Regulatory effects of protein S-acylation on insulin secretion and insulin action

Post-translational modifications (PTMs) such as phosphorylation and ubiquitination are well-studied events with a recognized importance in all aspects of cellular function. By contrast, protein S-acylation, although a widespread PTM with important functions in most physiological systems, has received far less attention. Perturbations in S-acylation are linked to various disorders, including intellectual disability, cancer and diabetes, suggesting that this less-studied modification is likely to be of considerable biological importance. As an exemplar, in this review, we focus on the newly emerging links between S-acylation and the hormone insulin. Specifically, we examine how S-acylation regulates key components of the insulin secretion and insulin response pathways. The proteins discussed highlight the diverse array of proteins that are modified by S-acylation, including channels, transporters, receptors and trafficking proteins and also illustrate the diverse effects that S-acylation has on these proteins, from membrane binding and micro-localization to regulation of protein sorting and protein interactions

Systematic review of the effectiveness of preventing and treating Staphylococcus aureus carriage in reducing peritoneal catheter-related infections

Objectives: To determine the clinical effectiveness and cost-effectiveness of (1) alternative strategies for the prevention of Staphylococcus aureus carriage in patients on peritoneal dialysis (PD) and (2) alternative strategies for the eradication of S. aureus carriage in patients on PD. Data sources: Major electronic databases were searched up to December 2005 (MEDLINE Extra up to 6 January 2006). Review methods: Electronic searches were undertaken to identify published and unpublished reports of randomised controlled trials and systematic reviews evaluating the effectiveness of preventing and treating S. aureus carriage on peritoneal catheterrelated infections. The quality of the included studies was assessed and data synthesised. Where data were not sufficient for formal meta-analysis, a qualitative narrative review looking for consistency between studies was performed. Results: Twenty-two relevant trials were found. These fell into several groups: the first split is between prophylactic trials, aiming to prevent carriage, and trials which aimed to eradicate carriage in those who already had it; the second split is between antiseptics and antibiotics; and the third split is between those that included patients having the catheter inserted before dialysis started and people already on dialysis. Many of the trials were small or short-term. The quality was often not good by today’s standards. The body of evidence suggested a reduction in exit-site infections, but this did not seem to lead to a significant reduction in peritonitis, although to some extent this reflected insufficient power in the studies and a low incidence of peritonitis in them. The costs of interventions to prevent or treat S. aureus carriage are relatively modest. For example, the annual cost of antibiotic treatment of S. aureus carriage per identified carrier of S. aureus was estimated at £179 (£73 screening and £106 cost of antibiotic). However, without better data on the effectiveness of the interventions, it is not clear whether such costs are offset by the cost of treating infections and averting changes from peritoneal dialysis to haemodialysis. Although treatment is not expensive, the lack of convincing evidence of clinical effectiveness made cost-effectiveness analysis unrewarding at present. However, consideration was given to the factors needed in a hypothetical model describing patient pathways from methods to prevent S. aureus carriage, its detection and treatment and the detection and treatment of the consequences of S. aureus (e.g. catheter infections and peritonitis). Had data been available, the model would have compared the costeffectiveness of alternative interventions from the perspective of the UK NHS, but as such it helped identify what future research would be needed to fill the gaps. Conclusions: The importance of peritonitis isnot in doubt. It is the main cause of people having to switch from peritoneal dialysis to haemodialysis, which then leads to reduced quality of life for patients and increased costs to the NHS. Unfortunately, the present evidence base for the prevention of peritonitis is disappointing; it suggests that the interventions reduce exit-site infections, but not peritonitis, although this may be due to trials being in too small numbers for too short periods. Trials are needed with larger numbers of patients for longer durations.No peer reviewPublisher PD

An evaluation of 1 year of advice calls to a tropical and infectious disease referral Centre

OBJECTIVES:Many secondary care departments receive external advice calls. However, systematic advice-call documentation is uncommon and evidence on call nature and burden infrequent. The Liverpool tropical and infectious disease unit (TIDU) provides specialist advice locally, regionally and nationally. We created and evaluated a recording system to document advice calls received by TIDU. METHODS:An electronic advice-call recording system was created for TIDU specialist trainees to document complex, predominantly external calls. Fourteen months of advice calls were summarised, analysed and recommendations for other departments wishing to replicate this system made. RESULTS:Five-hundred and ninety calls regarding 362 patients were documented. Median patient age was 44 years (interquartile range 29-56 years) and 56% were male. Sixty-nine per cent of patients discussed were referred from secondary healthcare, half from emergency or acute medicine departments; 43% of patients were returning travellers; 59% of returning travellers had undifferentiated fever, one-third of whom returned from sub-Saharan Africa; 32% of patients discussed were further reviewed at TIDU. Interim 6-month review showed good user acceptability of the system. CONCLUSIONS:Implementing an advice-call recording system was feasible within TIDU. Call and follow-up burden was high with advice regarding fever in returned travellers predominating. Similar systems could improve clinical governance, patient care and service delivery in other secondary care departments

Validity of hand hygiene compliance measurement by observation: A systematic review

BACKGROUND: Hand hygiene is monitored by direct observation to improve practice, but this approach can potentially cause information, selection, and confounding bias, threatening the validity of findings. The aim of this study was to identify and describe the potential biases in hand hygiene compliance monitoring by direct observation; develop a typology of biases and propose improvements to reduce bias; and increase the validity of compliance measurements. METHODS: This systematic review of hospital-based intervention studies used direct observation to monitor health care workers' hand hygiene compliance. RESULTS: Seventy-one publications were eligible for review. None was free of bias. Selection bias was present in all studies through lack of data collection on the weekends (n = 61, 86%) and at night (n = 46, 65%) and observations undertaken in single-specialty settings (n = 35, 49%). We observed inconsistency of terminology, definitions of hand hygiene opportunity, criteria, tools, and descriptions of the data collection. Frequency of observation, duration, or both were not described or were unclear in 58 (82%) publications. Observers were trained in 56 (79%) studies. Inter-rater reliability was measured in 26 (37%) studies. CONCLUSIONS: Published research of hand hygiene compliance measured by direct observation lacks validity. Hand hygiene should be measured using methods that produce a valid indication of performance and quality. Standardization of methodology would expedite comparison of hand hygiene compliance between clinical settings and organizations

Critical Role for Cold Shock Protein YB-1 in Cytokinesis

High levels of the cold shock protein Y-box-binding protein-1, YB-1, are tightly correlated with increased cell proliferation and progression. However, the precise mechanism by which YB-1 regulates proliferation is unknown. Here, we found that YB-1 depletion in several cancer cell lines and in immortalized fibroblasts resulted in cytokinesis failure and consequent multinucleation. Rescue experiments indicated that YB-1 was required for completion of cytokinesis. Using confocal imaging we found that YB-1 was essential for orchestrating the spatio-temporal distribution of the microtubules, β-actin and the chromosome passenger complex (CPC) to define the cleavage plane. We show that phosphorylation at six serine residues was essential for cytokinesis, of which novel sites were identified using mass spectrometry. Using atomistic modelling we show how phosphorylation at multiple sites alters YB-1 conformation, allowing it to interact with protein partners. Our results establish phosphorylated YB-1 as a critical regulator of cytokinesis, defining precisely how YB-1 regulates cell division

Critical Role for Cold Shock Protein YB-1 in Cytokinesis

High levels of the cold shock protein Y-box-binding protein-1, YB-1, are tightly correlated with increased cell proliferation and progression. However, the precise mechanism by which YB-1 regulates proliferation is unknown. Here, we found that YB-1 depletion in several cancer cell lines and in immortalized fibroblasts resulted in cytokinesis failure and consequent multinucleation. Rescue experiments indicated that YB-1 was required for completion of cytokinesis. Using confocal imaging we found that YB-1 was essential for orchestrating the spatio-temporal distribution of the microtubules, β-actin and the chromosome passenger complex (CPC) to define the cleavage plane. We show that phosphorylation at six serine residues was essential for cytokinesis, of which novel sites were identified using mass spectrometry. Using atomistic modelling we show how phosphorylation at multiple sites alters YB-1 conformation, allowing it to interact with protein partners. Our results establish phosphorylated YB-1 as a critical regulator of cytokinesis, defining precisely how YB-1 regulates cell division

Cosmopolitan Sentiment: Politics, Charity, and Global Poverty

Duties to address global poverty face a motivation gap. We have good reasons for acting yet we do not, at least consistently. A ‘sentimental education’, featuring literature and journalism detailing the lives of distant others has been suggested as a promising means by which to close this gap (Nussbaum in Upheavals of Thought: The Intelligence of Emotions, CUP, Cambridge, 2001; Rorty in Truth and Progress: Philosophical Papers, vol. 3, CUP, Cambridge, 1998). Although sympathetic to this project, I argue that it is too heavily wed to a charitable model of our duties to address global poverty—understood as requiring we sacrifice a certain portion of our income. However, political action, aimed at altering institutions at both a global and a local level is likely to be necessary in order to provide effective long-term solutions to poverty globally. To rectify this, the article develops an alternative dialogical account of sentimental education, suitable for motivating support for political action to address global poverty

Influenza A (H3N2) Outbreak, Nepal

Worldwide emergence of variant viruses has prompted a change in the 2005–2006 H3N2 influenza A vaccine strain

Seroprevalence and distribution of arboviral infections among rural Kenyan adults: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Arthorpod-borne viruses (arboviruses) cause wide-spread morbidity in sub-Saharan Africa, but little research has documented the burden and distribution of these pathogens.</p> <p>Methods</p> <p>Using a population-based, cross-sectional study design, we administered a detailed questionnaire and used ELISA to test the blood of 1,141 healthy Kenyan adults from three districts for the presence of anti-viral Immunoglobulin G (IgG) antibodies to the following viruses: dengue (DENV), West Nile (WNV), yellow fever (YFV), Chikungunya (CHIKV), and Rift Valley fever (RVFV).</p> <p>Results</p> <p>Of these, 14.4% were positive for DENV, 9.5% were WNV positive, 9.2% were YFV positive, 34.0% were positive for CHIKV and 0.7% were RVFV positive. In total, 46.6% had antibodies to at least one of these arboviruses.</p> <p>Conclusions</p> <p>For all arboviruses, district of residence was strongly associated with seropositivity. Seroprevalence to YFV, DENV and WNV increased with age, while there was no correlation between age and seropositivity for CHIKV, suggesting that much of the seropositivity to CHIKV is due to sporadic epidemics. Paradoxically, literacy was associated with increased seropositivity of CHIKV and DENV.</p