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1.
Background
While the conserved positions of a multiple sequence alignment (MSA) are clearly of interest, non-conserved positions can also be important because, for example, destabilizing effects at one position can be compensated by stabilizing effects at another position. Different methods have been developed to recognize the evolutionary relationship between amino acid sites, and to disentangle functional/structural dependencies from historical/phylogenetic ones.Methodology/Principal Findings
We have used two complementary approaches to test the efficacy of these methods. In the first approach, we have used a new program, MSAvolve, for the in silico evolution of MSAs, which records a detailed history of all covarying positions, and builds a global coevolution matrix as the accumulated sum of individual matrices for the positions forced to co-vary, the recombinant coevolution, and the stochastic coevolution. We have simulated over 1600 MSAs for 8 protein families, which reflect sequences of different sizes and proteins with widely different functions. The calculated coevolution matrices were compared with the coevolution matrices obtained for the same evolved MSAs with different coevolution detection methods. In a second approach we have evaluated the capacity of the different methods to predict close contacts in the representative X-ray structures of an additional 150 protein families using only experimental MSAs.Conclusions/Significance
Methods based on the identification of global correlations between pairs were found to be generally superior to methods based only on local correlations in their capacity to identify coevolving residues using either simulated or experimental MSAs. However, the significant variability in the performance of different methods with different proteins suggests that the simulation of MSAs that replicate the statistical properties of the experimental MSA can be a valuable tool to identify the coevolution detection method that is most effective in each case. 相似文献2.
Prashant Shingate Malini Manoharan Anshul Sukhwal Ramanathan Sowdhamini 《BMC bioinformatics》2014,15(1)
Background
Various methods have been developed to computationally predict hotspot residues at novel protein-protein interfaces. However, there are various challenges in obtaining accurate prediction. We have developed a novel method which uses different aspects of protein structure and sequence space at residue level to highlight interface residues crucial for the protein-protein complex formation.Results
ECMIS (Energetic Conservation Mass Index and Spatial Clustering) algorithm was able to outperform existing hotspot identification methods. It was able to achieve around 80% accuracy with incredible increase in sensitivity and outperforms other existing methods. This method is even sensitive towards the hotspot residues contributing only small-scale hydrophobic interactions.Conclusion
Combination of diverse features of the protein viz. energy contribution, extent of conservation, location and surrounding environment, along with optimized weightage for each feature, was the key for the success of the algorithm. The academic version of the algorithm is available at http://caps.ncbs.res.in/download/ECMIS/ECMIS.zip.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-303) contains supplementary material, which is available to authorized users. 相似文献3.
Bernadette Calabek Stefan Meng Sabine Pollanz Walter Klepetko Konrad Hoetzenecker Felicitas Oberndorfer Wolfgang Grisold 《Journal of brachial plexus and peripheral nerve injury》2015,10(1):e53-e56
Introduction
The Pancoast syndrome (PS) has been termed after Henry Pancoast. Its neurologic core symptoms include pain, radicular sensory and motor syndromes, and Horner syndrome. A PS is often the presenting sign of lung cancer and bears a grim prognosis.Methods
This case report describes an atypical onset of a lung tumor causing a PS. Electrophysiological examination was not conclusive. The diagnosis was confirmed by MRI, CT scan, and biopsy. The intervention consisted of preoperative chemo- and radiotherapy and was followed by an extensive surgical approach with histologically confirmed perineural invasion of the brachial plexus.Results
The postoperative period was dominated by neuropathic pain. Despite considerable loss of distal sensorimotor function of the right hand, the patient uses the extremity and has returned to professional life.Discussion
This observation triggered by the advances in general oncology and surgery also demonstrates the management of a lesion of the peripheral nervous system caused by cancer. 相似文献4.
Sasha G. Hutchinson Jennifer S. Kuijlaars Ilse Mesters Jean W. M. Muris Constant P. van Schayck Edward Dompeling Frans J. M. Feron 《PloS one》2014,9(5)
Background
A significant number of parents are unaware or unconvinced of the health consequences of passive smoking (PS) in children. Physicians could increase parental awareness by giving personal advice.Aim
To evaluate the current practices of three Dutch health professions (paediatricians, youth health care physicians, and family physicians) regarding parental counselling for passive smoking (PS) in children.Methods
All physicians (n = 720) representing the three health professions in Limburg, the Netherlands, received an invitation to complete a self-administered electronic questionnaire including questions on their: sex, work experience, personal smoking habits, counselling practices and education regarding PS in children.Results
The response rate was 34%. One tenth (11%) of the responding physicians always addressed PS in children, 32% often, 54% occasionally and 4% reported to never attend to it. The three health professions appeared comparable regarding their frequency of parental counselling for PS in children. Addressing PS was more likely when children had respiratory problems. Lack of time was the most frequently mentioned barrier, being very and somewhat applicable for respectively 14% and 43% of the physicians. One fourth of the responders had received postgraduate education about PS. Additionally, 49% of the responders who did not have any education about PS were interested in receiving it.Conclusions
Physicians working in the paediatric field in Limburg, the Netherlands, could more frequently address PS in children with parents. Lack of time appeared to be the most mentioned barrier and physicians were more likely to counsel parents for PS in children with respiratory complaints/diseases. Finally, a need for more education on parental counselling for PS was expressed. 相似文献5.
Zheng Liu Qi Fei Bingqiang Wang Pengfei Lv Cheng Chi Yong Yang Fan Zhao Jisheng Lin Zhao Ma 《PloS one》2014,9(11)
Study Design
Meta-analysis.Background
Bilateral pedicle screw fixation (PS) after lumbar interbody fusion is a widely accepted method of managing various spinal diseases. Recently, unilateral PS fixation has been reported as effective as bilateral PS fixation. This meta-analysis aimed to comparatively assess the efficacy and safety of unilateral PS fixation and bilateral PS fixation in the minimally invasive (MIS) lumbar interbody fusion for one-level degenerative lumbar spine disease.Methods
MEDLINE/PubMed, EMBASE, BIOSIS Previews, and Cochrane Library were searched through March 30, 2014. Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on unilateral versus bilateral PS fixation in MIS lumbar interbody fusion that met the inclusion criteria and the methodological quality standard were retrieved and reviewed. Data on participant characteristics, interventions, follow-up period, and outcomes were extracted from the included studies and analyzed by Review Manager 5.2.Results
Six studies (5 RCTs and 1 CCT) involving 298 patients were selected. There were no significant differences between unilateral and bilateral PS fixation procedures in fusion rate, complications, visual analogue score (VAS) for leg pain, VAS for back pain, Oswestry disability index (ODI). Both fixation procedures had similar length of hospital stay (MD = 0.38, 95% CI = −0.83 to 1.58; P = 0.54). In contrast, bilateral PS fixation was associated with significantly more intra-operative blood loss (P = 0.002) and significantly longer operation time (P = 0.02) as compared with unilateral PS fixation.Conclusions
Unilateral PS fixation appears as effective and safe as bilateral PS fixation in MIS lumbar interbody fusion but requires less operative time and causes less blood loss, thus offering a simple alternative approach for one-level lumbar degenerative disease. 相似文献6.
Objectives
To quantify the proportion of adverse pregnancy outcome attributable to maternal obesity.Design
Cross sectional analysis of routine obstetric dataset.Setting
Guy’s and St Thomas’s NHS Foundation Trust (GSTFT).Population
23,668 women who had singleton deliveries at GSTFT between 2004 and 2008.Methods
Logistic regression was used to estimate the association between BMI and outcome in different ethnic groups. Adjusted odds ratios, and the proportions of obese women, were used to calculate population attributable risk fractions (PAFs).Main Outcome Measures
(i) Maternal outcomes: diabetes, type of delivery, post-partum haemorrhage, and preterm delivery. (ii) Perinatal outcomes: macrosomia, low birth weight, admission to neonatal intensive care/special care baby unit, and perinatal death.Results
The prevalence of maternal obesity was 14%. Increasing BMI was independently associated with increasing risk of adverse obstetric and neonatal outcome. At the individual level, the effect of obesity on diabetes was highest in Asian women compared to white women (p for interaction = 0.03). Calculation of population attributable risk fractions demonstrated that one third of diabetes cases and one in six Caesarean sections could be avoided in this population if all obese women were of normal BMI. At the population level, the contribution of obesity to diabetes was highest for Black women (42%), and lowest for oriental women (8%). Seven percent of neonatal macrosomia in all the population, and 13% in Black mothers, were attributable to obesity.Conclusions
Preventing obesity prior to pregnancy will substantially reduce the burden of obstetric and neonatal morbidity in this population. This reduction will be higher in Black women. 相似文献7.
Henri Augusto Korkes Nelson Sass Antonio F. Moron Niels Olsen S. Camara Tatiana Bonetti Ana Sofia Cerdeira Ismael Dale Cotrim Guerreiro Da Silva Leandro De Oliveira 《PloS one》2014,9(10)
Introduction
Adipose tissue is responsible for triggering chronic systemic inflammatory response and these changes may be involved in the pathophysiology of preeclampsia.Objective
To characterize the lipid profile in the placenta and plasma of patients with preeclampsia.Methodology
Samples were collected from placenta and plasma of 10 pregnant women with preeclampsia and 10 controls. Lipids were extracted using the Bligh–Dyer protocol and were analysed by MALDI TOF-TOF mass spectrometry.Results
Approximately 200 lipid signals were quantified. The most prevalent lipid present in plasma of patients with preeclampsia was the main class Glycerophosphoserines-GP03 (PS) representing 52.30% of the total lipid composition, followed by the main classes Glycerophosphoethanolamines-GP02 (PEt), Glycerophosphocholines-GP01 (PC) and Flavanoids-PK12 (FLV), with 24.03%, 9.47% and 8.39% respectively. When compared to the control group, plasma samples of patients with preeclampsia showed an increase of PS (p<0.0001), PC (p<0.0001) and FLV (p<0.0001). Placental analysis of patients with preeclampsia, revealed the PS as the most prevalent lipid representing 56.28%, followed by the main class Macrolides/polyketides-PK04 with 32.77%, both with increased levels when compared with patients control group, PS (p<0.0001) and PK04 (p<0.0001).Conclusion
Lipids found in placenta and plasma from patients with preeclampsia differ from those of pregnant women in the control group. Further studies are needed to clarify if these changes are specific and a cause or consequence of preeclampsia. 相似文献8.
Background
Protein sequence profile-profile alignment is an important approach to recognizing remote homologs and generating accurate pairwise alignments. It plays an important role in protein sequence database search, protein structure prediction, protein function prediction, and phylogenetic analysis.Results
In this work, we integrate predicted solvent accessibility, torsion angles and evolutionary residue coupling information with the pairwise Hidden Markov Model (HMM) based profile alignment method to improve profile-profile alignments. The evaluation results demonstrate that adding predicted relative solvent accessibility and torsion angle information improves the accuracy of profile-profile alignments. The evolutionary residue coupling information is helpful in some cases, but its contribution to the improvement is not consistent.Conclusion
Incorporating the new structural information such as predicted solvent accessibility and torsion angles into the profile-profile alignment is a useful way to improve pairwise profile-profile alignment methods. 相似文献9.
Paula Kuivasaari-Pirinen Heli Koivumaa-Honkanen Maritta Hippel?inen Kaisa Raatikainen Seppo Heinonen 《PloS one》2014,9(11)
Objective
To compare life satisfaction between women with successful or unsuccessful outcome after assisted reproductive treatment (ART) by taking into account the time since the last ART.Design
Cohort study.Setting
Tertiary hospital.Patients
A total of 987 consecutive women who had undergone ART during 1996–2007 were invited and altogether 505 women participated in the study.Interventions
A postal enquiry with a life satisfaction scale.Main Outcome Measure
Self-reported life satisfaction in respect to the time since the last ART.Results
In general, women who achieved a live birth after ART had a significantly higher life satisfaction than those who had unsuccessful ART, especially when compared in the first three years. The difference disappeared in the time period of 6–9 years after ART. The unsuccessfully treated women who had a child by some other means before or after the unsuccessful ART had comparable life satisfaction with successfully treated women even earlier.Conclusions
Even if unsuccessful ART outcome is associated with subsequent lower level of life satisfaction, it does not seem to threaten the long-term wellbeing. 相似文献10.
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Background
The ever increasing discovery of non-coding RNAs leads to unprecedented demand for the accurate modeling of RNA folding, including the predictions of two-dimensional (base pair) and three-dimensional all-atom structures and folding stabilities. Accurate modeling of RNA structure and stability has far-reaching impact on our understanding of RNA functions in human health and our ability to design RNA-based therapeutic strategies.Results
The Vfold server offers a web interface to predict (a) RNA two-dimensional structure from the nucleotide sequence, (b) three-dimensional structure from the two-dimensional structure and the sequence, and (c) folding thermodynamics (heat capacity melting curve) from the sequence. To predict the two-dimensional structure (base pairs), the server generates an ensemble of structures, including loop structures with the different intra-loop mismatches, and evaluates the free energies using the experimental parameters for the base stacks and the loop entropy parameters given by a coarse-grained RNA folding model (the Vfold model) for the loops. To predict the three-dimensional structure, the server assembles the motif scaffolds using structure templates extracted from the known PDB structures and refines the structure using all-atom energy minimization.Conclusions
The Vfold-based web server provides a user friendly tool for the prediction of RNA structure and stability. The web server and the source codes are freely accessible for public use at “http://rna.physics.missouri.edu”. 相似文献13.
Marta Luz Stephanie Spannl-Müller Günes ?zhan Birgit Kagermeier-Schenk Muriel Rhinn Gilbert Weidinger Michael Brand 《PloS one》2014,9(1)
Background
Wnt proteins are conserved signaling molecules that regulate pattern formation during animal development. Many Wnt proteins are post-translationally modified by addition of lipid adducts. Wnt8a provides a crucial signal for patterning the anteroposterior axis of the developing neural plate in vertebrates. However, it is not clear how this protein propagates from its source, the blastoderm margin, to the target cells in the prospective neural plate, and how lipid-modifications might influence Wnt8a propagation and activity.Results
We have dynamically imaged biologically active, fluorescently tagged Wnt8a in living zebrafish embryos. We find that Wnt8a localizes to membrane-associated, punctate structures in live tissue. In Wnt8a expressing cells, these puncta are found on filopodial cellular processes, from where the protein can be released. In addition, Wnt8a is found colocalized with Frizzled receptor-containing clusters on signal receiving cells. Combining in vitro and in vivo assays, we compare the roles of conserved Wnt8a residues in cell and non-cell-autonomous signaling activity and secretion. Non-signaling Wnt8 variants show these residues can regulate Wnt8a distribution in producing cell membranes and filopodia as well as in the receiving tissue.Conclusions
Together, our results show that Wnt8a forms dynamic clusters found on filopodial donor cell and on signal receiving cell membranes. Moreover, they demonstrate a differential requirement of conserved residues in Wnt8a protein for distribution in producing cells and receiving tissue and signaling activity during neuroectoderm patterning. 相似文献14.
15.
Background
Linear motifs are short modules of protein sequences that play a crucial role in mediating and regulating many protein–protein interactions. The function of linear motifs strongly depends on the context, e.g. functional instances mainly occur inside flexible regions that are accessible for interaction. Sometimes linear motifs appear as isolated islands of conservation in multiple sequence alignments. However, they also occur in larger blocks of sequence conservation, suggesting an active role for the neighbouring amino acids.Results
The evolution of regions flanking 116 functional linear motif instances was studied. The conservation of the amino acid sequence and order/disorder tendency of those regions was related to presence/absence of the instance. For the majority of the analysed instances, the pairs of sequences conserving the linear motif were also observed to maintain a similar local structural tendency and/or to have higher local sequence conservation when compared to pairs of sequences where one is missing the linear motif. Furthermore, those instances have a higher chance to co–evolve with the neighbouring residues in comparison to the distant ones. Those findings are supported by examples where the regulation of the linear motif–mediated interaction has been shown to depend on the modifications (e.g. phosphorylation) at neighbouring positions or is thought to benefit from the binding versatility of disordered regions.Conclusion
The results suggest that flanking regions are relevant for linear motif–mediated interactions, both at the structural and sequence level. More interestingly, they indicate that the prediction of linear motif instances can be enriched with contextual information by performing a sequence analysis similar to the one presented here. This can facilitate the understanding of the role of these predicted instances in determining the protein function inside the broader context of the cellular network where they arise. 相似文献16.
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