Workplace Accidents among Nepali Male Workers in the Middle East and Malaysia: A Qualitative Study

There are many Nepali men working in the Middle East and Malaysia and media reports and anecdotal evidence suggest a high risk of workplace-related accidents and injuries for male Nepali workers. Therefore, this study aims to explore the personal experiences of male Nepali migrants of unintentional injuries at their place of work. In-depth, face-to-face interviews (n = 20) were conducted with male Nepali migrant workers. Study participants were approached at Kathmandu International Airport, hotels and lodges around the airport. Interviews were transcribed and analysed using thematic analysis. Almost half of study participants experienced work-related accident abroad. The participants suggested that the reasons behind this are not only health and safety at work but also poor communication, taking risks by workers themselves, and perceived work pressure. Some participants experienced serious incidents causing life-long disability, extreme and harrowing accounts of injury but received no support from their employer or host countries. Nepali migrant workers would appear to be at a high risk of workplace unintentional injuries owing to a number of interrelated factors poor health and safety at work, pressure of work, risk taking practices, language barriers, and their general work environment. Both the Government of Nepal and host countries need to be better policing existing policies, introduce better legislation where necessary, ensure universal health (insurance) coverage for labour migrants, and improve preventive measures to minimize the number and severity of accidents and injuries among migrant workers

PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth.

BackgroundProgesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms.ResultsWe demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of the Warburg effect. This was associated with increased PI3K/AKT activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/AKT activation. Mutation of Y180F strongly attenuated subcutaneous xenograft tumor growth in NOD-SCID gamma mice. Elsewhere we demonstrate altered metabolism, mutation incidence, and epigenetic status in these cells.ConclusionsAltogether, these results indicate that mutational manipulation of PGRMC1 phosphorylation status exerts broad pleiotropic effects relevant to cancer and other cell biology

Groundwater Nitrogen Pollution and Assessment of Its Health Risks: A Case Study of a Typical Village in Rural-Urban Continuum, China

Protecting groundwater from nitrogen contamination is an important public-health concern and a major national environmental issue in China. In this study, we monitored water quality in 29 wells from 2009 to 2010 in a village in Shanghai city, whick belong to typical rural-urban continuum in China. The total N and NO3-N exhibited seasonal changes, and there were large fluctuations in NH4-N in residential areas, but without significant seasonal patterns. NO2-N in the water was not stable, but was present at high levels. Total N and NO3-N were significantly lower in residential areas than in agricultural areas. The groundwater quality in most wells belonged to Class III and IV in the Chinese water standard, which defines water that is unsuitable for human consumption. Our health risk assessments showed that NO3-N posed the greatest carcinogenic risk, with risk values ranging from 19×10−6 to 80×10−6, which accounted for more than 90% of the total risk in the study area

A Curated Database of miRNA Mediated Feed-Forward Loops Involving MYC as Master Regulator

BACKGROUND: The MYC transcription factors are known to be involved in the biology of many human cancer types. But little is known about the Myc/microRNAs cooperation in the regulation of genes at the transcriptional and post-transcriptional level. METHODOLOGY/PRINCIPAL FINDINGS: Employing independent databases with experimentally validated data, we identified several mixed microRNA/Transcription Factor Feed-Forward Loops regulated by Myc and characterized completely by experimentally supported regulatory interactions, in human. We then studied the statistical and functional properties of these circuits and discussed in more detail a few interesting examples involving E2F1, PTEN, RB1 and VEGF. CONCLUSIONS/SIGNIFICANCE: We have assembled and characterized a catalogue of human mixed Transcription Factor/microRNA Feed-Forward Loops, having Myc as master regulator and completely defined by experimentally verified regulatory interactions

Genomewide Analyses Define Different Modes of Transcriptional Regulation by Peroxisome Proliferator-Activated Receptor-β/δ (PPARβ/δ)

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors with essential functions in lipid, glucose and energy homeostasis, cell differentiation, inflammation and metabolic disorders, and represent important drug targets. PPARs heterodimerize with retinoid X receptors (RXRs) and can form transcriptional activator or repressor complexes at specific DNA elements (PPREs). It is believed that the decision between repression and activation is generally governed by a ligand-mediated switch. We have performed genomewide analyses of agonist-treated and PPARβ/δ-depleted human myofibroblasts to test this hypothesis and to identify global principles of PPARβ/δ-mediated gene regulation. Chromatin immunoprecipitation sequencing (ChIP-Seq) of PPARβ/δ, H3K4me3 and RNA polymerase II enrichment sites combined with transcriptional profiling enabled the definition of 112 bona fide PPARβ/δ target genes showing either of three distinct types of transcriptional response: (I) ligand-independent repression by PPARβ/δ; (II) ligand-induced activation and/or derepression by PPARβ/δ; and (III) ligand-independent activation by PPARβ/δ. These data identify PPRE-mediated repression as a major mechanism of transcriptional regulation by PPARβ/δ, but, unexpectedly, also show that only a subset of repressed genes are activated by a ligand-mediated switch. Our results also suggest that the type of transcriptional response by a given target gene is connected to the structure of its associated PPRE(s) and the biological function of its encoded protein. These observations have important implications for understanding the regulatory PPAR network and PPARβ/δ ligand-based drugs

Myc-regulated microRNAs attenuate embryonic stem cell differentiation

Myc proteins are known to have an important function in stem cell maintenance. As Myc has been shown earlier to regulate microRNAs (miRNAs) involved in proliferation, we sought to determine whether c-Myc also affects embryonic stem (ES) cell maintenance and differentiation through miRNAs. Using a quantitative primer-extension PCR assay we identified miRNAs, including, miR-141, miR-200, and miR-429 whose expression is regulated by c-Myc in ES cells, but not in the differentiated and tumourigenic derivatives of ES cells. Chromatin immunoprecipitation analyses indicate that in ES cells c-Myc binds proximal to genomic regions encoding the induced miRNAs. We used expression profiling and seed homology to identify genes specifically downregulated both by these miRNAs and by c-Myc. We further show that the introduction of c-Myc-induced miRNAs into murine ES cells significantly attenuates the downregulation of pluripotency markers on induction of differentiation after withdrawal of the ES cell maintenance factor LIF. In contrast, knockdown of the endogenous miRNAs accelerate differentiation. Our data show that in ES cells c-Myc acts, in part, through a subset of miRNAs to attenuate differentiation

Chlorin p(6) as a fluorescent probe for the investigation of surfactant-cyclodextrin interactions - art. no. 609708

Cyclodextrins (CD) are often projected as potential vehicles in targeted drug delivery. However, if the membrane structure is disrupted by CD, then it cannot be considered to be a good drug delivery vehicle. When an extrinsic fluorescence probe is used to monitor such interactions, there are no less than three possible equilibria that can operate simultaneously: surfactant-cyclodextrin, surfactant-fluorophore and cyclodextrin-fluorophore. The fluorescence intensity / lifetime might be affected by all these and so, the results depend strongly on the fluorophore used as well as the nature of the surfactant. This aspect highlights the importance of the suitability of the fluorescence probe to be used to study complicated systems and interaction. In the present work, chlorin p(6), prepared from chlorophyll from spinach leaves, has been used as the fluorescence probe to investigate the interaction between alpha-CD and beta-CD with the neutral surfactants TX 100 and CTAB. The fluorophore is found to be a sensitive one for the study of the interaction of alpha- and beta-CD with the surfactants Tritron X 100 (TX 100) and cetyl trimethyl ammonium bromide (CTAB). It is found that contrary to earlier reports, a complex between alpha-CD and TX 100 is formed, even though the binding constant is not very high. This observation can be obtained with chlorin p6, which does not bind to the CDs, but not with a fluorophore like TNS, which binds to the CD as well and thus complicates the situation as the binding with CID is stronger than that between TX 100 and alpha-CD as compared to that between TNS and CD

Chlorin p(6) as a fluorescent probe for the investigation of surfactant-cyclodextrin interactions

Cyclodextrins (CD) are often proposed as potential vehicles in targeted drug delivery. However, if the membrane structure is disrupted by CD, then it cannot be considered to be a good drug delivery vehicle. When an extrinsic fluorescence probe is used to monitor such interactions, there are no less than three possible equilibria that can operate simultaneously: surfactant-cyclodextrin, surfactant fluorophore and cyclodextrin fluorophore. The fluorescence intensity/lifetime might be affected by all these and so, the results depend strongly on the fluorophore used as well as the nature of the surfactant. This aspect highlights the importance of the suitability of the. fluorescence probe to be used to study complicated systems and interaction. In the present work, chlorin p(6), prepared from chlorophyll from spinach leaves, has been used as the fluorescence probe to investigate the interaction between alpha-CD and beta-CD with the neutral surfactants Triton X 100 (TX 100) and cetyl trimethyl ammonium bromide (CTAB). The fluorophore is found to be a sensitive one for the study of the interaction of alpha, beta and gamma-CD with the surfactants TX 100 and CTAB. It is found that contrary to earlier reports, a complex between alpha-CD and TX 100 is formed, even though the binding constant is not very high. This observation can be obtained with chlorin p(6), which does not bind to the CDs, but not with a fluorophore, which binds to the CD as well and thus complicates the situation as the binding with CD is stronger than that between TX 100 and alpha-CD as compared to that between TNS and CD

Not Available

Not AvailableIn the present study, standardized precipitation index (SPI) series at 3-month, 6-month, 9-month, 12-month and 24-month time scale has been used to assess the vulnerability of meteorological drought in the Bundelkhand region of Central India. SPI values revealed that the droughts in the region over the study period vary from moderately high to extremely high. Suitable linear stochastic model, viz. seasonal and non seasonal autoregressive integrated moving average (ARIMA) developed to predict drought at different time scale. The best model was selected based on minimum Akaike Information Criterion (AIC) and Schwarz Bayesian Criterion (SBC). Statistical analysis revealed that non-seasonal ARIMA model was appropriate for 3-month SPI series while seasonal ARIMA models have been found promising for SPI series at 6-, -9,-12 and 24-month time scale. Parameter estimation step indicates that the estimated model parameters are significantly different from zero. The predicted data using the best ARIMA model were compared to the observed data for model validation purpose in which the predicted data show reasonably good agreement with the actual data. Hence the models were applied to forecast drought in the Bundelhand region up to 3 months advanced with good accuracy.Not Availabl