Human Trichohyalin Gene Is Clustered with the Genes for Other Epidermal Structural Proteins and Calcium-Binding Proteins at Chromosomal Locus 1q21

Trichohyalin is a major differentiation product of hard keratinizing tissues such as the inner root sheath and medullary cells of the hair follicle and the filiform papillae of the tongue, as well as terminally differentiating epidermal cells. It consists largely of quasi-repeating peptide repeats and functions primarily as an intermediate filament-associated protein in these tissues. By mapping with human-rodent somatic cell hybrids and fluorescent in situ hybridization, we demonstrate that its gene maps to chromosomal region 1q21. Interestingly, genes encoding several other structural proteins expressed during terminal differentiation in the epidermis map to this region, as do also several members of the S-100 class of small calcium-binding proteins

Factors associated with adolescent pregnancy in Maharashtra, India: a mixed-methods study

Reducing the adolescent birth rate is paramount in achieving the health-related Sustainable Development Goals, given that pregnancy and childbirth are the leading cause of mortality among young women aged 15-19. This study aimed to explore predictors of adolescent pregnancy among girls aged 13-18 years in Maharashtra, India, during the COVID-19 pandemic. Using a mixed-methods approach, primary data were gathered from two regions in Maharashtra between February and April 2022. Quantitative data from face-to-face interviews with 3049 adolescent girls assessed various household, social, and behavioural factors, as well as the socioeconomic and health impacts of COVID-19. Qualitative data from seven in-depth interviews were analysed thematically. The findings reveal that girls from low socioeconomic backgrounds face a higher likelihood of adolescent pregnancy. Multivariable analysis identified several factors associated with increased risk, including older age, being married, having more sexual partners, and experiencing COVID-19-related economic vulnerability. On the other hand, rural residence, secondary and higher secondary education of the participants, and higher maternal education were associated with a decreased likelihood of adolescent pregnancy. In the sub-sample of 565 partnered girls, partner's emotional abuse also correlated with higher rates of adolescent pregnancy. Thematic analysis of qualitative data identified four potential pathways leading to adolescent pregnancy: economic hardships and early marriage; personal safety, social norms, and early marriage; social expectations; and lack of knowledge on contraceptives. The findings underscore the significance of social position and behavioural factors and the impact of external shocks like the COVID-19 pandemic in predicting adolescent pregnancy in Maharashtra, India

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated

Hierarchical Bayesian modeling for knowledge transfer across engineering fleets via multitask learning

A population-level analysis is proposed to address data sparsity when building predictive models for engineering infrastructure. Utilizing an interpretable hierarchical Bayesian approach and operational fleet data, domain expertise is naturally encoded (and appropriately shared) between different subgroups, representing (1) use-type, (2) component, or (3) operating condition. Specifically, domain expertise is exploited to constrain the model via assumptions (and prior distributions) allowing the methodology to automatically share information between similar assets, improving the survival analysis of a truck fleet (15% and 13% increases in predictive log-likelihood of hazard) and power prediction in a wind farm (up to 82% reduction in the standard deviation of maximum output prediction). In each asset management example, a set of correlated functions is learnt over the fleet, in a combined inference, to learn a population model. Parameter estimation is improved when subfleets are allowed to share correlated information at different levels in the hierarchy; the (averaged) reduction in standard deviation for interpretable parameters in the survival analysis is 70%, alongside 32% in wind farm power models. In turn, groups with incomplete data automatically borrow statistical strength from those that are data-rich. The statistical correlations enable knowledge transfer via Bayesian transfer learning, and the correlations can be inspected to inform which assets share information for which effect (i.e., parameter). Successes in both case studies demonstrate the wide applicability in practical infrastructure monitoring, since the approach is naturally adapted between interpretable fleet models of different in situ examples

Molecular Identification and Expression Analysis of Filaggrin-2, a Member of the S100 Fused-Type Protein Family

Genes of the S100 fused-type protein (SFTP) family are clustered within the epidermal differentiation complex and encode essential components that maintain epithelial homeostasis and barrier functions. Recent genetic studies have shown that mutations within the gene encoding the SFTP filaggrin cause ichthyosis vulgaris and are major predisposing factors for atopic dermatitis. As a vital component of healthy skin, filaggrin is also a precursor of natural moisturizing factors. Here we present the discovery of a member of this family, designated as filaggrin-2 (FLG2) that is expressed in human skin. The FLG2 gene encodes a histidine- and glutamine-rich protein of approximately 248 kDa, which shares common structural features with other SFTP members, in particular filaggrin. We found that FLG2 transcripts are present in skin, thymus, tonsils, stomach, testis and placenta. In cultured primary keratinocytes, FLG2 mRNA expression displayed almost the same kinetics as that of filaggrin following Ca2+ stimulation, suggesting an important role in molecular regulation of epidermal terminal differentiation. We provide evidences that like filaggrin, FLG2 is initially expressed by upper granular cells, proteolytically processed and deposited in the stratum granulosum and stratum corneum (SC) layers of normal epidermis. Thus, FLG2 and filaggrin may have overlapping and perhaps synergistic roles in the formation of the epidermal barrier, protecting the skin from environmental insults and the escape of moisture by offering precursors of natural moisturizing factors

Role-play for medical students learning about communication: Guidelines for maximising benefits

BACKGROUND: Role-play is widely used as an educational method for learning about communication in medical education. Although educational theory provides a sound rationale for using this form of simulation, there is little published evidence for its effectiveness. Students' prior experiences of role-play may influence the way in which they engage in this method. This paper explores students' experiences with the aim of producing guidelines for maximising the benefits of role-play within this learning context. METHODS: First-year undergraduate medical students participated in a role-play session as part of their communication programme. Before and after the session, students completed questionnaires. In the pre-session questionnaire, students were asked about their experiences of role-play and asked to identify helpful and unhelpful elements. Immediately after the session, students answered similar questions in relation to the role-play activity they had just completed. Descriptive statistics were used to analyse quantitative data and qualitative data was thematically analysed. RESULTS: 284 students completed evaluation forms. Although 63 (22.2%) had prior unhelpful experiences, most students (n = 274; 96.5%) found this experience helpful. Summary findings were that students reported the key aspects of helpful role-play were opportunities for observation, rehearsal and discussion, realistic roles and alignment of roles with other aspects of the curriculum. Unhelpful aspects were those that evoked strong negative emotional responses and factors that contributed to a lack of realism. CONCLUSION: Role-play was valued by students in the acquisition of communication skills even though some had prior unhelpful experiences. Guidelines for effective role-play include adequate preparation, alignment of roles and tasks with level of practice, structured feedback guidelines and acknowledgment of the importance of social interactions for learning

Implementation and testing of the first prompt search for gravitational wave transients with electromagnetic counterparts

Aims. A transient astrophysical event observed in both gravitational wave (GW) and electromagnetic (EM) channels would yield rich scientific rewards. A first program initiating EM follow-ups to possible transient GW events has been developed and exercised by the LIGO and Virgo community in association with several partners. In this paper, we describe and evaluate the methods used to promptly identify and localize GW event candidates and to request images of targeted sky locations. Methods. During two observing periods (Dec 17 2009 to Jan 8 2010 and Sep 2 to Oct 20 2010), a low-latency analysis pipeline was used to identify GW event candidates and to reconstruct maps of possible sky locations. A catalog of nearby galaxies and Milky Way globular clusters was used to select the most promising sky positions to be imaged, and this directional information was delivered to EM observatories with time lags of about thirty minutes. A Monte Carlo simulation has been used to evaluate the low-latency GW pipeline's ability to reconstruct source positions correctly. Results. For signals near the detection threshold, our low-latency algorithms often localized simulated GW burst signals to tens of square degrees, while neutron star/neutron star inspirals and neutron star/black hole inspirals were localized to a few hundred square degrees. Localization precision improves for moderately stronger signals. The correct sky location of signals well above threshold and originating from nearby galaxies may be observed with ~50% or better probability with a few pointings of wide-field telescopes.Comment: 17 pages. This version (v2) includes two tables and 1 section not included in v1. Accepted for publication in Astronomy & Astrophysic