HLBS-PopOmics: an online knowledge base to accelerate dissemination and implementation of research advances in population genomics to reduce the burden of heart, lung, blood, and sleep disorders.

Recent dramatic advances in multiomics research coupled with exponentially increasing volume, complexity, and interdisciplinary nature of publications are making it challenging for scientists to stay up-to-date on the literature. Strategies to address this challenge include the creation of online databases and warehouses to support timely and targeted dissemination of research findings. Although most of the early examples have been in cancer genomics and pharmacogenomics, the approaches used can be adapted to support investigators in heart, lung, blood, and sleep (HLBS) disorders research. In this article, we describe the creation of an HLBS population genomics (HLBS-PopOmics) knowledge base as an online, continuously updated, searchable database to support the dissemination and implementation of studies and resources that are relevant to clinical and public health practice. In addition to targeted searches based on the HLBS disease categories, cross-cutting themes reflecting the ethical, legal, and social implications of genomics research; systematic evidence reviews; and clinical practice guidelines supporting screening, detection, evaluation, and treatment are also emphasized in HLBS-PopOmics. Future updates of the knowledge base will include additional emphasis on transcriptomics, proteomics, metabolomics, and other omics research; explore opportunities for leveraging data sets designed to support scientific discovery; and incorporate advanced machine learning bioinformatics capabilities.

Advancement of Women in the Biomedical Workforce: Insights for Success.

Women continue to face unique barriers in the biomedical workforce that affect their advancement and retention in this field. The National Institutes of Health (NIH) formed the Working Group on Women in Biomedical Careers to address these issues. Through the efforts of the working group, the NIH funded 14 research grants to identify barriers or to develop and/or test interventions to support women in the biomedical workforce. The grantees that were funded through this endeavor later established the grassroots Research Partnership on Women in Biomedical Careers, and they continue to conduct research and disseminate information on the state of women in academic medicine. This Commentary explores the themes introduced in a collection of articles organized by the research partnership and published in this issue of Academic Medicine. The authors highlight the role that government plays in the advancement of women in academic medicine and highlight the findings put forward in this collection.

Eccentric muscle challenge shows osteopontin polymorphism modulation of muscle damage.

A promoter polymorphism of the osteopontin (OPN) gene (rs28357094) has been associated with multiple inflammatory states, severity of Duchenne muscular dystrophy (DMD) and muscle size in healthy young adults. We sought to define the mechanism of action of the polymorphism, using allele-specific in vitro reporter assays in muscle cells, and a genotype-stratified intervention in healthy controls. In vitro reporter constructs showed the G allele to respond to estrogen treatment, whereas the T allele showed no transcriptional response. Young adult volunteers (n = 187) were enrolled into a baseline study, and subjects with specific rs28357094 genotypes enrolled into an eccentric muscle challenge intervention [n = 3 TT; n = 3 GG/GT (dominant inheritance model)]. Female volunteers carrying the G allele showed significantly greater inflammation and increased muscle volume change as determined by magnetic resonance imaging T1- and T2-weighted images after eccentric challenge, as well as greater decrement in biceps muscle force. Our data suggest a model where the G allele enables enhanced activities of upstream enhancer elements due to loss of Sp1 binding at the polymorphic site. This results in significantly greater expression of the pro-inflammatory OPN cytokine during tissue remodeling in response to challenge in G allele carriers, promoting muscle hypertrophy in normal females, but increased damage in DMD patients.

In vitro cultivation of Microphallus turgidus (Trematoda: Microphallidae) from metacercaria to ovigerous adult with continuation of the life cycle in the laboratory.

In vitro cultivation of trematodes would aid studies on the basic biology of the parasites and the development of chemotherapies and vaccines. Our goal was to measure the in vitro survival and maturation of metacercariae of Microphallus turgidus under different culture conditions. Metacercariae of M. turgidus from grass shrimp (Palaemonetes pugio) were excysted and cultured in humidified air at 37 degrees C in RPMI-1640 medium supplemented with 20% calf, chicken, or horse serum. Deposition of eggs was greatest in media containing horse or calf serum. Worms survived longest at 37 C, but did not produce greater numbers of eggs than worms cultured in RPMI-1640-supplemented horse serum at 42 degrees C. Most eggs deposited in vitro (>80%) were normal in shape and, after incubation for 10 days at 30 degrees C in brackish water, approximately 30% of them contained miracidia. Eighteen percent of hydrobiid snails (Spurwinkia salsa) fed these eggs shed cercariae 5-6 wk later. The cercariae were infective to grass shrimp (Palaemonetes vulgaris) and developed into metacercariae. This study is significant because it is the second instance in which a digenean, and the first time that a microphallid, has been demonstrated to develop in vitro from metacercariae into adult worms capable of producing infective eggs.