The pH of the skin surface and its impact on the barrier function

The `acid mantle' of the stratum corneum seems to be important for both permeability barrier formation and cutaneous antimicrobial defense. However, the origin of the acidic pH, measurable on the skin surface, remains conjectural. Passive and active influencing factors have been proposed, e. g. eccrine and sebaceous secretions as well as proton pumps. In recent years, numerous investigations have been published focusing on the changes in the pH of the deeper layers of the stratum corneum, as well as on the influence of physiological and pathological factors. The pH of the skin follows a sharp gradient across the stratum corneum, which is suspected to be important in controlling enzymatic activities and skin renewal. The skin pH is affected by a great number of endogenous factors, e. g. skin moisture, sweat, sebum, anatomic site, genetic predisposition and age. In addition, exogenous factors like detergents, application of cosmetic products, occlusive dressings as well as topical antibiotics may influence the skin pH. Changes in the pH are reported to play a role in the pathogenesis of skin diseases like irritant contact dermatitis, atopic dermatitis, ichthyosis, acne vulgaris and Candida albicans infections. Therefore, the use of skin cleansing agents, especially synthetic detergents with a pH of about 5.5, may be of relevance in the prevention and treatment of those skin diseases. Copyright (c) 2006 S. Karger AG, Base

The Translation Initiation Factor 3f (eIF3f) Exhibits a Deubiquitinase Activity Regulating Notch Activation

The translation initiation factor complex eIF3f has an intrinsic deubiquitinase activity and regulates the Notch signaling pathway

Colon Capsule Endoscopy compared to Conventional Colonoscopy under routine screening conditions

Colonoscopy (CSPY) for colorectal cancer screening has several limitations. Colon Capsule Endoscopy (PillCam Colon, CCE) was compared to CSPY under routine screening conditions

The impact of gender and parenthood on physicians' careers - professional and personal situation seven years after graduation

BACKGROUND: The profile of the medical profession is changing in regard to feminization, attitudes towards the profession, and the lifestyle aspirations of young physicians. The issues addressed in this study are the careers of female and male physicians seven years after graduation and the impact of parenthood on career development. METHODS: Data reported originates from the fifth assessment (T5) of the prospective SwissMedCareer Study, beginning in 2001 (T1). At T5 in 2009, 579 residents (81.4% of the initial sample at T1) participated in the questionnaire survey. They were asked about occupational factors, career-related factors including specialty choice and workplace, work-life balance and life satisfaction. The impact of gender and parenthood on the continuous variables was investigated by means of multivariate and univariate analyses of variance; categorical variables were analyzed using Chi-square tests. RESULTS: Female physicians, especially those with children, have lower rates of employment and show lower values in terms of career success and career support experiences than male physicians. In addition, parenthood has a negative impact on these career factors. In terms of work-life balance aspired to, female doctors are less career-oriented and are more inclined to consider part-time work or to continue their professional career following a break to bring up a family. Parenthood means less career-orientation and more part-time orientation. As regards life satisfaction, females show higher levels of satisfaction overall, especially where friends, leisure activities, and income are concerned. Compared to their male colleagues, female physicians are less advanced in their specialty qualification, are less prone to choosing prestigious surgical fields, have a mentor less often, more often work at small hospitals or in private practice, aspire less often to senior hospital or academic positions and consider part-time work more often. Any negative impact on career path and advancement is exacerbated by parenthood, especially as far as women are concerned. CONCLUSION: The results of the present study reflect socially-rooted gender role stereotypes. Taking into account the feminization of medicine, special attention needs to be paid to female physicians, especially those with children. At an early stage of their career, they should be advised to be more proactive in seeking mentoring and career-planning opportunities. If gender equity in terms of career chances is to be achieved, special career-support measures will have to be provided, such as mentoring programs, role models, flexitime and flexible career structures

The Functions of Auxilin and Rab11 in Drosophila Suggest That the Fundamental Role of Ligand Endocytosis in Notch Signaling Cells Is Not Recycling

Notch signaling requires ligand internalization by the signal sending cells. Two endocytic proteins, epsin and auxilin, are essential for ligand internalization and signaling. Epsin promotes clathrin-coated vesicle formation, and auxilin uncoats clathrin from newly internalized vesicles. Two hypotheses have been advanced to explain the requirement for ligand endocytosis. One idea is that after ligand/receptor binding, ligand endocytosis leads to receptor activation by pulling on the receptor, which either exposes a cleavage site on the extracellular domain, or dissociates two receptor subunits. Alternatively, ligand internalization prior to receptor binding, followed by trafficking through an endosomal pathway and recycling to the plasma membrane may enable ligand activation. Activation could mean ligand modification or ligand transcytosis to a membrane environment conducive to signaling. A key piece of evidence supporting the recycling model is the requirement in signaling cells for Rab11, which encodes a GTPase critical for endosomal recycling. Here, we use Drosophila Rab11 and auxilin mutants to test the ligand recycling hypothesis. First, we find that Rab11 is dispensable for several Notch signaling events in the eye disc. Second, we find that Drosophila female germline cells, the one cell type known to signal without clathrin, also do not require auxilin to signal. Third, we find that much of the requirement for auxilin in Notch signaling was bypassed by overexpression of both clathrin heavy chain and epsin. Thus, the main role of auxilin in Notch signaling is not to produce uncoated ligand-containing vesicles, but to maintain the pool of free clathrin. Taken together, these results argue strongly that at least in some cell types, the primary function of Notch ligand endocytosis is not for ligand recycling