Regulation of Human Cystic Fibrosis Transmembrane Conductance Regulator (Cftr) by Serum- and Glucocorticoid-Inducible Kinase (Sgk1)

Background: Serum- and glucocorticoid-inducible kinase-1 (SGK1) increases CFTR Cl currents in Xenopus oocytes by an unknown mechanism. Because SGK increases the plasma membrane expression of other ion channels, the goal of this paper was to test the hypothesis that SGK1 stimulates CFTR Cl currents by increasing the number of CFTR Cl channels in the plasma membrane. Methods: CFTR Cl currents were measured in Xenopus oocytes by the two-electrode voltage clamp technique, and CFTR in the plasma membrane was determined by laser scanning confocal microscopy. Results: wt-SGK1 stimulated CFTR Cl currents by 42% and increased the amount of CFTR in the plasma membrane by 35%. A kinase-dead SGK mutant (K127N) had a dominant-negative effect on CFTR, reducing CFTR Cl currents by 38%. In addition, deletion of the C-terminal PDZ-interacting motif (SGK1-ΔSFL) increased CFTR Cl currents by 108%. Thus, SGK1-ΔSFL was more effective than wt-SGK1 in stimulating CFTR Cl currents. Neither wt-SGK nor the K127N mutant had any effect on Cl currents in oocytes when expressed alone in the absence of CFTR. Conclusion: SGK1 stimulates CFTR Cl currents in Xenopus oocytes by increasing the number of channels in the plasma membrane. Moreover, the effect of SGK may be mediated by protein-protein interactions involving the PDZ interacting motif

Superconducting Cosmc Strings and Primordial Magnetic Fields

We consider grand unified theories with superconducting cosmic strings and which admit the mechanism for generating primordial magnetic fields recently discussed by Vachaspati. We show that these models are severely constrained by cosmological arguments. Quite generically, either stable springs or vortons will form. Provided the mass per unit length of the strings is sufficiently large, these stable configurations will overclose the Universe.Comment: BROWN-HET-830, 14 pages, use phyzz

Dialogue Modelling and the Remit of Core Grammar

In confronting the challenge of providing formal models of dialogue, with its plethora of fragments and rich variation in modes of context-dependent construal, it might seem that linguists face two types of methodological choice: either (a) conversation employs dialogue-specific mechanisms, for which a grammar specific to such activity must be constructed; or (b) variation arises due to independent parsing/production systems which invoke a process-neutral grammar. However, as dialogue research continues to develop, there are intermediate possibilities, and in this paper we discuss the approach developed within Dynamic Syntax (DS, Kempson et al. 2001, Cann et al. 2005), a grammar framework within which, not only the parser, but indeed “syntax” itself are just a single mechanism allowing the progressive construction of semantic representations in context. Here we take as a case study the set of phenomena classifiable as clarifications, reformulations, fragment requests and corrections accompanied by extensions, and argue that though these may seem to be uniquely constitutive of dialogue, they are grounded in the mechanisms of apposition equivalently usable in monologue for presenting reformulations, extensions, self-corrections etc

Impaired perception of facial motion in autism spectrum disorder

Copyright: © 2014 O’Brien et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Facial motion is a special type of biological motion that transmits cues for socio-emotional communication and enables the discrimination of properties such as gender and identity. We used animated average faces to examine the ability of adults with autism spectrum disorders (ASD) to perceive facial motion. Participants completed increasingly difficult tasks involving the discrimination of (1) sequences of facial motion, (2) the identity of individuals based on their facial motion and (3) the gender of individuals. Stimuli were presented in both upright and upside-down orientations to test for the difference in inversion effects often found when comparing ASD with controls in face perception. The ASD group’s performance was impaired relative to the control group in all three tasks and unlike the control group, the individuals with ASD failed to show an inversion effect. These results point to a deficit in facial biological motion processing in people with autism, which we suggest is linked to deficits in lower level motion processing we have previously reported

Measuring the State of Disaster Philanthropy 2015: Data to Drive Decisions

Jointly produced by Foundation Center and the Center for Disaster Philanthropy, Measuring the State of Disaster Philanthropy 2015: Data to Drive Decisions analyzes funding trends for disasters and humanitarian crises in 2013. In addition to examining U.S. foundation funding, this second annual report integrates other disaster-related funding data, including bilateral and multilateral aid, corporate giving, and online giving, to paint a more detailed picture of how institutional philanthropy is situated within the broader disaster funding landscape. Collectively, this report, along with the dashboard and mapping platform, provides donors, practitioners, and other stakeholders with in-depth information on funding flows for disasters and humanitarian crises. Explore more at disasterphilanthropy.org

ISSCR standards for the use of human stem cells in basic research.

The laboratory culture of human stem cells seeks to capture a cellular state as an in vitro surrogate of a biological system. For the results and outputs from this research to be accurate, meaningful, and durable, standards that ensure reproducibility and reliability of the data should be applied. Although such standards have been previously proposed for repositories and distribution centers, no widely accepted best practices exist for laboratory research with human pluripotent and tissue stem cells. To fill that void, the International Society for Stem Cell Research has developed a set of recommendations, including reporting criteria, for scientists in basic research laboratories. These criteria are designed to be technically and financially feasible and, when implemented, enhance the reproducibility and rigor of stem cell research

The Grizzly, November 15, 2001

Second Annual Operation Christmas Child a Success Thanks to the Holiday Spirit in UC Students • Ribbon Cutting Ceremony Held to Dedicate the New Floy Lewis Bakes Field House • With a New Face Comes Changes at Zack\u27s • SASA Sponsors Bizarre Turkey Contest • Ursinus Students Help in Election Campaign • Career Services Helps Misdirected Students • Great American Smokeout Turns Twenty-Five • Opinions: Thanksgiving not Really a Holiday at Ursinus; Zack\u27s: Think Twice About That Price; Take Three Advil: The Universal Cure from the Wellness Center • Cheesecake Factory far from a Cheesy Experience • The Glass Menagerie is Coming to Ursinus! • Open Mic Night Steals the Stage! • Olevian Hall: The First Women\u27s Dormitory at Ursinus • Advantages and Disadvantages of Working at the Mall this Holiday Season • Club Review • The Real Deal About Birth Control • UC Swimming Left to Choke on the Wake of Swarthmore • The New, Buffer, Women\u27s Basketball Team • Four Athletes Attempt to Save Passengers of Flight 93 • Ursinus Performs Exorcism on Devils • Going Deep with the Ursinus Scuba Diving Team • Dougherty Headed to Nationalshttps://digitalcommons.ursinus.edu/grizzlynews/1501/thumbnail.jp

A transient disruption of fibroblastic transcriptional regulatory network facilitates trans-differentiation

Transcriptional Regulatory Networks (TRNs) coordinate multiple transcription factors (TFs) in concert to maintain tissue homeostasis and cellular function. The re-establishment of target cell TRNs has been previously implicated in direct trans-differentiation studies where the newly introduced TFs switch on a set of key regulatory factors to induce de novo expression and function. However, the extent to which TRNs in starting cell types, such as dermal fibroblasts, protect cells from undergoing cellular reprogramming remains largely unexplored. In order to identify TFs specific to maintaining the fibroblast state, we performed systematic knockdown of 18 fibroblast-enriched TFs and analyzed differential mRNA expression against the same 18 genes, building a Matrix-RNAi. The resulting expression matrix revealed seven highly interconnected TFs. Interestingly, suppressing four out of seven TFs generated lipid droplets and induced PPARG and CEBPA expression in the presence of adipocyte-inducing medium only, while negative control knockdown cells maintained fibroblastic character in the same induction regime. Global gene expression analyses further revealed that the knockdown-induced adipocytes expressed genes associated with lipid metabolism and significantly suppressed fibroblast genes. Overall, this study reveals the critical role of the TRN in protecting cells against aberrant reprogramming, and demonstrates the vulnerability of donor cell's TRNs, offering a novel strategy to induce transgene-free trans-differentiations