264 research outputs found

    Active removal of inorganic phosphate from cerebrospinal fluid by the choroid plexus

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    The P-i concentration of mammalian cerebrospinal fluid (CSF) is about one-half that of plasma, a phenomenon also shown here in the spiny dogfish, Squalus acanthias. The objective of the present study was to characterize the possible role of the choroid plexus (CP) in determining CSF P-i concentration. The large sheet-like fourth CP of the shark was mounted in Ussing chambers where unidirectional P-33(i) fluxes revealed potent active transport from CSF to the blood side under short-circuited conditions. The flux ratio was 8: 1 with an average transepithelial resistance of 87 +/- 17.9 Omega . cm(2) and electrical potential difference of + 0.9 +/- 0.17 mV (CSF side positive). Active P-i absorption from CSF was inhibited by 10 mM arsenate, 0.2 mM ouabain, Na+ -free medium, and increasing the K+ concentration from 5 to 100 mM. Li+ stimulated transport twofold compared with Na+-free medium. Phosphonoformic acid (1 mM) had no effect on active Pi transport. RT-PCR revealed both P-i transporter (PiT) 1 and PiT2 (SLC20 family) gene expression, but no Na+ -P-i cotransporter II (SLC34 family) expression, in the shark CP. PiT2 immunoreactivity was shown by immunoblot analysis and localized by immunohistochemistry in (or near) the CP apical microvillar membranes of both the shark and rat. PiT1 appeared to be localized primarily to vascular endothelial cells. Taken together, these data indicate that the CP actively removes P-i from CSF. This process has transport properties consistent with a PiT2, Na+-dependent transporter that is located in the apical region of the CP epithelium.National Science Foundation [0843253]; Fundacao para a Ciencia e a Tecnologia, Portuga

    Magnetic Fields Produced by Phase Transition Bubbles in the Electroweak Phase Transition

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    The electroweak phase transition, if proceeding through nucleation and growth of bubbles, should generate large scale turbulent flow, which in turn generates magnetic turbulence and hence magnetic fields on the scale of turbulent flow. We discuss the seeding of this turbulent field by the motion of the dipole charge layers in the phase transition bubble walls, and estimate the strength of the produced fields.Comment: Revtex, 14 pages, 3 figures appended as uuencoded postscript-fil

    Community Engaged Cumulative Risk Assessment of Exposure to Inorganic Well Water Contaminants, Crow Reservation, Montana

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    An estimated 11 million people in the US have home wells with unsafe levels of hazardous metals and nitrate. The national scope of the health risk from consuming this water has not been assessed as home wells are largely unregulated and data on well water treatment and consumption are lacking. Here, we assessed health risks from consumption of contaminated well water on the Crow Reservation by conducting a community-engaged, cumulative risk assessment. Well water testing, surveys and interviews were used to collect data on contaminant concentrations, water treatment methods, well water consumption, and well and septic system protection and maintenance practices. Additive Hazard Index calculations show that the water in more than 39% of wells is unsafe due to uranium, manganese, nitrate, zinc and/or arsenic. Most families’ financial resources are limited, and 95% of participants do not employ water treatment technologies. Despite widespread high total dissolved solids, poor taste and odor, 80% of families consume their well water. Lack of environmental health literacy about well water safety, pre-existing health conditions and limited environmental enforcement also contribute to vulnerability. Ensuring access to safe drinking water and providing accompanying education are urgent public health priorities for Crow and other rural US families with low environmental health literacy and limited financial resources

    The evaluation of disability and its related factors among the elderly population in Kashan, Iran

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    <p>Abstract</p> <p>Background</p> <p>Recent literature indicates that developing countries in Asia are aging faster than other countries in the world and disability has become one of the greater public health concern in these countries. Pausity of published data on the elderly disability in Iran signifies the importance of this study designed to evaluate the disability and its related factors among the elderly population in Kashan, Iran during 2006–2007.</p> <p>Methods/Design</p> <p>A cross-sectional study is conducting on a multy-stage random sample of elderly people in Kashan ages 65 years and older. Volunteer participants were included by age 65 and older and excluded if they had the medical diagnosis of Alzhimer disease. The WHO DAS II was used as the generic disability measure in this survey. The original version of WHO DAS II was translated into Farsi according to the standardized guidelines for cross-cultural adaptation of health-related measures. Upon completion of data collection the descriptive statistics will compute all the variables. Chi-square, t-test analysis and ANOVA will be used to examine significant differences between the subgroups.</p> <p>Discussion</p> <p>This is the first research protocol to study disability among the Iranian elderly population. Presently, 80% of eligible subjects have been selected. The results of this study will help to develop more effective protocols to assist Iranian elderly population with disabilities.</p

    Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

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    Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al

    Aptamer-based multiplexed proteomic technology for biomarker discovery

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    Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine
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