MiR-20a regulates the PRKG1 gene by targeting its coding region in pulmonary arterial smooth muscle cells

AbstractChronic hypoxia triggers pulmonary vascular remodeling, which is associated with de-differentiation of pulmonary artery smooth muscle cells (PASMC). Here, we show that miR-20a expression is up-regulated in response to hypoxia in both mouse and human PASMC. We also observed that miR-20a represses the protein kinase, cGMP-dependent, type I (PRKG1) gene and we identified two crucial miR-20a binding sites within the coding region of PRKG1. Functional studies showed that miR-20a promotes the proliferation and migration of human PASMC, whereas it inhibits their differentiation. In summary, we provided a possible mechanism by which hypoxia results in decreased PRKG1 expression and in the phenotypic switching of PASMC

Transcriptomic and Physiological Variations of Three Arabidopsis Ecotypes in Response to Salt Stress.

Salt stress is one of the major abiotic stresses in agriculture worldwide. Analysis of natural genetic variation in Arabidopsis is an effective approach to characterize candidate salt responsive genes. Differences in salt tolerance of three Arabidopsis ecotypes were compared in this study based on their responses to salt treatments at two developmental stages: seed germination and later growth. The Sha ecotype had higher germination rates, longer roots and less accumulation of superoxide radical and hydrogen peroxide than the Ler and Col ecotypes after short term salt treatment. With long term salt treatment, Sha exhibited higher survival rates and lower electrolyte leakage. Transcriptome analysis revealed that many genes involved in cell wall, photosynthesis, and redox were mainly down-regulated by salinity effects, while transposable element genes, microRNA and biotic stress related genes were significantly changed in comparisons of Sha vs. Ler and Sha vs. Col. Several pathways involved in tricarboxylic acid cycle, hormone metabolism and development, and the Gene Ontology terms involved in response to stress and defense response were enriched after salt treatment, and between Sha and other two ecotypes. Collectively, these results suggest that the Sha ecotype is preconditioned to withstand abiotic stress. Further studies about detailed gene function are needed. These comparative transcriptomic and analytical results also provide insight into the complexity of salt stress tolerance mechanisms

Relaxation of the one child policy and trends in caesarean section rates and birth outcomes in China between 2012 and 2016: observational study of nearly seven million health facility births.

OBJECTIVE: To examine how the relaxation of the one child policy and policies to reduce caesarean section rates might have affected trends over time in caesarean section rates and perinatal and pregnancy related mortality in China. DESIGN: Observational study. SETTING: China's National Maternal Near Miss Surveillance System (NMNMSS). PARTICIPANTS: 6 838 582 births at 28 completed weeks or more of gestation or birth weight ≥1000 g in 438 hospitals in the NMNMSS between 2012 and 2016. MAIN OUTCOME MEASURES: Obstetric risk was defined using a modified Robson classification. The main outcome measures were changes in parity and age distributions and relative frequency of each Robson group, crude and adjusted trends over time in caesarean section rates within each risk category (using Poisson regression with a robust variance estimator), and trends in perinatal and pregnancy related mortality over time. RESULTS: Caesarean section rates declined steadily between 2012 and 2016 (crude relative risk 0.91, 95% confidence interval 0.89 to 0.93), reaching an overall hospital based rate of 41.1% in 2016. The relaxation of the one child policy was associated with an increase in the proportion of multiparous births (from 34.1% in 2012 to 46.7% in 2016), and births in women with a uterine scar nearly doubled (from 9.8% to 17.7% of all births). Taking account of these changes, the decline in caesarean sections was amplified over time (adjusted relative risk 0.82, 95% confidence interval 0.81 to 0.84). Caesarean sections declined noticeably in nulliparous women (0.75, 0.73 to 0.77) but also declined in multiparous women without a uterine scar (0.65, 0.62 to 0.77). The decrease in caesarean section rates was most pronounced in hospitals with the highest rates in 2012, consistent with the government's policy of targeting hospitals with the highest rates. Perinatal mortality declined from 10.1 to 7.2 per 1000 births over the same period (0.87, 0.83 to 0.91), and there was no change in pregnancy related mortality over time. CONCLUSIONS: China is the only country that has succeeded in reverting the rising trends in caesarean sections. China's success is remarkable given that the changes in obstetric risk associated with the relaxation of the one child policy would have led to an increase in the need for caesarean sections. China's experience suggests that change is possible when strategies are comprehensive and deal with the system level factors that underpin overuse as well as the various incentives at work during a clinical encounter

Nomogram incorporating ultrasonic markers of endometrial receptivity to determine the embryo-endometrial synchrony after in vitro fertilization

BackgroundA successful pregnancy using in vitro fertilization and embryo transfer (IVF-ET) requires a receptive endometrium, good-quality embryos, and a synchronized embryo-endometrial dialogue. Although embryo quality and endometrial receptivity (ER) have been fully assessed to exclude substandard conditions, the probability of successful ET is relatively low. Currently, embryo-endometrial synchrony is considered to be a possible explanation, because delayed, advanced, or narrowed window of implantation (WOI) may lead to ET failure.ObjectiveThis study aims to establish a nomogram incorporating a series of ultrasonic ER markers on the day before implantation to assess the embryo-endometrial synchrony, which may contribute to the improvement of clinical pregnancy outcomes.MethodsTotally 583 women with 1135 complete IVF cycles were retrospectively analyzed. Among them, 357 women with 698 cycles and 226 women with 437 cycles were assigned to the training and validation cohorts, respectively. Ultrasonic ER markers obtained on the day before implantation were collected for analyses. In the training cohort, the screened correlates of clinical pregnancy failure were utilized to develop a nomogram for determining whether an infertile woman is suitable for the ET next day. This model was validated both in the training and validation cohorts.ResultsSpiral artery (SA) resistance index (RI), vascularisation index (VI), and flow index (FI) were independently associated with the ET failure (all P < 0.05). They were served as the components of the developed nomogram to visualize the likelihood of implantation failure in IVF-ET. This model was validated to present good discrimination and calibration, and obtained clinical net benefits both in the training and validation cohorts.ConclusionWe developed a nomogram that included SA-RI, VI, and FI on the day before implantation. It may assist physicians to identify patients with displaced WOI, thus avoiding meaningless ET prior to implantation

Development of a High-Density Genetic Map Based on Specific Length Amplified Fragment Sequencing and Its Application in Quantitative Trait Loci Analysis for Yield-Related Traits in Cultivated Peanut

High-density genetic maps (HDGMs) are very useful for genomic studies and quantitative trait loci (QTL) mapping. However, the low frequency of DNA polymorphisms in peanut has limited the quantity of available markers and hindered the construction of a HDGM. This study generated a peanut genetic map with the highest number of high-quality SNPs based on specific locus amplified fragment sequencing (SLAF-seq) technology and a newly constructed RIL population (“ZH16” × “sd-H1”). The constructed HDGM included 3,630 SNP markers belonging to 2,636 bins on 20 linkage groups (LGs), and it covers 2,098.14 cM in length, with an average marker distance of 0.58 cM. This HDGM was applied for the following collinear comparison, scaffold anchoring and analysis of genomic characterization including recombination rates and segregation distortion in peanut. For QTL mapping of investigated 14 yield-related traits, a total of 62 QTLs were detected on 12 chromosomes across 3 environments, and the co-localization of QTLs was observed for these traits which were significantly correlated on phenotype. Two stable co-located QTLs for seed- and pod-related traits were significantly identified in the chromosomal end of B06 and B07, respectively. The construction of HDGM and QTL analysis for yield-related traits in this study provide useful information for fine mapping and functional analysis of genes as well as molecular marker-assisted breeding

Thioflavin T fluorescence and NMR spectroscopy 1 suggesting a non-G-quadruplex structure for a 2 sodium binding aptamer embedded in DNAzymes

Recently, a Na+-binding aptamer was reported to be embedded in a few RNA-cleaving DNAzymes including NaA43, Ce13d and NaH1. These DNAzymes require Na+ for activity but show no activity in the presence of K+ or other metal ions. Given that DNA can selectively bind K+ by forming a G-quadruplex structure, this work aims to answer whether this Na+ aptamer also uses a G-quadruplex to bind Na+. The Na+ aptamer embedded in Ce13d consists of multiple GG sequences, which is also a pre-requisite for the formation of G4 structures. To delineate the structural differences and similarities between Ce13d and G-quadruplex in terms of metal binding, thioflavin T (ThT) fluorescence spectroscopy, NMR spectroscopy and CD spectroscopy were used. Through comparative ThT fluorescence spectrometry studies, we deciphered that while a control G-quadruplex DNA exhibited notable fluorescence enhancement up to 5 mM K+ with a Kd of 0.52 mM, the Ce13d DNAzyme fluorescence was negligibly perturbed with similar concentrations of K+. Opposed to this, Ce13d displayed specific remarkable fluorescence decrease with low millimolar concentrations of Na+. NMR experiments at two different pH values suggest that Ce13d adopts a significantly different conformation or equilibrium of conformations in the presence of Na+ versus K+ and has a more stable structure in the presence of Na+. Additionally, absence of characteristic peaks expected for a G-quadruplex structure in 1D 1H NMR suggest that G4 is not responsible for the Na+ binding. This theory is confirmed by absence of characteristic peaks in the CD spectra of this sequence. Therefore, we concluded that the aptamer must be selective for Na+ and binds using a structural element that does not contain G4.Natural Sciences and Engineering Research Council of Canada, Discovery Grant 303454

Putative carboxylesterase gene identification and their expression patterns in Hyphantria cunea (Drury)

The olfactory system of insects is important for behavioral activities as it recognizes internal and external volatile stimuli in the environment. Insect odorant degrading enzymes (ODEs), including antennal-specific carboxylesterases (CXEs), are known to degrade redundant odorant molecules or to hydrolyze important olfactory sex pheromone components and plant volatiles. Compared to many well-studied Type-I sex pheromone-producing lepidopteran species, the molecular mechanisms of the olfactory system of Type-II sex pheromone-producing Hyphantria cunea (Drury) remain poorly understood. In the current study, we first identified a total of ten CXE genes based on our previous H. unea antennal transcriptomic data. We constructed a phylogenetic tree to evaluate the relationship of HcunCXEs with other insects\u27 CXEs, and used quantitative PCR to investigate the gene expression of H. cunea CXEs (HcunCXEs). Our results indicate that HcunCXEs are highly expressed in antennae, legs and wings, suggesting a potential function in degrading sex pheromone components, host plant volatiles, and other xenobiotics. This study not only provides a theoretical basis for subsequent olfactory mechanism studies on H. cunea, but also offers some new insights into functions and evolutionary characteristics of CXEs in lepidopteran insects. From a practical point of view, these HcunCXEs might represent meaningful targets for developing behavioral interference control strategies against H. cunea

Yersinia pestis Interacts With SIGNR1 (CD209b) for Promoting Host Dissemination and Infection

Yersinia pestis, a Gram-negative bacterium and the etiologic agent of plague, has evolved from Yersinia pseudotuberculosis, a cause of a mild enteric disease. However, the molecular and biological mechanisms of how Y pseudotuberculosis evolved to such a remarkably virulent pathogen, Y pestis, are not clear. The ability to initiate a rapid bacterial dissemination is a characteristic hallmark of Y pestis infection. A distinguishing characteristic between the two Yersinia species is that Y pseudotuberculosis strains possess an O-antigen of lipopolysaccharide (LPS) while Y pestis has lost the O-antigen during evolution and therefore exposes its core LPS. In this study, we showed that Y pestis utilizes its core LPS to interact with SIGNR1 (CD209b), a C-type lectin receptor on antigen presenting cells (APCs), leading to bacterial dissemination to lymph nodes, spleen and liver, and the initiation of a systemic infection. We therefore propose that the loss of O-antigen represents a critical step in the evolution of Y pseudotuberculosis into Y pestis in terms of hijacking APCs, promoting bacterial dissemination and causing the plague.Peer reviewe

Metabolomics combined with transcriptomics analyses of mechanism regulating testa pigmentation in peanut

Peanut testa (seed coat) contains large amounts of flavonoids that significantly influence seed color, taste, and nutritional qualities. There are various colors of peanut testa, however, their precise flavonoid components and regulatory mechanism of pigmentation remain unclear. In this study, a total of 133 flavonoids were identified and absolutely quantified in the seed coat of four peanut cultivars with different testa color using a widely targeted metabolomic approach. Black peanut skin had more types and substantial higher levels of cyanidin-based anthocyanins, which possibly contribute to its testa coloration. Procyanidins and flavan-3-ols were the major co-pigmented flavonoids in the red, spot and black peanuts, while flavanols were the most abundant constitutes in white cultivar. Although the concentrations as well as composition characteristics varied, the content ratios of procyanidins to flavan-3-ols were similar in all samples except for white peanut. Furthermore, MYB-like transcription factors, anthocyanidin reductases (ANR), and UDP-glycosyltransferases (UGT) were found to be candidate genes involved in testa pigmentation via RNA-seq and weighted gene co-expression network analysis. It is proposed that UGTs and ANR compete for the substrate cyanidin and the prevalence of UGTs activities over ANR one will determine the color pattern of peanut testa. Our results provide a comprehensive report examining the absolute abundance of flavonoid profiles in peanut seed coat, and the finding are expected to be useful for further understanding of regulation mechanisms of seed coat pigmentation in peanut and other crops