Interaktion der plasmid-codierten Serinprotease EspP aus Shiga-Toxin-produzierenden Escherichia coli mit Proteinen der humanen Blutgerinnung und der Immunantwort

Shiga Toxin-produzierende Escherichia coli (STEC) verursachen beim Menschen gastrointestinale Erkrankungen, die in einigen Fällen zu schwerwiegenden Komplikationen wie dem hämolytisch-urämischen Syndrom (HUS) führen können. STEC besitzen unterschiedliche Virulenzfaktoren, zu denen das Autotransporterprotein EspP (Extracellular serine protease, Plasmid encoded) gehört. Ziel dieser Arbeit die Untersuchung unterschiedlicher Substrate der humanen Immunantwort und Blutgerinnung hinsichtlich eines EspP-induzierten Funktionsverlusts. Es konnte gezeigt werden, dass an P-Selektin nach Inkubation mit EspP keine Leukozyten mehr binden und auf dem Zelladhäsionsmolekül rollen können. Von Willebrand Faktor (vWF), Fibronektin (FN), Fibrinogen (FG) und Thrombospondin-1 (TSP-1) werden ebenfalls durch EspP gespalten und verlieren die Fähigkeit die Thrombozytenadhäsion und Thrombozytenaggregation zu vermitteln. Des Weiteren besteht bei vWF eine verringerte Kollagenbindungsaktivität nach EspP-Inkubation

The relationship between age, sleep and health in shiftworking nurses.

SUMMARY In this study, the relationship between age, sleep, and health in a group of shiftworking nurses was investigated. The study forms part of a larger study into the health and well-being of shiftworking nurses and midwives in England and Wales (Department of Health, 1993). First the importance of the relation between age and sleep was considered. Next, the impact of two important moderating variables, shiftwork and gender (roles), was examined. The nurses worked two very different shift systems: permanent night shifts or rotating shifts. The gender distribution in the sample was very skewed, which resulted in the inclusion of gender roles as variables. Having established the relative importance of the three variables, the next step was to investigate effects of the relation between the variables. Reduced alertness was the most important acute effect considered. Health and well-being complaints were considered as the main chronic effects. It was concluded that age has an important impact on sleep. The results however contradicted the dominant view in the literature that with age sleep always deteriorates. It was important to distinguish between sleep quantity and sleep quality. Both shiftwork and gender (roles) moderated the negative impact of age. Alertness was affected in a counterintuitive manner: older nurses reported feeling more alert compared to younger nurses. With regard to health and well-being, again results were surprising: health and well-being appeared to be more affected by reported sleep quality than by sleep duration. The results from this study were more varied and less linear than could have been assumed on the basis of the literature. It is argued that research should beware of unjust generalisations and move away from simple dichotomies and allow for a more varied and colourful picture

Structure and Function Relationship of the Autotransport and Proteolytic Activity of EspP from Shiga Toxin-Producing Escherichia coli

BACKGROUND: The serine protease autotransporter EspP is a proposed virulence factor of Shiga toxin-producing Escherichia coli (STEC). We recently distinguished four EspP subtypes (EspPalpha, EspPbeta, EspPgamma, and EspPdelta), which display large differences in transport and proteolytic activities and differ widely concerning their distribution within the STEC population. The mechanisms underlying these functional variations in EspP subtypes are, however, unknown. METHODOLOGY/PRINCIPAL FINDINGS: The structural basis of proteolytic and autotransport activity was investigated using transposon-based linker scanning mutagenesis, site-directed mutagenesis and structure-function analysis derived from homology modelling of the EspP passenger domain. Transposon mutagenesis of the passenger domain inactivated autotransport when pentapeptide linker insertions occurred in regions essential for overall correct folding or in a loop protruding from the beta-helical core. Loss of proteolytic function was limited to mutations in Domain 1 in the N-terminal third of the EspP passenger. Site-directed mutagenesis demonstrated that His(127), Asp(156) and Ser(263) in Domain 1 form the catalytic triad of EspP. CONCLUSIONS/SIGNIFICANCE: Our data indicate that in EspP i) the correct formation of the tertiary structure of the passenger domain is essential for efficient autotransport, and ii) an elastase-like serine protease domain in the N-terminal Domain 1 is responsible for the proteolytic phenotype. Lack of stabilizing interactions of Domain 1 with the core structure of the passenger domain ablates proteolytic activity in subtypes EspPbeta and EspPdelta

An inventory of psychosocial oncological interventions in The Netherlands:identifying availability, gaps, and overlap in care provision

Purpose: While a wide range of psychosocial oncological (PO) interventions has been developed, a systematic overview of interventions to inform patients, care providers, as well as researchers, policy makers and health insurers, is lacking. The aims of this paper were (1) to describe the attainment of this overview, which may be used in other jurisdictions and for other health conditions and (2) to reflect on what determines developments in this field. Methods: Dutch researchers and care providers were invited to describe PO-interventions they apply in research or clinical practice. Selection criteria for what constituted a PO-intervention were determined. The input was organized in 12 predefined categories (e.g. physical functioning, genetics). Findings: Sixty-six PO-interventions were included in the overview. Two major categories were psychosocial functioning (24%) and physical functioning and recovery (24%). Interventions are mostly directed at adults (65%) and not aimed at a specific type of cancer (61%). Nearly 25% of the interventions lacked scientific underpinning. Conclusions: This paper provides an overview of Dutch PO-interventions and input on what drives their development. The categorizing method can be used in other jurisdictions and for other health care conditions. A next step would be to investigate the effectiveness and evidence of PO-interventions. Implications for Psychosocial Providers and Policy: The open access overview of interventions provides referral information for care providers. By identifying possible gaps and overlap, the overview looks at possible drivers behind developments in this field which will be of interest to policy makers

Influence of atmospheric circulation on turbulent air-sea heat fluxes over the Mediterranean Sea during winter

The influence of the winter atmospheric circulation on the turbulent variables of the air-sea boundary layer in the Mediterranean Sea is investigated. We examine the effects of several climatic indices and the corresponding large scale atmospheric patterns on the above variables by using a correlation analysis. The spatial characteristics and the behavior of the turbulent variables are also examined based on standard deviation and EOF analysis. Two main types of response to the index-specified atmospheric patterns have been identified: (1) A relatively uniform response of the entire basin associated with the influence of the East Atlantic pattern and (2) opposite responses in the western and eastern sub-basins linked mainly to the intrabasin SLP. The latter is a combined effect of the first four modes of atmospheric variability in the North Atlantic/Eurasia region, the North Atlantic Oscillation (NAO), the East Atlantic Pattern (EA), the Scandinavian Pattern (SCAND), and the East Atlantic-West Russia Pattern (EAWR). The two identified responses of the Mediterranean Sea to the atmospheric forcing are also in accordance with the primary modes of variability of the turbulent variables that result in the EOF analysis. All of the statistically independent indices (NAO, EA, SCAND, EAWR) have to be considered in order to fully account for the modulation of the turbulent variables in the Mediterranean Sea. As an example we refer to the mechanism through which, independent modes of atmospheric variability contributed to the Eastern Mediterranean Transient event between 1987 and 1995. © 2012 by the American Geophysical Union.Peer Reviewe

Экономические перспективы повышения уровня использования попутного нефтяного газа

A novel method employing filter arrays of a cDNA expression library for the identification of substrates for protein kinases was developed. With this technique, we identified a new member of the cyclin family, cyclin L2, as a substrate of the nuclear protein kinase DYRK1A. Cyclin L2 contains an N-terminal cyclin domain and a C-terminal arginine/serine-rich domain (RS domain), which is a hallmark of many proteins involved in pre-mRNA processing. The gene for cyclin L2 encodes the full-length cyclin L2, which is predominantly expressed in testis, as well as a truncated splicing variant (cyclin L2S) that lacks the RS domain and is ubiquitously expressed in human tissues. Full-length cyclin L2, but not cyclin L2S, was associated with the cyclin-dependent kinase PITSLRE. Cyclin L2 interacted with splicing factor 2 in vitro and was co-localized with the splicing factor SC35 in the nuclear speckle compartment. Photobleaching experiments showed that a fusion protein of green fluorescent protein and cyclin L2 in nuclear speckles rapidly exchanged with unbleached molecules in the nucleus, similar to other RS domain-containing proteins. In striking contrast, the closely related green fluorescent protein-cyclin L1 was immobile in the speckle compartment. DYRK1A interacted with cyclin L2 in pull-down assays, and overexpression of DYRK1A stimulated phosphorylation of cyclin L2 in COS-7 cells. These data characterize cyclin L2 as a highly mobile component of nuclear speckles and suggest that DYRK1A may regulate splicing by phosphorylation of cyclin L2

Seasonal cycles and variability of O3 and H2O in the UT/LMS during SPURT

Airborne high resolution in situ measurements of a large set of trace gases including ozone (O3) and total water (H2O) in the upper troposphere and the lowermost stratosphere (UT/LMS) have been performed above Europe within the SPURT project. SPURT provides an extensive data coverage of the UT/LMS in each season within the time period between November 2001 and July 2003. In the LMS a distinct spring maximum and autumn minimum is observed in O3, whereas its annual cycle in the UT is shifted by 2–3 months later towards the end of the year. The more variable H2O measurements reveal a maximum during summer and a minimum during autumn/winter with no phase shift between the two atmospheric compartments. For a comprehensive insight into trace gas composition and variability in the UT/LMS several statistical methods are applied using chemical, thermal and dynamical vertical coordinates. In particular, 2-dimensional probability distribution functions serve as a tool to transform localised aircraft data to a more comprehensive view of the probed atmospheric region. It appears that both trace gases, O3 and H2O, reveal the most compact arrangement and are best correlated in the view of potential vorticity (PV) and distance to the local tropopause, indicating an advanced mixing state on these surfaces. Thus, strong gradients of PV seem to act as a transport barrier both in the vertical and the horizontal direction. The alignment of trace gas isopleths reflects the existence of a year-round extra-tropical tropopause transition layer. The SPURT measurements reveal that this layer is mainly affected by stratospheric air during winter/spring and by tropospheric air during autumn/summer. Normalised mixing entropy values for O3 and H2O in the LMS appear to be maximal during spring and summer, respectively, indicating highest variability of these trace gases during the respective seasons

Professionaliteit van docenten: academische houding in het hbo

Teaching and Teacher Learning (ICLON

Perceptions and Interpretation of Contemporary Masculinities in Western Culture: A Systematic Review

The social construct of masculinity evolves in response to changes in society and culture. Orthodox masculinity is mostly considered to be hegemonic and is evidenced by the dominance of men over women and other, less powerful men. Contemporary shifts in masculinity have seen an emergence of new masculinities that challenge traditional male stereotypes. This systematic review aims to review and synthesize the existing empirical research on contemporary masculinities and to conceptualize how they are understood and interpreted by men themselves. A literature search was undertaken on 10 databases using terms regularly used to identify various contemporary masculinities. Analysis of the 33 included studies identified four key elements that are evident in men’s descriptions of contemporary masculinity. These four elements, (a) Inclusivity, (b) Emotional Intimacy, (c) Physicality, and (d) Resistance, are consistent with the literature describing contemporary masculinities, including Hybrid Masculinities and Inclusive Masculinity Theory. The synthesized findings indicate that young, middle-class, heterosexual men in Western cultures, while still demonstrating some traditional masculinity norms, appear to be adopting some aspects of contemporary masculinities. The theories of hybrid and inclusive masculinity suggest these types of masculinities have several benefits for both men and society in general