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Model-guided development of an evolutionarily stable yeast chassis.

Mol Syst Biol 2021 Jul;17(7):e10253

Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.

First-principle metabolic modelling holds potential for designing microbial chassis that are resilient against phenotype reversal due to adaptive mutations. Yet, the theory of model-based chassis design has rarely been put to rigorous experimental test. Here, we report the development of Saccharomyces cerevisiae chassis strains for dicarboxylic acid production using genome-scale metabolic modelling. Read More

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Genome-wide analysis of butterfly bush (Buddleja alternifolia) in three uplands provides insights into biogeography, demography and speciation.

New Phytol 2021 Jul 22. Epub 2021 Jul 22.

Yunnan Key Laboratory for Integrative Conservation of Plant Species with Extremely Small Populations, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, P.R. China.

Understanding processes that generate and maintain large disjunctions within plant species can provide valuable insights into plant diversity and speciation. The butterfly bush Buddleja alternifolia has an unusual disjunct distribution, occurring in the Himalaya, Hengduan Mountains (HDM) and the Loess Plateau (LP) in China. We generated a high-quality, chromosome-level genome assembly of B. Read More

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A non-canonical Δ9-desaturase synthesizing palmitoleic acid identified in the thraustochytrid Aurantiochytrium sp. T66.

Appl Microbiol Biotechnol 2021 Jul 22. Epub 2021 Jul 22.

Department of Biotechnology and Food Science, NTNU Norwegian University of Science and Technology, Trondheim, Norway.

Thraustochytrids are oleaginous marine eukaryotic microbes currently used to produce the essential omega-3 fatty acid docosahexaenoic acid (DHA, C22:6 n-3). To improve the production of this essential fatty acid by strain engineering, it is important to deeply understand how thraustochytrids synthesize fatty acids. While DHA is synthesized by a dedicated enzyme complex, other fatty acids are probably synthesized by the fatty acid synthase, followed by desaturases and elongases. Read More

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An Immune-Gene-Based Classifier Predicts Prognosis in Patients With Cervical Squamous Cell Carcinoma.

Front Mol Biosci 2021 5;8:679474. Epub 2021 Jul 5.

Department of Gynecology and Obstetrics, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Immunity plays a vital role in the human papilloma virus (HPV) persistent infection, and closely associates with occurrence and development of cervical squamous cell carcinoma (CSCC). Herein, we performed an integrated bioinformatics analysis to establish an immune-gene signature and immune-associated nomogram for predicting prognosis of CSCC patients. The list of immunity-associated genes was retrieved from ImmPort database. Read More

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Evidence of gene-gene interaction in Hidradenitis suppurativa - A nationwide register study of Danish twins.

Br J Dermatol 2021 Jul 21. Epub 2021 Jul 21.

Danish Twin Registry, Department of Epidemiology, Biostatistics and Biodemography, University of southern Denmark, Odense, Denmark.

Background: Hidradenitis suppurativa (HS) is a recurrent inflammatory skin disease that, apart from rare causative loss-of-function mutations, has a widely unknown genetic aetiology. Our objective was to estimate the relative importance of genetic and environmental factors underlying HS susceptibility.

Methods: Through the Danish Twin Registry and the Danish National Patient Registry we joined information on zygosity with that of HS status. Read More

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Deciphering the PTM codes of the tumor suppressor p53.

J Mol Cell Biol 2021 Jul 21. Epub 2021 Jul 21.

State Key Laboratory of Medical Molecular Biology & Department of Medical Genetics, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.

The genome guardian p53 functions as a transcription factor that senses numerous cellular stresses and orchestrates the corresponding transcriptional events involved in determining various cellular outcomes, including cell cycle arrest, apoptosis, senescence, DNA repair, and metabolic regulation. In response to diverse stresses, p53 undergoes multiple posttranslational modifications (PTMs) that coordinate with intimate interdependencies to precisely modulate its diverse properties in given biological contexts. Notably, PTMs can recruit 'reader' proteins that exclusively recognize specific modifications and facilitate the functional readout of p53. Read More

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A Simple RT-PCR Melting temperature Assay to Rapidly Screen for Widely Circulating SARS-CoV-2 Variants.

J Clin Microbiol 2021 Jul 21:JCM0084521. Epub 2021 Jul 21.

Public Health Research Institute; Center for Emerging Pathogens, Rutgers New Jersey Medical School; Institute of Genomic Medicine, Rutgers New Jersey Medical School, Newark, NJ.

. The increased transmission of SARS-CoV-2 variants of concern (VOC) which originated in the United Kingdom (B.1. Read More

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Evaluation of model refinement in CASP14.

Proteins 2021 Jul 20. Epub 2021 Jul 20.

Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.

We report here an assessment of the model refinement category of the 14th round of Critical Assessment of Structure Prediction (CASP14). As before, predictors submitted up to five ranked refinements, along with associated residue-level error estimates, for targets that had a wide range of starting quality. The ability of groups to accurately rank their submissions and to predict coordinate error varied widely. Read More

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Risk Score Based on Two microRNAs as a Prognostic Marker of Hepatocellular Carcinoma and the Corresponding Competitive Endogenous RNA Network.

Int J Gen Med 2021 13;14:3377-3385. Epub 2021 Jul 13.

Department of Transplantation, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People's Republic of China.

Purpose: Liver transplantation (LT) currently yields the best outcomes for hepatocellular carcinoma (HCC). However, tumor recurrence still occurs in some patients. Identifying markers that predict HCC recurrence after LT is an unmet medical need. Read More

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Genetic analysis of egg production traits in turkeys (Meleagris gallopavo) using a single-step genomic random regression model.

Genet Sel Evol 2021 Jul 20;53(1):61. Epub 2021 Jul 20.

Centre for Genetic Improvement of Livestock, Department of Animal Biosciences, University of Guelph, Guelph, N1G 2W1, Canada.

Background: Egg production traits are economically important in poultry breeding programs. Previous studies have shown that incorporating genomic data can increase the accuracy of genetic prediction of egg production. Our objective was to estimate the genetic and phenotypic parameters of such traits and compare the prediction accuracy of pedigree-based random regression best linear unbiased prediction (RR-PBLUP) and genomic single-step random regression BLUP (RR-ssGBLUP). Read More

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Characterization of genomic alterations in Chinese colorectal cancer patients with liver metastases.

J Transl Med 2021 Jul 19;19(1):313. Epub 2021 Jul 19.

Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Haidian District, Beijing, China.

Background: The exploration of genomic alterations in Chinese colorectal liver metastasis (CRLM) is limited, and corresponding genetic biomarkers for patient's perioperative management are still lacking. This study aims to understand genome diversification and complexity that developed in CRLM.

Methods: A custom-designed IDT capture panel including 620 genes was performed in the Chinese CRLM cohort, which included 396 tumor samples from metastatic liver lesions together with 133 available paired primary tumors. Read More

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Upregulation of Stress-Induced Protein Kinase CK1 Delta is associated with a Poor Prognosis for patients with Hepatocellular Carcinoma.

Genet Test Mol Biomarkers 2021 Jul;25(7):504-514

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.

This study was designed to analyze the expression of CSNK1D in hepatocellular carcinoma (HCC) and investigate the relationship between the expression of CSNK1D and the prognosis of HCC patients. The CSNK1D and alpha-fetoprotein (AFP) expression levels in patients with HCC and their corresponding clinical data were downloaded from The Cancer Genome Atlas (TCGA) and sorted with a Perl program. CSNK1D and AFP expression differences in liver tissue and liver cancer were compared and analyzed, based on the online database human cancer metastasis database, the relationships between the expression levels of CSNK1D and AFP and the proliferation and metastases of HCC were explored. Read More

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Dissecting locus regulation in .

J Bacteriol 2021 Jul 19:JB0023721. Epub 2021 Jul 19.

Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY, 12208, USA.

The pH 6 antigen of is a virulence factor that is expressed in response to high temperature (37°C) and low pH (6.0). Previous studies have implicated the PsaE and PsaF regulators in the temperature- and pH-dependent regulation of . Read More

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Occurrence of a novel strain of Moroccan watermelon mosaic virus infecting pumpkins in Kenya.

Plant Dis 2021 Jul 19. Epub 2021 Jul 19.

International Livestock Research Institute, 54661, Nairobi, Nairobi, Kenya;

The potyvirus Moroccan watermelon mosaic virus (MWMV) naturally infects and severely threatens production of cucurbits and papaya. In this study, we identified and characterized MWMV isolated from pumpkin (Cucurbita moschata) intercropped with MWMV-infected papaya plants through next generation and Sanger sequencing approaches. Complete MWMV genome sequences were obtained from two pumpkin samples through NGS and validated using Sanger sequencing. Read More

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Identification of genes associated with sudden cardiac death: a network- and pathway-based approach.

J Thorac Dis 2021 Jun;13(6):3610-3627

Key Laboratory of Neuroregeneration of Jiangsu and the Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.

Background: Sudden cardiac death (SCD) accounts for a large proportion of the total deaths across different age groups. Although numerous candidate genes related to SCD have been identified by genetic association studies and genome wide association studies (GWAS), the molecular mechanisms underlying SCD are still unclear, and the biological functions and interactions of these genes remain obscure. To clarify this issue, we performed a comprehensive and systematic analysis of SCD-related genes by a network and pathway-based approach. Read More

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Discovery and Characterization of a Novel Bipartite Botrexvirus From the Phytopathogenic Fungus .

Front Microbiol 2021 1;12:696125. Epub 2021 Jul 1.

College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, China.

In this study, we describe a novel positive, single-stranded (+ss) RNA mycovirus, named botrexvirus 1 (BdBV1), from a phytopathogenic fungus showing abnormal morphology and attenuated virulence. BdBV1 is phylogenetically related to Botrytis virus X (BotVX) and is the second potential member of the proposed genus in the family . However, it differs from the monopartite BotVX in that BdBV1 possesses a bipartite genome comprised of two ssRNA segments (RNA1 and RNA2 with lengths of 5,035 and 1,063 nt, respectively). Read More

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AmpliCoV: Rapid Whole-Genome Sequencing Using Multiplex PCR Amplification and Real-Time Oxford Nanopore MinION Sequencing Enables Rapid Variant Identification of SARS-CoV-2.

Front Microbiol 2021 1;12:651151. Epub 2021 Jul 1.

Highly Pathogenic Viruses, Centre for Biological Threats and Special Pathogens, WHO Reference Laboratory for SARS-CoV-2 and WHO Collaborating Centre for Emerging Infections and Biological Threats, Robert Koch Institute, Berlin, Germany.

Since the emergence of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in December 2019, the scientific community has been sharing data on epidemiology, diagnostic methods, and whole-genomic sequences almost in real time. The latter have already facilitated phylogenetic analyses, transmission chain tracking, protein modeling, the identification of possible therapeutic targets, timely risk assessment, and identification of novel variants. We have established and evaluated an amplification-based approach for whole-genome sequencing of SARS-CoV-2. Read More

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RMI2 is a prognostic biomarker and promotes tumor growth in hepatocellular carcinoma.

Clin Exp Med 2021 Jul 18. Epub 2021 Jul 18.

Cancer Center, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China.

Genomic instability is a hallmark of all cancers. RMI2 is a crucial component of the BLM-TopoIIIa-RMI1-RMI2 complex that maintains genome stability. It has been shown to accelerate tumor progression in lung cancer, cervical cancer, and prostate cancer. Read More

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Evolutionary history of Hemerocallis in Japan inferred from chloroplast and nuclear phylogenies and levels of interspecific gene flow.

Mol Phylogenet Evol 2021 Jul 14:107264. Epub 2021 Jul 14.

Department of Biology, Faculty of Science, Kyushu University, 744 Motooka, Fukuoka, 819-0395, Japan.

The perennial herb genus Hemerocallis (Asphodelaceae) shows four flowering types: diurnal half-day, diurnal one-day, nocturnal half-day, and nocturnal one-day flowering. These flowering types are corresponding to their main pollinators, and probably act as a primary mechanism of reproductive isolation. To examine how the four flowering types diverged, we reconstructed the phylogeny of the Japanese species of Hemerocallis using 1,615 loci of nuclear genome-wide SNPs and 2,078 bp sequences of four cpDNA regions. Read More

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Genomic insight into the divergence and adaptive potential of a forgotten landrace G. hirsutum L. purpurascens.

J Genet Genomics 2021 May 31. Epub 2021 May 31.

State Key Laboratory of Cotton Biology, Institute of Cotton Research, Chinese Academy of Agricultural Sciences, Anyang, Henan 455000, China; Research Base, State Key Laboratory of Cotton Biology, Zhengzhou University, Zhengzhou, Henan 450001, China. Electronic address:

Wild progenitors are an excellent source for strengthening the genetic basis and accumulation of desirable variation lost because of directional selection and adaptation in modern cultivars. Here, we re-evaluate a landrace of Gossypium hirsutum, formerly known as Gossypium purpurascens. Our study seeks to understand the genomic structure, variation, and breeding potential of this landrace, providing potential insights into the biogeographic history and genomic changes likely associated with domestication. Read More

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Single-cell and spatial analyses of cancer cells: toward elucidating the molecular mechanisms of clonal evolution and drug resistance acquisition.

Inflamm Regen 2021 Jul 16;41(1):22. Epub 2021 Jul 16.

Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa-shi, Chiba, 277-8561, Japan.

Even within a single type of cancer, cells of various types exist and play interrelated roles. Each of the individual cells resides in a distinct microenvironment and behaves differently. Such heterogeneity is the most cumbersome nature of cancers, which is occasionally uncountable when effective prevention or total elimination of cancers is attempted. Read More

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Simple, fast and efficient iTOP-mediated delivery of CRISPR/Cas9 RNP in difficult-to-transduce human cells including primary T cells.

J Biotechnol 2021 Jul 13;338:71-80. Epub 2021 Jul 13.

NTrans Technologies BV, Heidelberglaan 7, 3584 CS Utrecht, the Netherlands. Electronic address:

The advent of the CRISPR/Cas9 system has transformed the field of human genome engineering and has created new perspectives in the development of innovative cell therapies. However, the absence of a simple, fast and efficient delivery method of CRISPR/Cas9 into primary human cells has been limiting the progress of CRISPR/Cas9-based therapies. Here, we describe an optimized protocol for iTOP-mediated delivery of CRISPR/Cas9 in various human cells, including primary T cells, induced pluripotent stem cells (hiPSCs), Jurkat, ARPE-19 and HEK293 cells. Read More

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Prioritizing and characterizing functionally relevant genes across human tissues.

PLoS Comput Biol 2021 Jul 16;17(7):e1009194. Epub 2021 Jul 16.

Cancer Data Science Lab, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

Knowledge of genes that are critical to a tissue's function remains difficult to ascertain and presents a major bottleneck toward a mechanistic understanding of genotype-phenotype links. Here, we present the first machine learning model-FUGUE-combining transcriptional and network features, to predict tissue-relevant genes across 30 human tissues. FUGUE achieves an average cross-validation auROC of 0. Read More

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Species with Haploid or Doubled Haploid Protocols.

Methods Mol Biol 2021 ;2287:41-103

Cell Biology Group - COMAV Institute, Universitat Politècnica de València, Valencia, Spain.

In this chapter, we present a list of species (and few interspecific hybrids) where haploids and/or doubled haploids have been published, including the method by which they were obtained and the corresponding references. This list is an update of the compilation work of Maluszynski et al. published in 2003, including new species for which protocols were not available at that time, and also novel methodologies developed during these years. Read More

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January 2021

Construction and validation of a prognostic signature using CNV-driven genes for hepatocellular carcinoma.

Ann Transl Med 2021 May;9(9):765

Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.

Background: Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related deaths worldwide. Copy number variations (CNVs) affect the expression of genes and play critical roles in carcinogenesis. We aimed to identify specific CNV-driven genes and establish a prognostic model for HCC. Read More

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Stabilization of the SARS-CoV-2 Spike Receptor-Binding Domain Using Deep Mutational Scanning and Structure-Based Design.

Front Immunol 2021 29;12:710263. Epub 2021 Jun 29.

Institute for Protein Design, University of Washington, Seattle, WA, United States.

The unprecedented global demand for SARS-CoV-2 vaccines has demonstrated the need for highly effective vaccine candidates that are thermostable and amenable to large-scale manufacturing. Nanoparticle immunogens presenting the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein (S) in repetitive arrays are being advanced as second-generation vaccine candidates, as they feature robust manufacturing characteristics and have shown promising immunogenicity in preclinical models. Here, we used previously reported deep mutational scanning (DMS) data to guide the design of stabilized variants of the RBD. Read More

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Tissue-specific expression atlas of murine mitochondrial tRNAs.

J Biol Chem 2021 Jul 12:100960. Epub 2021 Jul 12.

Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine and National Clinical Research Center for Child Health, Hangzhou, Zhejiang 310058, China; Institute of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Center for Mitochondrial Genetics, Key Lab of Reproductive Genetics, Ministry of Education of PRC, Zhejiang University, Hangzhou, Zhejiang 310058, China; Division of Mitochondrial Biomedicine, Zhejiang University-University of Toronto Joint Institute of Genetics and Genome Medicine, Hangzhou, Zhejiang 310058, China. Electronic address:

Mammalian mitochondrial tRNA (mt-tRNA) plays a central role in the synthesis of the 13 subunits of the oxidative phosphorylation complex system (OXPHOS). However, many aspects of the context-dependent expression of mt-tRNAs in mammals remains unknown. To investigate the tissue-specific effects of mt-tRNAs, we performed a comprehensive analysis of mitochondrial tRNA expression across 5 mice tissues (brain, heart, liver, skeletal muscle, and kidney) using Northern blot analysis. Read More

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Genome-wide identification and expression analysis of the growth regulating factor (GRF) family in Jatropha curcas.

PLoS One 2021 15;16(7):e0254711. Epub 2021 Jul 15.

College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou, China.

GRF genes have been confirmed to have important regulatory functions in plant growth, development and response to abiotic stress. Although the genome of Jatropha curcas is sequenced, knowledge about the identification of the species' GRF genes and their expression patterns is still lacking. In this study, we characterized the 10 JcGRF genes. Read More

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A genome-wide analysis of the molecular alterations occurring in the adenomatous and carcinomatous components of the same tumor based on the adenoma-carcinoma sequence.

Pathol Int 2021 Jul 15. Epub 2021 Jul 15.

Department of Molecular Biology, School of Medicine, Sapporo Medical University, Cyuuouku, Sapporo, Japan.

Identification of molecular alterations occurring in the adenomatous and carcinomatous components within the same tumor would greatly enhance understanding of the neoplastic progression of colorectal cancer. We examined somatic copy number alterations (SCNAs) and mRNA expression at the corresponding loci involved in the adenoma-carcinoma sequence in the isolated adenomatous and cancer glands of the same tumor in 15 cases of microsatellite-stable "carcinoma in adenoma," using genome-wide SNP and global gene expression arrays. Multiple copy-neutral loss of heterozygosity events were detected at 4q13. Read More

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Confidence intervals for Markov chain transition probabilities based on next generation sequencing reads data.

Quant Biol 2020 Jul 25;8(2):143-154. Epub 2020 May 25.

Quantitative and Computational Biology Program, University of Southern California, Los Angeles, CA 90089, USA.

Background: Markov chains (MC) have been widely used to model molecular sequences. The estimations of MC transition matrix and confidence intervals of the transition probabilities from long sequence data have been intensively studied in the past decades. In next generation sequencing (NGS), a large amount of short reads are generated. Read More

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