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

Systematic Analysis of Cell Cycle Effects of Common Drugs Leads to the Discovery of a Suppressive Interaction between Gemfibrozil and Fluoxetine

Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation

The Unfolded Protein Response Is Not Necessary for the G1/S Transition, but It Is Required for Chromosome Maintenance in Saccharomyces cerevisiae

BACKGROUND: The unfolded protein response (UPR) is a eukaryotic signaling pathway, from the endoplasmic reticulum (ER) to the nucleus. Protein misfolding in the ER triggers the UPR. Accumulating evidence links the UPR in diverse aspects of cellular homeostasis. The UPR responds to the overall protein synthesis capacity and metabolic fluxes of the cell. Because the coupling of metabolism with cell division governs when cells start dividing, here we examined the role of UPR signaling in the timing of initiation of cell division and cell cycle progression, in the yeast Saccharomyces cerevisiae. METHODOLOGY/PRINCIPAL FINDINGS: We report that cells lacking the ER-resident stress sensor Ire1p, which cannot trigger the UPR, nonetheless completed the G1/S transition on time. Furthermore, loss of UPR signaling neither affected the nutrient and growth rate dependence of the G1/S transition, nor the metabolic oscillations that yeast cells display in defined steady-state conditions. Remarkably, however, loss of UPR signaling led to hypersensitivity to genotoxic stress and a ten-fold increase in chromosome loss. CONCLUSIONS/SIGNIFICANCE: Taken together, our results strongly suggest that UPR signaling is not necessary for the normal coupling of metabolism with cell division, but it has a role in genome maintenance. These results add to previous work that linked the UPR with cytokinesis in yeast. UPR signaling is conserved in all eukaryotes, and it malfunctions in a variety of diseases, including cancer. Therefore, our findings may be relevant to other systems, including humans

Modulation of Sn concentration in ZnO nanorod array: intensification on the conductivity and humidity sensing properties

Tin (Sn)-doped zinc oxide (ZnO) nanorod arrays (TZO) were synthesized onto aluminum-doped ZnO-coated glass substrate via a facile sonicated sol–gel immersion method for humidity sensor applications. These nanorod arrays were grown at different Sn concentrations ranging from 0.6 to 3 at.%. X-ray diffraction patterns showed that the deposited TZO arrays exhibited a wurtzite structure. The stress/strain condition of the ZnO film metamorphosed from tensile strain/compressive stress to compressive strain/tensile stress when the Sn concentrations increased. Results indicated that 1 at.% Sn doping of TZO, which has the lowest tensile stress of 0.14 GPa, generated the highest conductivity of 1.31 S cm− 1. In addition, 1 at.% Sn doping of TZO possessed superior sensitivity to a humidity of 3.36. These results revealed that the optimum performance of a humidity-sensing device can be obtained mainly by controlling the amount of extrinsic element in a ZnO film

From bit to it: How a complex metabolic network transforms information into living matter

Organisms live and die by the amount of information they acquire about their environment. The systems analysis of complex metabolic networks allows us to ask how such information translates into fitness. A metabolic network transforms nutrients into biomass. The better it uses information on available nutrient availability, the faster it will allow a cell to divide. I here use metabolic flux balance analysis to show that the accuracy I (in bits) with which a yeast cell can sense a limiting nutrient's availability relates logarithmically to fitness as indicated by biomass yield and cell division rate. For microbes like yeast, natural selection can resolve fitness differences of genetic variants smaller than 10-6, meaning that cells would need to estimate nutrient concentrations to very high accuracy (greater than 22 bits) to ensure optimal growth. I argue that such accuracies are not achievable in practice. Natural selection may thus face fundamental limitations in maximizing the information processing capacity of cells. The analysis of metabolic networks opens a door to understanding cellular biology from a quantitative, information-theoretic perspective

Modelling human visual navigation using multi-view scene reconstruction

It is often assumed that humans generate a 3D reconstruction of the environment, either in egocentric or world-based coordinates, but the steps involved are unknown. Here, we propose two reconstruction-based models, evaluated using data from two tasks in immersive virtual reality. We model the observer’s prediction of landmark location based on standard photogrammetric methods and then combine location predictions to compute likelihood maps of navigation behaviour. In one model, each scene point is treated independently in the reconstruction; in the other, the pertinent variable is the spatial relationship between pairs of points. Participants viewed a simple environment from one location, were transported (virtually) to another part of the scene and were asked to navigate back. Error distributions varied substantially with changes in scene layout; we compared these directly with the likelihood maps to quantify the success of the models. We also measured error distributions when participants manipulated the location of a landmark to match the preceding interval, providing a direct test of the landmark-location stage of the navigation models. Models such as this, which start with scenes and end with a probabilistic prediction of behaviour, are likely to be increasingly useful for understanding 3D vision

Breast cancer incidence highest in the range of one species of house mouse, Mus domesticus

Incidence of human breast cancer (HBC) varies geographically, but to date no environmental factor has explained this variation. Previously, we reported a 44% reduction in the incidence of breast cancer in women fully immunosuppressed following organ transplantation (Stewart et al (1995) Lancet346: 796–798). In mice infected with the mouse mammary tumour virus (MMTV), immunosuppression also reduces the incidence of mammary tumours. DNA with 95% identity to MMTV is detected in 40% of human breast tumours (Wang et al (1995) Cancer Res55: 5173–5179). These findings led us to ask whether the incidence of HBC could be correlated with the natural ranges of different species of wild mice. We found that the highest incidence of HBC worldwide occurs in lands where Mus domesticus is thse resident native or introduced species of house mouse. Given the similar responses of humans and mice to immunosuppression, the near identity between human and mouse MTV DNA sequences, and the close association between HBC incidence and mouse ranges, we propose that humans acquire MMTV from mice. This zoonotic theory for a mouse-viral cause of HBC allows testable predictions and has potential importance in prevention. © 2000 Cancer Research Campaig

Resource allocation of in vitro fertilization: a nationwide register-based cohort study

<p>Abstract</p> <p>Background</p> <p>Infertility is common and in vitro fertilization (IVF) is a widely used treatment. In IVF the need increases and the effectiveness and appropriateness decrease by age. The purpose of this study was to describe allocation of resources for IVF by women's age, socioeconomic position, area of residence and treatment sector (public vs. private) and to discuss how fairly the IVF resources are allocated in Finland.</p> <p>Methods</p> <p>Women who received IVF between 1996 and 1998 (N = 9175) were identified from the reimbursement records of the Social Insurance Institution (SII). Information on IVF women's background characteristics came from the Central Population Register and the SII, on treatment costs from IVF clinics and the SII, and on births from the Medical Birth Register. The main outcome measures were success of IVF by number of cycles and treated women, expenditures per IVF cycles, per women, per live-birth, and per treatment sector, and private and public expenditures. Expenditures were estimated from health care visits and costs.</p> <p>Results</p> <p>During a mean period of 1.5 years, older women (women aged 40 or older) received 1.4 times more IVF treatment cycles than younger women (women aged below 30). The success rate decreased by age: from 22 live births per 100 cycles among younger women to 6 per 100 among older women. The mean cost of a live birth increased by age: compared to younger women, costs per born live birth of older women were 3-fold. Calculated by population, public expenditure was allocated most to young women and women from the highest socioeconomic position. Regional differences were not remarkable.</p> <p>Conclusion</p> <p>Children of older infertile women involve more expense due to the lower success rates of IVF. Socioeconomic differences suggest unfair resource allocation in Finland.</p

Identification of the Biotransformation Products of 2-Ethylhexyl 4-(N,N-Dimethylamino)benzoate

Nowadays, 2-ethylhexyl 4-(N,N-dimethylamino)benzoate (EDP) is one of the most widely used UV filters in sunscreen cosmetics and other cosmetic products. However, undesirable processes such as percutaneous absorption and biological activity have been attributed to this compound. The in vitro metabolism of EDP was elucidated in the present work. First of all, the phase I biotransformation was studied in rat liver microsomes and two metabolites, N,N-dimethyl-p-aminobenzoic acid (DMP) and N-monomethyl-p-aminobenzoic acid (MMP), were identified by GC-MS analysis. Secondly, the phase II metabolism was investigated by means of LC-MS. The investigated reactions were acetylation and glucuronidation working with rat liver cytosol and with both human and rat liver microsomes, respectively. Analogue studies with p-aminobenzoic acid (PABA) were carried out in order to compare the well established metabolic pathway of PABA with the unknown biotransformation of EDP. In addition, a method for the determination of EDP and its two phase I metabolites in human urine was developed. The methodology requires a solid-phase extraction prior to LC-MS analysis. The method is based on standard addition quantification and has been fully validated. The repeatability of the method, expressed as relative standard deviation, was in the range 3.4–7.4% and the limit of detection for all quantified analytes was in the low ng mL−1 range