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 631 records · Page 35Linked to original sources

PubMed2003

Indirect mechanisms of genotoxicity.

Indirect mechanisms of genotoxicity correspond to interactions of mutagens with non-DNA targets, and are expected to show threshold concentration-effect response curves. If these thresholds can be proven experimentally they may provide a third alternative for risk assessment, besides the No Effect Level/Safety Factor approach and the low dose linear extrapolation method. We contributed significantly to the in vitro assessment of thresholds in human lymphocytes exposed to the spindle inhibitors nocodazole and carbendazim showing dose dependency and existence of lower thresholds for induction of non-disjunction as compared to chromosome loss. Micronuclei correlated with p53-independent or p53-dependent apoptosis and elimination of aneuploid cells. Extrapolation from in vitro threshold values to the in vivo situation remains unsolved. Comparing the in vitro threshold values for griseofulvin in human and rat lymphocytes with in vivo NOAEL/LOAEL in bone marrow/gut/erythrocytes suggests that the in vitro human system is the most sensitive. The threshold for induction of non-disjunction in in vitro maturing, nocodazole-exposed mouse oocytes was in the same low range. Regulators (UK Committee on Mutagenicity, http://www.doh.gov.uk/com/com.htm) considered the importance of thresholds for indirect mechanisms of genotoxicity. Acceptance of a non-linear extrapolation for mutagens requires mechanistic studies identifying the mutagen/target interactions. Moreover appropriate risk evaluation will require additional studies on individual susceptibility for indirect mutagenic effects and on interactions of aneugens in complex mixtures.

Animals↗

PubMed1999

Drosophila grapes/CHK1 mutants are defective in cyclin proteolysis and coordination of mitotic events.

The Drosophila grapes (grp) gene, which encodes a homolog of the Schizosaccharomyces pombe Chk1 kinase, provides a cell-cycle checkpoint that delays mitosis in response to inhibition of DNA replication [1]. Grp is also required in the undisturbed early embryonic cycles: in its absence, mitotic abnormalities appear in cycle 12 and chromosomes fail to fully separate in subsequent cycles [2] [3]. In other systems, Chk1 kinase phosphorylates and suppresses the activity of Cdc25 phosphatase: the resulting failure to remove inhibitory phosphate from cyclin-dependent kinase 1 (Cdk1) prevents entry into mitosis [4] [5]. Because in Drosophila embryos Cdk1 lacks inhibitory phosphate during cycles 11-13 [6], it is not clear that known actions of Grp/Chk1 suffice in these cycles. We found that the loss of grp compromised cyclin A proteolysis and delayed mitotic disjunction of sister chromosomes. These defects occurred before previously reported grp phenotypes. We conclude that Grp activates cyclin A degradation, and functions to time the disjunction of chromosomes in the early embryo. As cyclin A destruction is required for sister chromosome separation [7], a failure in Grp-promoted cyclin destruction can also explain the mitotic phenotype. The mitotic failure described previously for cycle 12 grp embryos might be a more severe form of the phenotypes that we describe in earlier embryos and we suggest that the underlying defect is reduced degradation of cyclin A.

Anaphase↗

PubMed2005

Negligible interchromosomal effect in embryos of Robertsonian translocation carriers.

It has been suggested that translocations, and perhaps other chromosome rearrangements, disturb meiotic disjunction of chromosome pairs not involved in the translocation, resulting in non-disjunction in those chromosomes (interchromosomal effect) and predisposition to trisomy offspring. Other reports have suggested an increased risk of mosaicism and chaotic embryos in translocation carriers. This study was designed to determine if such interchromosomal effects are producing significantly more chromosome abnormalities than those expected from unbalanced gametes. For that purpose, two groups of PGD patients were compared, Robertsonian translocation carriers (RBT) and carriers of X-linked diseases (XLI), of similar age. Both groups were analysed by FISH with similar DNA probes. The results indicate that overall, the higher rate of chromosome abnormalities in the RBT group was solely due to unbalanced gametes and not to an interchromosomal effect or higher incidence of mosaicism. If unbalanced and normal were combined, this proportion was 53% in XLI and 59% in RBT. However, when specific RBT translocations were studied, only a slight increase in embryos with aneuploidy for chromosome 22 was found for the t(13;14) translocation carriers, while a higher rate of post-zygotic abnormalities was observed in the more rare RBT. In conclusion, the overall rate of non-translocation related abnormalities was not increased in the RBT group compared with the control group, but a slight interchromosomal effect may exist, as some Robertsonian translocations may be more prone to produce mosaic and chaotic embryos.

Adult↗

PubMed1989

Relationship between chromosome content and nuclear diameter in early spermatids of Drosophila melanogaster.

We have studied, using light microscopy, the relationship between chromosome content and nuclear diameter in early spermatids of males carrying different combinations of wild-type and compound chromosomes in Drosophila melanogaster. By using these genotypes we have been able to observe spermatid nuclei bearing various numbers of chromosomes ranging from only one sex chromosome and no major autosomes to almost twice the normal chromosome complement. We have found that variations in the chromosome content are accompanied by increasing the variance in early spermatid nuclear diameter; the more gametic classes produced, the higher the variance of nuclear diameters. These results indicate that measuring nuclear diameters in early spermatids represents a useful way to estimate the levels of meiotic non-disjunction and thereby to improve the characterization of lethal or male sterile mutants in which analysis of meiotic chromosome non-disjunction cannot be achieved by conventional genetic methods.

Animals↗

PubMed2003

The proximate determinants of sex ratio in C. elegans populations.

The soil nematode Caenorhabditis elegans is an example of a species in which self-fertilizing hermaphrodites predominate, but functional males continue to persist--allowing outcrossing to persevere at low levels. Hermaphrodites can produce male progeny as a consequence of sex chromosome non-disjunction or via outcrossing with males. Consequently, the genetics of sex determination coupled with the efficiency by which males find, inseminate and obtain fertilizations with hermaphrodites will influence the frequency at which males and outcrossing occurs in such populations. Behavioural and physiological traits with a heritable basis, as well as ecological characters, may influence male reproductive success and therefore sex ratio. Because sex ratio is tied to male reproductive success, sex ratio greatly affects outcrossing rates, patterns of genetic variation, and the ability of natural selection to act within populations. In this paper we explore the determinants of male frequency in C. elegans with a mathematical model and experimental data. We address the role of the genetic machinery of sex determination via sex chromosome non-disjunction on sex ratio and the influence of physiological components of C. elegans' life history that contribute to variation in sex ratio by way of male reproductive success. Finally, we discuss the short-term and long-term factors that are likely to affect sex ratio and breeding system evolution in species like C. elegans.

Animals↗

PubMed2002

Mental models in deductive reasoning.

We report research investigating the role of mental models in deduction. The first study deals with conjunctive inferences (from one conjunction and two conditional premises) and disjunctive inferences (from one disjunction and the same two conditionals). The second study examines reasoning from multiple conditionals such as: If e then b; If a then b; If b then c; What follows between a and c? The third study addresses reasoning from different sorts of conditional assertions, including conditionals based on if then, only if, and unless. The paper also presents research on figural effects in syllogistic reasoning, on the effects of structure and believability in reasoning from double conditionals, and on reasoning from factual, counterfactual, and semifactual conditionals. The findings of these studies support the model theory, pose some difficulties for rule theories, and show the influence on reasoning of the linguistic structure and the semantic content of problems.

Cognition↗

PubMed2002

Forecasting trial outcomes: lawyers assign higher probability to possibilities that are described in greater detail.

The study of judgment under uncertainty has revealed that people judge the probability of an event to be higher when the event is described as a disjunction of constituent events or when they judge constituent events separately. These observations have motivated the development of support theory (Y. Rottenstreich & A. Tversky, 1997; A. Tversky & D. J. Koehler, 1994), a descriptive model of judgment under uncertainty. The major predictions of support theory are that (1) the judged probabilities of complementary events sum to 1; (2) the judged probabilities of n > 2 exclusive and exhaustive events generally sum to more than 1; and (3) the judged probability of an event generally increases when it is described as a disjunction of specific possibilities. We test these predictions in 6 studies of experienced attorneys who judged the likelihood of particular trial outcomes or were asked to offer advice on whether or not to accept a settlement offer. The results demonstrate that attorneys are indeed susceptible to bias in forecasting trial outcomes, consistent with support theory.

Forecasting↗

PubMed2000

On the roles of heterochromatin and euchromatin in meiosis in drosophila: mapping chromosomal pairing sites and testing candidate mutations for effects on X-Y nondisjunction and meiotic drive in male meiosis.

Mapping of pairing sites involved in meiotic homolog disjunction in Drosophila has led to conflicting hypotheses about the nature of such sites and the role of heterochromatin in meiotic pairing. In the female-specific distributive system, pairing regions appear to be exclusively heterochromatic and map to broad regions encompassing many different sequences. In male meiosis, autosomal pairing sites appear to be distributed broadly within euchromatin but to be absent from heterochromatin, whereas the X-pairing site maps in the centric heterochromatin. The X site has been shown to coincide with the intergenic spacer (IGS) repeats within the rDNA arrays shared between the X and Y. It has not been clear whether the heterochromatic location of this pairing site has any significance. A novel assay for genic modifiers of X-Y chromosome pairing was developed based on the intermediate nondisjunction levels observed in males whose X chromosome lacks the native pairing site but contains two transgenic insertions of single rDNA genes. This assay was used to test several mutations in Su(var) (Suppressor of position effect variegation), PcG (Polycomb-Group) recombination defective, and repair-defective genes. No strong effects on disjunction were seen. However, the tests did uncover several mutations that suppress or enhance the meiotic drive (distorted X-Y recovery ratio) that accompanies X-Y pairing failure.

Animals↗

PubMed2000

Somatic segregation errors predominantly contribute to the gain or loss of a paternal chromosome leading to uniparental disomy for chromosome 15.

Paternal uniparental disomy (UPD) for chromosome 15 (UPD15), which is found in approximately 2% of Angelman syndrome (AS) patients, is much less frequent than maternal UPD15, which is found in 25% of Prader-Willi syndrome patients. Such a difference cannot be easily accounted for if 'gamete complementation' is the main mechanism leading to UPD. If we assume that non-disjunction of chromosome 15 in male meiosis is relatively rare, then the gain or loss of the paternal chromosome involved in paternal and maternal UPD15, respectively, may be more likely to result from a post-zygotic rather than a meiotic event. To test this hypothesis, the origin of the extra chromosome 15 was determined in 21 AS patients with paternal UPD15 with a paternal origin of the trisomy. Only 4 of 21 paternal UPD15 cases could be clearly attributed to a meiotic error. Furthermore, significant non-random X-chromosome inactivation (XCI) observed in maternal UPD15 patients (p < 0.001) provides indirect evidence that a post-zygotic error is also typically involved in loss of the paternal chromosome. The mean maternal and paternal ages of 33.4 and 39.4 years, respectively, for paternal UPD15 cases are increased as compared with normal controls. This may be simply the consequence of an age association with maternal non-disjunction leading to nullisomy for chromosome 15 in the oocyte, although the higher paternal age in paternal UPD15 as compared with maternal UPD15 cases is suggestive that paternal age may also play a role in the origin of paternal UPD15.

Adult↗

PubMed1992

Propositional reasoning by model.

This article describes a new theory of propositional reasoning, that is, deductions depending on if, or, and, and not. The theory proposes that reasoning is a semantic process based on mental models. It assumes that people are able to maintain models of only a limited number of alternative states of affairs, and they accordingly use models representing as much information as possible in an implicit way. They represent a disjunctive proposition, such as "There is a circle or there is a triangle," by imagining initially 2 alternative possibilities: one in which there is a circle and the other in which there is a triangle. This representation can, if necessary, be fleshed out to yield an explicit representation of an exclusive or an inclusive disjunction. The theory elucidates all the robust phenomena of propositional reasoning. It also makes several novel predictions, which were corroborated by the results of 4 experiments.

Algorithms↗

PubMed1975

Effects of disulfiram on the amphetamine-induced behavioral syndrome in the cat as a model of psychosis.

We have previously reported that, from a phenomenological standpoint, the behavioral manifestations of cats chronically intoxicated with amphetamine parallel the evolution of the paranoid psychosis induced by the drug in humans. However, certain manifestations in the cat, such as frozen postures, disjunctive behaviors and postures, cataleptic-like phenomena, obstinate progression, loss of righting reflex and pupillary changes, did not appear to be consistent with the phenomenology of the paranoid psychosis. Since treatment of schizophrenic patients with disulfiram, an inhibitor of norepinephrine synthesis that acts at the level of the enzyme dopamine beta-hydroxylase, thereby leading to increased dopamine concentrations, had been found to profoundly exaggerate psychotic symptomatology, amphetamine behavioral syndrome in the cat as it is modified by pretreatment with disulfiram. Following such pretreatment, a faster development of certain end-stage components of the amphetamine syndrome was obtained. Thus, on the first day, development of a Reactive attitude and of more prominent behavioral disjunction occurred with the combined drug administration as compared with amphetamine alone. In contrast with the facilitation of these behaviors was the absence of dyskinesias and hyperreflexia on that day. Stereotyped behavior, loss of motor initiative and hyperkinetic activity were markedly enhanced and appeared with a shorter latency period on subsequent days of the intoxication cycle. Loss of righting reflex was an early manifestation in these animals. During the later days, the particularly high level of compulsive activity was evident from the occurrence of an obstinate progression syndrome and the performance of stereotyped movements of the head in the presence of a crucifixion posture. In general, modification of the amphetamine effects on behavior was in a direction consistent with comparable features in experimental catatonia and the catatonic form of schizophrenia. The need to integrate such phenomena in any amphetamine model of psychosis is stressed and analogies are drawn with similar features reported in animals treated with bulbocapnine or other psychotogenic compounds and with symptoms of human amphetamine psychosis and schizophrenia.

Animals↗

PubMedDate not supplied

Ethanol-induced chromosomal abnormalities at conception.

Preliminary findings have indicated that mouse eggs exposed briefly in vivo or in vitro to a dilute solution of ethanol activate parthenogenetically. Cytogenetic analysis of the first-cleavage chromosomes of haploid parthenogenetic embryos indicated that up to 20% of this population were aneuploid as a result of non-disjunction. Anaesthetics also can induce parthenogenesis of rodent eggs, and in studies using anaesthetics, colchicine and colcemid, abnormal chromosome segregation and heteroploidy of rodent embryos have been observed. I now report that when recently mated female mice are given a dilute solution of ethanol by mouth, non-disjunction can be induced in the female-derived, but apparently not in the male-derived, chromosome set of fertilized eggs. Taken together, these findings suggest that ethanol consumption (as well as exposure to other 'spindle-acting' agents) at the time of conception may be the cause of certain types of chromosomal defects commonly observed in human spontaneous abortions.

Abortion, Spontaneous↗

PubMed2000

Large-scale processes and the Asian bias in species diversity of temperate plants.

An important issue in the study of biodiversity is the extent to which global patterns of species richness reflect large-scale processes and historical contingencies. Ecological interactions in local assemblages may constrain the number of species that can coexist, but differences in diversity in similar habitats within different regions (diversity anomalies) suggest that this limit is not firm. Variation in rate of species production could influence regional and perhaps local diversity independently of the ecological capacity of an area to support coexisting species, thereby creating diversity anomalies. Temperate Zone genera of plants that are disjunct between similar environments in eastern Asia and eastern North America (EAS-ENA) have twice as many species in Asia as in North America. Because lineages of these genera in Asia and North America are mostly sister pairs, they share a common history of adaptation and ecological relationship before disjunction. Thus, the diversity anomaly in EAS-ENA genera is not an artefact of taxon or habitat sampling but reflects differences in the net diversification (speciation-extinction) of the lineages in each of the continents. Here we propose that the most probable cause of the EAS-ENA anomaly in diversity is the extreme physiographical heterogeneity of temperate eastern Asia, especially compared with eastern North America, which in conjunction with climate and sea-level change has provided abundant opportunities for evolutionary radiation through allopatric speciation.

Asia↗

PubMed2001

Population genetics of the hispid cotton rat (Sigmodon hispidus): patterns of genetic diversity at the major histocompatibility complex.

The hispid cotton rat, Sigmodon hispidus, is a common rodent widely distributed across the southern USA and south into South America. To characterize major histocompatibility complex (MHC) diversity in this species and to elucidate large-scale patterns of genetic partitioning, we examined MHC genetic variability within and among 13 localities, including a disjunct population in Arizona and a population from Costa Rica that may represent an undescribed species. We also tested the hypothesis that populations within the USA are at equilibrium with regard to gene flow and genetic drift, resulting in isolation-by-distance. Using single-strand conformation polymorphism (SSCP) analysis we identified 25 alleles from 246 individuals. Gene diversity within populations ranged from 0.000 to 0.908. Analysis of molecular variance (AMOVA) revealed that 83.7% of observed variation was accounted for by within-population diversity and 16.3% was accounted for by among-population divergence. The disjunct population in Arizona was fixed for a single allele. The Costa Rican population was quite divergent based on allelic composition and was the only population with unique alleles. Within the main portion of the geographical distribution of S. hispidus in the USA there was considerable divergence among some populations; however, there was no significant pattern of isolation-by-distance overall (P = 0.090). Based on the significant divergence of the only sampled population to its east, the Mississippi River appears to represent a substantial barrier to gene flow.

Alleles↗

PubMed1974

Genetic recombination and commitment to meiosis in Saccharomyces.

Diploid cells of the yeast Saccharomyces cerevisiae become committed to recombination at meiotic levels without becoming committed to the meiotic disjunction of chromosomes. These two events of the meiotic process can be separated by removing cells from a meiosis-inducing medium and returning them to a medium that promotes vegetative cell division. Cells removed at an appropriate time remain diploid, revert to mitosis, and display recombination with meiotic-like frequencies. Those removed after this time are committed to the completion of meiosis. Diploids of three conditional sporulation-deficient mutants (spo1-1, spo2-1, and spo3-1) have been examined for recombination at restrictive temperatures. All exhibit commitment to recombination without commitment to meiotic disjunction as in the wild type. Cells of spo1-1/spo1-1 do not replicate the spindle pole body for meiosis I; thus, recombination ability can be acquired by cells that do not proceed beyond this cytological stage.

Alleles↗

PubMed2002

The calmodulin-binding domain from a plant kinesin functions as a modular domain in conferring Ca2+-calmodulin regulation to animal plus- and minus-end kinesins.

Plant kinesin-like calmodulin-binding protein (KCBP) is a novel member of the kinesin superfamily that interacts with calmodulin (CaM) via its CaM-binding domain (CBD). Activated CaM (Ca(2+)-CaM) has been shown to inhibit KCBP interaction with microtubules (MTs) thereby abolishing its motor- and MT-dependent ATPase activities. To test whether the fusion of CBD to non-CaM-binding kinesins confers Ca(2+)-CaM regulation, we fused the CBD of KCBP to the N or C terminus of a minus-end (non-claret disjunction) or C terminus of a plus-end (Drosophila kinesin) motor. Purified chimeric kinesins bound CaM in a Ca(2+)-dependent manner whereas non-claret disjunction, Drosophila kinesin, and KCBP that lack a CBD did not. As in the case of KCBP with CBD, the interaction of chimeric motors with MTs, as well as their MT-stimulated ATPase activity, was inhibited by Ca(2+)-CaM. The presence of a spacer between the motor and CBD did not alter Ca(2+)-CaM regulation. However, KCBP interaction with MTs and its MT-stimulated ATPase activity were not inhibited when the motor domain and CBD were added separately, suggesting that Ca(2+)-CaM regulation of CaM-binding motors occurs only when the CBD is attached to the motor domain. These results show that the fusion of the CBD to animal motors confers Ca(2+)-CaM regulation and suggest that the CBD functions as a modular domain in disrupting motor-MT interaction. Our data also support the hypothesis that CaM-binding kinesins may have evolved by addition of a CBD to a kinesin motor domain.

Animals↗

PubMed1998

Enhancing the usability of a task analysis method: a notation and environment for requirements specification.

This paper presents a notation and computer-based tool for the Sub-Goal Template (SGT) method, a task-analytic approach to specifying information requirements. In particular, it focuses upon the ergonomic redesign of a notation used in the SGT method for specifying contingent sequences in operators' tasks. Two experiments are reported in which two notations for redescribing sequences that involve making a choice between task alternatives are compared: a disjunctive form (Either ... or ...)-used in the original SGT scheme, and a conditional form with a redundant negative (If ... then ... if not ...), which has been promoted as a notation for capturing procedural sequences in computer programming. In experiment 1, performance with the conditional notation was better than with the disjunctive notation for redescribing simple and moderately complex task plans, although there was no difference for the most complex task plans. In experiment 2, a computer environment for specifying task plans using the SGT method was compared with a paper-based equivalent. In general, the computer environment was found to be easier to use and led to greater accuracy in plan redescription, although it was slower perhaps as a result of the constraints that it placed on participants. This paper argues for the necessity of ergonomic design in developing notations and tools to support task analysis methods.

Computers↗

PubMed1979

Repairs of X-ray induced sublethal damage in class B oocytes of Drosophila melanogaster.

Repair of X-ray-induced sublethal damage (Elkind-type recovery) in class B oocytes of Drosophila melanogaster was studied. Newly hatched females of two different stocks were treated with either acute or fractionated exposures. For the fractionation experiments a constant time interval of one hour between the dose fractions was used. As genetic endpoints dominant lethality, chromosome aberrations (detachments) and non-disjunction were studied. The repair of X-ray-induced sublethal damage in class B oocytes is expressed as a reappearance on the initial shoulder in the fractionation curve. For dominant lethality it could be shown that less sublethal damage is repaired in oocytes of Berlin wild females than in those of attached-X females (on the average 76 per cent and 101 per cent respectively). Complete repair (about 100 per cent) was observed for detachments in occytes of attached-X females. Within the dose ranges used no radiation effects on non-disjunction could be observed. The results are interpreted to show that in class B oocytes (1) sublethal damage is due to chromosome breaks and/or lesions leading to breaks and (2) X-ray-induced dominant lethality is the consequence of chromosome damage (true dominant lethals).

Animals↗