Evidence for involvement of both IKCa and SKCa channels in hyperpolarizing responses of the rat middle cerebral artery

Endothelium-derived hyperpolarizing factor responses in the rat middle cerebral artery are blocked by inhibiting IKCa channels alone, contrasting with peripheral vessels where block of both IKCa and SKCa is required. As the contribution of IKCa and SKCa to endothelium-dependent hyperpolarization differs in peripheral arteries, depending on the level of arterial constriction, we investigated the possibility that SKCa might contribute to equivalent hyperpolarization in cerebral arteries under certain conditions. METHODS: Rat middle cerebral arteries (approximately 175 microm) were mounted in a wire myograph. The effect of KCa channel blockers on endothelium-dependent responses to the protease-activated receptor 2 agonist, SLIGRL (20 micromol/L), were then assessed as simultaneous changes in tension and membrane potential. These data were correlated with the distribution of arterial KCa channels revealed with immunohistochemistry. RESULTS: SLIGRL hyperpolarized and relaxed cerebral arteries undergoing variable levels of stretch-induced tone. The relaxation was unaffected by specific inhibitors of IKCa (TRAM-34, 1 micromol/L) or SKCa (apamin, 50 nmol/L) alone or in combination. In contrast, the associated smooth-muscle hyperpolarization was inhibited, but only with these blockers in combination. Blocking nitric oxide synthase (NOS) or guanylyl cyclase evoked smooth-muscle depolarization and constriction, with both hyperpolarization and relaxation to SLIGRL being abolished by TRAM-34 alone, whereas apamin had no effect. Immunolabeling showed SKCa and IKCa within the endothelium. CONCLUSIONS: In the absence of NO, IKCa underpins endothelium-dependent hyperpolarization and relaxation in cerebral arteries. However, when NOS is active SKCa contributes to hyperpolarization, whatever the extent of background contraction. These changes may have relevance in vascular disease states where NO release is compromised and when the levels of SKCa expression may be altered.

Community involvement in urban design: help or hindrance?

This paper examines the realities of community involvement in urban design in the context of a study of the West Itchen Neighbourhood of Southampton, a diverse inner city area accommodating some 7,000 households and 18,000 people. The findings are based on a literature review of community involvement in urban design and case study research into three government supported regeneration projects all located within the study area: a Neighbourhood Renewal Area - designated in 1994; an Estate Action Scheme - implemented between 1993 and 1996; and a Single Regeneration Budget programme - following a successful bid in 1995. The research was undertaken by Helen Gregory in 1997/8 as the basis of a dissertation, supervised by Alan Rowley, submitted for the award of an MPhil in Environmental Planning and Development from The University of Reading.

Causal evidence for frontal involvement in memory target maintenance by posterior brain areas during distracter interference of visual working memory

Dorsolateral prefrontal cortex (DLPFC) is recruited during visual working memory (WM) when relevant information must be maintained in the presence of distracting information. The mechanism by which DLPFC might ensure successful maintenance of the contents of WM is, however, unclear; it might enhance neural maintenance of memory targets or suppress processing of distracters. To adjudicate between these possibilities, we applied time-locked transcranial magnetic stimulation (TMS) during functional MRI, an approach that permits causal assessment of a stimulated brain region's influence on connected brain regions, and evaluated how this influence may change under different task conditions. Participants performed a visual WM task requiring retention of visual stimuli (faces or houses) across a delay during which visual distracters could be present or absent. When distracters were present, they were always from the opposite stimulus category, so that targets and distracters were represented in distinct posterior cortical areas. We then measured whether DLPFC-TMS, administered in the delay at the time point when distracters could appear, would modulate posterior regions representing memory targets or distracters. We found that DLPFC-TMS influenced posterior areas only when distracters were present and, critically, that this influence consisted of increased activity in regions representing the current memory targets. DLPFC-TMS did not affect regions representing current distracters. These results provide a new line of causal evidence for a top-down DLPFC-based control mechanism that promotes successful maintenance of relevant information in WM in the presence of distraction.

The use of public participation and economic appraisal for public involvement in large-scale hydropower projects: Case study of the Nam Theun 2 Hydropower Project

Gaining public acceptance is one of the main issues with large-scale low-carbon projects such as hydropower development. It has been recommended by the World Commission on Dams that to gain public acceptance, publicinvolvement is necessary in the decision-making process (WCD, 2000). As financially-significant actors in the planning and implementation of large-scale hydropowerprojects in developing country contexts, the paper examines the ways in which publicinvolvement may be influenced by international financial institutions. Using the casestudy of the NamTheun2HydropowerProject in Laos, the paper analyses how publicinvolvement facilitated by the Asian Development Bank had a bearing on procedural and distributional justice. The paper analyses the extent of publicparticipation and the assessment of full social and environmental costs of the project in the Cost-Benefit Analysis conducted during the projectappraisal stage. It is argued that while efforts were made to involve the public, there were several factors that influenced procedural and distributional justice: the late contribution of the Asian Development Bank in the projectappraisal stage; and the issue of non-market values and discount rate to calculate the full social and environmental costs.

Collagen, convulxin, and thrombin stimulate aggregation-independent tyrosine phosphorylation of CD31 in platelets. Evidence for the involvement of Src family kinases

Platelet endothelial cell adhesion molecule-1 (CD31) is a 130-kDa glycoprotein receptor present on the surface of platelets, neutrophils, monocytes, certain T-lymphocytes, and vascular endothelial cells. CD31 is involved in adhesion and signal transduction and is implicated in the regulation of a number of cellular processes. These include transendothelial migration of leukocytes, integrin regulation, and T-cell function, although its function in platelets remains unclear. In this study, we demonstrate the ability of the platelet agonists collagen, convulxin, and thrombin to induce tyrosine phosphorylation of CD31. Furthermore, we show that this event is independent of platelet aggregation and secretion and is accompanied by an increase in surface expression of CD31. A kinase capable of phosphorylating CD31 was detected in CD31 immunoprecipitates, and its activity was increased following activation of platelets. CD31 tyrosine phosphorylation was reduced or abolished by the Src family kinase inhibitor PP2, suggesting a role for these enzymes. In accordance with this, each of the Src family members expressed in platelets, namely Fyn, Lyn, Src, Yes, and Hck, was shown to co-immunoprecipitate with CD31. The involvement of Src family kinases in this process was confirmed through the study of mouse platelets deficient in Fyn.

Unusual isotope effect in the reaction of chlorosilylene with trimethylsilane-1-d: Absolute rate studies and quantum chemical and Rice–Ramsperger–Kassel–Marcus calculations provide strong evidence for the involvement of an intermediate complex

Time-resolved studies of chlorosilylene, ClSiH, generated by the 193 nm laser flash photolysis of 1-chloro-1- silacyclopent-3-ene, have been carried out to obtain rate constants for its bimolecular reaction with trimethylsilane-1-d, Me3SiD, in the gas phase. The reaction was studied at total pressures up to 100 Torr (with and without added SF6) over the temperature range of 295−407 K. The rate constants were found to be pressure independent and gave the following Arrhenius equation: log[(k/(cm3 molecule−1 s−1)] = (−13.22 ± 0.15) + [(13.20 ± 1.00) kJ mol−1]/(RT ln 10). When compared with previously published kinetic data for the reaction of ClSiH with Me3SiH, kinetic isotope effects, kD/kH, in the range from 7.4 (297 K) to 6.4 (407 K) were obtained. These far exceed values of 0.4−0.5 estimated for a single-step insertion process. Quantum chemical calculations (G3MP2B3 level) confirm not only the involvement of an intermediate complex, but also the existence of a low-energy internal isomerization pathway which can scramble the D and H atom labels. By means of Rice−Ramsperger−Kassel−Marcus modeling and a necessary (but small) refinement of the energy surface, we have shown that this mechanism can reproduce closely the experimental isotope effects. These findings provide the first experimental evidence for the isomerization pathway and thereby offer the most concrete evidence to date for the existence of intermediate complexes in the insertion reactions of silylenes.

The parental overprotection scale: associations with child and parental anxiety

Background: Parental overprotection has commonly been implicated in the development and maintenance of childhood anxiety disorders. Overprotection has been assessed using questionnaire and observational methods interchangeably; however, the extent to which these methods access the same construct has received little attention. Edwards, 2008 and Edwards et al., 2010 developed a promising parent-report measure of overprotection (OP) and reported that, with parents of pre-school children, the measure correlated with observational assessments and predicted changes in child anxiety symptoms. We aimed to validate the use of the OP measure with mothers of children in middle childhood, and examine its association with child and parental anxiety. Methods: Mothers of 90 children (60 clinically anxious, 30 non-anxious) aged 7–12 years completed the measure and engaged in a series of mildly stressful tasks with their child. Results: The internal reliability of the measure was good and scores correlated significantly with observations of maternal overprotection in a challenging puzzle task. Contrary to expectations, OP was not significantly associated with child anxiety status or symptoms, but was significantly associated with maternal anxiety symptoms. Limitations: Participants were predominantly from affluent social groups and of non-minority status. Overprotection is a broad construct, the use of specific sub-dimensions of behavioural constructs may be preferable. Conclusions: The findings support the use of the OP measure to assess parental overprotection among 7–12 year-old children; however, they suggest that parental responses may be more closely related to the degree of parental rather than child anxiety.

Direct involvement, partnership and setting: a study in bounded diversity

This paper brings a comparative aspect to the analysis of direct involvement as the foundation for partnership. It considers how various forms of direct involvement can represent components of a broader partnership paradigm of people management, or a limited shallow partnership concession to facilitate the diffusion of top-down human resource management policies. Through the use of survey evidence, we explore the settings in which involvement is more likely to be encountered. Contrary to predictions in much of the literature as to their universal applicability, we found that they tended to be concentrated in specific locales, organisational types and sectors, as part and parcel of wider cooperative production paradigms; in practical terms, if involvement is a prerequisite for meaningful partnership, then the latter is more likely to be encountered in more coordinated varieties of capitalism. This does not suggest, however, that ‘shallow’ or instrumentalist partnerships do not occur, or that in infertile ground genuine partnerships are not possible. On one hand, national variations encountered were broadly on the lines of the literature on comparative capitalism. On the other hand, there was much diversity within national settings; we identify the contexts in which such engagement is more or less likely and consider the implications.

fMRI evidence for the involvement of the procedural memory system in morphological processing of a second language

Behavioural evidence suggests that English regular past tense forms are automatically decomposed into their stem and affix (played  = play+ed) based on an implicit linguistic rule, which does not apply to the idiosyncratically formed irregular forms (kept). Additionally, regular, but not irregular inflections, are thought to be processed through the procedural memory system (left inferior frontal gyrus, basal ganglia, cerebellum). It has been suggested that this distinction does not to apply to second language (L2) learners of English; however, this has not been tested at the brain level. This fMRI study used a masked-priming task with regular and irregular prime-target pairs (played-play/kept-keep) to investigate morphological processing in native and highly proficient late L2 English speakers. No between-groups differences were revealed. Compared to irregular pairs, regular pairs activated the pars opercularis, bilateral caudate nucleus and the right cerebellum, which are part of the procedural memory network and have been connected with the processing of morphologically complex forms. Our study is the first to provide evidence for native-like involvement of the procedural memory system in processing of regular past tense by late L2 learners of English.

Parental death as a vital conjuncture? Intergenerational care and responsibility following bereavement in Senegal

This article explores the ways that parental death represents a 'vital conjuncture' for Serer young people that reconfigures and potentially transforms intergenerational caring responsibilities in different spatial and temporal contexts. Drawing on semi-structured interviews with young people (aged 15-27), family members, religious and community leaders and professionals in rural and urban Senegal, I explore young people's responses to parental death. 'Continuing bonds' with the deceased were expressed through memories evoked in homespace, shared family practices and gendered responsibilities to 'take care of' bereaved family members, to cultivate inherited farmland and to fulfil the wishes of the deceased. Parental death could reconfigure intergenerational care and lead to shifts in power dynamics, as eldest sons asserted their position of authority. While care-giving roles were associated with agency, the low social status accorded to young women's paid and unpaid domestic work undermined their efforts. The research contributes to understandings of gendered nuances in the experience of bereavement and continuing bonds and provides insight into intra-household decision-making processes, ownership and control of assets. Analysis of the culturally specific meanings of relationships and a young person's social location within hierarchies of gender, age, sibling birth order and wider socio-cultural norms and practices is needed.

Long-term depression activates transcription of immediate early transcription factor genes: involvement of serum response factor/Elk-1

Long-term depression (LTD) is one of the paradigms used in vivo or ex vivo for studying memory formation. In order to identify genes with potential relevance for memory formation we used mouse organotypic hippocampal slice cultures in which chemical LTD was induced by applications of 3,5-dihydroxyphenylglycine (DHPG). The induction of chemical LTD was robust, as monitored electrophysiologically. Gene expression analysis after chemical LTD induction was performed using cDNA microarrays containing >7,000 probes. The DHPG-induced expression of immediate early genes (c-fos, junB, egr1 and nr4a1) was subsequently verified by TaqMan polymerase chain reaction. Bioinformatic analysis suggested a common regulator element [serum response factor (SRF)/Elk-1 binding sites] within the promoter region of these genes. Indeed, here we could show a DHPG-dependent binding of SRF at the SRF response element (SRE) site within the promoter region of c-fos and junB. However, SRF binding to egr1 promoter sites was constitutive. The phosphorylation of the ternary complex factor Elk-1 and its localization in the nucleus of hippocampal neurones after DHPG treatment was shown by immunofluorescence using a phosphospecific antibody. We suggest that LTD leads to SRF/Elk-1-regulated gene expression of immediate early transcription factors, which could in turn promote a second broader wave of gene expression.

Patient and public involvement in healthcare quality improvement: how organizations can help patients and professionals to collaborate

Citizens across the world are increasingly called upon to participate in healthcare improvement. It is often unclear how this can be made to work in practice. This 4- year ethnography of a UK healthcare improvement initiative showed that patients used elements of organizational culture as resources to help them collaborate with healthcare professionals. The four elements were: (1) organizational emphasis on nonhierarchical, multidisciplinary collaboration; (2) organizational staff ability to model desired behaviours of recognition and respect; (3) commitment to rapid action, including quick translation of research into practice; and (4) the constant data collection and reflection process facilitated by improvement methods.