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The contrast between the disruption of genome topology after cohesin loss and the lack of downstream gene expression changes instigates intense debates regarding the structure-function relationship between genome and gene regulation. Here, by analyzing transcriptome and chromatin accessibility at the single-cell level, we discover that, instead of dictating population-wide gene expression levels, cohesin supplies a general function to neutralize stochastic coexpression tendencies of cis-linked genes in single cells. Notably, cohesin loss induces widespread gene coactivation and chromatin co-opening tens of million bases apart in cis. Spatial genome and protein imaging reveals that cohesin prevents gene co-bursting along the chromosome and blocks spatial mixing of transcriptional hubs. Single-molecule imaging shows that cohesin confines the exploration of diverse enhancer and core promoter binding transcriptional regulators. Together, these results support that cohesin arranges nuclear topology to control gene coexpression in single cells.

O Movimento Estudantil, emergido tal como o conhecemos atualmente, nasce após a década de 1930, com a fundação das agremiações estudantis nacionais. Fruto das mobilizações em torno de pautas políticas, o movimento estudantil se destaca na vida social brasileira. Em 2007, surge em São José dos Pinhais, município da Região Metropolitana de Curitiba, a União Municipal dos Estudantes Secundaristas (UMES), uma agremiação cujo objetivo era representar a comunidade estudantil ante o poder público local. Com base em pesquisa bibliográfica, documental e de campo, apoiada na história oral, o presente artigo discute os modos de agir e pensar que eram praticados pelos estudantes no interior da UMES, no período de 2007 a 2015. Destaca-se que as entrevistas que foram realizadas se deram com ex-participantes da entidade, jovens estudantes, na maioria provenientes de escolas públicas. Serve-se, neste estudo, das noções de campo político em Bourdieu; de tática em Certeau; e de poder em Foucault, no intuito de compreender as práticas estudantis, empreendidas no âmbito da referida agremiação, onde intentavam, a partir do campo da política, lograr suas bandeiras. Depreende-se, portanto, que a maioria dos estudantes, introduzidos na UMES, vislumbrava sua organização como instrumento de luta por seus direitos, embora fosse também um lugar de reflexão acerca da qualidade da educação.

Leptospirosis is a bacterial disease that affects humans and animals and is caused by Leptospira. The recommended treatment for leptospirosis is antibiotic therapy, which should be given early in the course of the disease. Despite the use of these antibiotics, their role during the course of the disease is still not completely clear because of the lack of effective clinical trials, particularly for severe cases of the disease. Here, we present the characterization of L. interrogans Lsa45 protein by gel filtration, protein crystallography, SAXS, fluorescence and enzymatic assays. The oligomeric studies revealed that Lsa45 is monomeric in solution. The crystal structure of Lsa45 revealed the presence of two subdomains: a large α/β subdomain and a small α-helical subdomain. The large subdomain contains the amino acids Ser122, Lys125, and Tyr217, which correspond to the catalytic triad that is essential for β-lactamase or serine hydrolase activity in similar enzymes. Additionally, we also confirmed the bifunctional promiscuity of Lsa45, in hydrolyzing both the 4-nitrophenyl acetate (p-NPA) and nitrocefin β-lactam antibiotic. Therefore, this study provides novel insights into the structure and function of enzymes from L. interrogans, which furthers our understanding of this bacterium and the development of new therapies for the prevention and treatment of leptospirosis.

A predominância de mulheres como docentes em creches, muito provavelmente por ocasião da relação que se instituiu entre cuidar e educar como qualidades privativas desse gênero, tem permitido o estabelecimento de múltiplas interrogações acerca da reiterada ausência do masculino nesses espaços. Em razão desse cenário, objetiva-se, no presente artigo, dar uma explicação ao processo de contenção que se emprega ao masculino quanto a sua atuação na educação infantil, mais especificamente no trabalho com bebês em creches. A partir da análise do relato de um dos autores sobre sua experiência na creche, aciona-se as noções de interdição implícita e interdição explícita para compreender o fenômeno de distanciamento do masculino dos berçários. Conclui-se que, embora seja preciso compromisso e seriedade com os sentimentos, expressões a aprendizados dos bebês, a fim de exercer um bom trabalho em turmas de berçário, o masculino é reiteradamente interditado a desempenhá-lo, pois regularmente são evocadas qualidades supostamente do feminino como ingredientes para atuar em creches, como sensibilidade, cuidado e atenção.

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According to the World Health Organization (WHO), the harmful use of alcohol stands as a primary risk factor affecting the global population’s health. In 2016, 5.5% of all deaths in the 30 countries of the European Union (EU) were attributed to alcohol. In the past year, 62.3% of adults in the WHO European Region consumed alcoholic beverages at least once, contributing to nearly one million deaths annually, averaging around 2,500 deaths per day.

Thermomechanical modeling of additively manufactured parts made by laser powder bed fusion aims to control stresses and distortions built during processing. This is, by nature, a multiscale metallurgical and mechanical problem, notably due to the strong texture of the grain structure that results from the process and may locally dictate the thermomechanical behavior law. Similarly, stresses and distortions are directly influenced by the heat transfer process at the system scale, including the consequences of the link between the part and the substrate and the weaker interactions with the powder bed and the gas environment. To achieve relevant modeling, we first demonstrate capabilities to assess at part scale, both i- the prediction of the grain structure and ii- the thermomechanical analyses. A discussion follows that summarizes the foreseen directions to achieve coupling and/or chaining between grain structure simulations and mechanical analyses at part scale.

Mechanical signals from the extracellular matrix are crucial in guiding cellular behavior. Two-dimensional hydrogel substrates for cell cultures serve as exceptional tools for mechanobiology studies because they mimic the biomechanical and adhesive characteristics of natural environments. However, the interdisciplinary knowledge required to synthetize and manipulate these biomaterials typically restricts their widespread use in biological laboratories, which may not have the material science expertise or specialized instrumentation. To address this, we propose a scalable method that requires minimal setup to produce 2D hydrogel substrates with independent modulation of the rigidity and adhesiveness within the range typical of natural tissues. In this method, norbornene-terminated 8-arm polyethylene glycol is stoichiometrically functionalized with RGD peptides and crosslinked with a di-cysteine terminated peptide via a thiol–ene click reaction. Since the synthesis process significantly influences the final properties of the hydrogels, we provide a detailed description of the chemical procedure to ensure reproducibility and high throughput results. We demonstrate examples of cell mechanosignaling by monitoring the activation state of the mechanoeffector proteins YAP/TAZ. This method effectively dissects the influence of biophysical and adhesive cues on cell behavior. We believe that our procedure will be easily adopted by other cell biology laboratories, improving its accessibility and practical application.

Abstract Space levitation processing allows researchers to conduct benchmark tests in an effort to understand the physical phenomena involved in rapid solidification processing, including alloy thermodynamics, nucleation and growth, heat and mass transfer, solid/liquid interface dynamics, macro- and microstructural evolution, and defect formation. Supported by ground-based investigations, a major thrust is to develop and refine robust computational tools based on theoretical and applied approaches. This work is accomplished in conjunction with experiments designed for precise model validation with application to a broad range of industrial processes.

mRNA translation is tightly regulated to preserve cellular homeostasis. Here live-cell spectroscopy and single-particle tracking are combined to interrogate the binding dynamics of endogenous initiation factors to mRNAs 5’cap, revealing the sequence of translation initiation factors assembly and disassembly; and the clustering of translation in neurons.

IntroductionWithin FAR SEAS, a multi-component evidence-based community intervention was implemented and evaluated in Mazovia (Poland), with the aim of preventing alcohol-exposed pregnancies, and therefore preventing FASD.MethodsMulti-disciplinary professionals from different services (social, addiction, and psychology), recruited women of child-bearing age (pregnant and not pregnant) in local communities, screened them for alcohol risk, and allocated participants (n = 441) to groups for low- (70%), moderate- (23%), or high-risk (7%) of alcohol exposed pregnancy, to provide interventions tailored to their needs. The non-parametric sign test, testing differences between pairs of observations before and after intervention was used to evaluate the outcomes.ResultsFollow-up data (collected from 93% of participants) indicated positive changes in the key outcome variables: risky alcohol consumption dropped by 81%, contraception use increased by 15% and visiting a gynecologist increased by 39%; as well as in associated psychosocial risk factors (decrease in cigarette and drug use, domestic violence and depressive symptoms). No changes were noted in frequency of other service use (medical, psychological, or social). The most prominent changes were observed in the moderate-risk group.DiscussionChanging risky behaviors (alcohol consumption and sex without contraception) to prevent alcohol exposed pregnancies is feasible at the local level, even without engagement of medical professionals. Key challenges, related to engaging professionals and local authorities, must be addressed; and procedures should be adapted to local contexts and needs.

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF

BackgroundStaging of melanoma and follow up after melanoma diagnosis aims at predicting risk and detecting progression or recurrence at early stage, respectively in order to timely start and/or change treatment. Tumor thickness according to Breslow, status of the sentinel node and value of the lactate dehydrogenase (LDH) are well-established prognostic markers for metastatic risk, but reliable biomarkers identifying early recurrence or candidates who may benefit best from medical treatment are still warranted. Liquid biopsy has emerged to be a suitable method for identifying biomarkers for early cancer diagnosis, prognosis, therapeutic response prediction, and patient follow-up. Liquid biopsy is a blood-based non-invasive procedure that allows analyzing circulating analytes, including extracellular vesicles.MethodsIn this study we have explored the use of 7 miRNAs, namely hsa-miR-149-3p, hsa-miR-150-5p, hsa-miR-21-5p, hsa-miR-200c-3p, hsa-miR-134-5p, hsa-miR-144-3p and hsa-miR-221-3p in plasma exosomes to discriminate melanoma patients from controls without melanoma in a cohort of 92 individuals.Results and discussionOur results showed that three out seven miRNAs, namely hsa-miR-200c-3p, hsa-miR-144-3p and hsa-miR-221-3p were differentially expressed in plasma-derived exosomes from melanoma patients and controls. Furthermore, the expression of the three miRNAs may be a promising ancillary tool as a melanoma biomarker, even for discriminating between nevi and melanoma.

Santa Catarina é o maior produtor de mel do Brasil, com um número de apicultores estimado em 15 mil famílias, que praticam a apicultura economicamente. Destas, 90% são constituídas de pequenos agricultores que complementam suas rendas através dos diversos produtos apícolas, especialmente o mel, considerado o melhor do Brasil, já tendo sido premiado como o melhor do mundo. Contando com um plantel de 400 mil colméias, que produzem aproximadamente 8 mil toneladas de mel por ano, esta atividade gera uma renda superior a 20 milhões de reais na economia estadual, eqüivalendo a aproximadamente 1.300 reais/família/ano. No entanto, a produtividade do mel catarinense ainda é baixa – cerca de 15kg de mel/colméia/ano.

Observando-se as populações crioulas de cebola cultivadas pelos produtores do Alto Vale do Itajaí em Santa Catarina, foi possível constatar que a variabilidade genética sempre esteve presente em grande escala neste germoplasma, principalmente para os caracteres de qualidade que atendem aos interesses do Mercosul. O atributo qualidade é fundamental quando se trata de competitividade econômica, e em cebola normalmente está associado à uniformidade dos bulbos em relação ao tamanho, formato, cor, sabor, firmeza e integridade da película externa, sanidade, ausência de brotação e enraizamento, e embalagem em alguns casos. Assim a grande alternativa que se apresentou para a cebolicultura catarinense foi melhorar a qualidade e a produtividade, o que foi iniciado pelo melhoramento genético, com o desenvolvimento de novas cultivares adaptadas às condições de cultivo do Estado.

A utilização de plantas medicinais e fitoterápicos vem sendo recomendada no Brasil para atender às demandas da Atenção Primária à Saúde. Assim, esta pesquisa investiga o conhecimento e o uso de plantas medicinais por idosos usuários de Estratégias de Saúde da Família de Palmeira das Missões, RS. A coleta de dados foi feita através de entrevistas semiestruturadas, em 2019, com 70 pessoas, que mencionaram 67 espécies. Os respondentes têm idade média de 69,9 anos, e houve predomínio de mulheres, pessoas com hipertensão arterial e/ou diabetes e que combinam medicamentos com plantas medicinais. As 15 plantas com maior Valor de Uso da espécie (UVs) foram analisadas quanto aos usos recomendados e efeitos adversos. Marcela (Achyrocline satureioides), camomila (Matricharia chamomilla) e boldo (Plectranthus barbatus) foram as espécies mais citadas. Os usos medicinais predominantes estão associados aos sistemas digestivo, respiratório, circulatório, urinário, endócrino (metabólico e nutricional) e estado psicológico. Os resultados demonstram a importância das plantas medicinais na vida das comunidades, evidenciando-se a necessidade de os serviços de atenção à saúde ofertarem orientações sobre o uso seguro e adequado das espécies. Palavras-chave: Atenção primária à saúde; plantas medicinais; etnobotânica; fitoterapia; valor de uso.