81 research outputs found

    Weed Control for Reduced Tillage Systems

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    Recurrence of Type 1 Diabetes After Simultaneous Pancreas-Kidney Transplantation, Despite Immunosuppression, Is Associated With Autoantibodies and Pathogenic Autoreactive CD4 T-Cells

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    ObjectiveTo investigate if recurrent autoimmunity explained hyperglycemia and C-peptide loss in three immunosuppressed simultaneous pancreas-kidney (SPK) transplant recipients.Research design and methodsWe monitored autoantibodies and autoreactive T-cells (using tetramers) and performed biopsy. The function of autoreactive T-cells was studied with in vitro and in vivo assays.ResultsAutoantibodies were present pretransplant and persisted on follow-up in one patient. They appeared years after transplantation but before the development of hyperglycemia in the remaining patients. Pancreas transplant biopsies were taken within approximately 1 year from hyperglycemia recurrence and revealed beta-cell loss and insulitis. We studied autoreactive T-cells from the time of biopsy and repeatedly demonstrated their presence on further follow-up, together with autoantibodies. Treatment with T-cell-directed therapies (thymoglobulin and daclizumab, all patients), alone or with the addition of B-cell-directed therapy (rituximab, two patients), nonspecifically depleted T-cells and was associated with C-peptide secretion for >1 year. Autoreactive T-cells with the same autoantigen specificity and conserved T-cell receptor later reappeared with further C-peptide loss over the next 2 years. Purified autoreactive CD4 T-cells from two patients were cotransplanted with HLA-mismatched human islets into immunodeficient mice. Grafts showed beta-cell loss in mice receiving autoreactive T-cells but not control T-cells.ConclusionsWe demonstrate the cardinal features of recurrent autoimmunity in three such patients, including the reappearance of CD4 T-cells capable of mediating beta-cell destruction. Markers of autoimmunity can help diagnose this underappreciated cause of graft loss. Immune monitoring during therapy showed that autoimmunity was not resolved by the immunosuppressive agents used

    Recognition of Human Proinsulin Leader Sequence by Class I–Restricted T-Cells in HLA-A*0201 Transgenic Mice and in Human Type 1 Diabetes

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    OBJECTIVE— A restricted region of proinsulin located in the B chain and adjacent region of C-peptide has been shown to contain numerous candidate epitopes recognized by CD8+ T-cells. Our objective is to characterize HLA class I–restricted epitopes located within the preproinsulin leader sequence

    Microalgae as a promising and sustainable nutrition source for managed honey bees

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    Managed honey bee colony losses are attributed to a number of interacting stressors, but many lines of evidence point to malnutrition as a primary factor. Commercial beekeepers have become increasingly reliant on artificial pollen substitute diets to nourish colonies during periods of forage scarcity and to bolster colony size before pollination services. These artificial diets may be deficient in essential macronutrients (proteins, lipids, prebiotic fibers), micronutrients (vitamins, minerals), and antioxidants. Therefore, improving the efficacy of pollen substitutes can be considered vital to modern beekeeping. Microalgae are prolific sources of plant‐based nutrition with many species exhibiting biochemical profiles that are comparable to natural pollen. This emerging feed source has been employed in a variety of organisms, including limited applications in honey bees. Herein, I introduce the nutritional value and functional properties of microalgae, extrapolating to central aspects of honey bee physiology and health. To conclude, I discuss the potential of microalgae‐based feeds to sustainably provision managed colonies on an agricultural scale
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