Genotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage

Annexin A2 is an abundant cellular protein that is mainly localized in the cytoplasm and plasma membrane, however a small population has been found in the nucleus, suggesting a nuclear function for the protein. Annexin A2 possesses a nuclear export sequence (NES) and inhibition of the NES is sufficient to cause nuclear accumulation. Here we show that annexin A2 accumulates in the nucleus in response to genotoxic agents including gamma-radiation, UV radiation, etoposide and chromium VI and that this event is mediated by the nuclear export sequence of annexin A2. Nuclear accumulation of annexin A2 is blocked by the antioxidant agent N-acetyl cysteine (NAC) and stimulated by hydrogen peroxide (H2O2), suggesting that this is a reactive oxygen species dependent event. In response to genotoxic agents, cells depleted of annexin A2 show enhanced phospho-histone H2AX and p53 levels, increased numbers of p53-binding protein 1 nuclear foci and increased levels of nuclear 8-oxo-2'-deoxyguanine, suggesting that annexin A2 plays a role in protecting DNA from damage. This is the first report showing the nuclear translocation of annexin A2 in response to genotoxic agents and its role in mitigating DNA damage.Natural Sciences and Engineering Research Council of Canada (NSERC); European Union [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Beatrice Hunter Cancer Research Institute; Terry Fox Foundationinfo:eu-repo/semantics/publishedVersio

Certifications of citizenship: the history, politics and materiality of identity documents in South Asian states and diasporas

Experiences in the post-partition Indian subcontinent refute the conventional expectation that the 'possession of citizenship enables the acquisition of documents certifying it' (Jayal, 2013, 71). Instead, identity papers of various types play a vital part in certifying and authenticating claims to citizenship. This is particularly important in a context where the history of state formation, continuous migration flows and the rise of right-wing majoritarian politics has created an uncertain situation for individuals deemed to be on the ‘margins’ of the state. The papers that constitute this special issue bring together a range of disciplinary perspectives in order to investigate the history, politics and materiality of identity documents, and to dismantle citizenship as an absolute and fixed notion, seeking instead to theorise the very mutable ‘hierarchies’ and ‘degrees’ of citizenship. Collectively they offer a valuable lens onto how migrants, refugees and socio-economically marginal individuals negotiate their relationship with the state, both within South Asia and in South Asian diaspora communities. This introduction examines the wider context of the complex intersections between state-issued identity documents and the nature of citizenship and draws out cross-cutting themes across the papers in this collection

The Caravan Rolls On

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68409/2/10.1177_107554707900100103.pd

A Genotype-First Approach for the Molecular and Clinical Characterization of Uncommon De Novo Microdeletion of 20q13.33

Background: Subtelomeric deletions of the long arm of chromosome 20 are rare, with only 11 described in the literature. Clinical features of individuals with these microdeletions include severe limb malformations, skeletal abnormalities, growth retardation, developmental and speech delay, mental retardation, seizures and mild, non-specific dysmorphic features. Methodology/Principal Findings: We characterized microdeletions at 20q13.33 in six individuals referred for genetic evaluation of developmental delay, mental retardation, and/or congenital anomalies. A comparison to previously reported cases of 20q13.33 microdeletion shows phenotypic overlap, with clinical features that include mental retardation, developmental delay, speech and language deficits, seizures, and behavior problems such as autistic spectrum disorder. There does not appear to be a clinically recognizable constellation of dysmorphic features among individuals with subtelomeric 20q microdeletions. Conclusions/Significance: Based on genotype-phenotype correlation among individuals in this and previous studies, we discuss several possible candidate genes for specific clinical features, including ARFGAP1, CHRNA4 and KCNQ2 and neurodevelopmental deficits. Deletion of this region may play an important role in cognitive development

Prevention of delirium (POD) for older people in hospital: study protocol for a randomised controlled feasibility trial

Background: Delirium is the most frequent complication among older people following hospitalisation. Delirium may be prevented in about one-third of patients using a multicomponent intervention. However, in the United Kingdom, the National Health Service has no routine delirium prevention care systems. We have developed the Prevention of Delirium Programme, a multicomponent delirium prevention intervention and implementation process. We have successfully carried out a pilot study to test the feasibility and acceptability of implementation of the programme. We are now undertaking preliminary testing of the programme. Methods/Design: The Prevention of Delirium Study is a multicentre, cluster randomised feasibility study designed to explore the potential effectiveness and cost-effectiveness of the Prevention of Delirium Programme. Sixteen elderly care medicine and orthopaedic/trauma wards in eight National Health Service acute hospitals will be randomised to receive the Prevention of Delirium Programme or usual care. Patients will be eligible for the trial if they have been admitted to a participating ward and are aged 65 years or over. The primary objectives of the study are to provide a preliminary estimate of the effectiveness of the Prevention of Delirium Programme as measured by the incidence of new onset delirium, assess the variability of the incidence of new-onset delirium, estimate the intracluster correlation coefficient and likely cluster size, assess barriers to the delivery of the Prevention of Delirium Programme system of care, assess compliance with the Prevention of Delirium Programme system of care, estimate recruitment and follow-up rates, assess the degree of contamination due to between-ward staff movements, and investigate differences in financial costs and benefits between the Prevention of Delirium Programme system of care and standard practice. Secondary objectives are to investigate differences in the number, severity and length of delirium episodes (including persistent delirium); length of stay in hospital; inhospital mortality; destination at discharge; health-related quality of life and health resource use; physical and social independence; anxiety and depression; and patient experience. Discussion: This feasibility study will be used to gather data to inform the design of a future definitive randomised controlled trial. Trial registration: ISRCTN01187372. Registered 13 March 2014

Broca's Region: Novel Organizational Principles and Multiple Receptor Mapping

A novel map of Broca's language region is proposed based on transmitter receptor distributions as functionally relevant molecular markers. It sheds new light on the relation between anatomy and functional segregation

Protein Phosphatase 2A Interacts with the Na+,K+-ATPase and Modulates Its Trafficking by Inhibition of Its Association with Arrestin

Background: The P-type ATPase family constitutes a collection of ion pumps that form phosphorylated intermediates during ion transport. One of the best known members of this family is the Na +,K +-ATPase. The catalytic subunit of the Na +,K +-ATPase includes several functional domains that determine its enzymatic and trafficking properties. Methodology/Principal Findings: Using the yeast two-hybrid system we found that protein phosphatase 2A (PP2A) catalytic C-subunit is a specific Na +,K +-ATPase interacting protein. PP-2A C-subunit interacted with the Na +,K +-ATPase, but not with the homologous sequences of the H +,K +-ATPase. We confirmed that the Na +,K +-ATPase interacts with a complex of A- and C-subunits in native rat kidney. Arrestins and G-protein coupled receptor kinases (GRKs) are important regulators of G-protein coupled receptor (GPCR) signaling, and they also regulate Na +,K +-ATPase trafficking through direct association. PP2A inhibits association between the Na +,K +-ATPase and arrestin, and diminishes the effect of arrestin on Na +,K +-ATPase trafficking. GRK phosphorylates the Na +,K +-ATPase and PP2A can at least partially reverse this phosphorylation. Conclusions/Significance: Taken together, these data demonstrate that the sodium pump belongs to a growing list of io

Contribution of discourse and morphosyntax skills to reading comprehension in Chinese dyslexic and typically developing children

This study aimed at identifying important skills for reading comprehension in Chinese dyslexic children and their typically developing counterparts matched on age (CA controls) or reading level (RL controls). The children were assessed on Chinese reading comprehension, cognitive, and reading-related skills. Results showed that the dyslexic children performed significantly less well than the CA controls but similarly to RL controls in most measures. Results of multiple regression analyses showed that word-level reading-related skills like oral vocabulary and word semantics were found to be strong predictors of reading comprehension among typically developing junior graders and dyslexic readers of senior grades, whereas morphosyntax, a text-level skill, was most predictive for typically developing senior graders. It was concluded that discourse and morphosyntax skills are particularly important for reading comprehension in the non-inflectional and topic-prominent Chinese system

Working conditions and Work-Family Conflict in German hospital physicians: psychosocial and organisational predictors and consequences

<p>Abstract</p> <p>Background</p> <p>Germany currently experiences a situation of major physician attrition. The incompatibility between work and family has been discussed as one of the major reasons for the increasing departure of German physicians for non-clinical occupations or abroad. This study investigates predictors for one particular direction of Work-Family Conflict – namely work interfering with family conflict (WIF) – which are located within the psychosocial work environment or work organisation of hospital physicians. Furthermore, effects of WIF on the individual physicians' physical and mental health were examined. Analyses were performed with an emphasis on gender differences. Comparisons with the general German population were made.</p> <p>Methods</p> <p>Data were collected by questionnaires as part of a study on <it>Psychosocial work hazards and strains of German hospital physicians </it>during April–July 2005. Two hundred and ninety-six hospital physicians (response rate 38.9%) participated in the survey. The Copenhagen Psychosocial Questionnaire (COPSOQ), work interfering with family conflict scale (WIF), and hospital-specific single items on work organisation were used to assess WIF, its predictors, and consequences.</p> <p>Results</p> <p>German hospital physicians reported elevated levels of WIF (mean = 74) compared to the general German population (mean = 45, <it>p </it>< .01). No significant gender difference was found. Predictors for the WIF were lower age, high quantitative demands at work, elevated number of days at work despite own illness, and consequences of short-notice changes in the duty roster. Good sense of community at work was a protective factor. Compared to the general German population, we observed a significant higher level of quantitative work demands among hospital physicians (mean = 73 vs. mean = 57, <it>p </it>< .01). High values of WIF were significantly correlated to higher rates of personal burnout, behavioural and cognitive stress symptoms, and the intention to leave the job. In contrast, low levels of WIF predicted higher job satisfaction, better self-judged general health status, better work ability, and higher satisfaction with life in general. Compared to the German general population, physicians showed significantly higher levels of individual stress and quality of life as well as lower levels for well-being. This has to be judged as an alerting finding regarding the state of physicians' health.</p> <p>Conclusion</p> <p>In our study, work interfering with family conflict (WIF) as part of Work-Family Conflict (WFC) was highly prevalent among German hospital physicians. Factors of work organisation as well as factors of interpersonal relations at work were identified as significant predictors for WIF. Some of these predictors are accessible to alteration by improving work organisation in hospitals.</p