Transapient Musings of an S6 Archailect

What's mine is mine: Brain scans reveal what's behind the aversion to loss of possessions
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Did you ever wonder why it is so difficult to part with your stuff? A new study reveals fascinating insights into the specific neuropsychological mechanisms that are linked with the potential loss of possessions. The research, published by Cell Press in the June 12 issue of the journal Neuron, has important implications for both neuroscience and economics and may even explain why you are reluctant to sell your iPod.

posted at: 12:00 | path: /sci/bio/neuro | permanent link to this entry

The hidden universal distribution of amino acids biosynthetic networks: a genomic perspective on its origins and evolution
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Background:
Twenty amino acids are the universal building blocks of proteins. However, their biosynthetic routes do not appear to be universal from an Escherichia coli-centric perspective. Nevertheless it is necessary to understand their origin and evolution in a global context - i.e. to include more 'model' species and alternative routes-. We use a comparative genomics approach to assess the origin and evolution of amino acid biosynthetic alternative network branches.
Results:
We predicted a core of widely distributed network branches biosynthesizing at least 16 out of the 20 standard amino acids, suggesting that this core occurred in the last common ancestor by tracking the taxonomic distribution of amino acids biosynthetic enzymes. Additionally, we detail the distribution of two types of alternative branches to this core: i) analogs - enzymes that catalyze the same reaction (using the same metabolites) and belong to different superfamilies; and ii) 'alternologs' - herein defined as branches that, proceeding via different metabolites converge to the same end product-. We suggest that the origin of alternative branches is closely related to different environmental metabolite sources and life-styles among species.
Conclusions:
The multi-organismal seed strategy employed in this work improves the precision of dating and evolutionary relationships among amino acids biosynthetic branches. This strategy could be extended to diverse metabolic routes and even other biological processes. Additionally, we introduce the concept of 'alternolog', which not only plays an important role in the relationships between structure and function in biological networks, but also as shown here, has strong implications on their evolution, almost equal to paralogy and analogy.

posted at: 11:54 | path: /sci/bio | permanent link to this entry

When we see a familiar face, or even a photo of a favorite car or pet, we're often flooded with memories from our past. Sometimes just seeing a person or object that's similar to the ones in our memory will trigger recollections we never knew we had. Maybe you've had a memory triggered by a scent or the texture of an object. Sometimes emotions such as happiness or anger will spur vivid memories, too.

A new study adds an unexpected method to the list of ways to spur memories about our past: body position. That's right: just holding your body in the right position means you'll have faster, more accurate access to certain memories. If you stand as if holding a golf club, you're quicker to remember an event that happened while you were golfing than if you position your body in a non-golfing pose.

Even more fascinating than the facts about body position and memory is how they were learned. A team led by Katinka Dijkstra actually had young adult and older adult volunteers assume different body positions while asking them to remember particular events from their lives. Sometimes the body position matched the memory:

I’m on a team that just got awarded a Keck Futures Initiative grant. This is the fruit of the NAKFI conference we attended last year on “The Future of Human Healthspan.” It was an unusual conference: instead of giving individual talks, the participants were split up into “task groups” that were each assigned a different question related to the biology of aging. At the end of the conference, each group gave a presentation. (The proceedings are available in overpriced booklet form here or as free HTML here).

Our group started off with one subject (stochasticity of gene expression) but took a sharp left turn and ended up thinking more broadly. We ended up focusing on what evolutionary biology might teach us about aging.

Within groups of species that share a given body plan (e.g., bats, birds, dogs, or primates), there is significant variation in maximum life expectancy, and we believe this variation is genetically determined. In other words, natural selection has performed dozens of parallel “experiments” in which more or less similarly constructed organisms end up with different lifespans, based on variations in a range of factors (some known or long-suspected, like antioxidant enzymes, and others as yet undetermined). Some of these factors may be unique to specific body plans, whereas others might be universal. The challenge we set ourselves was ambitious: How can we use the “data set” (i.e., variation in lifespan among related organisms) to identify novel determinants of longevity? Thus was born the Comparative Biogerontology Initiative.

We soon realized that we’d need a great deal of expertise, not only from within biogerontology but also from other fields, some with which we often have dealings (biostatistics, computational biology) and others with which we have almost no interaction in our daily professional lives (veterinary medicine, pathology, histology, comparative physiology). Identifying the relevant experts is a profound challenge in itself: How does one identify expertise in a field in which one has none? Hence a lot of what we’re going to be doing at first is figuring out who our collaborators will be — leading to the contorted mission statement:

These researchers will hold two meetings with senior scholars to develop a plan to test hypotheses about biological factors that control lifespan and healthspan, and compare tissues from multiple species of animals. The scholars are pathologists, comparative physiologists, methodologists, statisticians, and experts in the biology of aging.

“Hold…meetings…to develop a plan to test hypotheses”…no doubt, this will inflame the sensibilities of those who advocate a more direct frontal assault on the problem of aging; indeed, if this were all we were planning to do, they would have a point. We know a lot about aging and it makes sense to move forward aggressively where knowledge is already extensive — but those efforts are being undertaken already, and will continue. All of us are keeping our day jobs.

The CBI was conceived not as a replacement for more direct studies of more relevant models (like humans), but as a complement: by carefully examining aging in understudied organisms, and by systematically identifying the factors that contribute to their differential longevities, our hope is to discover entirely new determinants of aging and lifespan. By bringing in expertise from around the scientific world, including disciplines that don’t usually overlap with biogerontology, our hope is to break new ground in the biology of lifespan (and, if you like, to open new fronts in the battle against aging). In the process, we’ll learn more about the evolutionarily conserved bases of aging throughout the animal kingdom, identify new biomarkers of aging, and pose enough new questions to keep the next generation of biogerontologists busy for years to come.

The other members of the team are, dare I say it, eminences grises of biogerontology — some of whose work and thoughts (e.g., Steve Austad and Richard Miller) we’ve discussed here in the past (and one of whom is my current boss, Judy Campisi). I’m personally thrilled for a chance to work with and learn from them.

And who knows? After we hold our meetings to develop a plan to test a hypothesis, we might actually test one, and then I can blog about it here. Watch this space for further developments.

I am currently reading Daniel Moerman's "Meaning, medicine and the 'placebo effect'". As well as containing many interesting asides, the book discusses what is at the heart of the so-called placebo effect: patients' response to the meaning of their treatment. Moerman calls this the 'meaning response'. This response to meaning explains why two inert pills produce more cures than one inert pill, and why inert injections are even more effective (because "everybody knows" that injections are more powerful than pills). But importantly, it is possible to show that doctors are as important in producing the meaning response as patients. Gracely et al (1985) looked at the effect of placebo on pain in patients having their wisdom teeth extracted. The study was set up as a standard double-blind (neither the doctor nor the patient knows if the patient is getting a real medicine or an inert placebo), with the possibilities being a placebo, fentanyl (which usually reduces pain) and naloxone (which usually blocks reduction in pain, so could be expected to increase the pain of the procedure). The twist was that for the first half of the experiment the doctors, but not the patients, were told that a supply problem meant that no patient would be getting the pain-relieving fentanyl. In the second half the doctors were told that the problem had been resolved, so that now the patients might receive fentanyl. By comparing levels of patient pain in the placebo condition is possible to gauge the effect of doctor expectations on the meaning response of the patients. In this condition patients are all receiving inert substances, and they all 'know' the same thing: they might receive a placebo, pain-relief or 'pain-enhancement'. The doctors don't tell them about the supply problem and, for that matter, they don't know themselves for definite what the patient is given. The only difference is that for the patients in the first half, the doctors think they know that pain-relief is not a possibility, whereas in the second half it is. The graph of the results, copied from Moerman's book is below:

As you can see, patients in the PN group --- those whose doctors thought they might receive pain-relief had a large pain-relieving placebo effect. Those in the PNF group --- those whose doctors thought they couldn't receive pain-relief --- didn't have a pain-relieving placebo effect.

What I think is interesting about this study is, firstly, it confirms the need for rigorous double-blind controls in studies of medicine and, secondly, just how significant an effect this subtle manipulation has. The doctors don't know anything definite, and they certainly aren't telling the patients what they suspect or guess, but somehow --- a look? a slightly brighter smile? a slightly lowered tone? --- they communicate their knowledge of the probabilities to the patients who then experience a real change in their levels of pain because of it.

A striking aspect of the meaning response is that one could suppose that patients have control over their experience of different levels of pain. After all, we know that the pills are inert. Could we just imagine ourselves a 'placebo effect' in all situations where we have unnecessary pain? Sadly, normally we can't do this --- the meaning response doesn't work like that. Doctors are required to give patients permission to feel less pain. Perhaps a fundamental part of the creation of meaning is that it requires other people.

Gracely, R. H., Dubner, R., Deeter, W. R., & Wolskee, P. J. (1985). Clinicians' expectations influence placebo analgesia. Lancet, 1(8419), 43.

Moerman, D. E. (2002). Meaning, medicine, and the "placebo effect". Cambridge University Press: New York.

The same nanotech approaches being explored to deliver drugs exactly to the cells where they are needed also provide a technology base that might lead to permanent enhancements of human metabolism. Excerpts from “Cell ‘organs’ get plastic upgrades“, by Tamsin Osborne at NewScientist.com news service:

Although the immediate interest is in drug delivery, the researchers involved are mindful that more sophisticated artificial organelles could provide metabolic services beyond the natural human repertoire.

Not long ago we discussed work led by Deena Skolnick Weisberg showing that most people are more impressed by neuroscience explanations of psychological phenomena than plain-old psychology explanations. Talking about brains, it seems, is more convincing than simply talking about behavior, even when the neuroscience explanation doesn't actually add any substantive details.

Now David McCabe and Alan Castel have taken this work on the acceptance of neuroscience to a new level: now they've got pictures! They asked 156 students at Colorado State University to read three different newspaper articles about brain imaging studies. The articles were completely fake, and they all discussed brain imaging, but one of the articles included only text, one included a bar graph showing brain-scan results, and one showed pictures of brains. The articles were about three different topics, but an equal number of students saw each article with text only, the graph, or the brain image.

For example, in one of the fake studies, the claim was made that TV-watching is related to math ability. As evidence, students read a text explanation, or saw one of these two figures:

The [fake] claim was that since the same area of the brain is activated while doing arithmetic or watching TV, that the two activities are related. The students then rated this article for whether its scientific reading made sense, on a scale of 1 (strongly disagree) to 4 (strongly agree). Here are the results:

Janet Iwasa has had an unusual scientific career. After finishing her PhD with Dyche Mullins at UCSF she started a postdoc in Jack Szostak’s lab at Harvard but not to do bench work or even simulations like her postdoc colleagues. Instead, Janet is a full time animator and graphic designer. She takes the current work done in the lab and translates the experimental results and speculated mechanisms into beautiful animations. For more on her story, check out this post at Nature Network.

One of the results of her efforts is a recently completed web site on the origin(s) of life called Exploring Origins. It’s full of striking images and animations that depict RNA enzymes folding into their active structures, the dynamics of lipids in micelles and vesicles, and also more speculative processes like how micelles could have formed around an ancient geyser. And best of all, she’s used a creative commons license so her work is available for educational use including in presentations. If your interests overlap at all with hers then your future audiences are in for a treat because these videos can be used to quickly and entertainingly get across complex ideas.

Of course, this is just one of Iwasa’s projects and you can find more examples of her work on her website. I especially like the illustration of clathrin-mediated endocytosis.

Leuven, Belgium − Every year, one million Europeans are confronted with potentially irreparable brain or spinal cord injuries resulting from traffic accidents. Because the nerves in a damaged spinal cord cannot, or cannot fully, be repaired, the patient remains (partially) paralyzed. Now, VIB scientists connected to the K.U.Leuven have become the first to successfully develop a simple model that enables the study of injured brain tissue. The researchers have perfected a technique for keeping the cultured brain of a fruit fly alive and healthy for a longer period of time. With the aid of microsurgery, this new technique enables scientists to inflict injury on certain nerve bundles for research purposes. By means of this new fruit fly model, the researchers have already succeeded in showing that the activation of a particular signaling pathway (JNK) induces the regeneration of axons. This research offers positive perspectives for patients with nerve injuries that have been irreversible up to now.

Wed, 11 Jun 2008

1. Brain training

2. Drugs

3. Nutritional supplements

4. Meditation

5. Exercise

The results are in (for now)