Higher plants utilize nucleotide-binding leucine-rich repeat domain proteins (NLRs) as intracellular immune receptors to recognize pathogen-derived effectors and trigger a robust defense. The Activated Disease Resistance 1 (ADR1) family of coiled-coil NLRs (CNLs) have evolved as helper NLRs that function downstream of many TIR-type sensor NLRs (TNLs). Close homologs of ADR1s form the NRG1 family in Arabidopsis, the function of…
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The widespread use of accessible peripheral tissues for epigenetic analyses has prompted increasing interest in the study of tissue-specific DNA methylation (DNAm) variation in human populations. To date, characterizations of inter-individual DNAm variability and DNAm concordance across tissues have been largely performed in adult tissues and therefore are limited in their relevance to DNAm profiles from pediatric samples. Given that…
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Bottoms Up: The Role of Gut Microbiota in Brain Health

The gut microbiota affects many aspects of human health, and research, especially over the past decade, is demonstrating that the brain is no exception. This review summarizes existing human observational studies of the microbiota in brain health and neurological conditions at all ages, as well as animal studies that are advancing the field beyond correlation and into causality. Potential mechanisms…
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Human embryonic stem cells (hESCs) are a potential unlimited source of insulin-producing β cells for diabetes treatment. A greater understanding of how β cells form during embryonic development will improve current hESC differentiation protocols. All pancreatic endocrine cells, including β cells, are derived from Neurog3-expressing endocrine progenitors. This study characterizes the single-cell transcriptomes of 6,905 mouse embryonic day (E) 15.5 and…
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Purpose High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) has a poor outcome after standard chemoimmunotherapy. We sought to understand the biologic underpinnings of HGBL-DH/TH with BCL2rearrangements (HGBL-DH/TH-BCL2) and diffuse large B-cell lymphoma (DLBCL) morphology through examination of gene expression. Patients and Methods We analyzed RNA sequencing data from 157 de novo germinal center B-cell-like (GCB)-DLBCLs, including 25 with HGBL-DH/TH-BCL2, to define a gene…
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The results presented in this manuscript demonstrate the role for the IL13 receptor Rα2 in mediating repair of injured airway epithelium. The authors also demonstrated that the expression of IL13Rα2 is dramatically and significantly reduced in the airway epithelium of asthmatic individuals. This provides insight into the historical findings of epithelial damage and inflammation, in particular elevated IL13, in asthma. It may not be appropriate to block or absorb IL13 in asthma therapies, instead facilitating repair of the airway epithelium via IL13 becomes a new target for novel therapeutics.
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Intravenous Immunoglobulin (IVIg) is used to treat autoimmune or inflammatory diseases, but its mechanism of action is not completely understood. We asked whether IVIg can induce interleukin-10 (IL-10) and reduce pro-inflammatory cytokine production in human monocytes, and whether this response is reduced in monocytes from people with an Fcγ receptor IIA (FcγRIIA) gene variant, which is associated with increased risk…
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We have known for many years that these first-line responses, which are crucial to fight microbes, are turned off in early gestation. However, we did not know how. Studying monocytes from premature babies born at less than 33 weeks, we found that cells lack the capacity to rapidly increase glycolytic energy production required at the initiation of an inflammatory responses. These cells also lack protein synthesis capacity and are thus unable to produce key proteins involved in the immune response.
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A caspase-1 inhibitor was shown to decrease not only caspase-1-mediated cleavage of HTT at 572, but at the 586 caspase-6 site as well. When we blocked proteolysis or cleavage at this site in cell culture, we found that the mutant protein formed significantly less aggregates and that the half-life of the protein significantly decreased, suggesting it is cleared from the cell faster. Therefore, targeting caspase-1 could be beneficial two-fold; by inhibiting the new site of cleavage at 572 as well as by inhibiting activation of caspase-6 through caspase-1 leading to decreased 586 cleavage.
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Millions of clinical specimens are stored in the form of formalin-fixed paraffin-embedded (FFPE) samples. The capacity to tap into these samples is crucial for NGS analysis; however, there are two major challenges with FFPE samples. First, the extraction and sample preparation methods are tedious. Second, data quality is degraded following formalin fixation, storage and purification. The authors showed that among the sequencing artifacts are chimeric reads that appear to be derived from non-contiguous portions that align to both the ‘Watson’ and ‘Crick’ strands of the reference genome.
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