1,370 research outputs found
Alien Registration- Watson, Helen L. (Wilton, Franklin County)
https://digitalmaine.com/alien_docs/19620/thumbnail.jp
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Investigation of the TOCA1-Cdc42 interaction
Transducer of Cdc42-dependent actin assembly protein 1 (TOCA1) is an effector of the Rho family small G protein Cdc42. It contains a membrane-deforming F-BAR domain as well as a Src homology 3 (SH3) domain and a G protein-binding homology region 1 (HR1) domain. TOCA1 binding to Cdc42 leads to actin rearrangements, which are thought to be involved in processes such as endocytosis, filopodia formation, and cell migration. We have solved the structure of the HR1 domain of TOCA1, providing the first structural data for this protein. We have found that the TOCA1 HR1, like the closely related CIP4 HR1, has interesting structural features that are not observed in other HR1 domains. We have also investigated the binding of the TOCA HR1 domain to Cdc42 and the potential ternary complex between Cdc42 and the G protein-binding regions of TOCA1 and a member of the Wiskott-Aldrich syndrome protein family, N-WASP. TOCA1 binds Cdc42 with micromolar affinity, in contrast to the nanomolar affinity of the N-WASP G protein-binding region for Cdc42. NMR experiments show that the Cdc42-binding domain from N-WASP is able to displace TOCA1 HR1 from Cdc42, whereas the N-WASP domain but not the TOCA1 HR1 domain inhibits actin polymerization. This suggests that TOCA1 binding to Cdc42 is an early step in the Cdc42-dependent pathways that govern actin dynamics, and the differential binding affinities of the effectors facilitate a handover from TOCA1 to N-WASP, which can then drive recruitment of the actin-modifying machinery.JRW is supported by a Herchel Smith studentship. JLG is supported by a Wellcome Trust Research Career Development Fellowship (WT095829AIA), European Research Council Starting Grant (281971) and Gurdon Institute funding provided by the Wellcome Trust (092096) and CRUK (C6946/A14492). HMF is supported by a Wellcome Trust PhD Studentship (WT099740Z12Z). We would like to thank Dr A Walrant for help with the pyrene actin assays and liposome preparation. We are also grateful to Dr J.R. Peterson (Fox Chase Cancer Center) for human TOCA1 clones.This is the final version of the article. It first appeared from the American Society for Biochemistry and Molecular Biology via http://dx.doi.org/10.1074/jbc.M116.72429
Use of geographically weighted logistic regression to quantify spatial variation in the environmental and sociodemographic drivers of leptospirosis in Fiji: a modelling study.
BACKGROUND: Leptospirosis is a globally important zoonotic disease, with complex exposure pathways that depend on interactions between human beings, animals, and the environment. Major drivers of outbreaks include flooding, urbanisation, poverty, and agricultural intensification. The intensity of these drivers and their relative importance vary between geographical areas; however, non-spatial regression methods are incapable of capturing the spatial variations. This study aimed to explore the use of geographically weighted logistic regression (GWLR) to provide insights into the ecoepidemiology of human leptospirosis in Fiji. METHODS: We obtained field data from a cross-sectional community survey done in 2013 in the three main islands of Fiji. A blood sample obtained from each participant (aged 1-90 years) was tested for anti-Leptospira antibodies and household locations were recorded using GPS receivers. We used GWLR to quantify the spatial variation in the relative importance of five environmental and sociodemographic covariates (cattle density, distance to river, poverty rate, residential setting [urban or rural], and maximum rainfall in the wettest month) on leptospirosis transmission in Fiji. We developed two models, one using GWLR and one with standard logistic regression; for each model, the dependent variable was the presence or absence of anti-Leptospira antibodies. GWLR results were compared with results obtained with standard logistic regression, and used to produce a predictive risk map and maps showing the spatial variation in odds ratios (OR) for each covariate. FINDINGS: The dataset contained location information for 2046 participants from 1922 households representing 81 communities. The Aikaike information criterion value of the GWLR model was 1935·2 compared with 1254·2 for the standard logistic regression model, indicating that the GWLR model was more efficient. Both models produced similar OR for the covariates, but GWLR also detected spatial variation in the effect of each covariate. Maximum rainfall had the least variation across space (median OR 1·30, IQR 1·27-1·35), and distance to river varied the most (1·45, 1·35-2·05). The predictive risk map indicated that the highest risk was in the interior of Viti Levu, and the agricultural region and southern end of Vanua Levu. INTERPRETATION: GWLR provided a valuable method for modelling spatial heterogeneity of covariates for leptospirosis infection and their relative importance over space. Results of GWLR could be used to inform more place-specific interventions, particularly for diseases with strong environmental or sociodemographic drivers of transmission. FUNDING: WHO, Australian National Health & Medical Research Council, University of Queensland, UK Medical Research Council, Chadwick Trust
Infant sleep and anxiety disorders in early childhood: Findings from an Australian pregnancy cohort study
Emphasis on continuous infant sleep overnight may be driven by parental concern of risk to child mental health outcomes. The Mercy Pregnancy and Emotional Wellbeing Study (MPEWS) examined whether infant sleep at 6 and 12 months postpartum predicts anxiety disorders at 2–4 years, and whether this is moderated by maternal depression, active physical comforting (APC) or maternal cognitions about infant sleep. Data included 349 women and infants. Infant sleep was measured using the Brief Infant Sleep Questionnaire and child anxiety disorders by the Preschool Age Psychiatric Assessment. The risk of developing generalised anxiety or social phobia disorders at 3–4 years was reduced by 42% (p = 0.001) and 31% (p = 0.001), respectively, for a one standard deviation increase in total sleep at 12 months. No other infant sleep outcomes were associated. Maternal depression, APC and cognitions about infant sleep did not significantly moderate these relationships. Focus may need to be on total infant sleep, rather than when sleep is achieved. Highlights: To assess whether infant sleep outcomes (i.e., frequency of nocturnal wakes; nocturnal wakefulness and total sleep per day) at 6 and 12 months predict early childhood anxiety disorders at 3–4 years of age. Maternally reported infant sleep outcomes were not associated with the risk of developing early childhood anxiety disorders at 3–4 years. It may be total infant sleep, irrespective of when sleep occurs or night waking and, independently, active physical comforting that requires further investigation
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Using data insertion with the NAME model to simulate the 8 May 2010 Eyjafjallajökull volcanic ash cloud
A data insertion method, where a dispersion model is initialized from ash properties derived from a series of satellite observations, is used to model the 8 May 2010 Eyjafjallajökull volcanic ash cloud which extended from Iceland to northern Spain. We also briefly discuss the application of this method to the April 2010 phase of the Eyjafjallajökull eruption and the May 2011 Grímsvötn eruption. An advantage of this method is that very little knowledge about the eruption itself is required because some of the usual eruption source parameters are not used. The method may therefore be useful for remote volcanoes where good satellite observations of the erupted material are available, but little is known about the properties of the actual eruption. It does, however, have a number of limitations related to the quality and availability of the observations. We demonstrate that, using certain configurations, the data insertion method is able to capture the structure of a thin filament of ash extending over northern Spain that is not fully captured by other modeling methods. It also verifies well against the satellite observations according to the quantitative
object-based quality metric, SAL—structure, amplitude, location, and the spatial coverage metric, Figure of
Merit in Space
Migrant women's experiences of perinatal care in European countries: a systematic review
Background: Across Europe, there are increasing numbers of migrant women who are of childbearing age, pregnant or new mothers. Migrant women face many challenges and have particular needs during the perinatal period. In this age of super-diversity, provision of maternity care which is sensitive to the needs of all factions of our society is paramount to ensure a healthy and forward looking community.
Aim: As part of a larger multicentre study “Operational Refugee and Migrant Maternal Approach” (ORAMMA)*, this review aimed to evaluate the state of current evidence on migrant women’s experiences of pregnancy, childbirth and maternity care in their destination country within Europe.
Methods: A systematic search of..
Use of electronic medical records (EMR) for oncology outcomes research: assessing the comparability of EMR information to patient registry and health claims data
Electronic medical records (EMRs) are used increasingly for research in clinical oncology, epidemiology, and comparative effectiveness research (CER)
Aktivnost Poslovnog udruženja
The authors thank the University of Strathclyde for a PhD studentship (KLW) and Merck KGaA, Darmstadt, Germany, for financial and material support.Palladium-catalyzed bond forming reactions, such as the SuzukiMiyaura and Mizoroki-Heck reactions, are some of the most broadly utilized reactions within the chemical industry. These reactions frequently employ hazardous solvents; however, to adhere to increasing sustainability pressures and restrictions regarding the use of such solvents, alternatives are highly sought after. Here we demonstrate the utility of dimethyl isosorbide (DMI) as a bio-derived solvent in several benchmark Pd-catalysed reactions: Suzuki– Miyaura (13 examples, 62–100% yield), Mizoroki–Heck (13 examples, 47– 91% yield), and Sonogashira (12 examples, 65–98% yield).PostprintPeer reviewe
Formality and informality in the summative assessment of motor vehicle apprentices: a case study
This article explores the interaction of formal and informal attributes of competence‐based assessment. Specifically, it presents evidence from a small qualitative case study of summative assessment practices for competence‐based qualifications within apprenticeships in the motor industry in England. The data are analysed through applying an adaptation of a framework for exploring the interplay of formality and informality in learning. This analysis reveals informal mentoring as a significant element which influences not only the process of assessment, but also its outcomes. We offer different possible interpretations of the data and their analysis, and conclude that, whichever interpretation is adopted, there appears to be a need for greater capacity‐building for assessors at a local level. This could acknowledge a more holistic role for assessors; recognise the importance of assessors’ informal practices in the formal retention and achievement of apprentices; and enhance awareness of inequalities that may be reinforced by both informal and formal attributes of assessment practices
The Reliability and Validity of the Clinical Perfectionism Questionnaire in Eating Disorder and Community Samples
Background: Clinical perfectionism is a risk and maintaining factor for anxiety disorders, depression and eating disorders. Aims: The aim was to examine the psychometric properties of the 12-item Clinical Perfectionism Questionnaire (CPQ). Method: The research involved two samples. Study 1 comprised a nonclinical sample (n = 206) recruited via the internet. Study 2 comprised individuals in treatment for an eating disorder (n = 129) and a community sample (n = 80). Results: Study 1 factor analysis results indicated a two-factor structure. The CPQ had strong correlations with measures of perfectionism and psychopathology, acceptable internal consistency, and discriminative and incremental validity. The results of Study 2 suggested the same two-factor structure, acceptable internal consistency, and construct validity, with the CPQ discriminating between the eating disorder and control groups. Readability was assessed as a US grade 4 reading level (student age range 9–10 years). Conclusions: The findings provide evidence for the reliability and validity of the CPQ in a clinical eating disorder and two separate community samples. Although further research is required the CPQ has promising evidence as a reliable and valid measure of clinical perfectionism
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