The red giants in NGC 6633 as seen with CoRoT, HARPS and SOPHIE

The open cluster NGC 6633 was observed with CoRoT in 2011 and simultaneous high-resolution spectroscopy was obtained with the SOPHIE and HARPS spectrographs. One of the four targets was not found to be a cluster member. For all stars we provide estimates of the seismic and spectroscopic parameters.Comment: Proc. of the workshop "Asteroseismology of stellar populations in the Milky Way" (Sesto, 22-26 July 2013), Astrophysics and Space Science Proceedings, (eds. A. Miglio, L. Girardi, P. Eggenberger, J. Montalban

Mcl-1 integrates the opposing actions of signaling pathways that mediate survival and apoptosis

Mcl-1 is a member of the Bcl2-related protein family that is a critical mediator of cell survival. Exposure of cells to stress causes inhibition of Mcl-1 mRNA translation and rapid destruction of Mcl-1 protein by proteasomal degradation mediated by a phosphodegron created by glycogen synthase kinase 3 (GSK3) phosphorylation of Mcl-1. Here we demonstrate that prior phosphorylation of Mcl-1 by the c-Jun N-terminal protein kinase (JNK) is essential for Mcl-1 phosphorylation by GSK3. Stress-induced Mcl-1 degradation therefore requires the coordinated activity of JNK and GSK3. Together, these data establish that Mcl-1 functions as a site of signal integration between the proapoptotic activity of JNK and the prosurvival activity of the AKT pathway that inhibits GSK3

Integrated safety profile of atacicept: an analysis of pooled data from the atacicept clinical trial programme.

OBJECTIVE: To characterize the overall safety profile of atacicept, we conducted an integrated analysis of pooled safety data from all 17 clinical studies to date. METHODS: Three data sets were used to investigate safety endpoints: a double-blind placebo-controlled set (n = 1568), an SLE set (n = 761) and a full analysis set (n = 1845; including all 17 studies). RESULTS: Of 1568 patients in the double-blind placebo-controlled-set, 30.8% received placebo, and 8.2, 24.5 and 36.5% received atacicept 25, 75 and 150 mg, respectively. Treatment-emergent adverse event (TEAE) rates (adjusted by treatment-exposure) were generally higher with atacicept vs placebo, but no consistent association was found between atacicept dose and specific TEAEs or mortality. Serious infection and serious TEAE rates were similar for atacicept and placebo. The TEAE-related discontinuation rates were higher with atacicept vs placebo (16.1 vs 10.9/100 patient-years). In the full analysis set, 11 deaths occurred during treatment. Across indications, exposure-adjusted mortality rates/100 patient-years (95% CI) were 3.60 (0.90, 14.38), 0.34 (0.05, 2.43) and 1.18 (0.49, 2.82) with atacicept 25, 75 and 150 mg, respectively, and 0.44 (0.06, 3.12) with placebo. In SLE patients, exposure-adjusted mortality rates were 1.45 (0.54, 3.87) with atacicept 150 mg and 0.78 (0.29, 2.07) across all atacicept-treated patients. No deaths occurred with atacicept 75 mg or placebo. In the SLE and double-blind placebo-controlled sets, pharmacodynamic effects of atacicept were not associated with increased infection rates. CONCLUSION: The results of this integrated safety analysis support further development and evaluation of atacicept in selected patients for whom potential benefits might outweigh risks

El tratamiento con 5azadC regula al alza el nivel de miR-375 y reprime la expresión de HPV16 E6

High-risk human papillomaviruses are the etiological agents of cervical cancer and HPV16 is the most oncogenic genotype. Immortalization and transformation of infected cells requires the overexpression of the two viral oncoproteins E6 and E7 following HPV DNA integration into the host cell genome. Integration often leads to the loss of the E2 open reading frame and the corresponding protein can no longer act as a transcriptional repressor on p97 promoter. Recently, it has been proposed that long control region methylation also contributes to the regulation of E6/E7 expression. To determine which epigenetic mechanism is involved in HPV16 early gene regulation, 5-aza-2?-deoxycytidine was used to demethylate Ca Ski and SiHa cell DNA. Decreased expression of E6 mRNA and protein levels was observed in both cell lines in an E2-independent manner. E6 repression was accompanied by neither a modification of the main cellular transcription factor expression involved in long control region regulation, nor by a modification of the E6 mRNA splicing pattern. In contrast, a pronounced upregulation of miR-375, known to destabilize HPV16 early viral mRNA, was observed. Finally, the use of miR-375 inhibitor definitively proved the involvement of miR-375 in E6 repression. These results highlight that cellular DNA methylation modulates HPV16 early gene expression and support a role for epigenetic events in high-risk HPV associated-carcinogenesis

A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress

Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent cJun NH2-terminal kinase (JNK) signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV. These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1 scaffold protein, therefore, plays a dual role in FFA signaling by coordinating upstream SRC functions together with downstream effector signaling by the JNK pathway

Statistical Modelling of Sediment Supply in Torrent Catchments of the Northern French Alps

The ability to understand and predict sediment transport in torrent catchments is a key element for the protection and prevention against the associated hazards. In this study, we collected data describing sediment supply at 100 torrential catchments in the Northern French Alps. These catchments have long records of past events and sediment supply due to debris deposition basin management enabling estimation of sediment supply frequency. The mean annual, the 10-year return period and the reference volume (i.e. the 100-year return level or the largest observed volume) of sediment supply were derived for studied torrents. We examined the relationships between sediment supply volumes and several explanatory variables using multivariate statistical analyses. Several predictive models were developed in order to estimate the sediment supply in torrents that are not equipped with sedimentation structures