So, let's see what's new in PLoS Genetics, PLoS Computational Biology, PLoS Pathogens, PLoS ONE 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. Here are my own picks for the week - you go and look for your own favourites:
Copying and Evolution of Neuronal Topology:
We propose a mechanism for copying of neuronal networks that is of considerable interest for neuroscience for it suggests a neuronal basis for causal inference, function copying, and natural selection within the human brain. To date, no model of neuronal topology copying exists. We present three increasingly sophisticated mechanisms to demonstrate how topographic map formation coupled with Spike-Time Dependent Plasticity (STDP) can copy neuronal topology motifs. Fidelity is improved by error correction and activity-reverberation limitation. The high-fidelity topology-copying operator is used to evolve neuronal topologies. Possible roles for neuronal natural selection are discussed.
Newly Discovered Ebola Virus Associated with Hemorrhagic Fever Outbreak in Uganda:
In this report we describe a newly discovered ebolavirus species which caused a large hemorrhagic fever outbreak in western Uganda. The virus is genetically distinct, differing by more than 30% at the genome level from all other known ebolavirus species. The unique nature of this virus created challenges for traditional filovirus molecular based diagnostic assays and genome sequencing approaches. Instead, we quickly determined over 70% of the virus genome using a recently developed random-primed pyrosequencing approach that allowed the rapid development of a molecular detection assay that was deployed in the disease outbreak response. This draft sequence allowed easy completion of the whole genome sequence using a traditional primer walking approach and prompt confirmation that this virus represented a new ebolavirus species. Current efforts to design effective diagnostics, antivirals and vaccines will need to take into account the distinct nature of this important new member of the filovirus family.
Coding of Visual Object Features and Feature Conjunctions in the Human Brain:
Object recognition is achieved through neural mechanisms reliant on the activity of distributed coordinated neural assemblies. In the initial steps of this process, an object's features are thought to be coded very rapidly in distinct neural assemblies. These features play different functional roles in the recognition process - while colour facilitates recognition, additional contours and edges delay it. Here, we selectively varied the amount and role of object features in an entry-level categorization paradigm and related them to the electrical activity of the human brain. We found that early synchronizations (approx. 100 ms) increased quantitatively when more image features had to be coded, without reflecting their qualitative contribution to the recognition process. Later activity (approx. 200-400 ms) was modulated by the representational role of object features. These findings demonstrate that although early synchronizations may be sufficient for relatively crude discrimination of objects in visual scenes, they cannot support entry-level categorization. This was subserved by later processes of object model selection, which utilized the representational value of object features such as colour or edges to select the appropriate model and achieve identification.
Warmer Weather Linked to Tick Attack and Emergence of Severe Rickettsioses:
The impact of climate on the behaviour of the worldwide dog tick Rhipicephalus sanguineus is a cause of concern. This tick is a vector for life-threatening organisms including Rickettsia rickettsii, the agent of Rocky Mountain spotted fever, R. conorii, the agent of Mediterranean spotted fever, and the ubiquitous emerging pathogen R. massiliae. A focus of spotted fever was investigated in France in May 2007. One patient was found to be infected by R. conorii, whereas the other was infected by R. massiliae. Theses cases were original because of ophthalmic involvements, and the report of the second case of R. massiliae infection in the scientific literature. During an entomological survey, dense populations of Rh. sanguineus were found in the house where the patient had been bitten by ticks. Ticks were infected with either R. conorii or R. massiliae. Interestingly, April 2007 was the warmest since 1950, with summer-like temperatures. In this work, we show that the human affinity of Rh. sanguineus is increased in warmer temperatures, and provide evidence that this cluster of cases was related to a warming-mediated increase in the aggressiveness of Rh. sanguineus, leading to increased human attacks. From a global perspective, we predict that as a result of globalisation and warming, more pathogens transmitted by the brown dog tick may emerge in the future.
A variety of embryonic and adult stem cell lines require an intial co-culturing with feeder cells for non-differentiated growth, self renewal and maintenance of pluripotency. However for many downstream ES cell applications the feeder cells have to be considered contaminations that might interfere not just with the analysis of experimental data but also with clinical application and tissue engineering approaches. Here we introduce a novel technique that allows for the selection of pure feeder-freed stem cells, following stem cell proliferation on feeder cell layers. Complete and reproducible separation of feeder and embryonic stem cells was accomplished by adaptation of an automated cell selection system that resulted in the aspiration of distinct cell colonies or fraction of colonies according to predefined physical parameters. Analyzing neuronal differentiation we demonstrated feeder-freed stem cells to exhibit differentiation potentials comparable to embryonic stem cells differentiated under standard conditions. However, embryoid body growth as well as differentiation of stem cells into cardiomyocytes was significantly enhanced in feeder-freed cells, indicating a feeder cell dependent modulation of lineage differentiation during early embryoid body development. These findings underline the necessity to separate stem and feeder cells before the initiation of in vitro differentiation. The complete separation of stem and feeder cells by this new technology results in pure stem cell populations for translational approaches. Furthermore, a more detailed analysis of the effect of feeder cells on stem cell differentiation is now possible, that might facilitate the identification and development of new optimized human or genetically modified feeder cell lines.
Gene Regulation in Primates Evolves under Tissue-Specific Selection Pressures:
It has long been hypothesized that in addition to structural changes to proteins, changes in gene regulation might underlie many of the anatomic and behavioral differences between humans and other primates. However, to date, there are only a handful of examples of regulatory adaptations in humans. In this work, we present a genome-wide study of gene expression levels in livers, kidneys, and hearts from three species: humans, chimpanzees, and rhesus macaques. These data allowed us to identify genes and entire pathways in which regulation evolved under natural selection and therefore are likely to be functionally important. Our results provide some of the first examples of pathways that have been remodeled specifically in the human lineage. In particular, we find that the regulation of a large number of genes involved in metabolic pathways evolved under lineage-specific directional selection. This result is intriguing, because, in addition to the obvious cognitive and linguistic differences between humans and non-human apes, a clear lifestyle shift between us and other primates can be found in our diet. We also found evidence for tissue-specific selection pressures on gene regulation, an observation that provides strong support to the notion that adaptive circumscribed changes in gene regulation have fewer deleterious pleiotropic effects compared with changes at the protein sequence level.
Neutrality and Robustness in Evo-Devo: Emergence of Lateral Inhibition:
The diversity of life is a consequence of changes in the genotype (genes and their interdependence), but it is upon the observable organism's morphology (phenotype) that natural selection acts. Thus, the study of genotype-phenotype mapping can reveal key mechanisms driving life's capacity of continuous evolution and resilience in diverse environments. In this context, it has been observed that small numbers of genes form robust functional developmental modules, hierarchically reused throughout development. Here we analyze the evolution of small genetic modules toward higher diversity and robustness. Given the small size of the gene network, we can afford to analyze all possible topologies and thus the entire fitness landscape. This exhaustive study as well as simulations of evolutionary processes uncover a set of genetic interactions producing robust and diverse phenotypes. We single out the distinctive features of these networks responsible for their stability against environmental and structural perturbations. More precisely, all these robust genotypes can be related to the key mechanism of lateral inhibition for which a cell of a given type inhibits its neighbors to keep them from adopting the same type. Their distinctive features can thus shed light on the underlying mechanisms leading to pattern formation through lateral inhibition.
Behavioral Sequence Analysis Reveals a Novel Role for Ã2* Nicotinic Receptors in Exploration:
Understanding mechanisms underlying complex behaviors and the abnormalities that accompany most neuropathologies is a current challenge in biomedical research. A number of approaches is primarily based on the identification of genes and their associated molecular pathways implicated in complex motor or cognitive pathologies. However, optimal use of the large body of genetic, molecular, electro-physiological, and imaging data is hampered by the practical and theoretical limitations of currently available behavioral analysis methods. Complex behaviors consist of a finite number of actions combined in a variety of spatial and temporal patterns. In this paper we develop a sequential analysis of mouse displacement in an open-field paradigm and demonstrate that a description based on a Markov model can be used to describe quantitatively patterns of behaviors and to detect changes in the way that animals organize their displacement, especially in mice lacking nicotinic acetylcholine receptor subunits. This paper would be of broad interest not only to those concerned with this particular mice model but also generally to those interested in modeling complex behavior traits in mice.
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