Requirement of Estrogen Receptor-α in Insulin-like Growth Factor-1 (IGF-1)-induced Uterine Responses and in Vivo Evidence for IGF-1/Estrogen Receptor Cross-talk

In the uterus insulin-like growth factor-1 (IGF-1) signaling can be initiated by estradiol acting through its nuclear receptor (estrogen receptor (ER)) to stimulate the local synthesis of IGF-1. Conversely, in vitro studies have demonstrated that estradiol-independent ER transcriptional activity can be induced by IGF-1 signaling, providing evidence for a cross-talk mechanism between IGF-1 and ER. To investigate whether ER alpha is required for uterine responses to IGF-1 in vivo, both wild-type (WT) and ER alpha knockout (alpha ERKO) mice were administered IGF-1, and various uterine responses to IGF-1 were compared. In both WT and alpha ERKO mice, IGF-1 treatment resulted in phosphorylation of uterine IGF-1 receptor (IGF-1R) and formation of an IGF-1R/insulin receptor substrate-1/ phosphatidylinositol 3-kinase signaling complex. In addition, IGF-1 stimulated phosphorylation of uterine Akt and MAPK in both WT and alpha ERKO mice. However, IGF-1 treatment stimulated BrdUrd incorporation and proliferating cell nuclear antigen expression in WT uteri only. To determine whether ER alpha can be activated in vivo by IGF-1 signaling, transgenic mice carrying a luciferase gene driven by two estrogen response elements (ERE-luciferase mice) were utilized. Treatment of ovariectomized ERE-luciferase mice with IGF-1 resulted in an increase in uterine luciferase activity that was attenuated in the presence of the ER antagonist ICI 182,780. Together these data demonstrate that 1) functional signaling proximal to IGF-1R is maintained in the alpha ERKO mouse uterus, 2) ER alpha is necessary for IGF-1 induction of uterine nuclear proliferative responses, and 3) cross-talk between IGF-1R and ER signaling pathways exists in vivo

Improved Standardization of Type II-P Supernovae: Application to an Expanded Sample

In the epoch of precise and accurate cosmology, cross-confirmation using a variety of cosmographic methods is paramount to circumvent systematic uncertainties. Owing to progenitor histories and explosion physics differing from those of Type Ia SNe (SNe Ia), Type II-plateau supernovae (SNe II-P) are unlikely to be affected by evolution in the same way. Based on a new analysis of 17 SNe II-P, and on an improved methodology, we find that SNe II-P are good standardizable candles, almost comparable to SNe Ia. We derive a tight Hubble diagram with a dispersion of 10% in distance, using the simple correlation between luminosity and photospheric velocity introduced by Hamuy & Pinto 2002. We show that the descendent method of Nugent et al. 2006 can be further simplified and that the correction for dust extinction has low statistical impact. We find that our SN sample favors, on average, a very steep dust law with total to selective extinction R_V<2. Such an extinction law has been recently inferred for many SNe Ia. Our results indicate that a distance measurement can be obtained with a single spectrum of a SN II-P during the plateau phase combined with sparse photometric measurements.Comment: ApJ accepted version. Minor change

Point of View: The future of graduate and postdoctoral training in the biosciences

This article summarizes the outcomes of the second national conference on the Future of Bioscience Graduate and Postdoctoral Training. Five topics were addressed during the conference: diversity in leadership positions; mentoring; modernizing the curriculum; experiential learning; and the need for better data on trainees. The goal of the conference was to develop a consensus around these five topics and to recommend policies that can be implemented by academic and research institutions and federal funding agencies in the United States

The future of graduate and postdoctoral training in the biosciences

This article summarizes the outcomes of the second national conference on the Future of Bioscience Graduate and Postdoctoral Training. Five topics were addressed during the conference: diversity in leadership positions; mentoring; modernizing the curriculum; experiential learning; and the need for better data on trainees. The goal of the conference was to develop a consensus around these five topics and to recommend policies that can be implemented by academic and research institutions and federal funding agencies in the United States