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  1. Article ; Online: A Test to Comprehensively Capture the Known Genetic Component of Familial Pulmonary Fibrosis.

    Villeneuve, Judith / Tremblay, Élody / Gaudreault, Nathalie / Saavedra Armero, Victoria / Boudreau, Dominique K / Li, Zhonglin / Renaut, Sébastien / Dion, Geneviève / Bossé, Yohan

    American journal of respiratory cell and molecular biology

    2024  

    Abstract: The recent European Respiratory Society statement on familial pulmonary fibrosis (FPF) supports the need of genetic testing in the care of patients and their relatives. However, no solution (i.e., a concrete test) was provided to implemented genetic ... ...

    Abstract The recent European Respiratory Society statement on familial pulmonary fibrosis (FPF) supports the need of genetic testing in the care of patients and their relatives. However, no solution (i.e., a concrete test) was provided to implemented genetic testing in daily practice. Herein, we tabulated and standardized the nomenclature of 128 genetic variants in 20 genes implicated in adult-onset pulmonary fibrosis. The objective was to develop a laboratory developed test (LDT) based on standard Sanger sequencing in order to capture all known FPF-associated variants. Targeted DNA fragments were amplified with harmonized PCR conditions to perform the LDT in a single 96-well plate. The new genetic test was evaluated in 62 sporadic cases of idiopathic pulmonary fibrosis (IPF). As expected in this population, we observed a low yield of disease-causing mutations. More importantly, 100% of targeted variants by the LDT were successfully evaluated. Furthermore, four variants of uncertain significance with
    Language English
    Publishing date 2024-02-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1025960-0
    ISSN 1535-4989 ; 1044-1549
    ISSN (online) 1535-4989
    ISSN 1044-1549
    DOI 10.1165/rcmb.2024-0009MA
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    Zs.A 2851: Show issues Location:
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  2. Article ; Online: Cardiac reverse remodeling in a mouse model with many phenotypical features of heart failure with preserved ejection fraction: effects of modifying lifestyle.

    Aidara, Mohamed Lamine / Walsh-Wilkinson, Élisabeth / Thibodeau, Sara-Ève / Labbé, Emylie-Ann / Morin-Grandmont, Audrey / Gagnon, Geneviève / Boudreau, Dominique K / Arsenault, Marie / Bossé, Yohan / Couët, Jacques

    American journal of physiology. Heart and circulatory physiology

    2024  Volume 326, Issue 4, Page(s) H1017–H1036

    Abstract: Multiple factors cause heart failure with preserved ejection fraction (HFpEF) and involve various systems. HFpEF prevalence is rapidly rising, and its prognosis remains poor after the first hospitalization. Adopting a more active lifestyle has been shown ...

    Abstract Multiple factors cause heart failure with preserved ejection fraction (HFpEF) and involve various systems. HFpEF prevalence is rapidly rising, and its prognosis remains poor after the first hospitalization. Adopting a more active lifestyle has been shown to provide beneficial clinical outcomes for patients with HFpEF. Using a two-hit HfpEF murine model, we studied cardiac reverse remodeling (RR) after stopping the causing stress and introducing voluntary exercise (VE). We checked in 2-mo-old male and female C57Bl6/J mice the heart's response to angiotensin II (ANG II; 1.5 mg/kg/day for 28 days) fed or not with a high-fat diet (HFD). Then, ANG II and/or the HFD were stopped, and VE was started for an additional 4 wk. ANG II and ANG II + HFD (metabolic-hypertensive stress, MHS) caused cardiac hypertrophy (CH) and myocardial fibrosis, left ventricular (LV) concentric remodeling, atrial enlargement, and reduced exercise capacity. HFD alone induced CH and LV concentric remodeling in female mice only. CH and LV concentric remodeling were reversed 4 wk after stopping ANG II, starting VE, and a low-fat diet. Left atrial enlargement and exercise capacity were improved but differed from controls. We performed bulk LV RNA sequencing and observed that MHS upregulated 58% of the differentially expressed genes (DEGs) compared with controls. In the RR group, compared with MHS animals, 60% of the DEGs were downregulated. In an HfpEF mouse model, we show that correcting hypertension, diet, and introducing exercise can lead to extensive cardiac reverse remodeling.
    MeSH term(s) Humans ; Male ; Female ; Mice ; Animals ; Heart Failure ; Disease Models, Animal ; Stroke Volume/physiology ; Myocardium ; Hypertension ; Ventricular Remodeling/physiology ; Ventricular Function, Left/physiology
    Language English
    Publishing date 2024-02-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 603838-4
    ISSN 1522-1539 ; 0363-6135
    ISSN (online) 1522-1539
    ISSN 0363-6135
    DOI 10.1152/ajpheart.00462.2023
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  3. Article ; Online: Performance of an RNA-Based Next-Generation Sequencing Assay for Combined Detection of Clinically Actionable Fusions and Hotspot Mutations in NSCLC.

    Desmeules, Patrice / Boudreau, Dominique K / Bastien, Nathalie / Boulanger, Marie-Chloé / Bossé, Yohan / Joubert, Philippe / Couture, Christian

    JTO clinical and research reports

    2022  Volume 3, Issue 2, Page(s) 100276

    Abstract: Introduction: With its expanding list of approved and emerging therapeutic indications, NSCLC is the exemplar tumor type requiring upfront assessment of several biomarkers to guide clinical management. Next-generation sequencing allows identification of ...

    Abstract Introduction: With its expanding list of approved and emerging therapeutic indications, NSCLC is the exemplar tumor type requiring upfront assessment of several biomarkers to guide clinical management. Next-generation sequencing allows identification of different types of molecular alterations, each with specific analytical challenges. Library preparation using parallel DNA and RNA workflows can overcome most of them, but it increases complexity of laboratory operations, turnaround time, and costs. We describe the performance characteristics of a 15-gene RNA panel on the basis of anchored multiplex polymerase chain reaction for combined detection of clinically relevant oncogenic fusion transcripts and hotspot small variants.
    Methods: Formalin-fixed, paraffin-embedded NSCLC clinical samples (N = 58) were used along cell lines and commercial controls to validate the assay's analytical performance, followed by an exploratory prospective cohort (N = 87).
    Results: The raw assay sensitivity for hotspot mutations and fusions was 83% and 93%, respectively, reaching 100% after filtering for key assay metrics. Those include quantity and quality of input of nucleic acid and sequencing metric from primers on housekeeping genes included in the assay. In the prospective cohort, driver alterations were identified in most cases (≥58%).
    Conclusions: This ultrafocused RNA-next-generation sequencing assay offers an advantageous option with single unified workflow for simultaneous detection of clinically relevant hotspot mutations and fusions in NSCLC, focusing on actionable gene targets.
    Language English
    Publishing date 2022-01-10
    Publishing country United States
    Document type Journal Article
    ISSN 2666-3643
    ISSN (online) 2666-3643
    DOI 10.1016/j.jtocrr.2022.100276
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  4. Article ; Online: Characterization of vancomycin-resistance

    Brochu, Eliel / Huletsky, Ann / Boudreau, Dominique K / Raymond, Frédéric / Bérubé, Ève / Ouameur, Amin Ahmed / Frenette, Johanne / Boissinot, Maurice / Corbeil, Jacques / Bergeron, Michel G

    JAC-antimicrobial resistance

    2023  Volume 5, Issue 2, Page(s) dlad026

    Abstract: Objectives: To characterize vancomycin-resistance : Methods: Stool samples were collected before and after 7 days of cefprozil β-lactam antibiotic exposure of 18 participants and six control participants who were not exposed to the antibiotic at the ... ...

    Abstract Objectives: To characterize vancomycin-resistance
    Methods: Stool samples were collected before and after 7 days of cefprozil β-lactam antibiotic exposure of 18 participants and six control participants who were not exposed to the antibiotic at the same time points. Metagenomic sequencing and culture-enriched metagenomic sequencing (with and without β-lactam selection) were used to characterize
    Results: Culture enrichment allowed detection of
    Conclusions: This study showed that culture-enriched metagenomics allowed detection of
    Language English
    Publishing date 2023-03-24
    Publishing country England
    Document type Journal Article
    ISSN 2632-1823
    ISSN (online) 2632-1823
    DOI 10.1093/jacamr/dlad026
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  5. Article ; Online: Integrative genomic analyses identify candidate causal genes for calcific aortic valve stenosis involving tissue-specific regulation.

    Thériault, Sébastien / Li, Zhonglin / Abner, Erik / Luan, Jian'an / Manikpurage, Hasanga D / Houessou, Ursula / Zamani, Pardis / Briend, Mewen / Boudreau, Dominique K / Gaudreault, Nathalie / Frenette, Lily / Argaud, Déborah / Dahmene, Manel / Dagenais, François / Clavel, Marie-Annick / Pibarot, Philippe / Arsenault, Benoit J / Boekholdt, S Matthijs / Wareham, Nicholas J /
    Esko, Tõnu / Mathieu, Patrick / Bossé, Yohan

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2407

    Abstract: There is currently no medical therapy to prevent calcific aortic valve stenosis (CAVS). Multi-omics approaches could lead to the identification of novel molecular targets. Here, we perform a genome-wide association study (GWAS) meta-analysis including 14, ...

    Abstract There is currently no medical therapy to prevent calcific aortic valve stenosis (CAVS). Multi-omics approaches could lead to the identification of novel molecular targets. Here, we perform a genome-wide association study (GWAS) meta-analysis including 14,819 cases among 941,863 participants of European ancestry. We report 32 genomic loci, among which 20 are novel. RNA sequencing of 500 human aortic valves highlights an enrichment in expression regulation at these loci and prioritizes candidate causal genes. Homozygous genotype for a risk variant near TWIST1, a gene involved in endothelial-mesenchymal transition, has a profound impact on aortic valve transcriptomics. We identify five genes outside of GWAS loci by combining a transcriptome-wide association study, colocalization, and Mendelian randomization analyses. Using cross-phenotype and phenome-wide approaches, we highlight the role of circulating lipoproteins, blood pressure and inflammation in the disease process. Our findings pave the way for the development of novel therapies for CAVS.
    MeSH term(s) Humans ; Aortic Valve/metabolism ; Aortic Valve/pathology ; Genome-Wide Association Study ; Aortic Valve Stenosis/genetics ; Genomics ; Calcinosis
    Language English
    Publishing date 2024-03-18
    Publishing country England
    Document type Meta-Analysis ; Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-46639-4
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  6. Article ; Online: Tumor Mutational Burden by Whole-Genome Sequencing in Resected NSCLC of Never Smokers.

    Ruel, Louis-Jacques / Li, Zhonglin / Gaudreault, Nathalie / Henry, Cyndi / Saavedra Armero, Victoria / Boudreau, Dominique K / Zhang, Tongwu / Landi, Maria Teresa / Labbé, Catherine / Couture, Christian / Desmeules, Patrice / Joubert, Philippe / Bossé, Yohan

    Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

    2022  Volume 31, Issue 12, Page(s) 2219–2227

    Abstract: Background: Data are scarce about tumor mutational burden (TMB) as a biomarker in never smokers with non-small cell lung cancer (NSCLC).: Methods: TMB was assessed by whole-genome sequencing (WGS) and compared with in silico reduced whole-exome ... ...

    Abstract Background: Data are scarce about tumor mutational burden (TMB) as a biomarker in never smokers with non-small cell lung cancer (NSCLC).
    Methods: TMB was assessed by whole-genome sequencing (WGS) and compared with in silico reduced whole-exome sequencing (WES) and targeted commercial next-generation sequencing (NGS) gene panels in 92 paired tumor-normal samples from never smokers who underwent NSCLC resection with curative intent. Analyses were performed to test for association with survival after surgery and to identify the optimal prognostic TMB cutoff.
    Results: Tumors of never smokers with NSCLC had low TMB scores (median 1.57 mutations/Mb; range, 0.13-17.94). A TMB cutoff of 1.70 mutations/Mb was associated with a 5-year overall survival of 58% in the high-TMB (42% of cases) compared with 86% in low-TMB patients (Wald P = 0.0029). TMB scores from WGS and WES were highly correlated (Spearman ρ = 0.93, P < 2.2e-16). TMB scores from NGS panels demonstrated high intraindividual fluctuations and identified high-TMB patients with 65% concordance in average compared with WGS.
    Conclusions: In resected NSCLC of never smokers, high TMB was associated with worse prognosis. WES provided a good estimate of TMB while targeted NGS panels seem to lack adequate depth and resolution in the setting of low mutation burden.
    Impact: TMB is a prognostic indicator of survival in resected NSCLC from individuals who never smoked. In this setting of low mutation counts, TMB can be accurately measured by WGS or WES, but not NGS panels.
    MeSH term(s) Humans ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/surgery ; Lung Neoplasms/genetics ; Lung Neoplasms/surgery ; Smokers ; Biomarkers, Tumor/genetics ; Whole Exome Sequencing
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2022-09-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1153420-5
    ISSN 1538-7755 ; 1055-9965
    ISSN (online) 1538-7755
    ISSN 1055-9965
    DOI 10.1158/1055-9965.EPI-22-0630
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    Zs.A 3693: Show issues Location:
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  7. Article ; Online: Method for isolation of both lactose-fermenting and - non-fermenting Escherichia albertii strains from stool samples.

    Maheux, Andrée F / Brodeur, Stéphanie / Bérubé, Ève / Boudreau, Dominique K / Abed, Jehane Y / Boissinot, Maurice / Bissonnette, Luc / Bergeron, Michel G

    Journal of microbiological methods

    2018  Volume 154, Page(s) 134–140

    Abstract: Initially, Escherichia albertii has been described as a non-lactose fermenting bacterium and methods used to isolate it were first based on this phenotypic property. However, a recent study showed a variable lactose fermentation phenotype for E. albertii ...

    Abstract Initially, Escherichia albertii has been described as a non-lactose fermenting bacterium and methods used to isolate it were first based on this phenotypic property. However, a recent study showed a variable lactose fermentation phenotype for E. albertii suggesting that this microorganism could have been underestimated by previous studies using isolation methods based on lactose fermentation. In this study, we present a method for the isolation and identification of both lactose fermenting and non-fermenting-E. albertii cells in stool samples, said method combining culture and isolation on mEA agar, an indole test, as well as an E. albertii-specific PCR assay for formal species identification. The ability of the procedure to detect E. albertii strains was verified using 19 E. albertii strains and 132 non-E. albertii strains representing 88 species of different origins majoritary belonging to the Enterobacteriaceae family. All indole-positive white colonies grown on mEA agar were subjected to E. albertii-specific PCR amplification; all E. albertii strains tested were detected with this assay and none of the non-E. albertii strains tested was detected. To demonstrate the ability of the procedure to directly detect E. albertii in stool samples, E. albertii-inoculated stools were tested and for all inoculated samples, E. albertii colonies were easily detected and identified. The present study provides a method enable to recover both lactose-fermenting and -non-fermenting E. albertii strains from clinical samples. This method could help to provide a better portrait of the prevalence and pathogenicity of E. albertii in clinical samples.
    MeSH term(s) Bacteriological Techniques/methods ; Cell Culture Techniques/methods ; Culture Media/chemistry ; DNA, Bacterial ; Diarrhea/diagnosis ; Diarrhea/microbiology ; Enterobacteriaceae/genetics ; Enterobacteriaceae/isolation & purification ; Enterobacteriaceae Infections/diagnosis ; Enterobacteriaceae Infections/microbiology ; Escherichia/classification ; Escherichia/genetics ; Escherichia/isolation & purification ; Escherichia/metabolism ; Feces/microbiology ; Fermentation ; Humans ; Lactose/metabolism ; Polymerase Chain Reaction/methods ; Sensitivity and Specificity ; Specimen Handling
    Chemical Substances Culture Media ; DNA, Bacterial ; Lactose (J2B2A4N98G)
    Language English
    Publishing date 2018-09-18
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 604916-3
    ISSN 1872-8359 ; 0167-7012
    ISSN (online) 1872-8359
    ISSN 0167-7012
    DOI 10.1016/j.mimet.2018.09.008
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    Zs.A 1849: Show issues Location:
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  8. Article ; Online: Criibacterium bergeronii

    Maheux, Andrée F / Boudreau, Dominique K / Abed, Jehane Y / Bérubé, Ève / Brodeur, Stéphanie / Bernard, Kathryn A / Hashimi, Ameena / Ducrey, Éloïse / Guay, Émilie F / Raymond, Frédéric / Corbeil, Jacques / Domingo, Marc-Christian / Roy, Paul H / Boissinot, Maurice / Tocheva, Elitza I / Omar, Rabeea F

    International journal of systematic and evolutionary microbiology

    2021  Volume 71, Issue 3

    Abstract: A rod-shaped, motile anaerobic bacterium, designated CCRI- ... ...

    Abstract A rod-shaped, motile anaerobic bacterium, designated CCRI-22567
    Language English
    Publishing date 2021-02-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 2002336-4
    ISSN 1466-5034 ; 1466-5026
    ISSN (online) 1466-5034
    ISSN 1466-5026
    DOI 10.1099/ijsem.0.004691
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    Zs.A 409: Show issues Location:
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  9. Article ; Online: Influence of sequence mismatches on the specificity of recombinase polymerase amplification technology.

    Daher, Rana K / Stewart, Gale / Boissinot, Maurice / Boudreau, Dominique K / Bergeron, Michel G

    Molecular and cellular probes

    2015  Volume 29, Issue 2, Page(s) 116–121

    Abstract: Recombinase polymerase amplification (RPA) technology relies on three major proteins, recombinase proteins, single-strand binding proteins, and polymerases, to specifically amplify nucleic acid sequences in an isothermal format. The performance of RPA ... ...

    Abstract Recombinase polymerase amplification (RPA) technology relies on three major proteins, recombinase proteins, single-strand binding proteins, and polymerases, to specifically amplify nucleic acid sequences in an isothermal format. The performance of RPA with respect to sequence mismatches of closely-related non-target molecules is not well documented and the influence of the number and distribution of mismatches in DNA sequences on RPA amplification reaction is not well understood. We investigated the specificity of RPA by testing closely-related species bearing naturally occurring mismatches for the tuf gene sequence of Pseudomonas aeruginosa and/or Mycobacterium tuberculosis and for the cfb gene sequence of Streptococcus agalactiae. In addition, the impact of the number and distribution of mismatches on RPA efficiency was assessed by synthetically generating 14 types of mismatched forward primers for detecting five bacterial species of high diagnostic relevance such as Clostridium difficile, Staphylococcus aureus, S. agalactiae, P. aeruginosa, and M. tuberculosis as well as Bacillus atropheus subsp. globigii for which we use the spores as internal control in diagnostic assays. A total of 87 mismatched primers were tested in this study. We observed that target specific RPA primers with mismatches (n > 1) at their 3'extrimity hampered RPA reaction. In addition, 3 mismatches covering both extremities and the center of the primer sequence negatively affected RPA yield. We demonstrated that the specificity of RPA was multifactorial. Therefore its application in clinical settings must be selected and validated a priori. We recommend that the selection of a target gene must consider the presence of closely-related non-target genes. It is advisable to choose target regions with a high number of mismatches (≥36%, relative to the size of amplicon) with respect to closely-related species and the best case scenario would be by choosing a unique target gene.
    MeSH term(s) Bacteria ; Base Pair Mismatch ; Humans ; Polymerase Chain Reaction/methods ; Recombinases/chemistry ; Sensitivity and Specificity
    Chemical Substances Recombinases
    Language English
    Publishing date 2015-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639082-1
    ISSN 1096-1194 ; 0890-8508
    ISSN (online) 1096-1194
    ISSN 0890-8508
    DOI 10.1016/j.mcp.2014.11.005
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  10. Article: Draft Genome Sequence of

    Maheux, Andrée F / Boudreau, Dominique K / Bérubé, Ève / Boissinot, Maurice / Cantin, Philippe / Raymond, Frédéric / Corbeil, Jacques / Omar, Rabeea F / Bergeron, Michel G

    Genome announcements

    2017  Volume 5, Issue 40

    Abstract: Romboutsia ... ...

    Abstract Romboutsia weinsteinii
    Language English
    Publishing date 2017-10-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2704277-7
    ISSN 2169-8287
    ISSN 2169-8287
    DOI 10.1128/genomeA.00901-17
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