Thioredoxin-interacting protein regulates protein disulfide isomerases and endoplasmic reticulum stress

The endoplasmic reticulum (ER) is responsible for protein folding, modification, and trafficking. Accumulation of unfolded or misfolded proteins represents the condition of ER stress and triggers the unfolded protein response (UPR), a key mechanism linking supply of excess nutrients to insulin resistance and type 2 diabetes in obesity. The ER harbors proteins that participate in protein folding including protein disulfide isomerases (PDIs). Changes in PDI activity are associated with protein misfolding and ER stress. Here, we show that thioredoxin-interacting protein (Txnip), a member of the arrestin protein superfamily and one of the most strongly induced proteins in diabetic patients, regulates PDI activity and UPR signaling. We found that Txnip binds to PDIs and increases their enzymatic activity. Genetic deletion of Txnip in cells and mice led to increased protein ubiquitination and splicing of the UPR regulated transcription factor X-box-binding protein 1 (Xbp1s) at baseline as well as under ER stress. Our results reveal Txnip as a novel direct regulator of PDI activity and a feedback mechanism of UPR signaling to decrease ER stress

CANELC: constructing an e-language corpus

This paper reports on the construction of CANELC: the Cambridge and Nottingham e-language Corpus.3 CANELC is a one million word corpus of digital communication in English, taken from online discussion boards, blogs, tweets, emails and SMS messages. The paper outlines the approaches used when planning the corpus: obtaining consent; collecting the data and compiling the corpus database. This is followed by a detailed analysis of some of the patterns of language used in the corpus. The analysis includes a discussion of the key words and phrases used as well as the common themes and semantic associations connected with the data. These discussions form the basis of an investigation of how e-language operates in both similar and different ways to spoken and written records of communication (as evidenced by the BNC - British National Corpus). 3 CANELC stands for Cambridge and Nottingham e-language Corpus. This corpus has been built as part of a collaborative project between The University of Nottingham and Cambridge University Press with whom sole copyright of the annotated corpus resides. CANELC comprises one-million words of digital English taken from SMS messages, blogs, tweets, discussion board content and private/business emails. Plans to extend the corpus are under discussion. The legal dimension to corpus ‘ownership’ of some forms of unannotated data is a complex one and is under constant review. At the present time the annotated corpus is only available to authors and researchers working for CUP and is not more generally available

A Transcriptional Profile of Aging in the Human Kidney

In this study, we found 985 genes that change expression in the cortex and the medulla of the kidney with age. Some of the genes whose transcripts increase in abundance with age are known to be specifically expressed in immune cells, suggesting that immune surveillance or inflammation increases with age. The age-regulated genes show a similar aging profile in the cortex and the medulla, suggesting a common underlying mechanism for aging. Expression profiles of these age-regulated genes mark not only age, but also the relative health and physiology of the kidney in older individuals. Finally, the set of aging-regulated kidney genes suggests specific mechanisms and pathways that may play a role in kidney degeneration with age

Radio Astronomy

Contains reports on four research projects.Joint Services Electronics Program (Contract DAAB07-71-C-0300)California Institute of Technology (Contract 952568)National Aeronautics and Space Administration (Contract NAS1-10693)National Science Foundation (Grant GP-21348A#2

Increasing Colorectal Cancer Screening Among Hispanic Primary Care Patients: RE-AIM Analysis.

Context: Hispanic adults experience disparities in rates of colorectal cancer (CRC) screening. This RE-AIM analysis encompassed a multilevel decision support and navigation intervention (DSNI) for CRC screening. Interim findings were previously presented; we now aim to share the final analysis, particularly for effectiveness and implementation. Objective: Apply RE-AIM framework to a completed randomized controlled trial of a CRC screening intervention for Hispanic adults Setting: Five primary care practices Patients or Other Participants: Potential participants included a sampling frame of 2,720 screening-eligible patients, ages 50-75, Hispanic ethnicity, without history of CRC and polyps. 400 participants were enrolled. Intervention/Instrument: Decision support and navigation by a bilingual Patient Assistant (PA) as compared to a standard mailed intervention (SI) Main and Secondary Outcome Measures: 1) Reach- Study participants as compared to sampling frame 2) Effectiveness- Screening adherence 3) Adoption- Number of practice participants to complete intervention, engagement of patient and stakeholder advisory committee (PASAC) 4) Implementation- Quantitative data pertaining to patient contacts and communication of screening plan to primary care practices, Qualitative data on PA and Telephone Interviewer (TI) experiences 5) Maintenance- Health system dissemination (Pending). Results: 1) Reach- Study participants differed from the sampling frame in that ages 50-59 were overrepresented. There were no differences in race, gender, or language. 2) Effectiveness- Screening adherence was significantly increased in the DSNI group (73%) as compared to the SI group (44%) (OR=3.48, CI: 2.29-4.29,