Hypoxia enhances ILC3 responses through HIF-1α-dependent mechanism

Group 3 innate lymphoid cells (ILC3) have a prominent role in the maintenance of intestine mucosa homeostasis. The hypoxia-inducible factor (HIF) is an important modulator of immune cell activation and a key mechanism for cellular adaptation to oxygen deprivation. However, its role on ILC3 is not well known. In this study, we investigated how a hypoxic environment modulates ILC3 response and the subsequent participation of HIF-1 signaling in this process. We found increased proliferation and activation of intestinal ILC3 at low oxygen levels, a response that was phenocopied when HIF-1α was chemically stabilized and was reversed when HIF-1 was blocked. The increased activation of ILC3 relied on a HIF-1α-dependent transcriptional program, but not on mTOR-signaling or a switch to glycolysis. HIF-1α deficiency in RORyt compartment resulted in impaired IL-17 and IL-22 production by ILC3 in vivo, which reflected in a lower expression of their target genes in the intestinal epithelium and an increased susceptibility to Clostridiodes difficile infection. Taken together, our results show that HIF-1α activation in intestinal ILC3 is relevant for their functions in steady state and infectious conditions

Genes of cathepsin L-like proteases in Trypanosoma rangeli isolates: Markers for diagnosis, genotyping and phylogenetic relationships

We have sequenced genes encoding cathepsin L-like (CatL-like) cysteine proteases from isolates of Trypanosoma rangeli from humans, wild mammals and Rhodnius species of Central and South America. Phylogenetic trees of sequences encoding mature CatL-like enzymes of T rangeli and homologous genes from other trypanosomes, Leishmania spp. and bodonids positioned sequences of T rangeli (rangelipain) closest to T cruzi (cruzipain). Phylogenetic tree of kinetoplastids based on sequences of CatL-like was totally congruent with those derived from SSU rRNA and gGAPDH genes. Analysis of sequences from the CatL-like catalytic domains of 17 isolates representative of the overall phylogenetic diversity and geographical range of T rangeli supported all the lineages (A-D) previously defined using ribosomal and spliced leader genes. Comparison of the proteolytic activities of T rangeli isolates revealed heterogeneous banding profiles of cysteine proteases in gelatin gels, with differences even among isolates of the same lineage. CatL-like sequences proved to be excellent targets for diagnosis and genotyping of T rangeli by PCR. Data from CatL-like encoding genes agreed with results from previous studies of kDNA markers, and ribosomal and spliced leader genes, thereby corroborating clonal evolution, independent transmission cycles and the divergence of T rangeli lineages associated with sympatric species of Rhodnius. (c) 2009 Elsevier B.V. All rights reserved.CNPqConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESPFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)PNPD (CAPES

Search for new resonances decaying to a WW or ZZ boson and a Higgs boson in the ℓ+ℓ−bbˉ\ell^+ \ell^- b\bar b, ℓνbbˉ\ell \nu b\bar b, and ννˉbbˉ\nu\bar{\nu} b\bar b channels with pppp collisions at s=13\sqrt s = 13 TeV with the ATLAS detector

See paper for full list of authors, 18 pages (plus author list + cover pages: 36 pages total), 13 figures, 1 table. Submitted to PLB. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/EXOT-2015-18/International audienceA search is presented for new resonances decaying to a $W$ or $Z$ boson and a Higgs boson in the $\ell^+ \ell^- b\bar b$, $\ell\nu b\bar b$, and $\nu\bar{\nu} b\bar b$ channels in $pp$ collisions at $\sqrt s = 13$ TeV with the ATLAS detector at the Large Hadron Collider using a total integrated luminosity of 3.2 fb$^{-1}$. The search is conducted by looking for a localized excess in the $WH$/$ZH$ invariant or transverse mass distribution. No significant excess is observed, and the results are interpreted in terms of constraints on a simplified model based on a phenomenological Lagrangian of heavy vector triplets