On Purpose

"When Henry Fawcett commented to Charles Darwin that some scientists found Darwin too theoretical and believed that he should just let the facts speak for themselves, Darwin responded: 'How odd it is that anyone should not see that all observation must be for or against some view if it is to be of any service.'³"

This quote is taken from a review in Science magazine of cognitive neuroscientist Paul Thagard's book: The Brain and the Meaning of Life^1,2. I found the review intriguing, particularly the section which comment's on Thagard's attempts to use a scientific point of view to answer the question: "What kind of government should countries have?"

However, I reproduced the quote, above, because it struck a chord in my mind. To my mind, Darwin's viewpoint discards the great utility and pleasure that one may find in observation for the sake of observation. That is, scientific exploration. It is not always possible to observe, to collect information with a hypothesis in mind, and such exploratory behavior can inspire hypotheses or new avenues of scientific discovery. How limiting to always approach a situation with a theory, a reason, a preconception.

In fact, I don't believe that Darwin was suggesting anything so strong as to eliminate exploration from one's methods, his own travels as a young man were likely not begun with a plan of attack to corroborate his grandfather Erasmus' evolutionary theory, though this was the end result. However, science in the present day is extraordinary goal oriented; every scientist must compete for funding and the drive to present completed work is thus ever present. There is something romantic and collaborative in the idea that some men of science in Darwin's age wanted the facts to "speak for themselves."

Collaboration is something that we can always use more of.

References
1. Shermer, M (2010) Meaning-Making Neurons. Science, 328: 693-694; DOI: 10.1126/science.1189752
2. Thagard, Paul. The Brain and the Meaning of Life. Priceton: Princeton University Press.
3. Letter, C. R. Darwin to H. Fawcett, 18 September 1861; www.darwinproject.ac.uk/entry-3257.

On Goals / (I'm back)

Freeman Dyson's piece on Steven Weinberg's recently published collection of writings was a beautiful and informative exploration of science, history, and politics^1,2. One quote, about the differing goals of the Russian and American space programs, struck me in particular. Perhaps I found it so intriguing because it highlights a an ever-present conflict in my own life: short-term vs. long-term goals. An excerpt:

"[American] unmanned missions to explore the planets and stars and galaxies have made us truly at home in the universe, while our manned missions after the Apollo program to land on the moon have been scientifically fruitless. Forty years after Apollo, the manned program is still stuck aimlessly in low orbit around the earth, while politicians debate what it should try to do next.

...In Russia you do not go into space to do science. You go into space because it is a part of human destiny... Konstantin Tsiolkovsky, the schoolteacher who worked out the mathematics of interplanetary rocketry in the nineteenth century, said, “The earth is the cradle of the mind, but we cannot live forever in a cradle.” It may take us a few centuries to get to the planets, but we are on our way. We will keep going, no matter how long it takes.

If you think as Americans do, on a time scale of decades, then unmanned missions succeed and manned missions fail. The grandest unmanned missions, such as the Cassini mission now exploring the satellites of Saturn, take about one decade to build and another decade to fly. The grandest manned mission, the Apollo moon landing, ended after a decade and could not be sustained. The time scale of a decade is fundamentally right for unmanned missions and wrong for manned missions. If you think as Russians do, on a time scale of centuries, then the situation is reversed. Russian space science activities have failed to achieve much because they did not concentrate their attention on immediate scientific objectives. Russian manned mission activities, driven not by science but by a belief in human destiny, keep moving quietly forward. There is room for both cultures in our future. Space is big enough for both." (my emphasis)

Here's to moving quietly forward.

References
1. Dyson, F. (2010) What Price Glory?, The New York Review of Books LVII-10: 8-12
2. Weinberg, Steven. Lake Views: This World and the Universe, Belknap Press/Harvard University Press.

On Snake Walking

(from reference 1)


Human beings transition between from one style of gait to another as they transition from walking to running (see figure, above). The act of walking is fundamentally one of transferring weight from one limb to another, while running is primarily an act of maintaing inertia. Furthermore, these two gaits apparently have their origin in the minimization of energy costs associated with moving at a particular speed¹.



(from reference 2)


Interestingly, it seems that snakes do not make any such transition in their locomotive behavior. A study appearing in the Proceedings of the National Academy of Sciences has used theoretical modeling, friction measurements, and slithering-observations to demonstrate that snakes simply "speed-walk" at high speeds ². Although they have no limbs, and thus no "gait" to speak of, at slow speeds, they do move about by transferring weight from one part of their body to another. In contrast to other animals, however, they do the same thing, only faster, at high speeds. It is unclear why speedwalking is not an undue energetic costs for these animals, perhaps there is simply no less-costly way to move about. Further work will be needed to more completely understand the energetics of snake locomotion.

References:
1. Srinivasan M, Ruina A. (2006) Computer optimization of a minimal biped model discovers walking and running. Nature. 439(7072): 72-75.
2. Hu DL, Nirody J, Scott T, Shelley MJ. (2009) The mechanics of slithering locomotion. Proc Natl Acad Sci U S A. [Epub ahead of print]
PMID: 19506255 [PubMed - as supplied by publisher]

On The Tree-for-the-Forest in Autism

One commonly reported feature of autism-spectrum-disorder (ASD) is the tendency to favor details over whole-object properties. That is, to notice the forest and not the trees. A study appearing in the journal Vision Research quantifies this effect experimentally¹.

The authors of this study relied on a concept known as "visual crowding." This term refers to a commonly experienced phenomenon in which objects that are spaced closely together are more difficult to individually attend to or resolve. For example, some have invoked this idea to explain why it is difficult to pick individual faces out of a crowd. It is important to note, that there is a spatial-scale, a threshold, associated with visual crowding, such that objects of a given size must be spaced within some distance limit to be considered within the crowding limit (although some objects are so large that they are immune to such effects).

from reference 1

Interestingly, the authors found that children with ASD had much lower thresholds for visual crowding than those without the disorder (see figure, above). That is: those with ASD were able to resolve and report the properties of more densely packed objects than those without ASD. Furthermore, children with ASD out-performed non-ASD children in the employed task within the crowding limit (as defined by the threshold for non-ASD children) while underperforming outside this limit.

Such a finding suggests structural irregularities in the visual-corticies of these children; while this is nothing special in and of itself, there are many different cortical areas which are affected by ASD, which leads to the intriguing possibility (suggested by many) that the disorder might be a generalized structural deficit of the cerebral cortex.

References:
1. Baldassi S, Pei F, Megna N, Recupero G, Viespoli M, Igliozzi R, Tancredi R, Muratori F, Cioni G, Search superiority in autism within, but not outside the crowding regime, Vision Research, In Press, DOI: 10.1016/j.visres.2009.06.007.

On Leanness

Although many acknowledge that some people are inherently (perhaps genetically) leaner than others, it remains unclear what the biological basis for the body's "set-point" might be. A study appearing in the open-access journal PLoS One suggests one possible factor¹.


from reference 1

Both rat and human data were collected in this work, which concludes that "the lean phenotype is characterized by high endurance capacity and high activity and may stem from altered skeletal muscle energetics." These researchers gathered data from a population of people who they categorized as non-exercisers (less than 1 hour per week of activity exceeding 4 METS). They subjected these individuals to a treadmill test to determine their endurance (as assessed by oxygen consumption during exercise) and kept track of their average daily activity over a period of 10 days; finding that there was a significant relationship between endurance and leanness, as well as average daily activity and leanness. Furthermore, they found that there was no significant difference in the amount of food consumed by lean versus non-lean rats, and fascinatingly, that the skeletal muscle tissue of lean rats has significantly higher levels of the enzyme PEPCK-C.

Of course, it is not surprising that those individuals with higher daily activity are leaner in general, rather, this study is suggesting that there may be a fundamental, biological reason why certain individuals are more active: they simply have a greater capacity for activity. Indeed, if one fatigues more easily, it wouldn't be surprising if they were less active; it is also conceivable that reduced activity could feed-back on behavior in the sense that an individual with lower endurance might progressively reduce the amount of physical activity they engage in so as to reserve energy for other tasks. This is especially true in contemporary society, where mental activity is often the basis for work and play.

It is unclear as yet, however, whether the differential muscle-properties found in rats extend to humans; further work will be required to clarify what the molecular-biological basis for increased human endurance might be.

References
1. Novak CM, Escande C, Gerber SM, Chini EN, Zhang M, et al. (2009) Endurance Capacity, Not Body Size, Determines Physical Activity Levels: Role of Skeletal Muscle PEPCK. PLoS ONE 4(6): e5869. doi:10.1371/journal.pone.0005869

On Feedback

One of the most fascinating questions in neuroscience, is how "high-level" cognitive properties of mind like attention feed back on and affect our biology. For example, it is known that video-game players have better visual acuity than non-video game players¹. Another example of this phenomenon can be found in the result (described below) from Lee et. al., published in the Journal of Neuroscience².


from reference 2

The authors of this study found differences in the responses of the auditory brainstems of musicians as compared to non-musicians. Specifically, these two groups (musicians and non-musicians) were presented with pairs of consonant and dissonant tones; it was found that musicians showed larger response magnitudes to certain components of consonant tones than did non-musicians (see figure, above).

The hypothesized reason for this difference is that a musician's heightened attention to consonant tones (and their makeup or properties) leads to changes in his or her neurobiology, such that the neurons of the auditory brainstem eventually respond more strongly to certain aspects of these auditory signals. This is especially fascinating because the area of the brain that was measured was not the cortex (usually associated with consciousness and "high-level" cognitive activity), but the brainstem (the area of the brain that is evolutionarily much older; bearing greater resemblance to animal brains ).

How the conscious act of focusing on one aspect of a stimulus can lead to an enhancement of the responses of brain-regions devoted to their representation is an open question, and one with wide-ranging implications. Further research will be required to understand its basis.

References:
1. Green CS, Bavelier D. (2007) Action-video-game experience alters the spatial resolution of vision. Psychol Sci. 18(1):88-94. PMID: 17362383
2. Lee KM, Skoe E, Kraus N, Ashley R. (2009) Selective subcortical enhancement of musical intervals in musicians.
J Neurosci. 29(18):5832-40. PMID: 19420250

On Prefrontal Guilt

The field of Neuroeconomics has become quite popular in recent years. There are several reasons for this surge in interest; amongst these are: (1) the inevitable intrigue generated by scientific considerations of currency, (2) the utility of studying behaviors contingent on well defined rewards and punishments (losses), and (3) the value of scientifically exploring a human behavior that has been studied and theorized about for hundreds of years (namely by economists and others not specifically interested in the neurological bases of these behaviors).

One particularly rewarding research tactic has been the employment of economic games (a subset of those falling under the heading of game theory, widely associated with the mathematician John Nash). One example of such a game is the following: I (the "house") flip a coin. If it's heads, I pay you a dollar. If it's tails, I flip it again. If it's heads on the second toss, I give you 2 dollars. If it's tails, I flip it again. If it's heads on this second toss, I give you 4 dollars, et cetera. Thus, if you get a head on the nth roll, you receive $2ⁿ. The question is: how much would you be willing to pay initially to be a player in this game? Most people are only willing to pay perhaps $10-20 for the privilege, however, statistically (on average), the earnings in this game are infinite. If you play enough times, you will earn an infinite amount of money. This concept was quoted hundreds of years ago to give credence to the notion that when it comes to estimation of value, we operate far from optimally.

This sort of heuristic - describing performance in a prescribed setting - can be rendered quantitative in such a way that an individual's decision making in a particular game can be used to estimate parameters about their over-all behavior: how risk-averse they are, how benevolent, and even how likely they are to feel guilty.




A paper appearing in the Journal of Neuroscience addresses this last point in the context of relevant brain areas and brain damage. Krajbich et al compared the performance of individuals with certain types of brain damage (along with normal controls) in an economic game. As can be seen in the table above (from their paper), they concluded that those with damage to the prefrontal cortex (PFC) are far less likely to experience feelings of guilt¹.



Those familiar with the story of Phineas Gage may hear the ring of truth in this result. Phineas Gage was a railroad worker responsible for tamping down explosives into holes drilled in pieces of rock, using a long metal rod. During one such episode, the explosives went off, and the rod entered his head below the left eye socket, exiting through the top of the skull and destroying most of his PFC (see image, above). Amazingly, he survived, but with the intriguing effect that his personality changed completely. Before the accident, he was described by his employers as "a great favorite" and "the most efficient and capable foreman in their employ." After the accident, he was so changed that they subsequently "considered the change in his mind so marked that they could not give him his place again." He was furthermore said to be a "braggadocio,and "manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating.²"

It is likely that the experience of guilt is not the only function of the PFC; it is associated with planning functions and reasoning in general. However, this type of exploration and estimation of the parameters of human behavior is quite novel and powerful, and its utility will only increase as the complexity of our models and understanding of the parameters relevant to the generation of such behaviors increases.

References:
1. Krajbich I, Adolphs R, Tranel D, Denburg NL, Camerer CF. Economic Games Quantify Diminished Sense of Guilt in Patients with Damage to the Prefrontal Cortex. J Neurosci 29: 2188-2192, 2009.
2. Harlow JM. Recovery from the Passage of an Iron Bar through the Head. Pubs Mass Med Soc 2: 327-347, 1868.

On Insect Impersonation

Apparently humans aren't the only creatures that imitate others for social benefits. Writing in science, Barbero et al. report that the pupae of the butterfly Maculinea rebeli may have another tool to use in their ongoing infiltration of the societies of the ant species Myrmica schencki¹.

From the figure above, it is apparent that there is some similarity between the acoustic signals (bottom row) produced by these butterfly pupae (column C) and the ant queens (column A). The result is that ant workers behave around the butterfly pupae as they normally would around the ant queens.

Although it is apparent that these vocalizations are not identical, the authors report that - amongst the behaviors they took into consideration - there was no significant difference in the behaviors elicited from ant workers when comparing presentations of ant queen and butterfly pupa acoustic signals.

Of course the possibility remains that this auditory similarity is incidental and the butterflies have other tactics in their arsenal which are actually responsible for convincing these ants that the butterfly pupae are deserving of the social benefits normally reserved for ant queens. However, other forms of mimicry are common phenomena amongst insects, and it would not be surprising to find that auditory impersonation has evolved as well.

References:
1. Barbero F, Thomas JA, Bonelli S, Balletto E, Schönrogge K. Queen ants make distinctive sounds that are mimicked by a butterfly social parasite. Science 323: 782-785, 2009.

On Spermatozoic-Evolution

I recently listened to an episode of RadioLab concerned with the subject of sperm. It was highly enlightening, as most of their programming is, in my opinion, and it turned me on to one concept in particular that I found of particular interest. In general amongst our close animal relatives, promiscuity is the rule; approximately 3 percent of mammalian species are considered monogamous. One predicted result of this behavioral ubiquity is the specific evolution of sperm, for if male genes are to be carried on, an individual's sperm must compete with the sperm of others inside the female for the right to fertilize her egg(s). In fact, it has been known for some time that evolutionary selection will operate on sperm whenever access to a female's eggs is contested by sperm from more than one male¹. Furthermore, those who speculate about the subject speculate that such competition should yield larger sperm, based on the paired assumptions that larger sperm are faster, and faster sperm are more likely to fertilize an egg.


A study published in the Proceedings of the National Academy of Sciences has shown that female promiscuity does in fact, lead to the evolution of faster sperm in 29 closely related species of cichlid fishes of Lake Tanganyika, Africa. These fish in this lake are of particular interest to evolutionary researchers and theorists because the lake is large enough to constitute several environments - thus it harbors several closely related but distinct species of cichlids - and because of certain "explosive speciation events²," the relationships amongst these species is very well documented.



These researchers scored each species, assigning them a number according to their "sperm competition rank" (see table above). Which strongly predicted the speed of those species sperm (see table, below).




This research is quite intriguing because it represents an example of behavior feeding back on evolution. The effects of behavior on evolution are fascinating because such phenomena must have played a significant role in our own evolution, and continue to be perhaps the most important determinant of our biological fate.

References:
1. Parker GA. Sperm competition and its evolutionary consequences in the insects. Biol Rev 45: 525–567, 1970.
2. Fitzpatrick JL, Montgomerie R, Desjardins JK, Stiver KA, Kolm N, Balshine S. Female promiscuity promotes the evolution of faster sperm in cichlid fishes. Proc Natl Acad Sci U S A 106: 1128-32, 2009.

On Finding Yourself

The hippocampus and associated structures such as the entorhinal cortex, have long been known to play an extremely important role in navigation and memory formation (as previously discussed in this forum: 1, 2). For example, the hippocampus is enlarged in London taxicab drivers, who presumably employ it heavily for navigating around the city, and individuals with damage to this area are unable to form new memories at all, though they can recall past experiences with no loss of fidelity.

The entorhinal cortex feeds into the hippocampus, and it seems to be far more specialized for navigation purposes. There are cells in this area that seem to encode the direction that an animal's head is pointing. There is another varietal, referred to as the grid-cell, whose response-properties are illustrated below.

from reference 2

Grid-cells have the intriguing property of responding vigorously in a regular array of spatial locations. If an experimenter puts an animal in a small confined space, the regularity of these responses are evident after a brief period of exploration by the animal. On the left, you see the black trace of a rat's position as it wanders around this enclosure, with red traces representing locations where the response of a single neuron under consideration was strongest. In the middle, you can see a rasterized representation of this information, and on the right, a "cross-correlation" of the middle plot, showing the regularity of the responses.

Much of the pioneering work on the hippocampus and entorhinal cortex has come from the lab of Edvard and May-Britt Moser, a married pair of neuroscientists working at the Kavli Institute for Systems Neuroscience at the Norwegian University of Science and Technology. They have recently discovered another, infrequently occurring, class of cell in the entorhinal cortex, the border cell. Predicted from theoretical considerations in the year 2000 by Neil Burgess, these cells respond preferentially when the animal is placed near a border, of a certain orientation, of an environment (these can be walls, or drop-offs; see image, below).

from reference 1

Panel A shows that the response is independent of the size of the space, and that if the space is expanded, so too does the area over which the neuron responds (right). Panel B shows that if a new separation is inserted into the space, the cell begins to respond strongly to the boundary. Panel C shows that the response properties persist even after the walls are removed, leaving only a drop-off). Panel D shows that the orientation specific quality of the responses are independent of the shape of the room. If a landmark, in the form of a marker on one of the walls, is employed, the responses rotate along with the landmark (see below). Which is impressive, but also expected and necessary for these cells to function efficiently as part of a navigational system.



It is still a mystery how these cells produce these responses. It must be the case that a computational transformation of a variety of sensory and motor information must contribute to the computation of border location. These cells represent some of the few that have such clearly defined properties. That is to say, in many other parts of the brain, single neurons contribute only a small part of the over-all response to a stimulus, and it is thus surprising to find single cells devoted to the entire border of a space. Another impressive and enigmatic feature of the responses of these cells is the fact that they must rapidly re-compute and respond to the borders of a novel place. This sort of short-time-scale neuronal plasticity is of great interest to neuroscientists everywhere.

Understanding the properties of these cells, and their role in navigation and memory formation will be a great and rewarding challenge, one that I'm sure the Mosers are up to.

References:
1. Solstad T, Boccara CN, Kropff E, Moser MB, Moser EI. Representation of geometric borders in the entorhinal cortex. Science 322: 1865-1868, 2008.
2. Hafting T, Fyhn M, Molden S, Moser MB, Moser EI. Microstructure of a spatial map in the entorhinal cortex. Nature 436: 801-806, 2005.

On the Life Cycle of Stars

In honor of the 400th anniversary of Galileo Galilei's (and humankind's) first observations with a telescope, 2009 has been declared the International Year of Astronomy. I thus thought it only appropriate to devote at least one post to the heavens.


"Although stars are frequently assumed to be constant and unchanging features of the firmament, they are in fact evolving dynamic systems. New stars condense out of gaseous nebulae, and old stars evolve through planetary nebulae and supernovae into white dwarfs, neutron stars and black holes. These processes—star formation and evolution—are critical to understanding many features of the Universe, including the evolution of galaxies, the dispersal of chemical elements and the distribution and energetics of gas.

Some of the [Hubble Space Telescope's] HST's most lasting (and beautiful) contributions to stellar astronomy have been its studies of star-forming regions like the Orion nebula [see figure, above]. In these regions, luminous massive stars ionize the gas cloud from which they coalesced, causing the cloud to glow brightly in various emission lines. The HST's earliest observations of the Orion nebula revealed that it was peppered with a remarkable population of young stars surrounded by dense disks of gas and dust. These disks are undoubtedly remnants of the late accretion phase during which the stars condensed. Although the presence of such disks had been inferred from theory and from observations with the Very Large Array, the HST's superior image resolution revealed the first true pictures of the disks' structures and physical properties."¹

References:
1. Dalcanton JJ. 18 years of science with the Hubble Space Telescope. Nature 457: 41-50, 2009.

On The Agency Cortex

As previously reported, the mirror neuron system is a set of cortical circuits that are active both when an individual performs an act (picking up an apple, say) and when he observes that action being performed by another individual. This collection of cells is clearly important for understanding the intentions of others, and perhaps for learning by imitation. Furthermore, there is quite similar sensory activity associated with both active and passive limb movement (movement imposed on one's body).

This presents a problem. How do we attribute self-agency to our actions? This is a particularly important question if one subscribes to the theory (mentioned sporadically in this forum), that free will is not the cause of our actions, but the post-hoc assumption of agency for our actions. Even if one does take the stance that free will is the subjective experience of causing thoughts and acts, this question remains relevant since there must be some neural activity which distinguishes self-caused action from passively experienced action.

Of course, there is a wealth of non-cortical activity which accompanies moving one's arm (signals in the brain-stem and spinal column, in particular) which could provide this signal. However, because of the abstract nature of agency, some have the opinion that there must be a specialized cortical area whose job it is to integrate the diffuse, distributed neural activity associated with a single act and decide whether it was internally generated or externally imposed.

Writing in the pages of the Journal of Neuroscience, Zarinah Agnew and Richard J. S. Wise report that they've found an area of the brain that is a candidate for the job of agency detector, the Parietal Operculum¹.

This work pushes the boundaries of research into the nature of free will. One class of phenomena which motivates the free-will-as-post-hoc theory is the so-called automatisms: actions which are internally generated but feel as though they were caused by an outside agent. A well known example of automatism is the Ouija Board, where it is possible - most likely due to suggestion and the ability to ascribe agency directly to the other "players" - to feel as though one is not moving a planchette. Another is automatic writing, a phenomenon in which an individual composes pieces (in some cases entire novels) without any feeling of agency.

That the experience of will can break down in these ways is a very direct indication (along with a host of others) that our understanding of the phenomenon is minimal, at best. Localizing the brain areas responsible for the feeling of free will is one step towards understanding it.

References:
1. Agnew Z, Wise RJ. Separate areas for mirror responses and agency within the parietal operculum. J Neurosci 28: 12268-12273, 2008.

On The Ecosystem Within (UPDATE)

My last post was concerned with the way mice regulate the set of bacteria which reside in their intestines. Which specific bacteria are present in one's gut is known to be predictive of obesity, but new research suggests that it isn't the bacteria themselves that are important so much as the genes that they carry¹.

Scientists at Washington University in St. Louis studied the bacteria present in the intestines of pairs of twins (a useful methodology for exploring many kinds of similarities amongst individuals with similar genes) and their mothers, expecting to find that those who were obese would have similar species of gut flora (similarly expecting comparable special cross-sections in those who were not obese). Interestingly, they found that the set of bacteria differed widely, but that the core "bacteriome" (the set of all the genes in all the bacteria in a person's gut) was highly conserved across the obese (and separately across the non-obese). They further found that related individuals were more likely to harbor the same set of species.

This is not incredibly surprising. After all, the functional utility - in terms of digestive assistance, molecular synthesis, and nitrogen uptake - of these bacteria is defined by their genes. That is to say, bacteria can only be useful to us and our internal environment in that they are in possession of metabolic pathways that we lack. Furthermore, given the massive number of bacterial species, it is unsurprising that one person gets a specific part of the benefits from species A, while another person obtains that benefit from species B. It is a happy surprise to me that this research is progressing at an increasing pace. I hope it continues as such.

References:
1. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI. A core gut microbiome in obese and lean twins. Nature [Epub ahead of print], 2008.

On The Ecosystem Within

BIOMED. IMAGING UNIT, SOUTHAMPTON GEN. HOSP./SPL


There are more microbial cells than human cells in your body; this is a good thing. Bacteria help us break down foodstuffs by fermentation, synthesize vital molecules, and help us get rid of excess nitrogenous wastes. Furthermore, it has been demonstrated that the kind of bacteria you have in your gut is predictive of obesity: the right bacteria can help keep you thin^{1, 2}. Thus, it is important to have a source of good microbes in your diet, like yogurt or kombucha (a fermented tea drink rich in microbes), especially if you're engaging in activities that tend to kill off these organisms, like drinking heavily or taking antibiotics which don't discriminate between the good & the bad bacteria.

While drugs may not be able to discriminate between good and bad bacteria, our bodies must be able to in order to maintain intestinal homeostasis; how this happens has been unclear, to-date. However, new research demonstrates how one type of "bad bacteria" - the so called gram-negative strains - are selectively targeted by the body's immune system³. These microbes present an excess of a type of molecule on their membranes (peptidoglycans) which the body recognizes. The detection of these molecules causes the body to generate lymphatic tissue that specifically targets these bacteria.

As we come to understand more and more about the relationship between gut flora and health in general, this type of research will prove invaluable because it facilitates our understanding of the body's innate ability to regulate the subset of flora residing within. In other words, there is surely a gradient of immune system function such that some individuals are better able to select which flora to keep and which to oust; understanding how the body achieves this feat will thus widen the scope of western medicine.

References:
1. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444: 1027-1031, 2006.
2. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature 444(7122):1022-1023, 2006.
3. Bouskra D, Brézillon C, Bérard M, Werts C, Varona R, Boneca IG, Eberl G. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 456: 507-510, 2008.

On Anti-Aging

from reference 2


Throughout your life, your cells are continually replaced. The replacements are newly differentiated stem cells: cells which have somehow come to a decision regarding their fate in your body, and have thus undergone a transformation from a ready-to-become-something state, to a liver cell, a retinal cell, a skin cell, a brain cell (neuron). This further means that your stem cells (and others) are constantly dividing, a process called mitosis. The most fundamental operation in mitotic division is the replication (copying) of DNA. This is a multifaceted operation involving a large cast of molecular players including (amongst others) enzymes, cofactors, and nucleic acid building blocks.

When DNA is replicated, complementary nucleic acid bases are added one by one to each strand of the double helix as it is unwound, resulting in two copies of the original piece of DNA (chromosome). However, this presents a slight problem. The enzyme complex responsible for adding these base pairs (the process is called elongation) requires a bit of RNA at the end of the strand to get started. The solution is that part of the end of the DNA strand is snipped off and replaced with a chunk of RNA as a jumping off point. This would be an issue if these enzymes were chopping off pieces of "important" (functional) DNA; cells have so called "proofreading" mechanisms to look for the kinds of erroneous DNA sequences that would result from trimming parts off the end, which if found in large enough numbers, result in cellular suicide (apoptosis). Instead, and rather ingeniously, there are long sequences that cap the ends of the important parts of DNA called telomeres. The only function of these sequences is to be snipped apart, slowly ground down over time, by replication so that the important stuff in the middle doesn't get messed with in this process.

Telomeric DNA has been seen as a potential target for anti-aging therapy. The idea is simple: make telomeres longer, the animal lives longer because the animal's cells can replicate forever without ever being forced to snip "important" DNA during the replication part and ultimately apoptose. Furthermore, there is an enzyme whose job it is to lengthen telomeric DNA called, unsurprisingly, telomerase. Indeed, it is known that increased telomerase activity extends the lifespan of most human cell types in vitro¹. Sadly, high telomerase activity is correlated with the development of cancer, and the exploration of its use as an anti-aging therapy has thus been attenuated.

A recent study, published in the journal Cell, however, has explored the possibility of pumping-up telomerase activity in mice². The authors of this study enhanced telomerase activity in mice who had also been given a number of tumor-suppressing agents (p53, p16, and p19ARF) to render the rodents cancer resistant. This enhancement "improves the fitness of epithelial barriers, particularly the skin and the intestine, and produces a systemic delay in aging accompanied by extension of the median life span." (See figure, below.) The real significance of this study is that it is the first to demonstrate the ability of enhanced telomerase activity in extending lifespan in vivo, in a living organism.


from reference 2


Cells can only divide so many times before they become inviable (around 53 for humans). This hints at a fundamental limitation to the replication process. One component of this is surely that described herein of telomere shortening. However, there are many other ways that errors can accrue in DNA. On another note, it will be extremely intriguing to see how these sorts of aging stories regarding DNA and cell division relate to those concerning calorie restriction and associated metabolic pathways.

While the enhancement of telomerase activity is a piece of the aging puzzle, we have a long way to go in understanding the finite quality of cell division, and it may truly be inescapable, to say nothing of aging itself.

References:
1. Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE. Extension of life-span by introduction of telomerase into normal human cells. Science 279: 349-352, 1998.
2. Tomás-Loba A, Flores I, Fernández-Marcos PJ, Cayuela ML, Maraver A, Tejera A, Borrás C, Matheu A, Klatt P, Flores JM, Viña J, Serrano M, Blasco MA. Telomerase reverse transcriptase delays aging in cancer-resistant mice. Cell 135: 609-622, 2008.

On The Ways That Brains Change

from reference 1


It is well known that nervous system plasticity (the mutable quality of brains) underlies animals' ability to change their behaviors. However, it has been widely thought that such plasticity consists mostly of changes at synapses, the sites of communication between neurons, or in the intrinsic excitability of individual neurons - how likely a cell is to increase or decrease its voltage or to fire action potentials. New research challenges this view by showing that another type of alteration can be at work: single neurons can change the type of neurotransmitter they release in response to stimulation¹.

Specifically, this work addresses tadpole camouflage. Tadpoles can rapidly change (increase or decrease) the amount of pigmentation in their skin in order to blend in with their surroundings. The research I here refer to demonstrates that when frog tadpoles (Xenopus laevis) are stimulated with bright light, the number of dopamine-secreting (dopaminergic) neurons in the animals' brains increases, allowing them to adapt more rapidly to subsequent exposure to light.

When exposed to just hours of direct light, dark-reared tadpoles responded by doubling the number off dopaminergic neurons within a part of their central nervous system called the suprachiasmatic nucleus (SCN). Furthermore, these new dopaminergic neurons seem to integrate into the existing pathways for changing pigmentation. The authors were able to selectively destroy existing SCN dopaminergic neurons, eliminating the tadpoles ability to change pigment, and then rescue this ability with light exposure.

It remains unclear if this phenomenon is purely a developmental one, operating only prior to adulthood, an important caveat. None the less, the ability to change cell type is an as-yet unexplored form of neural plasticity which will have widespread implications for neuroscience research. Furthermore, this work may have even more direct application to human experience.

In human beings, the malfunction of certain dopamine-mediated signalling cascades (cell-level combinations of molecular interactions) have been implicated in seasonal affective disorder (winter depression). It is also well known that dopamine is intrinsically involved in the rewarding feelings delivered by food, sex and drugs. It may thus simply be the case that a lack of light stimulation leads to a lack of dopaminergic neurons, and thus to fewer episodes of rewarding experience during the winter months.

References:
1. Dulcis D, Spitzer NC. Illumination controls differentiation of dopamine neurons regulating behaviour. Nature 456: 195-201, 2008.

On Presidents and Science

I'm not the first by far to point this out, but I'm so happy that Barack Obama has been elected that I had to do something to mark the occasion. In fact I was totally oblivious to this imagistic event until Jessica excitedly picked up the magazine from my desk and proclaimed: "You have it!" Below are the front and back cover images from the September 25th issue of Nature magazine. It's not clear if this move was in any way intentional on the publisher's part, but it's pretty hilarious.

---

On Art from Science

Copyright © 2005 Hunter O'Reilly


"Hunter O’Reilly obtained a Ph.D. in genetics from the University of Wisconsin-Madison and graduated cum laude from the University of California, Berkeley. Her abstractions have been shown internationally including galleries in New York, San Francisco, England, Italy, Japan, the Czech Republic, Indiana and Wisconsin."





"Observations in the laboratory and the world around her inspire the shapes in her abstract oil paintings. Hunter's abstract art hints at both organic matter at the highest level (human faces) and at the smallest level (single cells). This section includes many images of artwork."

"O'Reilly teaches biology and art at Loyola University Chicago. She created a course, Biology Through Art, where students have the opportunity to create innovative artworks in a biology laboratory. Students view microorganisms, use DNA as an artistic medium, create music based on DNA sequence and see anatomy as art. The course culminates in students creating their own biological self-portrait."

More images here.

On What's Possible

"... it's just over fifty years since the launch of Sputnik. This event started the "space race," and led President Kennedy to innaugurate the program to land men on the moon. Kennedy's prime motive was of course superpower rivalry -- cynics could deride it as a stunt. But it was an extraordinary technical triumph -- especially as NASA's total computing power was far less than that of a single mobile phone today." (my emphasis)

This is how we're investing our technological capital?

References:
1. Rees M. Science: The Coming Century. The New York Review of Books LV: 41-44, 2008.

On Staying In Touch

from reference 1


In the world of neurotechnology, the prospect of exploiting the brain's inherently electrical quality by interfacing it with our own devices has become fairly commonplace. However, the main problem with such techniques is that the methods we have for making connections with the brain are inherently short term (on the order of weeks). This makes the dream of using implanted electronic interfaces for applications like controlling robot prosthetics one relegated to the future.

However, a study recently published in Nature details an advance in this field. The authors of this study were able to use brain signals from the motor cortex of a monkey to control his own limb (they'd anesthetized the normal neural pathways to make sure the endogenous connections were inoperable during the test). The unique quality of this feat lay, however, in the device used to read the signals from the monkey's brain. The implanted electrode had small piezoelectric motors which allowed it to move around in the monkeys brain in small steps (1 micrometer at a time), so that it was able to move towards strong signals, and back off neurons when it got to close, to keep from damaging them.

The connections are still only maintainable for about a month, but this type of technology and thinking is exactly what is needed to turn long-term electrical interfacing with the human brain into a reality.

References:
1. Moritz CT, Perlmutter SI, Fetz EE. Direct control of paralysed muscles by cortical neurons. Nature, doi:10.1038/nature07418