A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci

The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function

Pregnant Behind Bars: Meeting the Nutrition Needs of Incarcerated Pregnant Women

The number of women involved in the criminal justice system has increased dramatically over the past 20 years. Due to their marginalized background, incarcerated women have a complex set of health-related needs. This is especially true of those who are pregnant, a particularly vulnerable, high-risk group. Although guidelines have been developed that recommend pregnancy screening, provision of dietary supplements, regular nutritious meals, and nutritional counseling for incarcerated pregnant women, jail policies and health care protocols often fail to heed these recommendations. In this chapter, we discuss the nutritional needs of pregnant incarcerated women as well as breastfeeding in the context of the criminal justice system and consider some of the challenges in developing programming and policies to address these health-related needs. We also present findings from the William & Mary Healthy Beginnings Project, a nutrition intervention program developed for pregnant incarcerated women in Southeastern Virginia. Assessment of this program suggests that through the development of protocols and polices that consider the health-related needs of pregnant women, correctional facilities could play a pivotal role in helping incarcerated women develop healthier habits to better care for themselves and their newborns.https://scholarworks.wm.edu/asbookchapters/1106/thumbnail.jp

Developing community-based preventive interventions in Hong Kong: a description of the first phase of the family project

<p>Abstract</p> <p>Background</p> <p>This paper describes the development of culturally-appropriate family-based interventions and their relevant measures, to promote family health, happiness and harmony in Hong Kong. Programs were developed in the community, using a collaborative approach with community partners. The development process, challenges, and the lessons learned are described. This experience may be of interest to the scientific community as there is little information currently available about community-based development of brief interventions with local validity in cultures outside the West.</p> <p>Methods</p> <p>The academic-community collaborative team each brought strengths to the development process and determined the targets for intervention (parent-child relationships). Information from expert advisors and stakeholder discussion groups was collected and utilized to define the sources of stress in parent-child relationships.</p> <p>Results</p> <p>Themes emerged from the literature and discussion groups that guided the content of the intervention. Projects emphasized features that were appropriate for this cultural group and promoted potential for sustainability, so that the programs might eventually be implemented at a population-wide level. Challenges included ensuring local direction, relevance and acceptability for the intervention content, engaging participants and enhancing motivation to make behavior changes after a brief program, measurement of behavior changes, and developing an equal partner relationship between academic and community staff.</p> <p>Conclusions</p> <p>This work has public health significance because of the global importance of parent-child relationships as a risk-factor for many outcomes in adulthood, the need to develop interventions with strong evidence of effectiveness to populations outside the West, the potential application of our interventions to universal populations, and characteristics of the interventions that promote dissemination, including minimal additional costs for delivery by community agencies, and high acceptability to participants.</p

Children of Prisoners: Their Situation and Role in Long-Term Crime Prevention

Studies suggest that maintaining family ties can help reduce the likelihood of reoffending, and that while parental imprisonment can increase a child’s likelihood to offend, positive responses to the situation can aid the children’s well-being, attitude and attainment. Drawing on findings from the recently completed EU-funded COPING Project on the mental health of children of prisoners, this chapter explores the factors that aid a child’s ability to cope with parental imprisonment and the actions that different stakeholders can take to support them. It identifies some of the mental health impacts at different stages of parental imprisonment, the roles played by non-imprisoned parents/carers and by schools, and suggests options for further clarifying the factors that help and hinder children of prisoners in the short and long term

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN

Review of genetic factors in intestinal malrotation

Intestinal malrotation is well covered in the surgical literature from the point of view of operative management, but few reviews to date have attempted to provide a comprehensive examination of the topic from the point of view of aetiology, in particular genetic aetiology. Following a brief overview of molecular embryology of midgut rotation, we present in this article instances of and case reports and case series of intestinal malrotation in which a genetic aetiology is likely. Autosomal dominant, autosomal recessive, X-linked and chromosomal forms of the disorder are represented. Most occur in syndromic form, that is to say, in association with other malformations. In many instances, recognition of a specific syndrome is possible, one of several examples discussed being the recently described association of intestinal malrotation with alveolar capillary dysplasia, due to mutations in the forkhead box transcription factor FOXF1. New advances in sequencing technology mean that the identification of the genes mutated in these disorders is more accessible than ever, and paediatric surgeons are encouraged to refer to their colleagues in clinical genetics where a genetic aetiology seems likely