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

Sleep-disordered breathing-do we have to change gears in heart failure?

The majority of patients with heart failure have sleep-disordered breathing (SDB)-with central (rather than obstructive) sleep apnoea becoming the predominant form in those with more severe disease. Cyclical apnoeas and hypopnoeas are associated with sleep disturbance, hypoxaemia, haemodynamic changes, and sympathetic activation. Such patients have a worse prognosis than those without SDB. Mask-based therapies of positive airway pressure targeted at SDB can improve measures of sleep quality and partially normalise the sleep and respiratory physiology, but recent randomised trials of cardiovascular outcomes in central sleep apnoea have been neutral or suggested the possibility of harm, likely from increased sudden death. Further randomised outcome studies (with cardiovascular mortality and hospitalisation endpoints) are required to determine whether mask-based treatment for SDB is appropriate for patients with chronic systolic heart failure and obstructive sleep apnoea, for those with heart failure with preserved ejection fraction, and for those with decompensated heart failure. New therapies for sleep apnoea-such as implantable phrenic nerve stimulators-also require robust assessment. No longer can the surrogate endpoints of improvement in respiratory and sleep metrics be taken as adequate therapeutic outcome measures in patients with heart failure and sleep apnoea

Nightly sleep apnea severity in patients with atrial fibrillation: Potential applications of long-term sleep apnea monitoring

In patients with atrial fibrillation (AF), the prevalence of moderate-to-severe sleep-disordered breathing (SDB) ranges between 21% and 72% and observational studies have demonstrated that SDB reduces the efficacy of rhythm control strategies, while treatment with continuous positive airway pressure lowers the rate of AF recurrence. Currently, the number of apneas and hypopneas per hour (apnea-hypopnea-index, AHI) determined during a single overnight sleep study is clinically used to assess the severity of SDB. However, recent studies suggest that SDB-severity in an individual patient is not stable over time but exhibits a considerable night-to-night variability which cannot be detected by only one overnight sleep assessment. Nightly SDB-severity assessment rather than the single-night diagnosis by one overnight sleep study may better reflect the exposure to SDB-related factors and yield a superior metric to determine SDB-severity in the management of AF. In this review we discuss mechanisms of night-to-night SDB variability, arrhythmogenic consequences of night-to-night SDB variability, strategies for longitudinal assessment of nightly SDB-severity and clinical implications for screening and management of SDB in AF patients

Factors affecting the yield of microRNAs from laser microdissectates of formalin-fixed tissue sections

<p>Abstract</p> <p>Background</p> <p>Quantification of microRNAs in specific cell populations microdissected from tissues can be used to define their biological roles, and to develop and deploy biomarker assays. In this study, a number of variables were examined for their effect on the yield of microRNAs in samples obtained from formalin-fixed paraffin-embedded tissues by laser microdissection.</p> <p>Results</p> <p>MicroRNA yield was improved by using cresyl violet instead of hematoxylin-eosin to stain tissue sections in preparation for microdissection, silicon carbide instead of glass fiber as matrix in RNA-binding columns, and overnight digestion of dissected samples with proteinase K. Storage of slides carrying stained tissue sections at room temperature for up to a week before microdissection, and storage of the microdissectates at room temperature for up to a day before RNA extraction did not adversely affect microRNA yield.</p> <p>Conclusions</p> <p>These observations should be of value for the efficient isolation of microRNAs from microdissected formalin-fixed tissues with a flexible workflow.</p

Renormalization and redundancy in 2d quantum field theories

We analyze renormalization group (RG) flows in two-dimensional quantum field theories in the presence of redundant directions. We use the operator picture in which redundant operators are total derivatives. Our analysis has three levels of generality. We introduce a redundancy anomaly equation which is analyzed together with the RG anomaly equation previously considered by H.Osborn [8] and D.Friedan and A.Konechny [7]. The Wess-Zumino consistency conditions between these anomalies yield a number of general relations which should hold to all orders in perturbation theory. We further use conformal perturbation theory to study field theories in the vicinity of a fixed point when some of the symmetries of the fixed point are broken by the perturbation. We relate various anomaly coefficients to OPE coefficients at the fixed point and analyze which operators become redundant and how they participate in the RG flow. Finally, we illustrate our findings by three explicit models constructed as current-current perturbations of SU(2)_k WZW model. At each generality level we discuss the geometric picture behind redundancy and how one can reduce the number of couplings by taking a quotient with respect to the redundant directions. We point to the special role of polar representations for the redundancy groups.Comment: 59 pages, 5 pdf figures; V3: version equivalent to the version published in JHEP (up to an additional footnote

Numerical simulation of the edge stress singularity and the adhesion strength for compliant mushroom fibrils adhered to rigid substrates

Bio-inspired adhesion of micropatterned surfaces due to intermolecular interactions has attracted much research interest over the last decade. Experiments show that the best adhesion is achieved with compliant "mushroom"-shaped fibrils. This paper analyses numerically the effects of different mushroom shapes on adhesion to a rigid substrate. When a remote stress is applied on the free end of a fibril perfectly bonded to a rigid substrate, the resultant stress distribution along the fibril is found to change dramatically between the straight punch and mushroom fibrils. A singular stress field is present at the edge of the fibril where it contacts the substrate and, in this work, the amplitude of the singularity is evaluated for fibrils perfectly bonded to a flat substrate so that sliding cannot occur there. This exercise is carried out for fibril geometries involving combinations of different diameters and thicknesses of the mushroom cap. By assuming a pre-existing detachment length at the corner where the stress singularity lies, we predict the adhesive strength for various mushroom cap shapes. Our study shows that a smaller stalk diameter and a thinner mushroom cap lead to higher adhesive strengths. A limited number of results are also given for other shapes, including those having a fillet radius connecting the stalk to the cap. The results support the rational optimisation of synthetic micropatterned adhesives