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Article ; Conference proceedings: Das metastasierte Ösophaguskarzinom – eine chirurgisch therapierbare Erkrankung?

Knipper, K. / Krey, T. / Lyu, S. I. / Wirsik, N. M. / Schiffmann, L. M. / Fuchs, H. F. / Gebauer, F. / Schroeder, W. / Schloesser, H. A. / Popp, F. C. / Quaas, A. / Bruns, C. J. / Schmidt, T.

Zeitschrift für Gastroenterologie

2023 Volume 61, Issue 08

Event/congress	Viszeralmedizin 2023 77. Jahrestagung der DGVS mit Sektion Endoskopie Herbsttagung der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie mit den Arbeitsgemeinschaften der DGAV und Jahrestagung der CACP, Erst online. Dann Hamburg., 2023-09-11
Language	German
Publishing date	2023-08-01
Publisher	Georg Thieme Verlag
Publishing place	Stuttgart ; New York
Document type	Article ; Conference proceedings
ZDB-ID	201387-3
ISSN	1439-7803 ; 0044-2771 ; 0172-8504
ISSN (online)	1439-7803
ISSN	0044-2771 ; 0172-8504
DOI	10.1055/s-0043-1772038
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Zs.A 111: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Neuroprotektive Therapien bei Tauopathien.

Respondek, Gesine / Krey, Lea / Huber, Meret / Pflugrad, Henning / Wegner, Florian / Höglinger, Günter U

Der Nervenarzt

2021 Volume 92, Issue 12, Page(s) 1227–1238

Abstract: Tau pathology is now considered to be the main cause of a wide spectrum of neurodegenerative diseases, which are collectively referred to as tauopathies. These include primary tauopathies, in which tau plays the main role in the pathogenesis as well as ... ...

Title translation	Neuroprotective treatment of tauopathies.
Abstract	Tau pathology is now considered to be the main cause of a wide spectrum of neurodegenerative diseases, which are collectively referred to as tauopathies. These include primary tauopathies, in which tau plays the main role in the pathogenesis as well as secondary tauopathies, such as Alzheimer's disease, in which amyloid beta also plays a substantial role in the disease process in addition to the tau pathology. Primary tauopathies include progressive supranuclear palsy, corticobasal degeneration, Pick's disease and rare hereditary tauopathies, which are referred to as frontotemporal lobar degeneration with microtubule-associated protein tau (MAPT) mutation. Tauopathies differ from each other pathologically by the affected brain regions and cell types as well as by the biochemical characteristics of the aggregated tau protein. Various tau-centered neuroprotective treatment approaches are currently in preclinical and clinical development. They target different mechanisms, including the reduction of tau expression, inhibition of tau aggregation, dissolution of tau aggregates, improvement of cellular mechanisms to eliminate toxic tau species, stabilization of microtubules and prevention of intercellular tau spreading. This review article gives an overview of tauopathies and the current concepts for the development of disease-modifying treatment.
MeSH term(s)	Alzheimer Disease ; Amyloid beta-Peptides ; Corticobasal Degeneration ; Humans ; Tauopathies/drug therapy ; tau Proteins
Chemical Substances	Amyloid beta-Peptides ; tau Proteins
Language	German
Publishing date	2021-10-15
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	123291-5
ISSN	1433-0407 ; 0028-2804
ISSN (online)	1433-0407
ISSN	0028-2804
DOI	10.1007/s00115-021-01210-0
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Article ; Online: Is Continuous Eruption Related to Periodontal Changes? A 16-Year Follow-up.

Wiedemann, C / Pink, C / Daboul, A / Samietz, S / Völzke, H / Schulz-Kornas, E / Krey, K F / Holtfreter, B / Kocher, T

Journal of dental research

2021 Volume 100, Issue 8, Page(s) 875–882

Abstract: The aims of this study were to 1) determine if continuous eruption occurs in the maxillary teeth, 2) assess the magnitude of the continuous eruption, and 3) evaluate the effects of continuous eruption on the different periodontal parameters by using data ...

Abstract	The aims of this study were to 1) determine if continuous eruption occurs in the maxillary teeth, 2) assess the magnitude of the continuous eruption, and 3) evaluate the effects of continuous eruption on the different periodontal parameters by using data from the population-based cohort of the Study of Health in Pomerania (SHIP). The jaw casts of 140 participants from the baseline (SHIP-0) and 16-y follow-up (SHIP-3) were digitized as 3-dimensional models. Robust reference points were set to match the tooth eruption stage at SHIP-0 and SHIP-3. Reference points were set on the occlusal surface of the contralateral premolar and molar teeth, the palatal fossa of an incisor, and the rugae of the hard palate. Reference points were combined to represent 3 virtual occlusal planes. Continuous eruption was measured as the mean height difference between the 3 planes and rugae fix points at SHIP-0 and SHIP-3. Probing depth, clinical attachment levels, gingiva above the cementoenamel junction (gingival height), and number of missing teeth were clinically assessed in the maxilla. Changes in periodontal variables were regressed onto changes in continuous eruption after adjustment for age, sex, number of filled teeth, and education or tooth wear. Continuous tooth eruption >1 mm over the 16 y was found in 4 of 140 adults and averaged to 0.33 mm, equaling 0.021 mm/y. In the total sample, an increase in continuous eruption was significantly associated with decreases in mean gingival height (
MeSH term(s)	Adult ; Dental Occlusion ; Follow-Up Studies ; Humans ; Incisor ; Maxilla ; Tooth Eruption
Language	English
Publishing date	2021-03-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80207-4
ISSN	1544-0591 ; 0022-0345
ISSN (online)	1544-0591
ISSN	0022-0345
DOI	10.1177/0022034521999363
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Article ; Online: Spontaneous allelic variant in deafness-blindness gene Ush1g resulting in an expanded phenotype.

Vartanian, Vladimir / Krey, Jocelyn F / Chatterjee, Paroma / Curtis, Allison / Six, Makayla / Rice, Sean P M / Jones, Sherri M / Sampath, Harini / Allen, Charles N / Ryals, Renee C / Lloyd, R Stephen / Barr-Gillespie, Peter G

Genes, brain, and behavior

2023 Volume 22, Issue 4, Page(s) e12849

Abstract: Relationships between novel phenotypic behaviors and specific genetic alterations are often discovered using target-specific, directed mutagenesis or phenotypic selection following chemical mutagenesis. An alternative approach is to exploit deficiencies ... ...

Abstract	Relationships between novel phenotypic behaviors and specific genetic alterations are often discovered using target-specific, directed mutagenesis or phenotypic selection following chemical mutagenesis. An alternative approach is to exploit deficiencies in DNA repair pathways that maintain genetic integrity in response to spontaneously induced damage. Mice deficient in the DNA glycosylase NEIL1 show elevated spontaneous mutations, which arise from translesion DNA synthesis past oxidatively induced base damage. Several litters of Neil1 knockout mice included animals that were distinguished by their backwards-walking behavior in open-field environments, while maintaining frantic forward movements in their home cage environment. Other phenotypic manifestations included swim test failures, head tilting and circling. Mapping of the mutation that conferred these behaviors showed the introduction of a stop codon at amino acid 4 of the Ush1g gene. Ush1g
MeSH term(s)	Mice ; Animals ; Alleles ; Usher Syndromes/genetics ; Mutation ; Phenotype ; DNA Glycosylases/genetics
Chemical Substances	Neil1 protein, mouse (EC 3.2.2.-) ; DNA Glycosylases (EC 3.2.2.-)
Language	English
Publishing date	2023-06-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2075819-4
ISSN	1601-183X ; 1601-1848
ISSN (online)	1601-183X
ISSN	1601-1848
DOI	10.1111/gbb.12849
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Article ; Online: Drug repurposing screen identifies lonafarnib as respiratory syncytial virus fusion protein inhibitor.

Sake, Svenja M / Zhang, Xiaoyu / Rajak, Manoj Kumar / Urbanek-Quaing, Melanie / Carpentier, Arnaud / Gunesch, Antonia P / Grethe, Christina / Matthaei, Alina / Rückert, Jessica / Galloux, Marie / Larcher, Thibaut / Le Goffic, Ronan / Hontonnou, Fortune / Chatterjee, Arnab K / Johnson, Kristen / Morwood, Kaycie / Rox, Katharina / Elgaher, Walid A M / Huang, Jiabin /

Wetzke, Martin / Hansen, Gesine / Fischer, Nicole / Eléouët, Jean-Francois / Rameix-Welti, Marie-Anne / Hirsch, Anna K H / Herold, Elisabeth / Empting, Martin / Lauber, Chris / Schulz, Thomas F / Krey, Thomas / Haid, Sibylle / Pietschmann, Thomas

Nature communications

2024 Volume 15, Issue 1, Page(s) 1173

Abstract: ... 000 small molecules against RSV. We identify 21 primary candidates including RSV F and N protein ...

Abstract	Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infection in infants, older adults and the immunocompromised. Effective directly acting antivirals are not yet available for clinical use. To address this, we screen the ReFRAME drug-repurposing library consisting of 12,000 small molecules against RSV. We identify 21 primary candidates including RSV F and N protein inhibitors, five HSP90 and four IMPDH inhibitors. We select lonafarnib, a licensed farnesyltransferase inhibitor, and phase III candidate for hepatitis delta virus (HDV) therapy, for further follow-up. Dose-response analyses and plaque assays confirm the antiviral activity (IC
MeSH term(s)	Animals ; Female ; Mice ; Dibenzocycloheptenes ; Drug Repositioning ; Piperidines/pharmacology ; Piperidines/therapeutic use ; Pyridines ; Respiratory Syncytial Virus Infections/drug therapy ; Viral Fusion Proteins/genetics ; Viral Fusion Proteins/chemistry
Chemical Substances	Dibenzocycloheptenes ; lonafarnib (IOW153004F) ; Piperidines ; Pyridines ; Viral Fusion Proteins
Language	English
Publishing date	2024-02-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45241-y
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Article ; Online: Clinical and therapeutic significance of genetic variation in the GRIN gene family encoding NMDARs.

Benke, Tim A / Park, Kristen / Krey, Ilona / Camp, Chad R / Song, Rui / Ramsey, Amy J / Yuan, Hongjie / Traynelis, Stephen F / Lemke, Johannes

Neuropharmacology

2021 Volume 199, Page(s) 108805

Abstract: Considerable genetic variation of N-methyl-d-aspartate receptors (NMDARs) has recently become apparent, with many hundreds of de novo variants identified through widely available clinical genetic testing. Individuals with GRIN variants present with ... ...

Abstract	Considerable genetic variation of N-methyl-d-aspartate receptors (NMDARs) has recently become apparent, with many hundreds of de novo variants identified through widely available clinical genetic testing. Individuals with GRIN variants present with neurological conditions such as epilepsy, autism, intellectual disability (ID), movement disorders, schizophrenia and behavioral disorders. Determination of the functional consequence of genetic variation for NMDARs should lead to precision therapeutics. Furthermore, genetic animal models harboring human variants have the potential to reveal mechanisms that are shared among different neurological conditions, providing strategies that may allow treatment of individuals who are refractory to therapy. Preclinical studies in animal models and small open label trials in humans support this idea. However, additional functional data for variants and animal models corresponding to multiple individuals with the same genotype are needed to validate this approach and to lead to thoughtfully designed, randomized, placebo-controlled clinical trials, which could provide data in order to determine safety and efficacy of potential precision therapeutics.
MeSH term(s)	Animals ; Epilepsy/genetics ; Genetic Variation ; Humans ; Movement Disorders/genetics ; Neurodevelopmental Disorders/genetics ; Receptors, N-Methyl-D-Aspartate/genetics ; Schizophrenia/genetics
Chemical Substances	Receptors, N-Methyl-D-Aspartate
Language	English
Publishing date	2021-09-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2021.108805
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Article ; Online: Linked vaccination coverage surveys plus serosurveys among Ethiopian toddlers undertaken three years apart to compare coverage and serologic evidence of protection in districts implementing the RED-QI approach.

Campbell, James D / Pasetti, Marcela F / Oot, Lisa / Adam, Zenaw / Tefera, Mesfin / Beyane, Berhane / Mulholland, Nigisti / Steinglass, Robert / Krey, Rebecca / Chen, Wilbur H / Blackwelder, William C / Levine, Myron M

Vaccine

2021 Volume 39, Issue 40, Page(s) 5802–5813

Abstract: In low and middle-income countries, estimating the proportion of vaccinated toddlers in a population is important for controlling vaccine-preventable diseases by identifying districts where immunization services need strengthening. Estimates measured ... ...

Abstract	In low and middle-income countries, estimating the proportion of vaccinated toddlers in a population is important for controlling vaccine-preventable diseases by identifying districts where immunization services need strengthening. Estimates measured before and several years after specific interventions can assess program performance. However, employing different methods to derive vaccination coverage estimates often yield differing results. Methods: Linked vaccination coverage surveys and seroprotection surveys performed among ~300 toddlers 12-23 months of age in districts (woredas), one per region, of Ethiopia (total, ~900 toddlers) in 2013 to estimate the proportion vaccinated with tetanus toxoid (a proxy for pentavalent vaccine) and measles vaccine. The surveys were followed by implementation of the Reaching Every District using Quality Improvement (RED-QI) approach to strengthen the immunization system. Linked coverage/serosurveys were repeated in 2016 to assess effects of the interventions on vaccination coverage. Indicators included "documented coverage" (vaccination card and/or health facility register records) and "crude coverage" (documented plus parent/caretaker recall for children without cards). Seroprotection thresholds were IgG-ELISA tetanus antitoxin ≥0.05 IU/ml and plaque reduction neutralization (PRN) measles titers ≥120 mIU/ml. Findings: Improved markers in 2016 over 2013 include coverage of pentavalent vaccination, vaccination timeliness, and fewer missed opportunities to vaccinate. In parallel, tetanus seroprotection increased in the 3 woredas from 59.6% to 79.1%, 72.9% to 83.7%, and 94.3 to 99.3%. In 2015, the Ethiopian government conducted supplemental measles mass vaccination campaigns in several regions including one that involved a project woreda and the campaign overlapped with the RED-QI intervention timeframe; protective measles PRN titers there rose from 31.0% to 50.0%. Interpretation: The prevalence of seroprotective titers of tetanus antitoxin (stimulated by tetanus toxoid components within pentavalent vaccine) provides a reliable biomarker to identify children who received pentavalent vaccine. In the three study woredas, the RED-QI intervention appeared to improve immunization service delivery, as documented by enhanced pentavalent vaccine coverage, vaccination timeliness, and fewer missed vaccination opportunities. A measles mass vaccination campaign was followed by a markedly increased prevalence of measles PRN antibodies. Collectively, these observations suggest that wider implementation of RED-QI can strengthen immunization, and periodic linked vaccination surveys/serosurveys can monitor changes.
MeSH term(s)	Child, Preschool ; Humans ; Immunization Programs ; Measles/prevention & control ; Measles Vaccine ; Quality Improvement ; Vaccination Coverage
Chemical Substances	Measles Vaccine
Language	English
Publishing date	2021-08-28
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2021.08.071
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Article ; Conference proceedings: [No title information]

Laue, Fenja / Nörenberg, Pia / Kohn, Martin / Dinkelborg, Katja / Ssebyatika, George / Hüffner, Lucas / Zeiß, Frithjof / Wedemeyer, Heiner / Pietschmann, Thomas / Krey, Thomas / Behrendt, Patrick

Zeitschrift für Gastroenterologie

2023 Volume 61, Issue 01

Event/congress	39. Jahrestagung der Deutschen Arbeitsgemeinschaft zum Studium der Leber, Bochum, 2023-01-27
Language	German
Publishing date	2023-01-01
Publisher	Georg Thieme Verlag
Publishing place	Stuttgart ; New York
Document type	Article ; Conference proceedings
ZDB-ID	201387-3
ISSN	1439-7803 ; 0044-2771 ; 0172-8504
ISSN (online)	1439-7803
ISSN	0044-2771 ; 0172-8504
DOI	10.1055/s-0042-1760045
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Zs.A 111: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: A Hepatitis C virus genotype 1b post-transplant isolate with high replication efficiency in cell culture and its adaptation to infectious virus production in vitro and in vivo.

Heuss, Christian / Rothhaar, Paul / Burm, Rani / Lee, Ji-Young / Ralfs, Philipp / Haselmann, Uta / Ströh, Luisa J / Colasanti, Ombretta / Tran, Cong Si / Schäfer, Noemi / Schnitzler, Paul / Merle, Uta / Bartenschlager, Ralf / Patel, Arvind H / Graw, Frederik / Krey, Thomas / Laketa, Vibor / Meuleman, Philip / Lohmann, Volker

PLoS pathogens

2022 Volume 18, Issue 6, Page(s) e1010472

Abstract: Hepatitis C virus (HCV) is highly diverse and grouped into eight genotypes (gts). Infectious cell culture models are limited to a few subtypes and isolates, hampering the development of prophylactic vaccines. A consensus gt1b genome (termed GLT1) was ... ...

Abstract	Hepatitis C virus (HCV) is highly diverse and grouped into eight genotypes (gts). Infectious cell culture models are limited to a few subtypes and isolates, hampering the development of prophylactic vaccines. A consensus gt1b genome (termed GLT1) was generated from an HCV infected liver-transplanted patient. GLT1 replicated to an outstanding efficiency in Huh7 cells upon SEC14L2 expression, by use of replication enhancing mutations or with a previously developed inhibitor-based regimen. RNA replication levels almost reached JFH-1, but full-length genomes failed to produce detectable amounts of infectious virus. Long-term passaging led to the adaptation of a genome carrying 21 mutations and concomitant production of high levels of transmissible infectivity (GLT1cc). During the adaptation, GLT1 spread in the culture even in absence of detectable amounts of free virus, likely due to cell-to-cell transmission, which appeared to substantially contribute to spreading of other isolates as well. Mechanistically, genome replication and particle production efficiency were enhanced by adaptation, while cell entry competence of HCV pseudoparticles was not affected. Furthermore, GLT1cc retained the ability to replicate in human liver chimeric mice, which was critically dependent on a mutation in domain 3 of nonstructural protein NS5A. Over the course of infection, only one mutation in the surface glycoprotein E2 consistently reverted to wildtype, facilitating assembly in cell culture but potentially affecting CD81 interaction in vivo. Overall, GLT1cc is an efficient gt1b infectious cell culture model, paving the road to a rationale-based establishment of new infectious HCV isolates and represents an important novel tool for the development of prophylactic HCV vaccines.
MeSH term(s)	Animals ; Cell Culture Techniques ; Genotype ; Hepacivirus ; Hepatitis C ; Humans ; Mice ; Mutation ; Viral Nonstructural Proteins/metabolism ; Virus Replication
Chemical Substances	Viral Nonstructural Proteins
Language	English
Publishing date	2022-06-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1010472
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Article ; Online: A CMV-induced adaptive human Vδ1+ γδ T cell clone recognizes HLA-DR.

Deseke, Malte / Rampoldi, Francesca / Sandrock, Inga / Borst, Eva / Böning, Heike / Ssebyatika, George Liam / Jürgens, Carina / Plückebaum, Nina / Beck, Maleen / Hassan, Ahmed / Tan, Likai / Demera, Abdi / Janssen, Anika / Steinberger, Peter / Koenecke, Christian / Viejo-Borbolla, Abel / Messerle, Martin / Krey, Thomas / Prinz, Immo

The Journal of experimental medicine

2022 Volume 219, Issue 9

Abstract: The innate and adaptive roles of γδ T cells and their clonal γδ T cell receptors (TCRs) in immune responses are still unclear. Recent studies of γδ TCR repertoire dynamics showed massive expansion of individual Vδ1+ γδ T cell clones during viral ... ...

Abstract	The innate and adaptive roles of γδ T cells and their clonal γδ T cell receptors (TCRs) in immune responses are still unclear. Recent studies of γδ TCR repertoire dynamics showed massive expansion of individual Vδ1+ γδ T cell clones during viral infection. To judge whether such expansion is random or actually represents TCR-dependent adaptive immune responses, information about their cognate TCR ligands is required. Here, we used CRISPR/Cas9-mediated screening to identify HLA-DRA, RFXAP, RFX5, and CIITA as required for target cell recognition of a CMV-induced Vγ3Vδ1+ TCR, and further characterization revealed a direct interaction of this Vδ1+ TCR with the MHC II complex HLA-DR. Since MHC II is strongly upregulated by interferon-γ, these results suggest an inflammation-induced MHC-dependent immune response of γδ T cells.
MeSH term(s)	Clone Cells ; Cytomegalovirus Infections ; HLA-DR Antigens ; Humans ; Intraepithelial Lymphocytes ; Receptors, Antigen, T-Cell, gamma-delta ; T-Lymphocyte Subsets
Chemical Substances	HLA-DR Antigens ; Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2022-07-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20212525
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