LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 7 of total 7

Search options

  1. Article ; Online: Small-Molecule-Directed Endogenous Regeneration of Visual Function in a Mammalian Retinal Degeneration Model.

    Mokady, Daphna / Charish, Jason / Barretto-Burns, Patrick / Grisé, Kenneth N / Coles, Brenda L K / Raab, Susanne / Ortin-Martinez, Arturo / Müller, Alex / Fasching, Bernhard / Jain, Payal / Drukker, Micha / van der Kooy, Derek / Steger, Matthias

    International journal of molecular sciences

    2024  Volume 25, Issue 3

    Abstract: Degenerative retinal diseases associated with photoreceptor loss are a leading cause of visual impairment worldwide, with limited treatment options. Phenotypic profiling coupled with medicinal chemistry were used to develop a small molecule with ... ...

    Abstract Degenerative retinal diseases associated with photoreceptor loss are a leading cause of visual impairment worldwide, with limited treatment options. Phenotypic profiling coupled with medicinal chemistry were used to develop a small molecule with proliferative effects on retinal stem/progenitor cells, as assessed in vitro in a neurosphere assay and in vivo by measuring Msx1-positive ciliary body cell proliferation. The compound was identified as having kinase inhibitory activity and was subjected to cellular pathway analysis in non-retinal human primary cell systems. When tested in a disease-relevant murine model of adult retinal degeneration (MNU-induced retinal degeneration), we observed that four repeat intravitreal injections of the compound improved the thickness of the outer nuclear layer along with the regeneration of the visual function, as measured with ERG, visual acuity, and contrast sensitivity tests. This serves as a proof of concept for the use of a small molecule to promote endogenous regeneration in the eye.
    MeSH term(s) Humans ; Mice ; Animals ; Retinal Degeneration/metabolism ; Methylnitrosourea ; Retina/metabolism ; Photoreceptor Cells ; Regeneration ; Disease Models, Animal ; Mammals
    Chemical Substances Methylnitrosourea (684-93-5)
    Language English
    Publishing date 2024-01-26
    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/ijms25031521
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: RhoGTPases - A novel link between cytoskeleton organization and cisplatin resistance.

    Mokady, Daphna / Meiri, David

    Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy

    2015  Volume 19, Page(s) 22–32

    Abstract: For more than three decades, platinum compounds have been the first line treatment for a wide spectrum of solid tumors. Yet, cisplatin resistance is a major impediment in cancer therapy, and deciphering the mechanisms underlying chemoresistance is ... ...

    Abstract For more than three decades, platinum compounds have been the first line treatment for a wide spectrum of solid tumors. Yet, cisplatin resistance is a major impediment in cancer therapy, and deciphering the mechanisms underlying chemoresistance is crucial for the development of novel therapies with enhanced efficacy. The Rho subfamily of small GTPases plays a significant role in cancer progression, and a growing body of evidence points toward the involvement of these proteins in anticancer drug resistance, including cisplatin resistance. The cycling between active and inactive states, governed by the balance between their GEFs, GAPs and GDIs, RhoGTPases, acts as molecular switches with a pivotal role in actin cytoskeleton organization. The Rho subfamily of proteins is involved in many key cellular processes including adhesion, vesicular trafficking, proliferation, survival, cell morphology and cell-matrix interactions. Although RhoA, RhoB and RhoC are highly homologous and share some upstream regulators and downstream effectors, they each have different roles in cancer progression and chemoresistance. While RhoA and RhoC are upregulated in many tumors and can stimulate transformation, RhoB appears to exhibit tumor suppressor characteristics with proapoptotic effects. In the current review, we discuss the role of Rho subfamily of proteins in cancer, and focus on their involvement in intrinsic and acquired drug resistance.
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacology ; Cisplatin/pharmacology ; Cytoskeleton/metabolism ; Disease Progression ; Drug Design ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Neoplasms/drug therapy ; Neoplasms/pathology ; Up-Regulation/drug effects ; rho GTP-Binding Proteins/metabolism
    Chemical Substances Antineoplastic Agents ; rho GTP-Binding Proteins (EC 3.6.5.2) ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2015-03
    Publishing country Scotland
    Document type Journal Article ; Review
    ZDB-ID 1474513-6
    ISSN 1532-2084 ; 1368-7646
    ISSN (online) 1532-2084
    ISSN 1368-7646
    DOI 10.1016/j.drup.2015.01.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5099: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article: Extensive Gene Diversity in Septicemic Escherichia coli Strains

    Mokady, Daphna / Gophna, Uri / Ron, Eliora Z

    Journal of clinical microbiology. 2005 Jan., v. 43, no. 1

    2005  

    Abstract: Extraintestinal pathogenic Escherichia coli strains (ExPEC) are the cause of a diverse spectrum of invasive infections in humans and animals, and these infections often lead to septicemia. Strains of serogroups O2 and O78 of E. coli are involved in human ...

    Abstract Extraintestinal pathogenic Escherichia coli strains (ExPEC) are the cause of a diverse spectrum of invasive infections in humans and animals, and these infections often lead to septicemia. Strains of serogroups O2 and O78 of E. coli are involved in human urinary tract infections and newborn meningitis and also constitute the major serotypes involved in avian colisepticemia. In the present study we compared the unique genomic sequences of two such septicemic strains, strains O2-1772 and O78-9, obtained by suppression subtractive hybridization. Evaluation of the degree of similarity between these two strains, which cause the same disease, revealed a high degree of diversity, with only a few shared genes. Subsequently, additional strains of each serogroup of human and animal origin were screened by PCR, and the results provided further evidence for the existence of a high degree of genome plasticity. These results were unexpected, in view of data showing that the two O157:H7 strains that have been sequenced are nearly identical in terms of virulence factors. Furthermore, the data obtained for the septicemic strains suggest that each step in the infection can be mediated by a number of alternative virulence factors, indicating the existence of a mix-and-match combinatorial system. Although whole-genome comparisons of E. coli strains causing different diseases have shown great differences in gene contents, we show that such differences exist even within strains that cause the same disease and that target the same host tissues. Moreover, in addition to the high level of genome plasticity, we show that the large pool of virulence genes in the septicemic strains is independent of the host, implying a high degree of zoonotic risk.
    Language English
    Dates of publication 2005-01
    Size p. 66-73.
    Document type Article
    ZDB-ID 390499-4
    ISSN 1098-660X ; 0095-1137
    ISSN (online) 1098-660X
    ISSN 0095-1137
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1188: 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)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Mechanistic insight into GPCR-mediated activation of the microtubule-associated RhoA exchange factor GEF-H1.

    Meiri, David / Marshall, Christopher B / Mokady, Daphna / LaRose, Jose / Mullin, Michael / Gingras, Anne-Claude / Ikura, Mitsuhiko / Rottapel, Robert

    Nature communications

    2014  Volume 5, Page(s) 4857

    Abstract: The RhoGEF GEF-H1 can be sequestered in an inactive state on polymerized microtubules by the dynein motor light-chain Tctex-1. Phosphorylation of GEF-H1 Ser885 by PKA or PAK kinases creates an inhibitory 14-3-3-binding site. Here we show a new mode of ... ...

    Abstract The RhoGEF GEF-H1 can be sequestered in an inactive state on polymerized microtubules by the dynein motor light-chain Tctex-1. Phosphorylation of GEF-H1 Ser885 by PKA or PAK kinases creates an inhibitory 14-3-3-binding site. Here we show a new mode of GEF-H1 activation in response to the G-protein-coupled receptor (GPCR) ligands lysophosphatidic acid (LPA) or thrombin that is independent of microtubule depolymerization. LPA/thrombin stimulates disassembly of the GEF-H1:dynein multi-protein complex through the concerted action of Gα and Gβγ. Gα binds directly to GEF-H1 and displaces it from Tctex-1, while Gβγ binds to Tctex-1 and disrupts its interaction with the dynein intermediate chain, resulting in the release of GEF-H1. Full activation of GEF-H1 requires dephosphorylation of Ser885 by PP2A, which is induced by thrombin. The coordinated displacement of GEF-H1 from microtubules by G-proteins and its dephosphorylation by PP2A demonstrate a multistep GEF-H1 activation and present a unique mechanism coupling GPCR signalling to Rho activation.
    MeSH term(s) 14-3-3 Proteins/metabolism ; Animals ; Dyneins/metabolism ; GTP-Binding Protein alpha Subunits, G12-G13/drug effects ; GTP-Binding Protein alpha Subunits, G12-G13/metabolism ; GTP-Binding Protein beta Subunits/drug effects ; GTP-Binding Protein beta Subunits/metabolism ; GTP-Binding Protein gamma Subunits/drug effects ; GTP-Binding Protein gamma Subunits/metabolism ; Lysophospholipids/pharmacology ; Mice ; Mice, Knockout ; Microtubules/metabolism ; Phosphorylation ; Receptors, G-Protein-Coupled/drug effects ; Receptors, G-Protein-Coupled/metabolism ; Rho Guanine Nucleotide Exchange Factors/drug effects ; Rho Guanine Nucleotide Exchange Factors/metabolism ; Thrombin/pharmacology ; p21-Activated Kinases/metabolism
    Chemical Substances 14-3-3 Proteins ; Arhgef2 protein, mouse ; Dynlt1b protein, mouse ; GTP-Binding Protein beta Subunits ; GTP-Binding Protein gamma Subunits ; Lysophospholipids ; Receptors, G-Protein-Coupled ; Rho Guanine Nucleotide Exchange Factors ; p21-Activated Kinases (EC 2.7.11.1) ; Thrombin (EC 3.4.21.5) ; Dyneins (EC 3.6.4.2) ; GTP-Binding Protein alpha Subunits, G12-G13 (EC 3.6.5.1) ; lysophosphatidic acid (PG6M3969SG)
    Language English
    Publishing date 2014-09-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2041-1723
    ISSN (online) 2041-1723
    DOI 10.1038/ncomms5857
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article: Extensive gene diversity in septicemic Escherichia coli strains.

    Mokady, Daphna / Gophna, Uri / Ron, Eliora Z

    Journal of clinical microbiology

    2005  Volume 43, Issue 1, Page(s) 66–73

    Abstract: Extraintestinal pathogenic Escherichia coli strains (ExPEC) are the cause of a diverse spectrum of invasive infections in humans and animals, and these infections often lead to septicemia. Strains of serogroups O2 and O78 of E. coli are involved in human ...

    Abstract Extraintestinal pathogenic Escherichia coli strains (ExPEC) are the cause of a diverse spectrum of invasive infections in humans and animals, and these infections often lead to septicemia. Strains of serogroups O2 and O78 of E. coli are involved in human urinary tract infections and newborn meningitis and also constitute the major serotypes involved in avian colisepticemia. In the present study we compared the unique genomic sequences of two such septicemic strains, strains O2-1772 and O78-9, obtained by suppression subtractive hybridization. Evaluation of the degree of similarity between these two strains, which cause the same disease, revealed a high degree of diversity, with only a few shared genes. Subsequently, additional strains of each serogroup of human and animal origin were screened by PCR, and the results provided further evidence for the existence of a high degree of genome plasticity. These results were unexpected, in view of data showing that the two O157:H7 strains that have been sequenced are nearly identical in terms of virulence factors. Furthermore, the data obtained for the septicemic strains suggest that each step in the infection can be mediated by a number of alternative virulence factors, indicating the existence of a mix-and-match combinatorial system. Although whole-genome comparisons of E. coli strains causing different diseases have shown great differences in gene contents, we show that such differences exist even within strains that cause the same disease and that target the same host tissues. Moreover, in addition to the high level of genome plasticity, we show that the large pool of virulence genes in the septicemic strains is independent of the host, implying a high degree of zoonotic risk.
    MeSH term(s) Animals ; Bacteremia/microbiology ; Escherichia coli/classification ; Escherichia coli/pathogenicity ; Escherichia coli Infections/microbiology ; Escherichia coli Proteins/genetics ; Genetic Variation ; Genome, Bacterial ; Genomics ; Humans ; Nucleic Acid Hybridization/methods ; Poultry ; Poultry Diseases/microbiology ; Serotyping ; Virulence
    Chemical Substances Escherichia coli Proteins
    Language English
    Publishing date 2005-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 390499-4
    ISSN 1098-660X ; 0095-1137
    ISSN (online) 1098-660X
    ISSN 0095-1137
    DOI 10.1128/JCM.43.1.66-73.2005
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1188: 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)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article: Virulence factors of septicemic Escherichia coli strains.

    Mokady, Daphna / Gophna, Uri / Ron, Eliora Z

    International journal of medical microbiology : IJMM

    2005  Volume 295, Issue 6-7, Page(s) 455–462

    Abstract: Extraintestinal pathogenic Escherichia coli strains (ExPEC) are the cause of a diverse spectrum of invasive human and animal infections, often leading to septicemia. This review deals with the virulence genes of septicemic ExPEC strains. We discuss the ... ...

    Abstract Extraintestinal pathogenic Escherichia coli strains (ExPEC) are the cause of a diverse spectrum of invasive human and animal infections, often leading to septicemia. This review deals with the virulence genes of septicemic ExPEC strains. We discuss the meaning of a virulence gene and survey the genomic, genetic and physiological studies on these strains. Apparently, there are a few virulence factors, which are conserved in the septicemic strains, implying that they are essential for the infection. For the other virulence-related genes a high level of diversity is observed, demonstrating that all stages of the infection can be mediated by a number of alternative virulence factors. The variable profile of virulence genes in septicemic E. coli strains, as well as a prevalence of mobility-related sequences point out the existence of a "mix and match" combinatorial system.
    MeSH term(s) Adhesins, Escherichia coli/genetics ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Escherichia coli/classification ; Escherichia coli/pathogenicity ; Escherichia coli Infections/microbiology ; Escherichia coli Proteins/genetics ; Fimbriae Proteins/genetics ; Fimbriae Proteins/physiology ; Genome, Bacterial ; Humans ; Plasmids/genetics ; Virulence/genetics ; Virulence Factors/genetics
    Chemical Substances Adhesins, Escherichia coli ; Carrier Proteins ; Escherichia coli Proteins ; Virulence Factors ; Fimbriae Proteins (147680-16-8)
    Language English
    Publishing date 2005-10
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2006518-8
    ISSN 1618-0607 ; 1438-4221
    ISSN (online) 1618-0607
    ISSN 1438-4221
    DOI 10.1016/j.ijmm.2005.07.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5333: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: The RhoGEF GEF-H1 is required for oncogenic RAS signaling via KSR-1.

    Cullis, Jane / Meiri, David / Sandi, Maria Jose / Radulovich, Nikolina / Kent, Oliver A / Medrano, Mauricio / Mokady, Daphna / Normand, Josee / Larose, Jose / Marcotte, Richard / Marshall, Christopher B / Ikura, Mitsuhiko / Ketela, Troy / Moffat, Jason / Neel, Benjamin G / Gingras, Anne-Claude / Tsao, Ming-Sound / Rottapel, Robert

    Cancer cell

    2014  Volume 25, Issue 2, Page(s) 181–195

    Abstract: Cellular transformation by oncogenic RAS engages the MAPK pathway under strict regulation by the scaffold protein KSR-1. Here, we report that the guanine nucleotide exchange factor GEF-H1 plays a critical role in a positive feedback loop for the RAS/MAPK ...

    Abstract Cellular transformation by oncogenic RAS engages the MAPK pathway under strict regulation by the scaffold protein KSR-1. Here, we report that the guanine nucleotide exchange factor GEF-H1 plays a critical role in a positive feedback loop for the RAS/MAPK pathway independent of its RhoGEF activity. GEF-H1 acts as an adaptor protein linking the PP2A B' subunits to KSR-1, thereby mediating the dephosphorylation of KSR-1 S392 and activation of MAPK signaling. GEF-H1 is important for the growth and survival of HRAS(V12)-transformed cells and pancreatic tumor xenografts. GEF-H1 expression is induced by oncogenic RAS and is correlated with pancreatic neoplastic progression. Our results, therefore, identify GEF-H1 as an amplifier of MAPK signaling and provide mechanistic insight into the progression of RAS mutant tumors.
    MeSH term(s) Adenocarcinoma/genetics ; Adenocarcinoma/metabolism ; Adenocarcinoma/pathology ; Animals ; Cell Transformation, Neoplastic/pathology ; Cells, Cultured ; Embryo, Mammalian/cytology ; Embryo, Mammalian/metabolism ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Mice ; NIH 3T3 Cells ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/pathology ; Phosphorylation ; Promoter Regions, Genetic/genetics ; Protein Kinases/genetics ; Protein Kinases/metabolism ; Rho Guanine Nucleotide Exchange Factors/genetics ; Rho Guanine Nucleotide Exchange Factors/metabolism ; Signal Transduction ; Tumor Cells, Cultured ; ras Proteins/genetics ; ras Proteins/metabolism
    Chemical Substances ARHGEF2 protein, human ; Arhgef2 protein, mouse ; Rho Guanine Nucleotide Exchange Factors ; Protein Kinases (EC 2.7.-) ; KSR-1 protein kinase (EC 2.7.1.-) ; ras Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2014-02-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccr.2014.01.025
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5650: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 104: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top