898 resultados para site Hector-Trudel


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Abstract

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Bacterial transcription activators of the XylR/DmpR subfamily exert their expression control via σ(54)-dependent RNA polymerase upon stimulation by a chemical effector, typically an aromatic compound. Where the chemical effector interacts with the transcription regulator protein to achieve activation is still largely unknown. Here we focus on the HbpR protein from Pseudomonas azelaica, which is a member of the XylR/DmpR subfamily and responds to biaromatic effectors such as 2-hydroxybiphenyl. We use protein structure modeling to predict folding of the effector recognition domain of HbpR and molecular docking to identify the region where 2-hydroxybiphenyl may interact with HbpR. A large number of site-directed HbpR mutants of residues in- and outside the predicted interaction area was created and their potential to induce reporter gene expression in Escherichia coli from the cognate P(C) promoter upon activation with 2-hydroxybiphenyl was studied. Mutant proteins were purified to study their conformation. Critical residues for effector stimulation indeed grouped near the predicted area, some of which are conserved among XylR/DmpR subfamily members in spite of displaying different effector specificities. This suggests that they are important for the process of effector activation, but not necessarily for effector specificity recognition.

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The ground-penetrating radar (GPR) geophysical method has the potential to provide valuable information on the hydraulic properties of the vadose zone because of its strong sensitivity to soil water content. In particular, recent evidence has suggested that the stochastic inversion of crosshole GPR traveltime data can allow for a significant reduction in uncertainty regarding subsurface van Genuchten-Mualem (VGM) parameters. Much of the previous work on the stochastic estimation of VGM parameters from crosshole GPR data has considered the case of steady-state infiltration conditions, which represent only a small fraction of practically relevant scenarios. We explored in detail the dynamic infiltration case, specifically examining to what extent time-lapse crosshole GPR traveltimes, measured during a forced infiltration experiment at the Arreneas field site in Denmark, could help to quantify VGM parameters and their uncertainties in a layered medium, as well as the corresponding soil hydraulic properties. We used a Bayesian Markov-chain-Monte-Carlo inversion approach. We first explored the advantages and limitations of this approach with regard to a realistic synthetic example before applying it to field measurements. In our analysis, we also considered different degrees of prior information. Our findings indicate that the stochastic inversion of the time-lapse GPR data does indeed allow for a substantial refinement in the inferred posterior VGM parameter distributions compared with the corresponding priors, which in turn significantly improves knowledge of soil hydraulic properties. Overall, the results obtained clearly demonstrate the value of the information contained in time-lapse GPR data for characterizing vadose zone dynamics.

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The Doty Landfill encompasses 13 acres of land and is located in the southeastern quarter of Section 29, Township 81 North, Range 6 East, Clinton County, Iowa. The site was used as a landfill for municipal solid waste from 1970 to 1975. In addition, local residents have expressed concern that other chemical-or pesticide waste had been disposed at the site. Previous site investigations had been completed in 1992 and in 2005. In October 2007 water samples from private wells located in the vicinity of the Doty Landfill site were collected and analyzed for dissolved metals. Two of the water samples obtained from drinking water wells contained dissolved arsenic above the US EPA Maximum Contaminant Level (MCL) for arsenic of 10 μg/L (micrograms per liter) or 10 ppb (parts per billion). The water samples in question contained dissolved arsenic at concentrations of 19.3 and 14.9 μg/L or 19.3 and 14.9 ppb.

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The Iowa Department of Public Health (IDPH), Hazardous Waste Site Health Assessment Program was asked by the US Environmental Protection Agency (EPA) to review a round of air sampling data. The air data was collected and analyzed during a removal action at the Le Mars Coal Gas Site in Le Mars, Iowa. EPA asked IDPH to determine from the air data if additional monitoring is necessary throughout the removal action to protect nearby residents from exposure.

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An attorney representing seven property owners in Lowell, Iowa, requested the Iowa Department of Public Health (IDPH) Hazardous Waste Site Health Assessment Program to perform a health consultation for the Jet Gas Spill Site. The attorney asked the IDPH to provide comments concerning the potential and likely health effects to her clients due to exposure from the spill. The specific issues to be addressed are listed in this health consultation. The information in this health consultation was current at the time of writing. Data that emerges later could alter this document’s conclusions and recommendations.

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The Iowa Department of Natural Resources (IDNR) asked the Iowa Department of Public Health (IDPH) Hazardous Waste Site Health Assessment Program to perform a health consultation for the Climbing Hill, Iowa, groundwater contamination site. IDNR wants to know if the site poses a public health hazard. The information in this health consultation was current at the time of writing. Data that emerges later could alter this document’s conclusions and recommendations. Climbing Hill is an unincorporated town in Woodbury County, Iowa, approximately 15 miles southeast of Sioux City. The town has approximately 120 residents. All of the residents and most businesses within the town use private wells to supply their drinking water. The local restaurant has an individual well that is classified as a public water supply system because it has the potential to serve more than 25 people in a day. Several wells in the town have become contaminated with gasoline and diesel fuel leaking from two underground storage tanks. All of the wells are roughly 75–80 feet deep (R. Cardinale, IDNR, Underground Storage Tank Section, personal communication, January 30, 2004).

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The U. S. Environmental Protection Agency (EPA) Region 7, as well as concerned citizens, asked the Iowa Department of Public Health (IDPH) Hazardous Waste Site Health Assessment Program to perform a health consultation for the Hills, Iowa Perchlorate Groundwater Contamination Site. Specifically, IDPH was asked to determine if EPA’s action of providing bottled water to residents whose private wells had concentrations of greater than 18 μg/L (micrograms per liter) or 18 parts per billion (ppb) perchlorate is protective of public health, and to address some community health concerns. The information included in this health consultation was current at the time of writing. Data that emerges later could alter this document’s conclusions and recommendations.

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SCG10 is a neuron-specific, membrane-associated protein that is highly concentrated in growth cones of developing neurons. Previous studies have suggested that it is a regulator of microtubule dynamics and that it may influence microtubule polymerization in growth cones. Here, we demonstrate that in vivo, SCG10 exists in both phosphorylated and unphosphorylated forms. By two-dimensional gel electrophoresis, two phosphoisoforms were detected in neonatal rat brain. Using in vitro phosphorylated recombinant protein, four phosphorylation sites were identified in the SCG10 sequence. Ser-50 and Ser-97 were the target sites for protein kinase A, Ser-62 and Ser-73 for mitogen-activated protein kinase and Ser-73 for cyclin-dependent kinase. We also show that overexpression of SCG10 induces a disruption of the microtubule network in COS-7 cells. By expressing different phosphorylation site mutants, we have dissected the roles of the individual phosphorylation sites in regulating its microtubule-destabilizing activity. We show that nonphosphorylatable mutants have increased activity, whereas mutants in which phosphorylation is mimicked by serine-to-aspartate substitutions have decreased activity. These data suggest that the microtubule-destabilizing activity of SCG10 is regulated by phosphorylation, and that SCG10 may link signal transduction of growth or guidance cues involving serine/threonine protein kinases to alterations of microtubule dynamics in the growth cone.

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H3K4me3 is a histone modification that accumulates at the transcription-start site (TSS) of active genes and is known to be important for transcription activation. The way in which H3K4me3 is regulated at TSS and the actual molecular basis of its contribution to transcription remain largely unanswered. To address these questions, we have analyzed the contribution of dKDM5/LID, the main H3K4me3 demethylase in Drosophila, to the regulation of the pattern of H3K4me3. ChIP-seq results show that, at developmental genes, dKDM5/LID localizes at TSS and regulates H3K4me3. dKDM5/LID target genes are highly transcribed and enriched in active RNApol II and H3K36me3, suggesting a positive contribution to transcription. Expression-profiling show that, though weakly, dKDM5/LID target genes are significantly downregulated upon dKDM5/LID depletion. Furthermore, dKDM5/LID depletion results in decreased RNApol II occupancy, particularly by the promoter-proximal Pol lloser5 form. Our results also show that ASH2, an evolutionarily conserved factor that locates at TSS and is required for H3K4me3, binds and positively regulates dKDM5/LID target genes. However, dKDM5/LID and ASH2 do not bind simultaneously and recognize different chromatin states, enriched in H3K4me3 and not, respectively. These results indicate that, at developmental genes, dKDM5/LID and ASH2 coordinately regulate H3K4me3 at TSS and that this dynamic regulation contributes to transcription.

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The aim of the study was to assess the clinical performance of the model combining areal bone mineral density (aBMD) at spine and microarchitecural texture (TBS) for the detection of the osteoporotic fracture. The Eastern European Study is a multicenter study (Serbia, Bulgaria, Romania and Ukraine) evaluating the role of TBS in routine clinical practice as a complement to aBMD. All scans were acquired on Hologic Discovery and GE Prodigy densitometers in a routine clinical manner. The additional clinical values of aBMD and TBS were analyzed using a two steps classification tree approach (aBMD followed by TBS tertiles) for all type of osteoporotic fracture (All-OP Fx). Sensitivity, specificity and accuracy of fracture detection as well as the Net Reclassification Index (NRI) were calculated. This study involves 1031 women subjects aged 45 and older recruited in east European countries. Clinical centers were cross-calibrated in terms of BMD and TBS. As expected, areal BMD (aBMD) at spine and TBS were only moderately correlated (r (2) = 0.19). Prevalence rate for All-OP Fx was 26 %. Subjects with fracture have significant lower TBS and aBMD than subjects without fracture (p < 0.01). TBS remains associated with the fracture even after adjustment for age and aBMD with an OR of 1.27 [1.07-1.51]. When using aBMD T-score of -2.5 and the lowest TBS tertile thresholds, both BMD and TBS were similar in terms of sensitivity (35 vs. 39 %), specificity (78 vs. 80 %) and accuracy (64 vs. 66 %). aBMD and TBS combination, induced a significant improvement in sensitivity (+28 %) and accuracy (+17 %) compared to aBMD alone whereas a moderate improvement was observed in terms of specificity (+9 %). The overall combination gain was 36 % as expressed using the NRI. aBMD and TBS combination decrease significantly the number of subjects needed to diagnose from 7 for aBMD alone to 2. In a multi-centre Eastern European cohort, we have shown that the use of TBS in addition to the aBMD permit to reclassified correctly more than one-third of the overall subjects. Furthermore, the number of subjects needed to diagnose fell to 2 subjects. Economical studies have to be performed to evaluate the gain induced by the use of TBS for the healthcare system.