Flow dynamics of Byrd Glacier, East Antarctica

This is the published version. Copyright 2014Force-balance calculations on Byrd Glacier, East Antarctica, reveal large spatial variations in the along-flow component of driving stress with corresponding sticky spots that are stationary over time. On the large scale, flow resistance is partitioned between basal (∼80%) and lateral (∼20%) drag. Ice flow is due mostly to basal sliding and concentrated vertical shear in the basal ice layers, indicating the bed is at or close to the pressure-melting temperature. There is a significant component of driving stress in the across-flow direction resulting in nonzero basal drag in that direction. This is an unrealistic result and we propose that there are spatial variations of bed features resulting in small-scale flow disturbances. The grounding line of Byrd Glacier is located in a region where the bed slopes upward. Nevertheless, despite a 10% increase in ice discharge between December 2005 and February 2007, following drainage of two subglacial lakes in the catchment area, the position of the grounding line has not retreated significantly and the glacier has decelerated since then. During the speed-up event, partitioning of flow resistance did not change, suggesting the increase in velocity was caused by a temporary decrease in basal effective pressure

Evo-devo of human adolescence: beyond disease models of early puberty

Despite substantial heritability in pubertal development, much variation remains to be explained, leaving room for the influence of environmental factors to adjust its phenotypic trajectory in the service of fitness goals. Utilizing evolutionary development biology (evo-devo), we examine adolescence as an evolutionary life-history stage in its developmental context. We show that the transition from the preceding stage of juvenility entails adaptive plasticity in response to energy resources, other environmental cues, social needs of adolescence and maturation toward youth and adulthood. Using the evolutionary theory of socialization, we show that familial psychosocial stress fosters a fast life history and reproductive strategy rather than early maturation being just a risk factor for aggression and delinquency. Here we explore implications of an evolutionary-developmental-endocrinological-anthropological framework for theory building, while illuminating new directions for research

Anti-proliferative activity of the quassinoid NBT-272 in childhood medulloblastoma cells

BACKGROUND: With current treatment strategies, nearly half of all medulloblastoma (MB) patients die from progressive tumors. Accordingly, the identification of novel therapeutic strategies remains a major goal. Deregulation of c-MYC is evident in numerous human cancers. In MB, over-expression of c-MYC has been shown to correlate with anaplasia and unfavorable prognosis. In neuroblastoma – an embryonal tumor with biological similarities to MB – the quassinoid NBT-272 has been demonstrated to inhibit cellular proliferation and to down-regulate c-MYC protein expression. METHODS: To study MB cell responses to NBT-272 and their dependence on the level of c-MYC expression, DAOY (wild-type, empty vector transfected or c-MYC transfected), D341 (c-MYC amplification) and D425 (c-MYC amplification) human MB cells were used. The cells were treated with different concentrations of NBT-272 and the impact on cell proliferation, apoptosis and c-MYC expression was analyzed. RESULTS: NBT-272 treatment resulted in a dose-dependent inhibition of cellular proliferation (IC50 in the range of 1.7 – 9.6 ng/ml) and in a dose-dependent increase in apoptotic cell death in all human MB cell lines tested. Treatment with NBT-272 resulted in up to 90% down-regulation of c-MYC protein, as demonstrated by Western blot analysis, and in a significant inhibition of c-MYC binding activity. Anti-proliferative effects were slightly more prominent in D341 and D425 human MB cells with c-MYC amplification and slightly more pronounced in c-MYC over-expressing DAOY cells compared to DAOY wild-type cells. Moreover, treatment of synchronized cells by NBT-272 induced a marked cell arrest at the G1/S boundary. CONCLUSION: In human MB cells, NBT-272 treatment inhibits cellular proliferation at nanomolar concentrations, blocks cell cycle progression, induces apoptosis, and down-regulates the expression of the oncogene c-MYC. Thus, NBT-272 may represent a novel drug candidate to inhibit proliferation of human MB cells in vivo

M.c. Dougherty, Becoming a Woman in Rural Black Culture

Stearns Deborah Jay. M.c. Dougherty, Becoming a Woman in Rural Black Culture. In: L'Homme, 1979, tome 19 n°3-4. Les catégories de sexe en anthropologie sociale. pp. 245-248

Discovery of ligands for a novel target, the human telomerase RNA, based on flexible-target virtual screening and NMR

11 pags, 7 figs, 3 tabs. -- Supporting information is available at the Publisher's webThe human ribonucleoprotein telomerase is a validated anticancer drug target, and hTR-P2b is a part of the human telomerase RNA (hTR) essential for its activity. Interesting ligands that bind hTR-P2b were identified by iteratively using a tandem structure-based approach: docking of potential ligands from small databases to hTR-P2b via the program MORDOR, which permits flexibility in both ligand and target, with subsequent NMR screening of high-ranking compounds. A high percentage of the compounds tested experimentally were found via NMR to bind to the U-rich region of hTR-P2b; most have MW < 500 Da and are from different compound classes, and several possess a charge of 0 or +1. Of the 48 ligands identified, 24 exhibit a decided preference to bind hTR-P2b RNA rather than A-site rRNA and 10 do not bind A-site rRNA at all. Binding affinity was measured by monitoring RNA imino proton resonances for some of the compounds that showed hTR binding preference. © 2008 American Chemical Society.This work was partially supported by Grant AI46967 from the National Institutes of Health and by a grant from the UCSF Prostate Cancer Center Development Research Program