New and Exciting in PLoS this week

So, let’s see what’s new in PLoS Genetics, PLoS Computational Biology, PLoS Pathogens, and PLoS Neglected Tropical Diseases this week. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. You can now also easily place articles on various social services (CiteULike, Connotea, Stumbleupon, Facebook and Digg) with just one click. Here are my own picks for the week – you go and look for your own favourites:

A Hierarchy of Time-Scales and the Brain:

Currently, there is no theory that explains how the large-scale organization of the human brain can be related to our environment. This is astonishing because neuroscientists generally assume that the brain represents events in our environment by decoding sensory input. Here, we propose that the brain models the entire environment as a collection of hierarchical, dynamical systems, where slower environmental changes provide the context for faster changes. We suggest that there is a simple mapping between this temporal hierarchy and the anatomical hierarchy of the brain. Our theory provides a framework for explaining a wide range of neuroscientific findings by a single principle.

Controlled Chaos of Polymorphic Mucins in a Metazoan Parasite (Schistosoma mansoni) Interacting with Its Invertebrate Host (Biomphalaria glabrata):

Contrary to the traditional view that immunity in invertebrates is limited to non-specific mechanisms, recent studies have shown that they have diverse, specific immune receptors. An example is provided by the FREPs of the mollusk Biomphalaria glabrata, polymorphic members of the immunoglobulin superfamily. This capacity for an individual or population-based polymorphic immune response raises the question of whether a corresponding polymorphism exists in parasites of invertebrates, as would be expected in an “arms race” between host and parasite. We have indeed identified such polymorphic molecules in Schistosoma mansoni, a flatworm parasite of B. glabrata, by comparing two strains of schistosome that are respectively compatible and incompatible with the same mollusk host strain. However, in contrast to antigenic variation in protozoan parasites that is based on an extensive gene repertoire, we show here that a high level of polymorphism in these S. mansoni polymorphic mucins (SmPoMucs) is generated from a low number of genes by a complex cascade of mechanisms, a “controlled chaos”.

Correlative and Dynamic Imaging of the Hatching Biology of Schistosoma japonicum from Eggs Prepared by High Pressure Freezing:

Adult schistosomes live within portal veins of their human hosts. Their offspring, laid as eggs within the venous system, escape by traversing the tissues between the blood vessel and the gut or bladder lumen. Eggs voided into the external environment hatch spontaneously on contact with freshwater, and the hatched larva escapes in search of a snail, which acts as intermediate host of the parasite. In this study, we used correlative microscopy techniques to examine hatching of the larvae of Schistosoma japonicum. This species has an exquisite hatching behaviour, which allows us to trace the cellular changes in the egg that lead to hatching. By using a correlative microscopy approach, incorporating video microscopy, electron microscopy of eggs prepared by high pressure freezing and lectin immunocytochemistry, we were able to describe the pre-hatching state of the eggs, and trace changes that occur during hatching. The insights gained from these direct biological studies will be of value in understanding the host-parasite interplay of schistosome eggs in their hosts.

Alteration of Blood-Brain Barrier Integrity by Retroviral Infection:

The blood-brain barrier (BBB) forms the interface between the blood and the central nervous system (CNS). BBB disruption is considered to be a key event in the pathogenesis of retroviral-associated neurological diseases. The present paper deals with the susceptibility of the endothelial cells (i.e., one of the main cellular components of BBB) to retroviral infection, and with the impact of infection in BBB function. This study focuses on the Human T-Lymphotropic Virus (HTLV-1), which infects 20 million people worldwide, and is the etiological agent of a neurodegenerative disease called HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). We first demonstrated that the cerebral endothelial cells express the receptors for the retrovirus in vitro, and on spinal cord autopsy sections from non-infected and HAM/TSP patients. We found on these latter that vascular-like structures were infected and confirmed in vitro that the endothelial cells could be productively infected by HTLV-1. We demonstrated that such an infection impairs BBB properties in vitro, as well as tight junctions, that are cell adhesion structures. This study is the first to demonstrate the impact of HTLV-1 infection on human BBB integrity; such a susceptibility has to be considered in the design of future therapeutics strategies.

Cryoelectron Tomography of HIV-1 Envelope Spikes: Further Evidence for Tripod-Like Legs:

The envelope (Env) spikes on the surface of HIV-1 and SIV virions facilitate target cell tropism, binding, and entry, and serve as the sole targets of humoral (antibody-mediated) immunity. X-ray crystallography has previously revealed the atomic structures of key core domains and peptides of the gp120 and gp41 Env spike subunits, but the manner by which these components are arranged in the Env spike is still speculative. Cryoelectron tomography (cryoET) affords a view of the entire Env spike in the context of the intact virion. We have previously published a cryoET model of the SIV Env spike which showed a unique tripod-like leg configuration for the solvent-exposed (external) gp41 stalk region. This model is consistent with, and helps explain, many of the unique biophysical and immunological features of this region. Subsequently another group using similar technology and virions reported a spike model displaying a compact gp41 stalk inconsistent with our splayed-leg spike model. In this report, we apply enhanced analytical cryoET procedures to show that HIV-1 also displays the tripod-like leg configuration, and shows considerable gp41 leg flexibility/heteromorphology. These results have implications for the design of effective vaccines targeting this region and may provide new insights into Env spike function.

Synonymous Genes Explore Different Evolutionary Landscapes:

Evolutionary processes largely rely on the production of diversity. Genetic robustness, by allowing the accumulation of neutral diversity within a population, has been associated with increase in evolutionary potential (evolvability). In this work, we propose to use a well-known source of robustness, the redundancy of the genetic code, to alter the evolvability of any protein. The topology of the code allows synonymous codons to sample different mutational neighborhoods. Using this property, we developed an algorithm to design synonymous sequences with maximally divergent evolutionary potentials relative to the input sequences. At the population level, each of these sequences expands the scope of the evolutionary landscape that can be explored by the encoded protein, and ultimately increase the odds of uncovering adaptive mutants. We applied this principle to evolve new antibiotic resistance phenotype variants. Fundamentally, our results provide an example of how neutral diversity may favor evolvability. Moreover, in light of the rapid development in nucleic acid synthesis, the use of rationally designed synonymous genes offers a profitable enhancement to any directed evolution procedure.

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