UV-Independent Induction of Beta Defensin 3 in Neonatal Human Skin Explants

In order to determine the effect of UV radiation on β-defensin 3 (BD3) expression in human skin, freshly-isolated UV-naïve skin was obtained from newborn male infants undergoing planned circumcision. Skin explants sustained ex vivo dermis side down on RPMI media were exposed to 0.5 kJ/m2 UVB, and biopsies were taken from the explant through 72 hours after radiation. mRNA expression was measured by qRTPCR and normalized to TATA-binding protein. BD3 expression at each time point was compared with an untreated control taken at time 0 within each skin sample. Extensive variability in both the timing and magnitude of BD3 induction across individuals was noted and was not predicted by skin pigment phenotype, suggesting that BD3 induction was not influenced by epidermal melanization. However, a mock-irradiated time course demonstrated UV-independent BD3 mRNA increases across multiple donors which was not further augmented by treatment with UV radiation, suggesting that factors other than UV damage promoted increased BD3 expression in the skin explants. We conclude that BD3 expression is induced in a UV-independent manner in human skin explants processed and maintained in standard culture conditions, and that neonatal skin explants are an inappropriate model with which to study the effects of UV on BD3 induction in whole human skin

Wave function-dependent mobility and suppression of interface roughness scattering in a strained SiGe p-channel field-effect structure

The 4 K Hall mobility has been measured in a top-gated, inverted, modulation-doped Si/Si0.8Ge0.2 structure having a Si:B doping layer beneath the alloy. From comparisons with theoretical calculations, we argue that, unlike an ordinary enhancement-mode SiGe p-channel metal–oxide–semiconductor structure, this configuration leads to a decrease of interface roughness scattering with increasing sheet carrier density. We also speculate on the nature of the interface charge observed in these structures at low temperature

Melanocortin 1 Receptor: Structure, Function, and Regulation

The melanocortin 1 receptor (MC1R) is a melanocytic Gs protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3. Activation of cAMP signaling up-regulates melanin production and deposition in the epidermis which functions to limit UV penetration into the skin and enhances nucleotide excision repair (NER), the genomic stability pathway responsible for clearing UV photolesions from DNA to avoid mutagenesis. Herein we review MC1R structure and function and summarize our laboratory’s findings on the molecular mechanisms by which MC1R signaling impacts NER

Divergence of cAMP Signalling Pathways Mediating Augmented Nucleotide Excision Repair and Pigment Induction in Melanocytes

Loss‐of‐function melanocortin 1 receptor (MC1R) polymorphisms are common in UV‐sensitive fair‐skinned individuals and are associated with blunted cAMP second messenger signalling and higher lifetime risk of melanoma because of diminished ability of melanocytes to cope with UV damage. cAMP signalling positions melanocytes to resist UV injury by upregulating synthesis of UV‐blocking eumelanin pigment and by enhancing the repair of UV‐induced DNA damage. cAMP enhances melanocyte nucleotide excision repair (NER), the genome maintenance pathway responsible for the removal of mutagenic UV photolesions, through cAMP‐activated protein kinase (protein kinase A)‐mediated phosphorylation of the ataxia telangiectasia‐mutated and Rad3‐related (ATR) protein on the S435 residue. We investigated the interdependence of cAMP‐mediated melanin upregulation and cAMP‐enhanced DNA repair in primary human melanocytes and a melanoma cell line. We observed that the ATR‐dependent molecular pathway linking cAMP signalling to the NER pathway is independent of MITF activation. Similarly, cAMP‐mediated upregulation of pigment synthesis is independent of ATR, suggesting that the key molecular events driving MC1R‐mediated enhancement of genome maintenance (eg PKA‐mediated phosphorylation of ATR) and MC1R‐induced pigment induction (eg MITF activation) are distinct

Chronic disease self-management education courses: utilization by low-income, middle-aged participants

BACKGROUND: Individuals living in lower-income areas face an increased prevalence of chronic disease and, oftentimes, greater barriers to optimal self-management. Disparities in disease management are seen across the lifespan, but are particularly notable among middle-aged adults. Although evidence-based Chronic Disease Self-management Education courses are available to enhance self-management among members of this at-risk population, little information is available to determine the extent to which these courses are reaching those at greatest risk. The purpose of this study is to compare the extent to which middle-aged adults from lower- and higher-income areas have engaged in CDSME courses, and to identify the sociodemographic characteristics of lower-income, middle aged participants. METHODS: The results of this study were produced through analysis of secondary data collected during the Communities Putting Prevention to Work: Chronic Disease Self-Management Program initiative. During this initiative, data was collected from 100,000 CDSME participants across 45 states within the United States, the District of Columbia, and Puerto Rico. RESULTS: Of the entire sample included in this analysis (19,365 participants), 55 people lived in the most impoverished counties. While these 55 participants represented just 0.3% of the total study sample, researchers found this group completed courses more frequently than participants from less impoverished counties once enrolled. CONCLUSION: These results signal a need to enhance participation of middle-aged adults from lower-income areas in CDSME courses. The results also provide evidence that can be used to inform future program delivery choices, including decisions regarding recruitment materials, program leaders, and program delivery sites, to better engage this population

Access to Dental Care for Children and Young People in Care and Care Leavers: A Global Scoping Review

Aims: This scoping review aimed to explore three research questions: 1. What is the dental care access for children and young people (CYP) in care and care leavers? 2. What factors influence CYP in care and care leavers’ access to dental care? 3. What pathways have been developed to improve access to oral health care for CYP in care and care leavers? Methods: Five databases (Ovid MEDLINE, Ovid Embase, CINAHL, SocINDEX and Dentistry and Oral Sciences Source) and grey literature sources were systematically searched. Articles relating to CYP in care or care leavers aged 0–25 years old, published up to January 2023 were included. Abstracts, posters and publications not in the English language were excluded. The data relating to dental care access were analysed using thematic analysis. Results: The search identified 942 articles, of which 247 were excluded as duplicates. A review of the titles and abstracts yielded 149 studies. Thirty-eight were eligible for inclusion in the review: thirty-three peer-reviewed articles, one PhD thesis and four grey literature sources. All papers were published from very high or medium Human Development Index countries. The studies indicate that despite having higher treatment needs, CYP in care and care leavers experience greater difficulty in accessing dental services than those not care-experienced. Organisational, psycho-social and logistical factors influence their access to dental care. Their experience of dental care may be impacted by adverse childhood events. Pathways to dental care have been developed, but little is known of their impact on access. There are very few studies that include care leavers. The voices of care-experienced CYP are missing from dental access research. Conclusions: care-experienced CYP are disadvantaged in their access to dental care, and there are significant barriers to their treatment needs being met

Organisational participation and women - an attitude problem?

Employee participation is a dynamic and contested area of organisational behaviour, attracting continuing academic, practitioner and policy interest and debate. This chapter focuses on organisational participation and women

Occupational sex-segregation, specialized human capital and wages: evidence from Britain

Female-dominated occupations are poorly paid, but there is disagreement about why. Sociological explanations argue that pay in such occupations is low because society undervalues 'women's work', while economic theory argues that this is due to scant requirements for specialized skills. This article sheds light over these debates by examining the impact of occupational feminization on wages in Britain and exploring the mechanisms that produce it, using innovative statistical models that account for both observable and unobservable skill. Results confirm that occupational sex-segregation explains a sizeable portion of the gender wage gap and that wages in female-dominated occupations are lower than wages in other occupations. Inconsistent with human capital theory, low pay in female-dominated occupations cannot be explained fully by low skill specialization or by observable or unobservable characteristics of their workers. Remaining wage penalties in such occupations are consequently taken as evidence of institutional devaluation of 'women's work'

Nuclear materials stabilization and packaging. Quarterly status report, January 1--March 31, 1996

This report documents progress on the Los Alamos Nuclear Materials Stabilization and Packaging projects for the second quarter of FY 1996. It covers development and production activities for the Plutonium Packaging Project, the Plutonium Recovery and Processing Project, and the Uranium Recovery and Processing Project. In addition, it reports on quality assurance activities for the Plutonium Packaging Project