Action and Function of ASB Proteins in Compartment Size Regulation

One of the most important and defining processes during development is the pattern formation of the various compartments in embryos. In an effort to discover the participants involved in regulating compartment size, we identified, in Danio rerio (zebrafish) embryos, the ankyrin repeat and SOCS box-containing protein 11 (d-asb11) gene. We first showed that d-Asb11 is a key mediator of Delta-Notch Signaling, acting at the level of DeltaA ubiquitylation, important in fine-tuning the lateral inhibition gradients between DeltaA and Notch. We, then, isolated a zebrafish having a germline deletion of the d-Asb11 cullin box subdomain and showed that this deletion resulted in loss of d-Asb11 activity. As a consequence, the animals were defective for Notch signaling and proper cell fate specification within the neurogenic regions of zebrafish embryos. We also provided evidence that d-Asb11 is important in maintaining myogenic proliferation in the stem cell compartment of zebrafish embryos and muscle regenerative responses in adult animals. This finding is supported by the highly specific d-Asb11 expression found in proliferating satellite cells in zebrafish muscle. In addition, we have applied immunoaffinity chromatograpy followed by tandem mass spectrometry to identify human ASB11 interacting proteins. The data confirmed the role of ASB11 as a subs

Genetically modified lactococcus lactis for delivery of human interleukin-10 to dendritic cells

Interleukin-10 (IL-10) plays an indispensable role in mucosal tolerance by programming dendritic cells (DCs) to induce suppressor Th-cells. We have tested the modulating effect of L. lactis secreting human IL-10 (L.lacti s IL-10) on DC function in vitro. Monocyte-derived DC incubated with L.lacti s IL-10 induced effector Th-cells that markedly suppressed the proliferation of allogenic Th-cells as compared to L. lactis. This suppressive effect was only seen when DC showed increased CD83 and CD86 expression. Furthermore, enhanced production of IL-10 was measured in both L.lacti s IL-10 -derived DC and Th-cells compared to L. lactis-derived DC and Th-cells. Neutralizing IL-10 during DC-Th-cell interaction and coculturing L.lacti s IL-10 -derived suppressor Th-cells with allogenic Th-cells in a transwell system prevented the induction of suppressor Th-cells. Only 130pg/mL of bacterial-derived IL-10 and 40 times more exogenously added recombinant human IL-10 were needed during DC priming for the generation of suppressor Th-cells. The spatially restricted delivery of IL-10 by food-grade bacteria is a promising strategy to induce suppressor Th-cells in vivo and to treat inflammatory diseases

Jaboticaba berry peel intake prevents insulin-resistance-induced tau phosphorylation in mice

The hyperphosphorylation of microtubule-associated protein tau (tau) in the hippocampus can be caused by central and peripheral insulin resistance and these alterations are related to the development of tauopathies, such as Alzheimer's disease. In this study, we used a high-fat diet to induce obesity and insulin resistance in adult Swiss mice and checked whether supplementation with Myrciaria jaboticaba berry peel for 10 weeks could improve insulin sensitivity, learning/memory performance, and prevent tau phosphorylation in the hippocampus. Furthermore, adipocytokines, inflammatory markers, and oxidative stress were assessed. Myrciaria jaboticaba peel has phenolic compounds (e.g., cyanidin, ellagic acid), dietary fiber and carotenoids, which contribute to great antioxidant capacity. Supplementation of the high-fat diet with 4% M. jaboticaba peel prevented fat weight gain and reduced peripheral insulin resistance. The treated group also showed lower tau phosphorylation in the hippocampus corroborating better learning/memory performance in the Morris water maze test. Maintenance of neuronal viability, lower levels of hippocampal inflammatory markers, and improved brain antioxidant defenses were also related to the consumption of M. jaboticaba peel. These findings contribute to a better understanding of how a high-fat diet supplemented with jaboticaba berry peel counteracts the impairment of cognitive functions caused by high-fat diet intake and diet-induced insulin resistance.610CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP300533/2013-6 ; 305099/2011-6Sem informação2010/05262-5 ; 2015/50333-

Clinical analysis and parasite genetic diversity in human immunodeficiency virus/Chagas' disease coinfections in Brazil

To evaluate the possible role of parasitemia on Chagas' disease reactivation in Chagas' disease/human immunodeficiency viurs (HIV) coinfection cases and the impact of HIV coeinfection on #Trypanosoma cruzi genetic diversity, 71 patients with Chagas' disease (34 HIV+ and 37 HIV-) were surveyed. Moreover, 92 #T. cruzi stocks from 47 chronic chagasic patients (29 HIV+ and 18 HIV-) were isolated and analyzed by multilocus enzyme electrophoresis and a random amplified polymorphic DNA procedure. High parasitemia appeared to play a major role in cases of Chagas' disease reactivation. In HIV+ patients, the genetic diversity and population structure (clonality) of #T. cruzi was similar to that previously observed in HIV- patients, which indicates that immunodepression does not modify drastically genotype repartition of the parasite. There was no apparent association between given #T. cruzi genotypes and specific clinical forms of Chagas' disease/HIV associations. (Résumé d'auteur