ABSTRACT
Innovations in genomics have enabled the development of low‐cost, high‐resolution, single nucleotide polymorphism (SNP) genotyping arrays that accelerate breeding progress and support basic ...research in crop science. Here, we developed and validated the SoySNP618K array (618,888 SNPs) for the important crop soybean. The SNPs were selected from whole‐genome resequencing data containing 2,214 diverse soybean accessions; 29.34% of the SNPs mapped to genic regions representing 86.85% of the 56,044 annotated high‐confidence genes. Identity‐by‐state analyses of 318 soybeans revealed 17 redundant accessions, highlighting the potential of the SoySNP618K array in supporting gene bank management. The patterns of population stratification and genomic regions enriched through domestication were highly consistent with previous findings based on resequencing data, suggesting that the ascertainment bias in the SoySNP618K array was largely compensated for. Genome‐wide association mapping in combination with reported quantitative trait loci enabled fine‐mapping of genes known to influence flowering time, E2 and GmPRR3b, and of a new candidate gene, GmVIP5. Moreover, genomic prediction of flowering and maturity time in 502 recombinant inbred lines was highly accurate (>0.65). Thus, the SoySNP618K array is a valuable genomic tool that can be used to address many questions in applied breeding, germplasm management, and basic crop research.
To accelerate breeding progress and support basic research in soybean, the customized SoySNP618K array contains 618,888 SNPs selected from > 2,000 diverse, re‐sequenced soybean genomes. SoySNP618K is a valuable genomic tool to address questions in applied breeding, germplasm management, and basic research.
An effective synthetic method for 1,3,5-trisubstituted pyrazoles via 1,3-dipolar cycloaddition reaction has been developed. This reaction could smoothly proceed between ninhydrin-derived ...Morita–Baylis–Hillman carbonates and nitrilimines to provide a wide scope of differently substituted pyrazoles in high yields (up to 95%). In addition, the reaction mechanism was also proposed to explain its regioselectivity.
Abstract
Background
A significant proportion of women with preeclampsia (PE) exhibit persistent postpartum hypertension (PHTN) at 3 months postpartum associated with cardiovascular morbidity. This ...study aimed to screen patients with PE to identify the high-risk population with persistent PHTN.
Methods
This retrospective cohort study enrolled 1,000 PE patients with complete parturient and postpartum blood pressure (BP) profiles at 3 months postpartum. The enrolled patients exhibited new-onset hypertension after 20 weeks of pregnancy, while those with PE superimposed upon chronic hypertension were excluded. Latent class cluster analysis (LCCA), a method of unsupervised learning in machine learning, was performed to ascertain maternal exposure clusters from eight variables and 35 subordinate risk factors. Logistic regression was applied to calculate odds ratios (OR) indicating the association between clusters and PHTN.
Results
The 1,000 participants were classified into three exposure clusters (subpopulations with similar characteristics) according to persistent PHTN development: high-risk cluster (31.2%), medium-risk cluster (36.8%), and low-risk cluster (32.0%). Among the 1,000 PE patients, a total of 134 (13.4%) were diagnosed with persistent PHTN, while the percentages of persistent PHTN were24.68%, 10.05%, and 6.25% in the high-, medium-, and low-risk clusters, respectively. Persistent PHTN in the high-risk cluster was nearly five times higher (OR, 4.915; 95% confidence interval (CI), 2.92–8.27) and three times (OR, 2.931; 95% CI, 1.91–4.49) than in the low- and medium-risk clusters, respectively. Persistent PHTN did not differ between the medium- and low-risk clusters. Subjects in the high-risk cluster were older and showed higher BP, poorer prenatal organ function, more adverse pregnancy events, and greater medication requirement than the other two groups.
Conclusion
Patients with PE can be classified into high-, medium-, and low-risk clusters according to persistent PHTN severity; each cluster has cognizable clinical features. This study’s findings stress the importance of controlling persistent PHTN to prevent future cardiovascular disease.
The neutrophil is the major phagocyte and the final effector cell of the innate immunity, with a primary role in the clearance of extracellular pathogens. Using the broad array of cytokines, ...extracellular traps, and effector molecules as the humoral arm, neutrophils play a crucial role in the host defense against pathogen infections. On the other hand, the pathogen has the capacity to overcome neutrophil-mediated host defense to establish infection causing human disease. Pathogens, such as S. aureus, have the potential to thwart neutrophil chemotaxis and phagocytosis and thereby succeed in evading killing by neutrophils. Furthermore, S. aureus surviving within neutrophils promotes neutrophil cytolysis, resulting in the release of host-derived molecules that promote local inflammation. Here, we provide a detailed overview of the mechanisms by which neutrophils kill the extracellular pathogens and how pathogens evade neutrophils degradation. This review will provide insights that might be useful for the development of novel therapies against infections caused by antibiotic resistant pathogens.
Due to continuous spread of coronavirus disease 2019 (COVID-19) worldwide, long-term effective prevention and control measures should be adopted for public transport facilities, as they are ...increasing in popularity and serve as the principal modes for travel of many people. The human infection risk could be extremely high due to length of exposure time window, transmission routes and structural characteristics during travel or work. This can result in the rapid spread of the infection. Based on the transmission characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the nature of public transport sites, we identified comprehensive countermeasures toward the prevention and control of COVID-19, including the strengthening of personnel management, personal protection, environmental cleaning and disinfection, and health education. Multi-pronged strategies can enhance safety of public transportation. The prevention and control of the disease during the use of public transportation will be particularly important when all countries in the world resume production. The aim of this study is to introduce experience of the prevention and control measures for public transportation in China to promote the global response to COVID-19.
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•Comprehensive countermeasures have been identified, including: strengthening personnel management, personal protection, environmental cleaning and disinfection, health education.•Multi-pronged strategies can enhance safety during public transportation.•Experience of the prevention and control measures for public transportation in China have been reviewed.
Temporal modeling is key for action recognition in videos. It normally considers both short-range motions and long-range aggregations. In this paper, we propose a Temporal Excitation and Aggregation ...(TEA) block, including a motion excitation (ME) module and a multiple temporal aggregation (MTA) module, specifically designed to capture both short- and long-range temporal evolution. In particular, for short-range motion modeling, the ME module calculates the feature-level temporal differences from spatiotemporal features. It then utilizes the differences to excite the motion-sensitive channels of the features. The long-range temporal aggregations in previous works are typically achieved by stacking a large number of local temporal convolutions. Each convolution processes a local temporal window at a time. In contrast, the MTA module proposes to deform the local convolution to a group of sub-convolutions, forming a hierarchical residual architecture. Without introducing additional parameters, the features will be processed with a series of sub-convolutions, and each frame could complete multiple temporal aggregations with neighborhoods. The final equivalent receptive field of temporal dimension is accordingly enlarged, which is capable of modeling the long-range temporal relationship over distant frames. The two components of the TEA block are complementary in temporal modeling. Finally, our approach achieves impressive results at low FLOPs on several action recognition benchmarks, such as Kinetics, Something-Something, HMDB51, and UCF101, which confirms its effectiveness and efficiency.
The importance of intratumoral heterogeneity has been highlighted by the identification and characterization of cancer stem cells (CSCs). Based on the differential responsiveness to a Sox2 reporter, ...SRR2, we had found a novel dichotomy in esophageal squamous cell carcinoma (ESCC) cells, with reporter‐responsive (RR) cells showing more CSC‐like features than reporter‐unresponsive (RU) cells. Specifically, RR cells exhibited significantly higher tumorsphere formation capacity, proportions of CD44High cells, chemoresistance to cisplatin, and tumorigenic potential in vivo. H2O2, a potent inducer of oxidative stress and reactive oxygen species, was found to induce a conversion from RU to RR cells; importantly, converted RR cells acquired CSC‐like features. The PI3K/AKT/c‐MYC signalling axis is important in this context, since pharmacologic blockade of PI3K‐AKT or siRNA knockdown of c‐MYC effectively inhibited the RR phenotype and its associated CSC‐like features, as well as the H2O2‐induced RU/RR conversion. In a cohort of 188 ESCC patient samples, we found a significant correlation between strong c‐MYC expression and a short overall survival (p = .009). In conclusion, we have described a novel intratumoral heterogeneity in ESCC. The identification of the PI3K/AKT/c‐MYC axis as a driver of CSC‐like features carries therapeutic implications. Stem Cells 2016;34:2040–2051
Oxidative stress induced by H2O2 promotes RU/RR conversion and the acquisition of CSC‐like properties. (A) Reactive oxygen species (ROS) induced by H2O2 (500 μM for 24 hours) was measured by flow cytometry. (B) H2O2‐induced RU/RR conversion in KYSE150‐RU cells, as indicated by the increase of GFP‐positive cells and luciferase activity. Representative flow cytometry data at Day 4 was shown in the left panel. Note that cells grown at a 100% confluence were used in this assay. (C) Flow cytometry was performed to measure GFP expression and ROS levels to determine the effect of N‐Acetyl‐Cysteine (NAC), an antioxidant agent, on oxidative stress‐induced RU/RR conversion. Median ROS values are indicated by bidirectional arrows. (D) Tumorsphere formation assay was used to evaluate H2O2‐induced CSC‐like properties. The RU cells used in this assay were treated with different concentrations of H2O2 for four cycles, each cycle includes a 24 hours H2O2 treatment and a recovery phase for 3 days. Images were taken at ×100 magnification. (E) RU cells were treated with 300 μM H2O2 for 48 hours or left untreated, and CD44 expression was measured using flow cytometry. The size of the CD44High cell population was compared in untreated RU cells and the converted RR cells (Conv. RR). All data are presented as mean ± SD, *p < .05, **p < .01, ***p < .001, Student's t test.
Agents designed to block or alter cytokinesis can kill or stop proliferation of cancer cells. We aimed to identify cytokinesis-related proteins that are overexpressed in hepatocellular carcinoma ...(HCC) cells and might be targeted to slow liver tumor growth.
Using the Oncomine database, we compared the gene expression patterns in 16 cancer microarray datasets and assessed gene enrichment sets using gene ontology. We performed immunohistochemical analysis of an HCC tissue microarray and identified changes in protein levels that are associated with patient survival times. Candidate genes were overexpressed or knocked down with small hairpin RNAs in SMMC7721, MHCC97H, or HCCLM3 cell lines; we analyzed their proliferation, viability, and clone-formation ability and their growth as subcutaneous or orthotopic xenograft tumors in mice. We performed microarray analyses to identify alterations in signaling pathways and immunoblot and immunofluorescence assays to detect and localize proteins in tissues. Yeast 2-hybrid screens and mass spectrometry combined with co-immunoprecipitation experiments were used to identify binding proteins. Protein interactions were validated with co-immunoprecipitation and proximity ligation assays. Chromatin immunoprecipitation, promoter luciferase activity, and quantitative real-time polymerase chain reaction analyses were used to identify factors that regulate transcription of specific genes.
The genes that were most frequently overexpressed in different types of cancer cells were involved in cell division processes. We identified 3 cytokinesis-regulatory proteins among the 10 genes most frequently overexpressed by all cancer cell types. Rac GTPase activating protein 1 (RACGAP1) was the cytokinesis-regulatory protein that was most highly overexpressed in multiple cancers. Increased expression of RACGAP1 in tumor tissues was associated with shorter survival times of patients with cancer. Knockdown of RACGAP1 in HCC cells induced cytokinesis failure and cell apoptosis. In microarray analyses, we found knockdown of RACGAP1 in SMMC7721 cells to reduce expression of genes regulated by yes-associated protein (YAP) and WW domain containing transcription regulator 1 (WWTR1 or TAZ). RACGAP1 reduced activation of the Hippo pathway in HCC cells by increasing activity of RhoA and polymerization of filamentous actin. Knockdown of YAP reduced phosphorylation of RACGAP1 and redistribution at the anaphase central spindle. We found transcription of the translocated promoter region, nuclear basket protein (TPR) to be regulated by YAP and coordinately expressed with RACGAP1 to promote proliferation of HCC cells. TPR redistributed upon nuclear envelope breakdown and formed complexes with RACGAP1 during mitosis. Knockdown of TPR in HCC cells reduced phosphorylation of RACGAP1 by aurora kinase B and impaired their redistribution at the central spindle during cytokinesis. STAT3 activated transcription of RACGAP in HCC cells.
In an analysis of gene expression patterns of multiple tumor types, we found RACGAP1 to be frequently overexpressed, which is associated with shorter survival times of patients. RACGAP1 promotes proliferation of HCC cells by reducing activation of the Hippo and YAP pathways and promoting cytokinesis in coordination with TPR.
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Effects of the heavy metal copper (Cu), the metalloid arsenic (As), and the antibiotic oxytetracycline (OTC) on bacterial community structure and diversity during cow and pig manure composting were ...investigated. Eight treatments were applied, four to each manure type, namely cow manure with: (1) no additives (control), (2) addition of heavy metal and metalloid, (3) addition of OTC and (4) addition of OTC with heavy metal and metalloid; and pig manure with: (5) no additives (control), (6) addition of heavy metal and metalloid, (7) addition of OTC and (8) addition of OTC with heavy metal and metalloid. After 35 days of composting, according to the alpha diversity indices, the combination treatment (OTC with heavy metal and metalloid) in pig manure was less harmful to microbial diversity than the control or heavy metal and metalloid treatments. In cow manure, the treatment with heavy metal and metalloid was the most harmful to the microbial community, followed by the combination and OTC treatments. The OTC and combination treatments had negative effects on the relative abundance of microbes in cow manure composts. The dominant phyla in both manure composts included Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. The microbial diversity relative abundance transformation was dependent on the composting time. Redundancy analysis (RDA) revealed that environmental parameters had the most influence on the bacterial communities. In conclusion, the composting process is the most sustainable technology for reducing heavy metal and metalloid impacts and antibiotic contamination in cow and pig manure. The physicochemical property variations in the manures had a significant effect on the microbial community during the composting process. This study provides an improved understanding of bacterial community composition and its changes during the composting process.
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