Syk-dependent Phosphorylation of CLEC-2: A Novel Mechanism of Hem-Immunoreceptor Tyrosine-Based Activation Motif Signaling

The C-type lectin-like receptor CLEC-2 signals via phosphorylation of a single cytoplasmic YXXL sequence known as a hem-immunoreceptor tyrosine-based activation motif (hemITAM). In this study, we show that phosphorylation of CLEC-2 by the snake toxin rhodocytin is abolished in the absence of the tyrosine kinase Syk but is not altered in the absence of the major platelet Src family kinases, Fyn, Lyn, and Src, or the tyrosine phosphatase CD148, which regulates the basal activity of Src family kinases. Further, phosphorylation of CLEC-2 by rhodocytin is not altered in the presence of the Src family kinase inhibitor PP2, even though PLCγ2 phosphorylation and platelet activation are abolished. A similar dependence of phosphorylation of CLEC-2 on Syk is also seen in response to stimulation by an IgG mAb to CLEC-2, although interestingly CLEC-2 phosphorylation is also reduced in the absence of Lyn. These results provide the first definitive evidence that Syk mediates phosphorylation of the CLEC-2 hemITAM receptor with Src family kinases playing a critical role further downstream through the regulation of Syk and other effector proteins, providing a new paradigm in signaling by YXXL-containing receptors

Atypical Non-H2S-Producing Monophasic Salmonella Typhimurium ST3478 Strains from Chicken Meat at Processing Stage Are Adapted to Diverse Stresses

Poultry products are still an important cause of Salmonella infections worldwide, with an increasingly reported expansion of less-frequent serotypes or atypical strains that are frequently multidrug-resistant. Nevertheless, the ability of Salmonella to survive antimicrobials promoted in the context of antibiotic reducing/replacing and farming rethinking (e.g., organic acids and copper in feed/biocides) has been scarcely explored. We investigated Salmonella occurrence (conventional and molecular assays) among chicken meat at the processing stage (n = 53 batches/29 farms) and characterized their tolerance to diverse stress factors (antibiotics, copper, acid pH, and peracetic acid). Whole-genome sequencing was used to assess adaptive features and to perform comparative analysis. We found a low Salmonella occurrence (4%) and identified S. Enteritidis/ST11 plus atypical non-H2S-producing S. 1,4,[5],12:i:-/ST3478. The ST3478 presented the ability to grow under diverse stresses (antibiotics, copper, and acid-pH). Comparative genomics among ST3478 isolates showed similar antibiotic/metal resistance gene repertoires and identical nonsense phsA thiosulfate reductase mutations (related to H2S-negative phenotype), besides their close phylogenetic relationship by cgMLST and SNPs. This study alerts for the ongoing national and international spread of an emerging monophasic Salmonella Typhimurium clonal lineage with an enlarged ability to survive to antimicrobials/biocides commonly used in poultry production, being unnoticed by conventional Salmonella detection approaches due to an atypical non-H2S-producing phenotype

Association between parental perceptions of residential neighbourhood environments and childhood obesity in Porto, Portugal

Portugal has one of the highest rates of childhood obesity in Europe. Few studies have explored the relationship between parents’ perceptions of their residential neighbourhood (safety concerns and amenities of the built environment) and their children’s weight status. This study aims to examine the associations between parents’ perceptions of their residential neighbourhood and overweight/obesity among their children. Methods: Anthropometric measures of height and weight were taken for 2690 children in preschools and elementary schools in Porto. Body mass index (kg/m2 ) was calculated, and the International Obesity Taskforce (IOTF) cut-offs were used. Parents completed the ‘Environmental Module’ standard questionnaire of the International Physical Activity Prevalence Study. Chi-square tests and the logistic regression model adjusted for age, gender, maternal education and school cluster were used to examine the associations between parents’ perceptions of their residential neighbourhood and overweight/obesity among their children. Results: In this sample, 31.8% of the children were overweight (including obese). Significant associations were found between child obesity and the following residential environmental characteristics: the odds of children being obese were lower if their parents believed that it was safe (low/no crime rate) to walk/cycle at night (OR = 0.65, 95% CI = 0.54–0.79) and during the day (OR = 0.70, 95% CI = 0.55–0.86) and that it was easy and pleasant (pedestrian safety) to walk in their neighbourhoods (OR = 0.73, 95% CI = 0.58–0.90) and when local sidewalks were well maintained and unobstructed (OR = 1.18, 95% CI = 1.01–1.40). Conclusion: Parental perceptions of neighbourhood safety and the quality of local sidewalks are significantly associated with obesity values

The effects of varying colour-luminosity relations on supernova science

The success of Type Ia supernova (SN Ia) distance standardisation for cosmology relies on a single global linear relationship between their peak luminosity and colour, the $\beta$ parameter. However, there are several pieces of evidence and physical reasons to believe that this relation is not universal and may change within different subgroups, or even among individual objects. In this work, we allow $\beta$ to vary among subpopulations with different observed properties in the cosmological fits. Although the inferred cosmological parameters are consistent with previous studies that assume a single colour-luminosity relation, we find that the SN data favour nonuniversal distributions of $\beta$ when split according to SN colour and/or host-galaxy mass. For galaxy mass, we obtain a $\beta$-step relation in which low $\beta$ values occur in more massive galaxies, a trend that can be explained by differing dust reddening laws for two types of environments. For colour, we find that bluer/redder SNe Ia are consistent with a lower/larger $\beta$. This trend is explained with $\beta$ being a combination of a low intrinsic colour-luminosity relation dominant in bluer SNe and a higher extrinsic reddening relation dominant at redder colours. The host galaxy mass-step correction always provides better distance calibration, regardless of the multiple $\beta$ approaches, and we suggest that it may come from a difference in intrinsic colour-luminosity properties of SNe Ia in two types of environments. Additionally, we find that blue SNe in low-mass environments are better standard candles than the others.Comment: 11 pages, 7 figures, 2 tables. Accepted in MNRA