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Article ; Online: NAD(H) phosphates mediate tetramer assembly of human C-terminal binding protein (CtBP).

Nichols, Jeffry C / Schiffer, Celia A / Royer, William E

2021 Volume 296, Page(s) 100351

Abstract: C-terminal binding proteins (CtBPs) are cotranscriptional factors that play key roles in cell fate ...

Abstract	C-terminal binding proteins (CtBPs) are cotranscriptional factors that play key roles in cell fate. We have previously shown that NAD(H) promotes the assembly of similar tetramers from either human CtBP1 and CtBP2 and that CtBP2 tetramer destabilizing mutants are defective for oncogenic activity. To assist structure-based design efforts for compounds that disrupt CtBP tetramerization, it is essential to understand how NAD(H) triggers tetramer assembly. Here, we investigate the moieties within NAD(H) that are responsible for triggering tetramer formation. Using multiangle light scattering (MALS), we show that ADP is able to promote tetramer formation of both CtBP1 and CtBP2, whereas AMP promotes tetramer assembly of CtBP1, but not CtBP2. Other NAD(H) moieties that lack the adenosine phosphate, including adenosine and those incorporating nicotinamide, all fail to promote tetramer assembly. Our crystal structures of CtBP1 with AMP reveal participation of the adenosine phosphate in the tetrameric interface, pinpointing its central role in NAD(H)-linked assembly. CtBP1 and CtBP2 have overlapping but unique roles, suggesting that a detailed understanding of their unique structural properties might have utility in the design of paralog-specific inhibitors. We investigated the different responses to AMP through a series of site-directed mutants at 13 positions. These mutations reveal a central role for a hinge segment, which we term the 120s hinge that connects the substrate with coenzyme-binding domains and influences nucleotide binding and tetramer assembly. Our results provide insight into suitable pockets to explore in structure-based drug design to interfere with cotranscriptional activity of CtBP in cancer.
MeSH term(s)	Alcohol Oxidoreductases/chemistry ; Alcohol Oxidoreductases/metabolism ; Co-Repressor Proteins/chemistry ; Co-Repressor Proteins/metabolism ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/metabolism ; Humans ; Models, Molecular ; NAD/metabolism ; NADP/metabolism ; Protein Multimerization
Chemical Substances	Co-Repressor Proteins ; DNA-Binding Proteins ; NAD (0U46U6E8UK) ; NADP (53-59-8) ; Alcohol Oxidoreductases (EC 1.1.-) ; CTBP2 protein, human (EC 1.1.-) ; C-terminal binding protein (EC 1.1.1.-)
Language	English
Publishing date	2021-01-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2021.100351
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Book ; Online: Open Society Unresolved

Royer, Christof / Matei, Liviu

The Contemporary Relevance of a Contested Idea

2023

Keywords	Philosophy: metaphysics & ontology ; Society & social sciences ; Interdisciplinary studies ; Open society; theory and practice; contemporary relevance; diversity and plurality; geographically and intellectually global
Language	English
Size	1 electronic resource (228 pages)
Publisher	Central European University Press
Document type	Book ; Online
Note	English
HBZ-ID	HT030649953
ISBN	9789633865897 ; 9633865891
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Continuum of hepatitis C care in France: A 20-year cohort study.

Hermetet, Coralie / Dubois, Frederic / Gaudy-Graffin, Catherine / Bacq, Yannick / Royer, Bernard / Gaborit, Christophe / D'Alteroche, Louis / Desenclos, Jean Claude / Roingeard, Philippe / Grammatico-Guillon, Leslie

PloS one

2017 Volume 12, Issue 8, Page(s) e0183232

Abstract: Background: Hepatitis C virus (HCV)-infected patients require a specific continuum of care (CoC ...

Abstract	Background: Hepatitis C virus (HCV)-infected patients require a specific continuum of care (CoC) from HCV screening to treatment. We assessed CoC of HCV-infected patients in a longitudinal study. Methods: We established a cohort of subjects undergoing HCV screening (high alanine aminotransferase levels or risk factors) during preventive consultations at a French regional medical center from 1993 to 2013. Patients were considered to be HCV-infected if HCV RNA was detected in their serum. CoC was assessed as described by Viner et al. (Hepatology 2015): Stage 1, HCV screening; Stage 2, HCV RNA testing; Stage 3, continuing care; Stage 4, antiviral treatment. Cox multivariate analysis was performed to identify factors favoring CoC, defined as at least one course of antiviral treatment. Results: In total, 12,993 HCV tests were performed and 478 outpatients were found to be HCV-seropositive. We included 417 seropositive patients, after excluding false positives and patients lost to follow-up. The baseline characteristics of the patients were: sex ratio (M/F) 1.4; mean age 38.5 years; intravenous drug use (IDU) in 55%; and 28% in unstable social situations, estimated by the EPICES deprivation score. Antiviral treatment was initiated for 179 (42.9%) of the 379 (90.9%) patients attending specialist consultations. CoC was associated with screening after 1997 (HR 2.0, 95%CI 1.4-2.9), age > 45 years (HR 1.5, 95%CI 1.02-2.3), patient acceptance of care (HR 9.3, 95%CI 5.4-16.10), specialist motivation for treatment (HR 10.9, 95%CI 7.4-16.0), and absence of cancer (HR 6.7, 95%CI 1.6-27.9). Other comorbid conditions, such as depression and IDU, were not associated with CoC. Conclusions: Our 20-year cohort study reveals the real-life continuum of care for HCV-infected patients in France. The number of patients involved in HCV care after positive testing was substantial due to the organization of healthcare in France. An improved CoC along with new direct-acting antivirals should help to decrease chronic HCV infection.
MeSH term(s)	Adult ; Antiviral Agents/therapeutic use ; Continuity of Patient Care ; Female ; France ; Hepacivirus/isolation & purification ; Hepatitis C, Chronic/diagnosis ; Hepatitis C, Chronic/drug therapy ; Humans ; Longitudinal Studies ; Lost to Follow-Up ; Male ; Mass Screening ; Middle Aged
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0183232
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Article ; Online: Diagnostic reference levels during fluoroscopically guided interventions using mobile C-arms in operating rooms: A national multicentric survey.

Hadid-Beurrier, Lama / Dabli, Djamel / Royer, Brice / Demonchy, Mathilde / Le Roy, Julien

Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)

2021 Volume 86, Page(s) 91–97

Abstract: ... common fluoroscopically guided interventions (FGIs) performed in operating rooms using mobile C-arm ... performed in operating rooms using a mobile C-arm. We aim at providing a practical optimization tool ...

Abstract	Purpose: To establish diagnostic reference levels (DRLs) and achievable levels (ALs) for the most common fluoroscopically guided interventions (FGIs) performed in operating rooms using mobile C-arm equipment. Methods: A national survey was performed in 57 centers in France. Anonymous data from 6817 patients undergoing FGIs were prospectively collected over a period of 7 months. DRLs (third quartile of the distribution) and ALs (median of the distribution) were determined for each type of intervention in terms of kerma area product (KAP) and fluoroscopy time (FT). Results: DRLs and ALs were proposed for 31 procedure types related to seven surgical specialties: orthopedics (n = 9), urology (n = 3), vascular (n = 6), cardiology (n = 5), neurosurgery (n = 3), gastrointestinal (n = 3), and multi-specialty (n = 2). DRLs in terms of KAP ranged from 0.1 Gy·cm Conclusions: DRLs and ALs are suggested for a wide range of FGIs performed in operating rooms using a mobile C-arm. We aim at providing a practical optimization tool for medical physicists and surgeons.
MeSH term(s)	Diagnostic Reference Levels ; Fluoroscopy ; France ; Humans ; Operating Rooms ; Radiation Dosage ; Radiography, Interventional
Language	English
Publishing date	2021-05-29
Publishing country	Italy
Document type	Journal Article
ZDB-ID	1122650-x
ISSN	1724-191X ; 1120-1797
ISSN (online)	1724-191X
ISSN	1120-1797
DOI	10.1016/j.ejmp.2021.05.013
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Article ; Online: Is the C:N ratio a reliable indicator of C allocation to primary and defence-related metabolisms in tomato?

Royer, Mathilde / Larbat, Romain / Le Bot, Jacques / Adamowicz, Stéphane / Robin, Christophe

Phytochemistry

2013 Volume 88, Page(s) 25–33

Abstract: ... The ratio of carbon to nitrogen (C:N) of an organ is often regarded as a convenient indicator of growth and ... to characterize the trade-off between growth and defence processes. Therefore, we calculated C:N ratios ... ambient or enriched (700 vpm) air CO(2). These conditions yielded a large array of C:N in fully developed ...

Abstract	Plant growth and defence are both fuelled by compounds synthesized from a common pool of carbon and nitrogen, implying the existence of a competition for carbon and nitrogen allocation to both metabolisms. The ratio of carbon to nitrogen (C:N) of an organ is often regarded as a convenient indicator of growth and quality. The purpose of this work was to assess whether or not it is possible to extend its use to characterize the trade-off between growth and defence processes. Therefore, we calculated C:N ratios in the pool of resources and in the total plant, and correlated them to the concentrations of diverse compounds of the primary and secondary metabolisms in young tomatoes. Plants were grown hydroponically at N availabilities either limiting (0.1 mM) or not (7 mM) for growth in two glasshouses maintained either under ambient or enriched (700 vpm) air CO(2). These conditions yielded a large array of C:N in fully developed leaves, developing leaves, stem and roots, sampled 27, 35 and 47 days after sowing. Growth parameters and tissue concentrations of primary metabolites (carbohydrates, starch), defence-related compounds (polyphenols, glycoalkaloids), lignin, nitrate, ammonium, C and N were analyzed. Net CO(2) exchange rate was also measured at the last sampling date. Low N limited plant growth more than photosynthesis. The C:N in the resource pool was far higher than the total C:N. Starch was the most responsive compound, attaining high concentration under high C:N, whereas lignin remained stable. Chlorogenic acid, rutin, kaempferol-rutinoside and tomatine concentrations correlated positively to C:N. The same patterns were observed for most organs and molecules, except soluble carbohydrates in fully developed leaves whose concentration was not influenced. Among the organs, developing leaves showed the highest concentrations of secondary compounds and were the most responsive to C:N variations. Neither the biochemical nature of the compounds (C-based or N- containing metabolites) nor the calculation mode of C:N, influenced the patterns observed. Within the range of N availabilities considered (up to N limitation but not deficiency), the C:N can be considered as a good indicator of the secondary compounds concentrations in organs, especially for those involved in the chemical defence.
MeSH term(s)	Biomass ; Carbon/chemistry ; Carbon/metabolism ; Disease Resistance ; Hydroponics ; Lycopersicon esculentum/chemistry ; Lycopersicon esculentum/growth & development ; Lycopersicon esculentum/metabolism ; Nitrogen/chemistry ; Nitrogen/metabolism ; Plant Physiological Phenomena
Chemical Substances	Carbon (7440-44-0) ; Nitrogen (N762921K75)
Language	English
Publishing date	2013-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208884-8
ISSN	1873-3700 ; 0031-9422
ISSN (online)	1873-3700
ISSN	0031-9422
DOI	10.1016/j.phytochem.2012.12.003
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Article ; Online: Assembly of human C-terminal binding protein (CtBP) into tetramers.

Bellesis, Andrew G / Jecrois, Anne M / Hayes, Janelle A / Schiffer, Celia A / Royer, William E

The Journal of biological chemistry

2018 Volume 293, Issue 23, Page(s) 9101–9112

Abstract: C-terminal binding protein 1 (CtBP1) and CtBP2 are transcriptional coregulators that repress ...

Abstract	C-terminal binding protein 1 (CtBP1) and CtBP2 are transcriptional coregulators that repress numerous cellular processes, such as apoptosis, by binding transcription factors and recruiting chromatin-remodeling enzymes to gene promoters. The NAD(H)-linked oligomerization of human CtBP is coupled to its co-transcriptional activity, which is implicated in cancer progression. However, the biologically relevant level of CtBP assembly has not been firmly established; nor has the stereochemical arrangement of the subunits above that of a dimer. Here, multi-angle light scattering (MALS) data established the NAD
MeSH term(s)	Alcohol Oxidoreductases/chemistry ; Alcohol Oxidoreductases/metabolism ; Co-Repressor Proteins ; Crystallography, X-Ray ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/metabolism ; Humans ; Models, Molecular ; NAD/metabolism ; Nerve Tissue Proteins/chemistry ; Nerve Tissue Proteins/metabolism ; Protein Multimerization
Chemical Substances	Co-Repressor Proteins ; DNA-Binding Proteins ; Nerve Tissue Proteins ; NAD (0U46U6E8UK) ; Alcohol Oxidoreductases (EC 1.1.-) ; CTBP2 protein, human (EC 1.1.-) ; C-terminal binding protein (EC 1.1.1.-)
Language	English
Publishing date	2018-04-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RA118.002514
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Article ; Online: Active-Site Tryptophan, the Target of Antineoplastic C-Terminal Binding Protein Inhibitors, Mediates Inhibitor Disruption of CtBP Oligomerization and Transcription Coregulatory Activities.

Dcona, M Michael / Damle, Priyadarshan K / Zarate-Perez, Francisco / Morris, Benjamin L / Nawaz, Zaid / Dennis, Michael J / Deng, Xiaoyan / Korwar, Sudha / Singh, Sahib J / Ellis, Keith C / Royer, William E / Bandyopadhyay, Dipankar / Escalante, Carlos / Grossman, Steven R

Molecular pharmacology

2019 Volume 96, Issue 1, Page(s) 99–108

Abstract: C-terminal binding proteins (CtBP1/2) are oncogenic transcriptional coregulators and dehydrogenases ...

Abstract	C-terminal binding proteins (CtBP1/2) are oncogenic transcriptional coregulators and dehydrogenases often overexpressed in multiple solid tumors, including breast, colon, and ovarian cancer, and associated with poor survival. CtBPs act by repressing expression of genes responsible for apoptosis (e.g., PUMA, BIK) and metastasis-associated epithelial-mesenchymal transition (e.g., CDH1), and by activating expression of genes that promote migratory and invasive properties of cancer cells (e.g., TIAM1) and genes responsible for enhanced drug resistance (e.g., MDR1). CtBP's transcriptional functions are also critically dependent on oligomerization and nucleation of transcriptional complexes. Recently, we have developed a family of CtBP dehydrogenase inhibitors, based on the parent 2-hydroxyimino-3-phenylpropanoic acid (HIPP), that specifically disrupt cancer cell viability, abrogate CtBP's transcriptional function, and block polyp formation in a mouse model of intestinal polyposis that depends on CtBP's oncogenic functions. Crystallographic analysis revealed that HIPP interacts with CtBP1/2 at a conserved active site tryptophan (W318/324; CtBP1/2) that is unique among eukaryotic D2-dehydrogenases. To better understand the mechanism of action of HIPP-class inhibitors, we investigated the contribution of W324 to CtBP2's biochemical and physiologic activities utilizing mutational analysis. Indeed, W324 was necessary for CtBP2 self-association, as shown by analytical ultracentrifugation and in vivo cross-linking. Additionally, W324 supported CtBP's association with the transcriptional corepressor CoREST, and was critical for CtBP2 induction of cell motility. Notably, the HIPP derivative 4-chloro-HIPP biochemically and biologically phenocopied mutational inactivation of CtBP2 W324. Our data support further optimization of W318/W324-interacting CtBP dehydrogenase inhibitors that are emerging as a novel class of cancer cell-specific therapeutic.
MeSH term(s)	Alcohol Oxidoreductases/antagonists & inhibitors ; Alcohol Oxidoreductases/chemistry ; Alcohol Oxidoreductases/genetics ; Animals ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Catalytic Domain ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Survival/drug effects ; DNA-Binding Proteins/antagonists & inhibitors ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/genetics ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Epithelial-Mesenchymal Transition/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; HCT116 Cells ; Humans ; Hydroxylamines/chemistry ; Hydroxylamines/pharmacology ; Intestinal Polyposis/drug therapy ; Intestinal Polyposis/metabolism ; Mice ; Mutagenesis, Site-Directed ; Phenylpropionates/chemistry ; Phenylpropionates/pharmacology ; Protein Multimerization/drug effects ; Tryptophan/metabolism ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents ; DNA-Binding Proteins ; Enzyme Inhibitors ; Hydroxylamines ; Phenylpropionates ; Tryptophan (8DUH1N11BX) ; Alcohol Oxidoreductases (EC 1.1.-) ; C-terminal binding protein (EC 1.1.1.-)
Language	English
Publishing date	2019-04-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	124034-1
ISSN	1521-0111 ; 0026-895X
ISSN (online)	1521-0111
ISSN	0026-895X
DOI	10.1124/mol.118.114363
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Article ; Online: T Cells Promote Bronchial Epithelial Cell Secretion of Matrix Metalloproteinase-9 via a C-C Chemokine Receptor Type 2 Pathway: Implications for Chronic Lung Allograft Dysfunction.

Pain, M / Royer, P-J / Loy, J / Girardeau, A / Tissot, A / Lacoste, P / Roux, A / Reynaud-Gaubert, M / Kessler, R / Mussot, S / Dromer, C / Brugière, O / Mornex, J-F / Guillemain, R / Dahan, M / Knoop, C / Botturi, K / Pison, C / Danger, R /

Brouard, S / Magnan, A

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

2017 Volume 17, Issue 6, Page(s) 1502–1514

Abstract: ... from lung transplant recipients (LTRs): 49 stable, 29 with BOS, and 16 with RAS. We demonstrated that C-C motif ... chemokine 2 secreted by T cells supports TGF-β-induced MMP-9 production by BECs after binding to C-C ...

Abstract	Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. CLAD manifests as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). Alloimmune reactions and epithelial-to-mesenchymal transition have been suggested in BOS. However, little is known regarding the role of allogenicity in epithelial cell differentiation. Primary human bronchial epithelial cells (BECs) were treated with activated T cells in the presence or absence of transforming growth factor (TGF)-β. The expression of epithelial and mesenchymal markers was investigated. The secretion of inflammatory cytokines and matrix metalloproteinase (MMP)-9 was measured in culture supernatants and in plasma from lung transplant recipients (LTRs): 49 stable, 29 with BOS, and 16 with RAS. We demonstrated that C-C motif chemokine 2 secreted by T cells supports TGF-β-induced MMP-9 production by BECs after binding to C-C chemokine receptor type 2. Longitudinal investigation in LTRs revealed a rise in plasma MMP-9 before CLAD onset. Multivariate analysis showed that plasma MMP-9 was independently associated with BOS (odds ratio [OR] = 6.19, p = 0.002) or RAS (OR = 3.9, p = 0.024) and predicted the occurrence of CLAD 12 months before the functional diagnosis. Thus, immune cells support airway remodeling through the production of MMP-9. Plasma MMP-9 is a potential predictive biomarker of CLAD.
MeSH term(s)	Adult ; Allografts ; Biomarkers/blood ; Bronchi/immunology ; Bronchi/metabolism ; Bronchi/pathology ; Chronic Disease ; Cytokines/metabolism ; Epithelial Cells/immunology ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Female ; Follow-Up Studies ; Graft Rejection/blood ; Graft Rejection/diagnosis ; Graft Rejection/etiology ; Graft Survival/immunology ; Humans ; Longitudinal Studies ; Lung Diseases/complications ; Lung Diseases/surgery ; Lung Transplantation/adverse effects ; Male ; Matrix Metalloproteinase 9/blood ; Middle Aged ; Postoperative Complications ; Prognosis ; Receptors, CCR2/metabolism ; Risk Factors ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Transforming Growth Factor beta/metabolism
Chemical Substances	Biomarkers ; CCR2 protein, human ; Cytokines ; Receptors, CCR2 ; Transforming Growth Factor beta ; MMP9 protein, human (EC 3.4.24.35) ; Matrix Metalloproteinase 9 (EC 3.4.24.35)
Language	English
Publishing date	2017-01-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1111/ajt.14166
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Article ; Online: Hepatitis C virus drugs that inhibit SARS-CoV-2 papain-like protease synergize with remdesivir to suppress viral replication in cell culture.

Bafna, Khushboo / White, Kris / Harish, Balasubramanian / Rosales, Romel / Ramelot, Theresa A / Acton, Thomas B / Moreno, Elena / Kehrer, Thomas / Miorin, Lisa / Royer, Catherine A / García-Sastre, Adolfo / Krug, Robert M / Montelione, Gaetano T

Cell reports

2021 Volume 35, Issue 7, Page(s) 109133

Abstract: ... hepatitis C virus (HCV) protease-inhibitor drugs as potential SARS-CoV-2 antivirals. There is a striking structural ...

Abstract	Effective control of COVID-19 requires antivirals directed against SARS-CoV-2. We assessed 10 hepatitis C virus (HCV) protease-inhibitor drugs as potential SARS-CoV-2 antivirals. There is a striking structural similarity of the substrate binding clefts of SARS-CoV-2 main protease (M
MeSH term(s)	Adenosine Monophosphate/analogs & derivatives ; Adenosine Monophosphate/pharmacology ; Alanine/analogs & derivatives ; Alanine/pharmacology ; Antiviral Agents/pharmacology ; COVID-19/virology ; Cell Culture Techniques ; Cell Line ; Coronavirus Papain-Like Proteases/antagonists & inhibitors ; Coronavirus Papain-Like Proteases/metabolism ; Drug Repositioning/methods ; Drug Synergism ; Hepacivirus/drug effects ; Hepatitis C/drug therapy ; Humans ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Protease Inhibitors/pharmacology ; SARS-CoV-2/drug effects ; SARS-CoV-2/enzymology ; Virus Replication/drug effects ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents ; Protease Inhibitors ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Coronavirus Papain-Like Proteases (EC 3.4.22.2) ; papain-like protease, SARS-CoV-2 (EC 3.4.22.2) ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2021-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.109133
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Article ; Online: Continuum of hepatitis C care in France

Coralie Hermetet / Frederic Dubois / Catherine Gaudy-Graffin / Yannick Bacq / Bernard Royer / Christophe Gaborit / Louis D'Alteroche / Jean Claude Desenclos / Philippe Roingeard / Leslie Grammatico-Guillon

PLoS ONE, Vol 12, Iss 8, p e

A 20-year cohort study.

2017 Volume 0183232

Abstract: Hepatitis C virus (HCV)-infected patients require a specific continuum of care (CoC) from HCV ...

Abstract	Hepatitis C virus (HCV)-infected patients require a specific continuum of care (CoC) from HCV screening to treatment. We assessed CoC of HCV-infected patients in a longitudinal study.We established a cohort of subjects undergoing HCV screening (high alanine aminotransferase levels or risk factors) during preventive consultations at a French regional medical center from 1993 to 2013. Patients were considered to be HCV-infected if HCV RNA was detected in their serum. CoC was assessed as described by Viner et al. (Hepatology 2015): Stage 1, HCV screening; Stage 2, HCV RNA testing; Stage 3, continuing care; Stage 4, antiviral treatment. Cox multivariate analysis was performed to identify factors favoring CoC, defined as at least one course of antiviral treatment.In total, 12,993 HCV tests were performed and 478 outpatients were found to be HCV-seropositive. We included 417 seropositive patients, after excluding false positives and patients lost to follow-up. The baseline characteristics of the patients were: sex ratio (M/F) 1.4; mean age 38.5 years; intravenous drug use (IDU) in 55%; and 28% in unstable social situations, estimated by the EPICES deprivation score. Antiviral treatment was initiated for 179 (42.9%) of the 379 (90.9%) patients attending specialist consultations. CoC was associated with screening after 1997 (HR 2.0, 95%CI 1.4-2.9), age > 45 years (HR 1.5, 95%CI 1.02-2.3), patient acceptance of care (HR 9.3, 95%CI 5.4-16.10), specialist motivation for treatment (HR 10.9, 95%CI 7.4-16.0), and absence of cancer (HR 6.7, 95%CI 1.6-27.9). Other comorbid conditions, such as depression and IDU, were not associated with CoC.Our 20-year cohort study reveals the real-life continuum of care for HCV-infected patients in France. The number of patients involved in HCV care after positive testing was substantial due to the organization of healthcare in France. An improved CoC along with new direct-acting antivirals should help to decrease chronic HCV infection.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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Order via subito

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Inter-library loan at ZB MED