New and Exciting in PLoS this week

Thursday afternoon is the time when four out of seven PLoS journals publishe new articles and I pick those I find interesting myself. 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, Mendeley, 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:


Cardiorespiratory Phase-Coupling Is Reduced in Patients with Obstructive Sleep Apnea:

Cardiac and respiratory rhythms reveal transient phases of phase-locking which were proposed to be an important aspect of cardiorespiratory interaction. The aim of this study was to quantify cardio-respiratory phase-locking in obstructive sleep apnea (OSA). We investigated overnight polysomnography data of 248 subjects with suspected OSA. Cardiorespiratory phase-coupling was computed from the R-R intervals of body surface ECG and respiratory rate, calculated from abdominal and thoracic sensors, using Hilbert transform. A significant reduction in phase-coupling was observed in patients with severe OSA compared to patients with no or mild OSA. Cardiorespiratory phase-coupling was also associated with sleep stages and was significantly reduced during rapid-eye-movement (REM) sleep compared to slow-wave (SW) sleep. There was, however, no effect of age and BMI on phase coupling. Our study suggests that the assessment of cardiorespiratory phase coupling may be used as an ECG based screening tool for determining the severity of OSA.

High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men:

Understanding the biology of sexual transmission of HIV-1 could contribute importantly to the development of effective prevention measures. However, different routes of virus transmission (vaginal, rectal, penile or oral) and inaccessibility of tissues at or near the time of virus transmission make this goal elusive. Here, we apply single genome amplification and sequencing of plasma HIV-1 and a model of random virus evolution to a cohort of acutely infected men who have sex with men (MSM) and find that MSM are twice as likely as heterosexuals to become infected by multiple viruses as opposed to a single virus. Some MSM subjects were infected by as many as 7 to 10 or more genetically distinct viruses as a consequence of a single exposure event. We go on to molecularly clone the first full-length transmitted/founder subtype B HIV-1 virus and show that it is highly replicative in human CD4+ T-cells but not macrophages. Our study provides the first comparative, quantitative analysis of the multiplicity of HIV-1 infection in the two primary risk groups–MSM and heterosexuals–driving the global pandemic, and we discuss the implications of the findings to HIV-1 vaccine development and prevention research.

An Agent-Based Model of Signal Transduction in Bacterial Chemotaxis:

We report the application of agent-based modeling to examine the signal transduction network and receptor arrays for chemotaxis in Escherichia coli, which are responsible for regulating swimming behavior in response to environmental stimuli. Agent-based modeling is a stochastic and bottom-up approach, where individual components of the modeled system are explicitly represented, and bulk properties emerge from their movement and interactions. We present the Chemoscape model: a collection of agents representing both fixed membrane-embedded and mobile cytoplasmic proteins, each governed by a set of rules representing knowledge or hypotheses about their function. When the agents were placed in a simulated cellular space and then allowed to move and interact stochastically, the model exhibited many properties similar to the biological system including adaptation, high signal gain, and wide dynamic range. We found the agent based modeling approach to be both powerful and intuitive for testing hypotheses about biological properties such as self-assembly, the non-linear dynamics that occur through cooperative protein interactions, and non-uniform distributions of proteins in the cell. We applied the model to explore the role of receptor type, geometry and cooperativity in the signal gain and dynamic range of the chemotactic response to environmental stimuli. The model provided substantial qualitative evidence that the dynamic range of chemotactic response can be traced to both the heterogeneity of receptor types present, and the modulation of their cooperativity by their methylation state.

The Relationship among Gene Expression, the Evolution of Gene Dosage, and the Rate of Protein Evolution:

The analysis of gene evolution is a powerful approach to recognize the genetic features that contribute to the fitness of organisms. It was shown previously that selective constraints on protein sequences increase with expression level. This observation was surprising because there is a priori no reason why lowly expressed genes should be less important than highly expressed genes for the proper function of an organism. Here we show that selective pressure on the evolution of gene dosage, which is another important aspect of gene evolution, is also directly dependent on gene expression level. To explain these observations, we propose a model based on the fact that gene expression is a costly process (notably protein synthesis), so that there is an optimal expression level for each gene corresponding to a trade-off between the benefit and the cost of its expression. This model predicts that selective pressure on gene expression level or on the encoded protein should on average be stronger in highly expressed genes, providing a simple and common explanation for the general relationship observed between gene expression and the different facets of gene evolution.

Effects of Transcranial Direct Current Stimulation on Episodic Memory Related to Emotional Visual Stimuli:

The present study investigated emotional memory following bilateral transcranial electrical stimulation (direct current of 1 mA, for 20 minutes) over fronto-temporal cortical areas of healthy participants during the encoding of images that differed in affective arousal and valence. The main result was a significant interaction between the side of anodal stimulation and image emotional valence. Specifically, right anodal/left cathodal stimulation selectively facilitated the recall of pleasant images with respect to both unpleasant and neutral images whereas left anodal/right cathodal stimulation selectively facilitated the recall of unpleasant images with respect to both pleasant and neutral images. From a theoretical perspective, this double dissociation between the side of anodal stimulation and the advantage in the memory performance for a specific type of stimulus depending on its pleasantness supported the specific-valence hypothesis of emotional processes, which assumes a specialization of the right hemisphere in processing unpleasant stimuli and a specialization of the left hemisphere in processing pleasant stimuli. From a methodological point of view, first we found tDCS effects strictly dependent on the stimulus category, and second a pattern of results in line with an interfering and inhibitory account of anodal stimulation on memory performance. These findings need to be carefully considered in applied contexts, such as the rehabilitation of altered emotional processing or eye-witness memory, and deserve to be further investigated in order to understand their underlying mechanisms of action.

Inductive Game Theory and the Dynamics of Animal Conflict:

Persistent conflict is one of the most important contemporary challenges to the integrity of society and to individual quality of life. Yet surprisingly little is understood about conflict. Is resource scarcity and competition the major cause of conflict, or are other factors, such as memory for past conflicts, the drivers of turbulent periods? How do individual behaviors and decision-making rules promote conflict? To date, most studies of conflict use simple, elegant models based on game theory to investigate when it pays to fight. Although these models are powerful, they have limitations: they require that both the strategies used by individuals and the costs and benefits, or payoffs, of these strategies are known, and they are tied only weakly to real-world data. Here we develop a new method, Inductive Game Theory, and apply it to a time series gathered from detailed observation of a primate society. We are able to determine which types of behavior are most likely to generate periods of intense conflict, and we find that fights are not explained by single, aggressive individuals, but by complex interactions among groups of three or higher. Understanding how memory and strategy affect conflict dynamics is a crucial step towards designing better methods for prediction, management and control.

Using Population Genetic Theory and DNA Sequences for Species Detection and Identification in Asexual Organisms:

It is widely agreed that species are fundamental units of biology, but there is little agreement on a definition of species or on an operational criterion for delimiting species that is applicable to all organisms. We focus on asexual eukaryotes as the simplest case for investigating species and speciation. We describe a model of speciation in asexual organisms based on basic principles of population and evolutionary genetics. The resulting species are independently evolving populations as described by the evolutionary species concept or the general lineage species concept. Based on this model, we describe a procedure for using gene sequences from small samples of individuals to assign them to the same or different species. Using this method of species delimitation, we demonstrate the existence of species as independent evolutionary units in seven groups of invertebrates, fungi, and protists that reproduce asexually most or all of the time. This wide evolutionary sampling establishes the general existence of species and speciation in asexual organisms. The method is well suited for measuring species diversity when phenotypic data are insufficient to distinguish species, or are not available, as in DNA barcoding and environmental sequencing. We argue that it is also widely applicable to sexual organisms.

A Comprehensive Genome-Wide Map of Autonomously Replicating Sequences in a Naive Genome:

DNA replication is an evolutionarily conserved, cell cycle-regulated, spatially and temporally coordinated mechanism in eukaryotes. It is initiated by the binding of the Origin Recognition Complex (ORC) to multiple replication origins. While the ORC is highly conserved, its DNA binding specificity and the primary sequences of replication origins are not. Comparative functional genomics is an obvious approach to addressing questions about the positional conservation and chromosomal determinants of replication origins. However, to date, Saccharomyces cerevisiae is the only eukaryote with a complete genome-wide replication origin map, one which took three decades to compile. We have devised an iterative approach, combining computational prediction and functional validation by direct cloning of replication origins that efficiently identifies a high resolution, near complete repertoire of replication origins in Kluyveromyces lactis. Comparing these two yeast genome maps provides a wealth of information about the DNA elements and positional conservation of replication origins in these two distantly related yeast species. This approach is generally applicable to the construction of high-resolution genome maps of evolutionarily conserved sequences associated with assayable biological functions. Rapid generation of comprehensive functional maps of uncharacterized genomes is critical to whole genome studies of all biological functions.

Cross-National Analysis of the Associations between Traumatic Events and Suicidal Behavior: Findings from the WHO World Mental Health Surveys:

Community and clinical data have suggested there is an association between trauma exposure and suicidal behavior (i.e., suicide ideation, plans and attempts). However, few studies have assessed which traumas are uniquely predictive of: the first onset of suicidal behavior, the progression from suicide ideation to plans and attempts, or the persistence of each form of suicidal behavior over time. Moreover, few data are available on such associations in developing countries. The current study addresses each of these issues. Data on trauma exposure and subsequent first onset of suicidal behavior were collected via structured interviews conducted in the households of 102,245 (age 18+) respondents from 21 countries participating in the WHO World Mental Health Surveys. Bivariate and multivariate survival models tested the relationship between the type and number of traumatic events and subsequent suicidal behavior. A range of traumatic events are associated with suicidal behavior, with sexual and interpersonal violence consistently showing the strongest effects. There is a dose-response relationship between the number of traumatic events and suicide ideation/attempt; however, there is decay in the strength of the association with more events. Although a range of traumatic events are associated with the onset of suicide ideation, fewer events predict which people with suicide ideation progress to suicide plan and attempt, or the persistence of suicidal behavior over time. Associations generally are consistent across high-, middle-, and low-income countries. This study provides more detailed information than previously available on the relationship between traumatic events and suicidal behavior and indicates that this association is fairly consistent across developed and developing countries. These data reinforce the importance of psychological trauma as a major public health problem, and highlight the significance of screening for the presence and accumulation of traumatic exposures as a risk factor for suicide ideation and attempt.

Semen May Harbor HIV Despite Effective HAART: Another Piece in the Puzzle:

The risk of male-to-female intravaginal HIV-1 transmission is estimated at about 1 event per 200-2000 coital acts. The aim of this study was to assess the residual risk of HIV presence in semen in patients under HAART therapy. The study took place in France from October 2001 to March 2009. 394 paired blood and semen samples were provided from 332 HIV-1 infected men. The Roche Cobas AMPLICOR Monitor HIV assay was used to quantify HIV-1 RNA in blood and in seminal plasma. Three percent of 394 HIV-1 infected men enrolled in an assisted reproductive technology program harbored detectable HIV-1 RNA in semen, although they had no other sexually transmitted disease and their blood viral load was undetectable for at least 6 months under antiretroviral treatment. These data suggest that undetectable plasma HIV RNA means a lower risk of viral transmission through seminal fluid on a population level, but not necessarily at the level of the individual.

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