Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation of the histopathological features in fatal ...cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. We aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism.
In this case series, patients with a positive antemortem or post-mortem SARS-CoV-2 result were considered eligible for enrolment. Post-mortem examinations were done on 14 people who died with COVID-19 at the King County Medical Examiner's Office (Seattle, WA, USA) and Snohomish County Medical Examiner's Office (Everett, WA, USA) in negative-pressure isolation suites during February and March, 2020. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry, electron microscopy, and quantitative RT-PCR.
The median age of our cohort was 73·5 years (range 42–84; IQR 67·5–77·25). All patients had clinically significant comorbidities, the most common being hypertension, chronic kidney disease, obstructive sleep apnoea, and metabolic disease including diabetes and obesity. The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi. Coronavirus-like particles were detected in the respiratory system, kidney, and gastrointestinal tract. Lymphocytic myocarditis was observed in one patient with viral RNA detected in the tissue.
The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium. Microthrombi, where observed, were scarce and endotheliitis was not identified. Although other non-pulmonary organs showed susceptibility to infection, their contribution to the pathogenesis of SARS-CoV-2 infection requires further examination.
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Abstract
Motivation
DNA N6-methyladenine (6 mA) has recently been found as an essential epigenetic modification, playing its roles in a variety of cellular processes. The abnormal status of DNA 6 mA ...modification has been reported in cancer and other disease. The annotation of 6 mA marks in genome is the first crucial step to explore the underlying molecular mechanisms including its regulatory roles.
Results
We present a novel online DNA 6 mA site tool, 6 mA-Finder, by incorporating seven sequence-derived information and three physicochemical-based features through recursive feature elimination strategy. Our multiple cross-validations indicate the promising accuracy and robustness of our model. 6 mA-Finder outperforms its peer tools in general and species-specific 6 mA site prediction, suggesting it can provide a useful resource for further experimental investigation of DNA 6 mA modification.
Availability and implementation
https://bioinfo.uth.edu/6mA_Finder.
Supplementary information
Supplementary data are available at Bioinformatics online.
Bone morphogenetic protein (BMP) and Wnt pathways regulate cell proliferation and differentiation, but how these two pathways interact and mediate their nuclear actions in the heart, especially ...during late cardiac development, remains poorly defined. T-cell factor (TCF) and lymphoid enhancer factor (LEF) family transcriptional factors, including Lef1, Tcf7, Tcf7l1, and Tcf7l2, are important nuclear mediators of canonical Wnt/β-catenin signaling throughout cardiac development. We reveal that these TCF/LEF family members direct heart maturation through distinct temporal and spatial control. TCF7 and LEF1 decrease while TCF7L1 and TCF7L2 remain relatively stable during heart development. LEF1 is mainly expressed in mesenchymal cells in valvular regions. TCF7 and TCF7L1 are detected in the nucleus of mesothelial and endothelial cells, but not in cardiomyocytes or mesenchymal cells. Tcf7l2 is the primary TCF/LEF family member in cardiomyocytes and undergoes alternative splicing during heart development. A TCF7L2 intensity gradient opposite to that of β-catenin and cardiomyocyte proliferative activity is present in fetal hearts. Wnt activation by cardiac deletion of APC, a negative Wnt regulator, dramatically increases Cyclin D2 and Bmp4 expression. BMP signal transducing transcription factors, the mothers against decapentaplegic homologs (SMADs) are increasingly phosphorylated upon Wnt activation. LEF1/TCF7 displaces TCF7L2 and cooperates with pSMAD 1/5/8 in the regulatory elements of Cyclin D2 and Bmp4 promoters to promote β-catenin recruitment and transcriptional activation. Finally, we demonstrate that TCF7L2 is a transcriptional suppressor of Cyclin D2 and Bmp 4 in a cardiac cell line by overexpression and knockdown experiments.
This study investigated small microplastic particle (SMP, < 350 μm) contamination in the surface seabed sediment of the inner part of Tokyo Bay. The SMP concentration during the rainy season (May) ...was 100.3 ± 45.8 pieces g−1 dry weight and higher in the inner side of the bay, whereas that of the dry season (January) was 147.6 ± 19.5 pieces g−1 dry weight. There was no seasonal difference. The main plastic types found in the rainy season were polypropylene (PP), polyethylene (PE), and polyamide (PA). In the dry season (January), the concentration of PP decreased while that of PA increased. The mean SMP diameter did not change by site or season. Our results indicate that the seabed sediments in the inner part of Tokyo Bay are contaminated with relatively high concentrations of SMPs. Furthermore, the deposition rate of SMPs in the inner part of the bay was 12.4 mg cm−2 y−1.
•Small microplastic particles (SMPs) were studied in Tokyo Bay's seabed sediments.•SMP concentration during the rainy season was 100.3 ± 45.8 pcs g−1 DW.•The main plastic types were polypropylene, polyethylene, and polyamide.•SMP deposition rate in the inner part of the bay was an estimated 12.4 mg cm−2 y−1.
In eukaryotes, protein phosphorylation is specifically catalyzed by numerous protein kinases (PKs), faithfully orchestrates various biological processes, and reversibly determines cellular dynamics ...and plasticity. Here we report an updated algorithm of Group-based Prediction System (GPS) 5.0 to improve the performance for predicting kinase-specific phosphorylation sites (p-sites). Two novel methods, position weight determination (PWD) and scoring matrix optimization (SMO), were developed. Compared with other existing tools, GPS 5.0 exhibits a highly competitive accuracy. Besides serine/threonine or tyrosine kinases, GPS 5.0 also supports the prediction of dual-specificity kinase-specific p-sites. In the classical module of GPS 5.0, 617 individual predictors were constructed for predicting p-sites of 479 human PKs. To extend the application of GPS 5.0, a species-specific module was implemented to predict kinase-specific p-sites for 44,795 PKs in 161 eukaryotes. The online service and local packages of GPS 5.0 are freely available for academic research at http://gps.biocuckoo.cn.
Post-translational modifications（PTMs） occurring at protein lysine residues,or protein lysine modifications（PLMs）,play critical roles in regulating biological processes.Due to the explosive expansion ...of the amount of PLM substrates and the discovery of novel PLM types,here we greatly updated our previous studies,and presented a much more integrative resource of protein lysine modification database（PLMD）.In PLMD,we totally collected and integrated 284,780 modification events in 53,501 proteins across 176 eukaryotes and prokaryotes for up to 20 types of PLMs,including ubiquitination, acetylation, sumoylation, methylation ,succinylation,malonylation,glutarylation,giycation,formylation,hydroxylation,butyrylation,propionylation,crotonylation,pupylation,neddylation,2-hydroxyisobutyrylation,phosphoglycerylation,carboxylation,lipoylation and biotinylation.Using the data set,a motif-based analysis was performed for each PLM type,and the results demonstrated that different PLM types preferentially recognize distinct sequence motifs for the modifications.Moreover,various PLMs synergistically orchestrate specific cellular biological processes by mutual crosstalks with each other,and we totally found 65,297 PLM events involved in 90 types of PLM co-occurrences on the same lysine residues.Finally,various options were provided for accessing the data,while original references and other annotations were also present for each PLM substrate.Taken together,we anticipated the PLMD database can serve as a useful resource for further researches of PLMs.PLMD 3.0 was implemented in PHP ＋ MySQL and freely available at http：//plmd.biocuckoo.org.
Identification of B-cell epitopes (BCEs) plays an essential role in the development of peptide vaccines and immuno-diagnostic reagents, as well as antibody design and production. In this work, we ...generated a large benchmark dataset comprising 124,879 experimentally supported linear epitope-containing regions in 3567 protein clusters from over 1.3 million B cell assays. Analysis of this curated dataset showed large pathogen diversity covering 176 different families. The accuracy in linear BCE prediction was found to strongly vary with different features, while all sequence-derived and structural features were informative. To search more efficient and interpretive feature representations, a ten-layer deep learning framework for linear BCE prediction, namely NetBCE, was developed. NetBCE achieved high accuracy and robust performance with the average area under the curve (AUC) value of 0.8455 in five-fold cross-validation through automatically learning the informative classification features. NetBCE substantially outperformed the conventional machine learning algorithms and other tools, with more than 22.06% improvement of AUC value compared to other tools using an independent dataset. Through investigating the output of important network modules in NetBCE, epitopes and non-epitopes tended to be presented in distinct regions with efficient feature representation along the network layer hierarchy. The NetBCE is freely available at https://github.com/bsml320/NetBCE.
Various posttranslational modifications (PTMs) participate in nearly all aspects of biological processes by regulating protein functions, and aberrant states of PTMs are frequently implicated in ...human diseases. Therefore, an integral resource of PTM–disease associations (PDAs) would be a great help for both academic research and clinical use. In this work, we reported PTMD, a well-curated database containing PTMs that are associated with human diseases. We manually collected 1950 known PDAs in 749 proteins for 23 types of PTMs and 275 types of diseases from the literature. Database analyses show that phosphorylation has the largest number of disease associations, whereas neurologic diseases have the largest number of PTM associations. We classified all known PDAs into six classes according to the PTM status in diseases and demonstrated that the upregulation and presence of PTM events account for a predominant proportion of disease-associated PTM events. By reconstructing a disease–gene network, we observed that breast cancers have the largest number of associated PTMs and AKT1 has the largest number of PTMs connected to diseases. Finally, the PTMD database was developed with detailed annotations and can be a useful resource for further analyzing the relations between PTMs and human diseases. PTMD is freely accessible at http://ptmd.biocuckoo.org.
Abstract
In mechanical design, we often need to use CNC machining center, in which milling cutters are our indispensable and most common processing tools, milling machines. We often use two-edged ...milling cutters, three-edged milling cutters, four-edged milling cutters. In order to analyze the milling cutter, we need to draw the 3D modeling of the milling cutter in UG, import the 3D model into the workbench to analyze the tool finite meta, analyze a four-edged mill, analyze whether the natural frequency will resonate with the machine tool. Find 10th-order modes, stress analysis of tools, deformation analysis. Topology optimization is carried out to enhance existing effects, reduce costs and improve efficiency.
•A circular arc design is proposed for axial fan to reduce the noise.•The SPE can be increased by 2.1% for the axial fan with R7.•The axial fan with R7 design reduced 2.4 dB over the prototype ...fan.•The strong tonal components is suppressed by reducing the size of the vortex eddy.
The broadband noise of an axial fan is highly related to the vortex shedding at the blade trailing edge and the secondary flow at the blade tip. Herein, a circular arc design is proposed to modify the shape of blade tip and trailing edge together with the features of simple structure and easy manufacture. The experimental and numerical studies were conducted to investigate the effect of circular arc design on the aerodynamic and acoustic characteristics of a small cooling axial fan through the experimental method of the semi-anechoic chamber and LES simulation combined with FW-H. The tested and calculated results show that the SPE of the fan with R7 circular trailing edge can be improved for the entire flow rate range. And the SPC is decreaed as the increasing of arc radius. For the fan with R7, the SPE can be increased by 2.1% and the SPC is decreased by 4.8% at the designed flow rate. In terms of acoustic characteristics, the modified impeller can suppress the broadband noise in the range of 1000 ∼ 3000 Hz, and this suppression can be improved with the growth of flow rate. The R7 design shows the best noise reduction performance, with 2.4 dB reduction over the prototype.
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