Protein monoubiquitination and polyubiquitination generate structural diversity to control distinct biological processes

Ubiquitination involves the attachment of ubiquitin (Ub) to lysine residues on substrate proteins or itself, which can result in protein monoubiquitination or polyubiquitination. Polyubiquitination through different lysines (seven) or the N-terminus of Ub can generate different protein-Ub structures. These include monoubiquitinated proteins, polyubiqutinated proteins with homotypic chains through a particular lysine on Ub or mixed polyubiquitin chains generated by polymerization through different Ub lysines. The ability of the ubiquitination pathway to generate different protein-Ub structures provides versatility of this pathway to target proteins to different fates. Protein ubiquitination is catalyzed by Ub-conjugating and Ub-ligase enzymes, with different combinations of these enzymes specifying the type of Ub modification on protein substrates. How Ub-conjugating and Ub-ligase enzymes generate this structural diversity is not clearly understood. In the current review, we discuss mechanisms utilized by the Ub-conjugating and Ub-ligase enzymes to generate structural diversity during protein ubiquitination, with a focus on recent mechanistic insights into protein monoubiquitination and polyubiquitination.

Contribution of DEAF1 structural domains to the interaction with the breast cancer oncogene LMO4

The proteins LMO4 and DEAF1 contribute to the proliferation of mammary epithelial cells. During breast cancer LMO4 is upregulated, affecting its interaction with other protein partners. This may set cells on a path to tumour formation. LMO4 and DEAF1 interact, but it is unknown how they cooperate to regulate cell proliferation. In this study, we identify a specific LMO4-binding domain in DEAF1. This domain contains an unstructured region that directly contacts LMO4, and a coiled coil that contains the DEAF1 nuclear export signal (NES). The coiled coil region can form tetramers and has the typical properties of a coiled coil domain. Using a simple cell-based assay, we show that LMO4 modulates the activity of the DEAF NES, causing nuclear accumulation of a construct containing the LMO4-interaction region of DEAF1.

Socio-structural influences on the work participation of refugees : an exploratory systematic mixed studies review

This systematic mixed studies review aimed at synthesizing evidence from studies related to the influences on the work participation of people with refugee status (PWRS). The review focused on the role of proximal socio-structural barriers on work participation by PWRS while foregrounding related distal, intermediate, proximal, and meta-systemic influences. For the systematic search of the literature, we focused on databases that addressed work, well-being, and social policy in refugee populations, including, Medline, CINAHL, PsycInfo, Web of Science, Scopus, and Sociological Abstracts. Of the studies reviewed, 16 of 39 met the inclusion criteria and were retained for the final analysis. We performed a narrative synthesis of the evidence on barriers to work participation by PWRS, interlinking clusters of barriers potent to their effects on work participation. Findings from the narrative synthesis suggest that proximal factors, those at point of entry to the labor market, influence work participation more directly than distal or intermediate factors. Distal and intermediate factors achieve their effects on work participation by PWRS primarily through meta-systemic interlinkages, including host-country documentation and refugee administration provisions.

Machine prognostics based on health state estimation using SVM

The ability to accurately predict the remaining useful life of machine components is critical for machine continuous operation, and can also improve productivity and enhance system safety. In condition-based maintenance (CBM), maintenance is performed based on information collected through condition monitoring and an assessment of the machine health. Effective diagnostics and prognostics are important aspects of CBM for maintenance engineers to schedule a repair and to acquire replacement components before the components actually fail. All machine components are subjected to degradation processes in real environments and they have certain failure characteristics which can be related to the operating conditions. This paper describes a technique for accurate assessment of the remnant life of machines based on health state probability estimation and involving historical knowledge embedded in the closed loop diagnostics and prognostics systems. The technique uses a Support Vector Machine (SVM) classifier as a tool for estimating health state probability of machine degradation, which can affect the accuracy of prediction. To validate the feasibility of the proposed model, real life historical data from bearings of High Pressure Liquefied Natural Gas (HP-LNG) pumps were analysed and used to obtain the optimal prediction of remaining useful life. The results obtained were very encouraging and showed that the proposed prognostic system based on health state probability estimation has the potential to be used as an estimation tool for remnant life prediction in industrial machinery.

When does change begin following screening and brief intervention among depressed problem drinkers?

Brief interventions are effective for problem drinking and reductions are known to occur in association with screening and assessment. The present study sought to assess, among participants (N=202) in a clinical trial, how much change occurred between baseline assessment and a one-session brief intervention (S1), and the predictors of early change. The primary focus was on changes in the Beck Depression Inventory Fast Screen scores and alcohol consumption (standard drinks per week) prior to random allocation to nine further sessions addressing either depression, alcohol, or both problems. There were large and clinically significant reductions between baseline and S1, with the strongest predictors being baseline scores in the relevant domain and change in the other domain. Client engagement was also predictive of early depression changes. Monitoring progress in both domains from first contact, and provision of empathic care, followed by brief intervention appear to be useful for this high prevalence comorbidity.

Ask : a health advocacy program for adolescents with an intellectual disability : a cluster randomised controlled trial

Background Adolescents with intellectual disability often have poor health and healthcare. This is partly as a consequence of poor communication and recall difficulties, and the possible loss of specialised paediatric services. Methods/Design A cluster randomised trial was conducted with adolescents with intellectual disability to investigate a health intervention package to enhance interactions among adolescents with intellectual disability, their parents/carers, and general practitioners (GPs). The trial took place in Queensland, Australia, between February 2007 and September 2010. The intervention package was designed to improve communication with health professionals and families’ organisation of health information, and to increase clinical activities beneficial to improved health outcomes. It consisted of the Comprehensive Health Assessment Program (CHAP), a one-off health check, and the Ask Health Diary, designed for on-going use. Participants were drawn from Special Education Schools and Special Education Units. The education component of the intervention was delivered as part of the school curriculum. Educators were surveyed at baseline and followed-up four months later. Carers were surveyed at baseline and after 26 months. Evidence of health promotion, disease prevention and case-finding activities were extracted from GPs clinical records. Qualitative interviews of educators occurred after completion of the educational component of the intervention and with adolescents and carers after the CHAP. Discussion Adolescents with intellectual disability have difficulty obtaining many health services and often find it difficult to become empowered to improve and protect their health. The health intervention package proposed may aid them by augmenting communication, improving documentation of health encounters, and improving access to, and quality of, GP care. Recruitment strategies to consider for future studies in this population include ensuring potential participants can identify themselves with the individuals used in promotional study material, making direct contact with their families at the start of the study, and closely monitoring the implementation of the educational intervention.

Spatial modelling of population health screening : the role of accessibility in predicting expected patient flows

This paper describes a generalised linear mixed model (GLMM) approach for understanding spatial patterns of participation in population health screening, in the presence of multiple screening facilities. The models presented have dual focus, namely the prediction of expected patient flows from regions to services and relative rates of participation by region- service combination, with both outputs having meaningful implications for the monitoring of current service uptake and provision. The novelty of this paper lies with the former focus, and an approach for distributing expected participation by region based on proximity to services is proposed. The modelling of relative rates of participation is achieved through the combination of different random effects, as a means of assigning excess participation to different sources. The methodology is applied to participation data collected from a government-funded mammography program in Brisbane, Australia.

Molecular and structural requirements of the ß1L-adrenoceptor

Noradrenaline which occurs naturally in the body binds to beta-adrenoceptors on the heart, causing the heart to beat faster and with greater force in response to increased demand. This enables the heart to provide oxygenated blood to vital organs. Prolonged overstimulation by noradrenaline can be harmful to the heart and lead to the progression of heart disease. In these circumstances beta-adrenoceptors are blocked with drugs called beta-blockers. Beta-blockers block the effects of noradrenaline by binding to the same site on the beta-adrenoceptor. Some beta-blockers such as CGP12177 can also cause increases in heart rate. Therefore it was proposed that CGP12177 could bind in a different place to noradrenaline. The aim of this study was to determine where CGP12177 binds to on the beta-adrenoceptor. The results have revealed a separate binding site named beta-1-low. These results may lead to the development of improved -blockers for the management of heart conditions.

Real-time risk monitoring in business processes : a sensor-based approach

This article proposes an approach for real-time monitoring of risks in executable business process models. The approach considers risks in all phases of the business process management lifecycle, from process design, where risks are defined on top of process models, through to process diagnosis, where risks are detected during process execution. The approach has been realized via a distributed, sensor-based architecture. At design-time, sensors are defined to specify risk conditions which when fulfilled, are a likely indicator of negative process states (faults) to eventuate. Both historical and current process execution data can be used to compose such conditions. At run-time, each sensor independently notifies a sensor manager when a risk is detected. In turn, the sensor manager interacts with the monitoring component of a business process management system to prompt the results to process administrators who may take remedial actions. The proposed architecture has been implemented on top of the YAWL system, and evaluated through performance measurements and usability tests with students. The results show that risk conditions can be computed efficiently and that the approach is perceived as useful by the participants in the tests.

Tackling the health burden from household air pollution (HAP) : development and implementation of new WHO Guidelines

Household air pollution (HAP), arising mainly from the combustion of solid and other polluting fuels, is responsible for a very substantial public health burden, most recently estimated as causing 3.5 million premature deaths in 2010. These patterns of household fuel use have also important negative impacts on safety, prospects for poverty reduction and the environment, including climate change. Building on previous air quality guidelines, the WHO is developing new guidelines focused on household fuel combustion, covering cooking, heating and lighting, and although global, the key focus is low and middle income countries reflecting the distribution of disease burden. As discussed in this paper, currently in development, the guidelines will include reviews of a wide range of evidence including fuel use in homes, emissions from stoves and lighting, household air pollution and exposure levels experienced by populations, health risks, impacts of interventions on HAP and exposure, and also key factors influencing sustainable and equitable adoption of improved stoves and cleaner fuels. GRADE, the standard method used for guidelines evidence review may not be well suited to the variety and nature of evidence required for this project, and a modified approach is being developed and tested. Work on the guidelines is being carried out in close collaboration with the UN Foundation Global Alliance on Clean cookstoves, allowing alignment with specific tools including recently developed international voluntary standards for stoves, and the development of country action plans. Following publication, WHO plans to work closely with a number of countries to learn from implementation efforts, in order to further strengthen support and guidance. A case study on the situation and policy actions to date in Bhutan provide an illustration of the challenges and opportunities involved, and the timely importance of the new guidelines and associated research, evaluation and policy development agendas.

Physical characteristics of the indoor environment that affect health and wellbeing in healthcare facilities : a review

Understanding the physical characteristics of the indoor environment that affect human health and wellbeing is the key requirement underpinning the beneficial design of a healthcare facility (HCF). We reviewed and summarised physical factors of the indoor environment reported to affect human health and wellbeing in HCFs. Research materials included articles identified in a Pubmed search, guidelines, books, reports and monographs, as well as the bibliographies of review articles in the area studied. Of these, 209 publications were selected for this review. According to the literature, there is evidence that the following physical factors of the indoor environment affect the health and wellbeing of human beings in an HCF: safety, ventilation and HVAC systems, thermal environment, acoustic environment, interior layout and room type, windows (including daylight and views), nature and gardens, lighting, colour, floor covering, furniture and its placement, ergonomics, wayfinding, artworks and music. Some of these, in themselves, directly promote or hinder health and wellbeing, but the physical factors may also have numerous indirect impacts by influencing the behaviour, actions, and interactions of patients, their families and the staff members. The findings of this research enable a good understanding of the different physical factors of the indoor environment on health and wellbeing and provide a practical resource for those responsible for the design and operate the facilities as well as researchers investigating these factors. However, more studies are needed in order to inform the design of optimally beneficial indoor environments in HCFs for all user groups.

Experimental investigation of the governing parameters in the electrospinning of poly(3-hydroxybutyrate) scaffolds : structural characteristics of the pores

We sought to determine the impact of electrospinning parameters on a trustworthy criterion that could evidently improve the maximum applicability of fibrous scaffolds for tissue regeneration. We used an image analysis technique to elucidate the web permeability index (WPI) by modeling the formation of electrospun scaffolds. Poly(3-hydroxybutyrate) (P3HB) scaffolds were fabricated according to predetermined conditions of levels in a Taguchi orthogonal design. The material parameters were the polymer concentration, conductivity, and volatility of the solution. The processing parameters were the applied voltage and nozzle-to-collector distance. With a law to monitor the WPI values when the polymer concentration or the applied voltage was increased, the pore interconnectivity was decreased. The quality of the jet instability altered the pore numbers, areas, and other structural characteristics, all of which determined the scaffold porosity and aperture interconnectivity. An initial drastic increase was observed in the WPI values because of the chain entanglement phenomenon above a 6 wt % P3HB content. Although the solution mixture significantly (p < 0.05) changed the scaffold architectural characteristics as a function of the solution viscosity and surface tension, it had a minor impact on the WPI values. The solution mixture gained the third place of significance, and the distance was approved as the least important factor.