共查询到20条相似文献,搜索用时 31 毫秒
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Background
The exon junction complex (EJC) is a dynamic multi-protein complex deposited onto nuclear spliced mRNAs upstream of exon-exon junctions. The four core proteins, eIF4A3, Magoh, Y14 and MLN51, are stably bound to mRNAs during their lifecycle, serving as a binding platform for other nuclear and cytoplasmic proteins. Recent evidence has shown that the EJC is involved in the splicing regulation of some specific events in both Drosophila and mammalian cells.Results
Here, we show that knockdown of EJC core proteins causes widespread alternative splicing changes in mammalian cells. These splicing changes are specific to EJC core proteins, as knockdown of eIF4A3, Y14 and MLN51 shows similar splicing changes, and are different from knockdown of other splicing factors. The splicing changes can be rescued by a siRNA-resistant form of eIF4A3, indicating an involvement of EJC core proteins in regulating alternative splicing. Finally, we find that the splicing changes are linked with RNA polymerase II elongation rates.Conclusion
Taken together, this study reveals that the coupling between EJC proteins and splicing is broader than previously suspected, and that a possible link exists between mRNP assembly and splice site recognition.Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0551-7) contains supplementary material, which is available to authorized users. 相似文献6.
Albert Wu Chester Good John R. Downs Michael J. Fine Mary Jo V. Pugh Antonio Anzueto Eric M. Mortensen 《PloS one》2014,9(1)
Introduction
Little research has examined whether cardiovascular medications, other than statins, are associated with improved outcomes after pneumonia. Our aim was to examine the association between the use of beta-blockers, statins, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) with pneumonia-related outcomes.Materials and Methods
We conducted a retrospective population-based study on male patients ≥65 years of age hospitalized with pneumonia and who did not have pre-existing cardiac disease. Our primary analyses were multilevel regression models that examined the association between cardiovascular medication classes and either mortality or cardiovascular events.Results
Our cohort included 21,985 patients: 22% died within 90 days of admission, and 22% had a cardiac event within 90 days. The cardiovascular medications studied that were associated with decreased 90-day mortality included: statins (OR 0.70, 95% CI 0.63–0.77), ACE inhibitors (OR 0.82, 95% CI 0.74–0.91), and ARBs (OR 0.58, 95% CI 0.44–0.77). However, none of the medications were significantly associated with decreased cardiovascular events.Discussion
While statins, ACE inhibitors, and ARBs, were associated with decreased mortality, there was no significant association with decreased CV events. These results indicate that this decreased mortality is unlikely due to their potential cardioprotective effects. 相似文献7.
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Background
Although there are different strains of HIV-1 in a chronically infected individual, only one or limited virus strains are successfully transmitted to a new individual. The reason for this “transmission bottleneck” is as yet unknown.Methodology/Principal Findings
A human cervical explant model was used to measure HIV-1 transmission efficiency of viral strains from chronic infections, and transmitter/founder variants. We also evaluated the genetic characteristics of HIV-1 variants in the inoculums compared to those transmitted across the cervical mucosa. Eight different HIV-1 isolates were used in this study, six chronic isolates and two transmitter/founder viruses. The transmission efficiency of the chronic and transmitter/founder virus isolates and the viral diversity of chronic isolates before and after viral transmission were assessed. The results indicate that transmitter/founder viruses did not display higher transmission efficiency than chronic HIV-1 isolates. Furthermore, no evidence for a difference in diversity was found between the inoculums and transmitted virus strains. Phylogenetic analysis indicated that the sequences of variants in the inoculums and those present in transmitted virus intermingled irrespective of co-receptor usage. In addition, the inoculum and transmitted variants had a similar pairwise distance distribution.Conclusion
There was no selection of a single or limited number of viral variants during HIV-1 transmission across the cervical mucosa in the organ culture model, indicating that the cervical mucosa alone may not produce the transmission bottleneck of HIV-1 infection observed in vivo. 相似文献9.
Background
Previous studies using hierarchical clustering approach to analyze resting-state fMRI data were limited to a few slices or regions-of-interest (ROIs) after substantial data reduction.Purpose
To develop a framework that can perform voxel-wise hierarchical clustering of whole-brain resting-state fMRI data from a group of subjects.Materials and Methods
Resting-state fMRI measurements were conducted for 86 adult subjects using a single-shot echo-planar imaging (EPI) technique. After pre-processing and co-registration to a standard template, pair-wise cross-correlation coefficients (CC) were calculated for all voxels inside the brain and translated into absolute Pearson''s distances after imposing a threshold CC≥0.3. The group averages of the Pearson''s distances were then used to perform hierarchical clustering with the developed framework, which entails gray matter masking and an iterative scheme to analyze the dendrogram.Results
With the hierarchical clustering framework, we identified most of the functional connectivity networks reported previously in the literature, such as the motor, sensory, visual, memory, and the default-mode functional networks (DMN). Furthermore, the DMN and visual system were split into their corresponding hierarchical sub-networks.Conclusion
It is feasible to use the proposed hierarchical clustering scheme for voxel-wise analysis of whole-brain resting-state fMRI data. The hierarchical clustering result not only confirmed generally the finding in functional connectivity networks identified previously using other data processing techniques, such as ICA, but also revealed directly the hierarchical structure within the functional connectivity networks. 相似文献10.
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Background
Alternative splicing (AS) of precursor mRNA (pre-mRNA) is an important gene regulation process that potentially regulates many physiological processes in plants, including the response to abiotic stresses such as salt stress.Results
To analyze global changes in AS under salt stress, we obtained high-coverage (~200 times) RNA sequencing data from Arabidopsis thaliana seedlings that were treated with different concentrations of NaCl. We detected that ~49% of all intron-containing genes were alternatively spliced under salt stress, 10% of which experienced significant differential alternative splicing (DAS). Furthermore, AS increased significantly under salt stress compared with under unstressed conditions. We demonstrated that most DAS genes were not differentially regulated by salt stress, suggesting that AS may represent an independent layer of gene regulation in response to stress. Our analysis of functional categories suggested that DAS genes were associated with specific functional pathways, such as the pathways for the responses to stresses and RNA splicing. We revealed that serine/arginine-rich (SR) splicing factors were frequently and specifically regulated in AS under salt stresses, suggesting a complex loop in AS regulation for stress adaptation. We also showed that alternative splicing site selection (SS) occurred most frequently at 4 nucleotides upstream or downstream of the dominant sites and that exon skipping tended to link with alternative SS.Conclusions
Our study provided a comprehensive view of AS under salt stress and revealed novel insights into the potential roles of AS in plant response to salt stress.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-431) contains supplementary material, which is available to authorized users. 相似文献12.
Rachel E. Butler Priscille Brodin Jichan Jang Mi-Seon Jang Brian D. Robertson Brigitte Gicquel Graham R. Stewart 《PloS one》2012,7(10)
Background
An important mechanism of Mycobacterium tuberculosis pathogenesis is the ability to control cell death pathways in infected macrophages: apoptotic cell death is bactericidal, whereas necrotic cell death may facilitate bacterial dissemination and transmission.Methods
We examine M.tuberculosis control of spontaneous and chemically induced macrophage cell death using automated confocal fluorescence microscopy, image analysis, flow cytometry, plate-reader based vitality assays, and M.tuberculosis strains including H37Rv, and isogenic virulent and avirulent strains of the Beijing lineage isolate GC1237.Results
We show that bacterial virulence influences the dynamics of caspase activation and the total level of cytotoxicity. We show that the powerful ability of M.tuberculosis to inhibit exogenously stimulated apoptosis is abrogated by loss of virulence. However, loss of virulence did not influence the balance of macrophage apoptosis and necrosis – both virulent and avirulent isogenic strains of GC1237 induced predominantly necrotic cell death compared to H37Rv which induced a higher relative level of apoptosis.Conclusions
This reveals that macrophage necrosis and apoptosis are independently regulated during M. tuberculosis infection of macrophages. Virulence affects the level of host cell death and ability to inhibit apoptosis but other strain-specific characteristics influence the ultimate mode of host cell death and alter the balance of apoptosis and necrosis. 相似文献13.
Background
The quality of colonoscopies performed by primary care physicians (PCPs) is unknown.Objective
To determine whether PCP colonoscopists achieve colonoscopy quality benchmarks, and patient satisfaction with having their colonoscopy performed by a primary care physician.Design
Prospective multi-center, multi-physician observational study. Colonoscopic quality data collection occurred via completion of case report forms and pathological confirmation of lesions. Patient satisfaction was captured by a telephone survey.Setting
Thirteen rural and suburban hospitals in Alberta, Canada.Measurements
Proportion of successful cecal intubations, average number of adenomas detected per colonoscopy, proportion of patients with at least one adenoma, and serious adverse event rates; patient satisfaction with their wait time and procedure, as well as willingness to have a repeat colonoscopy performed by their primary care endoscopist.Results
In the two-month study period, 10 study physicians performed 577 colonoscopies. The overall adjusted proportion of successful cecal intubations was 96.5% (95% CI 94.6–97.8), and all physicians achieved the adjusted cecal intubation target of ≥90%. The average number of ademonas detected per colonoscopy was 0.62 (95% CI 0.5–0.74). 46.4% (95% CI 38.5–54.3) of males and 30.2% (95% CI 22.3–38.2) of females ≥50 years of age having their first colonoscopy, had at least one adenoma. Four serious adverse events occurred (three post polypectomy bleeds and one perforation) and 99.3% of patients were willing to have a repeat colonoscopy performed by their primary care colonoscopist.Limitations
Two-month study length and non-universal participation by Alberta primary care endoscopists.Conclusions
Primary care physician colonoscopists can achieve quality benchmarks in colonoscopy. Training additional primary care physicians in endoscopy may improve patient access and decrease endoscopic wait times, especially in rural settings. 相似文献14.
Edward C. Jones-López Soyeon Kim Geisa Fregona Patricia Marques-Rodrigues David Jamil Hadad Lucilia Pereira Dutra Molina Solange Vinhas Nancy Reilly Stephanie Moine Soumitesh Chakravorty Mary Gaeddert Rodrigo Ribeiro-Rodrigues Padmini Salgame Moises Palaci David Alland Jerrold J. Ellner Reynaldo Dietze 《PloS one》2014,9(7)
Rationale
The degree to which tuberculosis (TB) is transmitted between persons is variable. Identifying the factors that contribute to transmission could provide new opportunities for TB control. Transmission is influenced by host, bacterial and environmental factors. However, distinguishing their individual effects is problematic because measures of disease severity are tightly correlated, and assessing the virulence of Mycobacterium tuberculosis isolates is complicated by epidemiological and clinical confounders.Objectives
To overcome these problems, we investigated factors potentially associated with TB transmission within households.Methods
We evaluated patients with smear-positive (≥2+), pulmonary TB and classified M. tuberculosis strains into single nucleotide polymorphism genetic cluster groups (SCG). We recorded index case, household contact, and environmental characteristics and tested contacts with tuberculin skin test (TST) and interferon-gamma release assay. Households were classified as high (≥70% of contacts with TST≥10 mm) and low (≤40%) transmission. We used logistic regression to determine independent predictors.Result
From March 2008 to June 2012, we screened 293 TB patients to enroll 124 index cases and their 731 contacts. There were 23 low and 73 high transmission households. Index case factors associated with high transmission were severity of cough as measured by a visual analog cough scale (VACS) and the Leicester Cough Questionnaire (LCQ), and cavitation on chest radiograph. SCG 3b strains tended to be more prevalent in low (27.3%) than in high (12.5%) transmission households (p = 0.11). In adjusted models, only VACS (p<0.001) remained significant. SCG was associated with bilateral disease on chest radiograph (p = 0.002) and marginally associated with LCQ sores (p = 0.058), with group 3b patients having weaker cough.Conclusions
We found differential transmission among otherwise clinically similar patients with advanced TB disease. We propose that distinct strains may cause differing patterns of cough strength and cavitation in the host leading to diverging infectiousness. Larger studies are needed to verify this hypothesis. 相似文献15.
Fengyu Wang Jingfa Xiao Linlin Pan Ming Yang Guoqiang Zhang Shouguang Jin Jun Yu 《PloS one》2008,3(12)
Background
Mini-proteins, defined as polypeptides containing no more than 100 amino acids, are ubiquitous in prokaryotes and eukaryotes. They play significant roles in various biological processes, and their regulatory functions gradually attract the attentions of scientists. However, the functions of the majority of mini-proteins are still largely unknown due to the constraints of experimental methods and bioinformatic analysis.Methodology/Principal Findings
In this article, we extracted a total of 180,879 mini-proteins from the annotations of 532 sequenced genomes, including 491 strains of Bacteria and 41 strains of Archaea. The average proportion of mini-proteins among all genomic proteins is approximately 10.99%, but different strains exhibit remarkable fluctuations. These mini-proteins display two notable characteristics. First, the majority are species-specific proteins with an average proportion of 58.79% among six representative phyla. Second, an even larger proportion (70.03% among all strains) is hypothetical proteins. However, a fraction of highly conserved hypothetical proteins potentially play crucial roles in organisms. Among mini-proteins with known functions, it seems that regulatory and metabolic proteins are more abundant than essential structural proteins. Furthermore, domains in mini-proteins seem to have greater distributions in Bacteria than Eukarya. Analysis of the evolutionary progression of these domains reveals that they have diverged to new patterns from a single ancestor.Conclusions/Significance
Mini-proteins are ubiquitous in bacterial and archaeal species and play significant roles in various functions. The number of mini-proteins in each genome displays remarkable fluctuation, likely resulting from the differential selective pressures that reflect the respective life-styles of the organisms. The answers to many questions surrounding mini-proteins remain elusive and need to be resolved experimentally. 相似文献16.
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Karen K. Wong Jianrong Shi Hongjiang Gao Yenlik A. Zheteyeva Kimberly Lane Daphne Copeland Jennifer Hendricks LaFrancis McMurray Kellye Sliger Jeanette J. Rainey Amra Uzicanin 《PloS one》2014,9(12)
Introduction
We describe characteristics of unplanned school closures (USCs) in the United States over two consecutive academic years during a non-pandemic period to provide context for implementation of school closures during a pandemic.Methods
From August 1, 2011 through June 30, 2013, daily systematic internet searches were conducted for publicly announced USCs lasting ≥1 day. The reason for closure and the closure dates were recorded. Information on school characteristics was obtained from the National Center for Education Statistics.Results
During the two-year study period, 20,723 USCs were identified affecting 27,066,426 students. Common causes of closure included weather (79%), natural disasters (14%), and problems with school buildings or utilities (4%). Only 771 (4%) USCs lasted ≥4 school days. Illness was the cause of 212 (1%) USCs; of these, 126 (59%) were related to respiratory illnesses and showed seasonal variation with peaks in February 2012 and January 2013.Conclusions
USCs are common events resulting in missed school days for millions of students. Illness causes few USCs compared with weather and natural disasters. Few communities have experience with prolonged closures for illness. 相似文献19.
H. Irene Hall Jessica Halverson David P. Wilson Barbara Suligoi Mercedes Diez Stéphane Le Vu Tian Tang Ann McDonald Laura Camoni Caroline Semaille Chris Archibald 《PloS one》2013,8(11)
Background
Testing for HIV infection and entry to care are the first steps in the continuum of care that benefit individual health and may reduce onward transmission of HIV. We determined the percentage of people with HIV who were diagnosed late and the percentage linked into care overall and by demographic and risk characteristics by country.Methods
Data were analyzed from national HIV surveillance systems. Six countries, where available, provided data on two late diagnosis indicators (AIDS diagnosis within 3 months of HIV diagnosis, and AIDS diagnosis within 12 months before HIV diagnosis) and linkage to care (≥1 CD4 or viral load test result within 3 months of HIV diagnosis) for people diagnosed with HIV in 2009 or 2010 (most recent year data were available).Principal Findings
The percentage of people presenting with late stage disease at HIV diagnosis varied by country, overall with a range from 28.7% (United States) to 8.8% (Canada), and by transmission categories. The percentage of people diagnosed with AIDS who had their initial HIV diagnosis within 12 months before AIDS diagnosis varied little among countries, except the percentages were somewhat lower in Spain and the United States. Overall, the majority of people diagnosed with HIV were linked to HIV care within 3 months of diagnosis (more than 70%), but varied by age and transmission category.Conclusions
Differences in patterns of late presentation at HIV diagnosis among countries may reflect differences in screening practices by providers, public health agencies, and people with HIV. The percentage of people who received assessments of immune status and viral load within 3 months of diagnosis was generally high. 相似文献20.
Myles Horton Jayesh Modi Shiel K. Patel Andrew M. Demchuk Mayank Goyal Michael D. Hill Shelagh B. Coutts 《PloS one》2013,8(6)