Moderate mutation rate in the SARS coronavirus genome and its implications

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

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 β-thalassemia minor genotypes (βCD17(A>T)/β, βCD41/42 (–TTCT)/β, βCD71/72(+A)/β, βIVS–II–654(C>T)/β, and β–28(A>G)/β) was less than 10.85%. In addition, the APW with β-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 β-thalassemia minor genotypes

The cosmic ray test of MRPCs for the BESIII ETOF upgrade

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 100$ps$, efficiency is about 98$\%$ and the noise rate of strip is lower than 1$Hz/$($scm^{2}$) 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

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

Exploring the Node Importance and Its Influencing Factors in the Railway Freight Transportation Network in China

Node importance is a key factor affecting the overall operation efficiency of a railway freight transportation network (RFTN) that can be measured with the indicators of Hub and PageRank. Based on complex network theory and the national railway cargo exchange data of China’s provinces, this study constructs an RFTN model with the 31 provinces as the nodes and measures the values of Hub and PageRank for the 31 provinces. Then, the time evolution law of the importance of the provincial nodes is analyzed comprehensively, and, using a regression model, the influencing factors of the importance of the provincial nodes are identified. The results show the following. (1) The uneven distribution of natural resources will affect the spatial changes in the importance of RFTN nodes. The Hub values tended to cluster around the average, and the economic structure of the output-oriented provinces improved as a whole. At the same time, the PageRank values of many provinces in the central and western regions significantly increased, and those provinces exhibited more frequent exchanges of goods with other provinces and closer economic ties with other regions. (2) The traffic fixed asset investments and the population density have the most obvious influences on the importance of the provincial nodes with a positive effect. In contrast, the railway freight concentration (RFC) coefficient, geographical location (longitude and latitude), and coastal region all have negative effects on the importance of provincial nodes. The results of this study provide scientific decision-making support for the reasonable establishment and distribution of RFTN hubs in China

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

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

MiR-290 Family Maintains Pluripotency and Self-Renewal by Regulating MAPK Signaling Pathway in Intermediate Pluripotent Stem Cells

Mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) are derived from pre- and post-implantation embryos, representing the initial “naïve” and final “primed” states of pluripotency, respectively. In this study, novel reprogrammed pluripotent stem cells (rPSCs) were induced from mouse EpiSCs using a chemically defined medium containing mouse LIF, BMP4, CHIR99021, XAV939, and SB203580. The rPSCs exhibited domed clones and expressed key pluripotency genes, with both X chromosomes active in female cells. Furthermore, rPSCs differentiated into cells of all three germ layers in vivo through teratoma formation. Regarding epigenetic modifications, the DNA methylation of Oct4, Sox2, and Nanog promoter regions and the mRNA levels of Dnmt3a, Dnmt3b, and Dnmt1 were reduced in rPSCs compared with EpiSCs. However, the miR-290 family was significantly upregulated in rPSCs. After removing SB203580, an inhibitor of the p38 MAPK pathway, the cell colonies changed from domed to flat, with a significant decrease in the expression of pluripotency genes and the miR-290 family. Conversely, overexpression of pri-miR-290 reversed these changes. In addition, Map2k6 was identified as a direct target gene of miR-291b-3p, indicating that the miR-290 family maintains pluripotency and self-renewal in rPSCs by regulating the MAPK signaling pathway

Caridina sinanensis, a new species of stygobiotic atyid shrimp (Decapoda, Caridea, Atyidae) from a karst cave in the Guizhou Province, southwestern China

From a biodiversity survey of a subterranean habitat near Sinan County, Guizhou Province, southwestern China, a new atyid shrimp of the genus Caridina H. Milne Edwards, 1837, C. sinanensis sp. nov. was discovered. The new species can be separated from other congeners based on a combination of characters including depigmentation in body and reduction of eyes, small pigment spot at the centre of the cornea, the shape of rostrum and the endopod of the 1st male pleopod, and the relatively longer appendix interna on the appendix masculina of the 2nd pleopod. Mitochondrial COI and 16S rRNA gene sequences also support the establishment of the new species. Information on the habitat, and the levels of threat are discussed to guide the conservation of C. sinanensis sp. nov