Tellurium Compounds Prevent and Reverse Type-1 Diabetes in NOD Mice by Modulating α4β7 Integrin Activity, IL-1β, and T Regulatory Cells

The study shows that treatment of NOD mice with either of two tellurium-based small molecules, AS101 [ammonium trichloro(dioxoethylene-o,o')tellurate] or SAS [octa-O-bis-(R,R)-tartarate ditellurane] could preserve β cells function and mass. These beneficial effects were reflected in decreased incidence of diabetes, improved glucose clearance, preservation of body weight, and increased survival. The normal glucose levels were associated with increased insulin levels, preservation of β cell mass and increased islet size. Importantly, this protective activity could be demonstrated when the compounds were administered either at the early pre-diabetic phase with no or initial insulitis, at the pre-diabetic stage with advanced insulitis, or even at the advanced, overtly diabetic stage. We further demonstrate that both tellurium compounds prevent migration of autoimmune lymphocytes to the pancreas, via inhibition of the α4β7 integrin activity. Indeed, the decreased migration resulted in diminished pancreatic islets damage both with respect to their size, β cell function, and caspase-3 activity, the hallmark of apoptosis. Most importantly, AS101 and SAS significantly elevated the number of T regulatory cells in the pancreas, thus potentially controlling the autoimmune process. We show that the compounds inhibit pancreatic caspase-1 activity followed by decreased levels of the inflammatory cytokines IL-1β and IL-17 in the pancreas. These properties enable the compounds to increase the proportion of Tregs in the pancreatic lymph nodes. AS101 and SAS have been previously shown to regulate specific integrins through a unique redox mechanism. Our current results suggest that amelioration of disease in NOD mice by this unique mechanism is due to decreased infiltration of pancreatic islets combined with increased immune regulation, leading to decreased inflammation within the islets. As these tellurium compounds show remarkable lack of toxicity in clinical trials (AS101) and pre-clinical studies (SAS), they may be suitable for the treatment of type-1 diabetes

Reaction of families and lines of melon to powdery mildew Reação de famílias e linhagens de melão ao oídio

Powdery mildew, caused by Podosphaera xanthii, is an important disease of melon in the Brazilian Northeast. The objective of this work was to evaluate the reaction of families, lines and cultivars of melon to P. xanthii. Two experiments in simple lattice were carried out under field conditions in the municipalities of Mossoró and Baraúna to evaluate 144 families. In a greenhouse, an experiment was carried out in a completely randomized design to evaluate 19 lines and the cultivars Yellow Queen, Chilton and Hy Mark. Disease was assessed by a severity scale. There was genetic variability among families. The families 4, 5, 11, 14, 18, 23, 33, 42, 101, 112 and 140 were identified in both sites as resistant. The lines LOF-027, LOF-105, LPS-124, MEL-008 and cultivar Chilton showed resistance to race 1 of the fungus.<br>O oídio, causado por Podosphaera xanthii, é uma importante doença do melão no Nordeste brasileiro. O objetivo do presente trabalho foi avaliar a reação de famílias, linhagens e cultivares de melão a P. xanthii. Foram conduzidos, em condições de campo, nos municípios de Mossoró e Baraúna, experimentos em látice simples para avaliar 144 famílias. Em casa de vegetação, foi conduzido um experimento em delineamento inteiramente casualizado para avaliar 19 linhagens e as cultivares Yellow Queen, Chilton e Hy Mark. A severidade da doença foi avaliada mediante uma escala de notas. Houve variabilidade genética entre as famílias. Foram identificadas como resistentes, em ambos os locais, as famílias 4, 5, 11, 14, 18, 23, 33, 42, 101, 112 e 140. As linhagens LOF-027, LOF-105, LPS-124, MEL-008 e a cultivar Chilton mostraram resistência à raça 1 do fungo