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A genetically defined signature of responsiveness to erlotinib in early-stage pancreatic cancer patients: Results from the CONKO-005 trial.

EBioMedicine 2021 Apr 13;66:103327. Epub 2021 Apr 13.

Department of Hematology, Oncology, and Tumor Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, Berlin 13353, Germany; German Cancer Consortium (DKTK), partner site Berlin, Berlin, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address:

Background: high recurrence rates of up to 75% within 2 years in pancreatic ductal adenocarcinoma (PDAC) patients resected for cure indicate a high medical need for clinical prediction tools and patient specific treatment approaches. Addition of the EGFR inhibitor erlotinib to adjuvant chemotherapy failed to improve outcome but its efficacy in some patients warrants predictors of responsiveness.

Patients And Methods: we analysed tumour samples from 293 R0-resected patients from the randomized, multicentre phase III CONKO-005 trial (gemcitabine ± erlotinib) with targeted sequencing, copy number, and RNA expression analyses. Read More

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Evidence for frequent concurrent DCUN1D1, FGFR1, BCL9 gene copy number amplification in squamous cell lung cancer.

Pathol Res Pract 2021 Mar 24;221:153412. Epub 2021 Mar 24.

1(st) Department of Pathology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias str., 11527, Goudi, Athens, Greece. Electronic address:

Non-small cell lung cancer (NSCLC) targeted therapies are mostly based on activating mutations and rearrangements which are rare events in Lung Squamous Cell Carcinomas (LUSC). Recently advances in immunotherapy have improved the therapeutic repository for LUSC, but there is still an urgent need for novel targets and biomarkers. We examined 73 cases of LUSC for relative copy number amplification of DCUN1D1, BCL9, FGFR1 and ERBB2 genes and searched for correlations with molecular alterations and clinicopathological characteristics. Read More

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Mitochondrial DNA mutations contribute to high altitude pulmonary edema via increased oxidative stress and metabolic reprogramming during hypobaric hypoxia.

Biochim Biophys Acta Bioenerg 2021 Apr 13:148431. Epub 2021 Apr 13.

Defence Institute of Physiology and Allied Sciences (DIPAS), Defence R&D Organization (DRDO), Lucknow Road, Timarpur, Delhi 110054, India.

High altitude pulmonary edema (HAPE) is experienced by non-acclimatized sea level individuals on exposure to high altitude hypoxic conditions. Available evidence suggests that genetic factors and perturbed mitochondrial redox status may play an important role in HAPE pathophysiology. However, the precise mechanism has not been fully understood. Read More

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On the Role of Magnesium Ions in the DNA-Scissoring Activity of the Restriction Endonuclease ApaI: Stochastic Kinetics from a Single Molecule to Mesoscopic Paradigm.

J Phys Chem B 2021 Apr 16. Epub 2021 Apr 16.

S. N. Bose National Centre for Basic Sciences, Block JD, Sector III, Salt Lake City, Kolkata 700106, India.

Biochemical reactions occurring inside cells have significant stochastic signatures due to the low copy number of reacting species. Kinetics of DNA cleavage by restriction endonucleases are no exception as established by single-molecule experiments. Here, we propose a simple reaction scheme to understand the role of the cofactor magnesium ion in the action of the endonuclease ApaI. Read More

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A neurogenetic analysis of female autism.

Brain 2021 Apr 16. Epub 2021 Apr 16.

Department of Pediatrics, Yale School of Medicine, New Haven, CT 06510, USA.

Females versus males are less frequently diagnosed with autism spectrum disorder (ASD), and while understanding sex differences is critical to delineating the systems biology of the condition, female ASD is understudied. We integrated functional MRI and genetic data in a sex-balanced sample of ASD and typically developing youth (8-17 years old) to characterize female-specific pathways of ASD risk. Our primary objectives were to: (i) characterize female ASD (n = 45) brain response to human motion, relative to matched typically developing female youth (n = 45); and (ii) evaluate whether genetic data could provide further insight into the potential relevance of these brain functional differences. Read More

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Digital next-generation sequencing of cell-free DNA for pancreatic cancer.

JGH Open 2021 Apr 22;5(4):508-516. Epub 2021 Mar 22.

First Department of Internal Medicine, Faculty of Medicine University of Yamanashi Chuo Japan.

Background And Aim: The clinical applicability of digital next-generation sequencing (dNGS), which eliminates polymerase chain reaction (PCR) and sequencing error-derived noise by using molecular barcodes (MBs), has not been fully evaluated. We evaluated the utility of dNGS of cell-free DNA (cfDNA) in liquid biopsies obtained from patients with pancreatic cancer.

Methods: Fifty-eight patients with pancreatic cancer undergoing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) were included. Read More

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Performance of Chromosomal Microarray Analysis for Detection of Copy Number Variations in Fetal Echogenic Bowel.

Risk Manag Healthc Policy 2021 9;14:1431-1438. Epub 2021 Apr 9.

Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, 350001, Fujian Province, People's Republic of China.

Background: Fetal echogenic bowel (FEB) is associated with an increased risk of poor pregnant outcomes; however, karyotyping fails to detect copy number variations (CNVs) in FEB. This study aimed to evaluate the performance of chromosomal microarray analysis (CMA) for detection of FEB.

Methods: The medical records of 147 pregnant women with FEB recruited during December 2015 to December 2018 were retrospectively reviewed, and prenatal samples were collected for karyotyping and CMA. Read More

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Genome-wide specificity of prime editors in plants.

Nat Biotechnol 2021 Apr 15. Epub 2021 Apr 15.

State Key Laboratory of Plant Cell and Chromosome Engineering, Center for Genome Editing, Institute of Genetics and Developmental Biology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing, China.

Although prime editors (PEs) have the potential to facilitate precise genome editing in therapeutic, agricultural and research applications, their specificity has not been comprehensively evaluated. To provide a systematic assessment in plants, we first examined the mismatch tolerance of PEs in plant cells and found that the editing frequency was influenced by the number and location of mismatches in the primer binding site and spacer of the prime editing guide RNA (pegRNA). Assessing the activity of 12 pegRNAs at 179 predicted off-target sites, we detected only low frequencies of off-target edits (0. Read More

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Quantitative mapping of the cellular small RNA landscape with AQRNA-seq.

Nat Biotechnol 2021 Apr 15. Epub 2021 Apr 15.

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Current next-generation RNA-sequencing (RNA-seq) methods do not provide accurate quantification of small RNAs within a sample, due to sequence-dependent biases in capture, ligation and amplification during library preparation. We present a method, absolute quantification RNA-sequencing (AQRNA-seq), that minimizes biases and provides a direct, linear correlation between sequencing read count and copy number for all small RNAs in a sample. Library preparation and data processing were optimized and validated using a 963-member microRNA reference library, oligonucleotide standards of varying length, and RNA blots. Read More

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Computational identification of variables in neonatal vocalizations predictive for postpubertal social behaviors in a mouse model of 16p11.2 deletion.

Mol Psychiatry 2021 Apr 15. Epub 2021 Apr 15.

Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Autism spectrum disorder (ASD) is often signaled by atypical cries during infancy. Copy number variants (CNVs) provide genetically identifiable cases of ASD, but how early atypical cries predict a later onset of ASD among CNV carriers is not understood in humans. Genetic mouse models of CNVs have provided a reliable tool to experimentally isolate the impact of CNVs and identify early predictors for later abnormalities in behaviors relevant to ASD. Read More

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Epigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia.

Sci Rep 2021 Apr 15;11(1):8318. Epub 2021 Apr 15.

Division of Hematology, Mayo Clinic, Rochester, MN, USA.

T cell prolymphocytic leukemia (T-PLL) is a rare disease with aggressive clinical course. Cytogenetic analysis, whole-exome and whole-genome sequencing have identified primary structural alterations in T-PLL, including inversion, translocation and copy number variation. Recurrent somatic mutations were also identified in genes encoding chromatin regulators and those in the JAK-STAT signaling pathway. Read More

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Spatiotemporal 7q11.23 protein network analysis implicates the role of DNA repair pathway during human brain development.

Sci Rep 2021 Apr 15;11(1):8246. Epub 2021 Apr 15.

Shanghai Mental Health Center,' Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.

Recurrent deletions and duplications of chromosome 7q11.23 copy number variants (CNVs) are associated with several psychiatric disorders. Although phenotypic abnormalities have been observed in patients, causal genes responsible for CNV-associated diagnoses and traits are still poorly understood. Read More

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Soil CO emission and soil attributes associated with the microbiota of a sugarcane area in southern Brazil.

Sci Rep 2021 Apr 15;11(1):8325. Epub 2021 Apr 15.

School of Agricultural and Veterinarian Sciences (FCAV), São Paulo State University (Unesp), Via de Acesso Prof. Paulo Donato Castellane s/n, Jaboticabal, São Paulo, 14884-900, Brazil.

The spatial structure of soil CO emission (FCO) and soil attributes are affected by different factors in a highly complex way. In this context, this study aimed to characterize the spatial variability patterns of FCO and soil physical, chemical, and microbiological attributes in a sugarcane field area after reform activities. The study was conducted in an Oxisol with the measurement of FCO, soil temperature (Ts), and soil moisture (Ms) in a regular 90 × 90-m grid with 100 sampling points. Read More

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Identification of a Novel Copy Number Variation of EYA4 Causing Autosomal Dominant Non-Syndromic Hearing Loss.

Otol Neurotol 2021 Apr 14. Epub 2021 Apr 14.

Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University Department of Otorhinolaryngology, Shinshu University School of Medicine Division of Rehabilitation, Department of Clinical Practice and Support, Hiroshima University, Minami-ku, Hiroshima, Japan.

Objective: Eyes absent 4 (EYA4) is the causative gene of autosomal dominant non-syndromic hereditary hearing loss, DFNA10. We aimed to identify a copy number variation of EYA4 in a non-syndromic sensory neural hearing loss pedigree.

Family And Clinical Evaluation: A Japanese family showing late-onset and progressive hearing loss was evaluated. Read More

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The impact of immune checkpoint therapy on the latent reservoir in HIV infected individuals with cancer on antiretroviral therapy.

AIDS 2021 Apr 15. Epub 2021 Apr 15.

Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia The Westmead Institute for Medical Research, University of Sydney, Westmead, Australia Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity.

Objective: To quantify HIV specific immunological and virological changes in people living with HIV (PLWH) on antiretroviral therapy (ART) with malignancy who received immune checkpoint blockade (ICB).

Design: Observational cohort study.

Methods: Blood samples were collected before and after four cycles of ICB in HIV positive adults on ART. Read More

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Analysis of Genetic Alterations in Cutaneous Malignant Melanomas Unveils Unique Loco-Regional Variations and Novel Predictors of Metastatic Potential.

Am J Dermatopathol 2021 Apr 13. Epub 2021 Apr 13.

A.M. Rywlin, MD Department of Pathology, Mount Sinai Medical Center, Miami Beach, FL; Department of Pathology, Florida International University, Herbert Wertheim College of Medicine, Miami, FL; and Department of Medical Oncology, Mount Sinai Medical Center, Miami Beach, FL.

Abstract: Cutaneous malignant melanoma is an aggressive cancer that contributes significantly to cancer-related mortality. Over the years, a deeper scrutiny of melanoma biology has led to identification of diverse evolutionary patterns involving various genetic pathways. This study attempts to further understand the genetic landscape of cutaneous malignant melanoma in terms of loco-regional variations and malignant potential. Read More

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A prospective multicenter assessor-blinded randomized controlled study to compare the efficacy of short versus long protocols of electroconvulsive therapy as an augmentation strategy to clozapine in patients with ultra-resistant schizophrenia (SURECT study).

Trials 2021 Apr 15;22(1):284. Epub 2021 Apr 15.

University Department of Psychiatry, Centre d'Excellence Thérapeutique- Institut de Psychiatrie, Centre Hospitalier du Rouvray, Sotteville-lès-Rouen, France.

Background: Although clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia, it leads to a poor or partial response in 40 to 70% of patients. Augmentation of clozapine with electroconvulsive therapy (ECT) is a highly effective and relatively safe treatment for these clozapine-resistant patients. However, parameters are not yet well specified, such as the optimal number of sessions, their frequency, and the relevance of maintenance ECT. Read More

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Clinical pharmacogenomics in action: design, assessment and implementation of a novel pharmacogenetic panel supporting drug selection for diseases of the central nervous system (CNS).

J Transl Med 2021 Apr 15;19(1):151. Epub 2021 Apr 15.

iDNA Genomics Private Company, Evrota 25, Kifissia, 145 64, Athens, Greece.

Background: Pharmacogenomics describes the link between gene variations (polymorphisms) and drug responses. In view of the implementation of precision medicine in personalized healthcare, pharmacogenetic tests have recently been introduced in the clinical practice. However, the translational aspects of such tests have been limited due to the lack of robust population-based evidence. Read More

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[The incidence of high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements in diffuse large B-cell lymphoma].

Zhonghua Xue Ye Xue Za Zhi 2021 Feb;42(2):124-128

Department of Pathology, Third Hospital, School of Basic Medical Sciences, Peking University, Beijing 100191, China.

To investigate the incidence of high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement in Chinese diffuse large B-cell lymphoma (DLBCL) . From January 2013 to August 2020, 922 DLBCL cases were collected. C-MYC and BCL2 protein expression levels were analyzed by immunohistochemistry staining. Read More

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February 2021

Supervised extraction of near-complete genomes from metagenomic samples: A new service in PATRIC.

PLoS One 2021 15;16(4):e0250092. Epub 2021 Apr 15.

Fellowship for Interpretation of Genomes, Burr Ridge, IL, United States of America.

Large amounts of metagenomically-derived data are submitted to PATRIC for analysis. In the future, we expect even more jobs submitted to PATRIC will use metagenomic data. One in-demand use case is the extraction of near-complete draft genomes from assembled contigs of metagenomic origin. Read More

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Time or place? Dissociation between object-in-place and relative recency in young APPswe/PS1dE9 mice.

Behav Neurosci 2021 Feb;135(1):39-50

Leeds Institute of Biomedical and Clinical Sciences, University of Leeds.

This study tests the predictions of a novel analysis of recognition memory based on a theory of associative learning, according to which recognition comprises two independent underlying processes, one relying on the to-be-recognized item having been experienced recently (self-generated priming), and the other on it being predicted by some other stimulus (retrieval-generated priming). A single experiment examined recognition performance in the amyloid precursor protein (APP)swe/PS1dE9 (APP/PS1) mouse, a double-transgenic model of Alzheimer's disease (AD), and wild type (WT) littermates. Performance on two variants of the spontaneous object recognition (SOR) was compared in 5-month-old APPswe/PS1dE9 (APP/PS1) mice, a double-transgenic model of AD, and their WT littermates, using junk objects. Read More

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February 2021

Circulating tumor DNA (ctDNA) as a pan-cancer screening test: is it finally on the horizon?

Clin Chem Lab Med 2021 Apr 14. Epub 2021 Apr 14.

Department of Medical Oncology, St Vincent's University Hospital, Dublin, Ireland.

The detection of cancer at an early stage while it is curable by surgical resection is widely believed to be one of the most effective strategies for reducing cancer mortality. Hence, the intense interests in the development of a simple pan-cancer screening test. Lack of sensitivity and specificity when combined with the low prevalence of most types of cancer types in the general population limit the use of most of the existing protein biomarkers for this purpose. Read More

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Mitochondria-DNA copy-number and incident venous thromboembolism among middle-aged women: a population-based cohort study.

J Thromb Thrombolysis 2021 Apr 15. Epub 2021 Apr 15.

Center for Primary Health Care Research, Lund University/Region Skåne, Skåne University Hospital Malmö, University Hospital, Jan Waldenströms gata 35, SE-205 02, Malmö, Sweden.

Venous thromboembolism (VTE) is the third most common cardiovascular disease. Low amount of mitochondrial DNA copy number (mtDNA-CN) has been associated with arterial cardiovascular disease (CVD) and reflects mitochondrial dysfunctions. However, whether mtDNA-CN is associated with VTE has not been determined. Read More

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Backbone assignments, and effect of Asn deamidation, of the N-terminal region of the partitioning protein IncC1 from the plasmid RK2.

Biomol NMR Assign 2021 Apr 15. Epub 2021 Apr 15.

School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.

IncC from the low-copy number plasmid RK2, is a member of the ParA family of proteins required for partitioning DNA in many bacteria and plasmids. It is an ATPase that binds DNA and its ParB protein partner, KorB. Together, the proteins move replicated DNA to appropriate cellular positions, so that each daughter cell inherits a copy on cell division. Read More

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Smelling in the dark: phylogenomic insights into the chemosensory system of a subterranean beetle.

Mol Ecol 2021 Apr 15. Epub 2021 Apr 15.

Institute of Evolutionary Biology (CSIC - Universitat Pompeu Fabra), Passeig Marítim, 37-49. 08003, Barcelona, Spain.

The chemosensory system has experienced relevant changes in subterranean animals, facilitating the perception of specific chemical signals critical to survive in their particular environment. However, the genomic basis of chemoreception in cave-dwelling fauna is largely unexplored. We generated de novo transcriptomes for antennae and body samples of the troglobitic beetle Speonomus longicornis (whose characters suggest an extreme adaptation to a deep subterranean environment) in order to investigate the evolutionary origin and diversification of the chemosensory gene repertoire across coleopterans through a phylogenomic approach. Read More

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Tumor immune landscape of paediatric high-grade gliomas.

Brain 2021 Apr 15. Epub 2021 Apr 15.

Department of Oncological Sciences, The Tisch Cancer Institute, Mount Sinai Icahn School of Medicine, New York, New York, USA.

Over the last decade, remarkable progress has been made towards elucidating the origin and genomic landscape of childhood high-grade brain tumors. It has become evident that pediatric high-grade gliomas (pHGGs) differ from adult HGGs with respect to multiple defining aspects including: DNA copy number, gene expression profiles, tumor locations within the central nervous system, and genetic alterations such as somatic histone mutations. Despite these advances, clinical trials for children with glioma have historically been based on ineffective adult regimens that fail to take into consideration the fundamental biological differences between the two. Read More

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Genome Assembly of the Canadian two-row Malting Barley cultivar AAC Synergy.

G3 (Bethesda) 2021 Feb 4. Epub 2021 Feb 4.

Brandon Research and Development Centre, Agriculture and Agri-Food Canada, 2701 Grand Valley Road, Brandon, MB R7A 5Y3, Canada.

Barley (Hordeum vulgare L.) is one of the most important global crops. The six-row barley cultivar Morex reference genome has been used by the barley research community worldwide. Read More

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February 2021

Novel transgenic mice with Cre-dependent co-expression of GFP and human ACE2: a safe tool for study of COVID-19 pathogenesis.

Transgenic Res 2021 Apr 14. Epub 2021 Apr 14.

Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Vavilova st. 34/5, Moscow, Russian Federation, 119334.

The current coronavirus disease (COVID-19) pandemic remains one of the most serious public health problems. Increasing evidence shows that infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a very complex and multifaceted disease that requires detailed study. Nevertheless, experimental research on COVID-19 remains challenging due to the lack of appropriate animal models. Read More

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The complete chloroplast genome of (Ranunculaceae).

Mitochondrial DNA B Resour 2021 Mar 31;6(4):1319-1320. Epub 2021 Mar 31.

Tasly Pharmaceutical Group Co., Ltd, Tianjin, China.

The complete chloroplast genome of was determined in this study. The genome was 159,675 base pair (bp) in length, containing a large single-copy (LSC) region of 79,443 bp, a small single-copy region (SSC) of 18,100 bp and a pair of inverted repeats (IRs) of 31,066 bp. It contains 130 unique genes, including 86 protein-coding genes, 36 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. Read More

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The complete chloroplast genome of , an endemic to Europe.

Mitochondrial DNA B Resour 2021 Apr 1;6(4):1300-1302. Epub 2021 Apr 1.

Shandong Institute of Pomology, Shandong Academy of Agricultural Sciences, Taian, PR China.

Sweet chestnut () is an endemic species of genus in Europe, which is widespread in the southern part of continental Europe. The complete genome sequence of chloroplast was determined through Illumina NovaSeq platform. Totally the genome of chloroplast was 160,938 bp in length, GC rich (36. Read More

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