R534C mutation in hERG causes a trafficking defect in iPSC-derived cardiomyocytes from patients with type 2 long QT syndrome

Patient-specific cardiomyocytes obtained from induced pluripotent stem cells (CM-iPSC) offer unprecedented mechanistic insights in the study of inherited cardiac diseases. The objective of this work was to study a type 2 long QT syndrome (LQTS2)-associated mutation (c.1600C > T in KCNH2, p.R534C in hERG) in CM-iPSC. Peripheral blood mononuclear cells were isolated from two patients with the R534C mutation and iPSCs were generated. In addition, the same mutation was inserted in a control iPSC line by genome editing using CRISPR/Cas9. Cells expressed pluripotency markers and showed spontaneous differentiation into the three embryonic germ layers. Electrophysiology demonstrated that action potential duration (APD) of LQTS2 CM-iPSC was significantly longer than that of the control line, as well as the triangulation of the action potentials (AP), implying a longer duration of phase 3. Treatment with the IKr inhibitor E4031 only caused APD prolongation in the control line. Patch clamp showed a reduction of IKr on LQTS2 CM-iPSC compared to control, but channel activation was not significantly affected. Immunofluorescence for hERG demonstrated perinuclear staining in LQTS2 CM-iPSC. In conclusion, CM-iPSC recapitulated the LQTS2 phenotype and our findings suggest that the R534C mutation in KCNH2 leads to a channel trafficking defect to the plasma membrane.Fil: Mesquita, Fernanda C. P.. Universidade Federal do Rio de Janeiro; BrasilFil: Arantes, Paulo C.. Universidade Federal do Rio de Janeiro; BrasilFil: Kasai Brunswick, Tais H.. Universidade Federal do Rio de Janeiro; BrasilFil: Araujo, Dayana S.. Universidade Federal do Rio de Janeiro; BrasilFil: Gubert, Fernanda. Universidade Federal do Rio de Janeiro; BrasilFil: Monnerat, Gustavo. Universidade Federal do Rio de Janeiro; BrasilFil: Silva dos Santos, Danúbia. Universidade Federal do Rio de Janeiro; BrasilFil: Neiman, Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Leitão, Isabela C.. Universidade Federal do Rio de Janeiro; BrasilFil: Barbosa, Raiana A. Q.. Universidade Federal do Rio de Janeiro; BrasilFil: Coutinho, Jorge L.. National Institute Of Cardiology; BrasilFil: Vaz, Isadora M.. Pontificia Universidad Catolica de Parana; BrasilFil: dos Santos, Marcus N.. Universidade Federal do Rio de Janeiro; BrasilFil: Borgonovo, Tamara. Pontificia Universidad Catolica de Parana; BrasilFil: Cruz, Fernando E. S.. National Institute of Cardiology; BrasilFil: Miriuka, Santiago Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Medei, Emiliano H.. Universidade Federal do Rio de Janeiro; BrasilFil: Campos de Carvalho, Antonio C.. Universidade Federal do Rio de Janeiro; Brasil. National Institute of Cardiology; Brasil. National Institute for Science and Technology in Regenerative Medicine; BrasilFil: Carvalho, Adriana B.. Universidade Federal do Rio de Janeiro; Brasil. National Institute for Science and Technology in Regenerative Medicine; Brasi

Extracellular vesicles released from mesenchymal stromal cells modulate miRNA in renal tubular cells and inhibit ATP depletion injury

The mechanisms involved in renal repair by mesenchymal stromal cells (MSCs) are not entirely elucidated. The paracrine secretion of bioactive molecules has been implicated in the protective effects. Besides soluble mediators, MSCs have been shown to release extracellular vesicles (EVs), involved in renal repair process for different injury models. EVs have been shown to mediate communication between cells through the transference of several molecules, like protein, bioactive lipids, mRNA, and microRNAs (miRNAs). The miRNAs are noncoding RNAs that posttranscriptionally modulate gene expression and are involved in the regulation of several cellular processes, including those related to repair. The aim of the present study was to investigate the role of MSC-EVs in the modulation of miRNAs inside renal proximal tubular epithelial cells (PTECs) in an in vitro model of ischemia-reperfusion injury induced by ATP depletion. In this model we evaluated whether changes in miRNA expression were dependent on direct miRNA transfer or on transcription induction by MSC-EVs. The obtained results showed an enhanced incorporation of MSC-EVs in injured PTECs with protection from cell death. This biological effect was associated with EV-mediated miRNA transfer and with transcriptional modulation of miRNAs expressed by injured PTECs. Prediction of miRNA targets showed that miRNAs modulated in PTECs are involved in process of renal recovery with downregulation of coding-mRNAs associated with apoptosis, cytoskeleton reorganization, and hypoxia, such as CASP3 and 7, SHC1 and SMAD4. In conclusion, these results indicate that MSC-EVs may transfer and modulate the expression of several miRNAs involved in the repair and recovery process in PTECs

Organotin compounds in the Paranagua Estuarine Complex, Parana, Brazil: Evaluation of biological effects, surface sediment, and suspended particulate matter

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Duration of post-vaccination immunity against yellow fever in adults

Submitted by Nuzia Santos ([email protected]) on 2015-06-22T17:37:43Z No. of bitstreams: 1 2014_152.pdf: 756403 bytes, checksum: c18d98237e29e19e785cf895a2a68ddc (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-06-22T17:37:52Z (GMT) No. of bitstreams: 1 2014_152.pdf: 756403 bytes, checksum: c18d98237e29e19e785cf895a2a68ddc (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-06-22T17:58:36Z (GMT) No. of bitstreams: 1 2014_152.pdf: 756403 bytes, checksum: c18d98237e29e19e785cf895a2a68ddc (MD5)Made available in DSpace on 2015-06-22T17:58:36Z (GMT). No. of bitstreams: 1 2014_152.pdf: 756403 bytes, checksum: c18d98237e29e19e785cf895a2a68ddc (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Brasilia, DF, BrasilFundação Oswaldo Cruz. Escola Nacional de Saúde Pública. Rio de Janeiro, RJ, BrazilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Biomarcadores Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicosde Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Biomarcadores. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Biomarcadores. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Imunopatologia .Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Esquistossomose. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Biomarcadores. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Biomarcadores. Belo Horizonte, MG, BrasilFood and Drug Administration Center for Biologics Evaluation and Research. Bethesda, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Fla-vivirus. Rio de JaneiroFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Fla-vivirus. Rio de JaneiroFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Fla-vivirus. Rio de JaneiroInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilMinas Gerais. Secretaria Estadual de Saude. Belo Horizonte, MG, BrasilMinas Gerais. Secretaria Estadual de Saude. Belo Horizonte, MG, BrasilMinas Gerais. Secretaria Estadual de Saude. Belo Horizonte, MG, BrasilMinas Gerais. Secretaria Estadual de Saude. Belo Horizonte, MG, BrasilUniversidade Federal de Alfenas. Alfenas, MG, BrasilUniversidade de Brasília. Faculdade de Medicina. Brasilia, DF, BrasilFundação Oswaldo Cruz. Instituto Evandro Chagas. Ananindeua, PA, BrasilINTRODUCTION: Available scientific evidence to recommend or to advise against booster doses of yellow fever vaccine (YFV) is inconclusive. A study to estimate the seropositivity rate and geometric mean titres (GMT) of adults with varied times of vaccination was aimed to provide elements to revise the need and the timing of revaccination. METHODS: Adults from the cities of Rio de Janeiro and Alfenas located in non-endemic areas in the Southeast of Brazil, who had one dose of YFV, were tested for YF neutralising antibodies and dengue IgG. Time (in years) since vaccination was based on immunisation cards and other reliable records. RESULTS: From 2011 to 2012 we recruited 691 subjects (73% males), aged 18-83 years. Time since vaccination ranged from 30 days to 18 years. Seropositivity rates (95%C.I.) and GMT (International Units/mL; 95%C.I.) decreased with time since vaccination: 93% (88-96%), 8.8 (7.0-10.9) IU/mL for newly vaccinated; 94% (88-97), 3.0 (2.5-3.6) IU/mL after 1-4 years; 83% (74-90), 2.2 (1.7-2.8) IU/mL after 5-9 years; 76% (68-83), 1.7 (1.4-2.0) IU/mL after 10-11 years; and 85% (80-90), 2.1 (1.7-2.5) IU/mL after 12 years or more. YF seropositivity rates were not affected by previous dengue infection. CONCLUSIONS:Eventhough serological correlates of protection for yellow fever are unknown, seronegativity in vaccinated subjects may indicate primary immunisation failure, or waning of immunity to levels below the protection threshold. Immunogenicity of YFV under routine conditions of immunisation services is likely to be lower than in controlled studies. Moreover, infants and toddlers, who comprise the main target group in YF endemic regions, and populations with high HIV infection rates, respond to YFV with lower antibody levels. In those settings one booster dose, preferably sooner than currently recommended, seems to be necessary to ensure longer protection for all vaccinee

Revista Temas Agrarios Volumen 26; Suplemento 1 de 2021

1st International and 2nd National Symposium of Agronomic Sciences: The rebirth of the scientific discussion space for the Colombian Agro.1 Simposio Intenacional y 2 Nacional de Ciencias Agronómicas: El renacer del espacio de discusión científica para el Agro colombiano

A global metagenomic map of urban microbiomes and antimicrobial resistance

We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.Funding: the Tri-I Program in Computational Biology and Medicine (CBM) funded by NIH grant 1T32GM083937; GitHub; Philip Blood and the Extreme Science and Engineering Discovery Environment (XSEDE), supported by NSF grant number ACI-1548562 and NSF award number ACI-1445606; NASA (NNX14AH50G, NNX17AB26G), the NIH (R01AI151059, R25EB020393, R21AI129851, R35GM138152, U01DA053941); STARR Foundation (I13- 0052); LLS (MCL7001-18, LLS 9238-16, LLS-MCL7001-18); the NSF (1840275); the Bill and Melinda Gates Foundation (OPP1151054); the Alfred P. Sloan Foundation (G-2015-13964); Swiss National Science Foundation grant number 407540_167331; NIH award number UL1TR000457; the US Department of Energy Joint Genome Institute under contract number DE-AC02-05CH11231; the National Energy Research Scientific Computing Center, supported by the Office of Science of the US Department of Energy; Stockholm Health Authority grant SLL 20160933; the Institut Pasteur Korea; an NRF Korea grant (NRF-2014K1A4A7A01074645, 2017M3A9G6068246); the CONICYT Fondecyt Iniciación grants 11140666 and 11160905; Keio University Funds for Individual Research; funds from the Yamagata prefectural government and the city of Tsuruoka; JSPS KAKENHI grant number 20K10436; the bilateral AT-UA collaboration fund (WTZ:UA 02/2019; Ministry of Education and Science of Ukraine, UA:M/84-2019, M/126-2020); Kyiv Academic Univeristy; Ministry of Education and Science of Ukraine project numbers 0118U100290 and 0120U101734; Centro de Excelencia Severo Ochoa 2013–2017; the CERCA Programme / Generalitat de Catalunya; the CRG-Novartis-Africa mobility program 2016; research funds from National Cheng Kung University and the Ministry of Science and Technology; Taiwan (MOST grant number 106-2321-B-006-016); we thank all the volunteers who made sampling NYC possible, Minciencias (project no. 639677758300), CNPq (EDN - 309973/2015-5), the Open Research Fund of Key Laboratory of Advanced Theory and Application in Statistics and Data Science – MOE, ECNU, the Research Grants Council of Hong Kong through project 11215017, National Key RD Project of China (2018YFE0201603), and Shanghai Municipal Science and Technology Major Project (2017SHZDZX01) (L.S.