SEARCH · PubMed Health

Results for “Disjunction”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources

PubMed1977

Genetic damage induced by ethyl alcohol in Aspergillus nidulans.

Heterozygous diploid conidia of Aspergillus nidulans were treated during germination with ethyl alcohol in concentrations ranging from 0.25% to 20% (v/v). The diploid strain carried three recessive conidial color mutations, in addition to genetic markers on all eight pairs of linkage groups. It was thereby possible to detect events of crossing over, non-disjunction, and mutation. An increase in the dose of ethanol was associated with a decrease in conidial viability and an increase in the relative and absolute frequencies of formation of (a) normal colonies which produced colored sectors and (b) phenotypically abnormal colonies, the majority of which (83.1%) produced normal sectors. At a concentration of 5% (v/v) ethanol, the survivors included 17.59% of the former and 44.7% of the latter colonies. Genetic analysis of the various segregants suggested that the frequencies of both mitotic crossing over and non-disjunction or the misdistribution of chromosomes were increased by ethanol. Among 133 abnormal colonies which segregated normal clones, 79 (59.4%) were associated with one of these genetic events. A total of 297 haploids and 130 diploids arose as normal segregants from the abnormal colonies. There were 31 recognizable events of non-disjunction and 14 crossing over in linkage groups I and II, where these events could be distinguished. These data suggested that the predominant effect of ethanol was a disruption of chromosome distribution. A cytological examination of ethanol-treated, germinating conidia revealed an interference with the mitotic spindle apparatus. The frequency of detectable spindles decreased more than 3-fold after 8 h exposure to 5% (v/v) ethanol. This finding supported the conclusion that ethanol disrupted chromosome distribution, and suggested the mechanism by which it does so. Human clinical data on alcohol consumption were examined in light of these findings.

Aspergillus nidulans↗

PubMed1979

MMS induction of different types of genetic damage in Aspergillus nidulans: a comparative analysis in mutagenesis.

Methyl methanesulphonate (MMS) was used to test the induction of gene mutation, somatic crossing-over and mitotic non-disjunction in A. nidulans. Gene mutation was tested by inducing mutants resistant to 8-azaguanine and revertants of methG1 in a haploid strain. Somatic crossing-over was tested in heterozygous diploids, both with a selective method, i.e. inducing homozygosis to FPA resistance in a heterozygous fpa A1/+ strain, and with a non-selective method, i.e. identifying the frequencies of colour sectors. This latter method was also used to estimate the induction of non-disjunction because additional markers were present which permitted us to distinguish the two types of colour segregant. Generally, 3 different experimental procedures were used, namely the "plate test", i.e. plating of conidia in agar media containing MMS, and two types of "liquid test", i.e. brief treatment of quiescent or pre-germinated conidia in MMS solution before they were plated on agar media. Point mutations were induced with about equal efficiency with each method, whereas crossing-over was induced preferentially when germinating conidia were exposed to MMS. On the other hand, non-disjunction was induced in germinating and quiescent spores with equal efficiency, but such segregants were not recovered with the selective (fpa) method. The results are discussed for both their practical use in the mutagenic testing procedure and their theoretical implication.

Aspergillus nidulans↗

PubMed1982

Expression of genetic damage induced by alkylating agents in germ cells of female mice.

The purpose of the present experiments was to analyse the frequencies of meiotic non-disjunction and structural aberrations by comparative cytogenetic investigations in unfertilized mII oocytes and first-cleavage metaphases after pre-ovulatory treatment of female mice with alkylating agents. We also present data on the expression of both types of aberration during embryogenesis in terms of dominant lethal effects. Trenimon (TR, 1 mg/kg) induced meiotic non-disjunction, but no structural aberrations were detected at metaphase II. On the contrary, at first-cleavage metaphase, TR revealed a strong clastogenic effect. A dose of 0.25 mg TR/kg increased the frequency of cells with structural aberrations to 51.79%. Mainly chromatid and a few isochromatid aberrations were found. These results support the observations previously made (see Brewen and Preston, 1979; Obe and Beek, 1979) that an intervening round of DNA replication is necessary for a TR-induced DNA lesion to be transformed into a structural aberration. The frequency of aberrant eggs in toto analysed at first cleavage (63.39%) can be quantitatively correlated to the rate of embryonic mortality (55.17%) as measured in the dominant lethal assay at the first day after treatment. We also present data on the effects of cyclophosphamide (CYC) on the first meiotic division. CYC (150 mg/kg) enhanced the incidence of meiotic non-disjunction only slightly, but induced a high frequency of dominant lethal effects (58.94%) at the first day after application.

Alkylating Agents↗

PubMed1990

Drosophila ribosomal RNA genes function as an X-Y pairing site during male meiosis.

In Drosophila melanogaster males, the sex chromosomes pair during meiosis in the centric X heterochromatin and at the base of the short arm of the Y (YS), in the vicinity of the nucleolus organizers. X chromosomes deficient for the pairing region segregate randomly from the Y. In this report we show that a single ribosomal RNA (rRNA) gene stimulates X-Y pairing and disjunction when inserted onto a heterochromatically deficient X chromosome by P element-mediated transformation. We also show that insert-containing X chromosomes pair at the site of insertion, that autosomal rDNA inserts do not affect X-Y pairing or disjunction, and that the strength of an X pairing site is proportional to the dose of ectopic rRNA genes. These results demonstrate that rRNA genes can promote X-Y pairing and disjunction and imply that the nucleolus organizers function as X-Y pairing sites in wild-type Drosophila males.

Animals↗

PubMed1977

Mutagenic and recombinogenic action of pesticides in Aspergillus nidulans.

Thirteen pesticides, aminotriazole, benomyl, captafol, captan, dalapon-Na, dichlorvos, dinobuton, dodine, ioxynil, mecoprop, neburon, picloram and tordon were tested for ability to induce (1) point mutations to 8-azaguanine resistance, (2) mitotic crossing-over, and (3) mitotic non-disjunction and haploidization in Aspergillus nidulans. Tests were performed at three different pHs, i.e. 4.5, 7, 8.2. Three of the pesticides, captan , captafol and dichlorvos induced point mutations; dichlorvos also induced a high frequency of mitotic crossing-over and non-disjunction; benomyl induced a very high frequency of non-disjunction whereas aminotriazole induced weakly both types of somatic segregation.

Aspergillus nidulans↗

PubMed1983

Double Y as an indicator in a test of mitotic nondisjunction in cultured human lymphocytes.

A cytological test for the detection of non-disjunction in human cultured lymphocytes has been developed. The Y chromosome was used as a marker, because this chromosome is easily identifiable in mitosis after staining with quinacrine dihydrochloride without karyotyping. Non-disjunction can be directly revealed by scoring mitoses with two Ys. The test was applied to agents known for their ability to induce numerical and/or structural changes in chromosomes, namely benomyl, colcemid, distamycin A, mitomycin C and X-rays. In treated lymphocytes, increased frequencies of YY mitoses were found, ranging from 2.5 X 10(-4) to 61.2 X 10(-4) (control value less than or equal to 1.1 X 10(-4). The results suggest that the detection of fluorescent Y chromosomes on metaphases is suitable for determining induced non-disjunction in human cultured cells.

Cells, Cultured↗

PubMed2005

Distinct and shared cortical regions of the human brain activated by pictorial depictions versus verbal descriptions: an fMRI study.

Using fMRI, we observed that there were functionally disjunctive regions in the human brain that were specifically activated during the silent reading of sentences (i.e., the symbolical representation at the propositional level) but not during the perception of arranged objects (i.e., analogical representation), or vice versa: Parts of the left and right lingual gyri, the left fusiform gyrus, the left and right inferior occipital gyri, the right cuneus, and the left middle occipital gyrus were activated exclusively during the silent reading of sentences, whereas perception of the arranged objects activated distinct regions in the lingual gyrus, the declive, the fusiform gyrus, and the cuneus in the right hemisphere. A large proportion (86% in cortical volume) of the occipito-temporal regions was functionally conjunctive: these neural structures were activated during both silent reading of sentences and perception of arranged objects. We observed a similar trend of functional disjunction and conjunction between single words (the symbolical mode at the lexical level) and single objects (analogical mode): the degree of functional conjunction in the latter case was about 96%. These results suggest that the degree of functional disjunction between the pictorial depictions and the verbal descriptions tended to increase as the complexity of mental representation increased from the single word (lexical) level (4%) to the sentence (propositional) level (14%).

Adult↗

PubMed2002

Importance of detecting numerical versus structural chromosome aberrations.

The aim is to review briefly the key questions related to aneuploidy/polyploidy and to compare the advantages and disadvantages of the in vitro micronucleus test to assess aneuploidy/polyploidy in vitro. The key questions that will be addressed, concern the importance of polyploidy for health, and cancer in particular, the mechanisms leading to aneuploidy and polyploidy, and the survival of aneuploid/polyploid cells. The recently recognised contribution of numerical chromosome changes to carcinogenesis triggered the development and the implementation of tests specifically aiming at the detection of aneugens in the test battery for mutagenicity and carcinogenicity. The validation of the in vitro micronucleus test in combination with the identification of in vitro divided cells with the cytokinesis-block methodology and of centromeres with pancentromeric or chromosome specific centromeric probes fluorescence in situ hybridisation (FISH) provides a sensitive, easy to score and powerful test which allows assessment of cell proliferation, the discrimination between chromosome breaks, chromosome loss and chromosome non-disjunction and polyploidy. Moreover, classic histology permits the estimation of necrosis and apoptosis on the same slide. The cytokinesis-blocked micronucleus assay could be considered as a multi-endpoint test for genotoxic responses to clastogens/aneugens. This methodology has also shown to be capable of identifying threshold values for the induction of chromosome loss and/or non-disjunction by microtubule inhibitors, data which are particularly important for risk calculations. Similar approaches were conducted in vivo on bone marrow in mice and rats (except for identification of chromosome non-disjunction), and are in development for gut in mice.

Aneuploidy↗

PubMed2001

The schedule of destruction of three mitotic cyclins can dictate the timing of events during exit from mitosis.

BACKGROUND: Degradation of the mitotic cyclins is a hallmark of the exit from mitosis. Induction of stable versions of each of the three mitotic cyclins of Drosophila, cyclins A, B, and B3, arrests mitosis with different phenotypes. We tested a recent proposal that the destruction of the different cyclins guides progress through mitosis. RESULTS: Real-time imaging revealed that arrest phenotypes differ because each stable cyclin affects specific mitotic events differently. Stable cyclin A prolonged or blocked chromosome disjunction, leading to metaphase arrest. Stable cyclin B allowed the transition to anaphase, but anaphase A chromosome movements were slowed, anaphase B spindle elongation did not occur, and the monooriented disjoined chromosomes began to oscillate between the spindle poles. Stable cyclin B3 prevented normal spindle maturation and blocked major mitotic exit events such as chromosome decondensation but nonetheless allowed chromosome disjunction, anaphase B, and formation of a cytokinetic furrow, which split the spindle. CONCLUSIONS: We conclude that degradation of distinct mitotic cyclins is required to transit specific steps of mitosis: cyclin A degradation facilitates chromosome disjunction, cyclin B destruction is required for anaphase B and cytokinesis and for directional stability of univalent chromosome movements, and cyclin B3 degradation is required for proper spindle reorganization and restoration of the interphase nucleus. We suggest that the schedule of degradation of cyclin A, cyclin B, and then cyclin B3 contributes to the temporal coordination of mitotic events.

Anaphase↗

PubMed2001

Separase is required for chromosome segregation during meiosis I in Caenorhabditis elegans.

BACKGROUND: Chromosome segregation during mitosis and meiosis is triggered by dissolution of sister chromatid cohesion, which is mediated by the cohesin complex. Mitotic sister chromatid disjunction requires that cohesion be lost along the entire length of chromosomes, whereas homolog segregation at meiosis I only requires loss of cohesion along chromosome arms. During animal cell mitosis, cohesin is lost in two steps. A nonproteolytic mechanism removes cohesin along chromosome arms during prophase, while the proteolytic cleavage of cohesin's Scc1 subunit by separase removes centromeric cohesin at anaphase. In Saccharomyces cerevisiae and Caenorhabditis elegans, meiotic sister chromatid cohesion is mediated by Rec8, a meiosis-specific variant of cohesin's Scc1 subunit. Homolog segregation in S. cerevisiae is triggered by separase-mediated cleavage of Rec8 along chromosome arms. In principle, chiasmata could be resolved proteolytically by separase or nonproteolytically using a mechanism similar to the mitotic "prophase pathway." RESULTS: Inactivation of separase in C. elegans has little or no effect on homolog alignment on the meiosis I spindle but prevents their timely disjunction. It also interferes with chromatid separation during subsequent embryonic mitotic divisions but does not directly affect cytokinesis. Surprisingly, separase inactivation also causes osmosensitive embryos, possibly due to a defect in the extraembryonic structures, referred to as the "eggshell." CONCLUSIONS: Separase is essential for homologous chromosome disjunction during meiosis I. Proteolytic cleavage, presumably of Rec8, might be a common trigger for the first meiotic division in eukaryotic cells. Cleavage of proteins other than REC-8 might be necessary to render the eggshell impermeable to solutes.

Animals↗

PubMed2000

Evaluation of thresholds for benomyl- and carbendazim-induced aneuploidy in cultured human lymphocytes using fluorescence in situ hybridization.

Threshold mechanisms of activity for mutagenic agents have been debated for some time, especially for those substances which induce aneuploidy by inhibiting mitotic spindle function. No observed effect levels (NOELs) or "practical thresholds" have been demonstrated for several aneugens both in vitro and in vivo generally by either counting chromosomes in metaphase preparations or by observing micronuclei. Recently, fluorescence in situ hybridization (FISH) has proven to be a sensitive and useful technique for the assessment of aneuploidy at low concentrations. Using binucleate human lymphocytes coupled with FISH, we have been able to characterize a threshold mechanism of action for two spindle inhibitors, benomyl and its active metabolite, carbendazim. Test chemicals were added 24 h following culture initiation. After a further 20 h, cytochalasin B was added, and cells were harvested 28 h later (72 h post initiation). The distribution of chromosomes between the nuclei of binucleate cells was evaluated by fluorescence microscopy for the simultaneous detection of centromeres labeled with FITC (green) or Cy-3 (red). Six human chromosomes were investigated in pairs (1 and 8, 11 and 18, and X and 17). Abnormalities were classified as chromosome loss (including centromeric positive micronuclei), chromosome gain, non-disjunction, or polyploidy. Dose-response data were generated over a range of closely spaced concentrations at 100 ng/ml intervals. The threshold, defined as the lowest "effect" concentration using statistical methods, was determined for each chromosome. Non-disjunction proved to be the most sensitive endpoint for the detection of aneuploidy occurring at higher frequencies and lower concentrations. Results for the six chromosomes demonstrated similar dose-response data which included a series of concentrations with no statistically significant increase above background, followed by a second range of higher concentrations with a statistically significant, concentration-dependent increase. Nearly equimolar threshold concentrations were determined for benomyl- and carbendazim-induced non-disjunction.

Adult↗

PubMed2001

A kinetic study of nickel complexation in model systems by adsorptive cathodic stripping voltammetry.

Adsorptive cathodic stripping voltammetry (AdCSV) in conjunction with the competing ligand-exchange method (CLEM) was investigated as a tool for measuring dissociation rate coefficients of nickel complexes in model systems. Dimethylglyoxime (DMG) was used as the competing ligand. Citric acid (CA) and a well-characterized fulvic acid (FA) were used as model ligands. The rate coefficients were calculated, and the consistency of equilibrium and kinetic data was discussed. The contributions of the disjunctive pathway (proceeding by the dissociation of the initial complex) and the adjunctive pathway (proceeding by the formation of an intermediate complex as a result of direct attack of the competing ligand on the initial complex) on the overall reactions were investigated. The reactions of Ni-CA or Ni-FA complexes with DMG were demonstrated to proceed by both disjunctive and adjunctive pathways. The predominant pathway for the overall reaction depends on the nickel-to-initial ligand and the DMG-to-initial ligand ratios. The reactions follow predominantly the disjunctive pathway for [DMG] > or = 3 mM and Ni-to-dissolved organic carbon (DOC) ratios greater than 10 nM Ni 2+/g of DOC. Since free nickel ion in freshwaters is reported to be toxic, its rate and pathway of formation are of environmental concern.

Benzopyrans↗

PubMed2000

Replication asynchrony increases in women at risk for aneuploid offspring.

We attempted to demonstrate a relation between a loss of replication control, centromere dysfunction, and predisposition to non-disjunction. Couples with a Down syndrome offspring were the high-risk probands. One-color FISH (fluorescent in-situ hybridization) was applied to interphase nuclei (lymphocytes). Replication pattern of two pairs of alleles, RB-1 and 21q22, were studied, and the rate of aneuploidy was estimated using two alpha-satellite probes of chromosomes 8 and 18. Our results suggest the existence of an association between replication timing and the rate of non-disjunction. A higher rate of allele asynchrony and aneuploidy was found in older women and in mothers of a Down syndrome offspring. These findings may reflect a predisposition for meiotic non-disjunction in these women.

Adult↗

PubMed1983

Response selection and initiation in speeded reactions: a pupillometric analysis.

Three studies are described in which the task-evoked pupillary response is recorded during simple and disjunctive reactions in order to examine its contribution as a measure of the motoric and cognitive aspects of performance in these tasks. In simple reactions a pupillary dilation began about 1.5 sec before the imperative stimulus and peaked about 1 sec after the stimulus. The rate of dilation was inversely related to the interstimulus interval. In disjunctive reactions, both "Go" and "No-Go" responses elicited significant dilations but the No-Go dilation was smaller than the Go dilation. When the response was delayed 2.5 sec after the discrimination stimulus, the dilation to both Go and No-Go responses was much reduced. The pupillary response related to response selection was estimated at 55% of that associated with motor preparation and execution. The probability of responding was found to affect the amplitude of the dilation to No-Go responses but not that to Go responses. The data point to a significant contribution of preparatory motor processing in No-Go reactions and to an overlap between decisional and motoric processing in disjunctive reactions.

Female↗

PubMed2002

Mortality of pollen grains may result from errors of meiosis: study of pollen tetrads in Typha latifolia L.

In the cattail Typha latifolia the four haploid products of meiosis remain attached and form the flat tetrad of pollen grains. Gametophytic lethals arisen de novo in diploid cells of sporophyte must manifest themselves as pollen tetrads with two dead grains. This could allow to estimate the rate of recessive lethals arresting pollen grain development. We studied pollen samples collected from 44 sprouts in two populations in the vicinity of Novosibirsk. The anomalous tetrads T1, T2, T3, and T4 carrying one, two, three, and four dead grains, respectively, were detected in each sampled individual. The mean frequency of all anomalous tetrads in the two populations was 3.4% and 8.7%. The frequencies of tetrad classes varied widely among the individuals with correlation coefficient up to 0.94, but their ratios remained nearly constant. The majority of anomalous tetrads were presented by T1 and T2 classes (their sum comprising 72.7 and 74.0% in two populations), T1 being a little more abundant. The observed pattern of frequencies of tetrads with dead grains can be explained by errors of male meiosis such as chromosome non-disjunction in both meiotic divisions. The tetrads with two dead pollen grains may result mostly from non-disjunction in anaphase I, and those with one pollen grain from non-disjunction in anaphase II, thus making tetrad analysis ineffective for estimating the rate of gametophytic lethals.

Chromosome Mapping↗

PubMed2001

Intraspecific phylogeography of Percina evides (Percidae: Etheostomatinae): an additional test of the Central Highlands pre-Pleistocene vicariance hypothesis.

North America exhibits the most diverse freshwater fish fauna among temperate regions of the world. Species diversity is concentrated in the Central Highlands, drained by the Mississippi, Gulf Slope and Atlantic Slope river systems. Previous investigations of Central Highlands biogeography have led to conflicting hypotheses involving dispersal and vicariance to explain the diversity and distribution of the freshwater fish fauna. In this investigation predictions of the Central Highlands pre-Pleistocene vicariance hypothesis are tested with a phylogeographic analysis of the percid species Percina evides, which is widely distributed in several disjunct areas of the Central Highlands. Phylogenetic analysis of complete gene sequences of mitochondrially encoded cytochrome b recover three phylogroups, with very low levels of sequence polymorphism within groups. The two western phylogroups are monophyletic with respect to the eastern phylogroup. The recovery of two monophyletic lineages with an eastern and western distribution in the disjunct highland areas is a pattern expected from vicariance, but is not predicted by the Central Highlands pre-Pleistocene vicariance hypothesis. The recovery of very limited mitochondrial DNA polymorphism and lack of phylogeographic structuring across the entire range of the eastern clade, very shallow polymorphism between the disjunct Missouri River and upper Mississippi River populations, and lack of sequence polymorphism in the upper Mississippi River populations, support a hypothesis of dispersal during or following the Pleistocene. The present distribution of P. evides is best explained by both vicariant and dispersal events.

Animals↗

PubMed1991

Genetic analysis of microtubule motor proteins in Drosophila: a mutation at the ncd locus is a dominant enhancer of nod.

The nod (no distributive disjunction) and the ncd (non-claret disjunctional) mutations are both female-specific, recessive meiotic mutations in Drosophila melanogaster. Mutations at either locus show high frequencies of nondisjunction at meiosis I and both have been shown to encode kinesin-like proteins. Unlike the ncd mutation, which affects all chromosome pairs, the nod mutation affects only the disjunction of nonexchange chromosomes. Although both the nod and ncd mutations are fully recessive, females doubly heterozygous for nod and ncd mutations show levels of X and fourth chromosome nondisjunction that are 6- to 35-fold above those observed in control females. Exchange between chromosomes can suppress this effect; thus, only nonexchange chromosomes segregating via the distributive system are sensitive in double heterozygotes. Since the phenotype of double heterozygotes mimics that of the nod mutation, we infer that ncd is a dominant enhancer of nod. Failure of ncd to fully complement nod reveals the chromosome segregation machinery to be dosage sensitive. The probability that the distributive system will fail is enhanced in females simultaneously haploinsufficient at the nod and ncd loci.

Animals↗

PubMed1998

Essential mitotic functions of DNA topoisomerase IIalpha are not adopted by topoisomerase IIbeta in human H69 cells.

Unique functions of mammalian DNA-topoisomerases IIalpha and -beta are suggested by their distinct cellular distribution and chromatin binding at mitosis. Here, we studied H69-VP cells that, due to a homozygous mutation, express topoisomerase IIalpha mostly outside the nucleus. In these cells topoisomerase IIbeta showed a normal nuclear localization. However, at mitosis it diffused away from the chromatin despite the nuclear lack of the alpha-isoform. 80% of these cells performed chromosome condensation and disjunction with the aid of cytosolic topoisomerase IIalpha, which bound to the mitotic chromatin with low affinity. However, the genotype of these cells was highly polyploid indicating an increased rate of non-disjunction. In 20% of the mutant cells neither topoisomerase II isoform was bound to the mitotic chromatin, which appeared as an unstructured DNA spheroid unable to undergo disjunction and cytokinesis. Parental H69 cells expressing topoisomerase IIalpha inside the nucleus exhibited high affinity binding of the enzyme to the mitotic chromatin. Their genotype was mostly diploid and stable. We conclude (i) that high affinity chromatin binding of topoisomerase IIalpha is essential for chromosome condensation/disjunction and (ii) that topoisomerase IIbeta does not adopt these functions.

Antigens, Neoplasm↗