The effects of classic and variant infectious bursal disease viruses on lymphocyte populations in specific-pathogen-free White Leghorn chickens

Infectious bursal disease virus (IBDV) is a pathogen that primarily infects B lymphocytes in domestic avian species. This viral infection has been associated with immunosuppression, clinical disease/mortality, and enteric malabsorption effects. The purpose of this experiment was to compare the effects of a classic (USDA-STC) and a new variant IBDV (RB-4, known to induce primarily the enteric disease) on immune cell populations in lymphoid organs. Seventeen-dayold specific-pathogen-free (SPF) White Leghorn chickens were either not infected (control) or inoculated with either USDA-STC or RB-4 IBD viral isolate. On days 3 and 5 post-inoculation (PI), lymphoid tissues were collected to prepare cell suspensions for immunofluorescent staining and cell population analysis by flow cytometry. Portions of the tissues were snap frozen for immunohistochemistry to localize various immune cells and IBD virus in the tissues. Tissue homogenates were prepared to test for IBDV by quantitative MTT assay. Both the USDA-STC and RB-4 viruses greatly altered lymphocyte populations in the spleen and bursa. At 5 d PI, bursal B cells were approximately 25% and 60% of lymphocytes in chicks infected with USDA-STC and RB-4, respectively, whereas in control birds, B cells constituted 99% of bursal lymphocytes. This reduction in the proportions of bursal B cells was associated with an infiltration of T cells. In the spleen, IBDV infection also reduced the percentage of B cells and increased the percentage of T cells. The differential effects of classic and variant IBDV infection on immune cell populations in lymphoid organs may explain the differences in clinical effects induced by these viruse

Inference of Convergent Gene Acquisition Among Pseudomonas syringae Strains Isolated From Watermelon, Cantaloupe, and Squash

Pseudomonas syringae sensu strict , (phylogroup 2; referred to as P. syringae) consists of an environmentally ubiquitous bacterial population associated with diseases of numerous plant species. Recent studies using multilocus sequence analysis have indicated the clonal expansion of several P. syringae lineages, located in phylogroups 2a and 2b, in association with outbreaks of bacterial spot disease of watermelon, cantaloupe, and squash in the United States. To investigate the evolutionary processes that led to the emergence of these epidemic lineages, we sequenced the genomes of six P. syringae strains that were isolated from cucurbits grown in the United States, Europe, and China over a period of more than a decade, as well as eight strains that were isolated from watermelon and squash grown in six different Florida counties during the 2013 and 2014 seasons. These data were subjected to comparative analyses along with 42 previously sequenced genomes of P. syringae stains collected from diverse plant species and environments available from GenBank. Maximum likelihood reconstruction of the P. syringae core genome revealed the presence of a hybrid phylogenetic group, comprised of cucurbit strains collected in Florida, Italy, Serbia, and France, which emerged through genome-wide homologous recombination between phylogroups 2a and 2b. Functional analysis of the recombinant core genome showed that pathways involved in the ATP-dependent transport and metabolism of amino acids, bacterial motility, and secretion systems were enriched for recombination. A survey of described virulence factors indicated the convergent acquisition of several accessory type 3 secreted effectors (T3SEs) among phylogenetically distinct lineages through integrative and conjugative element and plasmid loci. Finally, pathogenicity assays on watermelon and squash showed qualitative differences in virulence between strains of the same clonal lineage, which correlated with T3SEs acquired through various mechanisms of horizontal gene transfer (HGT). This study provides novel insights into the interplay of homologous recombination and HGT toward pathogen emergence and highlights the dynamic nature of P. syringae sensu lato genomes

Exploring the use of rapport in professional information‐gathering contexts by systematically mapping the evidence base

A growing body of research illustrates consensus between researchers and practitioners that developing rapport facilitates cooperation and disclosure in a range of professional information gathering contexts. In such contexts, rapport behaviors are often intentionally used in an attempt to facilitate a positive interaction with another adult, which may or may not result in genuine mutual rapport. To examine how rapport has been manipulated and measured in professional contexts we systematically mapped the relevant evidence-base in this field. For each of the 35 studies that met our inclusion criteria, behaviors associated with building rapport were coded in relation to whether they were verbal, non-verbal, or para-verbal. Methods to measure rapport were also coded and recorded, as were different types of disclosure. A Searchable Systematic Map was produced to catalogue key study characteristics. Discussion focuses on the underlying intention of the rapport behaviors that featured most frequently across studies

Quality and Safety Aspects of Infant Nutrition

Quality and safety aspects of infant nutrition are of key importance for child health, but oftentimes they do not get much attention by health care professionals whose interest tends to focus on functional benefits of early nutrition. Unbalanced diets and harmful food components induce particularly high risks for untoward effects in infants because of their rapid growth, high nutrient needs, and their typical dependence on only one or few foods during the first months of life. The concepts, standards and practices that relate to infant food quality and safety were discussed at a scientific workshop organized by the Child Health Foundation and the Early Nutrition Academy jointly with the European Society for Paediatric Gastroenterology, Hepatology and Nutrition, and a summary is provided here. The participants reviewed past and current issues on quality and safety, the role of different stakeholders, and recommendations to avert future issues. It was concluded that a high level of quality and safety is currently achieved, but this is no reason for complacency. The food industry carries the primary responsibility for the safety and suitability of their products, including the quality of composition, raw materials and production processes. Introduction of new or modified products should be preceded by a thorough science based review of suitability and safety by an independent authority. Food safety events should be managed on an international basis. Global collaboration of food producers, food-safety authorities, paediatricians and scientists is needed to efficiently exchange information and to best protect public health. Copyright (C) 2012 S. Karger AG, Base

Myeloid-specific Asxl2 deletion limits diet-induced obesity by regulating energy expenditure

We previously established that global deletion of the enhancer of trithorax and polycomb (ETP) gene, Asxl2, prevents weight gain. Because proinflammatory macrophages recruited to adipose tissue are central to the metabolic complications of obesity, we explored the role of ASXL2 in myeloid lineage cells. Unexpectedly, mice without Asxl2 only in myeloid cells (Asxl2ΔLysM) were completely resistant to diet-induced weight gain and metabolically normal despite increased food intake, comparable activity, and equivalent fecal fat. Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. Energy expenditure and brown adipose tissue metabolism in Asxl2ΔLysM mice were protected from the suppressive effects of HFD, a phenomenon associated with relatively increased catecholamines likely due to their suppressed degradation by macrophages. White adipose tissue of HFD-fed Asxl2ΔLysM mice also exhibited none of the pathological remodeling extant in their control counterparts. Suppression of macrophage Asxl2 expression, via nanoparticle-based siRNA delivery, prevented HFD-induced obesity. Thus, ASXL2 controlled the response of macrophages to dietary factors to regulate metabolic homeostasis, suggesting modulation of the cells\u27 inflammatory phenotype may impact obesity and its complications

Avapritinib versus regorafenib in locally advanced unresectable or metastatic GI stromal tumor: A randomized, open-label phase III study

PURPOSE Primary or secondary mutations in KIT or platelet-derived growth factor receptor alpha (PDGFRA) underlie tyrosine kinase inhibitor resistance in most GI stromal tumors (GISTs). Avapritinib selectively and potently inhibits KIT- and PDGFRA-mutant kinases. In the phase I NAVIGATOR study (NCT02508532), avapritinib showed clinical activity against PDGFRA D842V–mutant and later-line KIT-mutant GIST. VOYAGER (NCT03465722), a phase III study, evaluated efficacy and safety of avapritinib versus regorafenib as third-line or later treatment in patients with unresectable or metastatic GIST. PATIENTS AND METHODS VOYAGER randomly assigned patients 1:1 to avapritinib 300 mg once daily (4 weeks continuously) or regorafenib 160 mg once daily (3 weeks on and 1 week off). Primary end point was progression-free survival (PFS) by central radiology per RECIST version 1.1 modified for GIST. Secondary end points included objective response rate, overall survival, safety, disease control rate, and duration of response. Regorafenib to avapritinib crossover was permitted upon centrally confirmed disease progression. RESULTS Four hundred seventy-six patients were randomly assigned (avapritinib, n 5 240; regorafenib, n 5 236). Median PFS was not statistically different between avapritinib and regorafenib (hazard ratio, 1.25; 95% CI, 0.99 to 1.57; 4.2 v 5.6 months; P 5 .055). Overall survival data were immature at cutoff. Objective response rates were 17.1% and 7.2%, with durations of responses of 7.6 and 9.4 months for avapritinib and regorafenib; disease control rates were 41.7% (95% CI, 35.4 to 48.2) and 46.2% (95% CI, 39.7 to 52.8). Treatment-related adverse events (any grade, grade $ 3) were similar for avapritinib (92.5% and 55.2%) and regorafenib (96.2% and 57.7%). CONCLUSION Primary end point was not met. There was no significant difference in median PFS between avapritinib and regorafenib in patients with molecularly unselected, late-line GIST

Method for Bacteriophage Delivery and Amplification

Methods of selecting wide host range bacteriophage capable of growing in a plurality of bacteria including pathogenic and non-pathogenic bacteria and bacteriophage selected are described. In addition to methods of treating a subject infected with a pathogenic bacterium using bacteriophage, of decontaminating objects using bacteriophage, of producing vaccines. In another aspect, methods of determining bacterial viability and methods of improving the sensitivity of a biosensor using wide host range bacteriophages are also disclosed