Substrate translocation and inhibition in human dicarboxylate transporter NaDC3.

The human high-affinity sodium-dicarboxylate cotransporter (NaDC3) imports various substrates into the cell as tricarboxylate acid cycle intermediates, lipid biosynthesis precursors and signaling molecules. Understanding the cellular signaling process and developing inhibitors require knowledge of the structural basis of the dicarboxylate specificity and inhibition mechanism of NaDC3. To this end, we determined the cryo-electron microscopy structures of NaDC3 in various dimers, revealing the protomer in three conformations: outward-open C, outward-occluded C and inward-open C.

Racial, ethnic and neighborhood socioeconomic differences in incidence of dementia: A regional retrospective cohort study.

Background: Evidence on the effects of neighborhood socioeconomic disadvantage on dementia risk in racially and ethically diverse populations is limited. Our objective was to evaluate the relative extent to which neighborhood disadvantage accounts for racial/ethnic variation in dementia incidence rates. Secondarily, we evaluated the spatial relationship between neighborhood disadvantage and dementia risk.

Evaluating and Modeling Neighborhood Diversity and Health Using Electronic Health Records.

Background: Electronic health records (EHRs) provide researchers with abundant sample sizes, detailed clinical data, and other advantages for performing high-quality observational health research on diverse populations. We review and demonstrate strategies for the design and analysis of cohort studies on neighborhood diversity and health, including evaluation of the effects of race, ethnicity, and neighborhood socioeconomic position on disease prevalence and health outcomes, using localized EHR data.

Methods: Design strategies include integrating and harmonizing EHR data across multiple local health systems and defining the population(s) of interest and cohort extraction procedures for a given analysis based on the goal(s) of the study.

Biosynthesis of Largimycins in Involves Transient β-Alkylation and Cryptic Halogenation Steps Unprecedented in the Leinamycin Family.

Largimycins A1 and A2 are key members of a recently identified family of hybrid nonribosomal peptide polyketides belonging to the scarcely represented group of antitumor leinamycins. They are encoded by the gene cluster of . This cluster contains a halogenase gene and two sets of genes for the biosynthesis and incorporation of β branches at C3 and C9.