Elevated Paracellular Glucose Flux across Cystic Fibrosis Airway Epithelial Monolayers Is an Important Factor for Pseudomonas aeruginosa Growth.

People with cystic fibrosis (CF) who develop related diabetes (CFRD) have accelerated pulmonary decline, increased infection with antibiotic-resistant Pseudomonas aeruginosa and increased pulmonary exacerbations. We have previously shown that glucose concentrations are elevated in airway surface liquid (ASL) of people with CF, particularly in those with CFRD. We therefore explored the hypotheses that glucose homeostasis is altered in CF airway epithelia and that elevation of glucose flux into ASL drives increased bacterial growth, with an effect over and above other cystic fibrosis transmembrane conductance regulator (CFTR)-related ASL abnormalities. The aim of this study was to compare the mechanisms governing airway glucose homeostasis in CF and non-CF primary human bronchial epithelial (HBE) monolayers, under normal conditions and in the presence of Ps. aeruginosa filtrate. HBE-bacterial co-cultures were performed in the presence of 5 mM or 15 mM basolateral glucose to investigate how changes in blood glucose, such as those seen in CFRD, affects luminal Ps. aeruginosa growth. Calu-3 cell monolayers were used to evaluate the potential importance of glucose on Ps. aeruginosa growth, in comparison to other hallmarks of the CF ASL, namely mucus hyperviscosity and impaired CFTR-dependent fluid secretions. We show that elevation of basolateral glucose promotes the apical growth of Ps. aeruginosa on CF airway epithelial monolayers more than non-CF monolayers. Ps. aeruginosa secretions elicited more glucose flux across CF airway epithelial monolayers compared to non-CF monolayers which we propose increases glucose availability in ASL for bacterial growth. In addition, elevating basolateral glucose increased Ps. aeruginosa growth over and above any CFTR-dependent effects and the presence or absence of mucus in Calu-3 airway epithelia-bacteria co-cultures. Together these studies highlight the importance of glucose as an additional factor in promoting Ps. aeruginosa growth and respiratory infection in CF disease

The influence of in-pregnancy smoking cessation programmes on partner quitting and women's social support mobilization: a randomized controlled trial [ISRCTN89131885]

BACKGROUND: Smoking cessation interventions in pregnancy could influence a woman's social behaviour and her partner's smoking behaviour, but this has not been examined in any published randomized trials. METHOD: 918 women smoking at booking for antenatal care were enrolled in a cluster-randomized trial of three interventions: standard care, self-help manual and enhanced stage-based counselling, or self-help manual, enhanced stage-based counselling and use of an interactive computer program. The outcomes were change in social support received by women between booking for maternity care and 30 weeks gestation and 10 days postpartum and reported cessation in the woman's partner at these times. RESULTS: Few pregnant women's partners stopped smoking (4.1% at 30 weeks of gestation and 5.8% at 10 days postpartum) and the probability of quitting did not differ significantly by trial arm. Women's scores on the Inventory of Socially Supportive Behaviors showed a slight decline from booking to 30 weeks gestation, and a slight increase to 10 days postpartum, but these changes did not differ significantly by trial arm. CONCLUSION: The stage-based interventions tested in this trial aimed partly to influence women's mobilization of support and might have influenced partners' quitting, but there was no evidence that they did so. Given that women and their partners often stopped smoking together, future interventions to prevent smoking in pregnant women could encourage both partners to quit together

Plastisol Foaming Process. Decomposition of the Foaming Agent, Polymer Behavior in the Corresponding Temperature Range and Resulting Foam Properties

The decomposition of azodicarbonamide, used as foaming agent in PVC - plasticizer (1/1) plastisols was studied by DSC. Nineteen different plasticizers, all belonging to the ester family, two being polymeric (polyadipates), were compared. The temperature of maximum decomposition rate (in anisothermal regime at 5 K min-1 scanning rate), ranges between 434 and 452 K. The heat of decomposition ranges between 8.7 and 12.5 J g -1. Some trends of variation of these parameters appear significant and are discussed in terms of solvent (matrix) and viscosity effects on the decomposition reactions. The shear modulus at 1 Hz frequency was determined at the temperature of maximum rate of foaming agent decomposition, and differs significantly from a sample to another. The foam density was determined at ambient temperature and the volume fraction of bubbles was used as criterion to judge the efficiency of the foaming process. The results reveal the existence of an optimal shear modulus of the order of 2 kPa that corresponds roughly to plasticizer molar masses of the order of 450 ± 50 g mol-1. Heavier plasticizers, especially polymeric ones are too difficult to deform. Lighter plasticizers such as diethyl phthalate (DEP) deform too easily and presumably facilitate bubble collapse

A pulsating auroral X-ray hot spot on Jupiter

Jupiter's X-ray aurora has been thought to be excited by energetic sulphur and oxygen ions precipitating from the inner magnetosphere into the planet's polar regions(1-3). Here we report high-spatial-resolution observations that demonstrate that most of Jupiter's northern auroral X-rays come from a 'hot spot' located significantly poleward of the latitudes connected to the inner magnetosphere. The hot spot seems to be fixed in magnetic latitude and longitude and occurs in a region where anomalous infrared(4-7) and ultraviolet(8) emissions have also been observed. We infer from the data that the particles that excite the aurora originate in the outer magnetosphere. The hot spot X-rays pulsate with an approximately 45-min period, a period similar to that reported for high-latitude radio and energetic electron bursts observed by near-Jupiter spacecraft(9,10). These results invalidate the idea that jovian auroral X-ray emissions are mainly excited by steady precipitation of energetic heavy ions from the inner magnetosphere. Instead, the X-rays seem to result from currently unexplained processes in the outer magnetosphere that produce highly localized and highly variable emissions over an extremely wide range of wavelengths.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62624/1/4151000a.pd

Identifying candidate genes affecting developmental time in Drosophila melanogaster: pervasive pleiotropy and gene-by-environment interaction

<p>Abstract</p> <p>Background</p> <p>Understanding the genetic architecture of ecologically relevant adaptive traits requires the contribution of developmental and evolutionary biology. The time to reach the age of reproduction is a complex life history trait commonly known as developmental time. In particular, in holometabolous insects that occupy ephemeral habitats, like fruit flies, the impact of developmental time on fitness is further exaggerated. The present work is one of the first systematic studies of the genetic basis of developmental time, in which we also evaluate the impact of environmental variation on the expression of the trait.</p> <p>Results</p> <p>We analyzed 179 co-isogenic single <it>P[GT1]-</it>element insertion lines of <it>Drosophila melanogaster </it>to identify novel genes affecting developmental time in flies reared at 25°C. Sixty percent of the lines showed a heterochronic phenotype, suggesting that a large number of genes affect this trait. Mutant lines for the genes <it>Merlin </it>and <it>Karl </it>showed the most extreme phenotypes exhibiting a developmental time reduction and increase, respectively, of over 2 days and 4 days relative to the control (a co-isogenic <it>P</it>-element insertion free line). In addition, a subset of 42 lines selected at random from the initial set of 179 lines was screened at 17°C. Interestingly, the gene-by-environment interaction accounted for 52% of total phenotypic variance. Plastic reaction norms were found for a large number of developmental time candidate genes.</p> <p>Conclusion</p> <p>We identified components of several integrated time-dependent pathways affecting egg-to-adult developmental time in <it>Drosophila</it>. At the same time, we also show that many heterochronic phenotypes may arise from changes in genes involved in several developmental mechanisms that do not explicitly control the timing of specific events. We also demonstrate that many developmental time genes have pleiotropic effects on several adult traits and that the action of most of them is sensitive to temperature during development. Taken together, our results stress the need to take into account the effect of environmental variation and the dynamics of gene interactions on the genetic architecture of this complex life-history trait.</p

Model-guided therapy for hepatocellular carcinoma: A role for information technology in predictive, preventive and personalized medicine

Predictive, preventive and personalized medicine (PPPM) may have the potential to eventually improve the nature of health care delivery. However, the tools required for a practical and comprehensive form of PPPM that is capable of handling the vast amounts of medical information that is currently available are currently lacking. This article reviews a rationale and method for combining and integrating diagnostic and therapeutic management with information technology (IT), in a manner that supports patients through their continuum of care. It is imperative that any program devised to explore and develop personalized health care delivery must be firmly rooted in clinically confirmed and accepted principles and technologies. Therefore, a use case, relating to hepatocellular carcinoma (HCC), was developed. The approach to the management of medical information we have taken is based on model theory and seeks to implement a form of model-guided therapy (MGT) that can be used as a decision support system in the treatment of patients with HCC. The IT structures to be utilized in MGT include a therapy imaging and model management system (TIMMS) and a digital patient model (DPM). The system that we propose will utilize patient modeling techniques to generate valid DPMs (which factor in age, physiologic condition, disease and co-morbidities, genetics, biomarkers and responses to previous treatments). We may, then, be able to develop a statistically valid methodology, on an individual basis, to predict certain diseases or conditions, to predict certain treatment outcomes, to prevent certain diseases or complications and to develop treatment regimens that are personalized for that particular patient. An IT system for predictive, preventive and personalized medicine (ITS-PM) for HCC is presented to provide a comprehensive system to provide unified access to general medical and patient-specific information for medical researchers and health care providers from different disciplines including hepatologists, gastroenterologists, medical and surgical oncologists, liver transplant teams, interventional radiologists and radiation oncologists. The article concludes with a review providing an outlook and recommendations for the application of MGT to enhance the medical management of HCC through PPPM

"Now we are in a different time; various bad diseases have come." understanding men's acceptability of male circumcision for HIV prevention in a moderate prevalence setting

Background: Adult male surgical circumcision (MC) has been shown to reduce HIV acquisition in men and is recommended by the WHO for inclusion in comprehensive national HIV prevention programs in high prevalence settings. Only limited research to date has been conducted in countries experiencing moderate burden epidemics, where the acceptability, operational feasibility and potential epidemiological impact of MC remain unclear. Methods. A multi-method qualitative research study was conducted at four sites in Papua New Guinea (PNG), with 24 focus group discussions and 65 in-depth interviews carried out among 276 men. Results: The majority of men were in favour of MC being introduced for HIV prevention in PNG and considered improved genital hygiene, enhanced sexual pleasure and culturally appropriateness key factors in the acceptability of a future intervention. A minority of men were against the introduction of MC, primarily due to concerns regarding sexual risk compensation and that the intervention went against prevailing cultural and religious beliefs. Conclusion: This is one of the first community-based MC acceptability studies conducted in a moderate prevalence setting outside of Africa. Research findings from this study suggest that a future MC program for HIV prevention would be widely accepted by men in PNG

A Glutathione Peroxidase, Intracellular Peptidases and the TOR Complexes Regulate Peptide Transporter PEPT-1 in C. elegans

The intestinal peptide transporter PEPT-1 in Caenorhabditis elegans is a rheogenic H+-dependent carrier responsible for the absorption of di- and tripeptides. Transporter-deficient pept-1(lg601) worms are characterized by impairments in growth, development and reproduction and develop a severe obesity like phenotype. The transport function of PEPT-1 as well as the influx of free fatty acids was shown to be dependent on the membrane potential and on the intracellular pH homeostasis, both of which are regulated by the sodium-proton exchanger NHX-2. Since many membrane proteins commonly function as complexes, there could be proteins that possibly modulate PEPT-1 expression and function. A systematic RNAi screening of 162 genes that are exclusively expressed in the intestine combined with a functional transport assay revealed four genes with homologues existing in mammals as predicted PEPT-1 modulators. While silencing of a glutathione peroxidase surprisingly caused an increase in PEPT-1 transport function, silencing of the ER to Golgi cargo transport protein and of two cytosolic peptidases reduced PEPT-1 transport activity and this even corresponded with lower PEPT-1 protein levels. These modifications of PEPT-1 function by gene silencing of homologous genes were also found to be conserved in the human epithelial cell line Caco-2/TC7 cells. Peptidase inhibition, amino acid supplementation and RNAi silencing of targets of rapamycin (TOR) components in C. elegans supports evidence that intracellular peptide hydrolysis and amino acid concentration are a part of a sensing system that controls PEPT-1 expression and function and that involves the TOR complexes TORC1 and TORC2

Commitment of cultural minorities in organizations:Effects of leadership and pressure to conform

PURPOSE: In this study, we investigated the commitment of cultural minorities and majorities in organizations. We examined how contextual factors, such as pressure to conform and leadership styles, affect the commitment of minority and majority members. DESIGN/METHODOLOGY/APPROACH: A field study was conducted on 107 employees in a large multinational corporation. FINDINGS: We hypothesize and found that cultural minorities felt more committed to the organization than majority members, thereby challenging the existing theoretical view that cultural minorities will feel less committed. We also found that organizational pressure to conform and effective leadership increased the commitment of minorities. IMPLICATIONS: Our findings indicate that organizational leaders and researchers should not only focus on increasing and maintaining the commitment of minority members, but should also consider how majority members react to cultural socialization and integration processes. The commitment of minority members can be further enhanced by effective leadership. ORIGINALITY/VALUE: In this study, we challenge the existing theoretical view based on similarity attraction theory and relational demography theory, that cultural minorities would feel less committed to the organization. Past research has mainly focused on minority groups, thereby ignoring the reaction of the majority to socialization processes. In this study, we show that cultural minorities can be more committed than majority members in organizations. Therefore, the perceptions of cultural majority members of socialization processes should also be considered in research on cultural diversity and acculturation