Replication of damaged DNA, also termed as translesion synthesis (TLS), involves specialized DNA polymerases that bypass DNA lesions. In Escherichia coli, although TLS can involve one or a combination of DNA polymerases depending on the nature of the lesion, it generally requires the Pol V DNA polymerase (formed by two SOS proteins, UmuD' and UmuC) and the RecA protein. In addition to being an essential component of translesion DNA synthesis, Pol V is also an antagonist of RecA-mediated recombination. We have recently isolated umuD' and umuC mutants on the basis of their increased capacity to inhibit homologous recombination. Despite the capacity of these mutants to form a Pol V complex and to interact with the RecA polymer, most of them exhibit a defect in TLS. Here, we further characterize the TLS activity of these Pol V mutants in vivo by measuring the extent of error-free and mutagenic bypass at a single (6-4)TT lesion located in double stranded plasmid DNA. TLS is markedly decreased in most Pol V mutants that we analyzed (8/9) with the exception of one UmuC mutant (F287L) that exhibits wild-type bypass activity. Somewhat unexpectedly, Pol V mutants that are partially deficient in TLS are more severely affected in mutagenic bypass compared to error-free synthesis. The defect in bypass activity of the Pol V mutant polymerases is discussed in light of the location of the respective mutations in the 3D structure of UmuD' and the DinB/UmuC homologous protein Dpo4 of Sulfolobus solfataricus. 相似文献
Direct plant uptake of metals bound to chelating agents has important implications for metal uptake and the free-ion activity model. Uptake of hydrophilic solutes such as metal–EDTA complexes is believed to occur via bypass apoplastic flow, but many questions remain about the relative importance and selectivity of this pathway. In this study, Brassica juncea (Indian mustard) plants grown in solution- and sand-culture conditions were exposed to metal–EDTA complexes and to PTS, a hydrophilic fluorescent dye previously used as a tracer of apoplastic flow. The results suggest that there are two general phases of solute uptake. Under normal conditions, xylem sap solute concentrations are relatively low (i.e., <0.5% of concentration in solution) and there is a high degree of selectivity among different solutes, while under conditions of stress, xylem sap concentrations are significantly higher (i.e., >3% of concentration in solution) and the selectivity among solutes is less. In healthy plants, xylem sap metal–EDTA concentrations were generally an order of magnitude higher than those of PTS and differences among complexes were observed, with CdEDTA2− exhibiting slightly higher xylem sap concentrations than PbEDTA2− or FeEDTA−. Metal–EDTA complexes were found to dominate xylem sap metal speciation and the fraction of metal in xylem sap present as metal–EDTA was greater for non-nutrient metals (Pb, Cd) than for the nutrient metal Fe. Despite differences in root morphology between plants grown under solution- and sand-culture conditions, uptake of solutes was similar under both sets of growth conditions. 相似文献
The global threat of terrorism raises questions about preparedness and risk communication in the context of public health and security. Although experts discriminate between chemical, biological, radiological, nuclear, and explosive (CNRNE) terrorist events, little is known about how the Canadian public represents these forms of terrorism. A stratified random sample of 1502 Canadians participated in a telephone survey on CBRNE terrorism. A word association technique was used to assess first words or images that came to mind while thinking about different types of terrorist scenarios. Content analysis of this data revealed a number of potential uncertainties and misconceptions regarding different types of terrorism scenarios. Despite most frequently providing agents in response questions surrounding chemical or biological terrorism, respondents frequently confounded agents of biological and chemical nature. Similarly, different aspects of nuclear events were not consistently distinguished. Most notably, however, a sizable proportion of respondents had difficulty providing word associations to the different types of terrorist events or only provided vague responses that closely mirrored the scenario in question. Finally, images regarding the potential impacts of scenarios were infrequent. Implications for risk communication and preparedness are discussed; in particular, the need to provide the public with more detailed information regarding the nature of different forms of CBRNE terrorism and how to best prepare for a potential event. 相似文献
Context: Acute dyspnea is a frequent complaint in patients attending the emergency department (ED).
Objective: To evaluate the accuracy of PCT, MR-proANP, MR-proADM, copeptin and CT-proET1 for the risk-stratification of severe acute dyspnea patients presenting to the ED.
Methods: Multicenter prospective study in adult patients with a chief complaint of acute dyspnea. Pro-hormone type biomarkers concentrations were measured on arrival. Combined primary endpoint was a poor outcome.
Results: Three hundred and ninety-four patients were included, 137 (35%) met the primary endpoint. MR-proADM was the only biomarker associated with the primary endpoint (odds ratio 1.43 [95%CI: 1.13–1.82], p?=?0.003) as were the presence of paradoxical abdominal breathing (odds ratio 2.48 [95%CI: 1.31–4.68]) or cyanosis (odds ratio 3.18 [1.46–6.89])
Conclusions: In patients with severe acute dyspnea in the ED, pro-hormone type biomarkers measurements have a low added value to clinical signs for the prediction of poor outcome. 相似文献
Purpose: In patients with a suspected acute myocardial infarction (AMI), to evaluate the potential for early triage based on measurement of high-sensitivity cardiac troponin T (hs-cTnT) and copeptin in blood samples collected in the prehospital phase.
Materials and methods: In this retrospective study, we measured hs-cTnT and copeptin in blood samples collected in the ambulance form 962 patients with suspected AMI. The diagnostic accuracy was estimated by receiver-operating characteristic (ROC) curve area under the curve (AUC) for both biomarkers and a combined model. Multivariable Cox regression modelling was used to estimate the predictive value of both biomarkers.
Results: In total, 178 (19%) cases had AMI. The AUC for hs-cTnT was 0.81. Adding copeptin increased the AUC to 0.85 (p?=?0.004) and the combined model allowed a prehospital rule-out of 45% of cases without AMI (negative predictive value, NPV 98%). Both biomarkers are highly predictive of outcome.
Conclusions: A future application of hs-cTnT and copeptin measurement, performed already in the prehospital phase, could potentially improve the prehospital diagnostic and prognostic classification of patients with a suspected AMI. 相似文献
Context: Diagnosis of sepsis in elderly is challenging.Objectives: We investigated whether procalcitonin concentrations in elderly differed from values for the general population.Methods: Procalcitonin measurement was assessed prospectively in 307 apyretic patients ≥75 years visiting the emergency department.Results: Median age was 86 years [IQR81–90] and 222 (72%) were female. Procalcitonin concentration was 0.057 µg/L [0.040–0.092]; 99th percentile was 0.661 µg/L. Patients with procalcitonin concentrations above decisional thresholds had lower glomerular filtration rate and higher C-reactive protein concentrations. Conclusions: Baseline procalcitonin levels are increased in elderly. Elevated values are common and associated to low-grade inflammation and lower eGFR. 相似文献