Effects of physical inactivity on skeletal muscle metabolic function

Being confined to bed rest has negative physiological consequences. Bed rest represents a unique model of physical inactivity and results in changes in cardiovascular, neural and metabolic function. In particular, reduced skeletal muscle mitochondrial capacity and a reduction in intrinsic mitochondrial function in response to physical inactivity may have broad implications for human disease. The aim of the present study was to test the hypothesis that physical inactivity, through the model of bed rest, will decrease mitochondrial function, insulin sensitivity and muscle mass in healthy young men. A reduction in lean muscle mass was evident after bed rest (p<0.05). This was accompanied by a reduction in skeletal muscle insulin sensitivity (p<0.05). Citrate synthase as a marker of mitochondrial content was reduced after bed rest (p<0.05). O2 flux expressed per mg of wet weight of muscle tissue was lower during LEAK respiration following 21 days of BR (p<0.05). OXPHOS and ETS capacity, indicative of maximal capacity, were increased following bed rest when normalized to citrate synthase activity (p<0.05). Mitochondrial proteins, COX5a, complex III core protein 2 and SDHb were down regulated. A reduction in CS in the present study suggests that there are fewer actively respiring mitochondria, however no change in mitochodnrial respiration was noted. A reduction in LEAK respiration as an indicator of reduced mitochondrial uncoupling may be associated with increased ROS production. A significant positive correlation between the reduction in maximal ETS and insulin sensitivity suggests a relationship between the two. The mechanisms involved in disuse muscle atrophy require further clarification, as do the mechanisms linking insulin sensitivity, mitochondrial function and muscle atrophy

OCORRÊNCIA E CARACTERIZAÇÃO MOLECULAR DE VÍRUS DE CUCURBITÁCEAS NO ESTADO DO PARÁ

As cucurbitáceas estão entre as principais hortaliças cultivadas no Brasil por ser importante fonte de minerais e vitaminas, especialmente vitaminas A e C, encontrados na polpa dos frutos na forma de carotenóides e ácido ascórbico. As espécies de cucurbitáceas são frequentemente acometidas por doenças de origem viral. No Brasil já foram relatados dez vírus infectando cucurbitáceas. Entretanto, sete se destacam como os principais, devido à frequência de detecção em plantios comerciais de cucurbitáceas e às perdas que podem causar na produção e na produtividade. Dentre esses, o vírus da mancha anelar do mamoeiro, estirpe melancia (Papaya ringspot virus – type watermelon – PRSV-w), o vírus do mosaico amarelo da abobrinha de moita (Zucchini yellow mosaic virus – ZYMV) e o vírus do mosaico da melancia (Watermelon mosaic virus – WMV) do gênero Potyvirus, são os mais importantes. No estado do Pará não há estudos sobre as viroses importantes na cultura, tendo apenas relatos de ocorrência dos vírus ZYMV e PRSV-w. Deste modo, este trabalho propôs registrar a ocorrência e a caracterização molecular das espécies virais prevalentes em alguns municípios produtores de cucurbitáceas no estado do Pará. Amostras de folhas de cucurbitáceas com suspeitas de viroses foram coletadas em 14 municípios do estado do Pará. A detecção das espécies virais foi feita pelo teste sorológico PTA-ELISA.&nbsp; A caracterização molecular foi feita por meio da análise das sequências de nucleotídeos e aminoácidos dos isolados. As sequências de nucleotídeos foram comparadas com os acessos depositados no GenBank utilizando os programas BLAST, ClustalW e MEGA 5.0. Os resultados obtidos mostraram a abrangência dos Potyvirus no estado, pois todas as espécies investigadas foram detectadas nas análises. O PRSV-w, como já relatado em outros estados, é o vírus mais frequente na cultura das cucurbitáceas, seguido dos vírus ZYMV e do WMV

An atlas of spider development at single-cell resolution provides new insights into arthropod embryogenesis

Spiders are a diverse order of chelicerates that diverged from other arthropods over 500 million years ago. Research on spider embryogenesis, particularly studies using the common house spider Parasteatoda tepidariorum, has made important contributions to understanding the evolution of animal development, including axis formation, segmentation, and patterning. However, we lack knowledge about the cells that build spider embryos, their gene expression profiles and fate. Single-cell transcriptomic analyses have been revolutionary in describing these complex landscapes of cellular genetics in a range of animals. Therefore, we carried out single-cell RNA sequencing of P. tepidariorum embryos at stages 7, 8 and 9, which encompass the establishment and patterning of the body plan, and initial differentiation of many tissues and organs. We identified 20 cell clusters, from 18.5 k cells, which were marked by many developmental toolkit genes, as well as a plethora of genes not previously investigated. We found differences in the cell cycle transcriptional signatures, suggestive of different proliferation dynamics, which related to distinctions between endodermal and some mesodermal clusters, compared with ectodermal clusters. We identified many Hox genes as markers of cell clusters, and Hox gene ohnologs were often present in different clusters. This provided additional evidence of sub- and/or neo-functionalisation of these important developmental genes after the whole genome duplication in an arachnopulmonate ancestor (spiders, scorpions, and related orders). We also examined the spatial expression of marker genes for each cluster to generate a comprehensive cell atlas of these embryonic stages. This revealed new insights into the cellular basis and genetic regulation of head patterning, hematopoiesis, limb development, gut development, and posterior segmentation. This atlas will serve as a platform for future analysis of spider cell specification and fate, and studying the evolution of these processes among animals at cellular resolution

Clinical and epidemiological factors associated with spontaneous preterm birth : a multicentre cohort of low risk nulliparous women

The objective of this study was to determine incidence and risk factors associated with spontaneous preterm birth (sPTB). It was a prospective multicentre cohort study performed in fve Brazilian referral maternity hospitals and enrolling nulliparous women at 19–21 weeks. Comprehensive maternal data collected during three study visits were addressed as potentially associated factors for sPTB. Bivariate and multivariate analysis estimated risk ratios. The main outcomes measures were birth before 37 weeks due to spontaneous preterm labour or premature rupture of membranes (sPTB). The comparison group was comprised of women with term births (≥37weeks). Outcome data was available for 1,165 women, 6.7% of whom had sPTB, 16% had consumed alcohol and 5% had used other illicit drugs during the frst half of pregnancy. Current drinking at 19–21 weeks (RR 3.96 95% CI [1.04–15.05]) and a short cervix from 18–24 weeks (RR 4.52 95% CI [1.08–19.01]) correlated with sPTB on bivariate analysis. Increased incidence of sPTB occurred in underweight women gaining weight below quartile 1 (14.8%), obese women gaining weight above quartile 3 (14.3%), women with a short cervix (<25mm) at 18–24 weeks (31.2%) and those with a short cervix and vaginal bleeding in the frst half of pregnancy (40%). Cervical length (RRadj 4.52 95% CI [1.08–19.01]) was independently associated with sPTB. In conclusion, the incidence of sPTB increased in some maternal phenotypes, representing potential groups of interest, the focus of preventive strategies. Similarly, nulliparous women with a short cervix in the second trimester require further exploration

Mitochondrial Reactive Oxygen Species in Lipotoxic Hearts Induces Post-Translational Modifications of AKAP121, DRP1 and OPA1 That Promote Mitochondrial Fission

Rationale: Cardiac lipotoxicity, characterized by increased uptake, oxidation and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood. Objective: To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo. Methods and Results: Using a transgenic mouse model of cardiac lipotoxicity overexpressing long-chain acyl-CoA synthetase 1 in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter. This is associated with increased palmitoyl-carnitine oxidation and increased reactive oxygen species (ROS) generation in isolated mitochondria. Mitochondrial morphological changes and elevated ROS generation are also observed in palmitate- treated neonatal rat ventricular cardiomyocytes (NRVCs). Palmitate exposure to NRVCs initially activates mitochondrial respiration, coupled with increased mitochondrial membrane potential and adenosine triphosphate (ATP) synthesis. However, long-term exposure to palmitate (\u3e8h) enhances ROS generation, which is accompanied by loss of the mitochondrial reticulum and a pattern suggesting increased mitochondrial fission. Mechanistically, lipid-induced changes in mitochondrial redox status increased mitochondrial fission by increased ubiquitination of A-kinase anchor protein (AKAP121) leading to reduced phosphorylation of DRP1 at Ser637 and altered proteolytic processing of OPA1. Scavenging mitochondrial ROS restored mitochondrial morphology in vivo and in vitro. Conclusions: Our results reveal a molecular mechanism by which lipid overload-induced mitochondrial ROS generation causes mitochondrial dysfunction by inducing post-translational modifications of mitochondrial proteins that regulate mitochondrial dynamics. These findings provide a novel mechanism for mitochondrial dysfunction in lipotoxic cardiomyopathy. 38 pp; includes supplemental materials

Prefácio

    PREFÁCIO   A Revista da Faculdade de Direito da UFRGS, no mesmo dia em que lança seu número ordinário do segundo semestre de 2018, publica este número especial. Ele foi possível graças ao grande interesse de autores no periódico, o que permitiu fazer um segundo número concomitantemente ao principal. Essa ocorrência se deu principalmente devido à qualidade das submissões, pois a quantidade de artigos com bom nível superava em muito os quinze espaços reservados para cada número.Pela organização decorrente dessa circunstância, os números tiveram alguns focos, reunindo os artigos de determinadas áreas. Este número especial tem trabalhos de Filosofia do Direito, Direito do Trabalho e artigos voltados a diversos temas conectados à proteção das mulheres e crianças, tráfico de pessoas e sexualidade. Os trabalhos foram agrupados por seus temas, mas eles apresentam grande pluralidade de opiniões, garantindo um debate aberto e, à revista, o papel de permitir que os artigos bem considerados pelos avaliadores possam efetivamente constar no número.Os dois convidados são de Filosofia do Direito. Duas visões de mundo distintas aparecem nos artigos. Primeiro, o professor da Faculdade de Direito de Recife, Pedro Parini, discorre sobre o discurso retórico e as reservas que o ceticismo pirrônico traz para diversas posições filosóficas que buscam dar conteúdo ao Direito. Por outro lado, o professor argentino Carlos Massini Correas apresenta características do Direito Natural no pós-modernismo, mostrando sua visão de mundo na qual a modernidade marcou o passo sobre essas reflexões e, então, ele sistematiza os principais elementos formadores desse momento.Os outros treze artigos foram recebidos por edital. O primeiro grupo trata de temas como a legislação brasileira envolvendo o tratamento de crianças, questões controversas sobre a "Lei Maria da Penha" em sua aplicação quotidiana, um estudo comparado sobre a retificação de nomes de pessoas transgênero e, por fim, o trabalho de um pesquisador africano sobre o tráfico de mulheres em países da Comunidade de Desenvolvimento da África Austral.O segundo grupo envolve o Direito do Trabalho. Os primeiros deles tratam de posicionamentos relacionando a área com considerações sociais mais amplas. Um mostrando o pensamento de Marx sobre o conceito de cidadania, o segundo, os princípios da solidariedade e fraternidade na proteção dos trabalhadores e um trabalho sobre a Teoria do Reconhecimento e o tratamento dos direitos trabalhistas. Por fim, o último trabalho trata da reforma trabalhista com foco no trabalho intermitente, buscando verificar seus efeitos sociais e possibilidades durante a sua execução.  O restante dos artigos trata de temas importantes de outras áreas. São contemplados trabalhos nas áreas de processo legislativo, financiamento de campanhas eleitorais, sistema brasileiro de solução de conflitos, deslistagens de ações em bolsas de valores e o tratamento de resíduos nanoparticulados. Cada um foi avaliado positivamente e consta na publicação por seus méritos.Desejamos que este número auxilie no desenvolvimento e traga novas perspectivas. A revista buscou, com esses trabalhos, se manter aberta aos mais diversos assuntos e visões, garantindo um debate acadêmico de alto nível e que possibilite o desenvolvimento de soluções buscadas pela sociedade. Boa leitura!  Porto Alegre, 31 de dezembro de 2018. Prof. Dr. Carlos Silveira NoronhaEditor-chefe Prof. Dr. Alfredo de Jesus Dal Molin FloresEditor-adjunto Prof. Dr. Gustavo Castagna MachadoProf. Dr. Wagner Silveira FeloniukDoutoranda Ana Helena Karnas Hoefel PamplonaDoutorando Kenny SontagMestre Pedro Prazeres Fraga PereiraMestrando Augusto Sperb MachadoEditores-Executivos 

Prefácio

 A revista chega ao número 38 com a publicação do primeiro semestre de 2018. É um número lançado dentro da periodicidade programada e aderindo a todas as normas para as publicações científicas na área do Direito. Mais de uma centena de artigos foram submetidos no edital que antecedeu o número e, após acirrada concorrência, mais um número foi formado e é agora publicado.Nessa continuidade, os agradecimentos sempre lembrados são aos avaliadores. Centenas de professores e pesquisadores, alguns de outros países, que se dedicam à revista em trabalho voluntário. Eles formam o momento mais relevante para a edição ser possível após a submissão, avaliando o mérito dos artigos nas suas áreas de especialidade. É um apoio necessário e cuja constante realização, por vezes repetida ao longo de diversos anos pelos professores, permite que a revista cumpra suas normas e se mantenha aberta aos melhores trabalhos, reconhecendo-os e permitindo sua indicação para publicação.Dentre os artigos convidados, temos duas traduções. A primeira do professor alemão de ciência política da Universidade de Frankfurt, Jens Borchert, com trabalho sobre a relação, dentro da teoria democrática contemporânea, entre sistema representativo e elites políticas, seu patamar de autonomia e como isso poderia ser conciliado com o anseio popular por uma democracia mais aberta à participação pública. O segundo artigo é do historiador argentino José María Díaz Couselo e trata de temas importantes para a metodologia da pesquisa na área da História do Direito.Por fim, o terceiro convidado é o professor Carlos Silveira Noronha, professor aposentado da Faculdade de Direito da UFRGS. O professor tem estado à frente da revista até este momento, mas a publicação é sobretudo uma homenagem a todos os anos anteriores à digitalização, em que ele esteve praticamente sozinho na elaboração de muitas edições, prestando importante papel na continuidade da publicação e à faculdade.Além dos autores convidados, como ocorre em cada número, foram publicados doze trabalhos recebidos durante o edital público de seleção. Os trabalhos iniciam pela atuação do Supremo Tribunal Federal e por considerações que envolvem Direito e Política em assuntos relevantes e atuais, contribuindo, na área acadêmica, com os temas em questão no Brasil. Além deles, são publicados artigos de Direito Administrativo, Econômico, da Concorrência e do Trabalho, todos considerados relevantes pelos avaliadores e com vieses que trazem contribuições às suas áreas. Por fim, três artigos têm relação com Direito Processual, tanto trazendo assuntos relacionados ao novo Código de Processo Civil, quanto a outras normas que recentemente ingressaram no ordenamento brasileiro e ainda geram questionamentos ou são passíveis de estudos sobre sua aplicação e sucesso.Os artigos publicados mantêm seu compromisso com a opinião dos avaliadores na escolha dos publicados, a inserção acadêmica de seus autores, a abertura aos diversos temas relevantes e a preocupação geográfica - com obras representando todas as regiões do Brasil.Desejamos a todos os leitores uma boa leitura, com a expectativa de que as obras contribuam com o cenário acadêmico e com outras pesquisas.

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Overexpression of circulating MiR-30b-5p identifies advanced breast cancer

Breast cancer (BrC) remains the leading cause of cancer-related death in women, mainly due to recurrent and/or metastatic events, entailing the need for biomarkers predictive of progression to advanced disease. MicroRNAs hold promise as noninvasive cancer biomarkers due to their inherent stability and resilience in tissues and bodily fluids. There is increasing evidence that specific microRNAs play a functional role at different steps of the metastatic cascade, behaving as signaling mediators to enable the colonization of a specific organ. Herein, we aimed to evaluate the biomarker performance of microRNAs previously reported as associated with prognosis for predicting BrC progression in liquid biopsies. Background Breast cancer (BrC) remains the leading cause of cancer-related death in women, mainly due to recurrent and/or metastatic events, entailing the need for biomarkers predictive of progression to advanced disease. MicroRNAs hold promise as noninvasive cancer biomarkers due to their inherent stability and resilience in tissues and bodily fluids. There is increasing evidence that specific microRNAs play a functional role at different steps of the metastatic cascade, behaving as signaling mediators to enable the colonization of a specific organ. Herein, we aimed to evaluate the biomarker performance of microRNAs previously reported as associated with prognosis for predicting BrC progression in liquid biopsies. Methods Selected microRNAs were assessed using a quantitative reverse transcription-polymerase chain reaction in a testing cohort of formalin-fixed paraffin-embedded primary (n = 16) and metastatic BrC tissues (n = 22). Then, miR-30b-5p and miR-200b-3p were assessed in a validation cohort #1 of formalin-fixed paraffin-embedded primary (n = 82) and metastatic BrC tissues (n = 93), whereas only miR-30b-5p was validated on a validation cohort #2 of liquid biopsies from BrC patients with localized (n = 20) and advanced (n = 25) disease. ROC curve was constructed to evaluate prognostic performance. Results MiR-30b-5p was differentially expressed in primary tumors and paired metastatic lesions, with bone metastases displaying significantly higher miR-30b-5p expression levels, paralleling the corresponding primary tumors. Interestingly, patients with advanced disease disclosed increased circulating miR-30b-5p expression compared to patients with localized BrC. Conclusions MiR-30b-5p might identify BrC patients at higher risk of disease progression, thus, providing a useful clinical tool for patients’ monitoring, entailing earlier and more effective treatment. Nonetheless, validation in larger multicentric cohorts is mandatory to confirm these findings.Research Center of Portuguese Oncology Institute of Porto (PI 74-CI-IPOP-19-2016). JL and CSG are supported by a PhD fellowship from FCT - Fundação para a Ciência e Tecnologia (SFRH/ BD/132751/2017 and SFRH/BD/92786/2013, respectively). SS is supported by a PhD fellowship IPO/ESTIMA-1 NORTE-01-0145-FEDER-000027. BMC is funded by FCT-Fundação para a Ciência e a Tecnologia (IF/00601/2012

Phenotypic Responses to a Lifestyle Intervention Do Not Account for Inter-Individual Variability in Glucose Tolerance for Individuals at High Risk of Type 2 Diabetes

Background: Lifestyle interventions have been shown to delay or prevent the onset of type 2 diabetes among high risk adults. A better understanding of the variability in physiological responses would support the matching of individuals with the best type of intervention in future prevention programmes, in order to optimize risk reduction. The purpose of this study was to determine if phenotypic characteristics at baseline or following a 12 weeks lifestyle intervention could explain the inter-individual variability in change in glucose tolerance in individuals with high risk for type 2 diabetes.Methods: In total, 285 subjects with normal glucose tolerance (NGT, FINDRISC score &gt; 12), impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were recruited for a 12 weeks lifestyle intervention. Glucose tolerance, insulin sensitivity, anthropometric characteristics and aerobic fitness were measured. Variability of responses was examined by grouping participants by baseline glycemic status, by cluster analysis based on the change in glucose tolerance and by Principal Component Analysis (PCA).Results: In agreement with other studies, the mean response to the 12 weeks intervention was positive for the majority of parameters. Overall, 89% improved BMI, 80% waist circumference, and 81% body fat while only 64% improved fasting plasma glucose and 60% 2 h glucose. The impact of the intervention by glycaemic group did not show any phenotypic differences in response between NGT, IFG, and IGT. A hierarchical cluster analysis of change in glucose tolerance identified four sub-groups of “responders” (high and moderate) and “non-responders” (no response or deteriorated) but there were few differences in baseline clincal and physiological parameters or in response to the intervention to explain the overall variance. A further PCA analysis of 19 clinical and physiological univariables could explain less than half (48%) of total variability.Conclusion: We found that phenotypic characteristics from standard clinical and physiological parameters were not sufficient to account for the inter-individual variability in glucose tolerance following a 12 weeks lifestyle intervention in inidivuals at high risk for type 2 diabetes. Further work is required to identify biomarkers that complement phenotypic traits and better predict the response to glucose tolerance