Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity

Indexación: Web of Science; Scopus.The Human Respiratory Syncytial Virus (hRSV) is a major cause of acute lower respiratory tract infections (ARTIs) and high rates of hospitalizations in children and in the elderly worldwide. Symptoms of hRSV infection include bronchiolitis and pneumonia. The lung pathology observed during hRSV infection is due in part to an exacerbated host immune response, characterized by immune cell infiltration to the lungs. HRSV is an enveloped virus, a member of the Pneumoviridae family, with a non-segmented genome and negative polarity-single RNA that contains 10 genes encoding for 11 proteins. These include the Fusion protein (F), the Glycoprotein (G), and the Small Hydrophobic (SH) protein, which are located on the virus surface. In addition, the Nucleoprotein (N), Phosphoprotein (P) large polymerase protein (L) part of the RNA-dependent RNA polymerase complex, the M2-1 protein as a transcription elongation factor, the M2-2 protein as a regulator of viral transcription and (M) protein all of which locate inside the virion. Apart from the structural proteins, the hRSV genome encodes for the non-structural 1 and 2 proteins (NS1 and NS2). HRSV has developed different strategies to evade the host immunity by means of the function of some of these proteins that work as virulence factors to improve the infection in the lung tissue. Also, hRSV NS-1 and NS-2 proteins have been shown to inhibit the activation of the type I interferon response. Furthermore, the hRSV nucleoprotein has been shown to inhibit the immunological synapsis between the dendritic cells and T cells during infection, resulting in an inefficient T cell activation. Here, we discuss the hRSV virulence factors and the host immunological features raised during infection with this virus.https://www.frontiersin.org/articles/10.3389/fcimb.2017.00367/ful

A Few More Examples May Be Worth Billions of Parameters

We investigate the dynamics of increasing the number of model parameters versus the number of labeled examples across a wide variety of tasks. Our exploration reveals that while scaling parameters consistently yields performance improvements, the contribution of additional examples highly depends on the task's format. Specifically, in open question answering tasks, enlarging the training set does not improve performance. In contrast, classification, extractive question answering, and multiple choice tasks benefit so much from additional examples that collecting a few hundred examples is often “worth” billions of parameters. We hypothesize that unlike open question answering, which involves recalling specific information, solving strategies for tasks with a more restricted output space transfer across examples, and can therefore be learned with small amounts of labeled data

Std fimbriae-fucose interaction increases Salmonella-induced intestinal inflammation and prolongs colonization

Author summary The intestinal epithelium is a crucial biological interface, interacting with both commensal and pathogenic microorganisms. It’s lined with heavily glycosylated proteins and glycolipids which can act as both attachment sites and energy sources for intestinal bacteria. Fut2, the enzyme governing epithelial α1,2-fucosylation, has been implicated in the interaction between microbes and intestinal epithelial cells. Salmonella is one of the most important bacterial gastrointestinal pathogens affecting millions of people worldwide. Salmonella possesses fimbrial and non-fimbrial adhesins which can be used to adhere to host cells. Here we show that Salmonella expresses Std fimbriae in the gastrointestinal tract in vivo and exploit Std fimbriae to bind fucosylated structures in the mucus and on the intestinal epithelium. Furthermore, we demonstrate that the Std fimbriae-fucose interaction is necessary for bacterial colonization of the intestine and for triggering intestinal inflammation. These data lend new insights into bacterial adhesion-epithelial interactions which are essential for bacterial pathogenesis and key factors in determining tissue tropism and host susceptibility to infectious disease

RAST Model: Simulation of Tensiotraces to Facilitate Drophad Engineering

Tensiography is a technique that determines the physical and chemical properties of a liquid by illuminating a growing pendant drop from within using a source fibre. Light reflected internally at the surface of the drop is recieved by a collector fibre and is converted into an electric signal called a tensiotrace, which is a graph of reflected light as a function of drop volume. The instrument obtaining this signal is called multianalyser. A numerical model that simulates tensiotraces through a raytracing analysis (RAST - Raytracing Analysis for the Simulation of Tensiotraces) of the multianalyser as been developed to define theoretically how the tensiotrace describes the physical and chemical properties of a liquid. The purpose of this study is to investigate the model as an engineering/design assistant leading to discoveries and improvements to the multianalyser

Efficacy of Prehabilitation Including Exercise on Postoperative Outcomes Following Abdominal Cancer Surgery: A Systematic Review and Meta-Analysis

OBJECTIVE: This systematic review set out to identify, evaluate and synthesise the evidence examining the effect of prehabilitation including exercise on postoperative outcomes following abdominal cancer surgery. METHODS: Five electronic databases (MEDLINE 1946-2020, EMBASE 1947-2020, CINAHL 1937-2020, PEDro 1999-2020, and Cochrane Central Registry of Controlled Trials 1991-2020) were systematically searched (until August 2020) for randomised controlled trials (RCTs) that investigated the effects of prehabilitation interventions in patients undergoing abdominal cancer surgery. This review included any form of prehabilitation either unimodal or multimodal that included whole body and/or respiratory exercises as a stand-alone intervention or in addition to other prehabilitation interventions (such as nutrition and psychology) compared to standard care. RESULTS: Twenty-two studies were included in the systematic review and 21 studies in the meta-analysis. There was moderate quality of evidence that multimodal prehabilitation improves pre-operative functional capacity as measured by 6 min walk distance (Mean difference [MD] 33.09 metres, 95% CI 17.69–48.50; p = <0.01) but improvement in cardiorespiratory fitness such as preoperative oxygen consumption at peak exercise (VO2 peak; MD 1.74 mL/kg/min, 95% CI −0.03–3.50; p = 0.05) and anaerobic threshold (AT; MD 1.21 mL/kg/min, 95% CI −0.34–2.76; p = 0.13) were not significant. A reduction in hospital length of stay (MD 3.68 days, 95% CI 0.92–6.44; p = 0.009) was observed but no effect was observed for postoperative complications (Odds Ratio [OR] 0.81, 95% CI 0.55–1.18; p = 0.27), pulmonary complications (OR 0.53, 95% CI 0.28–1.01; p = 0.05), hospital re-admission (OR 1.07, 95% CI 0.61–1.90; p = 0.81) or postoperative mortality (OR 0.95, 95% CI 0.43–2.09, p = 0.90). CONCLUSION: Multimodal prehabilitation improves preoperative functional capacity with reduction in hospital length of stay. This supports the need for ongoing research on innovative cost-effective prehabilitation approaches, research within large multicentre studies to verify this effect and to explore implementation strategies within clinical practise

Identification of novel subgroup a variants with enhanced receptor binding and replicative capacity in primary isolates of anaemogenic strains of feline leukaemia virus

&lt;b&gt;BACKGROUND:&lt;/b&gt; The development of anaemia in feline leukaemia virus (FeLV)-infected cats is associated with the emergence of a novel viral subgroup, FeLV-C. FeLV-C arises from the subgroup that is transmitted, FeLV-A, through alterations in the amino acid sequence of the receptor binding domain (RBD) of the envelope glycoprotein that result in a shift in the receptor usage and the cell tropism of the virus. The factors that influence the transition from subgroup A to subgroup C remain unclear, one possibility is that a selective pressure in the host drives the acquisition of mutations in the RBD, creating A/C intermediates with enhanced abilities to interact with the FeLV-C receptor, FLVCR. In order to understand further the emergence of FeLV-C in the infected cat, we examined primary isolates of FeLV-C for evidence of FeLV-A variants that bore mutations consistent with a gradual evolution from FeLV-A to FeLV-C.&lt;p&gt;&lt;/p&gt; &lt;b&gt;RESULTS:&lt;/b&gt; Within each isolate of FeLV-C, we identified variants that were ostensibly subgroup A by nucleic acid sequence comparisons, but which bore mutations in the RBD. One such mutation, N91D, was present in multiple isolates and when engineered into a molecular clone of the prototypic FeLV-A (Glasgow-1), enhanced replication was noted in feline cells. Expression of the N91D Env on murine leukaemia virus (MLV) pseudotypes enhanced viral entry mediated by the FeLV-A receptor THTR1 while soluble FeLV-A Env bearing the N91D mutation bound more efficiently to mouse or guinea pig cells bearing the FeLV-A and -C receptors. Long-term in vitro culture of variants bearing the N91D substitution in the presence of anti-FeLV gp70 antibodies did not result in the emergence of FeLV-C variants, suggesting that additional selective pressures in the infected cat may drive the subsequent evolution from subgroup A to subgroup C.&lt;p&gt;&lt;/p&gt; &lt;b&gt;CONCLUSIONS:&lt;/b&gt; Our data support a model in which variants of FeLV-A, bearing subtle differences in the RBD of Env, may be predisposed towards enhanced replication in vivo and subsequent conversion to FeLV-C. The selection pressures in vivo that drive the emergence of FeLV-C in a proportion of infected cats remain to be established

Retaining Expression on De-identified Faces

© Springer International Publishing AG 2017The extensive use of video surveillance along with advances in face recognition has ignited concerns about the privacy of the people identifiable in the recorded documents. A face de-identification algorithm, named k-Same, has been proposed by prior research and guarantees to thwart face recognition software. However, like many previous attempts in face de-identification, kSame fails to preserve the utility such as gender and expression of the original data. To overcome this, a new algorithm is proposed here to preserve data utility as well as protect privacy. In terms of utility preservation, this new algorithm is capable of preserving not only the category of the facial expression (e.g., happy or sad) but also the intensity of the expression. This new algorithm for face de-identification possesses a great potential especially with real-world images and videos as each facial expression in real life is a continuous motion consisting of images of the same expression with various degrees of intensity.Peer reviewe