GABA(A) receptor phospho-dependent modulation is regulated by phospholipase C-related inactive protein type 1, a novel protein phosphatase 1 anchoring protein

GABA(A) receptors are critical in controlling neuronal activity. Here, we examined the role for phospholipase C-related inactive protein type 1 (PRIP-1), which binds and inactivates protein phosphatase 1alpha (PP1alpha) in facilitating GABA(A) receptor phospho-dependent regulation using PRIP-1(-/-) mice. In wild-type animals, robust phosphorylation and functional modulation of GABA(A) receptors containing beta3 subunits by cAMP-dependent protein kinase was evident, which was diminished in PRIP-1(-/-) mice. PRIP-1(-/-) mice exhibited enhanced PP1alpha activity compared with controls. Furthermore, PRIP-1 was able to interact directly with GABA(A) receptor beta subunits, and moreover, these proteins were found to be PP1alpha substrates. Finally, phosphorylation of PRIP-1 on threonine 94 facilitated the dissociation of PP1alpha-PRIP-1 complexes, providing a local mechanism for the activation of PP1alpha. Together, these results suggest an essential role for PRIP-1 in controlling GABA(A) receptor activity via regulating subunit phosphorylation and thereby the efficacy of neuronal inhibition mediated by these receptors

Wandering behaviour prevents inter and intra oceanic speciation in a coastal pelagic fish

Small pelagic fishes have the ability to disperse over long distances and may present complex evolutionary histories. Here, Old World Anchovies (OWA) were used as a model system to understand genetic patterns and connectivity of fish between the Atlantic and Pacific basins. We surveyed 16 locations worldwide using mtDNA and 8 microsatellite loci for genetic parameters, and mtDNA (cyt b; 16S) and nuclear (RAG1; RAG2) regions for dating major lineage-splitting events within Engraulidae family. The OWA genetic divergences (0-0.4%) are compatible with intra-specific divergence, showing evidence of both ancient and contemporary admixture between the Pacific and Atlantic populations, enhanced by high asymmetrical migration from the Pacific to the Atlantic. The estimated divergence between Atlantic and Pacific anchovies (0.67 [0.53-0.80] Ma) matches a severe drop of sea temperature during the Gunz glacial stage of the Pleistocene. Our results support an alternative evolutionary scenario for the OWA, suggesting a coastal migration along south Asia, Middle East and eastern Africa continental platforms, followed by the colonization of the Atlantic via the Cape of the Good Hope.Portuguese Foundation for Science & Technology (FCT) [SFRH/BD/36600/2007]; FCT [UID/MAR/04292/2013, SFRH/BPD/65830/2009]; FCT strategic plan [UID/Multi/04326/2013]info:eu-repo/semantics/publishedVersio

Distributions of epistasis in microbes fit predictions from a fitness landscape model.

How do the fitness effects of several mutations combine? Despite its simplicity, this question is central to the understanding of multilocus evolution. Epistasis (the interaction between alleles at different loci), especially epistasis for fitness traits such as reproduction and survival, influences evolutionary predictions "almost whenever multilocus genetics matters". Yet very few models have sought to predict epistasis, and none has been empirically tested. Here we show that the distribution of epistasis can be predicted from the distribution of single mutation effects, based on a simple fitness landscape model. We show that this prediction closely matches the empirical measures of epistasis that have been obtained for Escherichia coli and the RNA virus vesicular stomatitis virus. Our results suggest that a simple fitness landscape model may be sufficient to quantitatively capture the complex nature of gene interactions. This model may offer a simple and widely applicable alternative to complex metabolic network models, in particular for making evolutionary predictions

Prevalence of Malaria Parasitemia and Purchase of Artemisinin-Based Combination Therapies (ACTs) among Drug Shop Clients in Two Regions in Tanzania with ACT Subsidies.

Throughout Africa, many people seek care for malaria in private-sector drug shops where diagnostic testing is often unavailable. Recently, subsidized artemisinin-based combination therapies (ACTs), a first-line medication for uncomplicated malaria, were made available in these drug shops in Tanzania. This study assessed the prevalence of malaria among and purchase of ACTs by drug shop clients in the setting of a national ACT subsidy program and sub-national drug shop accreditation program. A cross-sectional survey of drug shop clients was performed in two regions in Tanzania, one with a government drug shop accreditation program and one without, from March-May, 2012. Drug shops were randomly sampled from non-urban districts. Shop attendants were interviewed about their education, training, and accreditation status. Clients were interviewed about their symptoms and medication purchases, then underwent a limited physical examination and laboratory testing for malaria. Malaria prevalence and predictors of ACT purchase were assessed using univariate analysis and multiple logistic regression. Amongst 777 clients from 73 drug shops, the prevalence of laboratory-confirmed malaria was 12% (95% CI: 6-18%). Less than a third of clients with malaria had purchased ACTs, and less than a quarter of clients who purchased ACTs tested positive for malaria. Clients were more likely to have purchased ACTs if the participant was <5 years old (aOR: 6.6; 95% CI: 3.9-11.0) or the shop attendant had >5 years, experience (aOR: 2.8; 95% CI: 1.2-6.3). Having malaria was only a predictor of ACT purchase in the region with a drug shop accreditation program (aOR: 3.4; 95% CI: 1.5-7.4).\ud Malaria is common amongst persons presenting to drug shops with a complaint of fever. The low proportion of persons with malaria purchasing ACTs, and the high proportion of ACTs going to persons without malaria demonstrates a need to better target who receives ACTs in these drug shops

Graphical models for inferring single molecule dynamics

<p>Abstract</p> <p>Background</p> <p>The recent explosion of experimental techniques in single molecule biophysics has generated a variety of novel time series data requiring equally novel computational tools for analysis and inference. This article describes in general terms how graphical modeling may be used to learn from biophysical time series data using the variational Bayesian expectation maximization algorithm (VBEM). The discussion is illustrated by the example of single-molecule fluorescence resonance energy transfer (smFRET)<it> versus</it> time data, where the smFRET time series is modeled as a hidden Markov model (HMM) with Gaussian observables. A detailed description of smFRET is provided as well.</p> <p>Results</p> <p>The VBEM algorithm returns the model’s evidence and an approximating posterior parameter distribution given the data. The former provides a metric for model selection via maximum evidence (ME), and the latter a description of the model’s parameters learned from the data. ME/VBEM provide several advantages over the more commonly used approach of maximum likelihood (ML) optimized by the expectation maximization (EM) algorithm, the most important being a natural form of model selection and a well-posed (non-divergent) optimization problem.</p> <p>Conclusions</p> <p>The results demonstrate the utility of graphical modeling for inference of dynamic processes in single molecule biophysics.</p

Genetics of Microenvironmental Sensitivity of Body Weight in Rainbow Trout (Oncorhynchus mykiss) Selected for Improved Growth

Microenvironmental sensitivity of a genotype refers to the ability to buffer against non-specific environmental factors, and it can be quantified by the amount of residual variation in a trait expressed by the genotype’s offspring within a (macro)environment. Due to the high degree of polymorphism in behavioral, growth and life-history traits, both farmed and wild salmonids are highly susceptible to microenvironmental variation, yet the heritable basis of this characteristic remains unknown. We estimated the genetic (co)variance of body weight and its residual variation in 2-year-old rainbow trout (Oncorhynchus mykiss) using a multigenerational data of 45,900 individuals from the Finnish national breeding programme. We also tested whether or not microenvironmental sensitivity has been changed as a correlated genetic response when genetic improvement for growth has been practiced over five generations. The animal model analysis revealed the presence of genetic heterogeneity both in body weight and its residual variation. Heritability of residual variation was remarkably lower (0.02) than that for body weight (0.35). However, genetic coefficient of variation was notable in both body weight (14%) and its residual variation (37%), suggesting a substantial potential for selection responses in both traits. Furthermore, a significant negative genetic correlation (−0.16) was found between body weight and its residual variation, i.e., rapidly growing genotypes are also more tolerant to perturbations in microenvironment. The genetic trends showed that fish growth was successfully increased by selective breeding (an average of 6% per generation), whereas no genetic change occurred in residual variation during the same period. The results imply that genetic improvement for body weight does not cause a concomitant increase in microenvironmental sensitivity. For commercial production, however, there may be high potential to simultaneously improve weight gain and increase its uniformity if both criteria are included in a selection index

A more fine-grained measure towards animal welfare: a study with regards to gender differences in Spanish students

The environmental issue is nowadays taking more importance in the environmental awareness all around the world, and in this field, animal consideration is more and more spread. A highlighted part in globalisation is the animal welfare awareness. This article presents a study comparing attitudes towards animals among secondary and university students in reference to gender. It was carried out on 1394 Spanish participants from 11 to 26 years. The instrument used in the study is the reviewed version of the Animal Welfare Attitude Scale which was renamed as “Animal Welfare Attitude-Revised Scale” (AWA-R Scale), with a Cronbach a reliability value of 0.85. It is subdivided into four components namely C1: animal abuse for pleasure or due to ignorance; C2: leisure with animals; C3: farm animals; and C4: animal abandonment. These components have been deeply detailed by a confirmatory factor analysis (CFA), which highly contributes to define the position of participants for the different dimensions of animal welfare. It is concluded that significant differences exist between males’ and females’ attitudes in all components of the AWA-R Scale. It is also suggested that two social characteristics—people’s attitudes towards animals and towards environmental protection—are, at the very least, coexistent and may indeed be interdependent. These differences between gender in matters of socialisation could thus be reflected in environmental attitudes, and also in others related to them, i.e. animal welfare attitudes

Changing Selective Pressure during Antigenic Changes in Human Influenza H3

The rapid evolution of influenza viruses presents difficulties in maintaining the optimal efficiency of vaccines. Amino acid substitutions result in antigenic drift, a process whereby antisera raised in response to one virus have reduced effectiveness against future viruses. Interestingly, while amino acid substitutions occur at a relatively constant rate, the antigenic properties of H3 move in a discontinuous, step-wise manner. It is not clear why this punctuated evolution occurs, whether this represents simply the fact that some substitutions affect these properties more than others, or if this is indicative of a changing relationship between the virus and the host. In addition, the role of changing glycosylation of the haemagglutinin in these shifts in antigenic properties is unknown. We analysed the antigenic drift of HA1 from human influenza H3 using a model of sequence change that allows for variation in selective pressure at different locations in the sequence, as well as at different parts of the phylogenetic tree. We detect significant changes in selective pressure that occur preferentially during major changes in antigenic properties. Despite the large increase in glycosylation during the past 40 years, changes in glycosylation did not correlate either with changes in antigenic properties or with significantly more rapid changes in selective pressure. The locations that undergo changes in selective pressure are largely in places undergoing adaptive evolution, in antigenic locations, and in locations or near locations undergoing substitutions that characterise the change in antigenicity of the virus. Our results suggest that the relationship of the virus to the host changes with time, with the shifts in antigenic properties representing changes in this relationship. This suggests that the virus and host immune system are evolving different methods to counter each other. While we are able to characterise the rapid increase in glycosylation of the haemagglutinin during time in human influenza H3, an increase not present in influenza in birds, this increase seems unrelated to the observed changes in antigenic properties

On the thermodynamic origin of metabolic scaling

This work has been funded by projects AYA2013-48623-C2-2, FIS2013-41057-P, CGL2013-46862-C2-1-P and SAF2015-65878-R from the Spanish Ministerio de Economa y Competitividad and PrometeoII/2014/086, PrometeoII/2014/060 and PrometeoII/2014/065 from the Generalitat Valenciana (Spain). BL acknowledges funding from a Salvador de Madariaga fellowship, and L.L. acknowledges funding from EPSRC Early Career fellowship EP/P01660X/1