Wednesday, January 29, 2014

Detailed mapping of the human frontal lobe


Humans and monkeys are closely related,  and even though human brains are much larger, they share a great deal of similarity in organization with those of monkeys. But humans have capabilities, especially in language and abstract reasoning, which are only modest in monkey species. It remains an ongoing question how the expanded abilities of humans are reflected in brain organization. Are human brains just bigger versions of a monkey template? Or do human brains have fundamentally new brain areas, either anatomically or by virtue of their functional connections? A recent study in Neuron by Neubert et al. [pdf link] studied this issue by using magnetic resonance imaging (MRI) to compare the brains of humans and macaque monkeys.
The frontal lobe of the human brain (source: Wikipedia).
The ventrolateral  areas, studied by Neubert et al are 44-47 and
(roughly) 10 and 11.
Neubert et al focused on the ventrolateral frontal cortex  (vlFC), because this area is associated with processes, such as language (for example, Broca's area) and cognitive flexibility, which are notably developed in humans relative to monkeys. Their study relied on two major MRI methods. To map if human brains contained new areas, not present in monkeys, they used diffusion-weighted MRI . This method extracts the magnetic resonance signals arising from differences in water diffusion, based on local tissue properties such as cell bodies, white matter fibers, or connective tissue. This type of MRI can sensitively and non-invasively reveal the neuroanatomy. 
To ask whether brain areas were differently connected in humans compared to monkeys, they used resting state functional MRI , which relies on correlated firing patterns to identify which neuronal areas are wired together.
Neubert et al. used these two methods on 25 humans and 25 macaques, and found a great deal of consistency in both the neuroanatomy and in the functionally correlated
brains. What's more, within the ventrolateral frontal cortex that they were studying, most areas in humans had a direct correlate-- anatomically and functionally-- with the macaques. They did find evidence for one area in human brain scans that did not have a direct equivalent in macaques. The lateral frontal pole region (FPl; labelled in red at the font of the brain in the image to the left), was distinctively human. It seemed to be anatomically related to area 46 (which is present in macaque, and shown in yellow in the figure) but lacking a lot of the functional connectivity of that region. 
Neubert et al. comment that the FPl is used in humans for strategic planning, multitasking, and for calibrating a correct response when many alternatives are available. 
This work is a very valuable effort to make an apples-to-apples comparison of brains in a region that is important for many of the traits that we consider most human. To really understand the significance of this area, it would be really helpful to include brain information from the nearest human relative, i.e. chimpanzees. It would also be very interesting if a specialized old-world monkey It would also be helpful to see whether niche (tree dwelling versus forest floor) or gregariousness could be correlated with the functional properties of the frontal lobes. Finally, Neubert et al noted some differences in long-range connectivity between humans and macaques from most areas in the frontal lobe. It might be that much of what we consider uniquely human might be enabled by these longer connections. 

Sunday, January 26, 2014

Genomics and immune evasion in a transmissible dog cancer

Nature and several other news sources describe gene sequencing of Canine Transmissible Venereal Tumor (CTVT), a sexually transmitted neoplasm which has spread among dogs worldwide. Transmissible cancers are extremely rare;  usually, tumor cells transplanted from one individual to the other are quickly recognized by the immune system. The other well-known example of a transmissible tumor is the Tasmanian Devil facial tumor disease.
Evasion of the immune system by transmissible tumors.
Tasmanian Devil facial tumor (A) is not recognized as foreign
because the species has too little diversity in MCH I and II 
genes. CTVT temporarily succeeds in escaping detection
through lower MHC I expression and by secreting the
immune response suppressant TGFbeta .
Figure credit: E.P. Murchison, Oncogene 2007.
This tumor is indeed derived from one single dog, and has somehow managed to survive and propagate among all kinds of dogs. One clue to its possible evasion of the immune system is that it downregulates the major histocompatibility (MHC) genes, which are used by the immune system to distinguish self from non-self cells. It has been speculated that dogs and Tasmanian Devils both suffer increased risk of cancer-contagion via their reduced diversity of MHC genes, which makes immune surveillance much less efficient.  Similarly, human patients on immune suppressants can occasionally obtain cancer from organ transplants.

CTVT, like all cancers, accumulates genomic mutations as it divides and grows. To get more information about the population characteristics of the disease, the scientists sequenced the entire genomes of tumors obtained from widely separated dogs- one in Australia, and one in South America. These samples would give an idea of the range of genomic variation in the tumor worldwide, and give a clue about the origins of the cells. A surprise from the sequencing was the high degree of similarity of the two, widely separated tumor isolates. A molecular clock calculation suggested the cells were only separated by 460 or so years, putting the worldwide dispersal of the disease at around the same time as Christopher Columbus; and around the same time that intensive breeding of dogs for particular purposes took off.  Since the disease is sexually transmissible, the use of infected sires to breed for many litters may have amplified the disease's spread.

10 year anniversary of the Opportunity Mars Rover

Nobel Intent has a nice write-up of the Opportunity Rover, which is still exploring Mars 10 years after initial touchdown. The positive experience of Opportunity has affected NASA mission selection, science, and public relations, and this type of rover may be the paradigm for NASA surface probes for the foreseeable future.

Friday, January 24, 2014

Now showing in a galaxy near you

A supernova has erupted in a nearby galaxy, M82, and will be bright enough to be seen with amateur telescopes.  It should continue to brighten for the next two weeks, and it should be one of the brightest
Image and caption: Nature
such events for Earth observers since 1987.
The M82 galaxy is a frequent imaging target because of its unusual cigar shape, and so it might be possible to identify what lay in the region before the supernova event by going back to historical surveys of the galaxy.
Based on the early spectral readings, this supernova is thought to be of Type Ia, a class which reaches predictable absolute brightness peaks-- their brightness as seen from earth is then a function of their distance, and thus they can be used as standard candles to determine the distance of far-away objects. Because of their importance to astronomical surveying, there is a lot of interest in what exactly leads to their big explosion.  Although the parent body for this type explosion is almost certainly a white dwarf star, the details of the detonation have been hard to simulate with computer models.  The 1987 supernova was of a different type, and its parent body was probably a blue supergiant.  The different classes synthesize heavier elements to different degrees. For example with Aluminium-27 is produced at a bit more than 200 fold greater abundance by Type II supernovae compared to type Ia.

Thursday, January 23, 2014

A micro-predator limits the spread of amphibian chytrid disease

Amphibians worldwide are succumbing to a fungal infection driven by a parasitic chytrid fungus,  Batrachochytrium dendrobatidis , which infects amphibian skin,  interfering with their ability to regulate salts and causing cardiac arrest. This fungal disease is thought to be a major factor in
Possibly a frog's best friend
devastating declines in amphibian numbers in Australia, New Zealand, and Central America-- and it's still going.

B. dendrobatidis fungus appears to have originally been endemic to southern Africa.  A plausible hypothesis is that international trade of the south Africa toed frog, i.e.  Xenopus Laevis,  which started in the 1930s, may be behind its worldwide spread. It's a little uncomfortable to think that a laboratory organism studied by developmental biologists may have promoted such a devastating spread.

There may be some hope for control of this disease through fungus-eating protists native to the frog's home ponds. Even in heavily infected areas, amphibians in some ponds appear to remain relatively unscathed while populations in nearby ponds are decimated. A recent study of frog populations in the Pyrenees suggest that one key difference in the disease course is the numbers of rotifers, pond denizens which eat a lot of fungus. Importantly, the rotifers seem to preferentially eat the infectious stage, or zoospores, of the chytrid. Thus the fungus has trouble spreading from host to host, possibly keeping the whole amphibian population safer. If this observation is correct, then at least laboratory ponds could be stocked with rotifers or other fungus-eating protists to control chytrid.

Tuesday, January 21, 2014

Definition of life as accumulation of information

All known examples of life belong to the same biology, but across a range of scientific disciplines- astronomy, astrobiology, and synthetic biology—it is becoming conceivable that other forms of life may soon be detected or synthesized. But before we have that first life form that is truly independent of terrestrial life, it is still difficult to know what to look for—we are limited by the single known example. All of terrestrial life has shared properties. It is composed of cells, with cell membranes which enclose important contents and communicate with the outside. Living cells contain DNA and/or RNA and particular proteins. Cellular life furthermore transmits heritable information to progeny, and undergoes Darwinian evolution based on natural selection. Finally, life as we know it captures high-energy starting materials and converts them to lower-energy products to drive metabolic processes.
This single example of life has existed for multiple billions of years, out of an Earthly lifetime of something less than 5 billion years. So it works, and works well, and it might be a good template for looking elsewhere.

In a recent review in PLoS Biology, Gerald Joyce describes his ideas of a minimal definition of life, based just the information content and net information increase over time. Information would be very broadly described as the enrichment of one possible chemical configuration despite the availability of other probable configurations . Think of the DNA letter code, in which each position could be held by one of  four possible bases—a very lengthy strand of DNA, if  able to reproduce itself, would represent a process very high information content. If groups of such molecules were subject to mutations and natural selection, then the aggregate would be considered to be “accruing” information.
He gives an example from his own lab of a pair of RNA molecules which are able to reproduce one another. This is not yet life, because the investigator still must provide a template which does not change (accrue information in the above scheme). But the day might come in which a chemical system would accrue more information than is provided it by the scientist.

Monday, January 13, 2014

This is not your (great great great) grandfather's cholera

Cholera, caused by the bacterium Vibrio cholera via contact with contaminated water, affects millions of people each year. In contrast to diseases like smallpox and tuberculosis, the Vibrio strains causing cholera arose relatively recently from more benign relatives, with the first confirmed cholera epidemic occurring in 1817 in areas of present-day Bangladesh and north India. Starting with the 1817 outbreak, there have been 7 cholera pandemics, with the seventh dating from the late 60s and considered to still be ongoing.
In the modern era there have been two major disease causing strains, termed the classical and the El Tor strains, with slight differences in their epidemiology and their gene regulation of the disease-causing cholera toxin. The classical form is thought to have caused all of the first six epidemics, while El Tor, with slightly milder symptoms,  is implicated in the ongoing seventh epidemic and seems to be en route to becoming the more dominant form of the disease. Supporting the idea that the older epidemics were caused by the classical strain,  a study in the New England Journal of Medicine from last week has reported Vibrio sequences from a cholera victim from the second pandemic. The bacterial DNA was obtained from an unusual specimen-- a section of the intestine of a cholera victim from 1849 Philadelphia, which had been preserved in alcohol for 146 years.  The DNA sequences do show a great deal of similarity to the classical strain obtained from more recent epidemics.
Since the classical Vibrio strain had been on the scene for nearly 200 years, it remains to be seen why El Tor has suddenly come on the scene.There is some suggestion that the El Tor strain actively suppresses growth of the classical strain when the two are in co-culture.

The El Tor biotype has some variation over its shorter time on the world stage, and this may augur a continued evolution of the disease. Detailed analyses of bacterial DNA from the 7th (current) pandemic show 3 major genetic groupings from isolates collected over the past 4 decades, suggesting 3 sequential waves of emergence of this biotype from their origin in the northeast corner of the Indian subcontinent. By careful phylogenetic analysis, they provide evidence for intercontinental routes of transmission separated into three epochs, suggesting that the disease strains follow boom-and-bust behavior. Thus, disease-causing Vibrio is probably still evolving in the Bay of Bengal region and may yet give rise to more variant cholera epidemics in the near future.

Saturday, January 11, 2014

How much has life reshaped Earth?

Earth has hosted life for much of its geological existence, and living things have changed much of Earth's geological properties-- from local patterns of erosion to the composition of the atmosphere, living things put their visible stamp on Earth. A recent interview with Tilman Spohn in Astrobiology  magazine asks whether life has transformed Earth even more deeply, by affecting the process of continental drift.
The focus of the question is the extent to which biological weathering at the surface can change the contents of the underlying mantle on which the continents float. Living things such as lichen or bacteria accelerate the breakage of rocks, generating sediments, which are eventually washed to sea. At sea these sediments can accumulate in subduction zones, places where the earth's surface dips down toward the lower layers.
What makes this important is the enormous water content of weathered rock sediments. Water carried down into the mantle would soften the mantle, increasing the overall churn. In computer simulations, an increase churn of mantle rocks leads to increased continental movement and breakage.

So, if life has sufficiently changed (or is still changing) which rocks get weathered, and how fast, these changes would alter the entire face of the planet-- encouraging more tectonic plates and motions.  

Saturday, January 04, 2014

A link between Stonehenge and Orkney monument cultures

Science magazine has a pair of articles (and a segment in their weekly podcast) summarizing new interpretations of the Stonehenge site. I could not find a lay summary in English (German is here).
The extant Stonehenge is part of a repeatedly re-built burial complex, on a site that was evidently sacred for up to  6,000 years, predating the arrival of Neolithic culture in the area.
The new data suggest cultural connections linking the greater Stonehenge site to the Stones of Stenness
The Ring of Brodgar on Mainland, the largest 
of the Orkneys. 
Credit:Patrick Dieudonne/Robert Harding World Imagery/Corbis
and the Ring of Brodgar, structures in the Orkney islands which predate the major Stonehenge construction by several centuries. Michael Pearson has been excavating houses in Durrington Walls, a short distance from Stonehenge, which he believes housed the people who made both structures. The newly unearthed houses show construction methods identical to those used in far older buildings on the Orkneys. Combined with the similarity of
Neolithic sites around Stonehenge. 
the stone circles, the workers who built Stonehenge likely had at least familiarity with the older Orkney culture.
It has already been discovered that the cattle tended in the Durington Walls village came from Wales, and that artifacts in the barrows at Stonehenge come from as far away as the Italian Alps. So with people from the Orkneys in the mix, the emerging picture of the Stonehenge area is one of a very cosmopolitan meeting place. The Ring of Brogdar itself appears to be part of a vast complex and thus plausibly puts the Orkneys as the original heart of an interconnected Neolithic British culture.

This blog goes to 11

The Onion has a good parody of high-energy physics: scientists at Nabisco announce the synthesis of the highly unstable Quadriscuit, a hyper-wafer which cannot be accounted for by classical Fig Newtonian physics.
I'm still trying to understand candy corn, myself. There's some spooky action at a distance going on in there.