Life events and acute cardiovascular reactions to mental stress: a cohort study

Objective: This study addressed the issue of whether frequent exposure to life events is associated with aggravation or blunting of cardiovascular reactions to acute mental stress. Methods: In a substantial cohort of 585 healthy young adults, systolic and diastolic blood pressure and pulse rate were recorded at rest and in response to a mental arithmetic stress task. Participants indicated, from a list of 50 events, those they had experienced in the last year. Results: There was an overall association between life events and blunted cardiovascular reactivity that was driven by variations in the frequency of exposure to desirable events. The total number of events and the number of personal events were negatively associated with systolic blood pressure and pulse rate reactions to acute stress, whereas the number of work-related events was negatively associated with diastolic blood pressure and pulse rate reactivity. The negative association between total events and systolic blood pressure reactivity was stronger for women than men, whereas men exposed to frequent undesirable events showed enhanced diastolic blood pressure reactivity. The blunting of pulse rate reactivity associated with frequent personal life events was evident particularly for those who had a relatively large number of close friends. Conclusions: The nature and extent of the association between life events exposure and stress reactivity in young adults depends on the valence of the events together with the sex of the individual and their social network size

Hermaphrodite life history and the maintenance of partial selfing in experimental populations of Caenorhabditis elegans

Classic population genetics theory predicts that mixed reproductive systems, where self reproduction (selfing) and outcrossing co-exist, should not be as common as they are in nature. One means of reconciling theory with observations is to recognize that sexual conflict between males and hermaphrodites and/or constraints in the allocation of resources towards sex functions in hermaphrodites can balance the fitness components of selfing and outcrossing.PhD fellowship from Fundação para a Ciência e a Tecnologia (FCT; SFRH/BD/36726/2007); National Science Foundation - Funding (DEB-1120417

Robust Tests of Forward Exchange Market Efficiency with Empirical Evidence from the 1920’s

This paper provides a robust statistical approach to testing the unbiasedness hypothesis in forward exchange market efficiency studies. The methods we use allow us to work explicitly with levels rather than differenced data. They are statistically robust to data distributions with heavy tails, and they can be applied to data sets where the frequency of observation and the futures maturity do not coincide. In addition, our methods allow for stochastic trend nonstationarity and general forms of serial dependence. The methods are applied to daily data of spot exchange rates and forward exchange rates during the 1920’s, which marked the first episode of a broadly general floating exchange rate system. The tail behavior of the data is analyzed using an adaptive data-based method for estimating the tail slope of the density. The results confirm the need for the use of robust regression methods. We find cointegration between the forward rate and spot rate for the four currencies we consider (the Belgian and French francs, the Italian lira and the US dollar, all measured against the British pound), we find support for a stationary risk premium in the case of the Belgian franc, the Italian lira and the US dollar, and we find support for the simple market efficiency hypothesis (where the forward rate is an unbiased predictor of the future spot rate and there is a zero mean risk premium) in the case of the US dollar

Evolutionary rates and centrality in the yeast gene regulatory network

BACKGROUND: Transcription factors play a fundamental role in regulating physiological responses and developmental processes. Here we examine the evolution of the yeast transcription factors in the context of the structure of the gene regulatory network. RESULTS: In contrast to previous results for the protein-protein interaction and metabolic networks, we find that the position of a gene within the transcription network affects the rate of protein evolution such that more central transcription factors tend to evolve faster. Centrality is also positively correlated with expression variability, suggesting that the higher rate of divergence among central transcription factors may be due to their role in controlling information flow and may be the result of adaptation to changing environmental conditions. Alternatively, more central transcription factors could be more buffered against environmental perturbations and, therefore, less subject to strong purifying selection. Importantly, the relationship between centrality and evolutionary rates is independent of expression level, expression variability and gene essentiality. CONCLUSIONS: Our analysis of the transcription network highlights the role of network structure on protein evolutionary rate. Further, the effect of network centrality on nucleotide divergence is different among the metabolic, protein-protein and transcriptional networks, suggesting that the effect of gene position is dependant on the function of the specific network under study. A better understanding of how these three cellular networks interact with one another may be needed to fully examine the impact of network structure on the function and evolution of biological systems

The opportunity for canalization . . .

There has been a recent revival of interest in how genetic interactions evolve, spurred on by an increase in our knowledge of genetic interactions at the molecular level. Empirical work on genetic networks has revealed a surprising amount of robustness to perturbations, suggesting that robustness is an evolved feature of genetic networks. Here, we derive a general model for the evolution of canalization that can incorporate any form of perturbation. We establish an upper bound to the strength of selection on canalization that is approximately equal to the fitness load in the system. This method makes it possible to compare different forms of perturbation, including genetic, developmental, and environmental effects. In general, load that arises from mutational processes is low because the mutation rate is itself low. Mutation load can create selection for canalization in a small network that can be achieved through dominance evolution or gene duplication, and in each case selection for canalization is weak at best. In larger genetic networks, selection on genetic canalization can be reasonably strong because larger networks have higher mutational load. Because load induced through migration, segregation, developmental noise, and environmental variance is not mutation limited, each can cause strong selection for canalization

Preeclamptic placentae release factors that damage neurons: implications for foetal programming of disease

Prenatal development is a critical period for programming of neurological disease. Preeclampsia, a pregnancy complication involving oxidative stress in the placenta, has been associated with long-term health implications for the child, including an increased risk of developing schizophrenia and autism spectrum disorders in later life. To investigate if molecules released by the placenta may be important mediators in foetal programming of the brain, we analysed if placental tissue delivered from patients with preeclampsia secreted molecules that could affect cortical cells in culture. Application of culture medium conditioned by preeclamptic placentae to mixed cortical cultures caused changes in neurons and astrocytes that were related to key changes observed in brains of patients with schizophrenia and autism, including effects on dendrite lengths, astrocyte number as well as on levels of glutamate and γ-aminobutyric acid receptors. Treatment of the placental explants with an antioxidant prevented neuronal abnormalities. Furthermore, we identified that bidirectional communication between neurons and astrocytes, potentially via glutamate, is required to produce the effects of preeclamptic placenta medium on cortical cells. Analysis of possible signalling molecules in the placenta-conditioned medium showed that the secretion profile of extracellular microRNAs, small post-transcriptional regulators, was altered in preeclampsia and partially rescued by antioxidant treatment of the placental explants. Predicted targets of these differentially abundant microRNAs were linked to neurodevelopment and the placenta. The present study provides further evidence that the diseased placenta may release factors that damage cortical cells and suggests the possibility of targeted antioxidant treatment of the placenta to prevent neurodevelopmental disorders

Genetic Diversity of PCR-Positive, Culture-Negative and Culture-Positive Mycobacterium ulcerans Isolated from Buruli Ulcer Patients in Ghana.

Culture of Mycobacterium ulcerans from Buruli ulcer patients has very low sensitivity. Thus confirmation of M. ulcerans infection is primarily based on PCR directed against IS2404. In this study we compare the genotypes obtained by variable number of tandem repeat analysis of DNA from IS2404-PCR positive cultures with that obtained from IS2404 positive, culture-negative tissue. A significantly greater genetic heterogeneity was found among culture-negative samples compared with that found in cultured strains but a single genotype is over-represented in both sample sets. This study provides evidence that both the focal location of bacteria in a lesion as well as differences in the ability to culture a particular genotype may underlie the low sensitivity of culture. Though preliminary, data from this work also suggests that mycobacteria previously associated with fish disease (M. pseudoshottsii) may be pathogenic for humans

Natural and experimental evolution of sexual conflict within Caenorhabditis nematodes

BACKGROUND: Although males and females need one another in order to reproduce, they often have different reproductive interests, which can lead to conflict between the sexes. The intensity and frequency of male-male competition for fertilization opportunities is thought to be an important contributor to this conflict. The nematode genus Caenorhabditis provides an opportunity to test this hypothesis because the frequency of males varies widely among species with different mating systems. RESULTS: We find evidence that there is strong inter- and intra-sexual conflict within C. remanei, a dioecious species composed of equal frequencies of males and females. In particular, some C. remanei males greatly reduce female lifespan following mating, and their sperm have a strong competitive advantage over the sperm of other males. In contrast, our results suggest that both types of conflict have been greatly reduced within C. elegans, which is an androdioecious species that is composed of self-fertilizing hermaphrodites and rare males. Using experimental evolution in mutant C. elegans populations in which sperm production is blocked in hermaphrodites (effectively converting them to females), we find that the consequences of sexual conflict observed within C. remanei evolve rapidly within C. elegans populations experiencing high levels of male-male competition. CONCLUSIONS: Together, these complementary data sets support the hypothesis that the intensity of intersexual conflict varies with the intensity of competition among males, and that male-induced collateral damage to mates can evolve very rapidly within populations

Randomized clinical trials to identify optimal antibiotic treatment duration

Background Antibiotic resistance is a major barrier to the continued success of antibiotic treatment. Such resistance is often generated by overly long durations of antibiotic treatment. A barrier to identifying the shortest effective treatment duration is the cost of the sequence of clinical trials needed to determine shortest optimal duration. We propose a new method to identify the optimal treatment duration of an antibiotic treatment regimen. Methods Subjects are randomized to varying treatment durations and the cure proportions of these durations are linked using a logistic regression model, making effective use of information across all treatment duration groups. In this paper, Monte Carlo simulation is used to evaluate performance of such a model. Results Using a hypothetical dataset, the logistic regression model is seen to provide increased precision in defining the point estimate and confidence interval (CI) of the cure proportion at each treatment duration. When applied to the determination of non-inferiority, the regression model allows identification of the shortest duration meeting the predefined non-inferiority margin. Conclusions This analytic strategy represents a practical way to develop shortened regimens for tuberculosis and other infectious diseases. Application of this strategy to clinical trials of antibiotic therapy could facilitate decreased antibiotic usage, reduce cost, minimize toxicity, and decrease the emergence of antibiotic resistance

The Corpus Callosum in Primates: Processing Speed of Axons and the Evolution of Hemispheric Asymmetry

Interhemispheric communication may be constrained as brain size increases because of transmission delays in action potentials over the length of axons. Although one might expect larger brains to have progressively thicker axons to compensate, spatial packing is a limiting factor. Axon size distributions within the primate corpus callosum (CC) may provide insights into how these demands affect conduction velocity. We used electron microscopy to explore phylogenetic variation in myelinated axon density and diameter of the CC from 14 different anthropoid primate species, including humans. The majority of axons were less than 1 µm in diameter across all species, indicating that conduction velocity for most interhemispheric communication is relatively constant regardless of brain size. The largest axons within the upper 95th percentile scaled with a progressively higher exponent than the median axons towards the posterior region of the CC. While brain mass among the primates in our analysis varied by 97-fold, estimates of the fastest cross-brain conduction times, as conveyed by axons at the 95th percentile, varied within a relatively narrow range between 3 and 9 ms across species, whereas cross-brain conduction times for the median axon diameters differed more substantially between 11 and 38 ms. Nonetheless, for both size classes of axons, an increase in diameter does not entirely compensate for the delay in interhemispheric transmission time that accompanies larger brain size. Such biophysical constraints on the processing speed of axons conveyed by the CC may play an important role in the evolution of hemispheric asymmetry