Representing Americans Employed Abroad: The Extraterritorial Application Of Federal And State Anti-Discrimination Laws

More than two million American citizens work in civilian jobs outside of the United States

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Medical Burden in Late-Life Bipolar and Major Depressive Disorders

Background: Elderly patients with bipolar disorder have been found to have higher mortality than those with major depressive disorder. The authors compare medical burden in elderly patients with bipolar disorder with that in those with major depressive disorder. Methods: Fifty-four patients with bipolar I or II disorder who were 60 years of age and older were equated l-to-2 to 108 patients with nonpsychotic, major depressive disorder according to age, sex, race, and lifetime duration of mood disorder illness. Variables examined included the following: Cumulative Illness Rating Scale for Geriatrics (CIRS-G) total scores, body mass index (BMI), and CIRS-G subscale scores. Results: Compared with patients with major depressive disorder, patients with bipolar disorder had similar levels of general medical comorbidity on the CIRS-G total score and number of systems affected but higher BMI. After controlling for multiple comparisons, the endocrine/metabolic and respiratory subscale scores on the CIRS-G were higher for patients with bipolar disorder. Conclusion: Although overall medical burden appears comparable in elderly patients with bipolar and those with major depressive disorder, patients with bipolar disorder have higher BMI and greater burden of endocrine/metabolic and respiratory disease. © 2008 American Association for Geriatric Psychiatry

Pedagogy of Science Teaching Tests: Formative assessments of science teaching orientations

A critical aspect of teacher education is gaining pedagogical content knowledge of how to teach science for conceptual understanding. Given the time limitations of college methods courses, it is difficult to touch on more than a fraction of the science topics potentially taught across grades K-8, particularly in the context of relevant pedagogies. This research and development work centers on constructing a formative assessment resource to help expose pre-service teachers to a greater number of science topics within teaching episodes using various modes of instruction. To this end, 100 problem-based, science pedagogy assessment items were developed via expert group discussions and pilot testing. Each item contains a classroom vignette followed by response choices carefully crafted to include four basic pedagogies (didactic direct, active direct, guided inquiry, and open inquiry). The brief but numerous items allow a substantial increase in the number of science topics that pre-service students may consider. The intention is that students and teachers will be able to share and discuss particular responses to individual items, or else record their responses to collections of items and thereby create a snapshot profile of their teaching orientations. Subsets of items were piloted with students in pre-service science methods courses, and the quantitative results of student responses were spread sufficiently to suggest that the items can be effective for their intended purpose

A β-Peptide Agonist of the GLP-1 Receptor, a Class B GPCR

[Image: see text] Previous work has shown that certain β(3)-peptides can effectively mimic the side chain display of an α-helix and inhibit interactions between proteins, both in vitro and in cultured cells. Here we describe a β(3)-peptide analog of GLP-1, CC-3(Act), that interacts with the GLP-1R extracellular domain (nGLP-1R) in vitro in a manner that competes with exendin-4 and induces GLP-1R-dependent cAMP signaling in cultured CHO-K1 cells expressing GLP-1R