Modest Interference with Actin Dynamics in Primary T Cell Activation by Antigen Presenting Cells Preferentially Affects Lamellal Signaling

Dynamic subcellular distributions of signaling system components are critical regulators of cellular signal transduction through their control of molecular interactions. Understanding how signaling activity depends on such distributions and the cellular structures driving them is required for comprehensive insight into signal transduction. In the activation of primary murine T cells by antigen presenting cells (APC) signaling intermediates associate with various subcellular structures, prominently a transient, wide, and actin-associated lamellum extending from an interdigitated T cell:APC interface several micrometers into the T cell. While actin dynamics are well established as general regulators of cellular organization, their role in controlling signaling organization in primary T cell:APC couples and the specific cellular structures driving it is unresolved. Using modest interference with actin dynamics with a low concentration of Jasplakinolide as corroborated by costimulation blockade we show that T cell actin preferentially controls lamellal signaling localization and activity leading downstream to calcium signaling. Lamellal localization repeatedly related to efficient T cell function. This suggests that the transient lamellal actin matrix regulates T cell signaling associations that facilitate T cell activation

Gait changes in a line of mice artificially selected for longer limbs

In legged terrestrial locomotion, the duration of stance phase, i.e., when limbs are in contact with the substrate, is positively correlated with limb length, and negatively correlated with the metabolic cost of transport. These relationships are well documented at the interspecific level, across a broad range of body sizes and travel speeds. However, such relationships are harder to evaluate within species (i.e., where natural selection operates), largely for practical reasons, including low population variance in limb length, and the presence of confounding factors such as body mass, or training. Here, we compared spatiotemporal kinematics of gait in Longshanks, a long-legged mouse line created through artificial selection, and in random-bred, mass-matched Control mice raised under identical conditions. We used a gait treadmill to test the hypothesis that Longshanks have longer stance phases and stride lengths, and decreased stride frequencies in both fore- and hind limbs, compared with Controls. Our results indicate that gait differs significantly between the two groups. Specifically, and as hypothesized, stance duration and stride length are 8–10% greater in Longshanks, while stride frequency is 8% lower than in Controls. However, there was no difference in the touch-down timing and sequence of the paws between the two lines. Taken together, these data suggest that, for a given speed, Longshanks mice take significantly fewer, longer steps to cover the same distance or running time compared to Controls, with important implications for other measures of variation among individuals in whole-organism performance, such as the metabolic cost of transport

Gait changes in a line of mice artificially selected for longer limbs

In legged terrestrial locomotion, the duration of stance phase, i.e., when limbs are in contact with the substrate, is positively correlated with limb length, and negatively correlated with the metabolic cost of transport. These relationships are well documented at the interspecific level, across a broad range of body sizes and travel speeds. However, such relationships are harder to evaluate within species (i.e., where natural selection operates), largely for practical reasons, including low population variance in limb length, and the presence of confounding factors such as body mass, or training. Here, we compared spatiotemporal kinematics of gait in Longshanks, a long-legged mouse line created through artificial selection, and in random-bred, mass-matched Control mice raised under identical conditions. We used a gait treadmill to test the hypothesis that Longshanks have longer stance phases and stride lengths, and decreased stride frequencies in both fore- and hind limbs, compared with Controls. Our results indicate that gait differs significantly between the two groups. Specifically, and as hypothesized, stance duration and stride length are 810% greater in Longshanks, while stride frequency is 8% lower than in Controls. However, there was no difference in the touch- down timing and sequence of the paws between the two lines. Taken together, these data suggest that, for a given speed, Longshanks mice take significantly fewer, longer steps to cover the same distance or running time compared to Controls, with important implications for other measures of variation among individuals in whole-organism performance, such as the metabolic cost of transport

Sharing of either phenotypes or genetic variants can increase the accuracy of genomic prediction of feed efficiency.

BACKGROUND Sharing individual phenotype and genotype data between countries is complex and fraught with potential errors, while sharing summary statistics of genome-wide association studies (GWAS) is relatively straightforward, and thus would be especially useful for traits that are expensive or difficult-to-measure, such as feed efficiency. Here we examined: (1) the sharing of individual cow data from international partners; and (2) the use of sequence variants selected from GWAS of international cow data to evaluate the accuracy of genomic estimated breeding values (GEBV) for residual feed intake (RFI) in Australian cows. RESULTS GEBV for RFI were estimated using genomic best linear unbiased prediction (GBLUP) with 50k or high-density single nucleotide polymorphisms (SNPs), from a training population of 3797 individuals in univariate to trivariate analyses where the three traits were RFI phenotypes calculated using 584 Australian lactating cows (AUSc), 824 growing heifers (AUSh), and 2526 international lactating cows (OVE). Accuracies of GEBV in AUSc were evaluated by either cohort-by-birth-year or fourfold random cross-validations. GEBV of AUSc were also predicted using only the AUS training population with a weighted genomic relationship matrix constructed with SNPs from the 50k array and sequence variants selected from a meta-GWAS that included only international datasets. The genomic heritabilities estimated using the AUSc, OVE and AUSh datasets were moderate, ranging from 0.20 to 0.36. The genetic correlations (rg) of traits between heifers and cows ranged from 0.30 to 0.95 but were associated with large standard errors. The mean accuracies of GEBV in Australian cows were up to 0.32 and almost doubled when either overseas cows, or both overseas cows and AUS heifers were included in the training population. They also increased when selected sequence variants were combined with 50k SNPs, but with a smaller relative increase. CONCLUSIONS The accuracy of RFI GEBV increased when international data were used or when selected sequence variants were combined with 50k SNP array data. This suggests that if direct sharing of data is not feasible, a meta-analysis of summary GWAS statistics could provide selected SNPs for custom panels to use in genomic selection programs. However, since this finding is based on a small cross-validation study, confirmation through a larger study is recommended

Generating forms of media capital inside and outside a field: the strange case of David Cameron in the UK political field

As societies become more ‘mediated’ so the elevation of public figures is increasingly linked to their ability to generate a positive public profile through the mass media. Politicians, artists, film stars, authors and others each gain professional status, in part, based on how consumer-citizens actively respond to media representations of themselves. The linking of media to individual celebrity and symbolic power is now implicit in much writing. Individuals succeed because of their personal charisma (Weber, 1948) and an innate ability to present a media personality that directly engages with large publics (Ankersmit, 1997; Horton and Wohl, 1993; Pels, 2003; Street, 2003). Alternatively, one’s symbolic image is primarily manufactured by promotional professionals (Boorstin, 1962; Evans, 2005; Franklin, 2004; Hall Jamieson, 1996; Lilleker and LeesMarshment, 2006) and parts of themedia industry itself (Evans and Hesmondhalgh, 2005; Turner, 2004). However one’s public image develops, media exposure then bestows a ‘primary definer’ status on those placed in positions of power thus drawing additional media coverage (Bennett, 1990; Champagne, 2005; Hall et al., 1978, Herman and Chomsky, 2002)

Evaluation of a web-based intervention to reduce antibiotic prescribing for LRTI in six European countries: quantitative process analysis of the GRACE/INTRO randomised controlled trial.

To reduce the spread of antibiotic resistance, there is a pressing need for worldwide implementation of effective interventions to promote more prudent prescribing of antibiotics for acute LRTI. This study is a process analysis of the GRACE/INTRO trial of a multifactorial intervention that reduced antibiotic prescribing for acute LRTI in six European countries. The aim was to understand how the interventions were implemented and to examine effects of the interventions on general practitioners' (GPs') and patients' attitudes

A population-based study of race-specific risk for placental abruption

<p>Abstract</p> <p>Background</p> <p>Efforts to elucidate risk factors for placental abruption are imperative due to the severity of complications it produces for both mother and fetus, and its contribution to preterm birth. Ethnicity-based differences in risk of placental abruption and preterm birth have been reported. We tested the hypotheses that race, after adjusting for other factors, is associated with the risk of placental abruption at specific gestational ages, and that there is a greater contribution of placental abruption to the increased risk of preterm birth in Black mothers, compared to White mothers.</p> <p>Methods</p> <p>We conducted a population-based cohort study using the Missouri Department of Health's maternally-linked database of all births in Missouri (1989–1997) to assess racial effects on placental abruption and the contribution of placental abruption to preterm birth, at different gestational age categories (n = 664,303).</p> <p>Results</p> <p>Among 108,806 births to Black mothers and 555,497 births to White mothers, 1.02% (95% CI 0.96–1.08) of Black births were complicated by placental abruption, compared to 0.71% (95% CI 0.69–0.73) of White births (aOR 1.32, 95% CI 1.22–1.43). The magnitude of risk of placental abruption for Black mothers, compared to White mothers, increased with younger gestational age categories. The risk of placental abruption resulting in term and extreme preterm births (< 28 weeks) was higher for Black mothers (aOR 1.15, 95% CI 1.02–1.29 and aOR 1.98, 95% CI 1.58–2.48, respectively). Compared to White women delivering in the same gestational age category, there were a significantly higher proportion of placental abruption in Black mothers who delivered at term, and a significantly lower proportion of placental abruption in Black mothers who delivered in all preterm categories (p < 0.05).</p> <p>Conclusion</p> <p>Black women have an increased risk of placental abruption compared to White women, even when controlling for known coexisting risk factors. This risk increase is greatest at the earliest preterm gestational ages when outcomes are the poorest. The relative contribution of placental abruption to term births was greater in Black women, whereas the relative contribution of placental abruption to preterm birth was greater in White women.</p

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

"Give me some space" : exploring youth to parent aggression and violence

A small scale qualitative project, undertaken by an interdisciplinary domestic violence research group involving academic researchers and research assistants, with colleagues from Independent Domestic Abuse Services (IDAS), investigated youth aggression and violence against parents. Following the literature review, data was generated through several research conversations with young people (n = 2), through semi-structured interviews with mothers (n = 3) and practitioners (n = 5), and through a practitioner focus group (n = 8). Thematic analysis and triangulation of the data from parents, practitioners and young people, elicited interconnected and complex overarching themes. Young people could be both victim and perpetrator. The witnessing or experiencing of domestic aggression and violence raised the concept of ‘bystander children’. The impact of young people experiencing familial violence was underestimated by parents. For practitioners, the effects of working with domestic violence was shown to be significant - both positively and negatively