Expression and Distribution of Ectonucleotidases in Mouse Urinary Bladder

Background: Normal urinary bladder function requires bidirectional molecular communication between urothelium, detrusor smooth muscle and sensory neurons and one of the key mediators involved in this intercellular signaling is ATP. Ectonucleotidases dephosphorylate nucleotides and thus regulate ligand exposure to P2X and P2Y purinergic receptors. Little is known about the role of these enzymes in mammalian bladder despite substantial literature linking bladder diseases to aberrant purinergic signaling. We therefore examined the expression and distribution of ectonucleotidases in the mouse bladder since mice offer the advantage of straightforward genetic modification for future studies. Principal Findings: RT-PCR demonstrated that eight members of the ectonucleoside triphosphate diphosphohydrolase (NTPD) family, as well as 5'-nucleotidase (NT5E) are expressed in mouse bladder. NTPD1, NTPD2, NTPD3, NTPD8 and NT5E all catalyze extracellular nucleotide dephosphorylation and in concert achieve stepwise conversion of extracellular ATP to adenosine. Immunofluorescent localization with confocal microscopy revealed NTPD1 in endothelium of blood vessels in the lamina propria and in detrusor smooth muscle cells, while NTPD2 was expressed in cells localized to a region of the lamina propria adjacent to detrusor and surrounding muscle bundles in the detrusor. NTPD3 was urothelial-specific, occurring on membranes of intermediate and basal epithelial cells but did not appear to be present in umbrella cells. Immunoblotting confirmed NTPD8 protein in bladder and immunofluorescence suggested a primary localization to the urothelium. NT5E was present exclusively in detrusor smooth muscle in a pattern complementary with that of NTPD1 suggesting a mechanism for providing adenosine to P1 receptors on the surface of myocytes. Conclusions: Ectonucleotidases exhibit highly cell-specific expression patterns in bladder and therefore likely act in a coordinated manner to regulate ligand availability to purinergic receptors. This is the first study to determine the expression and location of ectonucleotidases within the mammalian urinary bladder

Th1 Disabled Function in Response to TLR4 Stimulation of Monocyte-Derived DC from Patients Chronically-Infected by Hepatitis C Virus

Background: Lack of protective antibodies and inefficient cytotoxic responses are characteristics of chronic hepatitis C infection. A defect in dendritic cell (DC) function has thus been suspected, but this remains a controversial issue. Methods and Findings: Here we show that monocyte-derived DC (MoDC) from chronically-infected patients can mature in response to TLR1/2, TLR2/6 or TLR3 ligands. In contrast, when stimulated with the TLR4 ligand LPS, MoDC from patients show a profound defect in inducing IFNc secretion by allogeneic T cells. This defect is not due to defective phenotypic maturation or to the presence of HCV-RNA in DC or monocytes but is correlated to reduced IL-12 secretion by DC. Restoration of DC ability to stimulate IFNc secretion can be obtained by blocking MEK activation in DC, indicating that MEK/ ERK pathway is involved in the Th1 defect of MoDC. Monocytes from HCV patients present increased spontaneous secretion of cytokines and chemokines, especially MIP-1b. Addition of MIP-1b on healthy monocytes during differentiation results in DC that have Th1 defect characteristic of MoDC from HCV patients, suggesting that MIP-1b secretion by HCV monocytes participates in the Th1 defect of DC. Conclusions: Our data indicate that monocytes from HCV patients are activated in vivo. This interferes with their differentiation into DC, leading to deficient TLR4 signaling in these cells that are enable to induce a Th1 response. Thi

Setting the stage: host invasion by HIV.

For more than two decades, HIV has infected millions of people worldwide each year through mucosal transmission. Our knowledge of how HIV secures a foothold at both the molecular and cellular levels has been expanded by recent investigations that have applied new technologies and used improved techniques to isolate ex vivo human tissue and generate in vitro cellular models, as well as more relevant in vivo animal challenge systems. Here, we review the current concepts of the immediate events that follow viral exposure at genital mucosal sites where most documented transmissions occur. Furthermore, we discuss the gaps in our knowledge that are relevant to future studies, which will shape strategies for effective HIV prevention

Can religious affiliation explain the disadvantage of Muslim women in the British labour market?

This article aims to explain the labour market penalties among Muslim women in Britain. It draws on theories of intersectionality and colour/cultural racism to argue that the labour market experience of British-Muslim women is multiply determined via criteria of ascription such as ethnicity, migration status, race and religion rather than criteria of achievement. The study uses data from the Labour Force Survey (2002–2013) with a large sample (N=245,391) of women aged 19–65 years. The overarching finding suggests that most Muslim women, regardless of their multiple ascriptive identities, generation and levels of qualifications, still face significant penalties compared with their White-British Christian counterparts. The penalties for some groups, such as Pakistani, Bangladeshi and Black-Muslim women, are harsher than for Indian and White-Muslim women, demonstrating how different social markers and multiple identities have contingent relationships to multiple determinants and outcomes

Financializing space, spacing financialization

The paper develops a sympathetic geographical critique of the concept of financialization which seeks to account for the growing influence of financial markets over the unfolding of economy, polity and society. Processes of financialization are claimed to be manifest at a number of scales, from higher levels of instability within the economy as a whole, through pressure exerted on corporations by capital markets, to the equity effects of the financial system on individuals and households. In seeking to explain change within contemporary society, financialization has circulated less widely than similar and related concepts such as neoliberalization. While financialization has the potential to unite researchers across cognate social science fields, thereby building critical mass and recognition within social studies of money and finance, we argue that research has been insufficiently attentive to space and place, both in terms of processes and effects. Financialization is a profoundly spatial phenomenon, representing as it does the search for a spatial-temporal fix, or quasi-resolution of the crisis tendencies of contemporary capitalism. The paper explores a number of possibly fruitful directions for work on financialization, focusing in particular on the idea of financial ecologies

Work-Related Musculoskeletal Disorders among Nurses in Ibadan, South-west Nigeria: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Musculoskeletal disorders represent a significant occupational problem among nurses; however, data on musculoskeletal health of nurses in Sub-Sahara Africa are sparse. This study sought to determine the lifetime, 12-months period and point prevalence of work-related musculoskeletal disorders (WMSDs); the associated job risk factors and the coping strategies toward reducing the risk among nurses from selected hospitals in Ibadan, South-west Nigeria</p> <p>Methods</p> <p>A previously validated self administered questionnaire which sought information on demographics, prevalence and pattern of WMSDs, associated job risk factors and coping strategies was employed as the survey instrument. A total of 160 questionnaires were distributed to nurses in the different hospitals but 128 questionnaires were returned yielding an 80% response rate. 10 of the returned questionnaires were excluded because of incomplete data.</p> <p>Results</p> <p>Eighty-four point four percent of the nurses have had WMSDs once or more in their occupational lives. The 12-months period and point prevalence rate of WMSDs at any body region was 78% and 66.1% respectively. WMSDs occurred mostly in low back (44.1%), neck (28.0%), and knees (22.4%). 30.3% treated themselves or had visited other health practitioners for care. Nurses with > 20 years of clinical experience are about 4 times more likely to develop WMSDs (OR 3.81; CI 1.08-13.4) than those with 11-20 years experience. Working in the same positions for long periods (55.1%), lifting or transferring dependent patients (50.8%) and treating an excessive number of patients in one day (44.9%) were the most perceived job risk factors for WMSDs. Getting help in handling heavy patients (50.4%), modification of nursing procedures in order to avoid re-injury (45.4%), and modifying patient's/nurse position (40.3%) were the top three coping strategies.</p> <p>Conclusions</p> <p>A high proportion of Nigerian nurses reported WMSDs at some body site in their occupational lives with the low back being injured most often. Education programmes on prevention and coping strategies for musculoskeletal disorders are recommended for nurses in order to reduce the rate of occupational hazards and also promote efficiency in patient care.</p