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Results for “Origin cell mapping”

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At least 451 records · Page 25Linked to original sources
PubMed2000

Detailed deletion mapping at chromosome 11q23 in colorectal carcinoma.

Loss of heterozygosity (LOH) is frequent at the chromosomal region 11q22-q23 in several types of tumours of diverse cell origin. Previous investigations of LOH at this chromosomal region in colorectal carcinoma have been contradictory in their findings, and have only included between 1-4 loci. In order to define any regions of LOH on 11q23, we investigated 16 loci between D11S940 and D11S934 on the long arm of chromosome 11 using microsatellite analysis. Of 57 colorectal carcinomas specimens, 36 (63.2%) demonstrated LOH at one or more marker, with the highest frequencies of LOH at D11S1340 (41.0%), located between 105.13-111.97 Mb from the centromere, and D11S924 (37.1%) and D11S4107 (40.5%), both located approximately 113 Mb from the centromere. No statistically significant associations between LOH and age-of-presentation or Dukes' stage were found. LOH was observed in colorectal tumours of all Dukes' stages, including Dukes' stages A and B, suggesting that the inactivation of a tumour suppressor gene(s) on 11q23 occurs in the early stages of colorectal carcinoma. These results confirm the presence of putative tumour suppressor gene(s) at chromosome 11q23, involved in the carcinogenesis of colorectal carcinoma, and will facilitate future identification of candidate genes.

Adenocarcinoma↗
PubMed1980

Absence of nucleosomes in a fraction of SV40 chromatin between the origin of replication and the region coding for the late leader RNA.

Electron microscopic examination of SV40 chromatin prepared 44 hr post-infection led to the visualization of a nucleosome-free region (gap) in 15-20% of the minichromosomes. Minichromosomes with and without a gap displayed a mean number of 24 nucleosomes. Measurements carried out on dark field micrographs yielded for the gap a mean length of 249 +/- 13 bp, with a maximum value of 385 bp. The gap was mapped following digestion with three single-cut restriction endonucleases: Bgl l, Bam HI and Eco RI. It was located in the region of the origin of replication in accordance with previous biochemical data. To assess the situ existence of a nucleosome-free region, nuclei from infected cells were digested with DNase I. A highly sensitive region was thus revealed and mapped by secondary digestion with Eco RI. It was located in the same region as the gap, between 0.67 and 0.74 on the physical map. The sensitive region could be detected throughout the late phase of the virus cycle. These findings strongly suggest that a nucleosome-free region exists in the cells. The gap is not likely to be involved in replication, since it is asymmetric with respect to the Bgl I cleavage site, from which replication proceeds symmetrically.

Chromatin↗
PubMed1995

A functional map of the pigeon basilar papilla: correlation of the properties of single auditory nerve fibres and their peripheral origin.

The purpose of the investigation was to correlate the functional properties of primary auditory fibres with the location of appertaining receptor cells in the avian basilar papilla. The functional properties of 425 single afferent fibres from the auditory nerve of adult pigeons were measured. The peripheral innervation site of 39 fibres was identified by intracellular labelling and correlated with the fibre's functional properties. Mean spontaneous firing rate (SR, 0.1-250/s) was distributed monomodally (mean: 91 +/- 47/s) but not normally. Characteristic frequencies (CFs) were in the range of 0.02-4 kHz. SR, threshold at CF (4-76 dB SPL) and sharpness of tuning (Q10 dB, 0.1-8.8) varied systematically with CF. For a given CF there was a strong correlation of threshold and Q10 dB and of threshold and SR. Labelled fibres innervated different hair cell types over 93% of the length and 97% of the width of the basilar papilla. The majority of fibres innervated hair cells located between 30 and 70% distance from the apex and 0 and 30% distance from the neural edge of the papilla. CFs are mapped tonotopically from high at the base to low at the apex of the papilla, with a mean mapping constant of 0.63 +/- 0.05 mm/octave (in vivo). The highest CF at the base extrapolates to 5.98 +/- 1.17 kHz. The lowest CF mapped at the apex is 0.021 kHz. From the data, together with data from mechanical measurements (Gummer et al., 1987), a frequency-place function of the pigeon papilla was calculated. Transverse gradients of threshold at CF and of Q10 dB were observed across the width of the papilla. Thresholds were lowest and sharpness of tuning was highest above the neural limbus at a distance of 23% from the neural edge of the papilla. Hair cells in this sensitive strip are the tallest and narrowest ones across the width of the papilla. They are packed most densely and receive the largest number of afferent fibres. Fibres innervating (mostly short) hair cells on the free basilar membrane were spontaneously active and responsive to sound. Their Q10 dB was less than average but their sensitivity and SR were comparable to the mean population values. It is concluded that functional properties change gradually not only along the length but also across the width of the pigeon basilar papilla. The results support the idea that sharp frequency tuning of avian primary auditory fibres involves tuning mechanisms supplementary to the tuning of the free part of the basilar membrane.

Acoustic Stimulation↗
PubMed1997

Role of nuclear architecture in the initiation of eukaryotic DNA replication.

The eukaryotic genome is compacted in the cell nucleus, in a way that allows its faithful and ordered replication each cell cycle. Chromatin is organized into topologically constrained loops that are anchored to the nuclear matrix by specific attachment regions (SARs). Chromatin loops were proposed to correspond to replication units. In particular, it has been suggested that replication origins coincide with SARs. Critical examination of these hypotheses has long been hampered by the elusive nature of higher eukaryotic DNA replication origins and termini. In recent years, however, a number of loci have been mapped for both SARs and replication units, and studies on the nuclear localization of replicating DNA and replication proteins have begun. We review these data and argue that they question this model. We then try to delineate other aspects of chromosome compartmentalization and cell-cycle remodeling which might be responsible for the specification and activation of metazoan DNA replication origins.

Animals↗
PubMed1978

Units of transcription for cytoplasmic RNA in mouse myeloma cells.

The size of transcription units for several of the abundant cytoplasmic mRNA species in mouse myeloma cells has been analyzed by the ultraviolet light mapping technique. Inactivation kinetics and target size analyses for production of the predominant RNA species indicate that the mRNAs originate in precursor molecules that are 2--14 times larger than the mature mRNA. This estimate of the size of the transcription unit may be a minimum one since it would not take into account promoter-distal sequences if these were not necessary for processing of the mRNA precursor.

Cell Line↗
PubMed1984

Origin of replication in episomal bovine papilloma virus type 1 DNA isolated from transformed cells.

The origin of replication of bovine papilloma virus type 1 (BPV-1) has been determined by isolating replicative intermediates (RI) of BPV-transformed hamster embryo fibroblasts (HEF-BPV). These RI were treated with single cut restriction enzymes to determine the start-position (origin) of the extending replication eyes using electron microscopic techniques. 'Cairns'-type RI molecules were shown to contain one replication eye in monomeric as well as in dimeric molecules. The position of this eye was localized at 6940 +/- 5% bp in the physical map. In a second set of experiments BPV-1 DNA fragments cloned in pBR322 were tested for transient episomal replication. Transfected cells were harvested after increasing periods of time and screened for replication with isoschizomeric restriction enzymes to differentiate between input and replicated DNA. The part of the BPV genome harboring the replication origin spans the BPV ClaI-C restriction fragment corresponding to the non-coding region of the BPV genome and coincides with the DNase I-hypersensitive control region in the chromatin, isolated from transformed cells.

Animals↗
PubMed1991

Functional reorganization of adult cat somatosensory cortex is dependent on NMDA receptors.

We studied effects of selective blockade of N-methyl-D-aspartate (NMDA) receptors in the primary somatosensory cortex (SI) of the adult cat on reorganization of cortical maps after selective deafferentation. About two weeks after hindlimb deafferentation, cortical loci representing the 'trunk' seemingly expanded and 'migrated' into areas originally devoted to the 'hindlimb'. Selective blockade of NMDA receptors of the SI cells by continuous infusion of 2-amino-5-phosphonovalerate (APV) into the cortex disrupted such change. The APV treatment also depressed responses of SI cells to natural sensory stimulation, but left no long-lasting side effects. The results suggest that the processes of map reorganization take place within the SI and involve mechanisms dependent on NMDA-receptor-mediated activity.

2-Amino-5-phosphonovalerate↗
PubMed2004

Collaborative activities of macrophage-stimulating protein and transforming growth factor-beta1 in induction of epithelial to mesenchymal transition: roles of the RON receptor tyrosine kinase.

Epithelial to mesenchymal transition (EMT) is a process occurring during embryonic development and cancer progression. Using recepteur d'origine nantais (RON)-expressing epithelial cells as a model, we showed that RON activation causes spindle-shaped morphology with increased cell motilities. These activities resemble those observed in EMT induced by transforming growth factor (TGF)-beta1 or by Ras-Raf signaling. By immunofluorescent and Western blot analyses, we found that constitutive RON expression results in diminished expression of E-cadherin, redistribution of beta-catenin, reorganization of actin cytoskeleton, and increased expression of vimentin, a mesenchymal filament. RON expression is also essential for TGF-beta1-induced expression of alpha-smooth muscle actin (alpha-SMA), a specialized mesenchymal marker. In the study of signaling pathways responsible for RON-mediated EMT, it was found that PD98059, a MAP kinase inhibitor, blocks the collaborative activities of RON and TGF-beta1 in induction of alpha-SMA expression and restores epithelial cells to their original morphology. Moreover, we showed that RON expression increases Smad2 gene promoter activities and protein expression, which significantly lowers TGF-beta1 threshold for EMT induction. These results suggest that persistent RON expression and activation cause the loss of epithelial phenotypes. These changes, collaborating with TGF-beta1 signaling, could play a critical role in epithelial transdifferentiation towards invasiveness and metastasis of certain cancers.

Actins↗
PubMed2000

Integrins alpha(v)beta3 and alpha(v)beta5 are expressed by endothelium of high-risk neuroblastoma and their inhibition is associated with increased endogenous ceramide.

Inhibition of the RGD-binding integrins, alpha(v)beta3 and alpha(v)beta5, prevents endothelial cell anchorage and induces endothelial apoptosis, which results in disruption of tumor angiogenesis and inhibition of tumor growth in animal models. In this study, we demonstrate by immunohistochemical analysis that integrin alpha(v)beta3 was expressed by 61% (mean) of microvessels in high-risk neuroblastomas (stage IV and MYCN-amplified stage III; n = 28) but only by 18% (mean) of microvessels in low-risk tumors (stages I and II and non-MYCN-amplified stage III; n = 12). Integrin alpha(v)beta5 was found on 60% (mean) of microvessels in 21 Stage IV tumors. These data suggest that neuroblastomas may be targeted for antiangiogenic treatment directed against endothelial integrins alpha(v)beta3 and alpha(v)beta5. In cell culture, inhibition of integrin-dependent endothelial cell anchorage to vitronectin by RGDfV, an RGD function-blocking cyclic peptide, induced apoptosis in bovine brain endothelial cells compared with the control peptide, RADfV (37.5% versus 8.7%, respectively), as detected by chromatin condensation and nuclear fragmentation. Treatment with RGDfV but not with RADfV, which prevented attachment of endothelial cells to vitronectin or fibronectin, was associated with up to a 50% increase in endogenous ceramide, a lipid second messenger that can mediate cell death. Furthermore, exogenous C2-ceramide was cytotoxic to bovine brain endothelial cells and induced activation of C-jun N-terminal kinase (JNK), a MAP kinase that can be activated in stress-induced apoptosis pathways. This suggests that ceramide may function in detachment-induced endothelial cell apoptosis, originating from inhibition of vitronectin binding to integrins such as alpha(v)beta3 and alpha(v)beta5. This is the first report to demonstrate expression of integrins alpha(v)beta3 and alpha(v)beta5 by microvascular endothelium of a childhood tumor and association of their expression with neuroblastoma aggressiveness. Furthermore, our data provide the first suggestion that inhibition of endothelial cell anchorage, resulting from specific blockade of RGD-binding integrins, increases endogenous ceramide, which may contribute to endothelial cell death.

Angiogenesis Inhibitors↗
PubMed1995

Cell mixing during early epiboly in the zebrafish embryo.

Descendants of early blastomeres in the zebrafish come to populate distinctive regions of the fate map. We present a model suggesting that the distribution of cells in the early gastrula (the fate map stage) results from the passive response of cells to reproducible forces that change the overall shape of the blastoderm just prior to gastrulation. We suggest that one of the morphogenetic changes that accompanies epiboly, the upward doming of the yolk cell into the overlying blastoderm, could be responsible for cell mixing. In support of the model, we show that the timing, extent, and directions of cell mixing in the embryo accurately reflect the expectations of the model. Finally, we show that one portion of the gastrula, a marginal region that later gives rise to many of the mesendodermal derivatives, experiences little cell mixing during the doming process. As a result, this region in the gastrula is populated by the descendants of the subset of the early blastomeres that were originally at the margin. The finding that cytoplasm initially at the edge of the 1-celled blastodisc is transmitted specifically to mesendodermal precursors at the fate map stage raises the possibility that maternal determinants may contribute to initiation of embryonic patterning in the zebrafish embryo.

Animals↗
PubMed1997

Mapping and characterization of the origin of DNA replication of porcine circovirus.

The origin of DNA replication of porcine circovirus (PCV) was mapped to a 111-bp fragment. On top of a hairpin, a nonanucleotide (TAGTATTAC) homologous to nonanucleotides of other viruses was identified. Mutation of this element abolishes replication. PCV may be related to a virus family characterized by single-stranded circular DNA genomes, rolling-circle replication, and homology of their rep proteins.

Amino Acid Sequence↗
PubMed1989

Topoisomerase I sites cluster asymmetrically at the ends of the simian virus 40 core origin of replication.

In vivo, topoisomerase I cleavage sites are located predominantly on the strands of simian virus 40 DNA that are the templates for discontinuous synthesis (S.E. Porter and J.J. Champoux, Mol. Cell. Biol. 9:541-550, 1989). This arrangement of sites suggests that topoisomerase I may associate with replication complexes in unique functional orientations at replication forks. We have mapped topoisomerase I cleavage sites in the simian virus 40 origin of replication in vitro under conditions suitable for DNA replication. Numerous sites cluster in the inverted repeat and AT-rich domains at the ends of the core origin and are arranged on the same strands that are cut most frequently in vivo. We propose that cleavage at these sites would allow bidirectional extension of the replication bubble induced by T antigen within the core origin of replication early in the initiation of DNA synthesis. A mutational analysis of the topoisomerase I sites confirms the importance of positions -4 to -1 and +1 in the consensus sequence 5'-A/T-A/G-A/T-T-break-G/A-3'. Surprisingly, more distant nucleotide positions also influence topoisomerase I sites in the inverted repeat and AT-rich domains of the core origin. The effects of distant sequences could be mediated by direct interactions with topoisomerase I or by the conformation of DNA in the core origin.

Animals↗
PubMed2006

Pseudogenes of the human HPRT1 gene.

Entrez Gene lists four HPRT1 gene pseudogenes (HPRTP1, HPRTP2, HPRTP3, and HPRTP4) mapping to chromosomes 3, 5, 11q, and 11q, respectively, as originally reported by Patel et al. in 1984 (Patel PI, et al. 1984 Somat Cell Mol Genet 10:483-493). However, the Entrez Gene reports for three of the four pseudogenes (HPRTP1, HPRTP3, and HPRTP4) are currently empty. A BLAST search of both GenBank (Homo sapiens) and the human genome found the chromosome 5 associated HPRTP2 sequence and a single chromosome 11q sequence (HPRTP3 or HPRTP4?). This chromosome 11 sequence had a unique 7.2 kb insert, which may explain why it originally appeared to be two separate pseudogenes. No evidence of a chromosome 3 associated sequence was found; however, a sequence highly homologous to HPRT1 was located on chromosome 4. All of these sequences are intronless processed pseudogenes. Lastly, a sequence highly homologous to HPRT1 exon 8 was found on chromosome 10. This homologous sequence was exactly exon 8 of a gene designated PRTFDC1, for phosphoribosyl transferase domain containing 1. This gene with unknown function is almost completely homologous to HPRT1 in exon structure (except for a 21 bp (seven amino acid) insertion in exon 1) and 68% homologous in amino acid sequence.

Animals↗
PubMed2000

A novel imprinted gene, HYMAI, is located within an imprinted domain on human chromosome 6 containing ZAC.

Transient neonatal diabetes mellitus (TNDM) is a rare disease characterized by intrauterine growth retardation, dehydration, and failure to thrive due to a lack of normal insulin secretion. This disease is associated with paternal uniparental disomy or paternal duplication of chromosome 6, suggesting that the causative gene(s) for TNDM is imprinted. Recently, Gardner et al. (1999, J. Med. Genet. 36: 192-196) proposed that a candidate gene for TNDM lies within chromosome 6q24.1-q24.3. To find human imprinted genes, we performed a database search for EST sequences that mapped to this region, followed by RT-PCR analysis using monochromosomal hybrid cells with a human chromosome 6 of defined parental origin. Here we report the identification of a novel imprinted gene, HYMAI. This gene exhibits differential DNA methylation between the two parental alleles at an adjacent CpG island and is expressed only from the paternal chromosome. A previously characterized imprinted gene, ZAC/LOT1, is located 70 kb downstream of HYMAI and is also expressed only from the paternal allele. In the pancreas, both genes are moderately expressed. HYMAI and ZAC/LOT1 are therefore candidate genes involved in TNDM. Furthermore, the human chromosome 6q24 region is syntenic to mouse chromosome 10 and represents a novel imprinted domain.

Alleles↗
PubMed1977

Uptake of horseradish peroxidase by geniculo-cortical axons in the golden hamster: analysis by computer reconstruction.

Micro-injections of horseradish peroxidase (HRP) were made into the visual cortex of the golden hamster. The "projection lines" of labelled neurons in the dorsal lateral geniculate nucleus (LGNd) were three-dimensionally reconstructed, using a computer graphics technique. The lines run rostrally and medially from their origins at the lateral surface of the nucleus. Using an anatomically determined retinotopic map of the LGNd, the positions of all labelled cells near the lateral surface were converted into equivalent visual field co-ordinates and displayed on a physiologically determined retinotopic map of the primary visual cortex. Comparison between the scatter of these equivalent retinotopic loci and an actual reconstruction of the injection site revealed that: 1. there was general agreement between the independent retinotopic maps of LGNd and visual cortex; 2. there was greater retinotopic scatter of labelled LGNd cells than could be accounted for by the area of tissue injury in the cortex; 3. the retinotopic scatter matched more closely the total visible halo of HRP staining in the grey matter; 4. HRP can be taken up from a cytoarchitectonic field into which it diffuses after injection into a neighbouring area; 5. HRP is probably not taken up by undamaged axons in the white matter. These results are compared with those obtained in other animals and other systems. No general rules emerge, but the possibility of uptake from wide areas of diffusion must be considered when interpreting results of HRP injection.

Animals↗
PubMed1989

Isolation and characterization of Saccharomyces cerevisiae mutants supersensitive to G1 arrest by the mating hormone a-factor.

Nine independent mutants which are supersensitive (ssl-) to G1 arrest by the mating hormone a-factor were isolated by screening mutagenized Saccharomyces cerevisiae MAT alpha cells on solid medium for increased growth inhibition with a-factor. These mutants carried lesions in two complementation groups, ssl1 and ssl2. Mutations at the ssl1 locus were mating type specific: MAT alpha ssl1- cells were supersensitive to a-factor but MATa ssl1- were not supersensitive to alpha-factor. In contrast, mutations at the ssl2 locus conferred supersensitivity to the mating hormone of the opposite mating type on both MAT alpha and MATa cells. The alpha-cell specific capacity to inactivate externally added a-factor was shown to be lacking in MAT alpha ssl1- mutants whereas MAT alpha ssl2- cells were able to inactivate a-factor. Complementation analysis showed that ssl2 and sst2, a mutation originally isolated as conferring supersensitivity to alpha-factor to MATa cells, are lesions in the same gene. The ssl1 gene was mapped 30.5 centiMorgans distal to ilv5 on chromosome XII.

Alleles↗
PubMed1991

Human acetylcholinesterase and butyrylcholinesterase are encoded by two distinct genes.

1. Various hybridization approaches were employed to investigate structural and chromosomal interrelationships between the human cholinesterase genes CHE and ACHE encoding the polymorphic, closely related, and coordinately regulated enzymes having butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) activities. 2. Homologous cosmid recombination with a 190-base pair 5' fragment from BuChEcDNA resulted in the isolation of four overlapping cosmid clones, apparently derived from a single gene with several introns. The Cosmid CHEDNA included a 700-base pair fragment known to be expressed at the 3' end of BuChEcDNA from nervous system tumors and which has been mapped by in situ hybridization to the unique 3q26-ter position. In contrast, cosmid CHEDNA did not hybridize with full-length AChEcDNA, proving that the complete CHE gene does not include AChE-encoding sequences either in exons or in its introns. 3. The chromosomal origin of BuChE-encoding sequences was further examined by two unrelated gene mapping approaches. Filter hybridization with DNA from human/hamster hybrid cell lines revealed BuChEcDNA-hybridizing sequences only in cell lines including human chromosome 3. However, three BuChEcDNA-homologous sequences were observed at chromosomal positions 3q21, 3q26-ter, and 16q21 by a highly stringent in situ hybridization protocol, including washes at high temperature and low salt. 4. These findings stress the selectivity of cosmid recombination and chromosome blots, raise the possibility of individual differences in BuChEcDNA-hybridizing sequences, and present an example for a family highly similar proteins encoded by distinct, nonhomologous genes.

Acetylcholinesterase↗