No abstract

Recently identified trace amine receptors are potential direct targets for drugs of abuse, including amphetamine and 3,4-methylenedioxymethamphetamine (MDMA). We cloned fulllength rhesus monkey trace amine receptor 1 (rhTA 1 ) that was 96% homologous to human TA 1 . The trace amines tyramine and ␤-phenylethylamine (PEA) and the monoamine transporter substrates (Ϯ)-amphetamine and (Ϯ)-MDMA stimulated cAMP accumulation in rhTA 1 -expressing cell lines, as measured by a cAMP response element-luciferase assay. Cocaine did not stimulate cAMP accumulation in rhTA 1 cells, but it blocked [ 3 H]PEA transport mediated by the dopamine transporter. Cotransfection with the human dopamine transporter enhanced PEA-, amphetamine-, and MDMA-mediated rhTA 1 receptor activation, but it diminished tyramine activation of rhTA 1 . Because TA 1 (EGFP-rhTA 1 chimera) was largely intracellular, conceivably the dopamine transporter can facilitate access of specific agonists to intracellular TA 1 . rhTA 1 mRNA expression was detected in rhesus monkey substantia nigra, implying that TA 1 may be colocalized with the dopamine transporter in dopamine neurons. In summary, primate TA 1 receptors are direct targets of trace amines, amphetamine, and MDMA. These receptors could also be indirect targets of amphetamine, MDMA, and cocaine through modification of monoamine transporter function. Conceivably, rhTA 1 receptors may be located on pre-or postsynaptic membranes. Interference with the carrier function of monoamine transporters with a consequent rise of extracellular levels of trace amines could activate these receptors. The cloning of a highly homologous TA 1 from rhesus monkey and demonstration that rhTA 1 receptors are activated by drugs of abuse, indicate that nonhuman primates may serve to model physiological and pharmacological TA 1 -mediated responses in humans.

Racial/ethnic disparities in breast cancer mortality continue to widen but genomic studies rarely interrogate breast cancer in diverse populations. Through genome, exome, and RNA sequencing, we examined the molecular features of breast cancers using 194 patients from Nigeria and 1037 patients from The Cancer Genome Atlas (TCGA). Relative to Black and White cohorts in TCGA, Nigerian HR + /HER2 − tumors are characterized by increased homologous recombination deficiency signature, pervasive TP53 mutations, and greater structural variation—indicating aggressive biology. GATA3 mutations are also more frequent in Nigerians regardless of subtype. Higher proportions of APOBEC-mediated substitutions strongly associate with PIK3CA and CDH1 mutations, which are underrepresented in Nigerians and Blacks. PLK2, KDM6A, and B2M are also identified as previously unreported significantly mutated genes in breast cancer. This dataset provides novel insights into potential molecular mechanisms underlying outcome disparities and lay a foundation for deployment of precision therapeutics in underserved populations.

A lifestyle intervention to prevent diabetes in at-risk women in community health centers in China is feasible and acceptable but effect sizes were small.

As Britain's imperial and colonial ambitions intensified toward the end of the nineteenth century, the preservation of white European health in tropical climates became an increasingly important concern. Since at least the seventeenth century, the "tropics" had been seen as spaces holding vast potential wealth but also death and disease. To combat these deadly but desirable landscapes, the British built a considerable commodity culture around the preservation of white European health, and for many, tropical clothing was one of the most important and essential items in their "kits." This article investigates the composition and use of such clothing in relation to British ideas of health and hygiene in tropical climates. First, it considers debates that ensued over the best material--wool, cotton, linen, silk, or a combination of these materials--and the role of "black" skin and local practice in the development of tropical clothing. Second, it demonstrates the importance of location in any discussion of tropical medicine and hygiene, and the tension and ambiguity that still surrounded British ideas of health and hygiene in the tropical colonies. Third, it argues that tropical clothing was important in the maintenance of climatic etiologies despite advances in parasitology and sanitary science. Finally, it considers the relationship of tropical clothing to the formation of a unique colonial identity. To British men and women embarking for any number of tropical destinations, proper clothing was not a banal and mundane component of their outfitting. For many, the clothing signified a departure from the safe and "civil" climes of Britain for adventure in the expanding tropical empire.