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111.
The determination of the solution structure of two self-complementary oligomers d(ATGACGTCAT)2 (CG10) and d(GAAAACGTTTTC)2 (CG12), both containing the 5'-pur-ACGT-pyr-3' sequence, is reported. The impact of the base context on the conformation of the central CpG site has been examined by a combined approach of: (a) 2D 1H-NMR and 31P-NMR; (b) molecular mechanics under experimental constraints; (c) back-calculations of NOESY spectra and iterative refinements of distances; and (d) 3D-homology search of the central tetrad ACGT within the complete oligonucleotides. A full NMR study of each fragment is achieved by means of standard 2D experiments: NOESY, 2D homonuclear Hartmann-Hahn spectroscopy, double-quantum-filtered COSY and heteronuclear 1H-31P correlation. Sugar phase angle, epsilon-zeta difference angle and NOE-derived distances are input as experimental constraints to generate molecular models by energy minimization with the help of jumna. The morass program is used to iteratively refine the structures obtained. The similarity of the two ACGTs within the whole oligonucleotides is investigated. Both the decamer and the dodecamer adopt a B-like DNA conformation. However, the helical parameters within this conformational type are significantly different in CG12 and CG10. The central CpG step conformation is not locked by its nearest environment (5'A and 3'T) as seen from the structural analysis of ACGT in the two molecules. In CG12, despite the presence of runs of A-T pairs, CpG presents a high twist of 43 degrees and a sugar phase at the guanine of about 180 degrees, previously observed in other ACGT-containing-oligomers. Conversely, ACGT in CG10 exhibits strong inclinations, positive rolls, a flat profile of sugar phase, twist and glycosidic angles, as a result of the nucleotide sequence extending beyond the tetrad. The structural specificity of CG10 and its flexibility (as reflected by its energy) are tentatively related to the process of recognition of the cyclic AMP response element by its cognate protein. 相似文献
112.
The solution structures of d(GAAAACGTTTTC)2 and of its methylated derivative d(GAAAAMe5CGTTTTC)2 have been determined by NMR and molecular modelling in order to examine the impact of cytosine methylation on the central CpG conformation. Detailed 1H NMR and 31P NMR investigation of the two oligomers includes quantitative NOESY, 2D homonuclear Hartmann-Hahn spectroscopy, double-quantum-filtered COSY and heteronuclear 1H-31P correlation. Back-calculations of NOESY spectra and simulations of double-quantum-filtered COSY patterns were performed to gain accurate information on interproton distances and sugar phase angles. Molecular models under experimental constraints were generated by energy minimization by means of the molecular mechanics program JUMNA. The MORASS software was used to iteratively refine the structures obtained. After methylation, the oligomer still has a B-DNA conformation. However, there are differences in the structural parameters and the thermal stability as compared to the unmethylated molecule. Careful structural analysis shows that after methylation CpG departs from the usual conformation observed in other ACGT tetramers with different surroundings. Subtle displacements of bases, sugars and backbone imposed by the steric interaction of the two methyl groups inside the major groove are accompanied by severe pinching of the minor groove at the C-G residues. 相似文献
113.
A P Element Containing Suppressor of Hairy-Wing Binding Regions Has Novel Properties for Mutagenesis in Drosophila Melanogaster 总被引:4,自引:0,他引:4
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R. R. Roseman E. A. Johnson C. K. Rodesch M. Bjerke R. N. Nagoshi P. K. Geyer PK 《Genetics》1995,141(3):1061-1074
P elements are widely used as insertional mutagens to tag genes, facilitating molecular cloning and analyses. We modified a P element so that it carried two copies of the suppressor of Hairy-wing [su(Hw)] binding regions isolated from the gypsy transposable element. This transposon was mobilized, and the genetic consequences of its insertion were analyzed. Gene expression can be altered by the su(Hw) protein as a result of blocking the interaction between enhancer/silencer elements and their promoter. These effects can occur over long distances and are general. Therefore, a composite transposon (SUPor-P for suppressor-P element) combines the mutagenic efficacy of the gypsy element with the controllable transposition of P elements. We show that, compared to standard P elements, this composite transposon causes an expanded repertoire of mutations and produces alleles that are suppressed by su(Hw) mutations. The large number of heterochromatic insertions obtained is unusual compared to other insertional mutagenesis procedures, indicating that the SUPor-P transposon may be useful for studying the structural and functional properties of heterochromatin. 相似文献
114.
115.
André Klussmann Hansjürgen Gebhardt Matthias Nübling Falk Liebers Emilio Quirós Perea Wolfgang Cordier Lars V von Engelhardt Markus Schubert Andreas Dávid Bertil Bouillon Monika A Rieger 《Arthritis research & therapy》2010,12(3):1-15
Introduction
A number of occupational risk factors are discussed in relation to the development and progress of knee joint diseases (for example, working in a kneeling or squatting posture, lifting and carrying heavy weights). Besides the occupational factors, a number of individual risk factors are important. The distinction between work-related and other factors is crucial in assessing the risk and in deriving preventive measures in occupational health.Methods
In a case-control study, patients with and without symptomatic knee osteoarthritis (OA) were questioned by means of a standardised questionnaire complemented by a semi-standardised interview. Controls were matched and assigned to the cases by gender and age. Conditional logistic regression was used in analysing data.Results
In total, 739 cases and 571 controls were included in the study. In women and men, several individual and occupational predictors for knee OA could be described: obesity (odds ratio (OR) up to 17.65 in women and up to 12.56 in men); kneeling/squatting (women, OR 2.52 (>8,934 hours/life); men, 2.16 (574 to 12,244 hours/life), 2.47 (>12,244 hours/life)); genetic predisposition (women, OR 2.17; men, OR 2.37); and sports with a risk of unapparent trauma (women, OR 2.47 (≥1,440 hours/life); men, 2.58 (≥3,232 hours/life)). In women, malalignment of the knee (OR 11.54), pain in the knee already in childhood (OR 2.08), and the daily lifting and carrying of loads (≥1,088 tons/life, OR 2.13) were related to an increased OR; sitting and smoking led to a reduced OR.Conclusions
The results support a dose-response relationship between kneeling/squatting and symptomatic knee OA in men and, for the first time, in women. The results concerning general and occupational predictors for knee OA reflect the findings from the literature quite well. Yet occupational risks such as jumping or climbing stairs/ladders, as discussed in the literature, did not correlate with symptomatic knee OA in the present study. With regards to occupational health, prevention measures should focus on the reduction of kneeling activities and the lifting and carrying of loads as well as general risk factors, most notably the reduction of obesity. More intervention studies of the effectiveness of tools and working methods for reducing knee straining activities are needed. 相似文献116.
Caterina Vacchi-Suzzi Florian Hahne Philippe Scheubel Magali Marcellin Valerie Dubost Magdalena Westphal Catherine Boeglen Stine Büchmann-M?ller Ming Sin Cheung André Cordier Christopher De Benedetto Mark Deurinck Moritz Frei Pierre Moulin Edward Oakeley Olivier Grenet Armelle Grevot Robert Stull Diethilde Theil Jonathan G. Moggs Estelle Marrer Philippe Couttet 《PloS one》2013,8(1)
117.
Johnny Tam Guillaume Alan Cordier ?tefan Bálint ángel Sandoval álvarez Joseph Steven Borbely Melike Lakadamyali 《PloS one》2014,9(12)
Recently, super-resolution microscopy methods such as stochastic optical reconstruction microscopy (STORM) have enabled visualization of subcellular structures below the optical resolution limit. Due to the poor temporal resolution, however, these methods have mostly been used to image fixed cells or dynamic processes that evolve on slow time-scales. In particular, fast dynamic processes and their relationship to the underlying ultrastructure or nanoscale protein organization cannot be discerned. To overcome this limitation, we have recently developed a correlative and sequential imaging method that combines live-cell and super-resolution microscopy. This approach adds dynamic background to ultrastructural images providing a new dimension to the interpretation of super-resolution data. However, currently, it suffers from the need to carry out tedious steps of sample preparation manually. To alleviate this problem, we implemented a simple and versatile microfluidic platform that streamlines the sample preparation steps in between live-cell and super-resolution imaging. The platform is based on a microfluidic chip with parallel, miniaturized imaging chambers and an automated fluid-injection device, which delivers a precise amount of a specified reagent to the selected imaging chamber at a specific time within the experiment. We demonstrate that this system can be used for live-cell imaging, automated fixation, and immunostaining of adherent mammalian cells in situ followed by STORM imaging. We further demonstrate an application by correlating mitochondrial dynamics, morphology, and nanoscale mitochondrial protein distribution in live and super-resolution images. 相似文献
118.
Sharmila Vaz Nathan Wilson Marita Falkmer Angela Sim Melissa Scott Reinie Cordier Torbj?rn Falkmer 《PloS one》2015,10(8)
Objective
Teachers'' attitudes toward inclusion are often based on the practical implementation of inclusive education rather than a specific ideology and understanding of inclusiveness. This study aimed to identify the factors associated with primary school teachers'' attitudes towards inclusion of students with all disabilities in regular schools.Method
Seventy four primary school teachers participated in a cross-sectional survey conducted in Western Australia. Teachers'' attitudes and efficacy toward integration of students with disabilities were measured using the Opinions Relative to Integration of Students with Disabilities scale and Bandura''s Teacher Efficacy scale respectively.Results
Four teacher attributes—age, gender, teaching self-efficacy and training collectively explained 42% of the variability in teachers'' attitude toward including students with disabilities.Conclusion
The current study further contributes to the accumulation of knowledge that can unpack the complex pattern of factors that should be considered to promote positive attitudes towards inclusive schools. 相似文献119.
120.
In computational neuroscience, decision-making may be explained analyzing models based on the evolution of the average firing
rates of two interacting neuron populations, e.g., in bistable visual perception problems. These models typically lead to
a multi-stable scenario for the concerned dynamical systems. Nevertheless, noise is an important feature of the model taking
into account both the finite-size effects and the decision’s robustness. These stochastic dynamical systems can be analyzed
by studying carefully their associated Fokker–Planck partial differential equation. In particular, in the Fokker–Planck setting,
we analytically discuss the asymptotic behavior for large times towards a unique probability distribution, and we propose
a numerical scheme capturing this convergence. These simulations are used to validate deterministic moment methods recently
applied to the stochastic differential system. Further, proving the existence, positivity and uniqueness of the probability
density solution for the stationary equation, as well as for the time evolving problem, we show that this stabilization does
happen. Finally, we discuss the convergence of the solution for large times to the stationary state. Our approach leads to
a more detailed analytical and numerical study of decision-making models applied in computational neuroscience. 相似文献