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Article ; Online: New ‘kids’ on the voltage‐gated proton channel block

Korpos, Éva / Papp, Ferenc

The FEBS Journal. 2023 Feb., v. 290, no. 4 p.970-973

2023

Abstract: So far one gene for Hv1 has been detected in studied species. The work presented by Chaves et al. in The FEBS Journal reported an ‘Unexpected expansion of the voltage‐gated proton channel family’. They searched for proton channel candidates and found ... ...

Abstract	So far one gene for Hv1 has been detected in studied species. The work presented by Chaves et al. in The FEBS Journal reported an ‘Unexpected expansion of the voltage‐gated proton channel family’. They searched for proton channel candidates and found three sequences in the genome of Aplysia californica (Ac), which were named AcHv1, AcHv2 and AcHv3. Based on electrophysiological experiments, AcHv1 and AcHv2 are voltage‐gated channels. While AcHv1 behaves like Hv1 in other species, that is, it is voltage and pH‐dependent, it can be inhibited by zinc and conducts protons outwardly, AcHv2 conducts protons inwards at symmetrical pH. AcHv3 constantly leaks protons, and its C‐terminal part contains several cytoplasmic retention motifs. Through carefully designed and carried out electrophysiological experiments, Chaves et al. determined the biophysical parameters of all three proton channels, such as the voltage and the pH dependence, the threshold‐voltage, the gating charge and the time constants of activation and inactivation. Comment on: https://doi.org/10.1111/febs.16617.
Keywords	Aplysia californica ; electric potential difference ; electrophysiology ; genes ; pH ; zinc
Language	English
Dates of publication	2023-02
Size	p. 970-973.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.16670
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: New 'kids' on the voltage-gated proton channel block.

Korpos, Éva / Papp, Ferenc

The FEBS journal

2022 Volume 290, Issue 4, Page(s) 970–973

Abstract: So far one gene for Hv1 has been detected in studied species. The work presented by Chaves et al. in The FEBS Journal reported an 'Unexpected expansion of the voltage-gated proton channel family'. They searched for proton channel candidates and found ... ...

Abstract	So far one gene for Hv1 has been detected in studied species. The work presented by Chaves et al. in The FEBS Journal reported an 'Unexpected expansion of the voltage-gated proton channel family'. They searched for proton channel candidates and found three sequences in the genome of Aplysia californica (Ac), which were named AcHv1, AcHv2 and AcHv3. Based on electrophysiological experiments, AcHv1 and AcHv2 are voltage-gated channels. While AcHv1 behaves like Hv1 in other species, that is, it is voltage and pH-dependent, it can be inhibited by zinc and conducts protons outwardly, AcHv2 conducts protons inwards at symmetrical pH. AcHv3 constantly leaks protons, and its C-terminal part contains several cytoplasmic retention motifs. Through carefully designed and carried out electrophysiological experiments, Chaves et al. determined the biophysical parameters of all three proton channels, such as the voltage and the pH dependence, the threshold-voltage, the gating charge and the time constants of activation and inactivation. Comment on: https://doi.org/10.1111/febs.16617.
MeSH term(s)	Protons ; Ion Channel Gating/genetics ; Ion Channels/metabolism ; Zinc/metabolism
Chemical Substances	Protons ; Ion Channels ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2022-10-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.16670
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Article ; Online: The Voltage-Gated Hv1 H

Cozzolino, Marco / Gyöngyösi, Adrienn / Korpos, Eva / Gogolak, Peter / Naseem, Muhammad Umair / Kállai, Judit / Lanyi, Arpad / Panyi, Gyorgy

International journal of molecular sciences

2023 Volume 24, Issue 7

Abstract: Myeloid-derived suppressor cells (MDSCs) are key determinants of the immunosuppressive microenvironment in tumors. As ion channels play key roles in the physiology/pathophysiology of immune cells, we aimed at studying the ion channel repertoire in tumor- ... ...

Abstract	Myeloid-derived suppressor cells (MDSCs) are key determinants of the immunosuppressive microenvironment in tumors. As ion channels play key roles in the physiology/pathophysiology of immune cells, we aimed at studying the ion channel repertoire in tumor-derived polymorphonuclear (PMN-MDSC) and monocytic (Mo-MDSC) MDSCs. Subcutaneous tumors in mice were induced by the Lewis lung carcinoma cell line (LLC). The presence of PMN-MDSC (CD11b
MeSH term(s)	Animals ; Mice ; Cell Line ; Monocytes ; Myeloid Cells ; Myeloid-Derived Suppressor Cells/metabolism ; Neoplasms/metabolism ; Tumor Microenvironment
Chemical Substances	Hv1 proton channel, mouse
Language	English
Publishing date	2023-03-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24076216
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Article: 5-Chloro-2-Guanidinobenzimidazole (ClGBI) Is a Non-Selective Inhibitor of the Human H

Szanto, Tibor G / Feher, Adam / Korpos, Eva / Gyöngyösi, Adrienn / Kállai, Judit / Mészáros, Beáta / Ovari, Krisztian / Lányi, Árpád / Panyi, Gyorgy / Varga, Zoltan

Pharmaceuticals (Basel, Switzerland)

2023 Volume 16, Issue 5

Abstract: 5-chloro-2-guanidinobenzimidazole (ClGBI), a small-molecule guanidine derivative, is a known effective inhibitor of the voltage-gated proton ( ... ...

Abstract	5-chloro-2-guanidinobenzimidazole (ClGBI), a small-molecule guanidine derivative, is a known effective inhibitor of the voltage-gated proton (H
Language	English
Publishing date	2023-04-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph16050656
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Influence of N-arylsulfonamido d-valine N-substituents on the selectivity and potency of matrix metalloproteinase inhibitors.

Paul Konken, Christian / Beutel, Bernd / Schinor, Benjamin / Song, Jian / Gerwien, Hanna / Korpos, Eva / Burmeister, Miriam / Riemann, Burkhard / Schäfers, Michael / Sorokin, Lydia / Haufe, Günter

Bioorganic & medicinal chemistry

2023 Volume 90, Page(s) 117350

Abstract: To develop matrix metalloproteinase inhibitors (MMPIs) for both therapy and medicinal imaging by fluorescence-based techniques or positron-emission tomography (PET), a small library of eighteen N-substituted N-arylsulfonamido d-valines were synthesized ... ...

Abstract	To develop matrix metalloproteinase inhibitors (MMPIs) for both therapy and medicinal imaging by fluorescence-based techniques or positron-emission tomography (PET), a small library of eighteen N-substituted N-arylsulfonamido d-valines were synthesized and their potency to inhibit two gelatinases (MMP-2, and MMP-9), two collagenases (MMP-8, and MMP-13) and macrophage elastase (MMP-12) was determined in a Structure-Activity-Relation study with ({4-[3-(5-methylthiophen-2-yl)-1,2,4-oxadiazol-5-yl]phenyl}sulfonyl)-d-valine (1) as a lead. All compounds were shown to be more potent MMP-2/-9 inhibitors (nanomolar range) compared to other tested MMPs. This is a remarkable result considering that a carboxylic acid group is the zinc binding moiety. The compound with a terminal fluoropropyltriazole group at the furan ring (P1' substituent) was only four times less potent in inhibiting MMP-2 activity than the lead compound 1, making this compound a promising probe for PET application (after using a prosthetic group approach to introduce fluorine-18). Compounds with a TEG spacer and a terminal azide or even a fluorescein moiety at the sulfonylamide N atom (P2' substituent) were almost as active as the lead structure 1, making the latter derivative a suitable fluorescence imaging tool.
MeSH term(s)	Matrix Metalloproteinase Inhibitors/pharmacology ; Matrix Metalloproteinase 2 ; Structure-Activity Relationship ; Valine ; Carboxylic Acids
Chemical Substances	Matrix Metalloproteinase Inhibitors ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Valine (HG18B9YRS7) ; Carboxylic Acids
Language	English
Publishing date	2023-05-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1161284-8
ISSN	1464-3391 ; 0968-0896
ISSN (online)	1464-3391
ISSN	0968-0896
DOI	10.1016/j.bmc.2023.117350
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Zs.A 3815: Show issues

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Article ; Online: Response to comment on: Korpos et al. The peri-islet basement membrane, a barrier to infiltrating leukocytes in type 1 diabetes in mouse and human. Diabetes 2013;62:531-542.

Korpos, Eva / Sorokin, Lydia

Diabetes

2013 Volume 62, Issue 8, Page(s) e14

MeSH term(s)	Animals ; Basement Membrane/immunology ; Chemotaxis, Leukocyte/immunology ; Diabetes Mellitus, Type 1/immunology ; Extracellular Matrix/immunology ; Humans ; Islets of Langerhans/immunology
Language	English
Publishing date	2013-07-24
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db13-0543
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Article: Matrilin-2, an extracellular adaptor protein, is needed for the regeneration of muscle, nerve and other tissues.

Korpos, Éva / Deák, Ferenc / Kiss, Ibolya

Neural regeneration research

2015 Volume 10, Issue 6, Page(s) 866–869

Abstract: The extracellular matrix (ECM) performs essential functions in the differentiation, maintenance and remodeling of tissues during development and regeneration, and it undergoes dynamic changes during remodeling concomitant to alterations in the cell-ECM ... ...

Abstract	The extracellular matrix (ECM) performs essential functions in the differentiation, maintenance and remodeling of tissues during development and regeneration, and it undergoes dynamic changes during remodeling concomitant to alterations in the cell-ECM interactions. Here we discuss recent data addressing the critical role of the widely expressed ECM protein, matrilin-2 (Matn2) in the timely onset of differentiation and regeneration processes in myogenic, neural and other tissues and in tumorigenesis. As a multiadhesion adaptor protein, it interacts with other ECM proteins and integrins. Matn2 promotes neurite outgrowth, Schwann cell migration, neuromuscular junction formation, skeletal muscle and liver regeneration and skin wound healing. Matn2 deposition by myoblasts is crucial for the timely induction of the global switch toward terminal myogenic differentiation during muscle regeneration by affecting transforming growth factor beta/bone morphogenetic protein 7/Smad and other signal transduction pathways. Depending on the type of tissue and the pathomechanism, Matn2 can also promote or suppress tumor growth.
Language	English
Publishing date	2015-06-25
Publishing country	India
Document type	Journal Article
ZDB-ID	2388460-5
ISSN	1876-7958 ; 1673-5374
ISSN (online)	1876-7958
ISSN	1673-5374
DOI	10.4103/1673-5374.158332
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Article ; Online: Identification and characterisation of tertiary lymphoid organs in human type 1 diabetes.

Korpos, Éva / Kadri, Nadir / Loismann, Sophie / Findeisen, Clais R / Arfuso, Frank / Burke, George W / Richardson, Sarah J / Morgan, Noel G / Bogdani, Marika / Pugliese, Alberto / Sorokin, Lydia

Diabetologia

2021 Volume 64, Issue 7, Page(s) 1626–1641

Abstract: Aims/hypothesis: We and others previously reported the presence of tertiary lymphoid organs (TLOs) in the pancreas of NOD mice, where they play a role in the development of type 1 diabetes. Our aims here are to investigate whether TLOs are present in ... ...

Abstract	Aims/hypothesis: We and others previously reported the presence of tertiary lymphoid organs (TLOs) in the pancreas of NOD mice, where they play a role in the development of type 1 diabetes. Our aims here are to investigate whether TLOs are present in the pancreas of individuals with type 1 diabetes and to characterise their distinctive features, in comparison with TLOs present in NOD mouse pancreases, in order to interpret their functional significance. Methods: Using immunofluorescence confocal microscopy, we examined the extracellular matrix (ECM) and cellular constituents of pancreatic TLOs from individuals with ongoing islet autoimmunity in three distinct clinical settings of type 1 diabetes: at risk of diabetes; at/after diagnosis; and in the transplanted pancreas with recurrent diabetes. Comparisons were made with TLOs from 14-week-old NOD mice, which contain islets exhibiting mild to heavy leucocyte infiltration. We determined the frequency of the TLOs in human type 1diabetes with insulitis and investigated the presence of TLOs in relation to age of onset, disease duration and disease severity. Results: TLOs were identified in preclinical and clinical settings of human type 1 diabetes. The main characteristics of these TLOs, including the cellular and ECM composition of reticular fibres (RFs), the presence of high endothelial venules and immune cell subtypes detected, were similar to those observed for TLOs from NOD mouse pancreases. Among 21 donors with clinical type 1 diabetes who exhibited insulitis, 12 had TLOs and had developed disease at younger age compared with those lacking TLOs. Compartmentalised TLOs with distinct T cell and B cell zones were detected in donors with short disease duration. Overall, TLOs were mainly associated with insulin-containing islets and their frequency decreased with increasing severity of beta cell loss. Parallel studies in NOD mice further revealed some differences in so far as regulatory T cells were essentially absent from human pancreatic TLOs and CCL21 was not associated with RFs. Conclusions/interpretation: We demonstrate a novel feature of pancreas pathology in type 1 diabetes. TLOs represent a potential site of autoreactive effector T cell generation in islet autoimmunity and our data from mouse and human tissues suggest that they disappear once the destructive process has run its course. Thus, TLOs may be important for type 1 diabetes progression.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Autoantibodies/analysis ; Autoantibodies/blood ; Autoimmunity/physiology ; Child ; Child, Preschool ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/pathology ; Female ; Humans ; Islets of Langerhans/pathology ; Male ; Mice ; Mice, Inbred NOD ; Microscopy, Fluorescence ; Middle Aged ; Pancreas/pathology ; Tertiary Lymphoid Structures/blood ; Tertiary Lymphoid Structures/immunology ; Tertiary Lymphoid Structures/pathology ; Young Adult
Chemical Substances	Autoantibodies
Language	English
Publishing date	2021-04-29
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s00125-021-05453-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Bone marrow laminins influence hematopoietic stem and progenitor cell cycling and homing to the bone marrow.

Susek, Katharina Helene / Korpos, Eva / Huppert, Jula / Wu, Chuan / Savelyeva, Irina / Rosenbauer, Frank / Müller-Tidow, Carsten / Koschmieder, Steffen / Sorokin, Lydia

Matrix biology : journal of the International Society for Matrix Biology

2018 Volume 67, Page(s) 47–62

Abstract: Hematopoietic stem and progenitor cell (HSPC) functions are regulated by a specialized microenvironment in the bone marrow - the hematopoietic stem cell niche - of which the extracellular matrix (ECM) is an integral component. We describe here the ... ...

Abstract	Hematopoietic stem and progenitor cell (HSPC) functions are regulated by a specialized microenvironment in the bone marrow - the hematopoietic stem cell niche - of which the extracellular matrix (ECM) is an integral component. We describe here the localization of ECM molecules, in particular the laminin α4, α3 and α5 containing isoforms in the bone marrow. Laminin 421 (composed of laminin α4, β2, γ1 chains) is identified as a major component of the bone marrow ECM, occurring abundantly surrounding venous sinuses and in a specialized reticular fiber network of the intersinusoidal spaces of murine bone marrow (BM) in close association with HSPC. Bone marrow from Lama4
MeSH term(s)	Animals ; Bone Marrow/metabolism ; Cell Cycle ; Cell Movement ; Extracellular Matrix/metabolism ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/metabolism ; Laminin/genetics ; Laminin/metabolism ; Mice ; Stem Cell Niche
Chemical Substances	Laminin
Language	English
Publishing date	2018-01-31
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1183793-7
ISSN	1569-1802 ; 0945-053X
ISSN (online)	1569-1802
ISSN	0945-053X
DOI	10.1016/j.matbio.2018.01.007
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Article ; Online: CCL21 Expression in β-Cells Induces Antigen-Expressing Stromal Cell Networks in the Pancreas and Prevents Autoimmune Diabetes in Mice.

Gonzalez Badillo, Freddy E / Zisi Tegou, Flavia / Abreu, Maria M / Masina, Riccardo / Sha, Divya / Najjar, Mejdi / Wright, Shane H / Bayer, Allison L / Korpos, Éva / Pugliese, Alberto / Molano, R Damaris / Tomei, Alice A

Diabetes

2019 Volume 68, Issue 10, Page(s) 1990–2003

Abstract: Tumors induce tolerance toward their antigens by producing the chemokine CCL21, leading to the formation of tertiary lymphoid organs (TLOs). Ins2-CCL21 transgenic, nonobese diabetic (NOD) mice express CCL21 in pancreatic β-cells and do not develop ... ...

Abstract	Tumors induce tolerance toward their antigens by producing the chemokine CCL21, leading to the formation of tertiary lymphoid organs (TLOs). Ins2-CCL21 transgenic, nonobese diabetic (NOD) mice express CCL21 in pancreatic β-cells and do not develop autoimmune diabetes. We investigated by which mechanisms CCL21 expression prevented diabetes. Ins2-CCL21 mice develop TLOs by 4 weeks of age, consisting of naive CD4
MeSH term(s)	Animals ; Chemokine CCL21/metabolism ; Diabetes Mellitus, Type 1/metabolism ; Insulin-Secreting Cells/metabolism ; Mice ; Mice, Inbred NOD ; Mice, Transgenic ; Pancreas/metabolism ; Stromal Cells/metabolism
Chemical Substances	Chemokine CCL21
Language	English
Publishing date	2019-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db19-0239
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