ATG proteins mediate efferocytosis and suppress inflammation in mammary involution.

Involution is the process of post-lactational mammary gland regression to quiescence and it involves secretory epithelial cell death, stroma remodeling and gland repopulation by adipocytes. Though reportedly accompanying apoptosis, the role of autophagy in involution has not yet been determined. We now report that autophagy-related (ATG) proteins mediate dead cell clearance and suppress inflammation during mammary involution. In vivo, Becn1(+/-) and Atg7-deficient mammary epithelial cells (MECs) produced 'competent' apoptotic bodies, but were defective phagocytes in association with reduced expression of the MERTK and ITGB5 receptors, thus pointing to defective apoptotic body engulfment. Atg-deficient tissues exhibited higher levels of involution-associated inflammation, which could be indicative of a tumor-modulating microenvironment, and developed ductal ectasia, a manifestation of deregulated post-involution gland remodeling. In vitro, ATG (BECN1 or ATG7) knockdown compromised MEC-mediated apoptotic body clearance in association with decreased RAC1 activation, thus confirming that, in addition to the defective phagocytic processing reported by other studies, ATG protein defects also impair dead cell engulfment. Using two different mouse models with mammary gland-associated Atg deficiencies, our studies shed light on the essential role of ATG proteins in MEC-mediated efferocytosis during mammary involution and provide novel insights into this important developmental process. This work also raises the possibility that a regulatory feedback loop exists, by which the efficacy of phagocytic cargo processing in turn regulates the rate of engulfment and ultimately determines the kinetics of phagocytosis and dead cell clearance

Strategic approaches to managing human relations within construction SMEs

Organisational success is dependent upon the effective management of people. At the heart of this process is an organisation’s HRM strategy, which should seek to align HRM practices with the wider organisational objectives. This paper investigates employee relations as one key area of Strategic Human resource management (SHRM) within construction SMEs. The aim of this part of the research is to examine the multi facetted nature of the SHRM function and particularly the perspectives of employee relations. These issues were explored via semi-structured interviews with the strategy makers and HR or middle mangers of construction SMEs. It provides an insight into the way in which employee relations are implemented as part of the SHRM function. A wide range of techniques were utilised within a small number of organisations, the larger organisations within the group exhibited highly structured objectives and procedures. It forms part of a wider study which aims to explore further the components and types of SHRM strategies used by construction SMEs in order to improve organisational performance. The ultimate outcome of the research is to develop a model of SME SHRM practice that helps firms to reconcile their HRM needs with the problematic operating context provided by the industry

Childcare Practitioners’ Knowledge and Perceptions of Play Therapy

This study investigated the awareness of play therapy in childcare practitioners working in the areas of health, social care, education and childcare. Questionnaires were distributed to 65 workers drawn from these occupational categories in order to investigate their understanding of issues such as the nature of play therapy, the referral process, and the distinction between play therapy and other forms of play based interventions. In addition, one child care professional from each of the four sectors was selected to take part in a follow-up interview to build on the information generated from the questionnaires. The results from the questionnaires and follow-up interviews showed that while most of the child care professionals had heard of this approach, they had a limited knowledge of the nature of play therapy. There was also much confusion amongst the child care professionals around the difference between play therapy and other play based interventions as well as around different professionals’ roles and responsibilities for referring children and young people to therapeutic interventions. The implications of these findings for the practice of play therapy are considered

Gendered Perceptions of Domestic Violence: how young females are more likely than young males to know controlling domestic violence behaviours

Research shows that young people hold narrow views about what is domestic violence. As such, some of their views indicate support for the use of violence in intimate relationships. Gender seems to impact upon such views. We sought to assess the impact of gender on students’ perceptions of domestic violence at a university in the North of England, using a survey. Our findings show that females considered a broader range of behaviours as domestic violence, particularly the psychological/emotional and financial violences, compared to males. Whilst most of the sample constructed domestic violence behaviours as committed by male perpetrators against female victims, females were more likely to strongly disagree that males and females are equally violent in relationships. Our argument is that females were more likely to know about controlling domestic violence behaviours because they are more likely victims of domestic violence. The research has important ramifications for challenging stereotypes of gender roles and expectations about gendered behaviours

Individual correlates of podoconiosis in areas of varying endemicity: a case-control study

BACKGROUND Podoconiosis is a non-filarial form of elephantiasis resulting in lymphedema of the lower legs. Previous studies have suggested that podoconiosis arises from the interplay of individual and environmental factors. Here, our aim was to understand the individual-level correlates of podoconiosis by comparing 460 podoconiosis-affected individuals and 707 unaffected controls. METHODS/PRINCIPAL FINDINGS This was a case-control study carried out in six kebeles (the lowest governmental administrative unit) in northern Ethiopia. Each kebele was classified into one of three endemicity levels: 'low' (prevalence 5%). A total of 142 (30.7%) households had two or more cases of podoconiosis. Compared to controls, the majority of the cases, especially women, were less educated (OR = 1.7, 95% CI = 1.3 to 2.2), were unmarried (OR = 3.4, 95% CI = 2.6-4.6) and had lower income (t = -4.4, p<0.0001). On average, cases started wearing shoes ten years later than controls. Among cases, age of first wearing shoes was positively correlated with age of onset of podoconiosis (r = 0.6, t = 12.5, p<0.0001). Among all study participants average duration of shoe wearing was less than 30 years. Between both cases and controls, people in 'high' and 'medium' endemicity kebeles were less likely than people in 'low' endemicity areas to 'ever' have owned shoes (OR = 0.5, 95% CI = 0.4-0.7). CONCLUSIONS Late use of shoes, usually after the onset of podoconiosis, and inequalities in education, income and marriage were found among cases, particularly among females. There were clustering of cases within households, thus interventions against podoconiosis will benefit from household-targeted case tracing. Most importantly, we identified a secular increase in shoe-wearing over recent years, which may give opportunities to promote shoe-wearing without increasing stigma among those at high risk of podoconiosis

Cytochrome P450 168A1 from Pseudomonas aeruginosa is involved in the hydroxylation of biologically relevant fatty acids

The cytochrome P450 CYP168A1 from Pseudomonas aeruginosa was cloned and expressed in Escherichia coli followed by purification and characterization of function. CYP168A1 is a fatty acid hydroxylase that hydroxylates saturated fatty acids, including myristic (0.30 min-1), palmitic (1.61 min-1) and stearic acids (1.24 min-1), at both the ω-1- and ω-2-positions. However, CYP168A1 only hydroxylates unsaturated fatty acids, including palmitoleic (0.38 min-1), oleic (1.28 min-1) and linoleic acids (0.35 min-1), at the ω-1-position. CYP168A1 exhibited a catalytic preference for palmitic, oleic and stearic acids as substrates in keeping with the phosphatidylcholine-rich environment deep in the lung that is colonized by P. aeruginosa

Vaccinia Virus Gene B7R Encodes an 18-kDa Protein That is Resident in the Endoplasmic Reticulum and Affects Virus Virulence

AbstractThis paper presents a characterisation of vaccinia virus (VV) gene B7R that was predicted to encode a polypeptide of 182 amino acids with an N-terminal signal peptide. In vitro transcription and translation analysis showed the B7R gene product was a 21-kDa protein that, in the presence of microsomes, was processed into an 18-kDa mature form. The 18-kDa form associated with the microsomal membranes and was within the lumen of the vesicle where it was inaccessible to exogenous protease or an antibody raised against the B7R C terminus. Within VV-infected cells, the 18-kDa form of B7R was detected late during infection in the endoplasmic reticulum where it colocalised with protein disulphide isomerase. The B7R protein was detected neither in the culture supernatant nor associated with virus particles. A virus deletion mutant lacking the B7R gene and a revertant virus were constructed. Compared to wild-type and revertant viruses, the deletion mutant replicated normally in cell culture and had unaltered virulence in a murine intranasal model of infection. However, the deletion mutant was attenuated in a murine intradermal model where it induced a smaller lesion than the control viruses