Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction

Run, Jump, Throw and Catch: How proficient are children attending English schools at the Fundamental Motor Skills identified as key within the school curriculum?

This study examined proficiency levels in fundamental motor skills (FMS) in children within Key Stage 1 and 2 of the English school system. Four hundred and ninety-two children aged 6–9 Years old (245 boys, 247 girls) from school Years Two (n = 130), Three (n = 154) and Four (n = 208) participated in this study. FMS for the run, jump, throw and catch were assessed using the Test of Gross Motor Development – 2. The proportion of children who achieved mastery or near mastery of the skills was determined. For the whole sample, 18.5% (n = 91) did not achieve mastery in any of the four skills. A similar proportion (18.7%, n = 92) achieved mastery in all four of the FMS examined in this study. The proportion of children achieving mastery of all four skills was lower for Year Two children (0%) compared to children in years Three (24%) and Four (25%). More boys (25.7%) achieved mastery in all four of the FMS compared to girls (11.7%). Individual behavioural components in skill performance were also examined. The results of the present study highlight that less than one-fifth of children aged 6–9 years old have mastered the four key FMS identified by the physical education (PE) curriculum despite having the developmental potential to become fundamentally competent by six years of age. Fostering positive trajectories of FMS development presents a challenge for PE specialists given the association between FMS mastery in childhood and physical activity, weight status and health.N/

Saving Lives With Advice: The Impact of Advice on the Health and Wellbeing of Citizens Advice Manchester clients

The aim of this report was to understand the impact of advice on health and wellbeing for the people of Manchester. Focusing specifically on Citizens Advice Manchester, it adopted a mixedmethods approach. 11 participants took part in either focus group, face-to-face interviews, or phone interviews in June and July 2015. In addition, a quantitative analysis of the data collected by Citizens Advice Manchester was conducted, covering the period from 1st April 2014-31st March 2015

Structure–activity relationships on the odor detectability of homologous carboxylic acids by humans

We measured concentration detection functions for the odor detectability of the homologs: formic, acetic, butyric, hexanoic, and octanoic acids. Subjects (14 ≤ n ≤ 18) comprised young (19–37 years), healthy, nonsmoker, and normosmic participants from both genders. Vapors were delivered by air dilution olfactometry, using a three-alternative forced-choice procedure against carbon-filtered air, and an ascending concentration approach. Delivered concentrations were established by gas chromatography (flame ionization detector) in parallel with testing. Group and individual olfactory functions were modeled by a sigmoid (logistic) equation from which two parameters are calculated: C, the odor detection threshold (ODT) and D, the steepness of the function. Thresholds declined with carbon chain length along formic, acetic, and butyric acid where they reached a minimum (ODTs = 514, 5.2, and 0.26 ppb by volume, respectively). Then, they increased for hexanoic (1.0 ppb) and octanoic (0.86 ppb) acid. Odor thresholds and interindividual differences in olfactory acuity among these young, normosmic participants were lower than traditionally thought and reported. No significant effects of gender on odor detectability were observed. The finding of an optimum molecular size for odor potency along homologs confirms a prediction made by a model of ODTs based on a solvation equation. We discuss the mechanistic implications of this model for the process of olfactory detection

The female perspective of personality in a wild songbird: repeatable aggressiveness relates to exploration behaviour

ABSTRACT: Males often express traits that improve competitive ability, such as aggressiveness. Females also express such traits but our understanding about why is limited. Intraspecific aggression between females might be used to gain access to reproductive resources but simultaneously incurs costs in terms of energy and time available for reproductive activities, resulting in a trade-off. Although consistent individual differences in female behaviour (i.e. personality) like aggressiveness are likely to influence these reproductive trade-offs, little is known about the consistency of aggressiveness in females. To quantify aggression we presented a female decoy to free-living female great tits (Parus major) during the egg-laying period, and assessed whether they were consistent in their response towards this decoy. Moreover, we assessed whether female aggression related to consistent individual differences in exploration behaviour in a novel environment. We found that females consistently differed in aggressiveness, although first-year females were on average more aggressive than older females. Moreover, conform life history theory predictions, ‘fast’ exploring females were more aggressive towards the decoy than ‘slow’ exploring females. Given that personality traits are often heritable, and correlations between behaviours can constrain short term adaptive evolution, our findings highlight the importance of studying female aggression within a multivariate behavioural framework

Renal epithelial cells retain primary cilia during human acute renal allograft rejection injury

OBJECTIVES: Primary cilia are sensory organelles which co-ordinate several developmental/repair pathways including hedgehog signalling. Studies of human renal allografts suffering acute tubular necrosis have shown that length of primary cilia borne by epithelial cells doubles throughout the nephron and collecting duct, and then normalises as renal function returns. Conversely the loss of primary cilia has been reported in chronic allograft rejection and linked to defective hedgehog signalling. We investigated the fate of primary cilia in renal allografts suffering acute rejection. RESULTS: Here we observed that in renal allografts undergoing acute rejection, primary cilia were retained, with their length increasing 1 week after transplantation and remaining elevated. We used a mouse model of acute renal injury to demonstrate that elongated renal primary cilia in the injured renal tubule show evidence of smoothened accumulation, a biomarker for activation of hedgehog signalling. We conclude that primary cilium-mediated activation of hedgehog signalling is still possible during the acute phase of renal allograft rejection