Allergy, Asthma, and Inflammation: Which Inflammatory Cell Type Is More Important?

<p/> <p>A recent review in <it>Allergy, Asthma, and Clinical Immunology </it>suggested that eosinophils play a minor role, if any, in the inflammatory spectrum of asthma and allergic inflammation. The article that dealt with mast cells suggested that the presence of these important cells within the smooth muscle layer in asthmatic airways renders this cell type primal in asthma and an obvious and important target for therapy. This article proposes that in a complex inflammatory milieu characterizing the complex syndromes we call asthma, no single cell phenotype is responsible for the condition and thus should be a sole target for therapeutic strategies. Our reductionist approach to research in asthma and related conditions has provided us with convincing evidence for multiple roles that immune, inflammatory, and structural cell types can play in complex diseases. The next stage in understanding and ameliorating these complex conditions is to move away from the simplistic notion of one cell type being more important than another. Instead, what is needed is to acquire knowledge of intricate and exquisite biological systems that regulate such conditions in both health and disease involving various cell types, mediators, pharmacologically active products, their multifaceted capacities, and their socio-biological networking.</p

TeAAL: A Declarative Framework for Modeling Sparse Tensor Accelerators

Over the past few years, the explosion in sparse tensor algebra workloads has led to a corresponding rise in domain-specific accelerators to service them. Due to the irregularity present in sparse tensors, these accelerators employ a wide variety of novel solutions to achieve good performance. At the same time, prior work on design-flexible sparse accelerator modeling does not express this full range of design features, making it difficult to understand the impact of each design choice and compare or extend the state-of-the-art. To address this, we propose TeAAL: a language and compiler for the concise and precise specification and evaluation of sparse tensor algebra architectures. We use TeAAL to represent and evaluate four disparate state-of-the-art accelerators--ExTensor, Gamma, OuterSPACE, and SIGMA--and verify that it reproduces their performance with high accuracy. Finally, we demonstrate the potential of TeAAL as a tool for designing new accelerators by showing how it can be used to speed up Graphicionado--by $38\times$ on BFS and $4.3\times$ on SSSP.Comment: 14 pages, 12 figure

Identification of a Ruminant Origin Group B Rotavirus Associated with Diarrhea Outbreaks in Foals

Equine rotavirus group A (ERVA) is one of the most common causes of foal diarrhea. Starting in February 2021, there was an increase in the frequency of severe watery to hemorrhagic diarrhea cases in neonatal foals in Central Kentucky. Diagnostic investigation of fecal samples failed to detect evidence of diarrhea-causing pathogens including ERVA. Based on Illumina-based metagenomic sequencing, we identified a novel equine rotavirus group B (ERVB) in fecal specimens from the affected foals in the absence of any other known enteric pathogens. Interestingly, the protein sequence of all 11 segments had greater than 96% identity with group B rotaviruses previously found in ruminants. Furthermore, phylogenetic analysis demonstrated clustering of the ERVB with group B rotaviruses of caprine and bovine strains from the USA. Subsequent analysis of 33 foal diarrheic samples by RT-qPCR identified 23 rotavirus B-positive cases (69.69%). These observations suggest that the ERVB originated from ruminants and was associated with outbreaks of neonatal foal diarrhea in the 2021 foaling season in Kentucky. Emergence of the ruminant-like group B rotavirus in foals clearly warrants further investigation due to the significant impact of the disease in neonatal foals and its economic impact on the equine industry

Eosinophil granules function extracellularly as receptor-mediated secretory organelles

Intracellular granules in several types of leukocytes contain preformed proteins whose secretions contribute to immune and inflammatory functions of leukocytes, including eosinophils, cells notably associated with asthma, allergic inflammation, and helminthic infections. Cytokines and chemokines typically elicit extracellular secretion of granule proteins by engaging receptors expressed externally on the plasma membranes of cells, including eosinophils. Eosinophil granules, in addition to being intracellular organelles, are found as intact membrane-bound structures extracellularly in tissue sites of eosinophil-associated diseases. Neither the secretory capacities of cell-free eosinophil granules nor the presence of functional cytokine and chemokine receptors on membranes of leukocyte granules have been recognized. Here, we show that granules of human eosinophils express membrane receptors for a cytokine, IFN-γ, and G protein–coupled membrane receptors for a chemokine, eotaxin, and that these receptors function by activating signal-transducing pathways within granules to elicit secretion from within granules. Capacities of intracellular granule organelles to function autonomously outside of eosinophils as independent, ligand-responsive, secretion-competent structures constitute a novel postcytolytic mechanism for regulated secretion of eosinophil granule proteins that may contribute to eosinophil-mediated inflammation and immunomodulation