The EHEC Type III Effector NleL Is an E3 Ubiquitin Ligase That Modulates Pedestal Formation

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic colitis and may result in potentially fatal hemolytic uremia syndrome in humans. EHEC colonize the intestinal mucosa and promote the formation of actin-rich pedestals via translocated type III effectors. Two EHEC type III secreted effectors, Tir and EspFu/TccP, are key players for pedestal formation. We discovered that an EHEC effector protein called Non-LEE-encoded Ligase (NleL) is an E3 ubiquitin ligase. In vitro, we showed that the NleL C753 residue is critical for its E3 ligase activity. Functionally, we demonstrated that NleL E3 ubiquitin ligase activity is involved in modulating Tir-mediated pedestal formation. Surprisingly, EHEC mutant strain deficient in the E3 ligase activity induced more pedestals than the wild-type strain. The canonical EPEC strain E2348/69 normally lacks the nleL gene, and the ectopic expression of the wild-type EHEC nleL, but not the catalytically-deficient nleL(C753A) mutant, in this strain resulted in fewer actin-rich pedestals. Furthermore, we showed that the C. rodentium NleL homolog is a E3 ubiquitin ligase and is required for efficient infection of murine colonic epithelial cells in vivo. In summary, our study demonstrated that EHEC utilizes NleL E3 ubiquitin ligase activity to modulate Tir-mediated pedestal formation.National Institutes of Health (U.S.) (grant AI078092)National Institutes of Health (U.S.) (grant AI068655

Leisure-time physical activity, cardiorespiratory fitness and feelings of hopelessness in men

<p>Abstract</p> <p>Background</p> <p>Leisure-time physical activity (LTPA) and cardiorespiratory fitness contribute to mental health. Hopelessness has been linked to impaired mental health, cardiovascular events and mortality. Previous studies have focused on physical exercise and depression. We examined the associations of LTPA and cardiorespiratory fitness with feelings of hopelessness.</p> <p>Methods</p> <p>In this cross-sectional study leisure-time physical activity, maximal oxygen uptake (VO_2max), hopelessness and cardiovascular risk factors were assessed in a population-based cohort of 2428 men aged 42 – 60 years old at baseline.</p> <p>Results</p> <p>Men feeling more hopeless about their future and reaching goals were less physically active, less fit and had a higher prevalence of many cardiovascular risk factors than men with lower levels of hopelessness. In a logistic regression model adjusted for age, smoking, alcohol consumption, cardiovascular disease and socioeconomic status, men engaging in less than 60 min/week of moderate-to-vigorous LTPA were 37% (95% CI 11 – 67%) more likely to feel hopeless than those engaging in at least 2.5 h/wk of LTPA. After further adjusting for elevated depressive symptoms the association of LTPA and hopelessness remained significant. VO_2maxwas also associated with hopelessness, but not after adjustment for depressive symptoms.</p> <p>Conclusion</p> <p>Moderate and vigorous LTPA and cardiorespiratory fitness were inversely associated with hopelessness in these middle-aged men. These findings suggest that physical inactivity and poor cardiorespiratory fitness is an important associate of hopelessness, a distinct element of low subjective well-being.</p

Brief psychological therapies for anxiety and depression in primary care: meta-analysis and meta-regression

Psychological therapies provided in primary care are usually briefer than in secondary care. There has been no recent comprehensive review comparing their effectiveness for common mental health problems. We aimed to compare the effectiveness of different types of brief psychological therapy administered within primary care across and between anxiety, depressive and mixed disorders

Study protocol: healthy urban living and ageing in place (HULAP): an international, mixed methods study examining the associations between physical activity, built and social environments for older adults the UK and Brazil

Abstract Background The ability to ‘age in place’ is dependent on a range of inter-personal, social and built environment attributes, with the latter being a key area for potential intervention. There is an emerging body of evidence that indicates the type of built environment features that may best support age friendly communities, but there is a need to expand and consolidate this, while generating a better understanding of how on how research findings can be most effectively be translated in to policy and practice. Methods The study is based on two case study cities, Curtiba (Brazil) and Belfast (UK), which have highly contrasting physical, social and policy environments. The study deploys a mix methods approach, mirrored in each city. This includes the recruitment of 300 participants in each city to wear GPS and accelerometers, a survey capturing physical functioning and other personal attributes, as well as their perception of their local environment using NEWS-A. The study will also measure the built environments of the cities using GIS and develop a tool for auditing the routes used by participants around their neighbourhoods. The study seeks to comparatively map the policy actors and resources involved in healthy ageing in the two cities through interviews, focus groups and discourse analysis. Finally, the study has a significant knowledge exchange component, including the development of a tool to assess the capacities of both researchers and research users to maximise the impact of the research findings. Discussion The HULAP study has been designed and implemented by a multi-disciplinary team and integrates differing methodologies to purposefully impact on policy and practice on healthy ageing in high and low-middle income countries. It has particular strengths in its combination of objective and self-reported measures using validated tools and the integration of GPS, accelerometer and GIS data to provide a robust assessment of ‘spatial energetics’. The strong knowledge exchange strand means that the study is expected to also contribute to our understanding of how to maximise research impact in this field and create effective evidence for linking older adult’s physical activity with the social, built and policy environments

Integrative Network Biology: Graph Prototyping for Co-Expression Cancer Networks

Network-based analysis has been proven useful in biologically-oriented areas, e.g., to explore the dynamics and complexity of biological networks. Investigating a set of networks allows deriving general knowledge about the underlying topological and functional properties. The integrative analysis of networks typically combines networks from different studies that investigate the same or similar research questions. In order to perform an integrative analysis it is often necessary to compare the properties of matching edges across the data set. This identification of common edges is often burdensome and computational intensive. Here, we present an approach that is different from inferring a new network based on common features. Instead, we select one network as a graph prototype, which then represents a set of comparable network objects, as it has the least average distance to all other networks in the same set. We demonstrate the usefulness of the graph prototyping approach on a set of prostate cancer networks and a set of corresponding benign networks. We further show that the distances within the cancer group and the benign group are statistically different depending on the utilized distance measure

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Extending breastfeeding duration through primary care: a systematic review of prenatal and postnatal interventions.

This literature review provides an overview of the effectiveness of strategies and procedures used to extend breastfeeding duration. Interventions carried out during pregnancy and/or infant care conducted in primary health care services, community settings, or hospital clinics were included. Interventions covering only the delivery period were excluded. Interventions that were most effective in extending the duration of breastfeeding generally combined information, guidance, and support and were long term and intensive. During prenatal care, group education was the only effective strategy reported. Home visits used to identify mothers' concerns with breastfeeding, assist with problem solving, and involve family members in breastfeeding support were effective during the postnatal period or both periods. Individual education sessions were also effective in these periods, as was the combination of 2 or 3 of these strategies in interventions involving both periods. Strategies that had no effect were characterized by no face-to-face interaction, practices contradicting messages, or small-scale interventions