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  1. Article ; Online: EPD in 2020: enhanced data visualization and extension to ncRNA promoters.

    Meylan, Patrick / Dreos, René / Ambrosini, Giovanna / Groux, Romain / Bucher, Philipp

    Nucleic acids research

    2019  Volume 48, Issue D1, Page(s) D65–D69

    Abstract: The Eukaryotic Promoter Database (EPD), available online at https://epd.epfl.ch, provides accurate transcription start site (TSS) information for promoters of 15 model organisms plus corresponding functional genomics data that can be viewed in a genome ... ...

    Abstract The Eukaryotic Promoter Database (EPD), available online at https://epd.epfl.ch, provides accurate transcription start site (TSS) information for promoters of 15 model organisms plus corresponding functional genomics data that can be viewed in a genome browser, queried or analyzed via web interfaces, or exported in standard formats (FASTA, BED, CSV) for subsequent analysis with other tools. Recent work has focused on the improvement of the EPD promoter viewers, which use the UCSC Genome Browser as visualization platform. Thousands of high-resolution tracks for CAGE, ChIP-seq and similar data have been generated and organized into public track hubs. Customized, reproducible promoter views, combining EPD-supplied tracks with native UCSC Genome Browser tracks, can be accessed from the organism summary pages or from individual promoter entries. Moreover, thanks to recent improvements and stabilization of ncRNA gene catalogs, we were able to release promoter collections for certain classes of ncRNAs from human and mouse. Furthermore, we developed automatic computational protocols to assign orphan TSS peaks to downstream genes based on paired-end (RAMPAGE) TSS mapping data, which enabled us to add nearly 9000 new entries to the human promoter collection. Since our last article in this journal, EPD was extended to five more model organisms: rhesus monkey, rat, dog, chicken and Plasmodium falciparum.
    MeSH term(s) Animals ; Computational Biology/methods ; Databases, Nucleic Acid ; Eukaryotic Cells/metabolism ; Genomics/methods ; Humans ; Promoter Regions, Genetic ; RNA, Untranslated ; Software ; Web Browser
    Chemical Substances RNA, Untranslated
    Language English
    Publishing date 2019-10-31
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkz1014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: Genetic predisposition and environmental factors associated with the development of atopic dermatitis in infancy: a prospective birth cohort study.

    Gallay, Caroline / Meylan, Patrick / Mermoud, Sophie / Johannsen, Alexandre / Lang, Caroline / Rivolta, Carlo / Christen-Zaech, Stephanie

    European journal of pediatrics

    2020  Volume 179, Issue 9, Page(s) 1367–1377

    Abstract: The influence of environmental factors on atopic dermatitis (AD) has been investigated in many cross-sectional studies. It remains however unclear if they could influence AD development early in life. This prospective birth cohort study aimed to monitor ... ...

    Abstract The influence of environmental factors on atopic dermatitis (AD) has been investigated in many cross-sectional studies. It remains however unclear if they could influence AD development early in life. This prospective birth cohort study aimed to monitor aspects of family lifestyle and child's nutrition within a Caucasian population and to assess its association with AD development over the first 2 years of life. Genetic predisposition was evaluated based on family history and profilaggrin genotyping. Of 149 included children, 36 developed AD. Infants with a family history of atopy developed AD 2.6 times more frequently (30 of 97) than infants without atopic predisposition (6 of 52). Genotyping was carried out on 50% of the children included. Profilaggrin mutations (R501X, 2282del4, R2447X, and S3247X) were infrequent in our population. Lower incidence of AD was observed in infants exposed to a damp housing environment, lower household income, and smoking mothers with a higher but not with a lower education level.Conclusion: Family history of atopy was a significant risk factor for AD regardless of the most common, currently defined, FLG mutations. Humidity at home and passive smoking seem associated with AD development in infancy. What is Known: • Atopic dermatitis (AD) is associated with mutations in various genes of the immune system and the epidermal barrier complex in particular filaggrin (FLG) mutation. • Inherited factors alone cannot explain the rising AD; environmental factors are therefore likely to play a decisive role in this rise but the exact role that these factors may play in increasing AD risk in infancy remains unclear. Moreover, the relationship between environmental factors and AD has been the focus of mostly cross-sectional studies and not prospective studies. What is New: • This prospective birth cohort study demonstrates that family history of atopy is a significant risk factor for AD regardless of the most common, currently defined, FLG mutations. • A lower incidence of AD was observed in infants exposed to a moist housing environment, lower household income, and smoking of mothers with a higher but not with a lower education level.
    MeSH term(s) Child ; Cohort Studies ; Cross-Sectional Studies ; Dermatitis, Atopic/etiology ; Dermatitis, Atopic/genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Infant ; Mutation ; Prospective Studies
    Language English
    Publishing date 2020-03-06
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 194196-3
    ISSN 1432-1076 ; 0340-6199 ; 0943-9676
    ISSN (online) 1432-1076
    ISSN 0340-6199 ; 0943-9676
    DOI 10.1007/s00431-020-03616-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Low expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases.

    Meylan, Patrick / Pich, Christine / Winkler, Carine / Ginster, Stefanie / Mury, Lionel / Sgandurra, Marie / Dreos, René / Frederick, Dennie Tompers / Hammond, Marc / Boland, Genevieve Marie / Michalik, Liliane

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 7847

    Abstract: The thioredoxin system plays key roles in regulating cancer cell malignancy. Here we identify the Thioredoxin-interacting protein (TXNIP) as a gene, which expression is regulated by PPARγ in melanoma cells. We show that high TXNIP expression levels ... ...

    Abstract The thioredoxin system plays key roles in regulating cancer cell malignancy. Here we identify the Thioredoxin-interacting protein (TXNIP) as a gene, which expression is regulated by PPARγ in melanoma cells. We show that high TXNIP expression levels associate with benign melanocytic lesions, with tumor regression in patients on MAP kinase targeted therapy, with decreased proliferation in patients' melanoma biopsies, and with cell cycle arrest in human melanoma cell lines. In contrast, reduced TXNIP expression associates with advanced melanoma and with disease progression in patients. TXNIP depletion in human melanoma cells altered the expression of integrin beta-3 and the localization of the integrin alpha-v/beta-3 dimer at their surface. Moreover, TXNIP depletion affected human melanoma cell motility and improved their capacity to colonize mouse lungs in an in vivo assay. This study establishes TXNIP as a PPARγ-regulated gene in melanoma cells, thereby suggesting a link between these two proteins both involved in the regulation of cancer and of energy metabolism. It also reveals that the decrease in TXNIP expression, which is observed in advanced patient tumors, likely favors lung metastatic seeding of malignant cells.
    MeSH term(s) Animals ; Carrier Proteins/metabolism ; Cell Line, Tumor ; Female ; Humans ; Lung Neoplasms/metabolism ; Lung Neoplasms/secondary ; Melanoma/metabolism ; Melanoma/pathology ; Mice ; PPAR gamma/metabolism
    Chemical Substances Carrier Proteins ; PPAR gamma ; PPARG protein, human ; TXNIP protein, human
    Language English
    Publishing date 2021-04-12
    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/s41598-021-86329-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Extracellular microvesicles from astrocytes contain functional glutamate transporters: regulation by protein kinase C and cell activation.

    Gosselin, Romain-Daniel / Meylan, Patrick / Decosterd, Isabelle

    Frontiers in cellular neuroscience

    2013  Volume 7, Page(s) 251

    Abstract: Glutamate transport through astrocytic excitatory amino-acid transporters (EAAT)-1 and EAAT-2 is paramount for neural homeostasis. EAAT-1 has been reported in secreted extracellular microvesicles (eMV, such as exosomes) and because the protein kinase C ( ... ...

    Abstract Glutamate transport through astrocytic excitatory amino-acid transporters (EAAT)-1 and EAAT-2 is paramount for neural homeostasis. EAAT-1 has been reported in secreted extracellular microvesicles (eMV, such as exosomes) and because the protein kinase C (PKC) family controls the sub-cellular distribution of EAATs, we have explored whether PKCs drive EAATs into eMV. Using rat primary astrocytes, confocal immunofluorescence and ultracentrifugation on sucrose gradient we here report that PKC activation by phorbol myristate acetate (PMA) reorganizes EAAT-1 distribution and reduces functional [(3)H]-aspartate reuptake. Western-blots show that EAAT-1 is present in eMV from astrocyte conditioned medium, together with NaK ATPase and glutamine synthetase all being further increased after PMA treatment. However, nanoparticle tracking analysis reveals that PKC activation did not change particle concentration. Functional analysis indicates that eMV have the capacity to reuptake [(3)H]-aspartate. In vivo, we demonstrate that spinal astrocytic reaction induced by peripheral nerve lesion (spared nerve injury, SNI) is associated with a phosphorylation of PKC δ together with a shift of EAAT distribution ipsilaterally. Ex vivo, spinal explants from SNI rats release eMV with an increased content of NaK ATPase, EAAT-1 and EAAT-2. These data indicate PKC and cell activation as important regulators of EAAT-1 incorporation in eMV, and raise the possibility that microvesicular EAAT-1 may exert extracellular functions. Beyond a putative role in neuropathic pain, this phenomenon may be important for understanding neural homeostasis and a wide range of neurological diseases associated with astrocytic reaction as well as non-neurological diseases linked to eMV release.
    Language English
    Publishing date 2013-12-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2013.00251
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Induction of Paracrine Signaling in Metastatic Melanoma Cells by PPARγ Agonist Rosiglitazone Activates Stromal Cells and Enhances Tumor Growth.

    Pich, Christine / Meylan, Patrick / Mastelic-Gavillet, Beatris / Nguyen, Thanh Nhan / Loyon, Romain / Trang, Bao Khanh / Moser, Hélène / Moret, Catherine / Goepfert, Christine / Hafner, Jürg / Levesque, Mitchell P / Romero, Pedro / Jandus, Camilla / Michalik, Liliane

    Cancer research

    2018  Volume 78, Issue 22, Page(s) 6447–6461

    Abstract: In addition to improving insulin sensitivity in type 2 diabetes, the thiazolidinedione family of compounds and the pharmacologic activation of their best-characterized target PPARγ have been proposed as a therapeutic option for cancer treatment. In this ... ...

    Abstract In addition to improving insulin sensitivity in type 2 diabetes, the thiazolidinedione family of compounds and the pharmacologic activation of their best-characterized target PPARγ have been proposed as a therapeutic option for cancer treatment. In this study, we reveal a new mode of action for the thiazolidinedione rosiglitazone that can contribute to tumorigenesis. Rosiglitazone activated a tumorigenic paracrine communication program in a subset of human melanoma cells that involves the secretion of cytokines, chemokines, and angiogenic factors. This complex blend of paracrine signals activated nonmalignant fibroblasts, endothelial cells, and macrophages in a tumor-friendly way. In agreement with these data, rosiglitazone promoted human melanoma development in xenografts, and tumors exposed to rosiglitazone exhibited enhanced angiogenesis and inflammation. Together, these findings establish an important tumorigenic action of rosiglitazone in a subset of melanoma cells. Although studies conducted on cohorts of diabetic patients report overall benefits of thiazolidinediones in cancer prevention, our data suggest that exposure of established tumors to rosiglitazone may be deleterious.
    MeSH term(s) Angiogenesis Inducing Agents/metabolism ; Animals ; Carcinogenesis ; Cell Line, Tumor ; Fibroblasts/metabolism ; Human Umbilical Vein Endothelial Cells/drug effects ; Humans ; Inflammation ; Leukocytes, Mononuclear/cytology ; Macrophages/drug effects ; Melanoma/metabolism ; Melanoma/pathology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Monocytes/metabolism ; Neoplasm Metastasis ; Neoplasm Transplantation ; Oligonucleotide Array Sequence Analysis ; PPAR gamma/agonists ; PPAR gamma/metabolism ; Paracrine Communication ; Rosiglitazone/pharmacology ; Skin Neoplasms/metabolism ; Skin Neoplasms/pathology ; Stromal Cells/metabolism ; T-Lymphocytes/cytology
    Chemical Substances Angiogenesis Inducing Agents ; PPAR gamma ; Rosiglitazone (05V02F2KDG)
    Language English
    Publishing date 2018-09-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-18-0912
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uh III Zs.135/5: Show issues Location:
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  6. Article ; Online: Skin Colonization by Staphylococcus aureus Precedes the Clinical Diagnosis of Atopic Dermatitis in Infancy.

    Meylan, Patrick / Lang, Caroline / Mermoud, Sophie / Johannsen, Alexandre / Norrenberg, Sarah / Hohl, Daniel / Vial, Yvan / Prod'hom, Guy / Greub, Gilbert / Kypriotou, Magdalini / Christen-Zaech, Stéphanie

    The Journal of investigative dermatology

    2017  Volume 137, Issue 12, Page(s) 2497–2504

    Abstract: Atopic dermatitis (AD) has a well-established association with skin colonization or infection by Staphylococcus aureus, which can exacerbate the disease. However, a causal relationship between specific changes in skin colonization during the first years ... ...

    Abstract Atopic dermatitis (AD) has a well-established association with skin colonization or infection by Staphylococcus aureus, which can exacerbate the disease. However, a causal relationship between specific changes in skin colonization during the first years of life and AD development still remains unclear. In this prospective birth cohort study, we aimed to characterize the association between skin colonization and AD development in 149 white infants with or without a family history of atopy. We assessed infants clinically and collected axillary and antecubital fossa skin swabs for culture-based analysis at birth and at seven time points over the first 2 years of life. We found that at age 3 months, S. aureus was more prevalent on the skin of infants who developed AD later on. S. aureus prevalence was increased on infants' skin at the time of AD onset and also 2 months before it, when compared with age-matched, unaffected infants. Furthermore, at AD onset, infants testing positive for S. aureus were younger than uncolonized subjects. In conclusion, our results suggest that specific changes in early-life skin colonization may actively contribute to clinical AD onset in infancy.
    MeSH term(s) Dermatitis, Atopic/complications ; Dermatitis, Atopic/drug therapy ; Dermatitis, Atopic/microbiology ; Eczema/complications ; Eczema/drug therapy ; Eczema/microbiology ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Male ; Prospective Studies ; Skin/microbiology ; Staphylococcal Infections/complications ; Staphylococcal Infections/drug therapy ; Staphylococcus aureus ; Vagina/microbiology
    Language English
    Publishing date 2017-08-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2017.07.834
    Database MEDical Literature Analysis and Retrieval System OnLINE

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