Genetic and antigenic variation of foot-and-mouth disease virus during persistent infection in naturally infected cattle and Asian buffalo in India

Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. The role of foot-and-mouth disease virus (FMDV) persistently infected ruminants in initiating new outbreaks remains controversial, and the perceived threat posed by such animals hinders international trade in FMD-endemic countries. In this study we report longitudinal analyses of genetic and antigenic variations of FMDV serotype O/ME-SA/Ind2001d sublineage during naturally occurring, persistent infection in cattle and buffalo at an organised dairy farm in India. The proportion of animals from which FMDV RNA was recovered was not significantly different between convalescent (post-clinical) and sub-clinically infected animals or between cattle and buffalo across the sampling period. However, infectious virus was isolated from a higher proportion of buffalo samples and for a longer duration compared to cattle. Analysis of the P1 sequences from recovered viruses indicated fixation of mutations at the rate of 1.816 x 10-2substitution/site/year (s/s/y) (95% CI 1.362–2.31 x 10−2 s/s/y). However, the majority of point mutations were transitional substitutions. Within individual animals, the mean dN/dS (ω) value for the P1 region varied from 0.076 to 0.357, suggesting the selection pressure acting on viral genomes differed substantially across individual animals. Statistical parsimony analysis indicated that all of the virus isolates from carrier animals originated from the outbreak virus. The antigenic relationship value as determined by 2D-VNT assay revealed fluctuation of antigenic variants within and between carrier animals during the carrier state which suggested that some carrier viruses had diverged substantially from the protection provided by the vaccine strain. This study contributes to understanding the extent of within-host and within-herd evolution that occurs during the carrier state of FMDV

Genome sequences of seven foot-andmouth disease virus isolates collected from serial samples from one persistently infected carrier cow in Vietnam

Several foot-and-mouth disease virus (FMDV) carrier cattle were identified in Vietnam by the recovery of infectious virus from oropharyngeal fluid. This report contains the first near-complete genome sequences of seven viruses from sequential samples from one carrier animal collected over the course of 1 year. The characterization of within-host viral evolution has implications for FMDV control strategies

High magnetic field scales and critical currents in SmFeAs(O,F) crystals: promising for applications

Superconducting technology provides most sensitive field detectors, promising implementations of qubits and high field magnets for medical imaging and for most powerful particle accelerators. Thus, with the discovery of new superconducting materials, such as the iron pnictides, exploring their potential for applications is one of the foremost tasks. Even if the critical temperature Tc is high, intrinsic electronic properties might render applications rather difficult, particularly if extreme electronic anisotropy prevents effective pinning of vortices and thus severely limits the critical current density, a problem well known for cuprates. While many questions concerning microscopic electronic properties of the iron pnictides have been successfully addressed and estimates point to a very high upper critical field, their application potential is less clarified. Thus we focus here on the critical currents, their anisotropy and the onset of electrical dissipation in high magnetic fields up to 65 T. Our detailed study of the transport properties of optimally doped SmFeAs(O,F) single crystals reveals a promising combination of high (>2 x 10^6 A/cm^2) and nearly isotropic critical current densities along all crystal directions. This favorable intragrain current transport in SmFeAs(O,F), which shows the highest Tc of 54 K at ambient pressure, is a crucial requirement for possible applications. Essential in these experiments are 4-probe measurements on Focused Ion Beam (FIB) cut single crystals with sub-\mu\m^2 cross-section, with current along and perpendicular to the crystallographic c-axis and very good signal-to-noise ratio (SNR) in pulsed magnetic fields. The pinning forces have been characterized by scaling the magnetically measured "peak effect"

Phosphofructo-2-kinase/Fructose-2,6-bisphosphatase Modulates Oscillations of Pancreatic Islet Metabolism

Pulses of insulin from pancreatic beta-cells help maintain blood glucose in a narrow range, although the source of these pulses is unclear. It has been proposed that a positive feedback circuit exists within the glycolytic pathway, the autocatalytic activation of phosphofructokinase-1 (PFK1), which endows pancreatic beta-cells with the ability to generate oscillations in metabolism. Flux through PFK1 is controlled by the bifunctional enzyme PFK2/FBPase2 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase) in two ways: via (1) production/degradation of fructose-2,6-bisphosphate (Fru2,6-BP), a potent allosteric activator of PFK1, as well as (2) direct activation of glucokinase due to a protein-protein interaction. In this study, we used a combination of live-cell imaging and mathematical modeling to examine the effects of inducibly-expressed PFK2/FBPase2 mutants on glucose-induced Ca2+ pulsatility in mouse islets. Irrespective of the ability to bind glucokinase, mutants of PFK2/FBPase2 that increased the kinase:phosphatase ratio reduced the period and amplitude of Ca2+ oscillations. Mutants which reduced the kinase:phosphatase ratio had the opposite effect. These results indicate that the main effect of the bifunctional enzyme on islet pulsatility is due to Fru2,6-BP alteration of the threshold for autocatalytic activation of PFK1 by Fru1,6-BP. Using computational models based on PFK1-generated islet oscillations, we then illustrated how moderate elevation of Fru-2,6-BP can increase the frequency of glycolytic oscillations while reducing their amplitude, with sufficiently high activation resulting in termination of slow oscillations. The concordance we observed between PFK2/FBPase2-induced modulation of islet oscillations and the models of PFK1-driven oscillations furthermore suggests that metabolic oscillations, like those found in yeast and skeletal muscle, are shaped early in glycolysis

Fibrillization of Human Tau Is Accelerated by Exposure to Lead via Interaction with His-330 and His-362

and its mutants at physiological pH. interaction with His-330 and His-362, with sub-micromolar affinity. in the pathogenesis of Alzheimer disease and provide critical insights into the mechanism of lead toxicity

A pilot study on the effects of a team building process on the perception of work environment in an integrative hospital for neurological rehabilitation

<p>Abstract</p> <p>Background</p> <p>Neurological rehabilitation is one of the most care-intensive challenges in the health care system requiring specialist therapeutic and nursing knowledge. In this descriptive pilot study, we investigated the effects of a team building process on perceived work environment, self-ascribed professional competence, life satisfaction, and client satisfaction in an anthroposophic specialized hospital for neurological rehabilitation. The team-building process consisted of didactic instruction and training in problem-solving, teambuilding and constructive conflict resolution.</p> <p>Methods</p> <p>Seventy seven staff members and 44 patients' relatives were asked to complete a survey that included the Work Environment Scale (WES-10), a Life Satisfaction Scale (BMLSS), the Conviction of Therapeutic Competency (CTC) scale and the Client Satisfaction Questionnaire (CSQ-8). To evaluate the outcome of the team building process, we analyzed changes over time in the WES-10 subscales. Additionally the interrelationship between the WES-10 subscales with other subscales and with sociodemographic parameters like age, gender was calculated by means of a bivariate correlation analysis.</p> <p>Results</p> <p>The team building process had a significant positive effect on perceived work environment in only one area. There was a significant improvement in the ward staffs' perception of their ability to constructively resolve conflicts 3 years after inception of the team building process than there was before inception. However, even in a unit that utilized holistic treatment and nursing in the care of severely disable patients, such care necessitating a very heavy workload, the measurements on the Self Realization, Life Satisfaction and Conviction of Therapeutic Competency scales remained high and unchanged over the three year time period of the study.</p> <p>Conclusions</p> <p>Strategic interventions might be an option to improve interpersonal relationships and finally quality of patient care.</p

Alzheimer's risk variants in the clusterin gene are associated with alternative splicing

Genetic variation in CLU encoding clusterin has been associated with Alzheimer's disease (AD) through replicated genome-wide studies, but the underlying mechanisms remain unknown. Following earlier reports that tightly regulated CLU alternative transcripts have different functions, we tested CLU single-nucleotide polymorphisms (SNPs), including those associated with AD for quantitative effects on individual alternative transcripts. In 190 temporal lobe samples without pathology, we found that the risk allele of the AD-associated SNP rs9331888 increases the relative abundance of transcript NM_203339 (P=4.3 × 10−12). Using an independent set of 115 AD and control samples, we replicated this result (P=0.0014) and further observed that multiple CLU transcripts are at higher levels in AD compared with controls. The AD SNP rs9331888 is located in the first exon of NM_203339 and therefore, it is a functional candidate for the observed effects. We tested this hypothesis by in vitro dual luciferase assays using SK-N-SH cells and mouse primary cortical neurons and found allelic effects on enhancer function, consistent with our results on post-mortem human brain. These results suggest a biological mechanism for the genetic association of CLU with AD risk and indicate that rs9331888 is one of the functional DNA variants underlying this association

Water displacement leg volumetry in clinical studies - A discussion of error sources

<p>Abstract</p> <p>Background</p> <p>Water displacement leg volumetry is a highly reproducible method, allowing the confirmation of efficacy of vasoactive substances. Nevertheless errors of its execution and the selection of unsuitable patients are likely to negatively affect the outcome of clinical studies in chronic venous insufficiency (CVI).</p> <p>Discussion</p> <p>Placebo controlled double-blind drug studies in CVI were searched (Cochrane Review 2005, MedLine Search until December 2007) and assessed with regard to efficacy (volume reduction of the leg), patient characteristics, and potential methodological error sources. Almost every second study reported only small drug effects (≤ 30 mL volume reduction). As the most relevant error source the conduct of volumetry was identified. Because the practical use of available equipment varies, volume differences of more than 300 mL - which is a multifold of a potential treatment effect - have been reported between consecutive measurements. Other potential error sources were insufficient patient guidance or difficulties with the transition from the Widmer CVI classification to the CEAP (Clinical Etiological Anatomical Pathophysiological) grading.</p> <p>Summary</p> <p>Patients should be properly diagnosed with CVI and selected for stable oedema and further clinical symptoms relevant for the specific study. Centres require a thorough training on the use of the volumeter and on patient guidance. Volumetry should be performed under constant conditions. The reproducibility of short term repeat measurements has to be ensured.</p

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table