Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: CELLS ; EXPRESSION ; Germany ; human ; CDNA CLONES ; GENE ; GENES ; GENOME ; HYBRIDIZATION ; PROTEIN ; PROTEINS ; transcription ; data mining ; radiation ; murine ; FAMILY ; MEMBER ; SEQUENCE ; TRANSPORT ; MOUSE ; IN-SITU ; YEAST ; MEMBRANE ; REQUIRES ; AAA family ; DATABASE ; DISPLAY ; endocytosis ; ENDOSOMAL TRAFFICKING ; FISH ; FUSION PROTEINS ; HUMAN GENOME ; INTRACELLULAR PROTEIN TRAFFICKING ; LATE-GOLGI ; MOUSE SKD1 ; MULTIVESICULAR BODY ; TRAFFICKING ; vacuolar protein sorting ; VPS4- paralogue
    Abstract: The VPS4 gene is a member of the AAA-family; it codes for an ATPase which is involved in lysosomal/endosomal membrane trafficking. VPS4 genes are present in virtually all eukaryotes. Exhaustive data mining of all available genomic databases from completely or partially sequenced organisms revealed the existence of up to three paralogues, VPS4a, -b, and -c. Whereas in the genome of lower eukaryotes like yeast only one VPS4 representative is present, we found that mammals harbour two paralogues, VPS4a and VPS4b. Most interestingly, the Fugu fish contains a third VPS4 paralogue (VPS4c). Sequence comparison of the three VPS4 paralogues indicates that the Fugu VPS4c displays sequence features intermediate between VPS4a and VPS4b. Using complete mammalian VPS4a and VPS4b cDNA clones as probes, genomic clones of both VPS4 paralogues in human and mouse were identified and sequenced. The chromosomal loci of all four VPS4 genes were determined by independent methods. A BLAST search of the human genome database with the human VPS4A sequence yielded a double match, most likely due to a faulty assembly of sequence contigs in the human draft sequence. Fluorescent in situ hybridization and radiation hybrid analyses demonstrated that human and mouse VPS4A/a and VPS4B/b are located on syntenic chromosomal regions. Northern blot and semi-quantitative reverse transcription analyses showed that mouse VPS4a and VPS4b are differentially expressed in different organs, suggesting that the two paralogues have developed different functional properties since their divergence. To investigate the subcellular distribution of the murine VPS4 paralogues, we transiently expressed various fluorescent VPS4 fusion proteins in mouse 3T3 cells. All tested VPS4 fusion proteins were found in the cytosol. Expression of dominant- negative mutant VPS4 fusion proteins led to their concentration in the perinuclear region. Co-expression of VPS4a-GFP and VPS4b-dsRed fusion proteins revealed a partial co-localization that was most prominent with mutant VPS4a and VPS4b proteins. A physical interaction between the mouse paralogues was also supported by two-hybrid analyses. (C) 2003 Elsevier Science B.V. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 12594041
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: Germany ; CT ; DENSITY ; TOOL ; GENE ; DIFFERENTIATION ; DOMAIN ; CONTRAST ; fibroblasts ; NUCLEI ; CHROMATIN ; IN-SITU HYBRIDIZATION ; LYMPHOCYTES ; FISH ; HUMAN GENOME ; MAMMALIAN-CELLS ; SPATIAL-ORGANIZATION ; TERRITORIES ; CHROMOSOME TERRITORIES ; ARCHITECTURE ; INTERPHASE NUCLEUS ; FUNCTIONAL IMPLICATIONS ; CELL-NUCLEI ; ORDER CHROMATIN ARRANGEMENTS
    Abstract: Studies of higher-order chromatin arrangements are an essential part of ongoing attempts to explore changes in epigenome structure and their functional implications during development and cell differentiation. However, the extent and cell-type-specificity of three-dimensional (3D) chromosome arrangements has remained controversial. In order to overcome technical limitations of previous studies, we have developed tools that allow the quantitative 3D positional mapping of all chromosomes simultaneously. We present unequivocal evidence for a probabilistic 3D order of prometaphase chromosomes, as well as of chromosome territories (CTs) in nuclei of quiescent (G0) and cycling ( early S-phase) human diploid fibroblasts ( 46, XY). Radial distance measurements showed a probabilistic, highly nonrandom correlation with chromosome size: small chromosomes - independently of their gene density - were distributed significantly closer to the center of the nucleus or prometaphase rosette, while large chromosomes were located closer to the nuclear or rosette rim. This arrangement was independently confirmed in both human fibroblast and amniotic fluid cell nuclei. Notably, these cell types exhibit flat-ellipsoidal cell nuclei, in contrast to the spherical nuclei of lymphocytes and several other human cell types, for which we and others previously demonstrated gene-density-correlated radial 3D CT arrangements. Modeling of 3D CT arrangements suggests that cell-type-specific differences in radial CT arrangements are not solely due to geometrical constraints that result from nuclear shape differences. We also found gene-density-correlated arrangements of higher-order chromatin shared by all human cell types studied so far. Chromatin domains, which are gene-poor, form a layer beneath the nuclear envelope, while gene-dense chromatin is enriched in the nuclear interior. We discuss the possible functional implications of this finding
    Type of Publication: Journal article published
    PubMed ID: 15839726
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: EXPRESSION ; LUNG-CANCER ; DISEASE ; GENE ; BIOMARKERS ; PERIPHERAL-BLOOD ; MULTIPLE-SCLEROSIS ; SERUM ; SIGNATURE ; MICRORNA PROFILES
    Abstract: Background: miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists. Methods: We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR. Results: We discovered 34 miRNAs with strong disease association. Among those, we found substantially decreased levels of hsa-miR-144* and hsa-miR-20b with AUC of 0.751 ( 95% CI: 0.703-0.799), respectively. We also discovered a set of miRNAs, including hsa-miR-155*, as rather stable markers, offering reasonable control miRNAs for future studies. The strong downregulation of hsa-miR-144* and the less variable pattern of hsa-miR-155* has been validated in a cohort of 319 samples in three different centers. Here, breast cancer as an additional disease phenotype not included in the screening phase has been included as the 20th trait. Conclusions: Our study on 1,368 patients including 1,049 genome-wide miRNA profiles and 319 qRT-PCR validations further underscores the high potential of specific blood-borne miRNA patterns as molecular biomarkers. Importantly, we highlight 34 miRNAs that are generally dysregulated in human pathologies. Although these markers are not specific to certain diseases they may add to the diagnosis in combination with other markers, building a specific signature. Besides these dysregulated miRNAs, we propose a set of constant miRNAs that may be used as control markers.
    Type of Publication: Journal article published
    PubMed ID: 25465851
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...