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PubMed1988

The relationship between RNA catalytic processes.

Proposals that an RNA-based genetic system preceded DNA, stem from the ability of RNA to store genetic information and to promote simple catalysis. However, to be a valid basis for the RNA world, RNA catalysis must demonstrate or be related to intrinsic chemical properties which could have existed in primordial times. We analyze this question by first classifying RNA catalysis and related processes according to their mechanism. We define: (A) the disjunct nucleophile class which leads to 5'-phosphates. These include Group I and II intron splicing, nuclear mRNA splicing and RNase P reactions. Although Group I introns and its excision mechanism is likely to have existed in primordial times, present-day examples have arisen independently in different phyla much more recently. Comparative methodology indicates that RNase P catalysis originated before the divergence of the major kingdoms. In addition, all disjunct nucleophile reactions can be interrelated by a proposed mechanism involving a distant 2-OH nucleophile. (B) the conjunct nucleophile class leading to 3'-phosphates. This class is composed of self-cleaving RNAs found in plant viruses and the newt. We propose that tRNA splicing is related to this mechanism rather than the previous one. The presence of introns in tRNA genes of eukaryotes and archaebacteria supports the idea that tRNA splicing predates the divergence of these cell types.

Animals↗

PubMed2005

How important is lateral masking in visual search?

Five experiments are presented, providing empirical support of the hypothesis that the sensory phenomenon of lateral masking may explain many well-known visual search phenomena that are commonly assumed to be governed by cognitive attentional mechanisms. Experiment I showed that when the same visual arrays are used in visual search and in lateral masking experiments, the factors (1) number of distractors, (2) distractor density, and (3) search type (conjunction vs disjunction) have the same effect on search times as they have on lateral masking scores. Experiment II showed that when the number of distractors and eccentricity is kept constant in a search task, the effect of reducing density (which reduces the lateral masking potential of distractors on the target) is to strongly reduce the disjunction-conjunction difference. In experiment III, the lateral masking potential of distractors on a target was measured with arrays that typically yield asymmetric search times in visual search studies (a Q among Os vs. an O among Qs). The lateral masking scores showed the same asymmetry. Experiment IV was a visual search study with such asymmetric search arrays in which the number of distractors and eccentricity was kept constant, while manipulating density. Reducing density (i.e., reducing lateral masking) produced a strong reduction of the asymmetry effect. Finally in experiment V, we showed that the data from experiment IV cannot be explained due to a difference between a fine and a coarse grain attentional mechanism. Taken together with eye movement data and error scores from experiment II and with similar findings from the literature, these results suggest that the sensory mechanism of lateral masking could well be a very important (if not the main) factor causing many of the well-known effects that are traditionally attributed to higher level cognitive or attentional mechanisms in visual search.

Attention↗

PubMed1997

Binocular eye movements not coordinated during REM sleep.

Rapid eye movements (REMs) are a defining characteristic of REM sleep during which vivid dreams occur. It has been suggested that REMs may be binocularly coordinated and related to "watching" dream images. For the first time, binocular eye movements were recorded during natural REM sleep in monkeys to test the conjugate nature of the oculomotor system and the "scanning hypothesis" of REMs during sleep. During REM sleep, the lines of sight of the two eyes are frequently misaligned up to 30 degrees horizontally and/or vertically. Since the lines of sight usually don't intersect, there is no fixation point. Instead, each eye is aimed at a different part of the visual field during REM sleep. Furthermore, REMs are not usually conjugate, but are disjunctive or even monocular in horizontal or vertical directions. These data argue against the idea that REMs actually "track" dream images, unless each eye is watching its own dream! Binocular misalignment and disjunctive (even monocular) REMs during sleep suggest that separate left eye and right eye pathways generate saccades in each eye and control the position of each eye. Binocular coordination cannot be the passive result of anatomical connectivity as has been argued previously, but instead must result from a high-level process associated with the awake state that coordinates activity in left-eye and right-eye pathways. Hering's law of equal innervation is not consistent with these data.

Animals↗

PubMed1998

Meiotic pairing and segregation of translocation quadrivalents in yeast.

Meiotic pairing and segregation were studied in three different heterozygous reciprocal translocation strains of the baker's yeast, Saccharomyces cerevisiae. Pachytene translocation quadrivalents were identified by a combination of immunofluorescence and fluorescence in situ hybridization and the karyotypes of meiotic products were determined by pulsed-field gel electrophoresis. The translocations differed with respect to the relative sizes of the chromosomes involved and the positions of translocation breakpoints, and produced translocation quadrivalents of widely different shapes. This allowed us to study the influence of the morphology of quadrivalents on their segregation behaviour. In all cases alternate predominated over adjacent segregation. 3:1 disjunction of chromosomes was more frequent when translocation breakpoints were close to the centromeres. If a translocation breakpoint was distant from the centromere, the occurrence of an intervening chiasma influenced the pattern of segregation. In general, quadrivalent formation and segregation resembled the behaviour of translocation heterozygotes in most higher eukaryotes. We therefore conclude that, although chromosome condensation does not occur in yeast metaphase, centromere orientation and chromosome disjunction are governed in a way similar to that of higher eukaryotes.

Centromere↗

PubMed1999

Pentasomy X and hyper IgE syndrome: co-existence of two distinct genetic disorders.

We describe a 10-year-old girl with features of a penta-X syndrome. Cytogenetic analysis revealed a 49,XXXXX karyotype and molecular analysis of X-linked polymorphic markers showed that this aneuploidy arose by successive maternal non disjunctions. Apart from these features the patient has a lifelong history of eczema, recurrent pneumonia, and staphylococcal abscesses. Together with consistently increased serum IgE levels, low antibody responses, and low levels of serum IgA and IgG2, these findings are characteristic for the hyper IgE syndrome. While pentasomy X may be due to sequential non disjunctions in meiosis I and meiosis II in the mother, the underlying pathomechanism in hyper IgE syndrome remains unclear. This case is the first with co-existence of pentasomy X and hyper IgE syndromes.

Aneuploidy↗

PubMed1999

Prader-Willi syndrome in a child with XYY.

We report a 26-month-old boy with XYY syndrome, with the complication of Prader-Willi syndrome (PWS) due to uniparental maternal disomy of chromosome 15. To our knowledge, this is the first case of XYY syndrome and PWS. Clinical findings were fully compatible with the diagnostic criteria for PWS. Molecular analysis revealed a maternal heterodisomy of chromosome 15, indicating that non-disjunction of chromosome 15 had occurred at maternal meiosis I, and that the non-disjunction of chromosome Y and of chromosome 15 had occurred independently.

Child, Preschool↗

PubMed2006

Isolation and characterization of sex chromosome rearrangements generating male muscle dystrophy and female abnormal oogenesis in the silkworm, Bombyx mori.

In deletion-mapping of W-specific RAPD (W-RAPD) markers and putative female determinant gene (Fem), we used X-ray irradiation to break the translocation-carrying W chromosome (W( Ze )). We succeeded in obtaining a fragment of the W( Ze ) chromosome designated as Ze (W), having 3 of 12 W-RAPD markers (W-Bonsai, W-Yukemuri-S, W-Yukemuri-L). Inheritance of the Ze (W) fragment by males indicates that it does not include the Fem gene. On the basis of these results, we determined the relative positions of W-Yukemuri-S and W-Yukemuri-L, and we narrowed down the region where Fem gene is located. In addition to the Ze (W) fragment, the Z chromosome was also broken into a large fragment (Z(1)) having the +( sch ) (1-21.5) and a small fragment (Z(2)) having the +( od ) (1-49.6). Moreover, a new chromosomal fragment (Ze (W)Z(2)) was generated by a fusion event between the Ze (W) and the Z(2) fragments. We analyzed the genetic behavior of the Z(1) fragment and the Ze (W)Z(2) fragment during male (Z/Z(1) Ze (W)Z(2)) and female (Z(1) Ze (W)Z(2)/W) meiosis using phenotypic markers. It was observed that the Z(1) fragment and the Z or the W chromosomes separate without fail. On the other hand, non-disjunction between the Ze (W)Z(2) fragment and the Z chromosome and also between the Ze (W)Z(2) fragment and the W chromosome occurred. Furthermore, the females (2A: Z/Ze (W)Z(2)/W) and males (2A: Z/Z(1)) resulting from non-disjunction between the Ze (W)Z(2) fragment and the W chromosome had phenotypic defects: namely, females exhibited abnormal oogenesis and males were flapless due to abnormal indirect flight muscle structure. These results suggest that Z(2) region of the Z chromosome contains dose-sensitive gene(s), which are involved in oogenesis and indirect flight muscle development.

Animals↗

PubMedDate not supplied

Affective disorder: the new imperium.

Eugen Bleuler formulated schizophrenia as a disjunctive category based on universal, dimensional phenomena that were regarded as pathognomonic of the disorder. In consequence, schizophrenia came to dominate diagnostic practice in American psychiatry. This report suggests that affective disorder has been formulated in a similar way, and with a similar result. The nature of disjunctive categories is examined and their replacement by conjunctive categories for schizophrenia and affective disorder is anticipated.

Affective Disorders, Psychotic↗

PubMed1975

Trisomy and triploidy induced by X-irradiation of mouse spermatocytes.

Analysis of second meiotic metaphase divisions in control and irradiated male mice shows that while the spontaneous rates of autosomal and sex chromosomal anaphase I non-disjunction are extremely low, they can be enhanced by X ray treatment of prophase spermatocytes. Irradiation at pre-leptotene results in a higher rate of anaphase I non-disjunction than does irradiation at pachytene. Early spermatogonia are relatively insensitive. Experiments to detect trisomic progeny among the F1 foetal offspring of male mice mated during weeks 5 and 6 following irradiation (sampling of irradiated early spermatocytes and late spermatogonia) showed that none were present. Possible explanations for this are considered. Two triploid foetuses were however found.

Animals↗

PubMed1979

Cytology of aberrations induced by X-rays in oocytes of Drosophila melanogaster.

200 first-division configurations were analyzed for cytological aberrations induced by X-rays in late meiotic prophase in oocytes of Drosophila melanogaster. For the 3000 and 6000 r doses, 38 and 66%, respectively, were classified as abnormal. The aberrant divisions included displacement of the chromosomes suggesting their non-disjunction, loss of a whole chromosome, fragments and heterologous exchanges and unidentifiable aberrations. Non-disjunctional chromosomes were free of heterologous exchanges. The concept that a majority of X-ray-induced dominant lethals is due to chromosomal breakage is supported by the findings of the present study.

Animals↗

PubMed1981

Investigations on radiosensitive and radioresistant populations of Drosophila melanogaster. VIII. The system of relative radioresistance in immature oocytes of the irradiated population ROI4.

Prophase I oocytes of the irradiated population ROI4 of Drosophila melanogaster are radioresistant relative to those of a control population (+K). The system of relative radioresistance is apparently dose-modifying and can be described by Dose-Reduction Factors (DRFs). At least 3 constituent components of the system can be distinguished, as follows. The genetic factor rar-1 contributes to the system with respect to the induction of dominant (DRF = 1.31) and sex-linked recessive lethals (DRF = 1.31) in a way that is inhibited by caffeine. The factor rar-2, independently reduces both types of lethal to the same amount as does rar-1, but also affects the production of X-chromosome loss (DFR = 1.72). The results of several different approaches allow, as a working hypothesis, the interpretation that rar-2 reduces the association of heterologous, chiasmatic chromosomes in the chromocentre in time and/or space and thus minimizes the preconditions for the production of certain types of interchange and of non-disjunction. A third factor, rar-3, is postulated to contribute, independently from the others, to the system of relative radioresistance with respect to dominant lethals (DRF = 1.58), interchanges and non-disjunction (DRFs = 1.58), and sex-linked recessive lethals (DRF = 1.87).

Animals↗

PubMed1984

The synaptonemal complexes of Caenorhabditis elegans: pachytene karyotype analysis of the rad-4 radiation-sensitive mutant.

In the rad-4 mutant of C. elegans there is a specific increase in the number of 'Disjunction Regulator Regions' (DDR) present on the synaptonemal complexes (SC) in pachytene nuclei. These DRRs either promote disjunction or inhibit nondisjunction of the X-chromosome as evidenced by the 10-fold decrease in the rate of X-chromosome nondisjunction as compared to the wild-type. The structure of the tripartite SC is normal, thus, the decrease in the rate of X-chromosome nondisjunction in the rad-4 mutant is not related to the structure of the SC but may be related to the number of DRRs. Other changes are also associated with the sensitivity to irradiation, i.e. the pachytene nuclear morphology is altered such that nuclei and nucleoli are 50% the size of wild-type. In addition, the autosomal: X-chromosome size ratio is reduced in the rad-4 mutant. That there are six SCs confirms n = 6 in this mutant and of these six SCs three can be identified: (1) the XX bivalent, SC No. 1, is the shortest and pairs synchronously with the autosomes; (2) the longest bivalent, SC No. 6, carries the nucleolar organizer region at one extreme end; and (3) SC No. 5 has two DRRs located approximately one micron apart from each other.

Animals↗

PubMed1985

Mechanisms contributing to non-recovery of translocations induced in meiotic cells.

A cytological analysis of 22 and 7 autosomal (2;3) translocations induced, respectively, in mature and immature oocytes of Drosophila melanogaster appeared to be random in the distribution of the breaks. This finding is contrary to that expected if, as suggested by the mechanism of directed disjunction, the chromosomes involved in interchange at the centric region tended to be distributed to opposite poles at division I of meiosis. In each arm, the breaks were distributed more or less at random between the centromere and the telomere. However, in the translocations from the immature oocytes, the break-telomere distances of the segments interchanged showed a positive correlation, indicating that translocations induced in meiotic prophase and having a highly disproportionate length of segments interchanged are prone to be eliminated at division II by non-random disjunction of heteromorphic dyads.

Animals↗

PubMed1988

Aneuploidy detection with a short-term hexaploid wheat assay.

A new type of assay for the identification of agents causing aneuploidy is described. This assay takes advantage of allohexaploid wheat in which monosomic and nullisomic cell lineages can be genetically detected. The wheat strain used (Neatby's virescens) was homozygous for a pair of recessive alleles (v1) which in homozygous condition interfere with normal pigmentation of the leaves at low temperature whereas at higher temperature nearly normal green color formation is permitted. In a single dose this allele cannot suppress the formation of green color even at low temperature, i.e., it is hemizygous ineffective. This locus is in the short arm of chromosome 3B near the centromere. As a consequence of non-disjunction of this chromosome twin sectors may be detected, in which the monosomic cell lineages appear green whereas the trisomic sectors display with color on a cream-colored background at low temperature. This genetic system can also be used for the detection of deletions or duplications involving the short arm of chromosome 3B, and to some extent the A- and the D-genome homeologues. We have determined the pattern of differentiation of the shoot apex and on that basis we can separate the independent genetic events from reappearance of the sectors of common origin in the successive leaves. Such an understanding of development of the leaf sectors permits a quantitative estimation of the genetic response of the plants to mutagenic factors. We have found that X-rays, gamma-rays, p-fluorophenylalanine, 3-aminotriazole, caffeine, vinblastin sulfate, benzo[a]pyrene and auramine significantly increased aneuploidy, and diethylstilbestrol, sulfacetamide, safrole and dichlorvos caused some increase of sectoring. Cytological data on root tips of irradiated seeds support the interpretation of the mechanism of sector formation in the leaves. The test is simple, fast, inexpensive, and it does not require elaborate facilities or highly trained technicians. The trials were well reproducible during a period of 3 years in 2 laboratories. Therefore we consider the new assay a useful complement to other tests of chemicals or physical agents that may cause non-disjunction and other chromosomal aberrations in human populations.

Aneuploidy↗

PubMed1994

Genotoxic activity of mebendazole in Aspergillus nidulans.

Mebendazole is an anthelmintic drug widely used in Cuba and in Mexico. Its interaction with tubulin interferes with the assemblage of the mitotic apparatus in the parasite cells, thus suggesting a possible genotoxic activity leading to chromosomal malsegregation. The heterozygous diploid strain D30 of Aspergillus nidulans was used to establish the ability of mebendazole to induce mitotic recombination and/or chromosomal non-disjunction, and the haploid strain FGSC #219 of A. nidulans was used to study the ability of mebendazole to induce point mutations in the methG suppressor system. Our results show that mebendazole can induce chromosomal non-disjunction but it fails to promote point mutations.

Analysis of Variance↗

PubMed1994

Vergence compensation during binocularly- and monocularly-evoked horizontal optokinetic nystagmus in the pigmented rat.

During horizontal optokinetic nystagmus evoked by binocular stimulation in the rat, the slow phases are well-conjugate. The fast phases in the adducting eye are on average about 2 deg greater in amplitude than those of the abducting eye. This causes a transient convergence which is compensated for by a divergent drift within the 100 msec following the fast phase. The amplitudes of these convergence-divergence components fluctuates somewhat from one fast phase to another and their relative amplitudes may differ. As a consequence differences in vergence between successive slow phases may occur. Such differences are usually of small amplitude, but may be as large as 5 deg. When optokinetic nystagmus is evoked by monocular stimulation, the slow phase velocities are different in the two eyes, giving a disjunctive component which is compensated for by a difference in the relative amplitudes and velocities of the fast phases in the two eyes. However, the divergent drift immediately following the fast phases is very similar whatever form of stimulation is employed. It is suggested that during monocularly-evoked optokinetic nystagmus the oculomotor system compensates for the disjunctive component arising during the slow phases by giving a different balance to the pulses of innervation of two eyes, resulting in fast phases of different amplitude.

Animals↗

PubMed1991

Cerebral control for speech in right-handers and left-handers: an analysis of the views of Paul Broca, his contemporaries, and his successors.

According to several recent historical accounts, Broca (1865a) stated that left-handers are the mirror-reverse of right-handers for cerebral control of speech, with the right hemisphere being dominant in left-handers, and the left hemisphere dominant in right-handers. The same accounts then note Broca's error in light of current evidence that the majority of left-handers are left-dominant for speech just as are nearly all right-handers. Eling (1984) has called such statements misrepresentations of Broca's position and has argued that Broca's analysis actually was more compatible with the current view that there is a disjunction, meaning an absence of an intimate anatomical relationship, between cerebral control for handedness and speech. The current paper looks again at Broca's work, describes the context in which his views were first articulated, and traces the development of the mirror-reversal principle. The conclusion is reached that, judged by a narrow reading of the 1865 paper, Broca's views could indeed be construed as an anticipation of the modern disjunction principle. However, judged by a broader reading, by consideration of his other writing, and in the context of the philosophical and scientific tradition that shaped his work, it is suggested that it was the mirror-reversal principle to which Broca was actually disposed.

Cerebral Cortex↗

PubMed1986

Testing for the chemical induction of aneuploidy in the male mouse.

Dyad scores of metaphase II spermatocytes in the mouse have been used as an end point to assess the aneuploidy-inducing potential of three different chemicals; p-fluorophyalanine, phenylalanine and 6-mercaptopurine. The sensitivities of three different spermatogenic stages have been tested; pre-leptotene, zygotene and metaphase I. No effect was found at any treated stage for 6-mercaptopurine and phenylalanine. p-Fluorophenylalanine, when compared to control treatments, did, however, induce non-disjunction when applied at metaphase I. It also caused a delay to spermatogenesis when applied at this stage. The potential of mammalian test systems for the routine screening of chemicals as non-disjunction inducers, is discussed.

Aneuploidy↗