The structural impact of DNA mismatches

© 2015 © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. The structure and dynamics of all the transversion and transition mismatches in three different DNA environments have been characterized by molecular dynamics simulations and NMR spectroscopy. We found that the presence of mismatches produced significant local structural alterations, especially in the case of purine transversions. Mismatched pairs often show promiscuous hydrogen bonding patterns, which interchange among each other in the nanosecond time scale. This therefore defines flexible base pairs, where breathing is frequent, and where distortions in helical parameters are strong, resulting in significant alterations in groove dimension. Even if the DNA structure is plastic enough to absorb the structural impact of the mismatch, local structural changes can be propagated far from the mismatch site, following the expected through-backbone and a previously unknown through-space mechanism. The structural changes related to the presence of mismatches help to understand the different susceptibility of mismatches to the action of repairing proteins.Peer Reviewe

Efeito da osteotomia intertrocantérica no femur proximal de coelhos: avaliação com utra-sonografia power Doppler e cintilografia

OBJECTIVE: In bone injury, repair results in local increased vascularity and bone marrow remodeling. Characterizing the vascular and metabolic imaging patterns of the proximal femur following an intertrochanteric osteotomy may help clinicians decide proper management of the patient. Our objective was to measure Doppler sonography and scintigraphy interval changes in the proximal femur following intertrochanteric osteotomy and compare imaging and histomorphometric measurements in the late post-operative stage (6 weeks after surgery) in a rabbit model of bone injury. MATERIALS AND METHODS: Both hips of 12 adult rabbits were imaged with power Doppler sonography and scintigraphy prior to and after (7 days and 6 weeks) unilateral osteotomy. Accuracy of the imaging methods was evaluated using hip operative status and histomorphometric results (vascular fractional area and number of vessels per area unit) as reference standard measures. RESULTS: A significant difference in the mean number of pixels was noted between operated and non-operated femura in late post-operative power Doppler examinations (P=0.049). Although without reaching statistical significance, the AUC of Doppler measurements (AUC=0.99) was numerically greater than the AUC of scintigraphy measurements (AUC=0.857±0.099) (P=0.15) in differentiating proximal femura with regard to their fractional vascular areas in the late post-operative stage. In contrast, scintigraphy tended to perform better (AUC=0.984±0.022) than Doppler ultrasound (AUC=0.746±0.131) to demonstrate the vascularity intensity per area unit (P=0.07) in the late stage. CONCLUSION: Our results warrant further investigation to determine the value of different imaging modalities for assessment of pathologic changes following hip surgery. Power Doppler sonography demonstrated larger AUCs (representing higher accuracy) for the discrimination of vascular fractional areas and scintigraphy, for discrimination of the number of vessels per area unit.OBJETIVO: Regeneração em casos de lesão óssea resulta em aumento da vascularização local e remodelamento da medula óssea adjacente. A caracterização imagenológica de padrões vasculares e metabólicos no fêmur proximal após uma osteotomia intertrocantérica pode auxiliar ortopedistas a decidirem qual a terapêutica mais apropriada. O objetivo deste estudo foi avaliar as alterações temporais observadas por ultra-sonografia Doppler e cintilografia no fêmur proximal após a realização de uma osteotomia intertrocantérica; e comparar achados imagenológicos e histomorfométricos no estágio pós-operatório tardio (6 semanas após a cirurgia) num modelo animal de lesão óssea. MATERIAIS AND MÉTODOS: Ambos os quadris de 12 coelhos adultos foram examinados por ultra-sonografia power Doppler e cintilografia antes e após (7 dias e 6 semanas) uma osteotomia unilateral. A acurácia dos métodos de imagem foi avaliada usando-se o status operatório dos quadris and os resultados histomorfométricos (área vascular fracional e número de vasos/unidade de área) como medidas de referência. RESULTADOS: Uma diferença significativa foi observada entre o número médio de pixels presentes no fêmur proximal operado e não-operado ao exame de power Doppler obtido no estágio pós-operatório tardio (P=0.049). Embora ser atingir significância estatística, a área abaixo da curva ("area-under-the-curve") dos exames de power Doppler (AUC=0.99) for numericamente superior à área abaixo da curva dos exames de cintilografia (AUC= 0.857±0.099) (P=0.15) para diferenciar fêmures proximais com relação a suas áreas vasculares fracionais no estágio pós-operatório tardio. Ao contrário, a cintilografia tendeu a apresentar uma "performance" diagnóstica superior (AUC=0.984±0.022) em relação ao Doppler (AUC=0.746±0.131) para demonstrar a quantidade de vasos por unidade de área (P=0.07) no estágio tardio. CONCLUSÃO: Nossos resultados despertam a importância de continuar-se investigando o valor de diferentes métodos de imagem para se avaliar achados patológicos após a realização de cirurgias do quadril. A ultra-sonografia power Doppler demonstrou maiores áreas abaixo da curva (representando maior acurácia) para discriminar áreas vasculares fracionais e cintilografia, para discriminar quantidade de vasos/unidade de área

Augmented muscle vasodilatory responses in obese children with Glu27 beta(2)-adrenoceptor polymorphism

This study examined forearm vasodilatation during mental challenge and exercise in 72 obese children (OC; age = 10 +/- 0.1 years) homozygous with polymorphism in the allele 27 of the beta(2)-adrenoceptors: Gln27 (n = 61) and Glu27 (n = 11). Forearm blood flow was recorded during 3 min of each using the Stroop color-word test (MS) and handgrip isometric exercise. Baseline hemodynamic and vascular measurements were similar. During the MS, peak forearm vascular conductance was significantly greater in group Glu27 (Delta = 0.35 +/- 0.4 vs. 0.12 +/- 0.1 units, respectively, p = .042). Similar results were found during exercise (Delta = 0.64 +/- 0.1 vs. 0.13 +/- 0.1 units, respectively, p = .035). Glu27 OC increased muscle vasodilatory responsiveness upon the MS and exercise

Parmbsc1: a refined force field for DNA simulations

We present parmbsc1, a force field for DNA atomistic simulation, which has been parameterized from high-level quantum mechanical data and tested for nearly 100 systems (representing a total simulation time of ~140 μs) covering most of DNA structural space. Parmbsc1 provides high-quality results in diverse systems. Parameters and trajectories are available at http://mmb.irbbarcelona.org/ParmBSC1/

Hantavirus Pulmonary Syndrome, Central Plateau, Southeastern, and Southern Brazil

This syndrome is an increasing health problem because of human encroachment into habitats of rodent reservoirs

Sciatic lateral popliteal block with clonidine alone or clonidine plus 0.2% ropivacaine: effect on the intra-and postoperative analgesia for lower extremity surgery in children: a randomized prospective controlled study

<p>Abstract</p> <p>Background</p> <p>The effect of adding clonidine to local anesthetics for nerve or plexus blocks remains unclear. Most of the studies in adults have demonstrated the positive effects of clonidine on intra- and postoperative analgesia when used as an adjunctive agent or in some cases as a single to regional techniques. In the pediatric population, there are only few trials involving clonidine as an adjunct to regional anesthesia, and the analgesic benefits are not definite in this group of patients. The evidence concerning perineural administration of clonidine is so far inconclusive in children, as different types and volume of local anesthetic agents have been used in these studies. Moreover, the efficacy of regional anesthesia is largely affected by the operator's technique, accuracy and severity of operation.</p> <p>Methods</p> <p>The use of clonidine alone or combined with 0.2% ropivacaine for effective analgesia after mild to moderate painful foot surgery was assessed in 66 children, after combined sciatic lateral popliteal block (SLPB) plus femoral block. The patients were randomly assigned into three groups to receive placebo, clonidine, and clonidine plus ropivacaine. Time to first analgesic request in the groups was analyzed by using Kaplan-Meier and the log-rank test (mean time, median time, 95% CI).</p> <p>Results</p> <p>In our study, clonidine administered alone in the SLPB seems promising, maintaining intraoperatively the hemodynamic parameters SAP, DAP, HR to the lower normal values so that no patient needed nalbuphine under 0.6 MAC sevoflurane anesthesia, and postoperatively without analgesic request for a median time of 6 hours. In addition, clonidine administered as adjuvant enhances ropivacaine's analgesic effect for the first postoperative day in the majority of children (p = 0.001). Clonidine and clonidine plus ropivacaine groups also didn’t demonstrate PONV, motor blockade, and moreover, the parents of children expressed their satisfaction with the excellent perioperative management of their children, with satisfaction score 9.74 ± 0.45 and 9.73 ± 0.70 respectively. On the contrary all the patients in the control group required rescue nalbuphine in the recovery room, and postoperatively, along with high incidence of PONV, and the parents of children reported a low satisfaction score (7.50 ± 0.70).</p> <p>Conclusions</p> <p>Clonidine appears promising more as an adjuvant in 0.2% ropivacaine and less than alone in the SLPB plus femoral block in children undergoing mild to moderate painful foot surgery, with no side effects.</p> <p>Trial registration</p> <p>ClinicalTrials.gov, <a href="http://www.controlled-trials.com/ISRCTN90832436">ISRCTN90832436</a>, (ref: CCT-NAPN-20886).</p

Effect of intertrochanteric osteotomy on the proximal femur of rabbits: assessment with power Doppler sonography and scintigraphy

OBJECTIVE: In bone injury, repair results in local increased vascularity and bone marrow remodeling. Characterizing the vascular and metabolic imaging patterns of the proximal femur following an intertrochanteric osteotomy may help clinicians decide proper management of the patient. Our objective was to measure Doppler sonography and scintigraphy interval changes in the proximal femur following intertrochanteric osteotomy and compare imaging and histomorphometric measurements in the late post-operative stage (6 weeks after surgery) in a rabbit model of bone injury. MATERIALS AND METHODS: Both hips of 12 adult rabbits were imaged with power Doppler sonography and scintigraphy prior to and after (7 days and 6 weeks) unilateral osteotomy. Accuracy of the imaging methods was evaluated using hip operative status and histomorphometric results (vascular fractional area and number of vessels per area unit) as reference standard measures. RESULTS: A significant difference in the mean number of pixels was noted between operated and non-operated femura in late post-operative power Doppler examinations (P=0.049). Although without reaching statistical significance, the AUC of Doppler measurements (AUC=0.99) was numerically greater than the AUC of scintigraphy measurements (AUC=0.857&plusmn;0.099) (P=0.15) in differentiating proximal femura with regard to their fractional vascular areas in the late post-operative stage. In contrast, scintigraphy tended to perform better (AUC=0.984&plusmn;0.022) than Doppler ultrasound (AUC=0.746&plusmn;0.131) to demonstrate the vascularity intensity per area unit (P=0.07) in the late stage. CONCLUSION: Our results warrant further investigation to determine the value of different imaging modalities for assessment of pathologic changes following hip surgery. Power Doppler sonography demonstrated larger AUCs (representing higher accuracy) for the discrimination of vascular fractional areas and scintigraphy, for discrimination of the number of vessels per area unit.OBJETIVO: Regeneração em casos de lesão óssea resulta em aumento da vascularização local e remodelamento da medula óssea adjacente. A caracterização imagenológica de padrões vasculares e metabólicos no fêmur proximal após uma osteotomia intertrocantérica pode auxiliar ortopedistas a decidirem qual a terapêutica mais apropriada. O objetivo deste estudo foi avaliar as alterações temporais observadas por ultra-sonografia Doppler e cintilografia no fêmur proximal após a realização de uma osteotomia intertrocantérica; e comparar achados imagenológicos e histomorfométricos no estágio pós-operatório tardio (6 semanas após a cirurgia) num modelo animal de lesão óssea. MATERIAIS AND MÉTODOS: Ambos os quadris de 12 coelhos adultos foram examinados por ultra-sonografia power Doppler e cintilografia antes e após (7 dias e 6 semanas) uma osteotomia unilateral. A acurácia dos métodos de imagem foi avaliada usando-se o status operatório dos quadris and os resultados histomorfométricos (área vascular fracional e número de vasos/unidade de área) como medidas de referência. RESULTADOS: Uma diferença significativa foi observada entre o número médio de pixels presentes no fêmur proximal operado e não-operado ao exame de power Doppler obtido no estágio pós-operatório tardio (P=0.049). Embora ser atingir significância estatística, a área abaixo da curva ("area-under-the-curve") dos exames de power Doppler (AUC=0.99) for numericamente superior à área abaixo da curva dos exames de cintilografia (AUC= 0.857&plusmn;0.099) (P=0.15) para diferenciar fêmures proximais com relação a suas áreas vasculares fracionais no estágio pós-operatório tardio. Ao contrário, a cintilografia tendeu a apresentar uma "performance" diagnóstica superior (AUC=0.984&plusmn;0.022) em relação ao Doppler (AUC=0.746&plusmn;0.131) para demonstrar a quantidade de vasos por unidade de área (P=0.07) no estágio tardio. CONCLUSÃO: Nossos resultados despertam a importância de continuar-se investigando o valor de diferentes métodos de imagem para se avaliar achados patológicos após a realização de cirurgias do quadril. A ultra-sonografia power Doppler demonstrou maiores áreas abaixo da curva (representando maior acurácia) para discriminar áreas vasculares fracionais e cintilografia, para discriminar quantidade de vasos/unidade de área

Dengue Virus Type 4 Phylogenetics in Brazil 2011: Looking beyond the Veil

Dengue Fever and Dengue Hemorrhagic Fever are diseases affecting approximately 100 million people/year and are a major concern in developing countries. In the present study, the phylogenetic relationship of six strains of the first autochthonous cases of DENV-4 infection occurred in Sao Paulo State, Parana State and Rio Grande do Sul State, Brazil, 2011 were studied. Nucleotide sequences of the envelope gene were determined and compared with sequences representative of the genotypes I, II, III and Sylvatic for DEN4 retrieved from GenBank. We employed a Bayesian phylogenetic approach to reconstruct the phylogenetic relationships of Brazilian DENV-4 and we estimated evolutionary rates and dates of divergence for DENV-4 found in Brazil in 2011. All samples sequenced in this study were located in Genotype II. The studied strains are monophyletic and our data suggest that they have been evolving separately for at least 4 to 6 years. Our data suggest that the virus might have been present in the region for some time, without being noticed by Health Surveillance Services due to a low level of circulation and a higher prevalence of DENV-1 and DENV- 2

RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview

With both catalytic and genetic functions, ribonucleic acid (RNA) is perhaps the most pluripotent chemical species in molecular biology, and its functions are intimately linked to its structure and dynamics. Computer simulations, and in particular atomistic molecular dynamics (MD), allow structural dynamics of biomolecular systems to be investigated with unprecedented temporal and spatial resolution. We here provide a comprehensive overview of the fast-developing field of MD simulations of RNA molecules. We begin with an in-depth, evaluatory coverage of the most fundamental methodological challenges that set the basis for the future development of the field, in particular, the current developments and inherent physical limitations of the atomistic force fields and the recent advances in a broad spectrum of enhanced sampling methods. We also survey the closely related field of coarse-grained modeling of RNA systems. After dealing with the methodological aspects, we provide an exhaustive overview of the available RNA simulation literature, ranging from studies of the smallest RNA oligonucleotides to investigations of the entire ribosome. Our review encompasses tetranucleotides, tetraloops, a number of small RNA motifs, A-helix RNA, kissing-loop complexes, the TAR RNA element, the decoding center and other important regions of the ribosome, as well as assorted others systems. Extended sections are devoted to RNA-ion interactions, ribozymes, riboswitches, and protein/RNA complexes. Our overview is written for as broad of an audience as possible, aiming to provide a much-needed interdisciplinary bridge between computation and experiment, together with a perspective on the future of the field