48 research outputs found

    Moderate mutation rate in the SARS coronavirus genome and its implications

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    BACKGROUND: The outbreak of severe acute respiratory syndrome (SARS) caused a severe global epidemic in 2003 which led to hundreds of deaths and many thousands of hospitalizations. The virus causing SARS was identified as a novel coronavirus (SARS-CoV) and multiple genomic sequences have been revealed since mid-April, 2003. After a quiet summer and fall in 2003, the newly emerged SARS cases in Asia, particularly the latest cases in China, are reinforcing a wide-spread belief that the SARS epidemic would strike back. With the understanding that SARS-CoV might be with humans for years to come, knowledge of the evolutionary mechanism of the SARS-CoV, including its mutation rate and emergence time, is fundamental to battle this deadly pathogen. To date, the speed at which the deadly virus evolved in nature and the elapsed time before it was transmitted to humans remains poorly understood. RESULTS: Sixteen complete genomic sequences with available clinical histories during the SARS outbreak were analyzed. After careful examination of multiple-sequence alignment, 114 single nucleotide variations were identified. To minimize the effects of sequencing errors and additional mutations during the cell culture, three strategies were applied to estimate the mutation rate by 1) using the closely related sequences as background controls; 2) adjusting the divergence time for cell culture; or 3) using the common variants only. The mutation rate in the SARS-CoV genome was estimated to be 0.80 – 2.38 × 10(-3 )nucleotide substitution per site per year which is in the same order of magnitude as other RNA viruses. The non-synonymous and synonymous substitution rates were estimated to be 1.16 – 3.30 × 10(-3 )and 1.67 – 4.67 × 10(-3 )per site per year, respectively. The most recent common ancestor of the 16 sequences was inferred to be present as early as the spring of 2002. CONCLUSIONS: The estimated mutation rates in the SARS-CoV using multiple strategies were not unusual among coronaviruses and moderate compared to those in other RNA viruses. All estimates of mutation rates led to the inference that the SARS-CoV could have been with humans in the spring of 2002 without causing a severe epidemic

    Prevalence of iron-deficiency anemia in pregnant women with various thalassemia genotypes: Thoughts on iron supplementation in pregnant women with thalassemia genes

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    BackgroundThere are limited studies on iron-deficiency anemia (IDA) in carriers of various thalassemia genotypes. However, for pregnant women (PW) with high iron demand, ignoring the phenomenon of carrying the thalassemia genes combined with IDA may lead to adverse pregnancy outcomes.MethodsThe hematological phenotype indexes of 15,051 PW who received a prenatal diagnosis of thalassemia in our hospital were analyzed, and the plasma ferritin (PF) of 714 anemic pregnant women (APW) was determined.ResultsThe results showed that 87.43% of APW without thalassemia suffered from IDA. Among APW with various thalassemia genotypes, we found that 40.00∌77.78% of subjects with α-thalassemia silent genotypes [αCS (or QS)α/αα (40.00%), –α3.7(or4.2)/αα (57.65%), and αWSα/αα (77.78%)] and 18.18∌84.21% of subjects with α-thalassemia minor genotypes [αCS (or QS)α/–α3.7(or4.2) (18.18%), –α3.7(or4.2)/–α3.7(or4.2) (40.00%), αα/–SEA (44.55%), and αWSα/–α3.7(or4.2) (84.21%)] developed IDA, while in subjects with α-thalassemia intermedia genotypes, only αWSα/–SEA was associated with IDA, with an incidence of 16.67%. However, the incidence of IDA in APW with common ÎČ-thalassemia minor genotypes (ÎČCD17(A>T)/ÎČ, ÎČCD41/42 (–TTCT)/ÎČ, ÎČCD71/72(+A)/ÎČ, ÎČIVS–II–654(C>T)/ÎČ, and ÎČ–28(A>G)/ÎČ) was less than 10.85%. In addition, the APW with ÎČ-thalassemia minor had a higher PF level than the APW without thalassemia.ConclusionOur study is the first to reveal differences in the prevalence of IDA among PW with various thalassemia genotypes, indicating that the possibility of IDA should be fully considered when managing PW with α-thalassemia silent or minor genotypes in high-risk areas, and that iron supplementation should be monitored dynamically for PW with ÎČ-thalassemia minor genotypes

    The cosmic ray test of MRPCs for the BESIII ETOF upgrade

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    In order to improve the particle identification capability of the Beijing Spectrometer III (BESIII),t is proposed to upgrade the current endcap time-of-flight (ETOF) detector with multi-gap resistive plate chamber (MRPC) technology. Aiming at extending ETOF overall time resolution better than 100ps, the whole system including MRPC detectors, new-designed Front End Electronics (FEE), CLOCK module, fast control boards and time to digital modules (TDIG), was built up and operated online 3 months under the cosmic ray. The main purposes of cosmic ray test are checking the detectors' construction quality, testing the joint operation of all instruments and guaranteeing the performance of the system. The results imply MRPC time resolution better than 100psps, efficiency is about 98%\% and the noise rate of strip is lower than 1Hz/Hz/(scm2scm^{2}) at normal threshold range, the details are discussed and analyzed specifically in this paper. The test indicates that the whole ETOF system would work well and satisfy the requirements of upgrade

    Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children

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    Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader–Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation

    Study on soil and water conservation regionalization in Changji Prefecture

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    Taking once during as the study area, the course by using the DPSIR model and a lot of literatures screening of high frequency index, and quantitative analysis combined with the expert appraisal method, on once during regionalization index system establishment, course planning method was studied, determining the topographical features, water loss and soil erosion prevention and control system, land exploitation and utilization of direction, after years of average rainfall, population density, coverage of trees, soil and water loss area total area percentage as indicators of dividing the partition of soil and water conservation, such as in the villages and towns as the basic unit. Through principal component analysis, cluster analysis, the GIS space superposition method for regionalization, will once during divided into course will once during is divided into six course four areas: the southern mountain freeze-thaw district, Zhongshan in southern hilly water conservation ecological reserve, with low hills in southern soil conservation area, central oasis environment farmland protection area in northern desert ecological maintenance, low mountain in northern wind sand area, ecological maintenance area 6 level 4 area of water conservation, determine the various functional areas of soil erosion prevention and control of system layout, the direction of land use, for once during planning of soil and water conservation and soil erosion prevention and control system of the course layout provides the scientific basis

    Screening significantly hypermethylated genes in fetal tissues compared with maternal blood using a methylated-CpG island recovery assay-based microarray

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    Abstract Background The noninvasive prenatal diagnosis procedures that are currently used to detect genetic diseases do not achieve desirable levels of sensitivity and specificity. Recently, fetal methylated DNA biomarkers in maternal peripheral blood have been explored for the noninvasive prenatal detection of genetic disorders. However, such efforts have covered only chromosomal aneuploidy, and fetal methylated DNA biomarkers in maternal whole blood for detecting single-gene diseases remain to be discovered. Methods To address this issue, we systematically screened significantly hypermethylated genes in fetal tissues and compared them with maternal peripheral blood potential in an attempt to detect fetal genes in maternal peripheral blood. First, the methylated-CpG island recovery assay combined with a CpG island array was performed for four fetus-toward placental tissues and the corresponding maternal peripheral bloods. Subsequently, direct bisulfite sequencing and combined bisulfite restriction analysis (COBRA) were carried out to validate the methylation status of the hypermethylated genes that were identified by the microarray analysis. Results Three hundred and ten significantly hypermethylated genes in the placental tissues were detected by microarray. From the top 15 hypermethylated genes detected by microarray, two were selected for sequencing validation in placental tissue and chorionic villus samples and four were selected for COBRA validation in four placental tissues, ten amniotic fluids and five chorionic villus samples. The six selected genes were confirmed to be hypermethylated in placental tissue and chorionic villus samples, but methylation of the genes could not be detected in the amniotic fluids. Conclusions Of the many hypermethylated genes and methylation sites that were found in the fetal tissues, some have great potential to be developed into molecular markers for noninvasive prenatal diagnosis of monogenic disorders. Further clinical studies are warranted to confirm these findings.</p
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