Heat shock protein 27 is the major differentially phosphorylated protein involved in renal epithelial cellular stress response and controls focal adhesion organization and apoptosis

We used two-dimensional difference gel electrophoresis to determine early changes in the stress-response pathways that precede focal adhesion disorganization linked to the onset of apoptosis of renal epithelial cells. Treatment of LLC-PK1 cells with the model nephrotoxicant 1,2-(dichlorovinyl)-L-cysteine (DCVC) resulted in a >1.5-fold up- and down-regulation of 14 and 9 proteins, respectively, preceding the onset of apoptosis. Proteins included those involved in metabolism, i.e. aconitase and pyruvate dehydrogenase, and those related to stress responses and cytoskeletal reorganization, i.e. cofilin, Hsp27, and alpha-b-crystallin. The most prominent changes were found for Hsp27, which was related to a pI shift in association with an altered phosphorylation status of serine residue 82. Although both p38 and JNK were activated by DCVC, only inhibition of p38 with SB203580 reduced Hsp27 phosphorylation, which was associated with accelerated reorganization of focal adhesions, cell detachment, and apoptosis. In contrast, inhibition of JNK with SP600125 maintained cell adhesion as well as protection against apoptosis. Active JNK co-localized at focal adhesions after DCVC treatment in a FAK-dependent manner. Inhibition of active JNK localization at focal adhesions did not prevent DCVC-induced phosphorylation of Hsp27. Overexpression of a phosphorylation-defective mutant Hsp27 acted as a dominant negative and accelerated the DCVC-induced changes in the focal adhesions as well as the onset of apoptosis. Our data fit a model whereby early p38 activation results in a rapid phosphorylation of Hsp27, a requirement for proper maintenance of cell adhesion, thus suppressing renal epithelial cell apoptosis.

Heat shock protein 27 is the major differentially phosphorylated protein involved in renal epithelial cellular stress response and controls focal adhesion organization and apoptosis

We used two-dimensional difference gel electrophoresis to determine early changes in the stress-response pathways that precede focal adhesion disorganization linked to the onset of apoptosis of renal epithelial cells. Treatment of LLC-PK1 cells with the model nephrotoxicant 1,2-(dichlorovinyl)-L-cysteine ( DCVC) resulted in a > 1.5-fold up- and down-regulation of 14 and 9 proteins, respectively, preceding the onset of apoptosis. Proteins included those involved in metabolism, i.e. aconitase and pyruvate dehydrogenase, and those related to stress responses and cytoskeletal reorganization, i.e. cofilin, Hsp27, and alpha-b-crystallin. The most prominent changes were found for Hsp27, which was related to a pI shift in association with an altered phosphorylation status of serine residue 82. Although both p38 and JNK were activated by DCVC, only inhibition of p38 with SB203580 reduced Hsp27 phosphorylation, which was associated with accelerated reorganization of focal adhesions, cell detachment, and apoptosis. In contrast, inhibition of JNK with SP600125 maintained cell adhesion as well as protection against apoptosis. Active JNK co-localized at focal adhesions after DCVC treatment in a FAK-dependent manner. Inhibition of active JNK localization at focal adhesions did not prevent DCVC-induced phosphorylation of Hsp27. Overexpression of a phosphorylation-defective mutant Hsp27 acted as a dominant negative and accelerated the DCVC-induced changes in the focal adhesions as well as the onset of apoptosis. Our data fit a model whereby early p38 activation results in a rapid phosphorylation of Hsp27, a requirement for proper maintenance of cell adhesion, thus suppressing renal epithelial cell apoptosis.

Conversations around homework: links to parental mental health, family characteristics and child psychological functioning

Parents are increasingly expected to supplement their children's school-based learning by providing support for children's homework. However, parents' capacities to provide such support may vary and may be limited by the experience of depression. This may have implications for child development. In the course of a prospective, longitudinal study of children of postnatally depressed and healthy mothers, we observed mothers (N = 88) and fathers (N = 78) at home during maths homework interactions with their 8-year-old children. The quality of parental communication was rated and analysed in relation to child functioning. The quality of communication of each of the parents was related to their mental state, social class and IQ. While postnatal depression was not directly related to child development, there was some evidence of the influence of maternal depression occurring in the child's school years. Different aspects of parental communication with the child showed specific associations with different child outcomes, over and above the influence of family characteristics. In particular, child school attainment and IQ were associated with parental strategies to encourage representational thinking and mastery motivation, whereas child behavioural adjustment at school and self-esteem were linked to the degree of parental emotional support and low levels of coercion. Notably, the influence of maternal homework support was more strongly related to child outcome than was paternal support, a pattern reflected in mothers' greater involvement in children's schools and school-related activities. Some parents may need guidance in how to support their children's homework if it is to be of benefit to child functioning.

e-learning services provision and management

With the rapid development of information technology, learners demand effective personalised learning support, which imposes a new learning paradigm in learning content management. Standards as well as best practice in industry and research community have taken place to address the paradigm shift. With respect to this trend, it is recognised that finding learning content which meet personal learning requirements remains challenging. This paper describes a model of e-learning services provision which integrates the best practice in e-learning and Web services technology so that learning content management is capable of supporting applications of learning services.

Recommending flavanols and procyanidins for cardiovascular health: current knowledge and future needs

Data on the potential health benefits of dietary flavanols and procyanidins, especially in the context of cardiovascular health, are considerable and continue to accumulate. Significant progress has been made in flavanol analytics and the creation of phytonutrient-content food databases, and novel data emanated from epidemiological investigations as well as dietary intervention studies. However, a comprehensive understanding of the pharmacological properties of flavanols and procyanidins, including their precise mechanisms of action in vivo, and a conclusive, consensus-based accreditation of a causal relationship between intake and health benefits in the context of primary and secondary cardiovascular disease prevention is still outstanding. Thus, the objective of this review is to identify and discuss key questions and gaps that will need to be addressed in order to conclusively demonstrate whether or not dietary flavanols and procyanidins have a role in preventing, delaying the onset of, or treating cardiovascular diseases, and thus improving human life expectancy and quality of life.

Provider diversity in the NHS: impact on quality and innovation

The overall objective of the research project has been to assess the impact of provider diversity on quality and innovation in the NHS. The specific research aims were to identify the differences in performance between non-profit Third Sector organisations, for-profit private enterprises, and incumbent public sector institutions within the NHS as providers of health care services, as well as the factors that affect the entry and growth of new private and Third Sector providers. The study used both qualitative and quantitative methods based on case studies of four Local Health Economies (LHEs). Qualitative methods included documentary analysis and interviews with key informants and managers of both commissioning and provider organisations. To provide a focus to the study, two tracer conditions were followed: orthopaedic surgery and home health care for frail older people. In the case of hospital inpatient care, data on patient characteristics were also collected from the HES database. The analysis of this data provided preliminary estimates of the effects of provider type on quality, controlling for client characteristics and case mix. In addition, a survey of patient experience in diverse provider organisations was analysed to compare the different dimensions of quality of provision of acute services between incumbent NHS organisations and new independent sector treatment centres. The research has shown that, in respect of inpatient hospital services, diverse providers supply health services of at least as good quality as traditional NHS providers, and that there is ample opportunity to expand their scale and scope as providers of services commissioned by the NHS. The research used patient experience survey data to investigate whether hospital ownership affects the quality of services reported by NHS patients in areas other than clinical quality. The raw survey data appear to show that private hospitals provide higher quality services than the public hospitals. However, further empirical analysis leads to a more nuanced understanding of the performance differences. Firstly, the analysis shows that each sector offers greater quality in certain specialties. Secondly, the analysis shows that differences in the quality of patients’ reported experience are mainly attributable to patient characteristics, the selection of patients into each type of hospital, and the characteristics of individual hospitals, rather than to hospital ownership as such. Controlling for such differences, NHS patients are on average likely to experience a similar quality of care in a public or privately-run hospital. Nevertheless, for specific groups of patients and for specific types of treatments, especially the more straightforward ones, the private sector provides an improved patient experience compared to the public sector. Elsewhere, the NHS continues to provide a high quality service and outperforms the private sector in a range of services and for a range of clients.

The effects of explicit versus parameterized convection on the MJO in a large-domain high-resolution tropical case study. Part I: Characterization of large-scale organization and propagation

High-resolution simulations over a large tropical domain (∼20◦S–20◦N and 42◦E–180◦E) using both explicit and parameterized convection are analyzed and compared to observations during a 10-day case study of an active Madden-Julian Oscillation (MJO) event. The parameterized convection model simulations at both 40 km and 12 km grid spacing have a very weak MJO signal and little eastward propagation. A 4 km explicit convection simulation using Smagorinsky subgrid mixing in the vertical and horizontal dimensions exhibits the best MJO strength and propagation speed. 12 km explicit convection simulations also perform much better than the 12 km parameterized convection run, suggesting that the convection scheme, rather than horizontal resolution, is key for these MJO simulations. Interestingly, a 4 km explicit convection simulation using the conventional boundary layer scheme for vertical subgrid mixing (but still using Smagorinsky horizontal mixing) completely loses the large-scale MJO organization, showing that relatively high resolution with explicit convection does not guarantee a good MJO simulation. Models with a good MJO representation have a more realistic relationship between lower-free-tropospheric moisture and precipitation, supporting the idea that moisture-convection feedback is a key process for MJO propagation. There is also increased generation of available potential energy and conversion of that energy into kinetic energy in models with a more realistic MJO, which is related to larger zonal variance in convective heating and vertical velocity, larger zonal temperature variance around 200 hPa, and larger correlations between temperature and ascent (and between temperature and diabatic heating) between 500–400 hPa.

Health care rights and NHS rationing: turning theory into practice

How should we understand the nature of patients’ right in public health care systems? Are health care rights different to rights under a private contract for car insurance? This article distinguishes between public and private rights and the relevance of community interests and notions of social solidarity. It discusses the distinction between political and civil rights, and social and economic rights and the inherently political and redistributive nature of the latter. Nevertheless, social and economic rights certainly give rise to “rights” enforceable by the courts. In the UK (as in many other jurisdictions), the courts have favoured a “procedural” approach to the question, in which the courts closely scrutinise decisions and demand high standards of rationality from decision-makers. However, although this is the general rule, the article also discusses a number of exceptional cases where “substantive” remedies are available which guarantee patients access to the care they need.

Compensation and Rewards for Environmental Services (CRES) and efficient design of contracts in developing countries. Behavioral insights from a natural field experiment

The use of economic incentives for biodiversity (mostly Compensation and Reward for Environmental Services including Payment for ES) has been widely supported in the past decades and became the main innovative policy tools for biodiversity conservation worldwide. These policy tools are often based on the insight that rational actors perfectly weigh the costs and benefits of adopting certain behaviors and well-crafted economic incentives and disincentives will lead to socially desirable development scenarios. This rationalist mode of thought has provided interesting insights and results, but it also misestimates the context by which ‘real individuals’ come to decisions, and the multitude of factors influencing development sequences. In this study, our goal is to examine how these policies can take advantage of some unintended behavioral reactions that might in return impact, either positively or negatively, general policy performances. We test the effect of income's origin (‘Low effort’ based money vs. ‘High effort’ based money) on spending decisions (Necessity vs. Superior goods) and subsequent pro social preferences (Future pro-environmental behavior) within Madagascar rural areas, using a natural field experiment. Our results show that money obtained under low effort leads to different consumption patterns than money obtained under high efforts: superior goods are more salient in the case of low effort money. In parallel, money obtained under low effort leads to subsequent higher pro social behavior. Compensation and rewards policies for ecosystem services may mobilize knowledge on behavioral biases to improve their design and foster positive spillovers on their development goals.