Slides, for your enjoyment

Hi all. Here's my slides if you're at all interested by what I was talking about: references are attached! I really do recommend looking at the first reference on microtubule thermodynamics... it will blow your mind!

Last Year's Exam

Last year's exam is here.

EXAM LOCATION

The exam will be at 11am (officially, 11:15) in room 6-407. That is, it will be in the classroom we have been using. This should make you all more comfortable (although we may adopt a less Arthurian table arrangement).

Allergy as a guardian

A new study has found more experimental data that seems to support the theory that something about the way the body typically reacts to allergies also guards the brain against devloping tumours.

The study drew on data from tens of thousands of people who had previously participated in four other broad health studies.

They found that patients whose bloodstreams were filled with immunoglobin E (or IgE), which is the antibody the body produces to fight many allergies, were also statiscally speaking less likely to developing a brain tumour, and if they did, would tend to survive longer.

“In terms of fighting the cancer or preventing it from growing, people who have allergies might be protected. They might be able to better to fight the cancer,” said one of the study co-authors.

The results need to be taken with a grain of salt, it seems, with a couple of annomalies appearing in the data.

For instance, while the appearance of tumours lessened significantly for patients with slightly elevated levels of IgE, the same was not true for those patients with much higher levels of the antibody, which means there is either a failure somewhere in the data, or we simply don't understand enough about why IgE appears to have this protective effect.

Also, of the thousands of people included in the data, only 159 went on to develop brain tumours. These people were compared against a control group of over 500.

Still, this study is not without precedent. Earlier this year, a team at Chicago conducted a similar study into the glioma-fighting qualities of allergies, and also found that it had a positive effect on patients.

In any case, while it's not clear how or even whether it's this allergy-produced antibody doing the good things, it seems more and more likely that allergies might actually have an upside.

Source:

http://news.brown.edu/pressreleases/2011/10/allergies

BRCA1: Tumour suppresor gene for breast cancer?

The protein encoded by the tumour-suppressor gene BRCA1 may keep breast and ovarian cancer in check by preventing transcription of repetitive DNA sequences. This explanation brings together many disparate theories about how the gene functions and could also shed light on how other tumour suppressors work.

Since the discovery in the mid-1990s that defects in BRCA1 strongly predispose women to breast and ovarian cancer, researchers have suggested numerous ways in which the protein might stop cells from becoming cancerous. Some have focused on its ability to repair DNA damage, whereas others have studied how it regulates cell-cycle checkpoints, transcription or cell proliferation. But until now, no unifying theory of how these different functions might prevent breast and ovarian cancer has emerged.

The group studied cells from mice that lack the Brca1 gene. Along with the usual problems attributed to defects in BRCA1 (in areas such as cell-cycle regulation and DNA repair), the researchers also found in these cells a surprising paucity of 'heterochromatic centres' — dense packages of normally untranscribed, repetitive sequences of DNA near a chromosome's centromere. Instead, these DNA regions were highly active, churning out large numbers of RNA transcripts called satellite repeats.

In normal cells, the BRCA1 protein keeps these regions silent by tagging histones, or DNA packaging proteins, with a molecule called ubiquitin. When the researchers added artificial ubiquitin–histone complexes to the mutant cells, the cells recovered, suggesting this was indeed the Brca1 gene's core function. Conversely, flooding normal cells with satellite repeats brought on hallmarks of genomic instability such as chromosome breaks and accumulating mutations – all thought to be features of BRCA1 loss in cells.

People have found BRCA1 in many places, doing many things. All these processes involve heterochromatin, so maybe we have one mechanism that allows the explanation of a large number of observations people have made about BRCA1.

It's still not clear how this mechanism could explain the tumour suppressor's specificity to breast and ovarian tissue, but those tissues are, for some reason, especially sensitive to the loss of BRCA1 function.

Another research group had satellite repeats produced in many different types of tumour tissue, including those that lack BRCA1 mutations, suggesting that multiple pathways have gone awry in cancer to impair heterochromatin maintenance. However, the explanation is still not sufficient to give a clear answer to some puzzling questions on how satellite repeats could have such wide-reaching effects on cellular processes.

Patients with BRCA1 defects initially have one mutant copy of the gene and one normal copy, then lose the functioning copy as the tumour develops. But because the researchers studied cells completely lacking Brca1 , the findings do not explain why patients are initially predisposed to tumours, but rather why tumours develop after the functioning copy of BRCA1 shuts down. Thus there is a need to understand how one defective Brca1 copy can predispose people to tumors.


Source:

Zhu, Q., G. M. Pao, et al. (2011). "BRCA1 tumour suppression occurs via heterochromatin-mediated silencing." Nature 477(7363): 179-184.

Ting, D. T., D. Lipson, et al. (2011). "Aberrant Overexpression of Satellite Repeats in Pancreatic and Other Epithelial Cancers." Science 331(6017): 593-596 %R 510.1126/science.1200801.

Fatherhood: Makers of Men

Men may not go on a hormonal rollercoaster with their pregnant partners, but once the baby shows up, the levels of testosterone drop. The hormone drop is due to the property of testosterone, which tends to boost behaviors linked to competing for a mate, risky activities that may conflict with the responsibilities of fatherhood. The biggest testosterone drops were observed in fathers of newborns and those highly invested in child care. The finding that fathers are hardwired to care for children adds to previous cultural models of human evolution, which traditionally depict the mother as being hardwired for hands-on child care.

The study followed 465 men participating in the Cebu Longitudinal Health and Nutrition Survey, started in the Philippines in 1983, when the participants were 1 year old. At age 21.5 (in 2005), the researchers tested the single male participants' testosterone levels when they woke and when they went to sleep. The measurements were repeated at age 26 (in 2009), when about half of the participants had become fathers.

Men who stayed single showed a small age-related decline of about 12 to 15 percent in the male sex hormone, while the testosterone levels of new fathers — those with a baby between 1 month and 1 year — on average dropped about 30 percent. Hormone levels in fathers of newborns (1 month and younger) dropped four to five times lower than levels in single men levels and twice as much as fathers of older children.

Newborn babies come with really intense physical, emotional and psychological changes. This is seen in men's biology responding to that, in line with what is expected in men trying to transition into this new role of being a father to a newborn.

As to the effect of the lowered testosterone, the researchers can't be sure. There could be effects on libido and muscle mass, though they are probably mild, since the participants' levels are still within the normal range.

Lower testosterone could influence the amount of time a man spends with his family, essentially by tempering his urge to go out and reproduce. Higher testosterone has been associated with increased risk-taking and competition with other males. This could be why testosterone levels are even lower with increased child care investment.

The finding may also explain why having a partner and becoming a father are good for a man's health and longevity. This could be somewhat mediated by the changes in testosterone levels. Some researchers believe testosterone lowers immune function: Higher testosterone levels may interfere with the immune system's ability to fight off infection. If this is true, lowering testosterone could be an investment in men's health. The researchers plan on following up with these men at around age 30.

Source:

Gettler, L. T., T. W. McDade, et al. (2011). "Longitudinal evidence that fatherhood decreases testosterone in human males." Proceedings of the National Academy of Sciences %R 10.1073/pnas.1105403108.

Inheritability of Longetivity

In October 2009 Stanford University geneticist Anne Brunet was sitting in her office when graduate student Eric Greer came to her with a slightly heretical question. Brunet's lab had recently learned that they could lengthen a worm's lifetime by manipulating levels of an enzyme called SET2. "What if extending a worm's lifetime using SET2 can affect the life span of its descendants, even if the descendants have normal amounts of the enzyme?" he asked.

The question was unorthodox, Brunet says, "because it touches upon the Lamarckian idea that you can inherit acquired traits, which biologists have believed false for years." The biologist Jean-Baptiste Lamarck theorized in 1809 that the traits exhibited by an organism during its lifetime were augmented in its offspring; a giraffe that regularly stretched its neck to eat would father calves whose necks were longer. The idea was largely discredited by Darwin's theory of evolution, first published in 1859. More recently, scientists have begun to realize that an organism's behavior and environment may indeed influence the genes it passes to its offspring. The heritability of those acquired traits is not based on DNA, but on alterations in the molecular packaging that surrounds a gene. When Greer approached Brunet in 2009 with his question about worms and SET2, such "epigenetic" inheritance had only been discovered for simple traits such as eye color, flower symmetry and coat color.

The study used Caenorhabditis elegans worms with very low levels of SET2. The enzyme normally adds methyl molecules onto DNA's protein packaging material. In doing so, the enzyme opens up the packaging material, allowing the genes to be copied and expressed. Some of those genes appear to be pro-aging genes. The group knocked out SET2 by removing genes that code for it. This had the effect of significantly lengthening the worms' life spans, presumably because those pro-aging genes were no longer expressed.

Next, the long-lived, enzyme-lacking worms mated with normal ones. The offspring had the regular genes for making SET2, and even expressed normal amounts of the enzyme, but they lived significantly longer than control worms whose parents both had regular life spans. The life-extending effect carried over into the third generation, but returned to normal by the fourth generation (in the great-grandchildren of the original mutant worms). For the first few generations, having a long-lived ancestor increased life expectancy from 20 days to 25, extending a worm's longevity by 25 to 30 percent on average.

The group have not yet determined the exact mechanism for the lifetime extension, or which molecules are at work. The knowledge that epigenetics can impact a complex trait like life span has scientists curious to find out what other kinds of traits—such as disease susceptibility, metabolism and developmental patterns—are epigenetically heritable. Because epigenetic effects can be modified by environmental stimuli; it is possible that some of these traits "could be determined, at least in part, by the environment and lifestyle choices of parents, grandparents or even great-grandparents."

The study’s results are also exciting because the genes that code for the life-lengthening SET2 enzyme exist in other species, including humans. Brunet says she wants see if the results can be replicated in vertebrates, such as fish and mammals. Those questions will not be answered for many years, because it is unknown whether the SET2 complex has the same function in other species, and because those species have longer generational time frames.


Source:
Greer, E. L., T. J. Maures, et al. (2011). "Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans." Nature advance online publication.

Facebook and the brain

Scientists have discovered a link between Facebook friends and brain size, suggesting social networking could possibly change your brain - or that some people are just 'hard-wired' to make more friends.

Four brain areas, which are known to play a role in memory, emotional responses and social interactions, are larger in those with longer friend lists. But the English scientists say that so far, it i snot possible to say whether Facebook is a brain-changer.

"The exciting question now is whether these structures change over time -- this will help us answer the question of whether the Internet is changing our brains."

The team of scientists used magnetic resonance imaging to study the brains of Facebook-addicted 125 university students. They then cross examined the brain scans with those of a further 40 not-so-addicted, or non-using, students.

What they found was a correlation between the number of Facebook friends and the amount of 'grey matter' in the amygdala, the right superior temporal sulcus, the left middle temporal gyrus and the right entorhinal cortex. Or, in layman's terms, some fairly useful parts of the brain.

Grey matter is the layer of tissue where mental processing occurs, and its thickness, specifically in the amygdala, was also linked to the number of 'real-word' friends a person has. In the other three areas, the connection between grey matter thickness and friends applied to online only.

Technically, if the research is proven, we could scan a person's brain and find out how long they spend interacting online, and how long they communicate in the real world.

Source:

http://www.newsdaily.com/stories/tre79h89l-us-facebook/

New treatment for haemophaelia

Haemophilia is a group of hereditary genetic disorders that impair the body's ability to control blood clotting or coagulation, which is used to stop bleeding when a blood vessel is broken. Treatment to this disorder is usual costly, thus research on a new protein treatment is needed to solve this problem.

A research team at the Children's Hospital in Philadephia, USA found that a custom built variety of coagulation factor Xa (FXa) was effective in controlling and clotting bleeding in haemophilliac mice. It appeared to do so more safely, and with greater long term prospects.

Traditionally, haemophilliacs require fairly regular infusions of clotting proteins in order to avoid uncontrolled bleeding.

Often, the body perceives these proteins as foreign organisms that need to be eliminated, which creates an immune response that more or less makes protein treatment useless.

At this point, the only other option for sufferers is spend a small fortune on drug treatments instead, and even this isn't guaranteed to work.

The thrust of this new treatment, according to the study team, is to take the naturally occurring Fxa and reshape the actual protein into a customised shape, which not only means that it stays in the system for long and requires a lesser quantity of protein, but it also means doctors can much more easily control the way the protein interacts with other physiological systems, making it more predictable and safe to use that the unpredictable natural FXa.

"Our designed variant alters the shape of FXa to make it safer and efficacious compared to the [naturally occurring] wild-type factor, but much longer-lasting in blood circulation," said the head researcher.

Sneaky Shrimp Smash and See Sircularly

Yes, I am aware that it is spelled with a `c'. As Josh has already alluded to, I have had this draft sitting around for a while now...

Mantis shrimp are about as extreme as a small crustacean can get! Not only are they beautifully coloured, they can generate shock waves, smash glass and see circularly polarised light. They even feature in a trading card game. Needless to say they have also been the subject of many great articles.

The punch of the mantis shrimp is so forceful that it is capable of generating cavitation. Plenty of people talk about it but no-one really seems to explain how it is capable of punching so quickly, especially underwater! I did track down one guy who does discuss this, and the paper that it's all drawn from. Essentially, the mantis shrimp is able to get enough energy into the punch by pre-tensioning a resilient elastic mechanism within its arm. This means that it doesn't have to be able to generate a huge amount of power: it can tension the elastic relatively slowly, then release the whole lot of energy very quickly (this is the idea behind the flywheel in more mundane mechanical systems).

Their claws can accelerate at 100 thousand metres per square second and reach a top speed comparable to your car on the highway: the forces involved range into the thousands of newtons, which isn't bad considering they reach only a few dozen centimetres length (around 25cm). The rapid motion of the mantis shrimp's arms means that the shear rate at their surface is huge: so huge that the pressure difference between fluid streams around the claw (definitely high Re) are sufficient to cause cavitation.

Cavitation is the formation of a gas bubble inside a body of liquid as a result of rapid motions. It can be heard when you do donuts in your boat (not that I've done this.... *ahem*) and can cause quite a bit of damage: the rapid collapse of cavitation bubbles generates shockwaves that can cause pressures of up to 9MPa (with a bubble only 2.5mm across!). The collapse of these bubbles could be considered to be a great example of an irreversible adiabatic process... the compression of the gas raises its temperature to around 5000K, allowing it to briefly fluoresce, in a process collectively referred to as sonoluminescence.

The net effect is that a prey item gets smashed with a knobbly calcified arm, then battered by broadband sound at 240dB, then eaten! This seems a little excessive for catching and eating snails... hardly the most nimble prey.

In addition to their deadly cutlery, mantis shrimp are able to distinguish between circular and linear polarisations of light. They do this by passing light through a cell which acts like a broadband quarter waveplate, taking circularly polarised light in and giving linear polarisations out. As it happens, this waveplate is `better' than our own manufactured waveplates, in the sense that it outperforms any human-manufactured material over the visible spectrum (waveplates are generally manufactured with a specific wavelength or very narrow range of wavelengths in mind, so don't work well at other frequencies). Even more interesting, the cell itself is also a photoreceptor! This is just the beginning when it comes to mantis shrimp vision... but I'll leave that to those better qualified.

By the way, the actual shrimp is fluorescent too!

Enjoy!

Last Assignment

Your turn 10C, 10D,
Problems 10.1, 10.4

Due this friday (late policy up to Wayne, who by elimination is the one marking them).

-Seth

Presentation Marking Criteria

This is the marking criteria from PHYS3900 presentation, I think it's general enough to be used to grade our presentations.

Integrate-and-fire

The integrate-and-fire model of neural networks followings on nicely from my last post and also ties in with the subject of the next chapter. It's a phenomenological model of neurons which "integrates" the depolarizations incident on a neuron's cell body and "fires" an action potential down the axon when the depolarization reaches the threshold value. Often additional time dependent exponential decay terms are added to better replicate observed behaviour; when calibrated carefully this model is a cheap and robust method of investigating neural networks.

While integrate-and-fire doesn't allow for the investigation of temporal encoding, it can be used to model large neural networks and captures some of the effects of combining analogue and digital signals along with the topological structure in the network. It is a model liked by many computational neuroscientists and disliked by biologists a physicists in equal measure (just for different reasons).

For more details see: A review of the integrate-and-fire neuron model: II. Inhomogeneous synaptic input and network properties.

I have detected James' draft post on shrimp circularly polarised light detection: I have a National Geographic at home which says a particular species of shrimp can detect something around 21 wavelengths/polarisations of light. Quite impressive...

Another group from BIOL1040 that I asked questions of had found research on the different spectra that primates can detect. Humans are generally trichormats (3 frequencies + rods), as are most Old World primates (and most marsupials) whereas except for Howler Monkeys, New World primates and most other mammals are dichromats (2 frequencies + rods). The interesting bit about New World primates is that their gene structure allows females to be trichromats whilst males are dichromats. This occurs because the gene for red and green colour sensing (blue/violet apparently was the first type to develop) occupies the same locus (i.e. spot) on the NW primate X-chromosome, so females can have both genes (one on each X chromosome) and are trichormats (unless they recessively possess only the same gene on both X chromosomes) but males can only ever possess one of the genes (on their single X chromosome). Howler monkeys are thought to have re-developed trichromatic vision from gene duplication; apparently mammals in dinosaur times were tetrachromats (could see 4 colours). The evolutionary reason for this unusual set-up in NW primates was suggested to be that darker conditions favour dichromatism (it's better in low light conditions, apparently) whereas in lighter conditions, trichromatism is more useful (you can tell the differences between fruits, for example, or between paintings, local creatures of the Amazon)—communities of primates of one species can therefore utilise all of the members' vision ranges to the group's advantage. I was a little skeptical about this point, however, as I don't really see why trichromatism is a disadvantage in low light conditions; surely low light sensitivity is more dependent on rods and eye structure?

An analysis of the wavelengths of the opsin pigments would be interesting. I must also remember to post another BIOL1040 response on eye structure and detection pigments (e.g. opsin) in cubozoans (i.e. box jellyfish) compared with other lineages (e.g. vertebrates).

Other interesting visual patterns include lungfish, which see four wavelengths, bees, which see UV, green and blue, and many bird species in which juvenile members see four wavelengths but adults only see three or two.

Then there are crustaceans....

Also, an interesting thing I read in a Scientific American concerned the human brain's way of interpreting colours. Apparently, we see in a blue-yellow channel and a green-red channel, preculding the existence of greeny-reds and bluey-yellows. Unless you torture a subject's poor brain for some time. I may have to search for the issue, I read it in a doctor's surgery some time ago....

Gravity Tropism

Hello (yet again),
Today in BIOL1040, I came across an interesting problem: how do plants sense gravity and grow in response (separately from other stimuli, such as when a seed is deeply buried)? It seems very unlikely that plants have 'gravity' eyes, so my suggestion is that some mechanism can detect which direction requires the most energy to grow in. Another hypothesis is that the mechanism which facilitates growth orients itself via gravity and is then constrained to provide growth in the upwards direction by structure. These mechanisms might be proteins or hormones stimulate such growth. Plant cells can also restrict their growth to upwards or downwards based on the orientation of their cellulose microfibrils, and since turgor pressure drives this kind of elongation, perhaps the direction of growth is easier to achieve once the first cells are aligned.

Josh H

Light Torture

Hello (again),
A conversation with Devin the Canadian laser physicist this afternoon revealed an interesting phenomenon: while infrared lasers cause 'heat' burns to skin, UV lasers cause 'sun' burns to skin and green lasers vaporise cardboard, apparently 400 nm (violet) lasers stimulate one's nerve endings, causing pain (much like a green-ant bite) but no damage to cells. I thought that this was a very interesting phenomenon and I didn't immediately see any direct cause. It seems unlikely that human nerve endings have channel rhodopsins (otherwise we would feel sensations depending on the lighting we are in! Perhaps good for parties...), so is the light directly affecting cells? Perhaps there is a protein that is directly affected by violet light, and the high intensities of lasers in the laboratory are high enough to cause an effect (this may be why the average party elicits no stinging sensations)?

Perhaps those of use with access to laser laboratories could investigate this phenomenon first hand (James...)? I think it would be worth the sting (which doesn't appear to have long term effects, other than those normally experienced by physicists) to be able to say, "I was stung by light!"

Josh H
PS: This would also offer a way to 'humanely' torture victims without causing any physical damage (and so leaving no hard evidence). This would mean that the phenomenon is well known and that it is currently in use....

Electroreception (Wayne's 6th Sense)

Hello everyone,
Wayne has beaten me at posting about electroreception, but since my group's chosen BIOL1040 eConference assignment topic was electroreception differences between the Guiana dolphin and the Atlantic stingray, I thought I could provide some interesting information.

Wayne correctly summarises the origin of electroreception in fish: the lateral line. While I'm not sure what the lateral line has diversified into in the mammalian vertebrate lineage, the electroreception of monotremes and the Guiana dolphin arises from mechanosensory organs (and, interestingly, a different set of nerves). These same mechanosensory organs (whiskers, to us mortals) are widely used in marine mammal architectures (e.g. seals). The paper on the Guiana dolphin even suggested that the mechanosensory organs of other mammals may have branched into electroreceptive roles in other mammals, too.

Electroreception is quite an interesting phenomenon in itself: as far as I can tell, electroreception in mammals occurs directly via potentials across the nerve cells of the electroreception organs, usually with the assistance of a gel-like substance. Platypodes even have structural mechanisms that are thought to reduce noise ('daisy chains'). Fishies have far more structurally complex organs, but I'm not sure exactly how their sense works: it appears to be caused by a cell membrane potential gradient (as in mammals) but there are still 'kinocillia' in some electrosensory organs—perhaps movement of a kinocillium assists in detection?

Another interesting point is the fact that humans don't have mechanosensory whiskers. Is this because the nerve-blood vessel assemblies do not exist in humans, or do our lips (and 'fake' whiskers) occupy the same region? I have often heard that the lips are very sensitive to both pressure and temperature gradients. Would it be possible to biologically engineer electrosenses in humans? This brings up yet another interesting genetic biology question: how did electroreceptors evolve from mechanoreceptors? Did the nerve endings just become more exposed, until they could detect electric fields readily? This suggests that other animals could very easily have (limited) electroreceptive abilities, at least in water. Perhaps our lips can detect large electric field gradients, also?

I shall have to provide the paper references later, when I have more time. A search for 'Guiana dolphin electroreception' should reveal the paper on the Guiana dolphin, and a search for 'Euryhaline stingray electroreception) should reveal the Atlantic stingray paper. The stingray paper also considered the mechanisms of sensing, particularly whether or not the rays detect absolute field strength or field gradients: their findings suggest field gradients.

Josh H
PS: I have now received everyone's assignments, they are now awaiting marking (like good little assignments). Thank you.

Microchiroptera (Josh's Version, sort of...)

Hello everyone.
More on Wayne's original topic! Admittedly, I hadn't read much about this before, although it is interesting.

In the recent BIOL1040 Biohorizons eConference assessment event, we were tasked with asking questions of the other student responses in our area. My group's area was diversity and adaptations in sensory biology. One of the groups I asked a question of had researched microchiroptera, those bats which generally hunt insects with echolocation (also known as microbats). They have other anatomical differences to megabats (fruitbats etc., of which only one uses echolocation), but their main feature is echolocation. The papers the group used to create their response were investigating the possible use of echolocation abilities as a means of communication. The hypothesis was that microbats use and are sensitive only to very specific ranges of frequencies, and that they either diversified from one echolocating frequency or echolocation arose separately in several lineages/was lost in some and re-emerged. I thought that an interesting biophysical question is how sensitive a species can be to certain frequencies. It is my understanding that the current evidence suggests a strong bias in the brain to acknowledge only certain frequencies, but how is this enacted physically? Also, how specific can the frequency production and reception be, if we consider fundamental physical limits? Afterall, most microbats are of similar size and evolutionary background, so one would expect great similarities in their hearing and vocalising organs.

Josh H

Is it always best to be discrete?

When most of us think about the fundamental language of computational devices we think of ones and zeros; discrete representations of on and off. While this is overwhelmingly the case in modern computational devices, it was not always thus. Pre-1960's technology, such as that used in the second world war, often performed calculations using analogue computation. In an analogue computer, calculations are performed by using an "effectively" continuously-changable physical quantity such as electric potential. This has some significant advantages as well as many disadvantages, for a detailed discussion see: Analog Versus Digital: Extrapolating from Electronics to Neurobiology; Sarpeshkar. (A highly recommended read!)

Perhaps the most interesting aspect of analogue computing is how neurological systems use it in conjunction with digital signals (again see Sarpeshkar for details). There are two obvious aspects of analogue information processing in neurobiology, temporal encoding and the integration of passive membrane signals by the neuronal cell body. Temporal encoding works by coupling a neurons firing rate to a particular brain-wave's phase (by brain-waves I mean the background oscillations in brain activity, not ah ha! moments).

Perhaps the most crucial aspect of neural computation however is the structure of the networks themselves. Siegelmann and Sontag provide a theoretical model of analogue computing within neural networks.

Analogue computing is an understudied and (in my opinion) a fascinating field of research.

Crazy Concentrations

Hi everyone. I was pondering how big the concentration fluctuations of ATP at equilibrium would be in a (dead) cell, so started trying to apply some statistical mechanics. The results are attached... I am interested in your impressions/thoughts/simplifications/ridicule, etc.

A new way to view DNA replication

The traditional view of DNA replication is very conservative. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule. Each strand of the original double-stranded DNA molecule serves as template for the production of the complementary strand.

However, this group of researchers introduced a new idea. Elaborate webs of DNA have been made that can copy themselves outside cells. Unlike DNA in nature, which replicates inside cells, these webs exist freely and suggest how self-replication might one day be an alternative to conventional fabrication for very tiny structures.

A self-copying DNA double-helix would not be news. Living cells have been doing this for billions of years, and researchers have done it in test tubes for decades. But in a new twist, the group has created elaborate webs of DNA never seen in nature and persuaded these structures to make exact copies of themselves.

Each piece of the DNA web is a "tile" made by joining 10 double helices together. The team made two slightly different versions of these tiles, A and B, and joined them together to make a batch of identical strings of seven tiles. These "parent" strings then produced daughter strings made of tiles called A' and B', whose base pairs were exactly complementary to those on the A and B tiles. The researchers used the daughters as a further template to produce an exact copy of their parents

Although these particular strings were designed as a proof of principle, without any practical application in mind, the technique could allow more useful structures to be rapidly and easily grown. Other molecules, with useful or novel properties, could be attached to the DNA tiles. The DNA itself would act as a scaffold, arranging the other molecules into the desired structure, and then later creating more and more copies.

Source:

Wang, T., R. Sha, et al. (2011). "Self-replication of information-bearing nanoscale patterns." Nature 478(7368): 225-228.

Dark Matter for Genomes?

A study into mammalian genomes has found and documented large amounts of what has been referred to as the 'dark matter' of genetics responsible in large part for the way that the functions of genes themselves are regulated.

This dark matter is a simple term to describe large amounts of data there in your body that are not a component of your genes. Instead, this data helps regulate the way that your genes manifest and function.

The study examined the genetic material of 29 mammals, and compared these sequences of dark matter, trying to find similarities across the species.

This new map is said to reveal almost 3 million previously undetectable elements in non-coding regions that have been carefully preserved across all mammals, and whose disruptions appear to be associated with human disease.

Aside from the simple awesome factor of finding something new to have a look at in the genome, the researchers also think that because of the way this dark matter plays into genetic regulation, it may well help in finding out what causes the kinds of genetic disruption that results in disease in humans.

It also provides an interesting insight into the beginnings of the human race, showing the parts of the genome that are largely similar to other mammals, but also some 1,000 dark matter regions that have changed more recently, and are particular to the human and primate genome.

Source:

Lindblad-Toh, K., M. Garber, et al. (2011). "A high-resolution map of human evolutionary constraint using 29 mammals." Nature advance online publication.

Sixth Sense

Birds and some mammals are able to sense the Earth's magnetic field, using it to orient themselves and even look for prey. Other vertebrates can detect electric fields and use them for the same purpose. Apparently the fish from which humans and most other vertebrates are all descended had this sixth sense.

The development of hair in vertebrates - which is still not well understood - may also be related to this ancient ability, the study authors theorise. Understanding how such an ancient and essential system evolved could help evolutionary biologists examine the heritage of other complex organ systems, like eyes or the brain.

The vertebrates' common ancestor lived 500 million years ago and was probably a marine predator with good eyesight and a stripe along its side, which represented a lateral line system for detecting movement in the water. The line system, present in fish and some amphibians, contains sensory hair cells that are identical to the ones in our inner ears, which help the animal sense its environment. Fish use these cells to detect weak electrical signals in water, which helps them seek prey, avoid predators and even to communicate and school.

This line system is directly connected to the the evolution of other electrosensory abilities - the first time this connection has been described. Through millions of years of evolution, most birds, reptiles and mammals lost their lateral lines, as well as their electrosensory abilities (with a couple exceptions). Researchers at the University of Cambridge and Cornell University studied embryo development in paddlefish to watch how these electroreceptors form.

They noted that the cells form in the same pattern in developing embryos of fish and previously studied axolotls, which confirms it's an ancient system common to both lineages of vertebrates, actinopterygians and sarcopterygians. And they form immediately adjacent to the lateral line, which provides evidence that the two sensory systems share a common heritage.

This is interesting because these results will help biologists unravel the sensory capabilities of modern animals and their ancestors, and how the process of evolution allowed some animals, but not all, to keep this sixth sense. In my opinion, the reason why humans lost this sixth sense is maybe due to our capability to think over than using instinct as a drive to do something.


Source:
Modrell, M. S., W. E. Bemis, et al. (2011). "Electrosensory ampullary organs are derived from lateral line placodes in bony fishes." Nat Commun 2: 496.

SHAPELY ELECTRONS?

An electron bunch. (<10K)

As per the latest issues of Nature, there’s been some progress in the way of electron diffraction, specifically in ultrafast beam pulses and generation of “arbitrary shaped” electron bunches, and opening doors to new improvements in the study of biological molecules.  Using selective photo-ionization and acceleration of cold (~10K) Rubidium gas “ultra-fast” pulses are able to be generated yielding millions of cold electrons in a beam. These types of pulses may be useful for studying small biological molecules.

Biological molecules are small, obviously; they’re in t he order of a few nanometres sometimes and in order to study these by the method of electron diffraction, pulses, from a point-like source, are required to have intensities allowing for a large number of electrons. This feat has appeared almost impossible as short pulses of a few femtoseconds usually generate only a few electrons at a time.

Couldn’t one just up the intensity?

Apparently not. When generating pulses of a useful intensity so as to deliver more electrons, it is here where Coloumbic effects become significant (ie repulsion).  These effects cause the beam to “blow apart” and degrade the beam’s coherence – “Coloumb expansion”. (NB – coherence of the beam is a measure of how constant the phase remains throughout. Coherence length, Lc, is the distance from source to a point where coherence disintegrates.)

An ellipsoid electron "bunch".

The above was remedied by emitting the electron pulse from a large area rather than a point-like source, and also by tailoring the shape of the pulses to be 3D-ellipsoids – “electron bunches”.  These bunches are uniformly distributed in charge and have internal “self fields” which are linear. These internal fields allow for manipulation of the phase-space distribution of the electrons without compromising coherence of the beam.

Be that as it may, ellipsoid bunches are difficult to achieve, although it is possible to generate quasi-2D-pancake-like and 1-D-cigar-like approximations which are rough projections of the ellipsoid.  

More study in this field is definitely needed. However, it does indicate the possibility of significant improvements in electron diffraction.

Any thoughts on this?

Vredenbregt, E. & Luiten, J. (2011) "Electron Diffraction - Cool Beams in Great Shape". Nature Physics, Vol.7, October 2011, pp 747-748.

The Colour of Brownian Motion

Brownian motion in a fluid at thermal equilibrium is typically modelled (in the optical tweezers community at least) as a continuous stochastic process with a white power spectral density... this simply means that the thermal forces (or torques) are continuously differentiable in time, and randomly drawn from a distribution which carries an equal amount of power in every equally-sized frequency window, regardless of where that window is along the the frequency axis.

This is equivalent to saying that the that the thermal forces have no memory of the position or behaviour of a particle undergoing motion in the fluid i.e. they are uncorrelated in time.



Recent work has shown experimentally that this is not in fact true: thermal forces are correlated in time, even in very simple fluids. This is seen by calculating the power spectrum of a particle's motion. We can think of the power spectrum as a Fourier decomposition of the time-domain motion. Pure white noise results in a flat power spectrum, and 'coloured' noise has more or less energy at different frequencies (blue noise has more energy at high frequencies, and pink noise more at red).

If the particle is subjected to white noise its motions have a Brownian spectrum, with more energy at low frequencies (and a characteristic dependence on the inverse square of the noise). In their experiments, Franosch et al. found that their measurements indicated that the thermal noise actually is slightly blue: it has more energy content at high frequencies than expected.

What does this mean? It means that the thermal forces are correlated with the motion of the particle! Is this surprising? Not really: in fact, it makes perfect sense. The thermal motion cause the bead to move, but the bead causes the fluid to move, creating some sort of feedback loop which carries information about the motion of the particle.

Is this the whole story? Nope: a blue spectrum, just like a white one, carries infinite power, so cannot possibly apply over the whole range of frequencies. They just happen to be nice approximations. People have already seen where these fail: if the fluid is dilute enough (near vacuum) it is perfectly possible to see the ballistic motion which occurs between thermal impulses, and its even been shown that the same thing happens in liquids!

Enjoy!

Putting the Physics in Biophysics

True, we in the biophysics world aren't generally all that interested in the sub-atomic world, or the interstellar one for that matter (although random walks pop up in both cosmology and biophysics)... but that shouldn't stop us being interested in pure physics!

Of course, I am referring to the faster-than-light neutrino measurements made by the OPERA experiment. For those who haven't heard, the researchers at Gran Sasso (an underground lab in Italy) claim that neutrinos have broken the speed of light by around 20 parts per million.

If this is confirmed to be true then it will mean huge things for physics: not least because it goes against both general relativity and relativistic quantum mechanics!

Doing some reading around, it seems that their are two main competing refutations right at the minute. One is that people simply messed up the measurement by failing to account for the motion of GPS satellites relative to the planet: it would indeed be embarrassing if this turned out to be true. The second says that if neutrinos could exceed light speed they would be carrying so much energy that they'd release electron/positron pairs, creating light and slowing the particle down over a distance much shorter than that between CERN and OPERA.

There are also some string theory advocates out there.

It will be interesting to see how this pans out. In the meantime, I still haven't managed to go back in time and patent tomato sauce - perhaps I should work on a new theory of physics instead!

In all seriousness, I think the time for scoffing at the suggestion, if that time ever comes, is in the future when independent experiments have soundly trounced the idea of faster-than-light particle motion. Too often in the past have people been ostracised and ridiculed by the physics community, only to be proved correct a few decades down the track!

Quantitative Evidence of Rigged Accounting from the Statistics of Numbers

http://econerdfood.blogspot.com/2011/10/benfords-law-and-decreasing-reliability.html

Chapter 9 Assignment

Your Turn 9B, 9E, 9I, 9M
Due next friday (Oct. 21).

A seemingly contradictory result

I mentioned in my previous post that I would describe my favourite example of a seemly contradictory result in science. (The following is an edited excerpt from an article I wrote a couple of years ago.)

G. I. Taylor in 1909 under to tutelage of J.J Thompson conducted an experiment in which a double slit in front of a photographic plate was illumined by a very dim light source – equivalent to a candle burning at a distance of one mile away. The intensity was set to ensure that the hypothesized photons would pass through the slits one at a time; thus if the usual diffraction pattern was observed it would require the photons to ‘interfere with themselves’ – a truly immoral thought. After a three month exposure – conveniently timed so that Taylor could partake in a sailing trip he had planned – the usual diffraction pattern was observed. He concluded that light must be fundamentally wavelike as the idea that particles could interfere with themselves to generate a diffraction pattern was inconceivable. Not until 1987 when Robert Austin and Lyman Page conducted experiments in which they recorded single photons striking a surface behind a double slit was it irrefutably confirmed that Taylor had misinterpreted his results, in fact photons do “interfere with themselves”.

Three slit diffraction recorded using a single photon counting CCD camera: (A) after 0.033s exposure, (B) after 1s exposure and (C) after 100s exposure; work by Robert Austin and Lyman Page.

On the dependence of initial conditions on temporal dynamics in position space

When commenting on James’ post “Fruit flies smell vibrations?” I was reminded of a discussion I heard on the radio recently, the discussion was on the nature of politics in general and its parlous incarnation in this country at the moment. The point was made that perhaps the greatest flaw of politics is the attitude towards changing ones position on an issue. The norm seems to be that as a politician you form an initial position (or your party forms one for you) and you defend that position as if your political career depends on it, irrespective of changing information. Science, at its best, does not fall into this mindset. However I believe there are shades of gray on this issue.

It is often the case, particularly when a scientific field is in its infancy, that results seemingly contradict each other (my favourite example of this will be the subject of my next post). Due to this apparent contradiction, the point at which one of the interpretations is more strongly supported by the evidence than another is almost always a subjective matter (initially at least). Hold onto your initial position too strongly and you can become blind to the obvious, while if you are too fickle you run the risk of falling victim to herd mentality. The history of science is full of example of both cases. That is, in which individuals have held onto ideas well beyond their use-by date, or in which they have been the subject of derision by their peers for their position only to be vindicated a decade on with a Nobel.

As with most things there is no hard and fast rule which can be followed. However I believe politicians should heed the wise words of Maynard Keynes: when criticised for changing his position on an issue he replied, “When the facts change, I change my mind. What do you do, sir?”

Fruit Flies Smell Vibrations?

You probably recall our conversation on Friday concerning a recent paper which claims that fruit flies (Drosophila melanogaster) are capable of distinguishing between deuterated and undeuterated compounds.

Franco, M. I. et al., (2011), Molecular vibration-sensing component in Drosophila melanogaster olfaction, www.pnas.org/cgi/doi/10.1073/pnas.1012293108

This seemed like a tall order at the time, and still does, but after reading the paper I have to conclude that the authors were exceedingly thorough in ruling out as many experimental variables as possible: it definitely appears that the effect is completely real, and vibration sensing is a proposal which seems to be in keeping with the experimental results.

The paper is cogent and laid out in a thoroughly logical manner, systematically eliminating possible sources of bias. All the relevant data are given too.

Before we even get started, the authors point out that deuteration doesn't appreciably change bond length, stiffness or angle.

Potential bias #1 - humans have become accustomed to different scents throughout their life.
Solution -- use fruit flies: they have such short lives that you can ensure that they haven't become accustomed to a smell, and they are generally more sensitive to odotopes (odourant molecules) than humans to boot. Other studies have shown that humans can't perceive a difference between deuterated compounds and their regular isotopes, but the authors believe that (a) humans can't smell well and (b) we probably could tell the difference if the odourants were purified well.

The basic idea of the rest of experiment is simple: run two fragrances down either arm of a t-junction `maze' and see which direction the flies pick most often.

Potential bias #2 -- Some visual, auditory or other cues may lead to flies picking one arm over the other, even in the absence of olfactory stimuli.
Solution -- run a control: one with wildtype flies and no odours, and another with mutant fruit flies which cannot smell at all. It turns out that no significant differences are seen in either of these cases.

Big question #1 -- do flies show spontaneous (naive) responses to odourants?
Answer -- yes: no surprises here really.

Big Question #2 -- can flies distinguish between different isotopes of acetophenone (apparently a common perfume base)?
Answer -- yes! The hydrogen-bearing version is attractive, and as deuterium is added (3, 5 or 8 deuterium substitutions) the acetophenone becomes less attractive and then more and more repulsive. The same goes for octanol and benzaldehyde.

Big Question #3 -- can we teach flies to recognise a deuterated compound?
Answer: yes -- this was done by foot-shock, which apparently is a well-tested method of conditioning fruit flies. If conditioned to deuterated compounds the flies consistently chose that arm of the maze, even if it went against their naive reaction.

Potential bias #3 -- maybe it depends on the type of fruitfly chosen.
Solution -- try a different wildtype strain... which gives the same results.

Potential bias #4 -- perhaps the flies are only recognising and responding to different impurities left over from synthesis and purification of the different deuterated compounds.
Solution -- try conditioning them with one compound (deuterated or undeuterated), but then test them with a different type of compound that is also either deuterated or undeuterated (respectively). Amazingly, the flies can still differentiate the deuterated compound from its regular counterpart.
Potential bias #5 -- could there be residual odours?
Solution -- completely replace all of the tubing after every trial.

Big Question #4 -- if the mechanism underlying this discrimination is based on molecular vibrations we should be able to train fruit flies using deuterated/undeuterated compounds, but then test them using completely unrelated compounds that happen to have similar IR spectra in the region of 2200cm^-1 (C-D stretch vibration). Do we see similar effects?
Answer -- yes! It turns out that the CN triple bond has a similar vibrational frequency to C-D, so this was used to test against. Flies again could be conditioned with deuterated/undeuterated compounds, then select completely unrelated molecules with similar regions of the vibrational spectrum.

I have to admit that it sounds pretty conclusive: the flies are, in some way, sensing molecular vibrations, or something very closely related to them. The only really obvious way in which they could be wrong is if the whole thing were fabricated (I'm not suggesting it is though)!

The authors go on to outline the very core ideas behind inelastic electron tunneling spectroscopy, which they believe is a reasonable model for olfaction. An electron acceptor sits near a donor molecule, but electron transfer only occurs when a suitable intermediary is able to accept an amount of energy, becoming vibrationally excited. Perhaps this is how smell works: after all, we see light because the absorption of a few quanta of light are enough to cause a conformational change in a protein. Why shouldn't smell have a related mechanism?

I can see two obvious ways forward: the first is to selectively knock out each of the 62 different olfactory sensors that drosophila is endowed with, and test which is most important in the apparent discrimination of deuteration. With this determined, electrophysiology would be a must, probably along with gene expression analysis.

The second is to selectively deuterate different portions of materials, to see if the effect depends on the vibrational mode or just the frequency. This could involve some intense chemistry! Finally, perhaps some more dramatic investigations could be carried out: how about if tritium is used?

I'm interested to hear your thoughts!