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ER–mitochondria contact sites (ERMCSs) regulate processes, including calcium homoeostasis, energy metabolism and autophagy. Previously, it was shown that during growth factor signalling, mTORC2/Akt gets recruited to and stabilizes ERMCSs. Independent studies showed that GSK3β, a well-known Akt substrate, reduces ER–mitochondria connectivity by disrupting the VAPB–PTPIP51 tethering complex. However, the mechanisms that regulate ERMCSs are incompletely understood. Here we find that annulate lamellae (AL), relatively unexplored subdomains of ER enriched with a subset of nucleoporins, are present at ERMCSs. Depletion of Nup358, an AL-resident nucleoporin, results in enhanced mTORC2/Akt activation, GSK3β inhibition and increased ERMCSs. Depletion of Rictor, a mTORC2-specific subunit, or exogenous expression of GSK3β, was sufficient to reverse the ERMCS-phenotype in Nup358-deficient cells. We show that growth factor-mediated activation of mTORC2 requires the VAPB–PTPIP51 complex, whereas, Nup358's association with this tether restricts mTORC2/Akt signalling and ER–mitochondria connectivity. Expression of a Nup358 fragment that is sufficient for interaction with the VAPB–PTPIP51 complex suppresses mTORC2/Akt activation and disrupts ERMCSs. Collectively, our study uncovers a novel role for Nup358 in controlling ERMCSs by modulating the mTORC2/Akt/GSK3β axis. Synopsis: Nup358-positive annulate lamellae (AL) structures are present at ER-mitochondria contact sites (ERMCSs). Nup358 restricts growth factor mediated stabilization of ERMCSs by modulating mTORC2/Akt/GSK3β pathway. Annulate lamellae (AL) are present at ER-mitochondria contact sites. Depletion of Nup358, an AL-resident nucleoporin, leads to increased connectivity between ER and mitochondria. Nup358 suppresses growth factor-dependent activation of mTORC2/Akt pathway and thereby facilitates GSK3β activity to limit the ERMCSs. Nup358-positive annulate lamellae (AL) structures are present at ER-mitochondria contact sites (ERMCSs). Nup358 restricts growth factor mediated stabilization of ERMCSs by modulating mTORC2/Akt/GSK3β pathway. [ABSTRACT FROM AUTHOR]

Commensal bacteria play a major role in multiple skin functions by providing the first layer of defense against pathogens and maintaining the skin barrier. Staphylococcus epidermidis is one of the most common skin commensals. In this study, we showed that S. epidermidis ferments glycerol and uses it as a nutrient, while producing short‐chain and organic fatty acids, with the most notable being lactic acid. Lactic acid is an alpha‐hydroxy acid that inhibits the growth of pathogenic bacteria, without any negative effect on the commensal bacteria itself. Using in vivo experiments, we validated our in vitro results, showing that the skin microbiome is also capable of doing this. Finally, using 2D and 3D skin culture models, we showed that the fermentation of glycerol, mainly lactic acid, as determined by analytical methods, upregulates the expression levels of several key genes that are associated with the barrier properties of the skin. While the hydration effect of glycerol on the skin is well known, our study shows the overall benefits of glycerol on the skin microbiome, while revealing an alternate mode of action of glycerol for multiple skin benefits. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides ( AMPs) form a part of the skin's innate immune system. Their primary activity is to provide antimicrobial benefits and hence protect from infections. AMPs that are present on human skin include psoriasin (S100A7), RNase 7, lysozyme, LL-37 and defensins. Niacinamide is a well-known cosmetic ingredient that has been used traditionally for multiple skin benefits. Recent data indicate that niacinamide treatment can boost AMPs in human gut epithelial cells and in neutrophils. Treatment with niacinamide in mice also provided protection from skin infections by enhancing AMPs. In this article, we find that treatment with niacinamide formulation provides long-lasting protection against bacteria, potentially through the activation of an AMP response. [ABSTRACT FROM AUTHOR]

Key content Urinary incontinence ( UI) affects up to 69% of the female population at some point in their lives but remains under-reported. There are three main types of UI: stress, urgency and mixed., It is recommended to try conservative approaches as first-line measures in the management of all types of UI. These include lifestyle interventions such as adjustment of fluid intake and weight loss, physical and behavioural therapies (pelvic floor muscle training, electrical stimulation, vaginal cones and bladder training programmes) and occasionally containment devices., Initial management of UI, in most cases, renders itself to primary care settings: this involves appropriate assessment of women's symptoms, including quality of life ( QOL) assessment, appropriate simple investigations (such as urine analysis) and conservative treatment., Appropriate referral pathways to secondary and tertiary levels of care are necessary. Regular audit should take place to assess the efficacy of management options and referral pathways., UI has significant adverse affects on women's QOL. Hence patient reported outcome measures ( PROMs) have been highlighted in recent NHS reports as a means of assessing effectiveness of care from the patient's perspective by gauging patient health status or health-related QOL., Learning objectives To gain an understanding of the assessment and various conservative management options for common types of UI in women., To explore the existing evidence base for such conservative management modalities and to analyse the effect of the current economic climate and reorganisation of services on the conservative management approach., To recognise the important role of patient reported outcome measures as well as service and user involvement, in the assessment of clinical and cost-effectiveness of various treatment options of UI in women., Ethical issues Should conservative measures such as weight loss and smoking cessation be a pre-requisite for offering further management options?, In the present climate of scarce health resources should more emphasis be placed on the active role of patients in their own management? Will reorganisation of the NHS pose any threat to the conservative measures for treating UI in women?, Is it acceptable to take a 'one size fits all' approach to management of common types of UI? [ABSTRACT FROM AUTHOR]

Aims To evaluate whether the treatment based on urodynamics (UDS) leads to better treatment response compared to where the treatment is based on symptoms alone. Study design, materials and methods All patients referred with lower urinary tract symptoms (LUTS) were offered the opportunity to participate in this patient preference trial. Patients were asked to complete a Kings Health Questionnaire (KHQ) and a 3-day bladder diary. The patients were then offered treatment based on their preference for conservative therapy based on either symptoms alone or with additional UDS or randomization to the same two alternatives, if they had no preference. The primary outcomes studied were improvement in KHQ and reduction in Incontinence Episode Frequency (IEF) at 6 months. Logistic regression analysis was done to evaluate the effect of choice of treatment and effect of incontinence on KHQ. Results There was no statistically significant difference between the KHQ scores pre and post UDS in patient preference or randomized groups. Follow up attendance rates were significantly better in those who chose to undergo urodynamics when compared to those who chose conservative treatment. Conclusions This study suggests although UDS does not improve IEF, it may have utility in patient choice and subsequent compliance. Another relevant finding was the previously unreported high uptake of UDS by women when given the choice of whether to undergo UDS first or have treatment based on symptoms alone. Neurourol. Urodynam. 29:522-526, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Clathrin-mediated endocytosis (CME) is essential for maintaining many basic cellular processes. We monitored the dynamics of clathrin in live Drosophila melanogaster hemocytes overexpressing clathrin light chain fused to enhanced green fluorescent protein (EGFP) using evanescent wave microscopy. Membrane-associated clathrin-coated structures (CCS) constitutively appeared at the peripheral filopodial membrane, moved centripetally while growing in intensity, before being eventually endocytosed within a few tens of seconds. This directed CCS traffic was independent of microtubules but could be blocked by latrunculin A. Taking advantage of available mutants of Drosophila, we expressed clathrin–EGFP in wasp and shibire mutant backgrounds to study the role of actin and dynamin in CCS dynamics and CME in hemocytes. We show that actin plays an essential role in CME in these cells, and that actin and dynamin act at the same stage, but independent of each other. Drosophila melanogaster hemocytes proved to be a promising model system to uncover the molecular events during CME in combining live-cell imaging and genetic analysis. [ABSTRACT FROM AUTHOR]