Background: An increase in pandemics of zoonotic origin has led to a growing interest in using statistical prediction to identify hotspots of zoonotic emergence. However, the rare nature of pathogen emergence requires modellers to impose simplifying assumptions, which limit the model's validity. We present a novel approach to hotspot mapping that aims to improve validity by combining model-based insights with expert knowledge.
View Article and Find Full Text PDFThe Genotype-Tissue Expression (GTEx) project, sponsored by the NIH Common Fund, was established to study the correlation between human genetic variation and tissue-specific gene expression in non-diseased individuals. A significant challenge was the collection of high-quality biospecimens for extensive genomic analyses. Here we describe how a successful infrastructure for biospecimen procurement was developed and implemented by multiple research partners to support the prospective collection, annotation, and distribution of blood, tissues, and cell lines for the GTEx project.
View Article and Find Full Text PDFConverging in 2015 are the implementation of key pieces of the Affordable Care Act (ACA) and the implementation of the International Classification of Diseases, 10th edition (ICD-10). The implications for addiction care in the United States are substantial. This editorial discusses opportunities and challenges presented by these major changes to medicine and addiction specialty care.
View Article and Find Full Text PDFBackground: Guanine nucleotide exchange factors (GEFs) and their target Rho GTPases regulate cytoskeletal changes and membrane trafficking. Dynamin, a large force-generating GTPase, plays an essential role in membrane tubulation and fission in cells. Kalirin12, a neuronal RhoGEF, is found in growth cones early in development and in dendritic spines later in development.
View Article and Find Full Text PDFA large number of Rho guanine nucleotide exchange factors (GEFs) and Rho GTPase activating proteins (GAPs) are used in the CNS to activate specific Rho GTPase family members, thereby inducing various signaling mechanisms that regulate neuronal shape, growth, and plasticity, in part through their effects on the actin cytoskeleton. Kalirin is a large neuronal dual Rho GEF that activates Rac1, RhoA, and RhoG via its two Rho GEF domains. This activation, which is spatially and temporally regulated, allows Kalirin to influence neurite initiation, axonal growth, and dendritic morphogenesis.
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