Intracellular mGluR5 plays a critical role in neuropathic pain

Spinal mGluR5 is a key mediator of neuroplasticity underlying persistent pain. Although brain mGluR5 is localized on cell surface and intracellular membranes, neither the presence nor physiological role of spinal intracellular mGluR5 is established. Here we show that in spinal dorsal horn neurons >80% of mGluR5 is intracellular, of which ∼60% is located on nuclear membranes, where activation leads to sustained Ca(2+) responses. Nerve injury inducing nociceptive hypersensitivity also increases the expression of nuclear mGluR5 and receptor-mediated phosphorylated-ERK1/2, Arc/Arg3.1 and c-fos. Spinal blockade of intracellular mGluR5 reduces neuropathic pain behaviours and signalling molecules, whereas blockade of cell-surface mGluR5 has little effect. Decreasing intracellular glutamate via blocking EAAT-3, mimics the effects of intracellular mGluR5 antagonism. These findings show a direct link between an intracellular GPCR and behavioural expression in vivo. Blockade of intracellular mGluR5 represents a new strategy for the development of effective therapies for persistent pain

Single hepatocytes show persistence and transcriptional inactivity of hepatitis B

© 2020, Balagopal et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.There is no cure for the more than 270 million people chronically infected with HBV. Nucleos(t)ide analogs (NUCs), the mainstay of anti-HBV treatment, block HBV reverse transcription. NUCs do not eliminate the intranuclear covalently closed circular DNA (cccDNA), from which viral RNAs, including pregenomic RNA (pgRNA), are transcribed. A key gap in designing a cure is understanding how NUCs affect HBV replication and transcription because serum markers yield an incomplete view of intrahepatic HBV. We applied single-cell laser capture microdissection and droplet digital PCR to paired liver biopsies collected from 5 HBV/HIV-coinfected persons who took NUCs over 2-4 years. From biopsy 1 to 2, proportions of HBV-infected hepatocytes declined with adherence to NUC treatment (P < 0.05); we extrapolated that eradication of HBV will take over 10 decades with NUCs in these participants. In individual hepatocytes, pgRNA levels diminished 28- to 73-fold during NUC treatment, corresponding with decreased tissue HBV core antigen staining (P < 0.01). In 4 out of 5 participants, hepatocytes with cccDNA but undetectable pgRNA (transcriptionally inactive) were present, and these were enriched in 3 participants during NUC treatment. Further work to unravel mechanisms of cccDNA transcriptional inactivation may lead to therapies that can achieve this in all hepatocytes, resulting in a functional cure.info:eu-repo/semantics/publishedVersio

O Museu de Arte da UFC, por entre reinvenções e ressignificações: notas em tempos pandêmicos

This paper discusses the actions and projects developed by the Art Museum of the Federal University of Ceará (Mauc/UFC) during social isolation due to the COVID-19 pandemic. During that time, the museum staff began to carry out their work remotely, seeking strategies to serve the public, producing content for the digital environment, and offering professional qualification by courses and intra and interinstitutional partnerships. The actions generated new ways of articulating and making society present, strengthening previous ties and creating new ones, favoring dialogues, exchanges and new ways of being a museum. Based on a reading of institutional documents elaborated by the museum staff while carrying out the tasks during the pandemic, and other key documents on the history and management of the museum, the texts presents Mauc’s history and its management and performance policies before and during the COVID-19 pandemic. Thus, this is a multi-layered report on management policies and museum performance in times of crisis, reflecting on the challenges and experiences of a university museum to contribute with broader reflections on museology, its current dilemmas and on the role of art, culture and science in pandemic times.Este artigo tem por objetivo apresentar as ações e projetos desenvolvidos pelo Museu de Arte da Universidade Federal do Ceará (Mauc/UFC) durante o isolamento social em virtude da pandemia de covid-19. Durante este período, a equipe do museu passou a desenvolver seus trabalhos de maneira remota, buscando estratégias de atendimento ao público, de produção de conteúdo para o ambiente digital e de qualificação profissional por meio da participação em cursos e do estabelecimento de parcerias intra e interinstitucionais. As ações ensejaram novas modalidades de presentificação e articulação junto à sociedade, fortalecendo vínculos anteriores e deflagrando novos, favorecendo diálogos, intercâmbios e novas formas de ser museu. A metodologia consistiu na consulta aos documentos institucionais elaborados pela equipe na execução dos trabalhos durante este período, assim como outros documentos basilares sobre a história e a gestão do museu. A partir destas fontes, foram estruturadas a apresentação da história da instituição e de suas políticas de gestão e atuação antes e durante a pandemia de covid-19. Como resultado, este trabalho apresenta um relato multifacetado sobre políticas de gestão e atuação museal em tempos de crise, refletindo sobre os desafios e as experiências de um museu universitário na pandemia, com o objetivo de contribuir com as reflexões mais amplas sobre o campo museal, seus dilemas no contemporâneo e o papel da arte, da cultura e da ciência em tempos pandêmicos

Immunity against Ixodes scapularis Salivary Proteins Expressed within 24 Hours of Attachment Thwarts Tick Feeding and Impairs Borrelia Transmission

In North America, the black-legged tick, Ixodes scapularis, an obligate haematophagus arthropod, is a vector of several human pathogens including Borrelia burgdorferi, the Lyme disease agent. In this report, we show that the tick salivary gland transcriptome and proteome is dynamic and changes during the process of engorgement. We demonstrate, using a guinea pig model of I. scapularis feeding and B. burgdorferi transmission, that immunity directed against salivary proteins expressed in the first 24 h of tick attachment — and not later — is sufficient to evoke all the hallmarks of acquired tick-immunity, to thwart tick feeding and also to impair Borrelia transmission. Defining this subset of proteins will promote a mechanistic understanding of novel I. scapularis proteins critical for the initiation of tick feeding and for Borrelia transmission

BLOG LITERÁRIO: : O uso da tecnologia digital como instrumento de interação entre os alunos do IFC e a comunidade

O Blog é uma ferramenta de comunicação digital cuja adesão tem sido cada vez maior entre os jovens. Além de abrigar textos de gêneros diversos, nele, o blogueiro constrói-se e constrói uma relação com o leitor por meio de publicações ou posts. Levando-se em consideração o acesso, cada vez mais irrestrito, dos jovens à internet e a afinidade deles com o gênero blog, o presente projeto objetiva criar um blog literário no qual os alunos do IFC e a comunidade externa publiquem textos de tipologias diversas. Espera-se, com isto, ampliar o espaço de diálogo entre os envolvidos, bem como estimular a produção escrita em Língua portuguesa

Identification and Characterization of Ixodes scapularis Antigens That Elicit Tick Immunity Using Yeast Surface Display

Repeated exposure of rabbits and other animals to ticks results in acquired resistance or immunity to subsequent tick bites and is partially elicited by antibodies directed against tick antigens. In this study we demonstrate the utility of a yeast surface display approach to identify tick salivary antigens that react with tick-immune serum. We constructed an Ixodes scapularis nymphal salivary gland yeast surface display library and screened the library with nymph-immune rabbit sera and identified five salivary antigens. Four of these proteins, designated P8, P19, P23 and P32, had a predicted signal sequence. We generated recombinant (r) P8, P19 and P23 in a Drosophila expression system for functional and immunization studies. rP8 showed anti-complement activity and rP23 demonstrated anti-coagulant activity. Ixodes scapularis feeding was significantly impaired when nymphs were fed on rabbits immunized with a cocktail of rP8, rP19 and rP23, a hall mark of tick-immunity. These studies also suggest that these antigens may serve as potential vaccine candidates to thwart tick feeding

Extensão universitária e certificação orgânica: o caso das comunidades tradicionais no alto rio Urupadí, Maués-AM / University extension and organic certification: the case of traditional communities in the Urupadí upper river, Maués-AM

Existem diversas dificuldades para a inserção dos agricultores familiares no mercado de orgânicos, relacionados principalmente à falta de assistência técnica para a compreensão das legislações, decretos e normas, custos, capacitação e gestão da comercialização para os mercados de orgânicos. Nesse sentido, o objetivo deste estudo foi descrever a experiência de extensão universitária por meio da assistência técnica especializada em certificação orgânica e apresentar o processo de ensino-aprendizagem dos discentes envolvidos na extensão rural. O estudo foi realizado em 15 propriedades agrícolas familiares, distribuídas em oito comunidades tradicionais, localizadas na região do Alto Rio Urupadí, em Maués, no Amazonas, vinculadas à Associação dos Agricultores Familiares do Alto Urupadí (AAFAU). A metodologia utilizou uma abordagem baseada nas perspectivas epistemológicas construtivistas de Paulo Freire no estabelecimento de práticas extensionistas e participativas. Os principais resultados advindos de uma intensa campanha de extensão foram as emissões dos certificados de conformidade orgânica de 15 agricultores em 85 hectares de guaranazais certificados, e a incorporação de 17 agricultores de outras regiões de Maués com 140,5 hectares de áreas certificadas. Por fim, o estudo realizado nas comunidades rurais, a partir da extensão universitária promoveu a sustentabilidade ambiental, contribuiu com a inserção dos agricultores no mercado de orgânicos e principalmente, alavancando a formação de discentes para a extensão rural, formando novos técnicos extensionistas, sensíveis às questões ambientais, capacitados para dialogar com os agricultores locais e compreender os saberes tradicionais, impulsionando portanto, o desenvolvimento rural sustentável nessas comunidades

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.Peer reviewe