619 research outputs found

    Decrease in expression of bone morphogenetic proteins 4 and 5 in synovial tissue of patients with osteoarthritis and rheumatoid arthritis

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    Bone morphogenetic proteins (BMPs) have been identified as important morphogens with pleiotropic functions in regulating the development, homeostasis and repair of various tissues. The aim of this study was to characterize the expression of BMPs in synovial tissues under normal and arthritic conditions. Synovial tissue from normal donors (ND) and from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) were analyzed for BMP expression by using microarray hybridization. Differential expression of BMP-4 and BMP-5 was validated by semiquantitative RT-PCR, in situ hybridization and immunohistochemistry. Activity of arthritis was determined by routine parameters for systemic inflammation, by histological scoring of synovitis and by semiquantitative RT-PCR of IL-1β, TNF-α, stromelysin and collagenase I in synovial tissue. Expression of BMP-4 and BMP-5 mRNA was found to be significantly decreased in synovial tissue of patients with RA in comparison with ND by microarray analysis (p < 0.0083 and p < 0.0091). Validation by PCR confirmed these data in RA (p < 0.002) and also revealed a significant decrease in BMP-4 and BMP-5 expression in OA compared with ND (p < 0.015). Furthermore, histomorphological distribution of both morphogens as determined by in situ hybridization and immunohistochemistry showed a dominance in the lining layer of normal tissues, whereas chronically inflamed tissue from patients with RA revealed BMP expression mainly scattered across deeper layers. In OA, these changes were less pronounced with variable distribution of BMPs in the lining and sublining layer. BMP-4 and BMP-5 are expressed in normal synovial tissue and were found decreased in OA and RA. This may suggest a role of distinct BMPs in joint homeostasis that is disturbed in inflammatory and degenerative joint diseases. In comparison with previous reports, these data underline the complex impact of these factors on homeostasis and remodeling in joint physiology and pathology

    The laurentian record of neoproterozoic glaciation, tectonism, and eukaryotic evolution in Death Vally, California

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    Neoproterozoic strata in Death Valley, California contain eukaryotic microfossils and glacial deposits that have been used to assess the severity of putative Snowball Earth events and the biological response to extreme environmental change. These successions also contain evidence for syn-sedimentary faulting that has been related to the rifting of Rodinia, and in turn the tectonic context of the onset of Snowball Earth. These interpretations hinge on local geological relationships and both regional and global stratigraphic correlations. Here we present new geological mapping, measured stratigraphic sections, carbon and strontium isotope chemostratigraphy, and micropaleontology from the Neoproterozoic glacial deposits and bounding strata in Death Valley. These new data enable us to refine regional correlations both across Death Valley and throughout Laurentia, and construct a new age model for glaciogenic strata and microfossil assemblages. Particularly, our remapping of the Kingston Peak Formation in the Saddle Peak Hills and near the type locality shows for the first time that glacial deposits of both the Marinoan and Sturtian glaciations can be distinguished in southeastern Death Valley, and that beds containing vase-shaped microfossils are slump blocks derived from the underlying strata. These slump blocks are associated with multiple overlapping unconformities that developed during syn-sedimentary faulting, which is a common feature of Cyrogenian strata along the margin of Laurentia from California to Alaska. With these data, we conclude that all of the microfossils that have been described to date in Neoproterozoic strata of Death Valley predate the glaciations and do not bear on the severity, extent or duration of Neoproterozoic Snowball Earth events

    Integrating transposable elements in the 3D genome

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    Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

    Needlestick and sharps injuries among health care workers at public tertiary hospitals in an urban community in Mongolia

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    <p>Abstract</p> <p>Background</p> <p>Needlestick and sharps injuries (NSSIs) are one of the major risk factors for blood-borne infections at healthcare facilities. This study examines the current situation of NSSIs among health care workers at public tertiary hospitals in an urban community in Mongolia and explores strategies for the prevention of these injuries.</p> <p>Findings</p> <p>A survey of 621 health care workers was undertaken in two public tertiary hospitals in Ulaanbaatar, Mongolia, in July 2006. A semi-structured and self-administered questionnaire was distributed to study injection practices and the occurrence of NSSIs. A multiple logistic regression analysis was performed to investigate factors associated with experiencing NSSIs. Among the 435 healthcare workers who returned a completed questionnaire, the incidence of NSSIs during the previous 3 months was 38.4%. Health care workers were more likely to report NSSIs if they worked longer than 35 hours per week (odds ratio, OR: 2.47; 95% confidence interval, CI: 1.31-4.66) and administered more than 10 injections per day (OR: 4.76; 95% CI: 1.97-11.49). The likelihood of self-reporting NSSIs significantly decreased if health care workers adhered to universal precautions (OR: 0.34; 95% CI: 0.17-0.68).</p> <p>Conclusions</p> <p>NSSIs are a common public health problem at public tertiary hospitals in Mongolia. The promotion of adequate working conditions, elimination of excessive injection use, and adherence to universal precautions will be important for the future control of potential infections with blood-borne pathogens due to occupational exposures to sharps in this setting.</p

    Curcumin-Loaded Apotransferrin Nanoparticles Provide Efficient Cellular Uptake and Effectively Inhibit HIV-1 Replication In Vitro

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    Curcumin (diferuloylmethane) shows significant activity across a wide spectrum of conditions, but its usefulness is rather limited because of its low bioavailability. Use of nanoparticle formulations to enhance curcumin bioavailability is an emerging area of research.In the present study, curcumin-loaded apotransferrin nanoparticles (nano-curcumin) prepared by sol-oil chemistry and were characterized by electron and atomic force microscopy. Confocal studies and fluorimetric analysis revealed that these particles enter T cells through transferrin-mediated endocytosis. Nano-curcumin releases significant quantities of drug gradually over a fairly long period, ∼50% of curcumin still remaining at 6 h of time. In contrast, intracellular soluble curcumin (sol-curcumin) reaches a maximum at 2 h followed by its complete elimination by 4 h. While sol-curcumin (GI(50) = 15.6 µM) is twice more toxic than nano-curcumin (GI(50) = 32.5 µM), nano-curcumin (IC(50)<1.75 µM) shows a higher anti-HIV activity compared to sol-curcumin (IC(50) = 5.1 µM). Studies in vitro showed that nano-curcumin prominently inhibited the HIV-1 induced expression of Topo II α, IL-1β and COX-2, an effect not seen with sol-curcumin. Nano-curcumin did not affect the expression of Topoisomerase II β and TNF α. This point out that nano-curcumin affects the HIV-1 induced inflammatory responses through pathways downstream or independent of TNF α. Furthermore, nano-curcumin completely blocks the synthesis of viral cDNA in the gag region suggesting that the nano-curcumin mediated inhibition of HIV-1 replication is targeted to viral cDNA synthesis.Curcumin-loaded apotransferrin nanoparticles are highly efficacious inhibitors of HIV-1 replication in vitro and promise a high potential for clinical usefulness

    An ecological quantification of the relationships between water, sanitation and infant, child, and maternal mortality

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    <p>Abstract</p> <p>Background</p> <p>Water and sanitation access are known to be related to newborn, child, and maternal health. Our study attempts to quantify these relationships globally using country-level data: How much does improving access to water and sanitation influence infant, child, and maternal mortality?</p> <p>Methods</p> <p>Data for 193 countries were abstracted from global databases (World Bank, WHO, and UNICEF). Linear regression was used for the outcomes of under-five mortality rate and infant mortality rate (IMR). These results are presented as events per 1000 live births. Ordinal logistic regression was used to compute odds ratios for the outcome of maternal mortality ratio (MMR).</p> <p>Results</p> <p>Under-five mortality rate decreased by 1.17 (95%CI 1.08-1.26) deaths per 1000, <it>p </it>< 0.001, for every quartile increase in population water access after adjustments for confounders. There was a similar relationship between quartile increase of sanitation access and under-five mortality rate, with a decrease of 1.66 (95%CI 1.11-1.32) deaths per 1000, <it>p </it>< 0.001. Improved water access was also related to IMR, with the IMR decreasing by 1.14 (95%CI 1.05-1.23) deaths per 1000, <it>p </it>< 0.001, with increasing quartile of access to improved water source. The significance of this relationship was retained with quartile improvement in sanitation access, where the decrease in IMR was 1.66 (95%CI 1.11-1.32) deaths per 1000, <it>p </it>< 0.001. The estimated odds ratio that increased quartile of water access was significantly associated with increased quartile of MMR was 0.58 (95%CI 0.39-0.86), <it>p </it>= 0.008. The corresponding odds ratio for sanitation was 0.52 (95%CI 0.32-0.85), <it>p </it>= 0.009, both suggesting that better water and sanitation were associated with decreased MMR.</p> <p>Conclusions</p> <p>Our analyses suggest that access to water and sanitation independently contribute to child and maternal mortality outcomes. If the world is to seriously address the Millennium Development Goals of reducing child and maternal mortality, then improved water and sanitation accesses are key strategies.</p
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