A Blog Around The Clock

It's Friday - and time for new articles in PLoS Computational Biology, PLoS Pathogens and PLoS Genetics:

An Evolutionarily Conserved Sexual Signature in the Primate Brain:

The contribution of genetics versus environment to behavioral differences between the sexes is a fundamental question in neuroscience. We hypothesized that some differences between the sexes might be partially explained by sexually dependent gene expression differences in the brain. We further speculated that if differences in gene expression between males and females are functionally important, they may be conserved in the evolution of primates. To test these hypotheses, we measured gene expression in the brains of male and female primates from three species: humans (Homo sapiens), macaques (Macaca fascicularis), and marmosets (Callithrix jacchus). Our results point to a conserved signature of sexual gene expression dimorphism in the brains of primates. Interestingly, we found that genes with conserved sexual gene expression dimorphism in the brain also evolve under more evolutionary constraint, compared with other genes, suggesting that they may have important roles during evolution of sex in primates. Moreover, we found higher evolutionary constrains in the coding regions of female-biased genes as compared to both male-biased and non sex-biased brain expressed genes. The study of sex dimorphic genes may in the future shed light on the basis of psychiatric diseases with differences in prevalence between the sexes.

How To Record a Million Synaptic Weights in a Hippocampal Slice:

The circuitry of the brain is defined by the connections (synapses) between its cells. Synapses are very small, so it is difficult to identify more than a few at a time using standard methods like electron microscopy or high-precision electrical recordings from cells. This study shows that it is possible to measure single synapses using low-precision methods such as optical recordings from neuronal cell bodies. I model optical or electrical stimulation of many inputs to trigger a visible response from neurons, and find single synapses by testing how this response is modulated when a single additional input synapse is triggered as well. I predict that it should be possible to record from as many as a million synapses using new optical recording and stimulation methods. It is believed that memories are encoded in synaptic connection patterns, so such connectivity data may give us a picture of how memories are encoded. We now know a great deal about how individual neurons behave, so a synapse-level wiring diagram would go a long way to fill out the picture of how neurons work together in the brain to interpret sensory information and plan actions.

Quorum Sensing Coordinates Brute Force and Stealth Modes of Infection in the Plant Pathogen Pectobacterium atrosepticum:

Many Gram-negative bacteria use a population density-dependent regulatory mechanism called quorum sensing (QS) to control the production of virulence factors during infection. In the bacterial plant pathogen Pectobacterium atrosepticum (formerly Erwinia carotovora subsp. atroseptica), an important model for QS, this mechanism regulates production of enzymes that physically attack the host plant cell wall. This study used a whole genome microarray-based approach to investigate the entire QS regulon during plant infection. Results demonstrate that QS regulates a much wider set of essential virulence factors than was previously appreciated. These include virulence factors similar to those in other plant and animal pathogens that have not previously been associated with QS, e.g., a Type VI secretion system (and its potential substrates), shown for the first time to be required for virulence in a plant pathogen; and the plant toxin coronafacic acid, known in other pathogens to play a role in manipulating plant defences. This study provides the first evidence that Pectobacterium may target host defences simultaneously with a physical attack on the plant cell wall. Moreover, the study demonstrates that a wide range of previously known and unknown virulence regulators lie within the QS regulon, revealing it to be the master regulator of virulence.

Real-Time High Resolution 3D Imaging of the Lyme Disease Spirochete Adhering to and Escaping from the Vasculature of a Living Host:

Pathogenic spirochetes are bacteria that cause a number of emerging and re-emerging diseases worldwide, including syphilis, leptospirosis, relapsing fever, and Lyme disease. They exhibit an unusual form of motility and can infect many different tissues; however, the mechanism by which they disseminate from the blood to target sites is unknown. Direct visualization of bacterial pathogens at the single cell level in living hosts is an important goal of microbiology, since this approach is likely to yield critical insight into disease processes. We engineered a fluorescent strain of Borrelia burgdorferi, a Lyme disease pathogen, and used conventional and spinning disk confocal intravital microscopy to directly visualize these bacteria in real time and 3D in living mice. We found that spirochete interaction with and dissemination out of the vasculature was a multi-stage process of unexpected complexity and that spirochete movement appeared to play an integral role in dissemination. To our knowledge, this is the first report of high resolution 3D visualization of dissemination of a bacterial pathogen in a living mammalian host, and provides the first direct insight into spirochete dissemination in vivo.