The Biomolecular Interaction Network Database (BIND) (http://bind.ca) archives biomolecular interaction, reaction, complex and pathway information. Our aim is to curate the details about molecular interactions that arise from published experimental research and to provide this information, as well as tools to enable data analysis, freely to researchers worldwide. BIND data are curated into a comprehensive machinereadable archive of computable information and provides users with methods to discover interactions and molecular mechanisms. BIND has worked to develop new methods for visualization that amplify the underlying annotation of genes and proteins to facilitate the study of molecular interaction networks. BIND has maintained an open database policy since its inception in 1999. Data growth has proceeded at a tremendous rate, approaching over 100 000 records. New services provided include a new BIND Query and Submission interface, a Standard Object Access Protocol service and the Small Molecule Interaction Database (http://smid.blueprint.org) that allows users to determine probable small molecule binding sites of new sequences and examine conserved binding residues. INTRODUCTIONIn light of the vast scientific resources made available through genomics, the science of deciphering molecular mechanisms is expanding rapidly. Scientists who once hunted for disease genes or sought to distinguish key concepts in evolution are now turning their attention to the details of molecular assembly and mechanism to further understand medicine and the key concepts underlying biology. The Biomolecular Interaction Network Database (BIND) was designed to store complete information about molecular assembly through a database structure in order to archive interactions and reactions arising from biopolymers (protein, RNA and DNA), as well as small molecules, lipids and carbohydrates. Detailed information about molecular mechanism, such as the chemical product(s) of an enzymatic reaction, can be encoded in BIND. The underlying ontology of the BIND database is chemistry, and as such, BIND is capable of storing information about molecular interactions to atomic resolution. The taxonomic scope of BIND is

Esteban Gonzalez Burchard and colleagues explore how making medical research more diverse would aid not only social justice but scientific quality and clinical effectiveness, too.

Summary Points Health disparities persist across race/ethnicity for the majority of Healthy People 2010 health indicators. Most physicians and scientists are informed by research extrapolated from a largely homogenous population, usually White and male. A growing proportion of Americans are not fully benefiting from clinical and biomedical advances since racial and ethnic minorities make up nearly 40% of the U.S. population. Ignoring the racial/ethnic diversity of the U.S. population is a missed scientific opportunity to fully understand the factors that lead to disease or health. U.S. biomedical research and study populations must better reflect the country's changing demographics. Adequate representation of diverse populations in scientific research is imperative as a matter of social justice, economics, and science.

Purpose of review One-third of the world’s population has hypertension and it is responsible for almost 50% of deaths from stroke or coronary heart disease. These statistics do not distinguish salt-sensitive from salt-resistant hypertension or include normotensives who are salt-sensitive even though salt sensitivity, independent of blood pressure, is a risk factor for cardiovascular and other diseases, including cancer. This review describes new personalized diagnostic tools for salt sensitivity. Recent findings The relationship between salt intake and cardiovascular risk is not linear, but rather fits a J-shaped curve relationship. Thus, a low-salt diet may not be beneficial to everyone and may paradoxically increase blood pressure in some individuals. Current surrogate markers of salt sensitivity are not adequately sensitive or specific. Tests in the urine that could be surrogate markers of salt sensitivity with a quick turn-around time include renal proximal tubule cells, exosomes, and microRNA shed in the urine. Summary Accurate testing of salt sensitivity is not only laborious but also expensive, and with low patient compliance. Patients who have normal blood pressure but are salt-sensitive cannot be diagnosed in an office setting and there are no laboratory tests for salt sensitivity. Urinary surrogate markers for salt sensitivity are being developed.

The lack of minority data, despite a collaboration of eight universities and 13 individual laboratories, highlights the urgent need for a dedicated national effort to prioritize diversity in research. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations.

Rationale: Adverse effects of exposures to ambient air pollution on lung function are well documented, but evidence in racial/ethnic minority children is lacking.Objectives: To assess the relationship between air pollution and lung function in minority children with asthma and possible modification by global genetic ancestry. Methods:The study population consisted of 1,449 Latino and 519 African American children with asthma from five different geographical regions in the mainland United States and Puerto Rico. We examined five pollutants (particulate matter <10 mm and <2.5 mm in diameter, ozone, nitrogen dioxide, and sulfur dioxide), derived from participant residential history and ambient air monitoring data, and assessed over several time windows. We fit generalized additive models for associations between pollutant exposures and lung function parameters and tested for interaction terms between exposures and genetic ancestry. Measurements and Main Results:A 5 mg/m 3 increase in average lifetime particulate matter less than or equal to 2.5 mm in diameter exposure was associated with a 7.7% decrease in FEV 1 (95% confidence interval = 211.8 to 23.5%) in the overall study population. Global genetic ancestry did not appear to significantly modify these associations, but percent African ancestry was a significant predictor of lung function.Conclusions: Early-life particulate exposures were associated with reduced lung function in Latino and African American children with asthma. This is the first study to report an association between exposure to particulates and reduced lung function in minority children in which racial/ethnic status was measured by ancestry-informative markers.

The key factors underlying the development of allergic diseases—the propensity for a minority of individuals to develop dysfunctional responses to harmless environmental molecules—remain undefined. We report a pathway of immune counter-regulation that suppresses the development of aeroallergy and shrimp-induced anaphylaxis. In mice, signaling through epithelially expressed dectin-1 suppresses the development of type 2 immune responses through inhibition of interleukin-33 (IL-33) secretion and the subsequent recruitment of IL-13–producing innate lymphoid cells. Although this homeostatic pathway is functional in respiratory epithelial cells from healthy humans, it is dramatically impaired in epithelial cells from asthmatic and chronic rhinosinusitis patients, resulting in elevated IL-33 production. Moreover, we identify an association between a single-nucleotide polymorphism (SNP) in the dectin-1 gene loci and reduced pulmonary function in two cohorts of asthmatics. This intronic SNP is a predicted eQTL (expression quantitative trait locus) that is associated with reduced dectin-1 expression in human tissue. We identify invertebrate tropomyosin, a ubiquitous arthropod-derived molecule, as an immunobiologically relevant dectin-1 ligand that normally serves to restrain IL-33 release and dampen type 2 immunity in healthy individuals. However, invertebrate tropomyosin presented in the context of impaired dectin-1 function, as observed in allergic individuals, leads to unrestrained IL-33 secretion and skewing of immune responses toward type 2 immunity. Collectively, we uncover a previously unrecognized mechanism of protection against allergy to a conserved recognition element omnipresent in our environment.

An extensive literature links circadian irregularities and/or sleep abnormalities to mood disorders. Despite the strong genetic component underlying many mood disorders, however, previous genetic associations between circadian clock gene variants and major depressive disorder (MDD) have been weak. We applied a combined molecular/functional and genetic association approach to circadian gene polymorphisms in sex-stratified populations of control subjects and case subjects suffering from MDD. This approach identified significant sex-dependent associations of common variants of the circadian clock genes hClock, hPer3 and hNpas2 with major depression and demonstrated functional effects of these polymorphisms on the expression or activity of the hCLOCK and hPER3 proteins, respectively. In addition, hCLOCK expression is affected by glucocorticoids, consistent with the sex-dependency of the genetic associations and the modulation of glucocorticoid-mediated stress response, providing a mechanism by which the circadian clock controls outputs that may affect psychiatric disorders. We conclude that genetic polymorphisms in circadian genes (especially hClock and hPer3, where functional assays could be tested) influence risk of developing depression in a sex- and stress-dependent manner. These studies support a genetic connection between circadian disruption and mood disorders, and confirm a key connection between circadian gene variation and major depression.