共查询到20条相似文献，搜索用时 15 毫秒
1.
Zachary L. Fuller Elina L. Ni?o Harland M. Patch Oscar C. Bedoya-Reina Tracey Baumgarten Elliud Muli Fiona Mumoki Aakrosh Ratan John McGraw Maryann Frazier Daniel Masiga Stephen Schuster Christina M. Grozinger Webb Miller 《BMC genomics》2015,16(1)
Background
With the development of inexpensive, high-throughput sequencing technologies, it has become feasible to examine questions related to population genetics and molecular evolution of non-model species in their ecological contexts on a genome-wide scale. Here, we employed a newly developed suite of integrated, web-based programs to examine population dynamics and signatures of selection across the genome using several well-established tests, including FST, pN/pS, and McDonald-Kreitman. We applied these techniques to study populations of honey bees (Apis mellifera) in East Africa. In Kenya, there are several described A. mellifera subspecies, which are thought to be localized to distinct ecological regions.Results
We performed whole genome sequencing of 11 worker honey bees from apiaries distributed throughout Kenya and identified 3.6 million putative single-nucleotide polymorphisms. The dense coverage allowed us to apply several computational procedures to study population structure and the evolutionary relationships among the populations, and to detect signs of adaptive evolution across the genome. While there is considerable gene flow among the sampled populations, there are clear distinctions between populations from the northern desert region and those from the temperate, savannah region. We identified several genes showing population genetic patterns consistent with positive selection within African bee populations, and between these populations and European A. mellifera or Asian Apis florea.Conclusions
These results lay the groundwork for future studies of adaptive ecological evolution in honey bees, and demonstrate the use of new, freely available web-based tools and workflows (http://usegalaxy.org/r/kenyanbee) that can be applied to any model system with genomic information.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1712-0) contains supplementary material, which is available to authorized users. 相似文献2.
?zgün Babur Ugur Dogrusoz Merve ?ak?r Bülent Arman Aksoy Nikolaus Schultz Chris Sander Emek Demir 《BMC genomics》2014,15(1)
Background
Dynamic visual exploration of detailed pathway information can help researchers digest and interpret complex mechanisms and genomic datasets.Results
ChiBE is a free, open-source software tool for visualizing, querying, and analyzing human biological pathways in BioPAX format. The recently released version 2 can search for neighborhoods, paths between molecules, and common regulators/targets of molecules, on large integrated cellular networks in the Pathway Commons database as well as in local BioPAX models. Resulting networks can be automatically laid out for visualization using a graphically rich, process-centric notation. Profiling data from the cBioPortal for Cancer Genomics and expression data from the Gene Expression Omnibus can be overlaid on these networks.Conclusions
ChiBE’s new capabilities are organized around a genomics-oriented workflow and offer a unique comprehensive pathway analysis solution for genomics researchers. The software is freely available at http://code.google.com/p/chibe. 相似文献3.
Jyrki Selinummi Pekka Ruusuvuori Irina Podolsky Adrian Ozinsky Elizabeth Gold Olli Yli-Harja Alan Aderem Ilya Shmulevich 《PloS one》2009,4(10)
Background
Fluorescence microscopy is the standard tool for detection and analysis of cellular phenomena. This technique, however, has a number of drawbacks such as the limited number of available fluorescent channels in microscopes, overlapping excitation and emission spectra of the stains, and phototoxicity.Methodology
We here present and validate a method to automatically detect cell population outlines directly from bright field images. By imaging samples with several focus levels forming a bright field -stack, and by measuring the intensity variations of this stack over the -dimension, we construct a new two dimensional projection image of increased contrast. With additional information for locations of each cell, such as stained nuclei, this bright field projection image can be used instead of whole cell fluorescence to locate borders of individual cells, separating touching cells, and enabling single cell analysis. Using the popular CellProfiler freeware cell image analysis software mainly targeted for fluorescence microscopy, we validate our method by automatically segmenting low contrast and rather complex shaped murine macrophage cells.Significance
The proposed approach frees up a fluorescence channel, which can be used for subcellular studies. It also facilitates cell shape measurement in experiments where whole cell fluorescent staining is either not available, or is dependent on a particular experimental condition. We show that whole cell area detection results using our projected bright field images match closely to the standard approach where cell areas are localized using fluorescence, and conclude that the high contrast bright field projection image can directly replace one fluorescent channel in whole cell quantification. Matlab code for calculating the projections can be downloaded from the supplementary site: http://sites.google.com/site/brightfieldorstaining 相似文献4.
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Purpose
To determine whether oral doxycycline treatment reduces pterygium lesions.Design
Double blind, randomized, placebo controlled clinical trial.Participants
98 adult patients with primary pterygium.Methods
Patients were randomly assigned to receive 100 mg oral doxycycline twice a day (49 subjects), or placebo (49 subjects), for 30 days. Photographs of the lesion were taken at the time of recruitment and at the end of the treatment. Follow-up sessions were performed 6 and 12 months post-treatment. Statistical analyses for both continuous and categorical variables were applied. p values of less than 0.05 were considered to indicate statistical significance.Main Outcome Measures
The primary endpoint was the change in lesion size after 30 days of treatment.Results
The primary endpoint was not met for the whole population but subgroup analysis showed that doxycycline was effective in patients of Caucasian origin while other ethnicities, mostly Hispanic, did not respond to the treatment. Moreover, there was a correlation between age and better response (p = 0.003). Adverse events were uncommon, mild, and in agreement with previous reports on short doxycycline treatments.Conclusions
Oral doxycycline was superior to placebo for the treatment of primary pterygia in older Caucasian patients. These findings support the use of doxycycline for pterygium treatment in particular populations.Trial Registration
European Union Clinical Trials Register EudraCT 2008-007178-39 相似文献7.
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Wendy T. M. Pots Peter A. M. Meulenbeek Martine M. Veehof Jorinde Klungers Ernst T. Bohlmeijer 《PloS one》2014,9(10)
Objective
Although there has been growing evidence for the efficacy of mindfulness-based cognitive therapy (MBCT) for different clinical populations, its effectiveness as a public mental health intervention has not been studied. The present study evaluates a community-based MBCT intervention for adults with mild to moderate depressive symptomatology in a large multi-site, pragmatic randomized controlled trial.Method
The participants with mild to moderate depressive symptomatology were recruited from the general population and randomized to the MBCT intervention (n = 76) or to a waiting list control group (n = 75). Participants completed measures before and after the intervention. Participants in the experimental condition also completed these measures at a 3-month follow-up.Results
In the experimental condition significant reductions in depression, anxiety, and experiential avoidance, and improvements in mindfulness and emotional- and psychological mental health were found, compared to the waiting list (effect sizes Cohen''s d = 0.31–0.56). These effects were sustained at the 3-month follow-up. The likelihood of a clinically significant change in depressive symptoms was significantly higher for the MBCT group [odds ratio (OR) 3.026, p<0.01 at post-treatment; NNT = 5.10].Discussion
MBCT as a public mental health intervention for adults with mild to moderate depressive symptoms seems effective and applicable in a natural setting.Trial Registration
Nederlands Trial Register NTR2096 相似文献9.
Daniel Scott-Algara Maryline Mancini-Bourgine Hélène Fontaine Stanislas Pol Marie-Louise Michel 《PloS one》2010,5(1)
Background
Improvements to the outcome of adaptive immune responses could be achieved by inducing specific natural killer (NK) cell subsets which can cooperate with dendritic cells to select efficient T cell responses. We previously reported the induction or reactivation of T cell responses in chronic hepatitis B patients vaccinated with a DNA encoding hepatitis B envelope proteins during a phase I clinical trial.Methodology/Principal Findings
In this study, we examined changes in the peripheral NK cell populations occurring during this vaccine trial using flow cytometry analysis. Despite a constant number of NK cells in the periphery, a significant increase in the CD56bright population was observed after each vaccination and during the follow up. Among the 13 different NK cell markers studied by flow cytometry analysis, the expression of CD244 and NKG2D increased significantly in the CD56bright NK population. The ex vivo CD107a expression by CD56bright NK cells progressively increased in the vaccinated patients to reach levels that were significantly higher compared to chronically HBV-infected controls. Furthermore, modifications to the percentage of the CD56bright NK cell population were correlated with HBV-specific T cell responses detected by the ELISPOT assay.Conclusions/Significance
These changes in the CD56bright population may suggest a NK helper effect on T cell adaptive responses. Activation of the innate and adaptive arms of the immune system by DNA immunization may be of particular importance to the efficacy of therapeutic interventions in a context of chronic infections.Trial Registration
ClinicalTrials.gov NCT00988767 相似文献10.
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Background
Complex PCR applications for large genome-scale projects require fast, reliable and often highly sophisticated primer design software applications. Presently, such applications use pipelining methods to utilise many third party applications and this involves file parsing, interfacing and data conversion, which is slow and prone to error. A fully integrated suite of software tools for primer design would considerably improve the development time, the processing speed, and the reliability of bespoke primer design software applications.Results
The PD5 software library is an open-source collection of classes and utilities, providing a complete collection of software building blocks for primer design and analysis. It is written in object-oriented C++ with an emphasis on classes suitable for efficient and rapid development of bespoke primer design programs. The modular design of the software library simplifies the development of specific applications and also integration with existing third party software where necessary. We demonstrate several applications created using this software library that have already proved to be effective, but we view the project as a dynamic environment for building primer design software and it is open for future development by the bioinformatics community. Therefore, the PD5 software library is published under the terms of the GNU General Public License, which guarantee access to source-code and allow redistribution and modification.Conclusions
The PD5 software library is downloadable from Google Code and the accompanying Wiki includes instructions and examples: http://code.google.com/p/primer-design 相似文献12.
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Background
Large clinical genomics studies using next generation DNA sequencing require the ability to select and track samples from a large population of patients through many experimental steps. With the number of clinical genome sequencing studies increasing, it is critical to maintain adequate laboratory information management systems to manage the thousands of patient samples that are subject to this type of genetic analysis.Results
To meet the needs of clinical population studies using genome sequencing, we developed a web-based laboratory information management system (LIMS) with a flexible configuration that is adaptable to continuously evolving experimental protocols of next generation DNA sequencing technologies. Our system is referred to as MendeLIMS, is easily implemented with open source tools and is also highly configurable and extensible. MendeLIMS has been invaluable in the management of our clinical genome sequencing studies.Conclusions
We maintain a publicly available demonstration version of the application for evaluation purposes at http://mendelims.stanford.edu. MendeLIMS is programmed in Ruby on Rails (RoR) and accesses data stored in SQL-compliant relational databases. Software is freely available for non-commercial use at http://dna-discovery.stanford.edu/software/mendelims/.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-290) contains supplementary material, which is available to authorized users. 相似文献15.
Diederik Esser Els Oosterink Jos op 't Roodt Ronald M. A. Henry Coen D. A. Stehouwer Michael Müller Lydia A. Afman 《PloS one》2013,8(2)
Background
High fat meal challenges are known to induce postprandial low-grade inflammation and endothelial dysfunction. This assumption is largely based on studies performed in older populations or in populations with a progressed disease state and an appropriate control meal is often lacking. Young healthy individuals might be more resilient to such challenges. We therefore aimed to characterize the vascular and inflammatory response after a high fat meal in young healthy individuals.Methods
In a double-blind randomized cross-over intervention study, we used a comprehensive phenotyping approach to determine the vascular and inflammatory response after consumption of a high fat shake and after an average breakfast shake in 20 young healthy subjects. Both interventions were performed three times.Results
Many features of the vascular postprandial response, such as FMD, arterial stiffness and micro-vascular skin blood flow were not different between shakes. High fat/high energy shake consumption was associated with a more pronounced increase in blood pressure, heart rate, plasma concentrations of IL-8 and PBMCs gene expression of IL-8 and CD54 (ICAM-1), whereas plasma concentrations of sVCAM1 were decreased compared to an average breakfast.Conclusion
Whereas no difference in postprandial response were observed on classical markers of endothelial function, we did observe differences between consumption of a HF/HE and an average breakfast meal on blood pressure and IL-8 in young healthy volunteers. IL-8 might play an important role in dealing with high fat challenges and might be an early marker for endothelial stress, a stage preceding endothelial dysfunction.Trial Registration
ClinicalTrials.gov NCT00766623 相似文献16.
Qi Pei Yan Wang Zhe-Yi Hu Shi-Kun Liu Hong-Yi Tan Cheng-Xian Guo Ran-Ran Zhang Yu-Xia Xiang Jie Huang Lu Huang Hong Yuan Guo-Ping Yang 《PloS one》2014,9(10)
Objectives
We aim to obtain the intra-subject coefficient of variability of a highly variable antidepressant agomelatine in humans, and propose an adjusted bioequivalence assessment strategy.Methods
A single-dose, randomized crossover design was conducted in four periods (reference administered thrice, placebo administered once) separated by seven days. A validated LC-MS/MS assay was used to measure drug concentrations in serial blood samples.Results
The intra-subject coefficient of variability was calculated using the residual variance of ANOVA analysis, and the results for Cmax and AUC0-t was 78.34% and 43.52%, respectively, in Chinese healthy subjects. The sample size required for standard BE study were 124(192, 340) if the expected deviation between the reference and generic products was set to 0 (5%, 10%).Conclusions
Agomelatine meets the criteria for highly variable drug in Chinese healthy male subjects, and the traditional BE criteria for agomelatine needs to be adjusted to alleviate the resource and ethical burden of using a large numbers of subjects in clinical trials. Our clinical data on the intra-subject variability of agomelatine PK in Chinese healthy population enables to adjust bioequivalence (BE) assessment approach for agomelatine based on the RSABE approaches recommended by regulatory agencies.Trial Registration
ChiCTR.org ChiCTR-TTRCC-13003835 相似文献17.
Nickolai Titov Blake F. Dear Luke Johnston Carolyn Lorian Judy Zou Bethany Wootton Jay Spence Peter M. McEvoy Ronald M. Rapee 《PloS one》2013,8(7)
Background
Depression and anxiety are common, disabling and chronic. Self-guided internet-delivered treatments are popular, but few people complete them. New strategies are required to realise their potential.Aims
To evaluate the effect of automated emails on the effectiveness, safety, and acceptability of a new automated transdiagnostic self-guided internet-delivered treatment, the Wellbeing Course, for people with depression and anxiety.Method
A randomised controlled trial was conducted through the website: www.ecentreclinic.org. Two hundred and fifty seven people with elevated symptoms were randomly allocated to the 8 week course either with or without automated emails, or to a waitlist control group. Primary outcome measures were the Patient Health Questionnaire 9-Item (PHQ-9) and the Generalized Anxiety Disorder 7-Item (GAD-7).Results
Participants in the treatment groups had lower PHQ-9 and GAD-7 scores at post-treatment than controls. Automated emails increased rates of course completion (58% vs. 35%), and improved outcomes in a subsample with elevated symptoms.Conclusions
The new self-guided course was beneficial, and automated emails facilitated outcomes. Further attention to strategies that facilitate adherence, learning, and safety will help realise the potential of self-guided interventions.Trial Registration
Australian and New Zealand Clinical Trials Registry ACTRN12610001058066 相似文献18.
Aaron L. Leppin Pavithra R. Bora Jon C. Tilburt Michael R. Gionfriddo Claudia Zeballos-Palacios Megan M. Dulohery Amit Sood Patricia J. Erwin Juan Pablo Brito Kasey R. Boehmer Victor M. Montori 《PloS one》2014,9(10)
Importance
Poor mental health places a burden on individuals and populations. Resilient persons are able to adapt to life’s challenges and maintain high quality of life and function. Finding effective strategies to bolster resilience in individuals and populations is of interest to many stakeholders.Objectives
To synthesize the evidence for resiliency training programs in improving mental health and capacity in 1) diverse adult populations and 2) persons with chronic diseases.Data Sources
Electronic databases, clinical trial registries, and bibliographies. We also contacted study authors and field experts.Study Selection
Randomized trials assessing the efficacy of any program intended to enhance resilience in adults and published after 1990. No restrictions were made based on outcome measured or comparator used.Data Extraction and Synthesis
Reviewers worked independently and in duplicate to extract study characteristics and data. These were confirmed with authors. We conducted a random effects meta-analysis on available data and tested for interaction in planned subgroups.Main Outcomes
The standardized mean difference (SMD) effect of resiliency training programs on 1) resilience/hardiness, 2) quality of life/well-being, 3) self-efficacy/activation, 4) depression, 5) stress, and 6) anxiety.Results
We found 25 small trials at moderate to high risk of bias. Interventions varied in format and theoretical approach. Random effects meta-analysis showed a moderate effect of generalized stress-directed programs on enhancing resilience [pooled SMD 0.37 (95% CI 0.18, 0.57) p = .0002; I2 = 41%] within 3 months of follow up. Improvement in other outcomes was favorable to the interventions and reached statistical significance after removing two studies at high risk of bias. Trauma-induced stress-directed programs significantly improved stress [−0.53 (−1.04, −0.03) p = .03; I2 = 73%] and depression [−0.51 (−0.92, −0.10) p = .04; I2 = 61%].Conclusions
We found evidence warranting low confidence that resiliency training programs have a small to moderate effect at improving resilience and other mental health outcomes. Further study is needed to better define the resilience construct and to design interventions specific to it.Registration Number
PROSPERO #CRD42014007185 相似文献19.
Study Objectives
To investigate the effect of an eight-week, home-based, personalized, computerized cognitive training program on sleep quality and cognitive performance among older adults with insomnia.Design
Participants (n = 51) were randomly allocated to a cognitive training group (n = 34) or to an active control group (n = 17). The participants in the cognitive training group completed an eight-week, home-based, personalized, computerized cognitive training program, while the participants in the active control group completed an eight-week, home-based program involving computerized tasks that do not engage high-level cognitive functioning. Before and after training, all participants'' sleep was monitored for one week by an actigraph and their cognitive performance was evaluated.Setting
Community setting: residential sleep/performance testing facility.Participants
Fifty-one older adults with insomnia (aged 65–85).Interventions
Eight weeks of computerized cognitive training for older adults with insomnia.Results
Mixed models for repeated measures analysis showed between-group improvements for the cognitive training group on both sleep quality (sleep onset latency and sleep efficiency) and cognitive performance (avoiding distractions, working memory, visual memory, general memory and naming). Hierarchical linear regressions analysis in the cognitive training group indicated that improved visual scanning is associated with earlier advent of sleep, while improved naming is associated with the reduction in wake after sleep onset and with the reduction in number of awakenings. Likewise the results indicate that improved “avoiding distractions” is associated with an increase in the duration of sleep. Moreover, the results indicate that in the active control group cognitive decline observed in working memory is associated with an increase in the time required to fall asleep.Conclusions
New learning is instrumental in promoting initiation and maintenance of sleep in older adults with insomnia. Lasting and personalized cognitive training is particularly indicated to generate the type of learning necessary for combined cognitive and sleep enhancements in this population.Trial Registration
ClinicalTrials.gov NCT00901641http://clinicaltrials.gov/ct2/show/NCT00901641 相似文献20.
Bego?a Comin-Anduix Hooman Sazegar Thinle Chodon Douglas Matsunaga Jason Jalil Erika von Euw Helena Escuin-Ordinas Robert Balderas Bartosz Chmielowski Jesus Gomez-Navarro Richard C. Koya Antoni Ribas 《PloS one》2010,5(9)