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We addressed the question of mitochondrial lactate metabolism using genetically-encoded sensors. The organelle was found to contain a dynamic lactate pool that leads to dose- and time-dependent protein lactylation. In neurons, mitochondrial lactate reported blood lactate levels with high fidelity. The exchange of lactate across the inner mitochondrial membrane was found to be mediated by a high affinity H+-coupled transport system involving the mitochondrial pyruvate carrier MPC. Assessment of electron transport chain activity and determination of lactate flux showed that mitochondria are tonic lactate producers, a phenomenon driven by energization and stimulated by hypoxia. We conclude that an overflow mechanism caps the redox level of mitochondria, while saving energy in the form of lactate.

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The DNA mismatch repair (MMR) is a postreplicative system that guarantees genomic stability by correcting mispaired and unpaired nucleotides. In eukaryotic nuclei, MMR is initiated by the binding of heterodimeric MutS homologue (MSH) complexes to the DNA error or lesion. Among these proteins, MSH2-MSH6 is the most abundant heterodimer. Even though the MMR mechanism and proteins are highly conserved throughout evolution, physiological differences between species can lead to different regulatory features. Here, we investigated how light, sugar, and/or hormones modulate Arabidopsis thaliana MSH6 expression pattern. We first characterized the promoter region of MSH6. Phylogenetic shadowing revealed three highly conserved regions. These regions were analyzed by the generation of deletion constructs of the MSH6 full-length promoter fused to the ß-glucuronidase (GUS) gene. Combined, our in silico and genetic analyses revealed that a 121-bp promoter fragment was necessary for MSH6 expression and contained potential cis-acting elements involved in light- and hormone-responsive gene expression. Accordingly, light exposure or sugar treatment of four-day old A. thaliana seedlings triggered an upregulation of MSH6 in shoot and root apical meristems. Appropriately, MSH6 was also induced by the stem cell inducer WUSCHEL. Further, the stimulatory effect of light was dependent on the presence of phyA. In addition, treatment of seedlings with auxin or cytokinin also caused an upregulation of MSH6 under darkness. Consistent with auxin signals, MSH6 expression was suppressed in the GATA23 RNAi line compared with the wild type. Our results provide evidence that endogenous factors and environmental signals controlling plant growth and development regulate the MSH6 protein in A. thaliana.

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Central nervous system (CNS) pathologies are a public health concern, with viral infections one of their principal causes. These viruses are known as neurotropic pathogens, characterized by their ability to infiltrate the CNS and thus interact with various cell populations, inducing several diseases. The immune response elicited by neurotropic viruses in the CNS is commanded mainly by microglia, which, together with other local cells, can secrete inflammatory cytokines to fight the infection. The most relevant neurotropic viruses are adenovirus (AdV), cytomegalovirus (CMV), enterovirus (EV), Epstein-Barr Virus (EBV), herpes simplex virus type 1 (HSV-1), and herpes simplex virus type 2 (HSV-2), lymphocytic choriomeningitis virus (LCMV), and the newly discovered SARS-CoV-2. Several studies have associated a viral infection with systemic lupus erythematosus (SLE) and neuropsychiatric lupus (NPSLE) manifestations. This article will review the knowledge about viral infections, CNS pathologies, and the immune response against them. Also, it allows us to understand the relevance of the different viral proteins in developing neuronal pathologies, SLE and NPSLE.

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Exploring Brevibacterium strains from various ecosystems may lead to the discovery of new antibiotic-producing strains. Brevibacterium sp. H-BE7, a strain isolated from marine sediments from Northern Patagonia, Chile, had its genome sequenced to study the biosynthetic potential to produce novel natural products within the Brevibacterium genus. The genome sequences of 98 Brevibacterium strains, including strain H-BE7, were selected for a genomic analysis. A phylogenomic cladogram was generated, which divided the Brevibacterium strains into four major clades. A total of 25 strains are potentially unique new species according to Average Nucleotide Identity (ANIb) values. These strains were isolated from various environments, emphasizing the importance of exploring diverse ecosystems to discover the full diversity of Brevibacterium. Pangenome analysis of Brevibacterium strains revealed that only 2.5% of gene clusters are included within the core genome, and most gene clusters occur either as singletons or as cloud genes present in less than ten strains. Brevibacterium strains from various phylogenomic clades exhibit diverse BGCs. Specific groups of BGCs show clade-specific distribution patterns, such as siderophore BGCs and carotenoid-related BGCs. A group of clade IV-A Brevibacterium strains possess a clade-specific Polyketide synthase (PKS) BGCs that connects with phenazine-related BGCs. Within the PKS BGC, five genes, including the biosynthetic PKS gene, participate in the mevalonate pathway and exhibit similarities with the phenazine A BGC. However, additional core biosynthetic phenazine genes were exclusively discovered in nine Brevibacterium strains, primarily isolated from cheese. Evaluating the antibacterial activity of strain H-BE7, it exhibited antimicrobial activity against Salmonella enterica and Listeria monocytogenes. Chemical dereplication identified bioactive compounds, such as 1-methoxyphenazine in the crude extracts of strain H-BE7, which could be responsible of the observed antibacterial activity. While strain H-BE7 lacks the core phenazine biosynthetic genes, it produces 1-methoxyphenazine, indicating the presence of an unknown biosynthetic pathway for this compound. This suggests the existence of alternative biosynthetic pathways or promiscuous enzymes within H-BE7's genome.

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The aim of the review was to evaluate the evidence regarding the effectiveness of aquatic rehabilitation based on the Halliwick concept (HC) in psychomotor development, gross motor function and aquatic skills of children with cerebral palsy. We followed PRISMA recommendations, performing a systematic search in PubMed, Science Direct, LILACS, SciELO, and PEDro database. We identified 474 studies; five met the eligibility criteria and were included in the review. Four studies demonstrated a significant improvement in gross motor function and aquatic skills. Social interaction skills were also improved. However, the methodological quality of these studies was limited, and then, research that adopt controlled experimental designs are necessary.

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Keratinases present promising biotechnological applications, due to their ability to degrade keratin. Streptomyces appears as one of the main sources of these enzymes, but complete genome sequences of keratinolytic bacteria are still limited. This article reports the complete genomes of three marine-derived streptomycetes that show different levels of feather keratin degradation, with high (strain G11C), low (strain CHD11), and no (strain Vc74B-19) keratinolytic activity. A multi-step bioinformatics approach is described to explore genes encoding putative keratinases in these genomes. Despite their differential keratinolytic activity, multiplatform annotation reveals similar quantities of ORFs encoding putative proteases in strains G11C, CHD11, and Vc74B-19. Comparative genomics classified these putative proteases into 140 orthologous groups and 17 unassigned orthogroup peptidases belonging to strain G11C. Similarity network analysis revealed three network communities of putative peptidases related to known keratinases of the peptidase families S01, S08, and M04. When combined with the prediction of cellular localization and phylogenetic reconstruction, seven putative keratinases from the highly keratinolytic strain Streptomyces sp. G11C are identified. To our knowledge, this is the first multi-step bioinformatics analysis that complements comparative genomics with phylogeny and cellular localization prediction, for the prediction of genes encoding putative keratinases in streptomycetes.

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Resumen: Introducción: El tabaquismo es la principal causa de enfermedad y muerte a nivel mundial, siendo una comorbilidad frecuente en los pacientes hospitalizados, con estadías mayores y peores resultados. En el Hospital de Clínicas, no hay estudios que evalúen la prevalencia del tabaquismo en usuarios internados desde el 2005. Objetivo: valorar prevalencia de tabaquistas y sus características en los pacientes que ingresan a sala de cuidados moderados de un Hospital Universitario. Material y métodos: Estudio observacional, analítico, de corte transversal. Resultados: Se incluyeron 100 pacientes, 38% eran tabaquistas, 27% ex tabaquistas y 35% no tenían historia de tabaquismo. La edad media fue de 48.65 años entre los tabaquistas; 63,11 en los ex tabaquistas; 58,68 en los no tabaquistas. Refirieron abstinencia 44,73% de los tabaquistas y pretendían mantener la abstinencia. La media de internación del grupo de tabaquistas fue de 31,07 días, mientras que entre no tabaquistas fue de 20,11 (p=0.1337). Falleció 14% de la población del estudio durante la internación. De este grupo, 14,28% no eran tabaquistas, 28,57% eran ex tabaquistas y 57,14% eran tabaquistas (p=0.0569). La media de edad de fallecimiento en los tabaquistas fue de 49,37 años, en los ex tabaquistas de 70,75 años y de 76 años en los no tabaquistas. Conclusiones e Implicancias: alta prevalencia de tabaquismo en pacientes hospitalizados, con mayor estadía de internación, y mayor mortalidad a menor edad. Muchos fumadores están altamente motivados al cese y se verían beneficiados de equipos interdisciplinarios para su abordaje.

Abstract: Introduction: Smoking is the main cause of disease and death worldwide, being a frequent comorbidity in hospitalized patients, with longer stays and worse results. At Hospital de Clínicas, there are no studies evaluating the prevalence of smoking in hospitalized users since 2005. Objective: to assess the prevalence of smokers and their characteristics in patients admitted to the moderate care room of a University Hospital. Methods: Observational, analytical, cross-sectional study. Results: 100 patients were included, 38% were smokers, 27% ex-smokers and 35% had no history of smoking. The mean age was 48.65 years among the smokers; 63.11 in former smokers; 58.68 in non-smokers. 44.73% of the smokers reported abstinence and intended to maintain abstinence. The mean hospitalization of the group of smokers was 31.07 days, while among non-smokers it was 20.11 (p = 0.1337). 14% of the study population died during hospitalization. Of this group, 14.28% were not smokers, 28.57% were ex-smokers and 57.14% were smokers (p = 0.0569). The mean age of death in smokers was 49.37 years, in ex-smokers it was 70.75 years and 76 years in non-smokers. Conclusions and Implications: high prevalence of smoking in hospitalized patients, with longer hospital stays, and higher mortality at a younger age. Many smokers are highly motivated to quit and would benefit from interdisciplinary teams to address them.

Resumo: Introdução: O tabagismo é a principal causa de doença e morte em todo o mundo, sendo uma comorbidade frequente em pacientes hospitalizados, com maior tempo de permanência e piores resultados. No Hospital de Clínicas, não há estudos avaliando a prevalência de tabagismo em usuários hospitalizados desde 2005. Objetivo: avaliar a prevalência de fumantes e suas características em pacientes internados na unidade de terapia moderada de um Hospital Universitário. Métodos: Estudo observacional, analítico, transversal. Resultados: 100 pacientes foram incluídos, 38% eram fumantes, 27% ex-fumantes e 35% não tinham história de tabagismo. A média de idade foi de 48,65 anos entre os fumantes; 63,11 em ex-fumantes; 58,68 em não fumantes. 44,73% dos fumantes relataram abstinência e pretendem manter a abstinência. A média de internação do grupo de fumantes foi de 31,07 dias, enquanto entre os não fumantes foi de 20,11 (p = 0,1337). 14% da população do estudo morreu durante a hospitalização. Desse grupo, 14,28% não eram fumantes, 28,57% eram ex-fumantes e 57,14% eram fumantes (p = 0,0569). A idade média de morte em fumantes foi 49,37 anos, em ex-fumantes foi 70,75 anos e 76 anos em não fumantes. Conclusões e implicações: alta prevalência de tabagismo em pacientes hospitalizados, com maior tempo de internação e maior mortalidade em idades mais jovens. Muitos fumantes estão altamente motivados para parar de fumar e se beneficiariam de equipes interdisciplinares para abordá-los.

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Resumen: Introducción: Los resultados en cesación tabáquica son insatisfactorios, menores al 30% al año de finalizado el tratamiento. No existe suficiente evidencia sobre la relación entre el Nivel de Funcionamiento de la Personalidad (NFP) y cesación. La Escala de NFP (ENFP) del Manual Estadístico de los Trastornos Mentales 5ed. que evalúa la personalidad en relación consigo mismo y con los otros a través de cuatro dominios, podría ser útil para predecir y mejorar resultados. Objetivos: Evaluar la asociación entre el NFP y la abstinencia al final del tratamiento y a los 6 meses. Metodología: Estudio longitudinal y analítico de una muestra no probabilística de pacientes que consultaron en una Unidad de Tabaquismo. Se aplicó test de chi2 o test exacto de Fisher para evaluar asociación de variables categóricas. Se evaluó NFP con la ENFP y grado de dependencia física con el Test de Fagerström. Resultados: Participaron 28 pacientes, 57% mujeres, edad promedio 48 años (± 12,3). 16 de los 28 cesaron, de ellos 14 presentaron bajos puntajes en la ENFP, correspondiente a mejor NFP. A menores alteraciones en el NFP, mayor cesación al final del tratamiento. En relación a los dominios, la cesación se asoció con identidad, autodirección y empatía y no así con intimidad. La mayoría de los pacientes con enfermedades tabaco-dependientes que presentaban alteraciones del NFP no logró cesar. Conclusiones: Los pacientes sin alteraciones del NFP, tienen más probabilidad de dejar y mantenerse sin fumar. Esto sugiere la utilidad de evaluar el NFP para predecir resultados en la cesación.

Abstract: Introduction: The smoking cessation results are unsatisfactory, less than 30% a year after the end of treatment. There is insufficient evidence on the relationship between the Level of Personality Functioning (LPF) and cessation. The LPF Scale (LPFS) of the Statistical Manual of Mental Disorders 5ed. that evaluates personality in relation to yourself and others, through four domains, could be useful in predicting and improving outcomes. Objectives: To assess the association between LPF and abstinence at the end of treatment and at 6 months. Methodology: Longitudinal and analytical study of a non-probability sample of patients who consulted in a Cessation Unit. The chi2 test or Fisher's exact test was applied to evaluate the association of categorical variables. LPF was evaluated with the LPFS and degree of nicotine dependence with the Fagerström Test. Results: 28 patients participated, 57% women, average age 48 years (± 12.3). 16 of 28 stopped, of them 14 had low scores in the LPFS, corresponding to better LPF. A less alteration in the LPF, greater cessation at the end of the treatment. Regarding the domains, the association was found with identity, self-direction and empathy with cessation but not with intimacy. Most of the patients with tobacco-dependent diseases who presented LPF disorder did not quit. Conclusions: Patients without LPF disorders are more likely to achieve cessation and remain abstinent. This assumes the utility of evaluating the LPF to predict cessation outcomes.

Resumo: Introdução: Os resultados da cessação do tabaco são insatisfatórios, menos de 30% ao ano após o término do tratamento. Não há suficiente evidência sobre a relação entre o Nível de Funcionamento da Personalidade (NFP) e a cessação. Escala NFP (ENFP) do Manual Estatístico de Transtornos Mentais 5 ed. que avalia a personalidade em relação a si mesmo e os outros, através de quatro domínios poderia ser útil para prever e melhorar os resultados. Objetivos: Avaliar associação entre NFP e abstinência ao final do tratamento e aos 6 meses. Metodologia: Estudo longitudinal, analítico de uma amostra não probabilística de pacientes consultados numa unidade de fumantes. Foram aplicados teste de Chi2 ou teste exato de Fisher para avaliar associação de variáveis categóricas. O NFP foi avaliado com ENFP e o grau de dependência física com Teste de Fagerström. Resultados: 28 pacientes participaram no estudo, 57% mulheres, idade média 48 anos (± 12,3). 16 dos 28 conseguirem cessar, 14 deles tiveram escores baixos do ENFP, correspondendo num melhor NFP. Quanto menos alterações no NFP, maior cessação ao final do tratamento. Em relação aos domínios, foi encontrada associação com identidade, autodireção e empatia com cessação, mas não é assim com intimidade. A maioria das pessoas com doenças dependentes do tabaco, que apresentavam alterações no PFN não conseguiu parar. Conclusões: Pacientes sem alterações no NFP têm maior probabilidade de cessação e permanecem livres de fumo. Isso sugere a utilidade de avaliar o NFP pra prever resultados na cessação.

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Resumen: Introducción: los productos de tabaco están diseñados para ser atractivos, introduciéndose últimamente elementos aditivos y saborizantes. En Uruguay existen normativas que evitan la publicidad en cualquiera de sus formas, por esto, la atracción del propio producto de tabaco a través de su sabor y diseño es un factor importante para la elección por parte de los fumadores, en particular, jóvenes. Es relevante conocer qué productos se encuentran disponibles en nuestro medio y cuáles son accesibles cerca de centros educativos. Material y método: se realizó un estudio descriptivo, observacional, prospectivo de corte transversal. El protocolo de trabajo de campo se adaptó del Sistema de Vigilancia de paquetes de Tabaco de la Universidad de Johns Hopkins. Resultados: se identificaron 23 variedades. El 34,78% de los productos fueron saborizados, estando disponibles en 86,67% de los puntos de venta. Todas las cajas de los saborizados tenían alguna referencia que indicaba su condición. En la mitad, la marca sugería la presencia de sabor o su activación. El 87,5% de los filtros se referían a la activación del sabor y 37,5% agregaban caracteres tecnológicos para éste; 75% tenía sabor a menta y 24% doble sabor. Solo 39,1% tenía información de protección al menor. Conclusiones e implicancias: hay una gran disponibilidad de productos de tabaco saborizados, incrementado la variedad en los últimos años, siendo en Uruguay menor que en otros países. En ausencia de regulación específica sobre aditivos y saborizantes, los países podrían disminuir la oferta implementando presentación única por marca y prohibición total de la publicidad.

Summary: Introduction: tobacco products are designed to be attractive, and recently, flavour additives have been introduced in the market. In Uruguay, regulations in force prohibit all forms of publicity for these products. For this reason, attracting consumers to tobacco products by means of flavour and design constitutes an important factor in smokers' choice, in particular the young. Learning about products available in our market and those that are close to educational centers is relevant. Method: descriptive, observational, prospective and transversal study. The field work protocol was adapted from the Johns Hopkins University Tobacco Pack Surveillance System Project. Results: 23 varieties were identified. 34.78% of the products were flavoured, and they were available in 86,67% points of sale. All flavoured products' packs included a reference to its condition. In 50% of them, the brand suggested the presence or activation of flavour. 87.5% of filters referred to flavor activation and 37.5% added technological traits. 75% were mint flavoured and 24% were double-flavoured. Only 39.1% included minor protection information. Conclusions: there is great availability of flavoured tobacco products, the variety being greater in recent years, although lower in Uruguay if compared to other countries. In the absence of specific regulations on additives and flavouring substances, countries could reduce the offer by implementing a single presentation by brand and the complete banning of publicity.

Resumo: Introdução: os produtos do tabaco são projetados para serem atraentes, com aditivos e elementos aromatizantes recentemente introduzidos. No Uruguai, existem normas que proíbem a publicidade em qualquer de suas formas, portanto, a atração do próprio produto do tabaco pelo seu sabor e design é um fator importante na escolha dos fumantes, principalmente dos jovens. É importante saber quais produtos estão disponíveis em nosso ambiente e quais estão disponíveis próximos a centros educativos. Material e métodos: foi realizado um estudo transversal descritivo, observacional e prospectivo. O protocolo de trabalho de campo foi adaptado do Sistema de Vigilância de Pacotes de Tabaco da Universidade Johns Hopkins. Resultados: foram identificadas 23 marcas diferentes. 34,78% dos produtos eram aromatizados, estando disponíveis em 86,67% dos pontos de venda. A embalagem de todas as marcas com sabor tinha alguma referência indicando essa característica. A metade delas indicava a presença do sabor ou sua ativação. 87,5% dos filtros referiram-se à ativação do sabor e 37,5% agregaram sus características tecnológicas. 75% tinham sabor mentolado e 24% dois sabores. Apenas 39,1% possuíam informações de proteção à criança. Conclusões e implicações: há uma grande disponibilidade de produtos de tabaco aromatizados, e a variedade tem aumentado nos últimos anos, sendo menor no Uruguai que em outros países. Na ausência de regulamentação específica sobre aditivos e aromatizantes, os países poderiam reduzir a oferta implementando uma apresentação única por marca e a proibição total da publicidade.

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Marine actinobacteria are viewed as a promising source of enzymes with potential technological applications. They contribute to the turnover of complex biopolymers, such as pectin, lignocellulose, chitin, and keratin, being able to secrete a wide variety of extracellular enzymes. Among these, keratinases are a valuable alternative for recycling keratin-rich waste, which is generated in large quantities by the poultry industry. In this work, we explored the biocatalytic potential of 75 marine-derived actinobacterial strains, focusing mainly on the search for keratinases. A major part of the strains secreted industrially important enzymes, such as proteases, lipases, cellulases, amylases, and keratinases. Among these, we identified two streptomycete strains that presented great potential for recycling keratin wastes-Streptomyces sp. CHA1 and Streptomyces sp. G11C. Substrate concentration, incubation temperature, and, to a lesser extent, inoculum size were found to be important parameters that influenced the production of keratinolytic enzymes in both strains. In addition, proteomic analysis of culture broths from Streptomyces sp. G11C on turkey feathers showed a high abundance and diversity of peptidases, belonging mainly to the serine and metallo-superfamilies. Two proteases from families S08 and M06 were highly expressed. These results contributed to elucidate the mechanism of keratin degradation mediated by streptomycetes.

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