes, i have given the brain a term of endearment...) to another, if only in halves, seems as though it would carry enough information from one to the other to constitute a complete continuity between beings A, B1 and B2.

So even in the Korsgaardian profile, the implication is that even though identity probably isn't retained, the continuity that is there is sufficient to constitute survival: "although others will not directly remember events because they happened to me, they may certainly know of events because they happened to me."

Alright Rambler McGee, point of order.

So. I'm airing on the side of relation-R being sufficiently shared such that it is possible for any person to survive in any other. In what capacity, I'm not yet decided (surprise!?). However, it does begin to hold implications for the nature of recurring or past life experiences. Do our persons survive through fission (death) and fusion (reproduction) to retain continuity across lines of space/time? In denial of the Cartesian Order, probably. But do persons survive through parallel continuity to other people in the immediate space/time schema? I'm still not convinced. I still have some grounding in the energy being passed through the meat machine in a more chronological fashion. My neighbor's person isn't necessarily a shared part of my person just because we know some things about each other's physical lives. On the other hand, I do fancy the notion of parallel connectedness in terms of influencing energy flow, or "sending good vibes," or what have you... just not in terms of survival of character identity.

Tesla

2008-06-27T19:44:00.000-07:00

from "Man's Greatest Achievement" - would could I have but known this man...

There manifests itself in the fully developed being - Man - a desire mysterious, inscrutable and irresistible: to imitate nature, to create, to work himself the wonders he perceives. Inspired to this task he searches, discovers and invents, designs and constructs, and covers with monuments of beauty, grandeur and awe, the star of his birth. He descends into the bowels of he globe to bring forth its hidden treasures and to unlock its immense imprisoned energies for his use. He invades the dark depths of the ocean and the azure regions of the sky. He peers into the innermost nooks and recesses of molecular structure and lays bare to his gaze worlds infinitely remote. He subdues and puts to his serves the fierce, devastating spark of Prometheus, the titanic forces of the waterfall, the wind and the tide. He tames the thundering bolt of Jove and annihilates time and space. He makes the great Sun itself his obedient toiling slave. Such is his power and might that the heavens reverberate and the whole earth trembles by the mere sound of his voice.

What has the future in store for this strange being, born of a breath, of perishable tissue, yet immortal, with his powers fearful and divine? What magic will be wrought by him in the end? What is to be his greatest deed, his crowning achievement?

Long ago he recognized that all perceptible matter comes from a primary substance, or a tenuity beyond conception, filling all space, the Akasa or luminiferous ether, which is acted upon by the life-giving Prana or creative force, calling into existence, in never ending cycles, all things and phenomena. The primary substance, thrown into infinitesimal whirls of prodigious velocity, becomes gross matter; the force subsiding, the motion creases and matter disappears, reverting to the primary substance.

Can Man control this grandest, most awe-inspiring of all processes in nature? Can he harness her inexhaustible energies to perform all their functions at his bidding, more still cause them to operate simply by the force of his will?

If he could do this, he would have powers almost unlimited and supernatural. At his command, with but a slight effort on his part, old worlds would disappear and new ones of his planning would spring into being. he could fix, solidify and preserve the ethereal shapes of his imagining, the fleeting visions of his dreams. He could express all the creations of his mind on any scale, in forms concrete and imperishable. he could alter the size of this planet, control its seasons, guide it along any path he might choose through the depths of the Universe he could cause planets to collide and produce his suns and stars, his heat and light. He could originate and develop life in all its infinite forms.

To create and to annihilate material substance, cause it to aggregate in forms according to his desire, would be the supreme manifestation of the power of Man's mind, his most complete triumph over the physical world, his crowning achievement, which would place him beside his Creator, make him fulfill his ultimate destiny.

ADHD

2008-06-26T20:10:00.001-07:00

[disclaimer: incoherent thoughts brought on by benadryl and prednisone.. may or may not be refined at a later date]

this is my biff with amphetamines.

if the role of the 7R variation in the DRD4 allele is significant enough to be the primary candidate for insatiable novelty-seeking behavior characteristic of ADHD... why was Ritalin a good idea?

the idea is this. 7R variation in this particular dopamine receptor changes the metabotropic receptor's ability to control intracellular cAMP levels (cyclic adenosine monophosphate, which activates the membrane protein PKC (protein kinase C) releasing it from the membrane and allowing it to open potassium channels which then alter the electric potential of the cell which is what allows for DA release....for those who care). this means that cAMP is turned on constitutively, and as a result its cascade which eventually leads to the release of the cell's neurotransmitter (DA, in this case) is also kept running. so we've got the 7R mutation which is mostly responsible for overload of DA in several reward pathways. okay, so this addresses hyperactivity and abrupt and aberrant mood changes. why are we controlling this by introducing more amphetamine? this is not a neurotransmitter that is known to have a strong compensatory mechanism! introducing a consistent exogenous dose of amphetamine to try to control the amount of DA pumped into synapses does not work the same way as it does with steroids. your body takes longer to respond (namely, by reducing the amount of DA it is producing itself thereby reducing signal frequency)... and while it's trying to do so, the side effects of amphetamine take their toll. if the problem is the metabotropic DRD4 receptor, and the incessant activity of cAMP and its subsequent protein kinase cascade, altering DA levels exogenously is not going to cut it. right?

but here's my other objection. why do we need to cut it? why can't we accept it as a mutation and change our behavior to accommodate? step outside of the meme of conventional education and manipulate the outcome of this condition from the outside. this was, once upon a time, a beneficial characteristic, this insatiable novelty-seeking. can we look over our culture (particularly multi-nationally) and observe what its evolution has done to the minds of children and their capacity to explore? what were we meant to do if not explore? how does growth of any kind occur without exploration? how do we survive? okay enough with the annihilation of what are otherwise perfectly decent thoughts...

fragmentation

2008-06-23T18:45:00.000-07:00

David Bohm is a deity.

i am completely and utterly overwhelmed by this tidal wave of a theory into which i've recently dove.

Bohm's premise for the ideology of a new order of physics is that we - as humanity and as scientists - define the universe in terms of the Cartesian definitions of matter. that is to say, our perceived reality exists as a one-to-one correlation between the space/time coordinates of all matter. what Bohm suggests (and this is from 1980 so it's by no means a hot new thing) is that our reality is skewed by the fact that we perceive it in terms of fragments, or individual chunks of matter. namely, individual objects are the primary products of existence, and their continuity is secondary if regarded as important at all. to remove this fragmentation - which is implicated as paramount to reality being an illusion instead of, well, a reality - Bohm introduces the idea of Implicate and Explicate order.

Assumptions:

1. quantum particles are amplifiers of information contained in the quantum wave

2. two subatomic particles once interacted can respond to each others' motions thousands of years later, light years apart

3. space and time are derived from the Implicate Order; everything is connected such that any individual element can reveal information about any other element in the universe

The Holomovement:

a hologram is created when two interfering wavelengths collide, id est, information about the entire holograph is revealed by a single frequency of the film because every point is completely determined by the overall configuration of the interference patterns. the whole is implicit in each part. the holomovement, then, is essentially the feedback mechanisms between implicate and explicate orders.

Consciousness:
one moment gives rise to another in which the context that was previously implicate is now explicate, and explicate context has reverted to being implicate. is consciousness an interchanging feedback where implicate information forms the explicate world which then reverts to the implicate world and portrays to it new information? can we accumulate perception in such a way as to develop a self in this kind of fashion? what explains the exchange of information between implicate and explicate worlds? well, subalgebra. the superposition of series such that one enfolds into a transformation of the former. so an element undergoes a set of Euclidean metamorphic operations which can be used to describe the quantum content of an object. if two elements are similar in a set of operations, then there are a superimposed set of elements that describe the metamorphoses in a similar way. namely, Euclidean systems exercise superposition such that there will always be a system, E', enfolded relative to a previous system E. how the subsequent unfolding occurs such that E is mapped back onto E'... i have no idea. i'm getting there. for now i'm just blown away. phoosh.

But as an introduction to what i'm sure will be a series of flabbergasted nonsense regarding, i feel that i should state that my primary interest at this point relative to the Implicate Order is that each individual participates in the content of the explicate world as points in a holograph... without one, the explicate world is incomplete. we are fragmented by individual avoidance of dissonance and cultural memes. and we are whole as the exchange of implicit and perceived waveforms and interference patterns.

the longevity meme

2008-06-21T18:19:00.000-07:00

Calling aging research the quest for immortality trivializes so much of what's actually being speculated. Yes, there is a disturbing chunk of aging and longevity labs that is attempting to reorganize the biochemical processes of living, and not even necessarily the ones that disrupt living. They are fuckers. And because they get all the media's attention for being radical, many of them are excruciatingly misrepresented for what they're really up to... as is usually the case.

[Before I begin ranting, my disclaimer is to clarify that I am about to talk about longevity research as it pertains to the systemic processes of the body and not the decline of cognitive function. My opinion concerning cognition is that there is a disconnect between neural function and the ability of consciousness to hold its baring when that function is impaired, and that everything within reach should continue to be done to bridge that gap to prevent cognitive decline during aging. However it is also my biggest fear that bridging that gap will allow robotics to ascend to a new level which obliterates what it means to have a human mind... I'll shimmy across that bridge when it comes down to it. Lose a bit of physical functionality, fine - be slightly less active for the final decade of your life. Take on dementia in that decade... well to come to a point, it's the one thing in life I am determined to avoid.]

Aubrey de Grey is one of those particular fuckers who seems like he's in it with the right direction, and then he goes and says something like, "this is bona fide rejuvenation therapy for the sake of prolonging life-span." [but then he'll also go and say shit like, "I don't blame the journalists in question, you understand - they're just doing what they're paid to do. Ultimately, the reason why calling my goal 'immortality' sells papers is because it trivializes it - it confuses my work with something that we all know is impossible; the technological elimination of any risk of death."] Damn him and his perfectly directed Strategies for Engineering Negligible Senescence... which is probably the hottest title he could have given to his little proposal. He's essentially promoting modified gerontology to combat those biochemical mechanisms that accelerate the physical aging process, and to manipulate the nature of those mechanisms which are otherwise meant to be senescent. So here's what we're looking at. Geriatrics aims to stop biochemical damage from progressing into pathology, whereas it is gerontology's goal to stop metabolism from causing damage in the first place. were de Grey to base his SENS protocol off of gerontological approaches, he would immediately be dismissed as trying to override natural progression of biological processes. However, since he has disguised his proposal as more similar to the practice of geriatrics, he is facing controversy instead of socioeconomic heresy. The idea of SENS is to keep maintenance of damage that occurs as a byproduct of living/aging to prevent its exacerbation into pathology. Making only enough adjustment of systems to prevent transition of damage into pathology is where aging research should be directed. The objective to not inevitably die pathologically doesn't seem too unreasonable to me.

Sounds perfect, right? Don't stop life from happening, just keep the damage under control. I like the ideology because stopping damage entirely fights senescence on every level which, in turn, prevents the growth/development that occurs as a byproduct of living/aging. Ultimately, this screws with the natural progression of an organism's energy efficiency. I'm not a fan. Probably because I am more resistant to invasively altering energy fluctuation on a metabolic and molecular level. I'm partial to energy flux by non-invasive means, which allow only for changes in metabolism as can be controlled by organisms' behavior... on a quantum level [follow-up note to Buettner and blue zones]. Invasive techniques tend to have less catastrophic results if they don't venture beyond changes in the observable activity on a cytological level. Particularly in the name of intervening on the functionality of systems. Help them do their job correctly to improve the time we have and side-step pathological decline, don't make them do things they have never been known to do in order to extend life-span. Use RNAi to silence a genetic mutation in the mitochondria so that it more efficiently pumps electrons and doesn't leak quite so many extra protons and cause free radical formation... or combat the mutation by consuming fewer calories, eh? Increase expression of apolipoprotein E. But don't fucking stop the electron transport chain from producing a proton gradient... old people need to be able to keep themselves warm too. The goal of aging medicine should be to stave off diseases fostered by age, and let people die healthily exhausted from living, not from fighting death.

Here's the general problem. It's one thing to prolong health and quite another to prolong life-span. The idea of prolonging health is to allow people more time to do things with their existence (like redefine the pompously blind greed of government and societal consumption...ahem). Prolonging life-span increases the problem of overpopulation... why on Earth would you want to exacerbate that particular problem when it's already putting so much weight on the world that the sociological controversy isn't about whether we can, but whether we should give medical/financial support to AIDS/poverty stricken places whose governments are too dysfunctional to address the problem? Overpopulation, of course, is also controversial in terms of consumption. It just seems so insatiably and unforgivably greedy to me that people actually want to take away from the lives that their offspring might have by staying alive for so long that they're consuming resources that should be given to those who haven't already had 100 years to pursue what the world has to offer. What can you possibly have achieved in your natural lifetime to deserve the luxury of stealing from someone else's basic sustenance? [Besides curing AIDS, cancer and restructuring the American government?] But I'm getting off-topic...

So here's my wish. The romantic pragmatic approach: don't fucking delay or reverse aging, just guide it.

Eat fewer calories or take caloric restriction mimetics to decrease free radical production and stave off oxidative stress which is the staple of almost every age-related pathology.

Get enough sun to produce vitamin D but not so much as to cause DNA double strand breaks and cancer. Human skin is lighter in the North because when our ancestors migrated it was detrimental to have too much melanin blocking absorption of solar radiation to which we are exposed... and strong eumelanin with less intense exposure leads to deficits in vit. D synthesis. ["Why do we still have black people in the north?" Soo many reasons... including... thanks to human exacerbated climate change and particularly altered levels of ozone in the stratosphere we experience higher levels of exposure than thousands of years ago... it's also why there's a higher rate of skin cancer in "white folks"...]

Use stem cells to contribute to immune response to cytological damage so the white blood cells don't have to do quite so much work under otherwise catastrophic conditions... like multiple sclerosis.

Support decrepit and declining bone mineral density with nanotube structure to colonize and foster growth of new cartilage, just don't give people symptoms of asbestos...

Don't fuck with the cytokines. Development is development - aid its function, don't prevent it. [although if we must press forward with this commonsense idiocy of allowing people to live indefinitely, it wouldn't be so terrible if their offspring happened to be infertile...]

Buettner says he has identified four things people can do that can potentially increase a healthy life, and specifically, live healthier into your late years: create an environment that encourages physical activity, set up your kitchen in a way that you're not overeating, cultivate a sense of purpose... and surround yourself with the right people. This is the dude who defined "blue zones," those regions on earth where particular groups of people have mastered healthy longevity. Not immortality. Not reversing the biochemistry of aging. Living.

that's my wrap.

nuclear energy

2008-06-09T17:46:00.000-07:00

there's too much talk about the controversy of stashing nuclear waste at Yucca Mountain in Nevada, and not nearly enough talk about the reason that the government is leaning toward storage and accumulation as opposed to development of nuclear waste reprocessing. so i needed to mull over this one for a bit.

until 1976, there was a reprocessing plant in West Valley, New York, which extracted various elements of nuclear waste and recirculated them into reactors. plutonium as well as other actinide components (essentially, radioactive rare earth elements) were separated/burned off by nuclear fission and recycled as fuel to generate electricity. the reprocessing plant was closed by Pres. Ford, not because it was detrimental to the economy, but because of paranoia regarding nuclear weapons proliferation. but. during the time it was active, the nuclear fuel service plant (nfs) recovered 1926 kg of plutonium, shipping ~80% to the atomic energy commission (aec). the other remaining 20% was re-sold to industry for use in plutonium recycling [fas.org/sgp/crs/nuke/RS22542.pdf]. as i understand it, nfs blended their recovered plutonium with other metal oxides, precluding its use in weapons production. which seems to me like it addresses the issue of safety at least adequately. so then why was Ford so bent on closing the reprocessing plant? recycling nuclear waste into its more-or-less innocuous components for recirculation seems like the better alternative to shoving the still-reactive mixture under Yucca, eh? this is where i become garbled...

1) how is nuclear waste less dangerous than blended plutonium? 2) what was Ford's other incentive? 3) and why does the Bush administration actually sound like they know what's going on here?

"the United States should also consider technologies... that are cleaner, more efficient, less waste intensive and more proliferation-resistant" [Report of the National Energy Policy Development Group, May 2001]

1) ok. well, nuclear waste is typically blended with cementitious material (20/80) supposedly shielding against radioactive awakening/travesty. there's also the mixed oxide fuel burning method, mixing plutonium with uranium to burn off the plutonium by nuclear fission. and the other is vitrification; the storage of actinide components in borosilicate glass logs and - you got it - burying them deep, deep underground [Bullen and McCormick 1998]. is this less dangerous though? not really. the difference is making a somewhat neutralizing mixture which you then stuff into the ground to accumulate and wait for something to possibly wake it up. or. making a somewhat neutralizing mixture which you then recycle, keeping new highly reactive mixtures from being created in the first place, lessening the threat to the earth's safe-keeping. i may just be a hippie (and i like to think i'm not...), but i'm quite partial to the latter. reusing what we've already procured as opposed to incessantly taking more and more. one of the arguments against nuclear waste reprocessing is that it only recaptures plutonium (which really isn't entirely true either, but for the sake of argument...). plutonium is ~1% of actinides in nuclear waste, the rest would still need to be stored in a repository. so why is it worth it to spend the extra money on reprocessing in the first place? because it makes use of what we already have, and prevents us from accumulating so many tons of nuclear waste (GNEP estimates 96,000 metric tons by 2050 when Yucca will only be able to hold 77,000). if we have to stash our garbage at Yucca, we might as well do our best to reuse what we've already got planned to put there instead of accumulating more. eh? here comes the notion of Yucca and nuclear energy being a transitional tool from coal to entirely clean renewable energy [see section post numbers].

2) Ford. it actually turns out that proliferation was his main concern. as it was through Carter until Reagan lifted the ban in '81. so where are we now? we're paranoid about the crashing state of the economy. fair enough. Yucca Mt is terrorist-resistant (as much as any place can be), and inexpensive. i don't think this gives it substantial theoretical leverage over reprocessing. an accident or infiltrative attack of Yucca would be just as expensive as a few decades of reprocessing. and what's more, burning off plutonium that otherwise has a 10,000 year half-life just seems the safer bet. but we're not talking safe, we're talking money (go figure...).

3) because i ordinarily default into staunch disagreement with Bush, and not being able to instantly do so leaves me monstrously befuddled.

which leads me to wonder... why now, especially because we are even considering nuclear energy as an alternative to coal, are we shying away from nuclear waste reprocessing? fine, i understand the economy is chaotic of late whose rescue has become a fiasco all its own. so stash some more waste at Yucca Mt for a few more years. but at least show some signs of interest in pursuing funding for development of efficient nuclear waste reprocessing. fighting climate change is all about baby steps. minor transitions that are concretely progressive in their direction away from dirty energy. endorse Yucca for a few more years while the economy climbs out of Bush's toilet... use that time to begin endorsing nuclear reprocessing plants that produce non-proliferative blended components... meanwhile, don't produce such massive amounts of fresh actinides, but use the recycled components... then relieve Yucca. but don't fucking fall backward.

i have a problem accepting the idea that the government's idea of combating climate chaos is to ignore the problems we've already created and begin, instead, by thinking about possibly addressing the issues regarding our current production on our future. which is also extremely important, but you cannot ignore the mess we've already made. especially in this particular case, where the mess is a perfectly transition-renewable energy fuel until we are able to invest in enough wind turbines and solar panels to take over. all part of the baby steps.

catfish

2008-06-06T20:20:00.000-07:00

i run on water and thought, but only as it consumes me and not because i am human.

an overwhelming subpopulous of humanity pursues thought as if it were food. not as if it were a delicacy, and not in the way we sought after food when food was/is scarce, but in the same greedy insatiable way that is characteristic of fast food nations... dare i say "brain obesity"... actually no... i'm not going to go there... because then i'd have to talk about omega six and placental malleability and the origins of intelligence and i don't have it in me at the moment. but. why are we so hungry for thought? and not just thought for the sake of wonder; we have conglomerated on this idea that thought is worthless if it doesn't lead to concrete ends. answers. explanations. and this... is extremism. and this... is what intraspecies competition has come to (and you... can think about that one because i'm not going to follow it up just now).

i do not fit in well in the world of medicine for two reasons: patients, and the government.

patients - unless they are of the mindset that i am about to indulge - expect medicine to perform miracles. to be god in a 400 mg tablet of compressed powder. the thing is that medicine doesn't work that way... because your body's biochemistry doesn't work that way. nobody has the same performance of metabolism, digestion or cellular transduction mechanisms. ergo, exogenous chemicals do not affect everyone in the same way (to the same end that diets don't work the same way for everyone and people give up on them because their body didn't respond optimally, which is why being conscious of your active health is the better alternative). for the most part, we're built to perform the same biological functions and a high enough concentration of a drug will do similar things in us all: alleviate the system malfunction it was designed to target. however. because we are not built like appliances, we respond differently. tylenol works for the most part with innocuous residue because its target is so well understood, and happens to be fairly well behaviorally conserved across humans. most biochemical mechanisms are not so simple. yes, there are myriad side effects for every drug. that is because almost any patient who takes that drug will have at least one of those side effects. almost nobody will have all of them, because your reaction depends on the particular idiosyncrasies of your system. to bring about a point, i do not fit in well in the world of medicine because patients do not understand or accept this, and i am totally okay with it. because i understand that if you're going to endogenously assault the body, you had better damn well cater to the specific nature of that body in the best way you can. or, if you're going to take a drug that's on the market but not quite yet understood in its entirety, you had better damn well not expect it to work perfectly in your very particular system. because i think that there is no single answer to any question, and that more often than not the answers end up making the questions more mysterious and any concrete answer more elusive (for the same reason, i could never be a politician, lawyer or historian). point: if we did not so vehemently lust after thought as a provider of perfect answers, we would not have unfathomable expectations of medicine, would not be so disappointed, would not lose confidence in science, and i would fit perfectly in the world of medicine.

the government - on whom i will not get started because the rant is unending - protects the patient, and is not only unyielding to the nature of medicine as a science, but is the propago mater that defines the patient's expectations of medicine... fucking conservative tyrannical government... screwing up what i want to do with my life...

-----

i really don't think this is scheherazade's fault. yes, intelligence is attractive, and helps propagate the species and all that junk (not that we're prized machines to be replicated anymore, but that's another problem). but really, intrigue is always in the invigorating mystery, and being able to speculate without needing to arrive at an end, but enough to shape our tendancies... that should be what our species runs on. r o m a n t i c p r a g m a t i s m.

and so i am a catfish. benthic, beneath the chaos created by the noise of humanity's greedy hunger for this particular kind of knowledge. detritivorous, feeding on the development of thoughts that people discard because they are unrefined and inconclusive. and running on water. i could carry this one even further and say that like the male catfish, i house and nurture eggs of thought with my mouth until they are ready to hatch... but i'm not going to...

really? with the metaphor and the disgusting cliche? yes, yes i did.

limbo

2008-06-01T16:37:00.000-07:00

in this state that i can’t stand being, yet that i can’t help but approach no matter from or en-route-to where, i am sitting again.

there are two ways that i know of to perceive the direction of your life. either. you are working toward that plateau where everything you have reached for or done is acquired or accomplished, and all is settled. or. you are of the insight that there is no plateau but a mountain, and for each step you take to climb it the next is its own accomplishment. i prefer the latter. yet in spite of this here i am sitting and waiting in limbo again for the next thing to come along. it’s not time yet to move into my own home because i have to wait for funds to accumulate. it’s not time yet to make the most of the season because it is still gray outside and i am still trying to shiver off this fat suit. it’s not time yet reach out into the new circumstances of my social scene because i do not have my own home. it’s not time yet to dive head long into the NICE because i’m waiting to know exactly what it is i’m going to be doing. and it’s not time yet to begin my summer projects at the lab because i’m in training, and we’re still figuring out how to finish my training and at the same time prepare me to train the PhD rotation student and the summer undergrad student, both of whom have to come before i begin any of my projects.

i feel like despite these conditions limbo is the last place i should be. i hate the waiting. i hate wanting to be doing so many things right now and not being able to because i’m waiting. and yet. people keep reminding me that this is exactly where i should be. transition sometimes requires waiting before the next climb begins. i should just be thinking about this as my time to remove my day pack and sit on the tree stump with some trail mix before the next push. pacing? isn’t the purpose of pacing to be able to constantly keep going? at a particular pace? so that limbo is stealthily and entirely debarred?

is it time yet?

cosmological natural selection

2008-05-30T21:15:00.000-07:00

so i have a question.

if universes are created by the collapse, matter compression and explosion into a new layer of universe, where are the replicators? the black holes themselves, yes, but where on the microcosmic scale of creating the sentient characteristics of the new universe? why, oh mighty hawking (and everyone else who has addressed this theory including lee smolin for whom i have a great deal of respect), do you not address the necessity of replicators in the atomic binding and splitting that gives birth to stars, black holes and life as we understand it? you can't just spill matter into a gravitational vacuum and watch it go, something has to be introduced to use the matter to make its copies.

and aligning with the heavily reliable proposition that matter is neither created nor destroyed but recycled and re-synthesized, why do particular minds who recall living past lives never recall living those lives in past universes? as a chemist, it seems a little obscure that the first thing my brain averts to with regard to the big bang as a child of black hole implosion is christine korsgaard and the continuity and connectedness of minds. nonetheless, that's where i go.

my romantic side wants to believe that if matter is neither created nor destroyed in the recycling of universes (so to speak; and yes, i regard replication of life on earth as biochemical recycling), then the minds that accompany and/or exist in association with that matter are of no less substance and should be recycled as well. so i feel as though if you've got access to your past selves, that has to include the self of a past universe. right? why does nobody recollect their alien or other creaturely self? maybe it's an artifact of universe replication via the black hole replicator. no copying process is perfect, errors are wont to crop up. maybe the lost connectedness of selves and minds was lost in the spitting out of our universe. a macromutation, if you will.

science

2008-05-22T01:37:00.000-07:00

i’ve never understood the whole “the science has been settled on this issue” argument. it kind of gives science a bad name. it’s statements like this that make conservatives hate science and deem its arguments meaningless or frivolous.

the real deal is that science never settles on anything. anything. that is why i love it so ardently. scientific research doesn’t prove things, or provide succinct answers… rather, it makes the questions more invigorating, and answers more mysterious.

[note: the question of the earth being flat and other such self withstanding phenomena are outside of the realm i am addressing because they are not correlational with other phenomena. likewise, we may someday discover that earth really isn't round after all, but is part of a ten dimensional schema which gives us the perception of its being round.]

how do i place any weight in the arguments made by science if i believe this to be the case? well first of all, you have to make the distinction between basic science and pseudoscience (or the politically preferred, applied science). the former being research for the sake of making connections between cause and effect, and discovering interaction between phenomena with the understanding that what the discovery reveals may or may not be the answer to an important question… like the cure for cancer (which for the record, i believe is RNAi). the latter, then, is science for the purpose of moving money: find this cure, find that technology, we will fund you if you provide us with an answer, we will fund you if you side with us on this policy issue. i fucking hate money.

that being said, in believing that scientific answers lead to heightened mystery, i avoid discrediting the substance science provides by referring only to basic science, and excluding pseudoscience. pseudoscience takes the hints and suggestions of scientific findings and exaggerates and tweaks them to make a pronounced argument (lead levels in kids causes this behavior, tobacco causes cancer, etc.). basic science takes the same hints and suggestions and throws them into society as just that – possibility. this has been shown to work under a set of conditions which are all we have to rely on at this point in time to mimic the conditions of the public. let’s throw the information (or drug) out into society and see if those conditions were accurately mimicked and if our discovery has enduring merit. i astutely believe that the answers provided by basic science - if properly interpreted by the public in the way i’ve just described – can provide answers to questions while at the same time be subject to contradiction by progression of scientific inquiry. that is the nature of science. all answers are subject to being proven wrong, or to one of several possible answers.

so yes, the science is settled in pseudoscience to the end that it settles where the money tells it to, and does not respond well to criticism or contradiction. basic science, on the other hand, is never settled. and yet, i believe the latter is the genre that lends greater value to expanding our understanding of the world and our implementation of technology and healing processes.

polar bears

2008-05-20T17:29:00.000-07:00

interior secretary dirk kempthorne, you are a douchebag. i don't even care how little control you had over the decision; your so fervently speaking on its behalf is quite sufficient to deem you worthy of being sent to the corner stool to baste in shame.

dirk: arctic sea ice is essential to polar bear survival. sea ice has melted in recent decades. computer models say that it is likely to recede more in the near future. therefore, melting sea ice is linked to global climate change and is a threat to the polar bear species.

natalie: thank you sir, for that illuminating gesture of disclosure.

[note: there was a subtext to this in which he more or less said that computer models don't necessarily predict the future, they're just tools for analyzing possibilities so we shouldn't jump to the assumption that polar bears are endangered based on climate change models. well yeah, jackass, there is no medical cure that is 100% correct, there is no scientific analysis that is 100% fool-proof, there are no political policies that are so thorough in content and application that they outlast time. we still use these tools to make predictions because they are the best we can do without being omniscient. if we don't employ action to exercise what we do know, what is the point of knowing it? we might as well just sit around and wait to rot. but, i digress...]

environmentalists shouldn’t use this threatened species status to force govt action on climate change, our man so adamantly declared immediately following this announcement. to be fair, what he really said was, "we need to reduce avoidable losses of polar bears, but this should not open the door to use ESA [endangered species act] to regulate greenhouse gas emissions from automobiles, power plants and other sources." come on. are you serious? so then how, my gentle snowflake, do you propose we go about "avoiding the loss" if we're not using the loss to entice the govt to protect what we're losing?

there must be something i'm missing here...

essentially what he’s saying is, we’re going to say this animal is threatened, but we’re not taking responsibility for it, and we sure as hell aren’t going to change our behavior to protect it. doesn’t that seem a little retarded? i consider myself fairly informed as far as climate change activists go – meaning i actually know what i’m lobbying or campaigning for when i’m doing it, and have a personal crafted investment doing so – and still i seem to be missing the key constructive benefit of dirk’s caveat. and yes, we are on a first name basis because he is an ass hole.

someone clearly needs to explain to me the purpose of listing polar bears as threatened if the statement specifically prohibits using this categorization to impact the decisions of the energy industry. it just seems like that particular caveat nullifies the entire purpose of listing the animal in the first place.

stepping back a piece, the reason i got into this battle had nothing to do with saving the polar bears or penguins – they just happen to be the poster children of the environmental crisis. i got into this with the hope that dealing with this umbrella issue (being human-induced/exacerbated/whathaveyou climate change) would enable us to simultaneously ameliorate its effects on poverty stricken regions who are in such condition because climate change is dramatically increasing the agricultural devastation caused by their monsoon season... or forcing them to cross borders in illegal migration to escape deadly drought and heat wave. my concern is that most of the American public does not seem to understand that this issue goes beyond polar bears. which on the one hand pisses me off, but on the other i am very aware of the fact that if people are not already invested in the severity of the climate crisis, polar bears and penguins are needed to reel in their emotional speculation.

which brings me to summarizing why i’m pissed off at dirk (which i've more or less already stated): you cannot “avoid the loss of the polar bear species” unless you protect its habitat. you cannot protect its habitat unless you fight greenhouse gas and other environmentally unfriendly emissions. and you sure as fuck cannot fight emissions without approaching the govt about setting caps, limiting consumption, transitioning away from dirty energy and responding to the ESA.

so explain to me the purpose of declaring polar bears "threatened" if you are going to include a clause specifically preventing the world from protecting them.

organizers

2008-05-14T23:10:00.000-07:00

i'm realizing something about myself as i step into a more active role in the CCN: i don't regard project proposals for community activism in the same way as project proposals for scientific research.

when i think of a scientific research project, i zoom in to methodology. have a target question, have several collaborative methods of addressing that question, request funding for each of those methods, follow through with the implementation of all of those methods. my tiny, unexposed world is completely turned by the alteration of this process in sustainable community organization.

the NICE project (previous entry). this is an institute that was proposed and initially funded before my involvement. an incredible project was developed by my CCN comrades (and gurus) to work with the Sunnyside Neighborhood Energy (SunNE) group to research the feasibility of implementing a geo/solar thermal energy district, whereby community heating and cooling is provided not through individual water heater and cooling systems, but by a community source. the feasibility report would be used to convince a few engineering companies to invest in the geothermal energy district.

initially, the objective of the NICE project was to provide several college students with paid internships to head research groups in four areas of primary focus in the feasibility report: economics, policy, engineering and sociology. a new development as of this evening's conference call has required the alteration of funding distribution such that interns will no longer be paid. interestingly, the focus of the NICE project's direction seems to have been shifted almost entirely from research and the feasibility report to providing volunteer students with training/engaging/organizing experience. now, i whole heartedly support the necessity of such a direction. that being said, i feel that the SSC's Sprog was designed specifically for that purpose (previous entry). the NICE had incorporated Sprog into it's agenda so that student interns could take a break from their research to participate in these trainings. now that funding shortages have seemed to cause a refocusing of the project objectives to a part of the project that is already being provided by another organization... this is where i get a little knocked off my rocker.

in scientific research, you expect things to go wrong and cause a divergence from the original plan due to failed methods or unexpected data from a technique which causes a redirection to correctly answer the target question. in fact, you plan for things to go wrong. troubleshooting is the key to a successful laboratory... which is something that they don't emphasize in college, which was one of my critiques of the program upon graduation but that's entirely tangential and irrelevant to my rant. it's really not a rant so much as a pondering. nevertheless. despite the arise of obstacles, you remain focused on the original question. my discomfort with the alteration of the NICE project objectives is that in refocusing on student training we lose the original objective of the community energy research itself. it may be because i am so enthusiastic about the benefit of this project that i am not willing to accept the transition. but i would like to think it is a rational concern that the NICE seems to be transforming into a program to simply fund the participation of students in Sprog.

what i would like to come out of the next week or so is the restructuring of the NICE agenda in a way that keeps the focus on the community energy research and the collaboration of SunNE (previous entry) with NICE, CCN and the Sunnyside Elementary School. i prefer to not give up on acquisition of additional funding for individual interns, and to maintain the unique focus of the NICE project. i'm not as familiar as i'd like to be with the stipulations of the initial funding grant, but i maintain that they cannot be so different from those of scientific research that changing the objective of the NICE wouldn't have a negative effect on our credibility with our sponsors.

i can't tell yet if i'm even cut out for this kind of position.

election hysteria

2008-05-13T01:09:00.000-07:00

alright folks, here it is.

i voted today. for the united states democratic presidential candidate, among other things. you may have noticed that i did not disclose my preference before now. that being said, your jaw may hit the floor. fair warning.

i am pissed off at the democratic party. i am furious that they have pitted against each other the best two candidates we have ever had, and may ever have. and i am severely irritated that they coaxed obama into running for this term. if i had it my way, obama would be the vp on hillary's ticket for 2008 so that he could get his foot in the door in washington, and get some ground established onto which he would step in the next term as the president and actually make the changes he wants to make with some indisputable certainty. unfortunately for america, we have forced such disdain between the two dem candidates that neither one will likely be willing to run as the other's vp. we've turned them into all-or-noners. travesty. as it is now, obama's wanting to dive into washington with so many things he wants to completely about face. it's not that he's unproven or novice that concerns me, it's that i don't think god could pull off in eight years what obama wants to achieve in washington after the devastation that the bush administration has fostered. i'd rather have hillary do the initial cleaning up of bush's mess. she already knows everything about how washington works and who she's dealing with, and they know her. obama should take over for hillary later, and clean up after whatever mess she leaves over. that is what i would like to see.

there's so much hysteria on the democratic side of this election that people don't seem to be thinking about the complete picture. the democrats don't seem to be able to acknowledge that we have the opportunity to take back washington for sixteen years.

if obama takes washington this term, we might hold the white house for eight years. maybe. unless it turns out that the man is not superhuman, and fails to follow through on all of his ambitions as president. then people will lose faith in him and the pendulum could swing back the other direction. ergo, the democrats lose washington to the republicans again after four years. there's also the fact that she is sixty and he forty. obama can run for president again in eight years. hillary can't, and wont. if hillary wins now, democrats could hold the white house for up to sixteen years. sixteen fucking years. eight of hillary, and eight of obama because eight years from now he wont even be fifty, and he can run as strong a campaign as ever - stronger because he would run as former vp. that would be beautiful... since i don't forsee the appearance of any democratic candidates in the near future that will be anywhere near as amazing as either of these two. the longer democrats hold washington, the more likely it is that obama's change is really going to happen. if hillary gets in there first, she has the vigor and the direction to get the stones turning in the white house. the complete about face that is necessary in this government might actually occur in her hands. then obama will have the optimal place from which to take over.

there is not a single college student i know who looks at it this way. not a single one. every liberal college student is an obama maniac. which is understandable - the man is the real deal. but come on... i know evolutionarily humans are not built to deal with foresight, and long-term planning, but i also know that we have developed an insane level of intelligence and capacity for creative thinking which allows us to understand the importance of long-term foresight.

somebody explain to me why the hysteria of fulfilling the immediate needs and short-term satisfaction is winning this battle.

:::

so i voted for hillary. even though i like obama better. even though i know that he is going to win the democratic vote.

the roo cow

2008-05-05T15:45:00.000-07:00

you have got to be fucking kidding me.

it is unbelievable to me what we are willing to do to other creatures to avoid making changes in our own behavior. in sydney, scientists are trying to isolate a bacteria present in the kangaroo digestive system that increases the efficiency of digestion such that they do not produce methane in their flatulence. they want to make transgenic anti-methane-farting cows.

my immediate reaction to this is to emphasize the extent to which we already use hormones and steroids to manipulate the physiology of sheep and cattle to support our consumption habits.

secondarily, i migrate to thoughts about feed production and the amount of grain used to fatten cattle that could be used in fair trade to help poverty stricken areas of drought and lack of food. supposedly, this bacteria increases efficiency of digestion such that farmers could reduce the amount of feed used to fatten cattle... of course, "decreasing the cost to farmers by millions of dollars," but who really cares about what benefit that might have to the animal, right?

here's my dilemma. do you fight against yet another forced alteration in cow physiology in the name of turning the action toward changing human behavior? or do you allow the isolation and transduction of this bacteria that might make our forced feeding protocol easier on the cow, but continue to steer responsibility away from humans?

http://www.iol.co.za/index.php?click_id=29&art_id=vn20071207092135298C758249&set_id=1

autonoetic awareness and episodic memory

2008-05-05T13:37:00.000-07:00

Much of the human experience – the way we characterize ourselves as persons – can be attributed to our episodic memory. This is the ability to travel through time, in the form of recollection, to past experiences in order to know how and why we acquired certain knowledge. Episodic memory is characterized by Endel Tulving by three qualities: sense of time, self, and autonoetic awareness. He describes it as a phenomenological quality distinct to humans, and not experienced by non-human animals. But here's where it gets hazy... it is difficult to assess whether non-human animals exercise episodic memory because they can't linguistically report their personal experiences. As such, our best shot at at studying episodic memory in non-human animal models is to assess the animal’s memory of what happened, where it happened and when it happened. Because such tests do not require a consciously directed inference to memory, they are said to assess episodic-like memory.

This consciously directed inference is what Tulving called autonoetic awareness... being the directed retrieval of a specific object of memory. This is distinct from autonoetic consciousness, which Tulving does not reference in describing episodic memory, but which is important to defining the phenomenon in non-human animals. Autonoetic consciousness has no object; rather, it is the fluid link throughout one’s past memories, present, and future projections.

Autonoetic awareness requires the use of mental time travel: reliving a targeted event of the past and using it to consider possible future scenarios. Autonoetic consciousness, because it does not require identifying the context of a specific event, does not imply mental time travel. One can conceivably travel back in time along a conscious continuum without targeting a specific time and place for an event, but knowing that it occurred somewhere in the past. For example, a person knows when and where they were born without remembering the experience. It becomes difficult to assess which of the two phenomena occurs in non-human animals because they can't declare thoughts about specific events of the past. We can't assume that because non-human animals can’t verbalize mental time travel that they do not have it, and therefore do not have autonoetic awareness. This confound requires the development of tests that allow non-human animals to declare their thoughts not with verbalization, but gesture or other physical expression.

Rhesus monkeys can appropriately refuse to submit to a visual image test when they do not think they will choose the correct answers. This test design successfully demonstrates that monkeys know when they remember a learning event or not. However, it does not directly implicate mental time travel, or presume autonoetic awareness. More likely, it suggests autonoetic consciousness - knowing that a particular piece of information is lodged somewhere in memory, but not necessarily targeting it on the streamline of consciousness. Because studies like this one more closely imply autonoetic consciousness, they support the theory of episodic-like memory, and not human-like episodic memory.

Clayton and Dickinson are pretty famous for their studies on Scrub jays argue, again, that non-human animals exhibit episodic-like memory based on an experimental design which targeted two of the three qualities of episodic memory: sense of time, and self. Clayton and Dickinson designed a caching apparatus in which scrub jays could store both preferred perishable (worms), and less preferred non-perishable (peanuts) foods. After a short period away from the caching apparatus, Scrub jays preferred to recover the worms. But... after a longer delay, they chose to recover the non-perishable although less preferred food. This fairly ingeniusly exemplifies the use of autonoetic consciousness in the birds... but in spite of its brilliant layout does not speak to autonoetic awareness.

It's worth noting that an argument could be made for the presence of autonoetic awareness in scrub jays based on their ability to distinguish between a 4hr and 124hr time period. This observation (part of the Clayton/Dickinson study) suggests that the jays were able to target a general place in time when they cached both foods so as to be able to discern that the preferred food (worm) had likely decayed since. Inferring this kind of targeting argues for autonoetic awareness... However!, it may also be the case that as with the Rhesus monkeys, the 124hr delay may have allowed scrub jays simply to forget when they cached an item. It has been shown to be the case in both rat and primates modeled in similar tasks that the memory of “when” was poorer than “what,” and “where." So... if this was the case with the scrub jays, then not being able to recall exactly when they cached the food stuff, they may have recovered the less-perishable but less preferable food simply to avoid the risk that the preferred food may have decayed. The propensity of risk averse behavior in scrub jays may give stronger baring to the argument for autonoetic consciousness than autonoetic awareness... eh?

So my last blip of this rant is this: there has been insight into the anatomical component of episodic memory in humans that may provide a link between behavioral demonstrations in humans and non-human animals. In humans, the right prefrontal cortex has been identified as a key brain region in the recall of episodic memories. Given that Clayton/Dickinson claim that their experimental design targets episodic-like memory retrieval, it would be a valuable experiment to investigate the prefrontal cortex activity in these birds as they are retrieving cached food. If the same region of the prefrontal cortex is activated during this activity, it suggests the biochemical validity of the Scrub jay findings. However, the Scrub jay is evolutionarily several orders of phylogeny removed from humans... this presents the confound of their significantly less developed prefrontal cortex. In the primate and rat models of episodic-like memory, it would be invaluable to compare a PET assessment of right prefrontal cortex activity during memory tasks. If, in the primate model, there were both a behavioral correlate in episodic-like memory tasks and activity in the right prefrontal cortex, we might be able to definitively say that animals experience episodic memory in the same way that humans do. That is, that they exercise sense of self, time and autonoetic awareness.

For now, we are only able to infer that non-human animals exhibit episodic-like memory. It remains to be concluded whether non-human animals exercise autonoetic consciousness or awareness. Determining which phenomenon is occuring will give greater insight into the behavior of non-human animals, and better address the question of whether episodic-like memory is as close to episodic memory as non-human animals get. It is entirely possible that non-human animals have only episodic-like memory because they have autonoetic consciousness, and not autonoetic awareness. However, it may also be the case that we have not found a way to enable non-human animals to declare their past experiences in a suitable way...