Research Data MANTRA (or Management Training) is a labour of love. It has been an integral part of the University of Edinburgh's Research Data Management (RDM) programme since 2012. The staff at EDINA and Data Library at the University of Edinburgh has been curating this resource, based on internal and external feedback and has just published its fourth release since 2011. MANTRA is an open, web-based training course intended for self-paced learning by PhD students and early career researchers or others who manage digital data as part of a research project. It informs about good practice in research data management with real life stories. MANTRA’s approach is to be fun, relevant, useful, interactive and timely (FRUIT!). Librarians’ training needs are catered for through a companion resource, the DIY RDM Training Kit for Librarians.
An Analysis of Data Management Plans in University of Illinois National Science Foundation Grant Proposals
The University of Illinois at Urbana-Champaign (UIUC) Library conducted an analysis of 1,260 Data Management Plans (DMPs) submitted in National Science Foundation (NSF) proposals from July 2011 through November 2013. Each DMP was assigned controlled vocabulary and keyword terms which summarized the proposed data management mechanisms for storing and sharing data. A database composed of the proposal’s title, PI (Principal Investigator), PI’s department and college, NSF grant number, funded status, assigned DMP vocabulary, and keyword terms was constructed. As of May 2014, a total of 298 of these UIUC proposals had been funded by the NSF. Our analysis of this sample revealed no significant statistical differences in proposed data storage and reuse venues between funded and unfunded proposals. However, there was a statistically higher frequency of use of the campus institutional repository and disciplinary repositories in proposals submitted after October 2012.
This chapter in Cancer Concepts: A Guidebook for the Non-Oncologist is about cancers of the endometrium and uterus, including the epidemiology, risk factors, diagnosis, genetic risk, histology, grading and type categorization, management, and prognosis.
The Transitions RTC and Thresholds Young Adult Program (YAP) developed a supported employment/ education model based on the Individual Placement and Support1 model (IPS) and added a vocational peer mentor for emerging adults with serious mental health conditions (SMHC). This model is still being developed, but preliminary research has identified several guidelines that could be helpful for others thinking about implementing peer mentors into their vocational services for emerging adults with SMHC.
To review the impact of sleep, stress, and/or depression on postpartum weight retention. METHODS:
We searched three electronic databases, PubMed, ISI Web of Science, and PsycInfo. Studies were included if they were published between January 1990 and September 2013 in English, measured sleep, stress, and/or depression in the postpartum period, and assessed the association of these factors with postpartum weight retention. Two reviewers reviewed included articles and rated study quality using a modified version of the Downs and Black scale. RESULTS:
Thirteen studies met our pre-defined eligibility criteria, reporting on 9 study samples. Two were cross-sectional studies and eleven were longitudinal studies. The study sample size ranged from 74 to 37,127. All four studies examining short sleep duration and postpartum weight retention reported a positive association. The four studies examining postpartum stress and weight retention reported non-significant associations only. Of 7 studies examining postpartum depression and weight retention, 3 reported non-significant associations, and 4 reported positive associations. CONCLUSION:
Research investigating the impact of postpartum sleep, stress, depression on weight retention is limited. Future longitudinal studies are needed.
This is the December 2014 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
Autophagy is a conserved process that delivers components of the cytoplasm to lysosomes for degradation. The E1 and E2 enzymes encoded by Atg7 and Atg3 are thought to be essential for autophagy involving the ubiquitin-like protein Atg8. Here, we describe an Atg7- and Atg3-independent autophagy pathway that facilitates programmed reduction of cell size during intestine cell death. Although multiple components of the core autophagy pathways, including Atg8, are required for autophagy and cells to shrink in the midgut of the intestine, loss of either Atg7 or Atg3 function does not influence these cellular processes. Rather, Uba1, the E1 enzyme used in ubiquitylation, is required for autophagy and reduction of cell size. Our data reveal that distinct autophagy programs are used by different cells within an animal, and disclose an unappreciated role for ubiquitin activation in autophagy.
Mesenchymal stem cells utilize CXCR4-SDF-1 signaling for acute, but not chronic, trafficking to gastric mucosal inflammation
BACKGROUND: Helicobacter infection is the main risk factor in developing gastric cancer. Mesenchymal stem cells (MSCs) are non-hematopoietic stromal cells, which are able to differentiate into different cell lineages. MSC contribute to cancer development by forming the tumor directly, contributing to the microenvironment, or by promoting angiogenesis and metastasis. CXCR4/SDF-1 axis is used by MSC in trafficking, homing, and engraftment at chronic inflammation sites, and plays an important role in tumorigenesis.
AIM: To determine if CXCR4 receptor has a role in MSC contribution to the development of Helicobacter-mediated gastric cancer.
METHODS: SDF-1 and CXCR4 expression in mouse gastric mucosa in the setting of acute and chronic inflammation was measured using RT-PCR. Mouse culture-adapted MSC express CXCR4. Wild-type C57BL/6 mice infected with Helicobacter felis for 6 months or controls were given IV injections of CXCR4 knock-down MSC. Animals were followed for another 4 months. Homing of MSC in the stomach was quantified using RT-PCR. MSC differentiation into gastric epithelia lineages was analyzed using immunohistochemistry and fluorescent in situ hybridization.
RESULTS: CXCR4 and SDF-1 are both upregulated in the settings of Helicobacter-induced chronic gastric inflammation. CXCR4 is fully required for homing of MSC to the stomach in acute gastric inflammation, but only partially in Helicobacter-induced gastric cancer. MSC lead to gastric intraepithelial neoplasia as early as 10 months of Helicobacter infection.
CONCLUSIONS: Our results show that MSC have a tumorigenic effect by promoting an accelerated form of gastric cancer in mice. The engraftment of MSC in chronic inflammation is only partially CXCR4-dependent.
BACKGROUND: There are limited data informing the optimal treatment strategy for acute myocardial infarction in the oldest old (aged > /= 85 years). The study aim was to examine whether decade-long increases in guideline-based cardiac medication use mediate declines in post-discharge mortality among oldest old patients hospitalized with acute myocardial infarction.
METHODS: The study sample included 1137 patients aged > /= 85 years hospitalized in 6 biennial periods between 1997 and 2007 for acute myocardial infarction at all 11 greater Worcester, Massachusetts, medical centers. We examined trends in 90-day survival after hospital discharge and guideline-based medication use (aspirin, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, lipid-lowering agents) for acute myocardial infarction during hospitalization and at discharge. Sequential multivariable Cox regression models examined the relationship among guideline-based medication use, study year, and 90-day post-discharge survival rates.
RESULTS: Patients hospitalized between 2003 and 2007 experienced higher 90-day survival rates than those hospitalized between 1997 and 2001 (69.1% vs 59.8%, P < .05). Between 1997 and 2007, the average number of guideline-based medications prescribed at discharge increased significantly (1.8 to 2.9, P < .001). The unadjusted hazard ratio for 90-day post-discharge mortality in 2003-2007 compared with 1997-2001 was 0.73 (95% confidence interval, 0.60-0.89); after adjustment for patient characteristics and guideline-based cardiac medication use, this relationship was no longer significant (hazard ratio, 1.26; 95% confidence interval, 1.00-1.58).
CONCLUSIONS: Between 1997 and 2007, 90-day survival improved among a population-based sample of patients aged > /= 85 years hospitalized for acute myocardial infarction. This encouraging trend was explained by increased use of guideline-based medications.
BACKGROUND: Evidence about the beneficial effects of statins on reducing infections is accumulating. Identifying ways to reduce infection risk in patients with cirrhosis is important because of increased mortality risk and costs associated with infections.
AIM: To estimate the extent to which statin use prolongs time to infection among patients with cirrhosis.
METHODS: We identified Veterans with cirrhosis, but without decompensation (n = 19,379) using US Veterans Health Administration data from 2001 to 2009. New users of statins were identified and propensity matched to non-users and users of other cholesterol-lowering medications (1:1 matching). The cohort was followed up for hospitalisations with infections. Cox regression models with time-varying exposures provided estimates of adjusted hazard ratios (HR) and 95% confidence intervals (CI).
RESULTS: New statin use was present among 13% of VA patients with cirrhosis without decompensation. Overall, 12.4% of patients developed a serious infection, and 0.1% of patients died. In the propensity-matched sample, statin users experienced hospitalisations with infections at a rate 0.67 less than non-users (95% Confidence Interval: 0.47-0.95).
CONCLUSIONS: Infections are a major concern among cirrhotic patients and have the potential to seriously impact both life expectancy and quality of life. Statin use may potentially reduce the risk of infections among patients with cirrhosis.
Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons
The recently identified GGGGCC repeat expansion in the noncoding region of C9ORF72 is the most common pathogenic mutation in patients with frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS). We generated a human neuronal model and investigated the pathological phenotypes of human neurons containing GGGGCC repeat expansions. Skin biopsies were obtained from two subjects who had > 1,000 GGGGCC repeats in C9ORF72 and their respective fibroblasts were used to generate multiple induced pluripotent stem cell (iPSC) lines. After extensive characterization, two iPSC lines from each subject were selected, differentiated into postmitotic neurons, and compared with control neurons to identify disease-relevant phenotypes. Expanded GGGGCC repeats exhibit instability during reprogramming and neuronal differentiation of iPSCs. RNA foci containing GGGGCC repeats were present in some iPSCs, iPSC-derived human neurons and primary fibroblasts. The percentage of cells with foci and the number of foci per cell appeared to be determined not simply by repeat length but also by other factors. These RNA foci do not seem to sequester several major RNA-binding proteins. Moreover, repeat-associated non-ATG (RAN) translation products were detected in human neurons with GGGGCC repeat expansions and these neurons showed significantly elevated p62 levels and increased sensitivity to cellular stress induced by autophagy inhibitors. Our findings demonstrate that key neuropathological features of FTD/ALS with GGGGCC repeat expansions can be recapitulated in iPSC-derived human neurons and also suggest that compromised autophagy function may represent a novel underlying pathogenic mechanism.
The thymus is required for T cell differentiation; a process that depends on which antigens are encountered by thymocytes, the environment surrounding the differentiating cells, and the thymic architecture. These features are altered by local infection of the thymus and by the inflammatory mediators that accompany systemic infection. Although once believed to be an immune privileged site, it is now known that antimicrobial responses are recruited to the thymus. Resolving infection in the thymus is important because chronic persistence of microbes impairs the differentiation of pathogen-specific T cells and diminishes resistance to infection. Understanding how these mechanisms contribute to disease susceptibility, particularly in infants with developing T cell repertoires, requires further investigation.
Cardiac expression of human type 2 iodothyronine deiodinase increases glucose metabolism and protects against doxorubicin-induced cardiac dysfunction in male mice
Altered glucose metabolism in the heart is an important characteristic of cardiovascular and metabolic disease. Because thyroid hormones have major effects on peripheral metabolism, we examined the metabolic effects of heart-selective increase in T3 using transgenic mice expressing human type 2 iodothyronine deiodinase (D2) under the control of the alpha-myosin heavy chain promoter (MHC-D2). Hyperinsulinemic-euglycemic clamps showed normal whole-body glucose disposal but increased hepatic insulin action in MHC-D2 mice as compared to wild-type (WT) littermates. Insulin-stimulated glucose uptake in heart was not altered, but basal myocardial glucose metabolism was increased by more than two-fold in MHC-D2 mice. Myocardial lipid levels were also elevated in MHC-D2 mice, suggesting an overall up-regulation of cardiac metabolism in these mice. The effects of doxorubicin (DOX) treatment on cardiac function and structure were examined using M-mode echocardiography. DOX treatment caused a significant reduction in ventricular fractional shortening and resulted in more than 50% death in WT mice. In contrast, MHC-D2 mice showed increased survival rate after DOX treatment, and this was associated with a six-fold increase in myocardial glucose metabolism and improved cardiac function. Myocardial activity and expression of AMPK, GLUT1, and Akt were also elevated in MHC-D2 and WT mice following DOX treatment. Thus, our findings indicate an important role of thyroid hormone in cardiac metabolism and further suggest a protective role of glucose utilization in DOX-mediated cardiac dysfunction.
OBJECTIVE: This study examined gender differences in smoking and quitting among individuals diagnosed with schizophrenia in Korea. In addition, the study investigated differences in caffeine use by gender and smoking status. METHOD: An anonymous self-report survey was conducted with psychiatric inpatients. RESULTS: Compared to males, females were less likely to be current smokers (P < .001) and more likely to be former smokers (P < .01). Females were also less likely to be daily caffeine users (P < .001). Having more years of education (P < .05) and higher nicotine dependence scores (P<.05) were associated with decreased odds of intending to quit smoking, whereas having more previous quit attempts (P<.01) was associated with increased odds. These findings were significant even after adjusting for gender. Smokers were more likely to be daily caffeine users (P < .001) than their non-smoking counterparts. CONCLUSION: Nurses in Korea should play an active role in tobacco control for patients with schizophrenia by providing cessation counseling and educating the effect of caffeine use on cigarette consumption, while tailoring the service to gender differences found in this study.
Despite their predominance in the nervous system, the precise ways in which glial cells develop and contribute to overall neural function remain poorly defined in any organism. Investigations in simple model organisms have identified remarkable morphological, molecular, and functional similarities between invertebrate and vertebrate glial subtypes. Invertebrates like Drosophila and Caenorhabditis elegans offer an abundance of tools for in vivo genetic manipulation of single cells or whole populations of glia, ease of access to neural tissues throughout development, and the opportunity for forward genetic analysis of fundamental aspects of glial cell biology. These features suggest that invertebrate model systems have high potential for vastly improving the understanding of glial biology. This review highlights recent work in Drosophila and other invertebrates that reveal new insights into basic mechanisms involved in glial development.
We describe two unreported types of congenital disorders of glycosylation (CDG) which are caused by mutations in different isoforms of the catalytic subunit of the oligosaccharyltransferase (OST). Each isoform is encoded by a different gene (STT3A or STT3B), resides in a different OST complex and has distinct donor and acceptor substrate specificities with partially overlapping functions in N-glycosylation. The two cases from unrelated consanguineous families both show neurologic abnormalities, hypotonia, intellectual disability, failure to thrive and feeding problems. A homozygous mutation (c.1877T > C) in STT3A causes a p.Val626Ala change and a homozygous intronic mutation (c.1539 + 20G > T) in STT3B causes the other disorder. Both mutations impair glycosylation of a GFP biomarker and are rescued with the corresponding cDNA. Glycosylation of STT3A- and STT3B-specific acceptors is decreased in fibroblasts carrying the corresponding mutated gene and expression of the STT3A (p.Val626Ala) allele in STT3A-deficient HeLa cells does not rescue glycosylation. No additional cases were found in our collection or in reviewing various databases. The STT3A mutation significantly impairs glycosylation of the biomarker transferrin, but the STT3B mutation only slightly affects its glycosylation. Additional cases of STT3B-CDG may be missed by transferrin analysis and will require exome or genome sequencing.
A 7-month-old girl was evaluated for V-shaped ridging of the fingernails consistent with chevron nails. Chevron nails are a normal variant in the pediatric population that is frequently outgrown. This case nicely demonstrates this normal finding that has so rarely been reported in the literature.
Hox genes encode transcription factors with important roles during embryogenesis and tissue differentiation. Genetic analyses initially demonstrated that interfering with Hox genes has profound effects on the specification of cell identity, suggesting that Hox proteins regulate very specific sets of target genes. However, subsequent biochemical analyses revealed that Hox proteins bind DNA with relatively low affinity and specificity. Furthermore, it became clear that a given Hox protein could activate or repress transcription, depending on the context. A resolution to these paradoxes presented itself with the discovery that Hox proteins do not function in isolation, but interact with other factors in complexes. The first such "cofactors" were members of the Extradenticle/Pbx and Homothorax/Meis/Prep families. However, the list of Hox-interacting proteins has continued to grow, suggesting that Hox complexes contain many more components than initially thought. Additionally, the activities of the various components and the exact mechanisms whereby they modulate the activity of the complex remain puzzling. Here, we review the various proteins known to participate in Hox complexes and discuss their likely functions. We also consider that Hox complexes of different compositions may have different activities and discuss mechanisms whereby Hox complexes may be switched between active and inactive states.
One, two, or three? Constructs of the brief pain inventory among patients with non-cancer pain in the outpatient setting
CONTEXT: Either a two-factor representation (pain intensity and interference) or a three-factor representation (pain intensity, activity interference, and affective interference) of the modified Brief Pain Inventory (BPI) is appropriate among cancer patients.
OBJECTIVES: To evaluate the extent to which a three-factor representation (pain intensity, activity interference, and affective interference) is appropriate for BPI among patients with noncancer pain seen in an outpatient setting.
METHODS: We conducted a prospective, multicenter, observational, nonrandomized study using patient pain registry data from outpatient settings. Seven hundred forty-one patients with acute episodes of noncancer pain requiring treatment with a prescription medication containing oxycodone immediate-release on an as-needed basis for at least five days participated. Baseline measurements included the modified BPI pain intensity (right now, average, and worst in 24 hours) and pain interference with general activities, walking, work, mood, relations with others, sleep, and life enjoyment. Confirmatory factor analysis was conducted for the overall sample and among postoperative patients (n = 133), patients with back and neck pain (n = 202), patients with arthritis (n = 148), and patients with injury or trauma (n = 204).
RESULTS: Both the two-factor and three-factor models were statistically better than the one-factor model (P < 0.05), with the two-factor model performing better than the three-factor model. Configural invariance, but not metric invariance by patient cohort group was demonstrated.
CONCLUSION: Consistent with analyses among cancer patients, a two-factor representation of BPI is appropriate for noncancer patients seen in an ambulatory setting. This work lends additional support for the psychometric properties of BPI. All rights reserved.
A systematic review of cancer GWAS and candidate gene meta-analyses reveals limited overlap but similar effect sizes
Candidate gene and genome-wide association studies (GWAS) represent two complementary approaches to uncovering genetic contributions to common diseases. We systematically reviewed the contributions of these approaches to our knowledge of genetic associations with cancer risk by analyzing the data in the Cancer Genome-wide Association and Meta Analyses database (Cancer GAMAdb). The database catalogs studies published since January 1, 2000, by study and cancer type. In all, we found that meta-analyses and pooled analyses of candidate genes reported 349 statistically significant associations and GWAS reported 269, for a total of 577 unique associations. Only 41 (7.1%) associations were reported in both candidate gene meta-analyses and GWAS, usually with similar effect sizes. When considering only noteworthy associations (defined as those with false-positive report probabilities