Large-scale proteomic analysis of T. spiralis muscle-stage ESPs identifies a novel upstream motif for in silico prediction of secreted products

The Trichinella genus contains parasitic nematodes capable of infecting a wide range of hosts including mammals, birds and reptiles. Like other helminths, T. spiralis secretes a complex mixture of bioactive molecules capable of modulating its immediate surroundings and creating a hospitable environment for growth, survival and ultimately transmission. The constitution of these excretory-secretory products (ESPs) changes depending on the tissue niche and the specific stage of parasite development. Unique to T. spiralis is a true intracellular stage wherein larvae develop inside striated myotubes. Remarkably, the parasite larvae do not destroy the host cell but rather reprogram it to support their presence and growth. This transformation is largely mediated through stage-specific secretions released into the host cell cytoplasm. In this study, we apply state of the art proteomics and computational approaches to elucidate the composition and functions of muscle-stage T. spiralis ESPs. Moreover, we define a recurring, upstream motif associated with the stichosome, the main secretory organ of this worm, and can be used to predict secreted proteins across experimentally less tractable T. spiralis life cycle stages

Threshold FlipThem:when the winner does not need to take all

We examine a FlipIt game in which there are multiple resources which a monolithic attacker is trying to compromise. This extension to FlipIt was considered in a paper in GameSec 2014, and was there called FlipThem. Our analysis of such a situation is focused on the situation where the attacker’s goal is to compromise a threshold of the resources. We use our game theoretic model to enable a defender to choose the correct configuration of resources (number of resources and the threshold) so as to ensure that it makes no sense for a rational adversary to try to attack the system. This selection is made on the basis of the relative costs of the attacker and the defender

Economic Outcomes of Patients Receiving Antiretroviral Therapy for HIV/AIDS in South Africa Are Sustained through Three Years on Treatment

BACKGROUND. Although the medical outcomes of antiretroviral therapy (ART) for HIV/AIDS are well described, less is known about how ART affects patients' economic activities and quality of life, especially after the first year on ART. We assessed symptom prevalence, general health, ability to perform normal activities, and employment status among adult antiretroviral therapy patients in South Africa over three full years following ART initiation. METHODOLOGY/PRINCIPAL FINDINGS. A cohort of 855 adult pre-ART patients and patients on ART for <6 months was enrolled and interviewed an average of 4.4 times each during routine clinic visits for up to three years after treatment initiation using an instrument designed for the study. The probability of pain in the previous week fell from 74% before ART initiation to 32% after three years on ART, fatigue from 66% to 12%, nausea from 28% to 4%, and skin problems from 55% to 10%. The probability of not feeling well physically yesterday fell from 46% to 23%. Before starting ART, 39% of subjects reported not being able to perform their normal activities sometime during the previous week; after three years, this proportion fell to 10%. Employment rose from 27% to 42% of the cohort. Improvement in all outcomes was sustained over 3 years and for some outcomes increased in the second and third year. CONCLUSIONS/SIGNIFICANCE. Improvements in adult ART patients' symptom prevalence, general health, ability to perform normal activities, and employment status were large and were sustained through the first three years on treatment. These results suggest that some of the positive economic and social externalities anticipated as a result of large-scale treatment provision, such as increases in workforce participation and productivity and the ability of patients to carry on normal lives, may indeed be accruing.South Africa Mission of the U.S. Agency for International Development (GHSA-00-00020-00, 674-A-00-09-00018-00, 674-A-00-02-00018); National Institute of Allergies and Infectious Diseases (PEPFAR 13, K01AI083097); APDA Advanced Center for Parkinson Research at UAB (NIH F30NS065661, NIH R01CA122930); National Institutes of Health Blueprint Core for Neuroscience Research (NS057098

Using Evolutionary Algorithms for Fitting High-Dimensional Models to Neuronal Data

In the study of neurosciences, and of complex biological systems in general, there is frequently a need to fit mathematical models with large numbers of parameters to highly complex datasets. Here we consider algorithms of two different classes, gradient following (GF) methods and evolutionary algorithms (EA) and examine their performance in fitting a 9-parameter model of a filter-based visual neuron to real data recorded from a sample of 107 neurons in macaque primary visual cortex (V1). Although the GF method converged very rapidly on a solution, it was highly susceptible to the effects of local minima in the error surface and produced relatively poor fits unless the initial estimates of the parameters were already very good. Conversely, although the EA required many more iterations of evaluating the model neuron’s response to a series of stimuli, it ultimately found better solutions in nearly all cases and its performance was independent of the starting parameters of the model. Thus, although the fitting process was lengthy in terms of processing time, the relative lack of human intervention in the evolutionary algorithm, and its ability ultimately to generate model fits that could be trusted as being close to optimal, made it far superior in this particular application than the gradient following methods. This is likely to be the case in many further complex systems, as are often found in neuroscience

HIV prevalence and HIV clinical outcomes of transgender and gender-diverse people in England

Objectives: We provide the first estimate of HIV prevalence among trans and gender‐diverse people living in England and compare outcomes of people living with HIV according to gender identity. Methods: We analysed a comprehensive national HIV cohort and a nationally representative self‐reported survey of people accessing HIV care in England (Positive Voices). Gender identity was recorded using a two‐step question co‐designed with community members and civil society. Responses were validated by clinic follow‐up and/or self‐report. Population estimates were obtained from national government offices. Results: In 2017, HIV prevalence among trans and gender‐diverse people was estimated at 0.46–4.78 per 1000, compared with 1.7 (95% credible interval: 1.6–1.7) in the general population. Of 94 885 people living with diagnosed HIV in England, 178 (0.19%) identified as trans or gender‐diverse. Compared with cisgender people, trans and gender‐diverse people were more likely to be London residents (57% vs. 43%), younger (median age 42 vs. 46 years), of white ethnicity (61% vs. 52%), under psychiatric care (11% vs. 4%), to report problems with self‐care (37% vs. 13%), and to have been refused or delayed healthcare (23% vs. 11%). Antiretroviral uptake and viral suppression were high in both groups. Conclusions: HIV prevalence among trans and gender‐diverse people living in England is relatively low compared with international estimates. Furthermore, no inequalities were observed with regard to HIV care. Nevertheless, trans and gender‐diverse people with HIV report poorer mental health and higher levels of discrimination compared with cisgender people

High levels of genetic variability and differentiation in hilsa shad, Tenualosa ilisha (Clupeidae, Clupeiformes) populations revealed by PCR-RFLP analysis of the mitochondrial DNA D-loop region

The hilsa shad, Tenualosa ilisha (Clupeidae, Clupeiformes) is an important anadromous clupeid species from the Western division of the Indo-Pacific region. It constitutes the largest single fishable species in Bangladesh. Information on genetic variability and population structure is very important for both management and conservation purposes. Past reports on the population structure of T. ilisha involving morphometric, allozyme and RAPD analyses are contradictory. We examined genetic variability and divergence in two riverine (the Jamuna and the Meghna), two estuarine (Kuakata and Sundarbans) and one marine (Cox's Bazar) populations of T. ilisha by applying PCR-RFLP analysis of the mtDNA D-loop region. The amplified PCR products were restricted with four restriction enzymes namely, XbaI, EcoRI, EcoRV, and HaeIII. High levels of haplotype and gene diversity within and significant differentiations among, populations of T. ilisha were observed in this study. Significant FST values indicated differentiation among the river, estuary and marine populations. The UPGMA dendrogram based on genetic distance resulted in two major clusters, although, these were subsequently divided into three, corresponding to the riverine, estuarine and marine populations. The study underlines the usefulness of RFLP of mtDNA D-loop region as molecular markers, and detected at least two differentiated populations of T. ilisha in Bangladesh waters

Dry weather induces outbreaks of human West Nile virus infections

<p>Abstract</p> <p>Background</p> <p>Since its first occurrence in the New York City area during 1999, West Nile virus (WNV) has spread rapidly across North America and has become a major public health concern in North America. By 2002, WNV was reported in 40 states and the District of Columbia with 4,156 human and 14,539 equine cases of infection. Mississippi had the highest human incidence rate of WNV during the 2002 epidemic in the United States. Epidemics of WNV can impose enormous impacts on local economies. Therefore, it is advantageous to predict human WNV risks for cost-effective controls of the disease and optimal allocations of limited resources. Understanding relationships between precipitation and WNV transmission is crucial for predicting the risk of the human WNV disease outbreaks under predicted global climate change scenarios.</p> <p>Methods</p> <p>We analyzed data on the human WNV incidences in the 82 counties of Mississippi in 2002, using standard morbidity ratio (SMR) and Bayesian hierarchical models, to determine relationships between precipitation and human WNV risks. We also entertained spatial autocorrelations of human WNV risks with conditional autocorrelative (CAR) models, implemented in WinBUGS 1.4.3.</p> <p>Results</p> <p>We observed an inverse relationship between county-level human WNV incidence risk and total annual rainfall during the previous year. Parameters representing spatial heterogeneity in the risk of human exposure to WNV improved model fit. Annual precipitation of the previous year was a predictor of spatial variation of WNV risk.</p> <p>Conclusions</p> <p>Our results have broad implications for risk assessment of WNV and forecasting WNV outbreaks. Assessing risk of vector-born infectious diseases will require understanding of complex ecological relationships. Based on the climatologically characteristic drought occurrence in the past and on climate model predictions for climate change and potentially greater drought occurrence in the future, we suggest that the frequency and relative risk of WNV outbreaks could increase.</p

Lattice Boltzmann simulations of soft matter systems

This article concerns numerical simulations of the dynamics of particles immersed in a continuum solvent. As prototypical systems, we consider colloidal dispersions of spherical particles and solutions of uncharged polymers. After a brief explanation of the concept of hydrodynamic interactions, we give a general overview over the various simulation methods that have been developed to cope with the resulting computational problems. We then focus on the approach we have developed, which couples a system of particles to a lattice Boltzmann model representing the solvent degrees of freedom. The standard D3Q19 lattice Boltzmann model is derived and explained in depth, followed by a detailed discussion of complementary methods for the coupling of solvent and solute. Colloidal dispersions are best described in terms of extended particles with appropriate boundary conditions at the surfaces, while particles with internal degrees of freedom are easier to simulate as an arrangement of mass points with frictional coupling to the solvent. In both cases, particular care has been taken to simulate thermal fluctuations in a consistent way. The usefulness of this methodology is illustrated by studies from our own research, where the dynamics of colloidal and polymeric systems has been investigated in both equilibrium and nonequilibrium situations.Comment: Review article, submitted to Advances in Polymer Science. 16 figures, 76 page

Inhibition of apoptosis prevents West Nile virus induced cell death

We found that WNV infection induces cell death in the brain-derived tumour cell line T98G by apoptosis under involvement of constituents of the extrinsic as well as the intrinsic apoptotic pathways. Our results illuminate the molecular mechanism of WNV-induced neural cell death