Relationship Between Cardiovascular Disease Knowledge and Race/Ethnicity, Education, and Weight Status

Background: Inadequate cardiovascular disease (CVD) knowledge has been cited to account for the imperfect decline in CVD among women over the last 2 decades. Hypothesis: Due to concerns that at-risk women might not know the leading cause of death or symptoms of a heart attack, our goal was to assess the relationship between CVD knowledge race/ethnicity, education, and body mass index (BMI). Methods: Using a structured questionnaire, CVD knowledge, socio-demographics, risk factors, and BMI were evaluated in 681 women. Results: Participants included Hispanic, 42.1% (n = 287); non-Hispanic white (NHW), 40.2% (n = 274); non-Hispanic black (NHB), 7.3% (n = 50); and Asian/Pacific Islander (A/PI), 8.7% (n = 59). Average BMI was 26.3 ± 6.1 kg/m2. Hypertension was more frequent among overweight (45%) and obese (62%) than normal weight (24%) (P 12 years (both P < 0.0001). Conclusions: Effective prevention strategies for at-risk populations need to escalate CVD knowledge and awareness among the undereducated and minority women

Over-Expression of DSCAM and COL6A2 Cooperatively Generates Congenital Heart Defects

A significant current challenge in human genetics is the identification of interacting genetic loci mediating complex polygenic disorders. One of the best characterized polygenic diseases is Down syndrome (DS), which results from an extra copy of part or all of chromosome 21. A short interval near the distal tip of chromosome 21 contributes to congenital heart defects (CHD), and a variety of indirect genetic evidence suggests that multiple candidate genes in this region may contribute to this phenotype. We devised a tiered genetic approach to identify interacting CHD candidate genes. We first used the well vetted Drosophila heart as an assay to identify interacting CHD candidate genes by expressing them alone and in all possible pairwise combinations and testing for effects on rhythmicity or heart failure following stress. This comprehensive analysis identified DSCAM and COL6A2 as the most strongly interacting pair of genes. We then over-expressed these two genes alone or in combination in the mouse heart. While over-expression of either gene alone did not affect viability and had little or no effect on heart physiology or morphology, co-expression of the two genes resulted in ≈50% mortality and severe physiological and morphological defects, including atrial septal defects and cardiac hypertrophy. Cooperative interactions between DSCAM and COL6A2 were also observed in the H9C2 cardiac cell line and transcriptional analysis of this interaction points to genes involved in adhesion and cardiac hypertrophy. Our success in defining a cooperative interaction between DSCAM and COL6A2 suggests that the multi-tiered genetic approach we have taken involving human mapping data, comprehensive combinatorial screening in Drosophila, and validation in vivo in mice and in mammalian cells lines should be applicable to identifying specific loci mediating a broad variety of other polygenic disorders

Genome-Wide SNP-genotyping array to study the evolution of the human pathogen Vibrio vulnificus Biotype 3

Vibrio vulnificus is an aquatic bacterium and an important human pathogen. Strains Of V. vulnificus are classified into three different biotypes. The newly emerged biotype 3 has been found to be clonal and restricted to Israel. In the family Vibrionaceae , horizontal gene transfer is the main mechanism responsible for the emergence of new pathogen groups. To better understand the evolution of the bacterium, and in particular to trace the evolution of biotype 3, we performed genome-wide SNP genotyping of 254 clinical and environmental V. vulnificus isolates with worldwide distribution recovered over a 30-year period, representing all phylogeny groups. A custom single-nucleotide polymorphism (SNP) array implemented on the Illumina GoldenGate platform was developed based on 570 SNPs randomly distributed throughout the genome. In general, the genotyping results divided the V. vulnificus species into three main phylogenetic lineages and an additional subgroup, clade B, consisting of environmental and clinical isolates from Israel. Data analysis suggested that 69% of biotype 3 SNPs are similar to SNPs from clade B, indicating that biotype 3 and clade B have a common ancestor. The rest of the biotype 3 SNPs were scattered along the biotype 3 genome, probably representing multiple chromosomal segments that may have been horizontally inserted into the clade B recipient core genome from other phylogroups or bacterial species sharing the same ecological niche. Results emphasize the continuous evolution of V. vulnificus and support the emergence of new pathogenic groups within this species as a recurrent phenomenon. Our findings contribute to a broader understanding of the evolution of this human pathogen

Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome

SPTBN1 mutations cause a neurodevelopmental syndrome characterized by intellectual disability, language and motor delays, autism, seizures and other features. The variants disrupt beta II-spectrin function and disturb cytoskeletal organization and dynamics. SPTBN1 encodes beta II-spectrin, the ubiquitously expressed beta-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal beta II-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays;mild to severe intellectual disability;autistic features;seizures;behavioral and movement abnormalities;hypotonia;and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect beta II-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of beta II-spectrin in the central nervous system

Plasmonic DNA: Towards Genetic Diagnosis Chips

"Plasmonics and DNA" special issueInternational audienc

At the Interfaces of the Hydrologic Sciences: Connecting Water, Elements, Ecosystems, and People Through the Major Contributions of Dr. Emily Bernhardt

In this paper, we describe the major contributions of Professor Emily Bernhardt to the hydrologic sciences. Dr. Bernhardt’s work addresses how carbon, nutrient, and contaminant dynamics respond to a wide range of environmental perturbations that alter hydrologic dynamics within and connectivity among ecosystems. Her research leverages intensive and extensive field sampling, experimental manipulations, macroscale data harmonization and exploration, and continental to global-scale synthesis activities to uncover key drivers and patterns of the impacts human perturbations have on water and elemental cycles. Dr. Bernhardt’s research program is defined by her ability to ask questions and use approaches that explicitly consider connectivity and interfaces in a variety of ways. Here, we highlight significant contributions from Dr. Bernhardt’s work, organized by connectivity, interfaces, and interactions among and across (1) elemental cycles, (2) ecosystems, (3) watersheds, (4) scales, and (5) disciplines. We conclude with a section on Dr. Bernhardt’s impact on the hydrologic sciences and beyond through her exceptional dedication to mentorship, engagement, and service