Explore the vast range of titles available.

Este artículo propone una aproximación etnográfica al estudio de las perspectivas, motivaciones e intereses de los individuos participantes en el proyecto “Ancestría genética e identidad”. Basados en un corpus de entrevistas y en un marco teórico que utiliza los conceptos de genealogía y pedigrí, indagamos la significación que el dato genético adquiere en la recreación de las historias e identidades personales y familiares, así como el modo en que el test de ancestría genética se articula y entra en negociación con otras experiencias y registros de tipo oral o escrito. En el marco de las investigaciones desarrolladas en este campo, también señalamos la importancia de considerar los contextos sociales, jurídicos y políticos para comprender el impacto de estas nuevas tecnologías.

Abstract Since the late nineteenth century, people in Argentina consider to be a homogeneous society of white-European culture and phenotypic traits, with Buenos Aires as an epicenter. In this article we work with interviews and genetic analysis results of 40 participants of the project \"Genetic Ancestry and Identity\", to contextualize the social processes that underlie this concept and to relate the individual genetic data to the history of society. Gene admixture estimation through genetic markers and demographic data in a sample from Buenos Aires Metropolitan Area. Gender bias in the multi-ethnic genetic composition of central Argentina.

Tendo em conta a investigação médica, a doação de órgãos vai continuar a ser a fonte fundamental de órgãos para transplante. O reconhecimento e a manutenção dos potenciais dadores em morte cerebral estão entre os grandes desafios enfrentados pelas equipas que trabalham em cuidados intensivos e urgências (Duarte, Salviano & Gresta, 2004). Como membro da equipa de saúde, o enfermeiro, apesar de não ser responsável pela decisão no processo, participa nos cuidados ao potencial dador de órgãos.Este estudo tem como objectivo analisar eventuais relações entre um conjunto de variáveis sócio-demográficas, de caracterização da experiência dos enfermeiros e as suas atitudes perante morte cerebral e transplantação de órgãos, para, assim, se compreenderem as suas atitudes perante a temática.A amostra foi constituída por 130 enfermeiros, correspondendo a uma taxa de resposta de 76%. Os dados foram recolhidos nos serviços de Urgência e Unidade de Cuidados Intensivos do Hospital de Faro e do Centro Hospitalar do Barlavento Algarvio.Para avaliação das variáveis em estudo utilizaram-se três questionários: de dados sócio-demográficos; de caracterização da experiência dos enfermeiros em relação à morte cerebral e transplantação de órgãos e das suas atitudes perante morte cerebral e transplantação de órgãos (Kim, Fisher & Elliott, 2006a).Os resultados obtidos sugerem que os enfermeiros apresentam disposição para serem dadores de órgãos, assim como consideram o transplante de órgãos importante na melhoria da qualidade de vida do receptor. O estudo sugere também que o desconhecimento e a inexperiência dos enfermeiros nesta temática estão relacionados com o seu desconforto em relação à doação de órgãos.Torna-se, assim, importante promover programas de informação/formação sobre o processo de doação de órgãos, com o objectivo de colmatar a falta de informação e de conhecimentos. Este estudo poderá ser útil no desenvolvimento desses programas, procurando reforçar a atitude positiva dos enfermeiros e melhorar a sua capacidade para actuação no processo de doação de órgãos.

Mycobacterium tuberculosis is a pathogen with a unique cell envelope including very long fatty acids, implicated in bacterial resistance and host immune modulation. FasR is a TetR-like transcriptional activator that plays a central role in sensing mycobacterial long-chain fatty acids and regulating lipid biosynthesis. Here we disclose crystal structures of M. tuberculosis FasR in complex with acyl effector ligands and with DNA, uncovering its molecular sensory and switching mechanisms. A long tunnel traverses the entire effector-binding domain, enabling long fatty acyl effectors to bind. Only when the tunnel is entirely occupied, the protein dimer adopts a rigid configuration with its DNA-binding domains in an open state, leading to DNA dissociation. The protein-folding hydrophobic core connects the two domains, and is completed into a continuous spine when the effector binds. Such a transmission spine is conserved in a large number of TetR-like regulators, offering insight into effector-triggered allosteric functional control. FasR is a TetR-like transcriptional activator that plays a central role in sensing mycobacterial long-chain fatty acids and regulating lipid biosynthesis in Mycobacterium tuberculosis . Here authors present crystal structures of M. tuberculosis FasR in complex with acyl effector ligands and with DNA, uncovering its molecular sensory and switching mechanisms.

ObjectivesS100A9, an alarmin that can form calprotectin (CP) heterodimers with S100A8, is mainly produced by keratinocytes and innate immune cells. The contribution of keratinocyte-derived S100A9 to psoriasis (Ps) and psoriatic arthritis (PsA) was evaluated using mouse models, and the potential usefulness of S100A9 as a Ps/PsA biomarker was assessed in patient samples.MethodsConditional S100A9 mice were crossed with DKO* mice, an established psoriasis-like mouse model based on inducible epidermal deletion of c-Jun and JunB to achieve additional epidermal deletion of S100A9 (TKO* mice). Psoriatic skin and joint disease were evaluated in DKO* and TKO* by histology, microCT, RNA and proteomic analyses. Furthermore, S100A9 expression was analysed in skin, serum and synovial fluid samples of patients with Ps and PsA.ResultsCompared with DKO* littermates, TKO* mice displayed enhanced skin disease severity, PsA incidence and neutrophil infiltration. Altered epidermal expression of selective pro-inflammatory genes and pathways, increased epidermal phosphorylation of STAT3 and higher circulating TNFα were observed in TKO* mice. In humans, synovial S100A9 levels were higher than the respective serum levels. Importantly, patients with PsA had significantly higher serum concentrations of S100A9, CP, VEGF, IL-6 and TNFα compared with patients with only Ps, but only S100A9 and CP could efficiently discriminate healthy individuals, patients with Ps and patients with PsA.ConclusionsKeratinocyte-derived S100A9 plays a regulatory role in psoriatic skin and joint disease. In humans, S100A9/CP is a promising marker that could help in identifying patients with Ps at risk of developing PsA.

Classical non-homologous end joining (NHEJ) is a molecular pathway that detects, processes, and ligates DNA double-strand breaks (DSBs) throughout the cell cycle. Mutations in several NHEJ genes result in neurological abnormalities and immunodeficiency both in humans and mice. The NHEJ pathway is required for V(D)J recombination in developing B and T lymphocytes, and for class switch recombination in mature B cells. The Ku heterodimer formed by Ku70 and Ku80 recognizes DSBs and facilitates the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, Paxx and Mri/Cyren) and downstream core factor subunits X-ray repair cross-complementing group 4 (XRCC4), XRCC4-like factor (XLF), and DNA ligase 4 (Lig4). Accessory factors might be dispensable for the process, depending on the genetic background and DNA lesion type. To determine the physiological role of Mri in DNA repair and development, we introduced a frame-shift mutation in the Mri gene in mice. We then analyzed the development of Mri-deficient mice as well as wild type and immunodeficient controls. Mice lacking Mri possessed reduced levels of class switch recombination in B lymphocytes and slow proliferation of neuronal progenitors when compared to wild type littermates. Human cell lines lacking Mri were as sensitive to DSBs as the wild type controls. Overall, we concluded that Mri/Cyren is largely dispensable for DNA repair and mouse development.

Brazilian health workers and students must face, added to the coronavirus, the lack of Personal Protective Equipments (PPEs), keeping of same work force in the frontlines, as well as an unstable and uninformative public health policy, contributing to an exhausting endeavor. This research evaluates the effects of the Covid-19 pandemic on the different profiles of healthcare workers and students in the state of São Paulo. The online semi structured validated survey was applied, with quantitative analysis through data processing by STATA 13.0, and qualitative, through content analysis according to Bardin. Our findings corroborate the prevalence of an important overload within the students and healthcare workers, manifested through mood, sleep and cognition alteration, anxiety, physical discomfort, pessimism and increase in nightmares. As a counterpoint to these challenges, the pandemic has brought a powerful learning process, by understanding the need to adapt and the importance of scientific research. Keywords: Covid-19. Mental health. Healthcare workers. Exhaustion. No Brasil, além do Coronavirus, enfrentam-se escassez de de Equipamentos de Proteção Individual (EPIs), manutenção da mesma força de trabalho na linha de frente e política pública de saúde instável, com informações discordantes, tornando esse período extremamente desgastante. Esta pesquisa avalia as repercussões da pandemia da Covid-19 sobre os diferentes perfis de profissionais e estudantes da Saúde no estado de São Paulo. Utilizou-se questionário on-line semiestruturado validado, com análise quantitativa, via processamento de dados pelo software STATA 13.0, e qualitativa, por análise de conteúdo proposta por Bardin. Os achados corroboram a prevalência de importante sobrecarga nos estudantes e profissionais da Saúde, manifestada por alterações em humor, sono e cognição, ansiedade, desconforto físico, pessimismo e aumento de pesadelos. Como contraponto aos desafios, a pandemia trouxe potente processo de aprendizagem e a possibilidade prática de compreender a necessidade de adaptação e reconhecer a importância da pesquisa científica. Palavras-chave: Covid-19. Saúde mental. Profissionais da saúde. Exaustão. En Brasil, además del coronavirus, hay que enfrentar la escasez de Equipos de Protección Individual (EPIs), el mantenimiento de la misma fuerza de trabajo en la línea de frente y una política pública de salud inestable, con informaciones discordantes, haciendo que este episodio sea extremadamente desgastante. Esta encuesta evalúa las repercusiones de la pandemia de Covid-19 sobre los diferentes perfiles de profesionales y estudiantes de la salud en el estado de São Paulo. Se utilizo un cuestionario online semiestructurado, validado, con análisis cuantitativo vía procesamiento de datos por el software STATA 13.0, y cualitativa, por medio de análisis de contenido propuesto por Bardin. Los hallazgos corroboran la prevalencia de una importante sobrecarga en los estudiantes y profesionales de la salud, manifestada por alteraciones en el humor, sueno y cognición, ansiedad, incómodo físico, pesimismo y aumento de pesadillas. Como contrapunto a los desafíos, la pandemia brindó un potente proceso de aprendizaje y la posibilidad práctica de comprender la necesidad de adaptación y reconocer la importancia de la investigación científica. Palabras clave: Covid-19. Salud mental. Profesionales de la salud. Agotamiento.

Pathogenic variants in the mitochondrial tyrosyl-tRNA synthetase gene (YARS2) were associated with myopathy, lactic acidosis, and sideroblastic anemia (MLASA). However, patients can present mitochondrial myopathy, with exercise intolerance and muscle weakness, leading from mild to lethal phenotypes. Genes implicated in mtDNA replication were studied by Next Generation Sequencing (NGS) and whole exome sequence with the TruSeq Rapid Exome kit (Illumina, San Diego, CA, USA). Mitochondrial protein translation was studied following the Sasarman and Shoubridge protocol and oxygen consumption rates with Agilent Seahorse XF24 Analyzer Mitostress Test, (Agilent, Santa Clara, CA, USA). We report two siblings with two novel compound heterozygous pathogenic variants in YARS2 gene: a single nucleotide deletion in exon 1, c.314delG (p.(Gly105Alafs*4)), which creates a premature stop codon in the amino acid 109, and a single nucleotide change in exon 5 c.1391T>C (p.(Ile464Thr)), that cause a missense variant in amino acid 464. We demonstrate the pathogenicity of these new variants associated with reduced YARS2 mRNA transcript, reduced mitochondrial protein translation and dysfunctional organelle function. These pathogenic variants are responsible for late onset MLASA, herein accompanied by pancreatic insufficiency, observed in both brothers, clinically considered as Pearson’s syndrome. Molecular study of YARS2 gene should be considered in patients presenting Pearson’s syndrome characteristics and MLASA related phenotypes.

Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3–6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin’s lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.