Distance constraints on activation of TRPV4 channels by AKAP150-bound PKCα in arterial myocytes.

TRPV4 (transient receptor potential vanilloid 4) channels are Ca2+-permeable channels that play a key role in regulating vascular tone. In arterial myocytes, opening of TRPV4 channels creates local increases in Ca2+ influx, detectable optically as "TRPV4 sparklets." TRPV4 sparklet activity can be enhanced by the action of the vasoconstrictor angiotensin II (AngII). This modulation depends on the activation of subcellular signaling domains that comprise protein kinase C α (PKCα) bound to the anchoring protein AKAP150. Here, we used super-resolution nanoscopy, patch-clamp electrophysiology, Ca2+ imaging, and mathematical modeling approaches to test the hypothesis that AKAP150-dependent modulation of TRPV4 channels is critically dependent on the distance between these two proteins in the sarcolemma of arterial myocytes. Our data show that the distance between AKAP150 and TRPV4 channel clusters varies with sex and arterial bed. Consistent with our hypothesis, we further find that basal and AngII-induced TRPV4 channel activity decays exponentially as the distance between TRPV4 and AKAP150 increases. Our data suggest a maximum radius of action of ∼200 nm for local modulation of TRPV4 channels by AKAP150-associated PKCα

How people with dementia use twitter: A qualitative analysis

This is the final version. Available from Elsevier via the DOI in this record. People with dementia are publicly sharing their experiences of living with the condition and acting collectively to produce social change. Social media could support them in doing this, but no previous studies have comprehensively analysed their use of Twitter. The aims of this study were to identify how people with dementia use Twitter and examine the illness identities they create and promote online. Tweetcatcher was used to collect 2774 tweets posted over six months by 12 account holders with dementia, across three countries. Tweets were analysed thematically. Six themes were identified through the analysis: nothing about us without us, collective action, experts by experience, living with dementia not suffering from it, community, and stories of dementia. On Twitter, people with dementia are developing a collective illness identity to further a social movement that is focused on improving the lives of people with dementia. They are also communicating their personal identities by documenting their lived experiences. Twitter is being used to convey positive, rather than negative, messages about dementia. The findings of this study also show that thematic analysis can be applied to micro texts that can combine over time to form longer narratives.National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula (PenCLAHRC)

PhylOTU: a high-throughput procedure quantifies microbial community diversity and resolves novel taxa from metagenomic data.

Microbial diversity is typically characterized by clustering ribosomal RNA (SSU-rRNA) sequences into operational taxonomic units (OTUs). Targeted sequencing of environmental SSU-rRNA markers via PCR may fail to detect OTUs due to biases in priming and amplification. Analysis of shotgun sequenced environmental DNA, known as metagenomics, avoids amplification bias but generates fragmentary, non-overlapping sequence reads that cannot be clustered by existing OTU-finding methods. To circumvent these limitations, we developed PhylOTU, a computational workflow that identifies OTUs from metagenomic SSU-rRNA sequence data through the use of phylogenetic principles and probabilistic sequence profiles. Using simulated metagenomic data, we quantified the accuracy with which PhylOTU clusters reads into OTUs. Comparisons of PCR and shotgun sequenced SSU-rRNA markers derived from the global open ocean revealed that while PCR libraries identify more OTUs per sequenced residue, metagenomic libraries recover a greater taxonomic diversity of OTUs. In addition, we discover novel species, genera and families in the metagenomic libraries, including OTUs from phyla missed by analysis of PCR sequences. Taken together, these results suggest that PhylOTU enables characterization of part of the biosphere currently hidden from PCR-based surveys of diversity

Kv2.1 channels play opposing roles in regulating membrane potential, Ca2+ channel function, and myogenic tone in arterial smooth muscle.

The accepted role of the protein Kv2.1 in arterial smooth muscle cells is to form K+ channels in the sarcolemma. Opening of Kv2.1 channels causes membrane hyperpolarization, which decreases the activity of L-type CaV1.2 channels, lowering intracellular Ca2+ ([Ca2+]i) and causing smooth muscle relaxation. A limitation of this model is that it is based exclusively on data from male arterial myocytes. Here, we used a combination of electrophysiology as well as imaging approaches to investigate the role of Kv2.1 channels in male and female arterial myocytes. We confirmed that Kv2.1 plays a canonical conductive role but found it also has a structural role in arterial myocytes to enhance clustering of CaV1.2 channels. Less than 1% of Kv2.1 channels are conductive and induce membrane hyperpolarization. Paradoxically, by enhancing the structural clustering and probability of CaV1.2-CaV1.2 interactions within these clusters, Kv2.1 increases Ca2+ influx. These functional impacts of Kv2.1 depend on its level of expression, which varies with sex. In female myocytes, where expression of Kv2.1 protein is higher than in male myocytes, Kv2.1 has conductive and structural roles. Female myocytes have larger CaV1.2 clusters, larger [Ca2+]i, and larger myogenic tone than male myocytes. In contrast, in male myocytes, Kv2.1 channels regulate membrane potential but not CaV1.2 channel clustering. We propose a model in which Kv2.1 function varies with sex: in males, Kv2.1 channels control membrane potential but, in female myocytes, Kv2.1 plays dual electrical and CaV1.2 clustering roles. This contributes to sex-specific regulation of excitability, [Ca2+]i, and myogenic tone in arterial myocytes

Global marine bacterial diversity peaks at high latitudes in winter.

Genomic approaches to characterizing bacterial communities are revealing significant differences in diversity and composition between environments. But bacterial distributions have not been mapped at a global scale. Although current community surveys are way too sparse to map global diversity patterns directly, there is now sufficient data to fit accurate models of how bacterial distributions vary across different environments and to make global scale maps from these models. We apply this approach to map the global distributions of bacteria in marine surface waters. Our spatially and temporally explicit predictions suggest that bacterial diversity peaks in temperate latitudes across the world's oceans. These global peaks are seasonal, occurring 6 months apart in the two hemispheres, in the boreal and austral winters. This pattern is quite different from the tropical, seasonally consistent diversity patterns observed for most macroorganisms. However, like other marine organisms, surface water bacteria are particularly diverse in regions of high human environmental impacts on the oceans. Our maps provide the first picture of bacterial distributions at a global scale and suggest important differences between the diversity patterns of bacteria compared with other organisms

Patterns of Objectively Measured Moderate-to-Vigorous Physical Activity in Preschool Children.

BACKGROUND: Identifying periods of the day which are susceptible to varying levels of physical activity (PA) may help identify key times to intervene and potentially change preschool children's PA behaviors. This study assessed variability of objectively measured moderate-to-vigorous physical activity (MVPA) during weekdays and weekend days among preschool children. METHODS: One hundred and eighty-eight children (aged 3 to 5 years; 53.2% boys) from a northwest English city wore uni-axial accelerometers for 7 consecutive days. RESULTS: Higher levels of MVPA were recorded in boys, particularly those who attended preschool for a half day. Children who attended preschool for a full day engaged in 11.1 minutes less MVPA than children who attended for a half day. After-school hours were characterized by a decrease in activity for all groups. Patterns of activity during the weekend were smoother with less variability. CONCLUSION: This study identified discrete segments of the week, specifically afterschool and during the weekend, when preschoolers engage in low levels of PA. Higher levels of MVPA among children who attended preschool for less time each day suggests that the structured preschool environment is related to decreased activity. Consequently, there is a need for interventions in young children to focus on school and home environments

Benefits of daddy play

The Fathers’ Engagement Project was designed to assess the impact and feasibility of a six week physically active play based programme on fathers’ engagement with their three to five year old children. Sessions were held at City based Children’s Centres. Fathers’ engagement and attitudes to child PA were measured pre- and post-intervention via questionnaire. Acceptability of the intervention was explored through participant and staff focus groups. Results from questionnaires showed that fathers felt more in control of their children and had increased awareness of their role in motivating their child to play. Fathers also suggested that sessions provided opportunities to spend quality time with their children despite there being no significant increase in the overall time fathers self-reported spending with their child during the week or at the weekend. A number of recommendations for both research and practice are provided

Bayesian Power Spectrum Analysis of the First-Year WMAP data

We present the first results from a Bayesian analysis of the WMAP first year data using a Gibbs sampling technique. Using two independent, parallel supercomputer codes we analyze the WMAP Q, V and W bands. The analysis results in a full probabilistic description of the information the WMAP data set contains about the power spectrum and the all-sky map of the cosmic microwave background anisotropies. We present the complete probability distributions for each C_l including any non-Gaussianities of the power spectrum likelihood. While we find good overall agreement with the previously published WMAP spectrum, our analysis uncovers discrepancies in the power spectrum estimates at low l multipoles. For example we claim the best-fit Lambda-CDM model is consistent with the C_2 inferred from our combined Q+V+W analysis with a 10% probability of an even larger theoretical C_2. Based on our exact analysis we can therefore attribute the "low quadrupole issue" to a statistical fluctuation.Comment: 5 pages. 4 figures. For additional information and data see http://www.astro.uiuc.edu/~iodwyer/research#wma