Targeting a phospho-STAT3-miRNAs pathway improves vesicular hepatic steatosis in an in vitro and in vivo model

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. Although genetic predisposition and epigenetic factors contribute to the development of NAFLD, our understanding of the molecular mechanism involved in the pathogenesis of the disease is still emerging. Here we investigated a possible role of a microRNAs-STAT3 pathway in the induction of hepatic steatosis. Differentiated HepaRG cells treated with the fatty acid sodium oleate (fatty dHepaRG) recapitulated features of liver vesicular steatosis and activated a cell-autonomous inflammatory response, inducing STAT3-Tyrosine-phosphorylation. With a genome-wide approach (Chromatin Immunoprecipitation Sequencing), many phospho-STAT3 binding sites were identified in fatty dHepaRG cells and several STAT3 and/or NAFLD-regulated microRNAs showed increased expression levels, including miR-21. Innovative CARS (Coherent Anti-Stokes Raman Scattering) microscopy revealed that chemical inhibition of STAT3 activity decreased lipid accumulation and deregulated STAT3-responsive microRNAs, including miR-21, in lipid overloaded dHepaRG cells. We were able to show in vivo that reducing phospho-STAT3-miR-21 levels in C57/BL6 mice liver, by long-term treatment with metformin, protected mice from aging-dependent hepatic vesicular steatosis. Our results identified a microRNAs-phosphoSTAT3 pathway involved in the development of hepatic steatosis, which may represent a molecular marker for both diagnosis and therapeutic targeting

Genome-wide identification of direct HBx genomic targets

Background: The Hepatitis B Virus (HBV) HBx regulatory protein is required for HBV replication and involved in HBV-related carcinogenesis. HBx interacts with chromatin modifying enzymes and transcription factors to modulate histone post-translational modifications and to regulate viral cccDNA transcription and cellular gene expression. Aiming to identify genes and non-coding RNAs (ncRNAs) directly targeted by HBx, we performed a chromatin immunoprecipitation sequencing (ChIP-Seq) to analyse HBV recruitment on host cell chromatin in cells replicating HBV. Results: ChIP-Seq high throughput sequencing of HBx-bound fragments was used to obtain a high-resolution, unbiased, mapping of HBx binding sites across the genome in HBV replicating cells. Protein-coding genes and ncRNAs involved in cell metabolism, chromatin dynamics and cancer were enriched among HBx targets together with genes/ncRNAs known to modulate HBV replication. The direct transcriptional activation of genes/miRNAs that potentiate endocytosis (Ras-related in brain (RAB) GTPase family) and autophagy (autophagy related (ATG) genes, beclin-1, miR-33a) and the transcriptional repression of microRNAs (miR-138, miR-224, miR-576, miR-596) that directly target the HBV pgRNA and would inhibit HBV replication, contribute to HBx-mediated increase of HBV replication. Conclusions: Our ChIP-Seq analysis of HBx genome wide chromatin recruitment defined the repertoire of genes and ncRNAs directly targeted by HBx and led to the identification of new mechanisms by which HBx positively regulates cccDNA transcription and HBV replication

Whose shoulders is health research standing on? Determining the key actors and contents of the prevailing biomedical research agenda

BACKGROUND: Conflicts of interest in biomedical research can influence research results and drive research agendas away from public health priorities. Previous agenda-setting studies share two shortfalls: they only account for direct connections between academic institutions and firms, as well as potential bias based on researchers' personal beliefs. This paper's goal is to determine the key actors and contents of the prevailing health and biomedical sciences (HBMS) research agenda, overcoming these shortfalls. METHODS: We performed a bibliometric and lexical analysis of 95,415 scientific articles published between 1999 and 2018 in the highest impact factor journals within HBMS, using the Web of Science database and the CorText platform. HBMS's prevailing knowledge network of institutions was proxied with network maps where nodes represent affiliations and edges the most frequent co-authorships. The content of the prevailing HBMS research agenda was depicted through network maps of prevalent multi-terms found in titles, keywords, and abstracts. RESULTS: The HBMS research agendas of large private firms and leading academic institutions are intertwined. The prevailing HBMS agenda is mostly based on molecular biology (40% of the most frequent multi-terms), with an inclination towards cancer and cardiovascular research (15 and 8% of the most frequent multi-terms, respectively). Studies on pathogens and biological vectors related to recent epidemics are marginal (1% of the most frequent multi-terms). Content of the prevailing HBMS research agenda prioritizes research on pharmacological intervention over research on socio-environmental factors influencing disease onset or progression and overlooks, among others, the study of infectious diseases. CONCLUSIONS: Pharmaceutical corporations contribute to set HBMS's prevailing research agenda, which is mainly focused on a few diseases and research topics. A more balanced research agenda, together with epistemological approaches that consider socio-environmental factors associated with disease spreading, could contribute to being better prepared to prevent and treat more diverse pathologies and to improve overall health outcomes

Academic dependency: the influence of the prevailing international biomedical research agenda on Argentina’s CONICET

Background The prevailing health and biomedical sciences (HBMS) research agenda, not only determined by leading academic institutions but also by large pharmaceutical companies, has been shown to prioritize the exploration of novel pharmacological interventions over the study of the socio-environmental factors influencing illness onset and progression. The aim of this investigation is to quantitatively explore whether and to what extent the prevailing international HBMS research agenda and the key actors setting this agenda influence research in non-core countries. Methods We used the Web of Science database and the CorText platform to proxy the HBMS research agenda of a prestigious research institution from Latin America: Argentina’s National Research Council (CONICET). We conducted a bibliometric and lexical analysis of 16,309 HBMS academic articles whereby CONICET was among the authors' affiliations. The content of CONICET’s agenda was represented through co-occurrence network maps of the most frequent concatenation of terms found in titles, keywords, and abstracts. We compared our findings with previous reports on the international HBMS research agenda. Results In line with the results previously reported for the prevailing international agenda, we found that terms linked to molecular biology and cancer research hegemonize CONICET’s HBMS research agenda, whereas terms connecting HBMS research with socio-environmental cues are marginal. However, we also found differences with the international agenda: CONICET's HBMS agenda shows a marginal presence of terms linked to translational medicine, while terms associated with categories such as pathogens, plant research, agrobiotechnology, and food industry are more represented than in the prevailing agenda. Conclusions CONICET’s HBMS research agenda shares topics, priorities, and methodologies with the prevailing HBMS international research agenda. However, CONICET's HBMS research agenda is internally heterogeneous, appearing to be mostly driven by a combination of elements that not only reflect academic dependency (the adoption of the prevailing research agenda by non-core research institutions) but also local economic determinants associated with Argentina’s place in the international division of labor as an exporter of primary goods

Erratum: Whose shoulders is health research standing on? Determining the key actors and contents of the prevailing biomedical research agenda (PLoS ONE (2021) 16:4 (e0249661) DOI: 10.1371/journal.pone.0249661)

The following information is missing from the Funding statement: This study was supported by the Canadian Social Sciences and Humanities Research Council (SSHRC)

A Toolchain Architecture for Condition Monitoring Using the Eclipse Arrowhead Framework

Condition Monitoring is one of the most critical applications of the Internet of Things (IoT) within the context of Industry 4.0. Current deployments typically present interoperability and management issues, requiring human intervention along the engineering process of the systems; in addition, the fragmentation of the IoT landscape, and the adoption of poor architectural solutions often make it difficult to integrate third-party devices in a seamless way. In this paper, we tackle these issues by proposing a tool-driven architecture that supports heterogeneous sensor management through well-established interoperability solutions for the IoT domain, i.e. the Eclipse Arrowhead framework and the recent Web of Things (WoT) standard released by the W3C working group. We deploy the architecture in a real Structural Health Monitoring (SHM) scenario, which validates each developed tool and demonstrates the increased automation derived from their combined usage

Information Literacy Needs Open Access or: Open Access is not Only for Researchers

The Open Access was initially (blandly) conceived in view not only of researchers but also of lay readers, then this perspective slowly faded out. The Information Literacy movement wants to teach citizens how to arrive at trustable information but the amount of paywalled knowledge is still big. So, their lines of development are somehow complementary: Information Literacy needs Open Access for the citizens to freely access high quality information while Open Access truly fulfils its scope when it is conceived and realized not only for the researchers (an aristocratic view which was the initial one) but for the whole society