159 research outputs found

    Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator

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    The IncP (Incompatibility group P) plasmids are important carriers in the spread of antibiotic resistance across Gram-negative bacteria. Gene expression in the IncP-1 plasmids is stringently controlled by a network of four global repressors, KorA, KorB, TrbA and KorC interacting cooperatively. Intriguingly, KorA and KorB can act as co-repressors at varying distances between their operators, even when they are moved to be on opposite sides of the DNA. KorA is a homodimer with the 101-amino acid subunits, folding into an N-terminal DNA-binding domain and a C-terminal dimerization domain. In this study, we have determined the structures of the free KorA repressor and two complexes each bound to a 20-bp palindromic DNA duplex containing its consensus operator sequence. Using a combination of X-ray crystallography, nuclear magnetic resonance spectroscopy, SAXS and molecular dynamics calculations, we show that the linker between the two domains is very flexible and the protein remains highly mobile in the presence of DNA. This flexibility allows the DNA-binding domains of the dimer to straddle the operator DNA on binding and is likely to be important in cooperative binding to KorB. Unexpectedly, the C-terminal domain of KorA is structurally similar to the dimerization domain of the tumour suppressor p53

    Characterisation of Co@Fe3O4 core@shell nanoparticles using advanced electron microscopy

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    Cobalt nanoparticles were synthesised via the thermal decomposition of Co2(CO)8 and were coated in iron oxide using Fe(CO)5. While previous work focused on the subsequent thermal alloying of these nanoparticles, this study fully elucidates their composition and core@shell structure. State-of-the-art electron microscopy and statistical data processing enabled chemical mapping of individual particles through the acquisition of energy-filtered transmission electron microscopy (EFTEM) images and detailed electron energy loss spectroscopy (EELS) analysis. Multivariate statistical analysis (MSA) has been used to greatly improve the quality of elemental mapping data from core@shell nanoparticles. Results from a combination of spatially resolved microanalysis reveal the shell as Fe3O4 and show that the core is composed of oxidatively stable metallic Co. For the first time, a region of lower atom density between the particle core and shell has been observed and identified as a trapped carbon residue attributable to the organic capping agents present in the initial Co nanoparticle synthesis.Junta de Andalucía Feder PE2009-FQM-4554 TEP-217EU FP7 AL-NANOFUNC CT-REGPOT2011-1-28589

    Preparation of bifunctional Au-Pd/TiO 2 catalysts and research on methanol liquid phase one-step oxidation to methyl formate

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    A series of Au-Pd/TiO2 bifunctional catalysts with different Au, Pd loading percents have been prepared by sol-immobilization method. The related XRD, HR-TEM and XPS characterizations have been tested for understanding the structure of catalysts. The catalysis activity for methanol liquid phase one-step oxidation to methyl formate have been studied in batch reactor. The results show that the nanoparticles are highly dispersed on TiO2 with 6.4nm mean size. Also, bifunctional catalysts could catalysis transfer methanol to methyl formate with high efficiency. With 1wt%Au-1wt%Pd/TiO2 catalysts, when the molar ratio between active components and methanol is 1/2000, the conversion of methanol is 55.7% for 4h under 100oC and 25 bar. At the same time, the selectivity of methyl formate is up to 74.2%. The Au-Pd/TiO2 bifunctional catalysts also shows great stability for the reaction with stable conversion and selectivity after 5 cycle

    Case report 16

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46771/1/256_2004_Article_BF00347143.pd

    Symmetry and topology in antiferromagnetic spintronics

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    Antiferromagnetic spintronics focuses on investigating and using antiferromagnets as active elements in spintronics structures. Last decade advances in relativistic spintronics led to the discovery of the staggered, current-induced field in antiferromagnets. The corresponding N\'{e}el spin-orbit torque allowed for efficient electrical switching of antiferromagnetic moments and, in combination with electrical readout, for the demonstration of experimental antiferromagnetic memory devices. In parallel, the anomalous Hall effect was predicted and subsequently observed in antiferromagnets. A new field of spintronics based on antiferromagnets has emerged. We will focus here on the introduction into the most significant discoveries which shaped the field together with a more recent spin-off focusing on combining antiferromagnetic spintronics with topological effects, such as antiferromagnetic topological semimetals and insulators, and the interplay of antiferromagnetism, topology, and superconductivity in heterostructures.Comment: Book chapte

    Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes - A Meta-analysis.

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    BACKGROUND: Recent meta-analyses show that individuals with high risk variants in CHRNA5 on chromosome 15q25 are likely to develop lung cancer earlier than those with low-risk genotypes. The same high-risk genetic variants also predict nicotine dependence and delayed smoking cessation. It is unclear whether smoking cessation confers the same benefits in terms of lung cancer risk reduction for those who possess CHRNA5 risk variants versus those who do not. METHODS: Meta-analyses examined the association between smoking cessation and lung cancer risk in 15 studies of individuals with European ancestry who possessed varying rs16969968 genotypes (N=12,690 ever smokers, including 6988 cases of lung cancer and 5702 controls) in the International Lung Cancer Consortium. RESULTS: Smoking cessation (former vs. current smokers) was associated with a lower likelihood of lung cancer (OR=0.48, 95%CI=0.30-0.75, p=0.0015). Among lung cancer patients, smoking cessation was associated with a 7-year delay in median age of lung cancer diagnosis (HR=0.68, 95%CI=0.61-0.77, p=4.9∗10(-10)). The CHRNA5 rs16969968 risk genotype (AA) was associated with increased risk and earlier diagnosis for lung cancer, but the beneficial effects of smoking cessation were very similar in those with and without the risk genotype. CONCLUSION: We demonstrate that quitting smoking is highly beneficial in reducing lung cancer risks for smokers regardless of their CHRNA5 rs16969968 genetic risk status. Smokers with high-risk CHRNA5 genotypes, on average, can largely eliminate their elevated genetic risk for lung cancer by quitting smoking- cutting their risk of lung cancer in half and delaying its onset by 7years for those who develop it. These results: 1) underscore the potential value of smoking cessation for all smokers, 2) suggest that CHRNA5 rs16969968 genotype affects lung cancer diagnosis through its effects on smoking, and 3) have potential value for framing preventive interventions for those who smoke

    Long working hours as a risk factor for atrial fibrillation: A multi-cohort study

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    Aims Studies suggest that people who work long hours are at increased risk of stroke, but the association of long working hours with atrial fibrillation, the most common cardiac arrhythmia and a risk factor for stroke, is unknown. We examined the risk of atrial fibrillation in individuals working long hours (>55 per week) and those working standard 35-40 hours per week. Methods In this prospective multi-cohort study from the Individual-Participant-Data Meta-analysis in and results Working Populations (IPD-Work) Consortium, the study population was 85,494 working men and women (mean age 43.4 years) with no recorded atrial fibrillation. Working hours were assessed at study baseline (1991-2004). Mean follow-up for incident atrial fibrillation was 10 years and cases were defined using data on electrocardiograms, hospital records, drug reimbursement registers, and death certificates. We identified 1061 new cases of atrial fibrillation (10-year cumulative incidence 12.4 per 1000). After adjustment for age, sex and socioeconomic status, individuals working long hours had a 1.4-fold increased risk of atrial fibrillation compared to those working standard hours (hazard ratio=1.42, 95%CI=1.13-1.80, P=0.003). There was no significant heterogeneity between the cohortspecific effect estimates (I2=0%, P=0.66) and the finding remained after excluding participants with coronary heart disease or stroke at baseline or during the follow-up (N=2006, hazard ratio=1.36, 95%CI=1.05-1.76, P=0. 0180). Adjustment for potential confounding factors, such as obesity, risky alcohol use and high blood pressure, had little impact on this association. Conclusion Individuals who worked long hours were more likely to develop atrial fibrillation than those working standard hours

    Associated Links Among Smoking, Chronic Obstructive Pulmonary Disease, and Small Cell Lung Cancer: A Pooled Analysis in the International Lung Cancer Consortium.

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    Background The high relapse and mortality rate of small-cell lung cancer (SCLC) fuels the need for epidemiologic study to aid in its prevention. Methods We included 24 studies from the ILCCO collaboration. Random-effects panel logistic regression and cubic spline regression were used to estimate the effects of smoking behaviors on SCLC risk and explore their non-linearity. Further, we explored whether the risk of smoking on SCLC was mediated through COPD. Findings Significant dose–response relationships of SCLC risk were observed for all quantitative smoking variables. Smoking pack-years were associated with a sharper increase of SCLC risk for pack-years ranged 0 to approximately 50. The former smokers with longer cessation showed a 43%quit_for_5–9 years to 89%quit_for_≥ 20 years declined SCLC risk vs. subjects who had quit smoking < 5 years. Compared with non-COPD subjects, smoking behaviors showed a significantly higher effect on SCLC risk among COPD subjects, and further, COPD patients showed a 1.86-fold higher risk of SCLC. Furthermore, smoking behaviors on SCLC risk were significantly mediated through COPD which accounted for 0.70% to 7.55% of total effects. Interpretation This is the largest pooling study that provides improved understanding of smoking on SCLC, and further demonstrates a causal pathway through COPD that warrants further experimental study. Abbreviations COPD, chronic obstructive pulmonary disease; CPG, cigarettes per day; ILCCO, International Lung Cancer Consortium; MeSH, medical subject headings; NSCLC, non-small cell lung cancer; OR, odds ratio; SCLC, small cell lung cancer

    The phenotype of Floating-Harbor syndrome: Clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

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    Background: Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome. Methods and results. Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from
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