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Article ; Online: Analysis of flow-induced transcriptional response and cell alignment of different sources of endothelial cells used in vascular tissue engineering.

Rojas-González, Diana M / Babendreyer, Aaron / Ludwig, Andreas / Mela, Petra

2023 Volume 13, Issue 1, Page(s) 14384

Abstract: Endothelialization of tissue-engineered vascular grafts has proven crucial for implant functionality and thus clinical outcome, however, the choice of endothelial cells (ECs) is often driven by availability rather than by the type of vessel to be ... ...

Abstract	Endothelialization of tissue-engineered vascular grafts has proven crucial for implant functionality and thus clinical outcome, however, the choice of endothelial cells (ECs) is often driven by availability rather than by the type of vessel to be replaced. In this work we studied the response to flow of different human ECs with the aim of examining whether their response in vitro is dictated by their original in vivo conditions. Arterial, venous, and microvascular ECs were cultured under shear stress (SS) of 0, 0.3, 3, 1, 10, and 30 dyne/cm
MeSH term(s)	Humans ; Endothelial Cells ; Tissue Engineering ; Antioxidants ; Blood Vessel Prosthesis ; Cell Cycle
Chemical Substances	Antioxidants
Language	English
Publishing date	2023-09-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-41247-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Mechanic Forces Promote Brain Endothelial Activation by SARS-CoV-2 Spike Protein.

Babendreyer, Aaron / Ludwig, Andreas

Stroke

2020 Volume 52, Issue 1, Page(s) 271–273

MeSH term(s)	Brain/metabolism ; COVID-19 ; Humans ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/metabolism
Chemical Substances	Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-11-09
Publishing country	United States
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	80381-9
ISSN	1524-4628 ; 0039-2499 ; 0749-7954
ISSN (online)	1524-4628
ISSN	0039-2499 ; 0749-7954
DOI	10.1161/STROKEAHA.120.033119
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Article: Mechanic Forces Promote Brain Endothelial Activation by SARS-CoV-2 Spike Protein

Babendreyer, Aaron / Ludwig, Andreas

Stroke

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #916326
Database	COVID19

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Article ; Online: Mechanic Forces Promote Brain Endothelial Activation by SARS-CoV-2 Spike Protein

Babendreyer, Aaron / Ludwig, Andreas

Stroke ; ISSN 0039-2499 1524-4628

2020

Keywords	Advanced and Specialised Nursing ; Clinical Neurology ; Cardiology and Cardiovascular Medicine ; covid19
Language	English
Publisher	Ovid Technologies (Wolters Kluwer Health)
Publishing country	us
Document type	Article ; Online
DOI	10.1161/strokeaha.120.033119
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Functional changes in long-term incubated rat precision-cut lung slices.

Nußbaum, Sarah Marie / Krabbe, Julia / Böll, Svenja / Babendreyer, Aaron / Martin, Christian

Respiratory research

2022 Volume 23, Issue 1, Page(s) 261

Abstract: Background: Respiratory diseases represent a global health burden. Because research on therapeutic strategies of airway diseases is essential, the technique of precision-cut lung slices (PCLS) has been developed and widely studied. PCLS are an ... ...

Abstract	Background: Respiratory diseases represent a global health burden. Because research on therapeutic strategies of airway diseases is essential, the technique of precision-cut lung slices (PCLS) has been developed and widely studied. PCLS are an alternative ex vivo model and have the potential to replace and reduce in vivo animal models. So far, the majority of studies was conducted with short-term cultivated PCLS (≤ 72 h). As there is large interest in research of chronic diseases and chronic toxicity, feasibility of cultivating human PCLS long-term over 2 weeks and recently over 4 weeks was investigated by another research group with successful results. Our aim was to establish a model of long-term cultivated rat PCLS over a period of 29 days. Methods: Rat PCLS were cultured for 29 days and analysed regarding viability, histopathology, reactivity and gene expression at different time points during cultivation. Results: Cultivation of rat PCLS over a 29-day time period was successful with sustained viability. Furthermore, the ability of bronchoconstriction was maintained between 13 and 25 days, depending on the mediator. However, reduced relaxation, altered sensitivity and increased respiratory tone were observed. Regarding transcription, alteration in gene expression pattern of the investigated target genes was ascertained during long-term cultivation with mixed results. Furthermore, the preparation of PCLS seems to influence messenger ribonucleic acid (mRNA) expression of most target genes. Moreover, the addition of fetal bovine serum (FBS) to the culture medium did not improve viability of PCLS. In contrast to medium without FBS, FBS seems to affect measurements and resulted in marked cellular changes of metaplastic and/or regenerative origin. Conclusions: Overall, a model of long-term cultivated rat PCLS which stays viable for 29 days and reactive for at least 13 days could be established. Before long-term cultivated PCLS can be used for in-depth study of chronic diseases and chronic toxicity, further investigations have to be made.
MeSH term(s)	Animals ; Bronchoconstriction ; Humans ; Lung/pathology ; RNA ; RNA, Messenger ; Rats ; Serum Albumin, Bovine ; Tissue Culture Techniques
Chemical Substances	RNA, Messenger ; Serum Albumin, Bovine (27432CM55Q) ; RNA (63231-63-0)
Language	English
Publishing date	2022-09-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-993X
ISSN (online)	1465-993X
ISSN	1465-993X
DOI	10.1186/s12931-022-02169-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Differential maturation and chaperone dependence of the paralogous protein kinases DYRK1A and DYRK1B.

Papenfuss, Marco / Lützow, Svenja / Wilms, Gerrit / Babendreyer, Aaron / Flaßhoff, Maren / Kunick, Conrad / Becker, Walter

Scientific reports

2022 Volume 12, Issue 1, Page(s) 2393

Abstract: The HSP90/CDC37 chaperone system not only assists the maturation of many protein kinases but also maintains their structural integrity after folding. The interaction of mature kinases with the HSP90/CDC37 complex is governed by the conformational ... ...

Abstract	The HSP90/CDC37 chaperone system not only assists the maturation of many protein kinases but also maintains their structural integrity after folding. The interaction of mature kinases with the HSP90/CDC37 complex is governed by the conformational stability of the catalytic domain, while the initial folding of the protein kinase domain is mechanistically less well characterized. DYRK1A (Dual-specificity tyrosine (Y)-phosphorylation Regulated protein Kinase 1A) and DYRK1B are closely related protein kinases with discordant HSP90 client status. DYRK kinases stoichiometrically autophosphorylate on a tyrosine residue immediately after folding, which served us as a traceable marker of successful maturation. In the present study, we used bacterial expression systems to compare the capacity of autonomous maturation of DYRK1A and DYRK1B in the absence of eukaryotic cofactors or chaperones. Under these conditions, autophosphorylation of human DYRK1B was severely compromised when compared with DYRK1A or DYRK1B orthologs from zebrafish and Xenopus. Maturation of human DYRK1B could be restored by bacterial expression at lower temperatures, suggesting that folding was not absolutely dependent on eukaryotic chaperones. The differential folding properties of DYRK1A and DYRK1B were largely due to divergent sequences of the C-terminal lobes of the catalytic domain. Furthermore, the mature kinase domain of DYRK1B featured lower thermal stability than that of DYRK1A when exposed to heat challenge in vitro or in living cells. In summary, our study enhances the mechanistic understanding of the differential thermodynamic properties of two closely related protein kinases during initial folding and as mature kinases.
MeSH term(s)	Animals ; Catalytic Domain ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Chaperonins/genetics ; Chaperonins/metabolism ; HSP90 Heat-Shock Proteins/genetics ; HSP90 Heat-Shock Proteins/metabolism ; Humans ; Phosphorylation ; Protein Domains ; Protein Folding ; Protein Kinases/chemistry ; Protein Kinases/genetics ; Protein Kinases/metabolism ; Protein Serine-Threonine Kinases/chemistry ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Protein-Tyrosine Kinases/chemistry ; Protein-Tyrosine Kinases/genetics ; Protein-Tyrosine Kinases/metabolism ; Xenopus/genetics ; Xenopus/metabolism ; Xenopus Proteins/chemistry ; Xenopus Proteins/genetics ; Xenopus Proteins/metabolism ; Zebrafish/genetics ; Zebrafish/metabolism ; Zebrafish Proteins/chemistry ; Zebrafish Proteins/genetics ; Zebrafish Proteins/metabolism ; Dyrk Kinases
Chemical Substances	CDC37 protein, human ; Cell Cycle Proteins ; HSP90 Heat-Shock Proteins ; Xenopus Proteins ; Zebrafish Proteins ; Protein Kinases (EC 2.7.-) ; dyrk1aa protein, zebrafish (EC 2.7.-) ; Dyrk1A protein, Xenopus (EC 2.7.1.-) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Chaperonins (EC 3.6.1.-)
Language	English
Publishing date	2022-02-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-06423-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Influence of Aerosolization on Endothelial Cells for Efficient Cell Deposition in Biohybrid and Regenerative Applications.

Cheremkhina, Maria / Klein, Sarah / Babendreyer, Aaron / Ludwig, Andreas / Schmitz-Rode, Thomas / Jockenhoevel, Stefan / Cornelissen, Christian G / Thiebes, Anja Lena

Micromachines

2023 Volume 14, Issue 3

Abstract: The endothelialization of gas exchange membranes can increase the hemocompatibility of extracorporeal membrane oxygenators and thus become a long-term lung replacement option. Cell seeding on large or uneven surfaces of oxygenator membranes is ... ...

Abstract	The endothelialization of gas exchange membranes can increase the hemocompatibility of extracorporeal membrane oxygenators and thus become a long-term lung replacement option. Cell seeding on large or uneven surfaces of oxygenator membranes is challenging, with cell aerosolization being a possible solution. In this study, we evaluated the endothelial cell aerosolization for biohybrid lung application. A Vivostat
Language	English
Publishing date	2023-02-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2620864-7
ISSN	2072-666X
ISSN	2072-666X
DOI	10.3390/mi14030575
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Article ; Online: EGF-Receptor against Amphiregulin (AREG) Influences Costimulatory Molecules on Monocytes and T Cells and Modulates T-Cell Responses.

Dreschers, Stephan / Platen, Christopher / Oppermann, Louise / Doughty, Caitlin / Ludwig, Andreas / Babendreyer, Aaron / Orlikowsky, Thorsten W

Journal of immunology research

2023 Volume 2023, Page(s) 8883045

Abstract: Amphiregulin (AREG) is a ligand of the epidermal growth factor receptor (EGFR) and has been shown to regulate the phagocytosis-induced cell death of monocytes in peripheral blood. AREG-dependent apoptotic signaling engages factors of the intrinsic and ... ...

Abstract	Amphiregulin (AREG) is a ligand of the epidermal growth factor receptor (EGFR) and has been shown to regulate the phagocytosis-induced cell death of monocytes in peripheral blood. AREG-dependent apoptotic signaling engages factors of the intrinsic and extrinsic apoptotic pathway, such as BCL-2, BCL-XL, and death ligand/receptor CD95/CD95L. Here, we tested the hypothesis that AREG influences costimulatory monocyte functions, which are crucial for T-cell responses. We found a stronger expression of AREG and EGFR in monocytes compared to lymphocytes. As a novel function of AREG, we observed reduced T-cell proliferation following polyclonal T-cell stimulation with OKT3. This reduction of proliferation occurred in the presence of monocytes as well as in their absence, monocyte signaling being replaced by crosslinking of OKT3. Increasing concentrations of AREG down-modulated the concentration of costimulatory B7 molecules (CD80/CD86) and HLA-DR on monocytes. In proliferation assays, CD28 expression on T cells was down-modulated on the application of OKT3 but unaltered by AREG. LcK activation, following OKT3-stimulation, was reduced in T cells that had been coincubated with AREG. The effects of AREG on T-cell phenotypes were also present when monocytes were depleted and OKT3 was crosslinked. The rearranged expression of immunological synapse proteins was accompanied by an alteration of T-cell polarization. Although the proportion of regulatory T cells was not shifted by AREG, IL-17-expressing T cells were significantly enhanced, with a bias toward TH1-polarization. Taken together, these results suggest that AREG acts as an immunoregulatory molecule at the interface between antigen-presenting cells and T cells.
MeSH term(s)	Amphiregulin/metabolism ; Monocytes ; Epidermal Growth Factor/metabolism ; Ligands ; Muromonab-CD3/metabolism ; ErbB Receptors/genetics
Chemical Substances	Amphiregulin ; Epidermal Growth Factor (62229-50-9) ; Ligands ; Muromonab-CD3 ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2023-11-24
Publishing country	Egypt
Document type	Journal Article
ZDB-ID	2817541-4
ISSN	2314-7156 ; 2314-7156
ISSN (online)	2314-7156
ISSN	2314-7156
DOI	10.1155/2023/8883045
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity.

Bläsius, Katharina / Ludwig, Lena / Knapp, Sarah / Flaßhove, Charlotte / Sonnabend, Friederike / Keller, Diandra / Tacken, Nikola / Gao, Xintong / Kahveci-Türköz, Selcan / Grannemann, Caroline / Babendreyer, Aaron / Adrain, Colin / Huth, Sebastian / Baron, Jens Malte / Ludwig, Andreas / Düsterhöft, Stefan

Cellular and molecular life sciences : CMLS

2024 Volume 81, Issue 1, Page(s) 102

Abstract: The protease ADAM17 plays an important role in inflammation and cancer and is regulated by iRhom2. Mutations in the cytosolic N-terminus of human iRhom2 cause tylosis with oesophageal cancer (TOC). In mice, partial deletion of the N-terminus results in a ...

Abstract	The protease ADAM17 plays an important role in inflammation and cancer and is regulated by iRhom2. Mutations in the cytosolic N-terminus of human iRhom2 cause tylosis with oesophageal cancer (TOC). In mice, partial deletion of the N-terminus results in a curly hair phenotype (cub). These pathological consequences are consistent with our findings that iRhom2 is highly expressed in keratinocytes and in oesophageal cancer. Cub and TOC are associated with hyperactivation of ADAM17-dependent EGFR signalling. However, the underlying molecular mechanisms are not understood. We have identified a non-canonical, phosphorylation-independent 14-3-3 interaction site that encompasses all known TOC mutations. Disruption of this site dysregulates ADAM17 activity. The larger cub deletion also includes the TOC site and thus also dysregulated ADAM17 activity. The cub deletion, but not the TOC mutation, also causes severe reductions in stimulated shedding, binding, and stability of ADAM17, demonstrating the presence of additional regulatory sites in the N-terminus of iRhom2. Overall, this study contrasts the TOC and cub mutations, illustrates their different molecular consequences, and reveals important key functions of the iRhom2 N-terminus in regulating ADAM17.
MeSH term(s)	Humans ; Mice ; Animals ; Phosphorylation ; Carrier Proteins/metabolism ; ADAM17 Protein/genetics ; ADAM17 Protein/metabolism ; Signal Transduction/genetics ; Mutation ; Esophageal Neoplasms/genetics ; Keratoderma, Palmoplantar
Chemical Substances	Carrier Proteins ; ADAM17 Protein (EC 3.4.24.86) ; ADAM17 protein, human (EC 3.4.24.86) ; iRhom2 protein, mouse
Language	English
Publishing date	2024-02-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-024-05132-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Mechanical activation of lung epithelial cells through the ion channel Piezo1 activates the metalloproteinases ADAM10 and ADAM17 and promotes growth factor and adhesion molecule release.

Grannemann, Caroline / Pabst, Alessa / Honert, Annika / Schieren, Jana / Martin, Christian / Hank, Sophia / Böll, Svenja / Bläsius, Katharina / Düsterhöft, Stefan / Jahr, Holger / Merkel, Rudolf / Leube, Rudolf / Babendreyer, Aaron / Ludwig, Andreas

Biomaterials advances

2023 Volume 152, Page(s) 213516

Abstract: In the lung, pulmonary epithelial cells undergo mechanical stretching during ventilation. The associated cellular mechanoresponse is still poorly understood at the molecular level. Here, we demonstrate that activation of the mechanosensitive cation ... ...

Abstract	In the lung, pulmonary epithelial cells undergo mechanical stretching during ventilation. The associated cellular mechanoresponse is still poorly understood at the molecular level. Here, we demonstrate that activation of the mechanosensitive cation channel Piezo1 in a human epithelial cell line (H441) and in primary human lung epithelial cells induces the proteolytic activity of the metalloproteinases ADAM10 and ADAM17 at the plasma membrane. These ADAMs are known to convert cell surface expressed proteins into soluble and thereby play major roles in proliferation, barrier regulation and inflammation. We observed that chemical activation of Piezo1 promotes cleavage of substrates that are specific for either ADAM10 or ADAM17. Activation of Piezo1 also induced the synthesis and ADAM10/17-dependent release of the growth factor amphiregulin (AREG). In addition, junctional adhesion molecule A (JAM-A) was shed in an ADAM10/17-dependent manner resulting in a reduction of cell contacts. Stretching experiments combined with Piezo1 knockdown further demonstrated that mechanical activation promotes shedding via Piezo1. Most importantly, high pressure ventilation of murine lungs increased AREG and JAM-A release into the alveolar space, which was reduced by a Piezo1 inhibitor. Our study provides a novel link between stretch-induced Piezo1 activation and the activation of ADAM10 and ADAM17 in lung epithelium. This may help to understand acute respiratory distress syndrome (ARDS) which is induced by ventilation stress and goes along with perturbed epithelial permeability and release of growth factors.
MeSH term(s)	Humans ; Mice ; Animals ; Amyloid Precursor Protein Secretases/genetics ; Amyloid Precursor Protein Secretases/metabolism ; Lung/metabolism ; ADAM10 Protein/genetics ; ADAM10 Protein/metabolism ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Epithelial Cells/metabolism ; Ion Channels/metabolism ; Intercellular Signaling Peptides and Proteins/genetics ; Intercellular Signaling Peptides and Proteins/metabolism ; Metalloproteases/metabolism ; ADAM17 Protein/genetics ; ADAM17 Protein/metabolism
Chemical Substances	Amyloid Precursor Protein Secretases (EC 3.4.-) ; ADAM10 Protein (EC 3.4.24.81) ; Membrane Proteins ; Ion Channels ; Intercellular Signaling Peptides and Proteins ; Metalloproteases (EC 3.4.-) ; ADAM10 protein, human (EC 3.4.24.81) ; ADAM17 protein, human (EC 3.4.24.86) ; ADAM17 Protein (EC 3.4.24.86) ; Piezo1 protein, mouse
Language	English
Publishing date	2023-06-12
Publishing country	Netherlands
Document type	Journal Article
ISSN	2772-9508
ISSN (online)	2772-9508
DOI	10.1016/j.bioadv.2023.213516
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