Integrative Network Analysis of Predicted miRNA-Targets Regulating Expression of Immune Response Genes in Bovine Coronavirus Infection.

Bovine coronavirus (BCoV) infection that causes disease outbreaks among farm animals, resulting in significant economic losses particularly in the cattle industry, has the potential to become zoonotic. miRNAs, which are short non-coding segments of RNA that inhibits the expression of their target genes, have been identified as potential biomarkers and drug targets, though this potential in BCoV remains largely unknown. We hypothesize that certain miRNAs could simultaneously target multiple genes, are significantly conserved across many species, thereby demonstrating the potential to serve as diagnostic or therapeutic tools for bovine coronavirus infection. To this end, we utilized different existing and publicly available computational tools to conduct system analysis predicting important miRNAs that could affect BCoV pathogenesis. Eleven genes including CEBPD, IRF1, TLR9, SRC, and RHOA, significantly indicated in immune-related pathways, were identified to be associated with BCoV, and implicated in other coronaviruses. Of the 70 miRNAs predicted to target the identified genes, four concomitant miRNAs (bta-miR-11975, bta-miR-11976, bta-miR-22-3p, and bta-miR-2325c) were found. Examining the gene interaction network suggests IL-6, IRF1, and TP53 as key drivers. Phylogenetic analysis revealed that miR-22 was completely conserved across all 14 species it was searched against, suggesting a shared and important functional role. Functional annotation and associated pathways of target genes, such as positive regulation of cytokine production, IL-6 signaling pathway, and regulation of leukocyte differentiation, indicate the miRNAs are major participants in multiple aspects of both innate and adaptive immune response. Examination of variants evinced a potentially deleterious SNP in bta-miR-22-3p and an advantageous SNP in bta-miR-2325c. Conclusively, this study provides new insight into miRNAs regulating genes responding to BCoV infection, with bta-miR-22-3p particularly indicated as a potential drug target or diagnostic marker for bovine coronavirus.

Dissecting Transcription Factor-Target Interaction in Bovine Coronavirus Infection.

Coronaviruses are RNA viruses that cause significant disease within many species, including cattle. Bovine coronavirus (BCoV) infects cattle and wild ruminants, both as a respiratory and enteric pathogen, and possesses a significant economic threat to the cattle industry. Transcription factors are proteins that activate or inhibit transcription through DNA binding and have become new targets for disease therapies. This study utilized in silico tools to identify potential transcription factors that can serve as biomarkers for regulation of BCoV pathogenesis in cattle, both for testing and treatment. A total of 11 genes were identified as significantly expressed during BCoV infection through literature searches and functional analyses. Eleven transcription factors were predicted to target those genes (AREB6, YY1, LMO2, C-Rel, NKX2-5, E47, RORAlpha1, HLF, E4BP4, ARNT, CREB). Function, network, and phylogenetic analyses established the significance of many transcription factors within the immune response. This study establishes new information on the transcription factors and genes related to host-pathogen interactome in BCoV infection, particularly transcription factors YY1, AREB6, LMO2, and NKX2, which appear to have strong potential as diagnostic markers, and YY1 as a potential target for drug therapies.

Survey of Phthalate Mitigation and Distribution in Water, Sediment, and Typha in a Fully Operational Constructed Wetland: A Pilot Study.

Wastewater treatment plants (WTTPs) contribute to anthropogenic chemical contamination through the release of treated effluent. A constructed wetland (CW) interfaced with a WTTP could potentially purify and naturalize effluent water. This pilot study aimed to acquire baseline chemical data on the fate and distribution of phthalates in the water, sediment, and vegetation (Typha spp.) of a fully operational horizontal subsurface flow CW adjoined to a WWTP in Oregon, USA. Sample collection followed the flow of water from entrance to exit of the CW. Dibutyl phthalate (DBP) and bis(2-ethylhexyl) phthalate (DEHP) were the most abundant analogs in all matrices. Results indicate reduction of phthalates in water exiting the CW. Significant concentrations of DBP, DEHP, and other water-soluble phthalates were found in the shoots of Typha, indicating plant uptake as a potentially important removal mechanism.

The NIH "BEST" programs: Institutional programs, the program evaluation, and early data.

Biomedical research training has undergone considerable change over the past several years. At its core, the goal of graduate and postdoctoral training is to provide individuals with the skills and knowledge to become outstanding scientists and expand knowledge through the scientific method. Historically, graduate school training has focused on preparation for academic positions. Increasingly, however, a shift toward preparation for a wider range of career options has emerged. This is largely because most biomedical PhD graduates do not become Principal Investigators in academic laboratories. Here we describe an National Institutes of Health Common Fund program with the major goal of culture change for biomedical research training and training that prepares individuals for a broader expanse of careers in the biomedical research enterprise. These "Broadening Experiences in Scientific Training" (BEST) awards, issued in 2012 and 2013, provided support to institutions to develop innovative approaches to achieving these goals, as a complement to traditional training. Awardees were tasked with catalyzing change at their institutions and sharing best practices across the training community. Awardees were required to participate in a cross-site evaluation that assessed the impact of BEST activities on three main areas: (a) trainee confidence and knowledge to make career decisions, (b) influence of this added activity on time in training, and (c) ability of the institutions to sustain activities deemed to be beneficial. Here we present the fundamental approach to the BEST program and early evaluative data.

Evolutionarily Conserved Long Non-coding RNA Regulates Gene Expression in Cytokine Storm During COVID-19.

Coronavirus is a family of viruses including alpha-, beta-, gamma-, delta-coronaviruses. Only alpha- and betacoronaviruses have been observed to infect humans. Past outbreaks of SARS-CoV and MERS-CoV, both betacoronavirus, are the result of a spillover from animals. Recently, a new strain termed SARS-CoV-2 emerged in December 2019 in Wuhan, China. Severe cases of COVID-19, the disease caused by SARS-CoV-2, lead to acute respiratory distress syndrome (ARDS). One contributor to the development of ARDS is cytokine storm, an overwhelming inflammatory immune response. Long non-coding RNAs (lncRNAs) are genetic regulatory elements that, among many functions, alter gene expression and cellular processes. lncRNAs identified to be pertinent in COVID-19 cytokine storm have the potential to serve as disease markers or drug targets. This project aims to computationally identify conserved lncRNAs potentially regulating gene expression in cytokine storm during COVID-19. We found 22 lncRNAs that can target 10 cytokines overexpressed in COVID-19 cytokine storm, 8 of which targeted two or more cytokine storm cytokines. In particular, the lncRNA non-coding RNA activated by DNA damage (NORAD), targeted five out of the ten identified cytokine storm cytokines, and is evolutionarily conserved across multiple species. These lncRNAs are ideal candidates for further in vitro and in vivo analysis.

NHLBI step-by-step approach to adapting cardiovascular training and education curricula for diverse audiences.

Racial and ethnic minority communities need to be involved in developing health information to ensure its cultural appropriateness, improve its acceptability, and stimulate adoption of healthy behaviors. The National Heart, Lung, and Blood Institute at the National Institutes of Health adapted a heart-health curriculum for Latinos into culturally appropriate curricula for American Indians/Alaska Natives, African Americans, and Filipinos. Lessons learned from this process can assist public health practitioners interested in adapting science-based heart-health information into practical health education messages that meet the cultural and contextual needs of diverse groups.

Role of community programs in controlling blood pressure.

Despite more than 30 years of intense activity to improve control--and more recently prevention--high blood pressure continues to be a major public health problem. Evidence-based reviews have identified best practices and quality improvement strategies to address prevention and control. Since the 1970s, community-based programs have been instrumental in raising awareness, increasing knowledge, and promoting changes in health behavior to improve blood pressure control. Most of these programs have emphasized the use of partnerships and involvement of community residents in conducting screening and referral activities, implementing clinical practice guidelines, and increasing healthy eating and physical activity. Many also have used health care team approaches, including the use of trained community health workers to deliver targeted, culturally sensitive heart health education, particularly related to the prevention of cardiovascular disease risk factors in general and high blood pressure in particular. Increased focus on implementation of evidence-based lifestyle and clinical management strategies coupled with community-based approaches may help increase blood pressure control rates within communities.