A Transgenic Marker for Newly Born Granule Cells in Dentate Gyrus

Neurogenesis in the dentate gyrus continues into adulthood, yet little is known about the function of newly born neurons or how they integrate into an existing network of mature neurons. We made transgenic mice that selectively and transiently express enhanced green fluorescent protein (EGFP) in newly born granule cells of the dentate gyrus under the transcriptional control of proopiomelanocortin (POMC) genomic sequences. Analysis of transgenic pedigrees with truncation or deletion mutations indicated that EGFP expression in the dentate gyrus required cryptic POMC promoter regions dispensable for arcuate hypothalamic or pituitary expression. Unlike arcuate neurons, dentate granule cells did not express the endogenous POMC gene. EGFP-positive neurons had immature properties, including short spineless dendrites and small action potentials. Colocalization with bromodeoxyuridine indicated that EGFP-labeled granule cells were 2 weeks postmitotic. EGFP-labeled cells expressed markers for immature granule cells but not the glial marker GFAP. The number of EGFP-labeled neurons declined with age and increased with exercise, paralleling neurogenesis. Our results indicate that POMC-EGFP marks immature granule cells and that adult-generated granule cells integrate quite slowly into the hippocampal circuitry

Selective pressure against horizontally acquired prokaryotic genes as a driving force of plastid evolution

Altres ajuts: del Consejo Nacional de Investigaciones Científicas y Técnicas- Argentina (CONICET) i del Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo (IBERCAROT).The plastid organelle comprises a high proportion of nucleus-encoded proteins that were acquired from different prokaryotic donors via independent horizontal gene transfers following its primary endosymbiotic origin. What forces drove the targeting of these alien proteins to the plastid remains an unresolved evolutionary question. To better understand this process we screened for suitable candidate proteins to recapitulate their prokaryote-to-eukaryote transition. Here we identify the ancient horizontal transfer of a bacterial polyphenol oxidase (PPO) gene to the nuclear genome of an early land plant ancestor and infer the possible mechanism behind the plastidial localization of the encoded enzyme. Arabidopsis plants expressing PPO versions either lacking or harbouring a plastid-targeting signal allowed examining fitness consequences associated with its subcellular localization. Markedly, a deleterious effect on plant growth was highly correlated with PPO activity only when producing the non-targeted enzyme, suggesting that selection favoured the fixation of plastid-targeted protein versions. Our results reveal a possible evolutionary mechanism of how selection against heterologous genes encoding cytosolic proteins contributed in incrementing plastid proteome complexity from non-endosymbiotic gene sources, a process that may also impact mitochondrial evolution

The cyanobacterial saxitoxin exacerbates neural cell death and brain malformations induced by zika virus

The northeast (NE) region of Brazil commonly goes through drought periods, which favor cyanobacterial blooms, capable of producing neurotoxins with implications for human and animal health. The most severe dry spell in the history of Brazil occurred between 2012 and 2016. Coincidently, the highest incidence of microcephaly associated with the Zika virus (ZIKV) outbreak took place in the NE region of Brazil during the same years. In this work, we tested the hypothesis that saxitoxin (STX), a neurotoxin produced in South America by the freshwater cyanobacteria Raphidiopsis raciborskii, could have contributed to the most severe Congenital Zika Syndrome (CZS) profile described worldwide. Quality surveillance showed higher cyanobacteria amounts and STX occurrence in human drinking water sup-plies of NE compared to other regions of Brazil. Experimentally, we described that STX dou-bled the quantity of ZIKV-induced neural cell death in progenitor areas of human brain organoids, while the chronic ingestion of water contaminated with STX before and during gestation caused brain abnormalities in offspring of ZIKV-infected immunocompetent C57BL/6J mice. Our data indicate that saxitoxin-producing cyanobacteria is overspread in water reservoirs of the NE and might have acted as a co-insult to ZIKV infection in Brazil. These results raise a public health concern regarding the consequences of arbovirus outbreaks happening in areas with droughts and/or frequent freshwater cyanobacterial blooms.Fil: Pedrosa, Carolina da S. G.. D’Or Institute for Research and Education; BrasilFil: Souza, Leticia R. Q.. D’Or Institute for Research and Education; BrasilFil: Gomes, Tiago A.. Universidade Federal do Rio de Janeiro; Brasil. Instituto Oswaldo Cruz; BrasilFil: de Lima, Caroline V. F.. D’Or Institute for Research and Education; BrasilFil: Ledur, Pitia F.. D’Or Institute for Research and Education; BrasilFil: Karmirian, Karina. D’Or Institute for Research and Education; Brasil. Universidade Federal do Rio de Janeiro; BrasilFil: Barbeito Andrés, Jimena. Universidade Federal do Rio de Janeiro; Brasil. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Costa, Marcelo do N.. Universidade Federal do Rio de Janeiro; BrasilFil: Higa, Luiza M.. Universidade Federal do Rio de Janeiro; BrasilFil: Rossi, Átila D.. Universidade Federal do Rio de Janeiro; BrasilFil: Bellio, Maria. Universidade Federal do Rio de Janeiro; BrasilFil: Tanuri, Amilcar. Universidade Federal do Rio de Janeiro; BrasilFil: Prata Barbosa, Arnaldo. D’Or Institute for Research and Education; BrasilFil: Tovar Moll, Fernanda. D’Or Institute for Research and Education; Brasil. Universidade Federal do Rio de Janeiro; BrasilFil: Garcez, Patricia P.. Universidade Federal do Rio de Janeiro; BrasilFil: Lara, Flavio A.. Instituto Oswaldo Cruz; BrasilFil: Molica, Renato J. R.. Universidad Federal Rural Pernambuco; BrasilFil: Rehen, Stevens K.. D’Or Institute for Research and Education; Brasil. Universidade Federal do Rio de Janeiro; Brasi

Observation of J/ψpJ/\psi p resonances consistent with pentaquark states in Λb0→J/ψK−p{\Lambda_b^0\to J/\psi K^-p} decays

Observations of exotic structures in the $J/\psi p$ channel, that we refer to as pentaquark-charmonium states, in $\Lambda_b^0\to J/\psi K^- p$ decays are presented. The data sample corresponds to an integrated luminosity of 3/fb acquired with the LHCb detector from 7 and 8 TeV pp collisions. An amplitude analysis is performed on the three-body final-state that reproduces the two-body mass and angular distributions. To obtain a satisfactory fit of the structures seen in the $J/\psi p$ mass spectrum, it is necessary to include two Breit-Wigner amplitudes that each describe a resonant state. The significance of each of these resonances is more than 9 standard deviations. One has a mass of $4380\pm 8\pm 29$ MeV and a width of $205\pm 18\pm 86$ MeV, while the second is narrower, with a mass of $4449.8\pm 1.7\pm 2.5$ MeV and a width of $39\pm 5\pm 19$ MeV. The preferred $J^P$ assignments are of opposite parity, with one state having spin 3/2 and the other 5/2.Comment: 48 pages, 18 figures including the supplementary material, v2 after referee's comments, now 19 figure

Determination of germ tube, phospholipase, and proteinase production by bloodstream isolates of Candida albicans

Candida albicans is a commensal and opportunistic agent that causes infection in immunocompromised individuals. Several attributes contribute to the virulence and pathogenicity of this yeast, including the production of germ tubes (GTs) and extracellular hydrolytic enzymes, particularly phospholipase and proteinase. This study aimed to investigate GT production and phospholipase and proteinase activities in bloodstream isolates of C. albicans. Methods: One hundred fi fty-three C. albicans isolates were obtained from blood samples and analyzed for GT, phospholipase, and proteinase production. The assays were performed in duplicate in egg yolk medium containing bovine serum albumin and human serum. Results: Detectable amounts of proteinase were produced by 97% of the isolates, and 78% of the isolates produced phospholipase. GTs were produced by 95% of the isolates. A majority of the isolates exhibited low levels of phospholipase production and high levels of proteinase production. Conclusions: Bloodstream isolates of C. albicans produce virulence factors such as GT and hydrolytic enzymes that enable them to cause infection under favorable conditions

Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions

Measurement of the Ξ^-_b and Ω^-_b baryon lifetimes

Using a data sample of pp collisions corresponding to an integrated luminosity of $3~ \rm fb^{-1}$, the $\Xi_b^-$ and $\Omega_b^-$ baryons are reconstructed in the $\Xi_b^- \rightarrow J/\psi \Xi^-$ and $\Omega_b^- \rightarrow J/\psi \Omega^-$ decay modes and their lifetimes measured to be \tau (\Xi_b^-) = 1.55\, ^{+0.10}_{-0.09}~{\rm(stat)} \pm 0.03\,{\rm(syst)} ps, \tau (\Omega_b^-) = 1.54\, ^{+0.26}_{-0.21}~{\rm(stat)} \pm 0.05\,{\rm(syst)} ps. These are the most precise determinations to date. Both measurements are in good agreement with previous experimental results and with theoretical predictions

First observation and amplitude analysis of the B−→D+K−π− decay

The B−→D+K−π− decay is observed in a data sample corresponding to 3.0  fb−1 of pp collision data recorded by the LHCb experiment during 2011 and 2012. Its branching fraction is measured to be B(B−→D+K−π−)=(7.31±0.19±0.22±0.39)×10−5 where the uncertainties are statistical, systematic and from the branching fraction of the normalization channel B−→D+π−π−, respectively. An amplitude analysis of the resonant structure of the B−→D+K−π− decay is used to measure the contributions from quasi-two-body B−→D∗0(2400)0K−, B−→D∗2(2460)0K−, and B−→D∗J(2760)0K− decays, as well as from nonresonant sources. The D∗J(2760)0 resonance is determined to have spin 1