The recent Blood article by Schroeder et al. demonstrates that plerixafor mobilizes a unique hematopoietic stem and progenitor cell (HSPC) product that is enriched in plasmacytoid dendritic cell precursors (pre-pDCs). This study further reports that enrichment of these cells in plerixafor-mobilized allografts is associated with lower cumulative incidence of acute and chronic graft-versus-host disease (GvHD). In an earlier study, Waller…
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Chemically Controlled Aggregation of Pluripotent Stem Cells

This study develops a novel technology to control aggregation of pluriportent stem cells in suspension manufacturing processes. Aggregation is a critical and highly variable property in stem cell bioreactor manufacturing. We discovered a chemical method to control the way stem cells aggregate in a predictable and reproducible manner. This technology will improve the robustness of pluripotent stem cell manufacturing processes and help move these therapies towards efficient clinical production…
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The Intestinal Epithelium: Central Coordinator of Mucosal Immunity

The gastrointestinal (GI) tract represents a unique challenge to the mammalian immune system. It must tolerate the presence of the luminal microbiota and thus not respond to their products, but still protect the intestinal mucosa from potentially harmful dietary antigens and invading pathogens. The intestinal epithelium, composed of a single layer of cells, is crucial for preserving gut homeostasis and…
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For the past 35 years, scientists have been seeking a candidate therapeutic “smart-drug” that can cleave a specific RNA sequence under cellular conditions.  In past riboyzmes and DNAyzmes had offered promise for this but have not lived up to this promise.  In our case, we’ve developed a new DNA-based catalyst that can cleave RNA without metal ions where the catalytic “power” comes from synthetic appendages…
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Cortical capillaries are prone to obstruction, which over time, could have a major impact on brain angioarchitecture and function. The mechanisms that govern the removal of these obstructions and what long-term fate awaits obstructed capillaries, remains a mystery. We estimate that ~0.12% of mouse cortical capillaries are obstructed each day (lasting >20 min), preferentially in superficial layers and lower order…
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Oncolytic Viruses as Engineering Platforms for Combination Immunotherapy

To effectively build on the recent successes of immune checkpoint blockade, adoptive T cell therapy and cancer vaccines, it is critical to rationally design combination strategies that will increase and extend efficacy to a larger proportion of patients. For example, the combination of anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and anti-programmed cell death protein 1 (PD1) immune checkpoint inhibitors essentially…
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Viral Proteins as a Potential Driver of Histone Depletion in Dinoflagellates

The packaging of DNA with histones is a hallmark of eukaryotic chromosomes.  One surprising exception is dinoflagellates, a group of unicellular eukaryotic algae, which have abandoned histones as the primary DNA packaging protein and instead employ a viral-derived proteins termed dinoflagellate-viral-nucleoproteins (DVNPs).  In this study, we sought to understand the molecular events…
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Salicylic acid (SA) is a plant defense hormone required for immunity. Arabidopsis NPR1 and NPR3/NPR4 were previously shown to bind SA and all three proteins were proposed as SA receptors. NPR1 functions as a transcriptional co-activator, whereas NPR3/NPR4 were suggested to function as E3 ligases that promote NPR1 degradation. Here we report that NPR3/NPR4 function as transcriptional co-repressors and SA inhibits their activities to promote the expression of downstream…
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Mild Suppression of Hyperinsulinemia to Treat Obesity and Insulin Resistance

Insulin plays roles in lipid uptake, lipolysis, and lipogenesis, in addition to controlling blood glucose levels. Excessive circulating insulin is associated with adipose tissue expansion and obesity, yet a causal role for hyperinsulinemia in the development of mammalian obesity has proven controversial, with many researchers suggesting it as a consequence of insulin resistance. Recently, evidence that specifically reducing hyperinsulinemia can…
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Phenotypic plasticity occurs at a variety of time-scales, but little is known about the degree to which plastic responses at different time-scales are associated with similar underlying molecular processes, which is critical for assessing the effects of plasticity on evolutionary trajectories. To address this issue, we identified differential gene expression in response to developmental temperature in the muscle transcriptome of…
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