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Negative segregation of Mtv loci in H-2E+ mice selected for high antibody response.

Endogenous mouse mammary tumor proviruses (Mtvs) encode superantigens (Sags), which can delete T lymphocytes expressing particular Tcrb-V genes when associated with the H-2E molecule. In the present work, distribution of Mtvs was investigated in six independent pairs of mouse lines genetically selected for high (H) or low (L) Ab production to specific T-cell-dependent Ags. These experiments were performed to evaluate the role of Mtv-encoded Sags in the determination of H and L phenotypes. No systematic difference is observed in Mtv segregation between H-2E- H and L mouse lines. However, a clear differential segregation of Mtv loci is observed between H-2E+ H and L mice from three independent selections. The number of endogenous Mtvs in L lines is close to that found in laboratory mice. In contrast, Mtv loci-encoding Sags are almost absent in H animals. Although Sags profoundly affect the available Tcrb-V repertoire in H-2E+ L mice, it seems unlikely that Mtvs account for the L phenotype which can be achieved independently of Mtv segregation in H-2E- lines. More importantly, the results suggest that negative segregation of Mtv-encoding Sags contribute to determine the super-responder phenotype of H lines.

Animals↗

Nucleolar segregation as an early marker for DNA damage; an experimental study in rats treated with 4-hydroxyaminoquinoline 1-oxide.

Male 6-week-old Sprague Dawley rats were given a single intravenous injection of 4-hydroxyaminoquinoline 1-oxide (4HAQO) at a dose of 20 mg/kg in order to produce ultrastructural changes as possible morphological biomarkers for toxicity. Immunohistochemically demonstrated formation of 4HAQO-DNA adduct was correlated with the changes found. Nucleolar alteration, demonstrable by electron microscopy as segregation of nucleolar components into granular and fibrillar compartments, was evident in cells of the target organs, exocrine pancreas and adrenocortex, but not of the non-target liver parenchyma. Sequential observation clarified that such alteration was highest in frequency 6 h and 4 h after 4HAQO administration in pancreatic acinar cells and adrenocortical cells respectively. Electron microscopically, apoptotic changes of acinar cells were evident 2 h after injection of 4HAQO. DNA adduct formation was consistently demonstrated in the same target organs showing nucleolar segregation, the highest frequency being noted 4 h after 4HAQO treatment in both pancreatic acinar cells and adrenocortical cells. Our results thus indicate an identity of the target cells for nucleolar segregation and 4HAQO-DNA adduct formation which correlates with 4HAQO-toxicity. We suggest that nucleolar segregation occurs subsequent to the generation of DNA damage.

4-Hydroxyaminoquinoline-1-oxide↗

Putative non-Mendelian transmission of retinoblastoma in males: a phenotypic segregation analysis of 150 pedigrees.

In a previous genotypic study of eight families, we described paternal segregation distortion favoring the transmission of mutant alleles at the retinoblastoma gene locus (RB1). In the current study, we reviewed all published retinoblastoma pedigrees with defined ascertainment (n = 150), to determine whether the phenotypic segregation frequency at the RB1 locus is in general influenced by the sex of the transmitting parent. Segregation analysis under complete ascertainment revealed that 49.1% of the offspring of male transmitters were affected, while 44.3% of the offspring of female transmitters were affected. While this difference is not statistically significant, it is consistent with the previous findings. No significant sex distortion could be detected among the progeny of carrier fathers and mothers. In order to quantify the transmission ratio more precisely further prospective molecular genetic analysis is warranted. We propose a biological mechanism to account for a putative segregation distortion, namely that genetic recombination creates clones of spermatogonia that are homozygous for the mutant RB1 allele leading to a non-Mendelian ratio of sperm. This model can be experimentally tested using amplification of DNA from single sperm cells.

Female↗

Segregation analysis in hereditary retinoblastoma.

Segregation analysis was performed in 211 nuclear families belonging to 166 pedigrees of hereditary retinoblastoma found in a number of series which have been gathered from the literature. Bilaterally affected carriers appear homogeneous. The segregation ratio in their offspring is 0.49 and the proportion of bilateral cases among affected offspring is 0.87. Both unilaterally affected and unaffected carriers appear heterogeneous. The very low segregation ratio (0.08) in the offspring of unilateral carriers who are not detected through an affected child, suggests the possibility of two types of carriers. "high" and "low transmitters." The proportions of "low transmitters" was estimated as 0.14 among all familial unilateral carriers and as 0.45 among all detected unaffected carriers. Unilateral and unaffected "high transmitters" give a significantly lower segregation ratio than bilaterally affected carriers. On the one hand, the existence of these two different types of carriers provides arguments in support of the hypothesis of delayed mutation. On the other hand, the differences in penetrance among "high transmitters." according to their phenotype, supports the hypothesis of host resistance. Under the two-mutation hypothesis, the possibility that the mutation rate is variable among individuals and partly genetically determined, is suggested.

Genes, Dominant↗

Meiosis in Mesostoma ehrenbergii ehrenbergii (Turbellaria, Rhabdocoela). III. Univalent chromosome segregation during the first meiotic division in spermatocytes.

At metaphase I of meiosis in spermatocytes of Mesostoma ehrenbergii ehrenbergii [2n = 10] three bivalents and four univalents form. The same two chromosome pairs always form the univalents. Analysis of metaphase I, anaphase I and metaphase II configurations in fixed testis material suggested that the distribution of the four univalents is not a random process but the correct segregation of one member of each pair to each pole is actively achieved before the end of metaphase I. In live preparations of testis material univalents were observed to move between the poles of metaphase I cells, eventually reaching the correct segregation. All cells observed to enter anaphase I had the correct segregation of univalents. It is proposed that the univalent movement during metaphase I is directed towards obtaining the correct segregation of univalents before the cells enter anaphase.

Animals↗

Regeneration of a chimeric retina from single cells in vitro: cell-lineage-dependent formation of radial cell columns by segregated chick and quail cells.

We report here that similar to E6-chicken retinal cells, dissociated cells from 5.5-day-old (E5.5) quail retinae reaggregate in rotary culture, multiply about tenfold and reestablish histotypical areas. These cellular aggregates include all nuclear layers either with inversed or correct laminar polarity, depending on the local origin of the cells (called "rosetted" and "laminar" in-vitro-retinae (IVR), respectively; Layer and Willbold 1989). In combined cultures, chick and quail cells are evenly mixed only during the first two days of culture. Along with the assembly of single cells into rosettes and then into discrete laminae, sectors of chick and quail cells begin to segregate. They are delineated by borders running radially through all three nuclear layers. Thus, interspecies migration of cells at this advanced stage of differentiation is strongly inhibited. Concomitant with this segregation, coherent radial columns spanning all three layers but containing cells from either species only, can be traced histologically. We conclude that a weak segregation of chick and quail retinal cells takes place already at the single cell level, but that the permanent segregation of entire tissue parts must be due to clonal cellular proliferation within the IVR in conjunction with some developmental-structure mechanism retaining clonal progenies within a columnar order.

Animals↗

Meiotic segregation of five different reciprocal translocations in the onion fly, Hylemya antiqua (Meigen).

For one translocation (T14) with short interstitial segments in Hylemya antiqua significant differences in segregation behaviour between males and females were observed. In males the ratio of alternate:adjacent 1:adjacent 2 was approximately 7:3:0 and in females about 8:1:3. This difference is attributed to the difference in type of chromosome association. Female meiosis is chiasmate and male meiosis is achiasmate. It is suggested that meiotic pairing in males results in relative short "Coorientation Determining Distances" (CDDs) between homologous centromeres which favours alternate and adjacent 1 segregation. In females because of non-localized chiasmata on the average no differences in CDD between homologous and nonhomologous centromeres are expected. This might explain the occurrence of coorientation between non-homologous centromeres resulting in adjacent 2 segregations. Four other translocations with longer interstitial segments than T14 showed in males as well as females predominantly an alternate and adjacent 1 segregation, adjacent 2 was hardly found (0-3.6%). The longer distance between non-homologous centromeres is probably the reason.

Animals↗

Induced segregation in interspecific hybrids of Aspergillus nidulans and Aspergillus rugulosus obtained by protoplast fusion.

Interspecific hybrids produced by polyethylene glycol induced fusion of protoplasts from auxotrophic mutants of Aspergillus nidulans and Aspergillus rugulosus were grown in the presence of the recombinogens benomyl and chloral hydrate to stimulate segregation. The A. nidulans parental strains used had a known genetic marker in each linkage group. Hybrids grown on complete medium containing benomyl yielded more segregants. Analysis of the segregants showed that the distribution of A. nidulans linkage groups was random. No specific linkage group appeared in all the segregants. The two parents are closely related taxonomically and the findings from these experiments suggest that a high degree of chromosomal homology may exist between them.

Aspergillus↗

Meiotic analysis by FISH of a human male 46,XY,t(15;20)(q11.2;q11.2) translocation heterozygote: quadrivalent configuration, orientation and first meiotic segregation.

Understanding the segregational behaviour of reciprocal translocations in man is of both theoretical and clinical importance. Generally, information for genetic counselling is obtained from empirical data although knowledge of gametic output can now be obtained by karyotyping individual human spermatozoa. However, neither empirical studies nor sperm karyotyping data provide detailed information on how the combinations of normal, balanced and unbalanced gametes arise. For this knowledge of quadrivalent orientation and first meiotic segregation is required. We have used dual colour fluorescence in situ hybridisation (FISH) to identify normal and derived chromosomes during meiosis in testicular biopsy material from a 46,XY,t(15;20)(q11.2;q11.2) heterozygote. We were able to determine the frequencies of different quadrivalent structures at first metaphase (MI) and the proportion of first meiotic divisions subject to interstitial chiasmata. Having identified all 2:2, 3:1 and 4:0 segregation products at second metaphase, it was possible to correlate segregation categories with the various forms of MI quadrivalent possibly indicating their modes of orientation. Finally the ratios of normal:balanced:unbalanced gametes expected to be produced by this translocation heterozygote were calculated.

Adult↗

Differential mechanisms governing segregation of a univalent in oocytes and spermatocytes of Drosophila melanogaster.

In tricomplex heterozygotes in Drosophila melanogaster three metacentric autosomes (the TRI chromosomes) appear as a trivalent in meiosis while one autosome consisting of two homologous arms attached to the same centromere (a compound) behaves as an obligatory univalent. Cytological analysis of meiosis of tri-complex heterozygotes indicates that in oocytes the univalent compound behaves non-independently in relation to segregation of the trivalent. The compound is distributed preferentially to the same pole as one TRI chromosome. In spermatocytes the compound is distributed at random. In some oocytes the directed segregation is shown to be due to a disjunctional interaction between the compound and one partner of the trivalent at the same time as the other two chromosomes of the trivalent are separating from each other. The basic difference between the segregational mechanisms in the two sexes is discussed with a review of evidence indicating that in males segregation is determined by physical linkage that produces a stable orientation of the homologues at metaphase I. On the other hand, both genetic and cytological evidence indicate that in females a physical linkage (a chiasma) is non-essential for maintenance of co-orientation and stability after the onset of prometaphase. Genetic and cytological evidence support the hypothesis that disjunction is predetermined by non-random arrangement of the centromeric regions of chromosomes in the chromocentre - a suprachromosomal organization characteristic of maturing oocytes.

Animals↗

Segregation distortion within the equine MHC; analogy to a mouse T/t-complex trait.

Segregation distortion was found for a haplotype of the equine lymphocyte antigen (ELA) system in an extended family of American Standardbred horses. In one sire family, consisting of a stallion and his 17 sons and grandsons, the gene for ELA-A10 (A10) was transmitted to 57.7% of 638 offspring scored (P = 0.001). Significant segregation distortion was not seen for mares or for unrelated stallions, regardless of the ELA markers they possessed. Since the effect was seen for this one sire family and not seen for other stallions with A10, it is unlikely that the gene for A10 is the cause of this phenomenon, but rather A10 is linked to another major histocompatibility complex (MHC) gene causing this trait. This trait appeared analogous to the segregation distortion observed for the T/t complex of the mouse. Since segregation distortion involving MHC genes has been seen in other species, genes for this trait may be a general feature of the MHC.

Animals↗

The distribution of male meiotic pairing sites on chromosome 2 of Drosophila melanogaster: meiotic pairing and segregation of 2-Y transpositions.

The distribution of meiotic pairing sites on a Drosophila melanogaster autosome was studied by characterizing patterns of prophase pairing and anaphase segregation in males heterozygous for a number of 2-Y transpositions, collectively covering all of chromosome arm 2R and one-fourth of chromosome arm 2L. It was found that all transpositions involving euchromatin from chromosome 2, even short stretches, increased the frequency of prophase I quadrivalents involving the sex and second chromosome bivalents above background levels. Quadrivalent frequencies were the same whether the males carried both elements of the transposition or just the Dp(2:Y) element along with two normal chromosome 2s, indicating that pairing is non-competitive. The frequency of quadrivalents was proportional to the size of the transposed region, suggesting that pairing sites are widely distributed on chromosome 2. Moreover, all but the smallest transpositions caused a detectable bias in the segregation ratio, in favor of alternate segregations, indicating that the prophase associations were effective in orienting centromeres to opposite poles. One transposition involving only heterochromatin of chromosome 2 had no effect on quadrivalent frequency, consistent with previous evidence that autosomal heterochromatin lacks meiotic pairing ability in males. One region at the base of chromosome arm 2L proved to be especially effective in stimulating quadrivalent formation and anaphase segregation, indicating the presence of a strong pairing site in this region. It is concluded that autosomal pairing in D. melanogaster males is based on general homology, despite the lack of homologous recombination.

Animals↗

Segregation of the isozymes of flax genotrophs.

The segregation of isozymes of peroxidase and acid phosphatase in progenies of crosses between large (L) and small (S and L6) flax genotrophs has been determined. The peroxidase isozymes segregated as expected on a simple Mendelian model with a dominant and a recessive allele and with the L genotroph being a homozygous dominant. All the peroxidase isozymes which differed segregated together, so the isozymes are controlled by either a single locus or closely linked loci. The acid phosphatase isozymes in the F1 were all L type, but the segregations observed in the F2 were not always consistent with a simple Mendelian model.

Acid Phosphatase↗

Segregation distortions for the ABO system in pairs of sibs.

The influence of maternal phenotype was observed in 471 consecutive sib pairs to explore the segregation distortions for the ABO system. The ABO typing was done using the standard technique of haemagglutination reaction and the sib pairs were named according to their phenotypes. Thus A-B is the pair where first sib was A and the consecutive one was B. The statistical computations involved calculations of ABO gene frequencies, and application of chi-square and Z test for proportions to study the segregation distortions in sibs. A significant excess of B gene in the first sib and reduction of O in the second sib was observed when the Z test was applied to study the covariance, whereas no significant distortions were observed with simple Chi-square test. Heterozygote AO mothers segregated insignificantly in favour of A allele whereas BO mothers segregated significantly in favour of B allele in the first as well as in the second sib indicating that selection is favouring the B gene in our population.

ABO Blood-Group System↗

Introgression into the allotetraploid coffee ( Coffea arabica L.): segregation and recombination of the C. canephora genome in the tetraploid interspecific hybrid ( C. arabicax C. canephora).

Transfer of desired characters from the diploid relative species such as Coffea canephora into the cultivated allotetraploid coffee species ( Coffea arabica L.) is essential to the continued improvement of varieties. Behaviour of the C. canephora genome and its interaction with the C. arabica genome were investigated in tetraploid interspecific hybrids ( C. arabicax C. canephora 4 x) resulting from a cross between an accession of C. arabica and a tetraploid plant of C. canephora obtained following colchicine treatment. Segregation and co-segregation of restriction fragment length polymorphism (RFLP) and microsatellite loci-markers were studied in two BC(1) populations. These two populations of 28 and 45 individuals, respectively, resulted from the backcross of two tetraploid F(1)plants to C. arabica. The presence in BC(1) plants of specific C. canephora markers was scored for 24 loci (11 RFLP and 13 microsatellites) distributed on at least 7 of the 11 linkage groups identified in C. canephora. At almost all loci analysed, the segregation of C. canephora alleles transmitted by the ( C. arabicax C. canephora 4 x) hybrids conformed to the expected ratio assuming random chromosome segregation and the absence of selection. The recombination fractions of C. canephorachromosome segments were estimated for seven marker intervals, and compared with the recombination fractions previously observed in C. canephora for the equivalent marker intervals. The recombination frequencies estimated in both plant materials were rather similar, suggesting that recombination in the ( C. arabicax C. canephora 4 x) hybrid is not significantly restricted by the genetic differentiation between chromosomes belonging to the different genomes. The hybrid ( C. arabicax C. canephora 4 x) therefore appeared particularly favourable to intergenomic recombination events and gene introgressions.

Journal Article↗

Specific properties of fine SnO2 powders connected with surface segregation.

The effect of surface segregation in Sb- and In-doped SnO2 fine-grained powders has been analyzed in comparison with single-crystalline samples. The kinetics and thermodynamics of the Sb and In segregation processes were studied as a function of annealing temperature by X-ray photoelectron spectroscopy (XPS) after annealing in an oxygen-containing atmosphere. Significant differences between diffusion and segregation were revealed for doped powders and single crystals, obviously because of simultaneous diffusion and particle-growth processes proceeding during annealing of powders. For doped single crystals the thermodynamic equilibrium is approached after 24 h annealing above 850 degrees C and at 1000 degrees C for Sb and In, respectively. Higher effective activation energies of diffusion are observed for doped powders and the thermodynamic equilibrium is not achieved under technologically relevant annealing conditions. On the basis of dopant profile measurements anomalies in the electrical resistivity at 300 degrees C of Sb-doped SnO2 powders annealed at 700 and 900 degrees C were attributed to an Sb-depleted zone formed beneath the segregated surface during the kinetic regime. To achieve optimum resistivity behavior for commercial application, inhomogeneous doping of powders must be avoided by appropriate preparation steps.

Journal Article↗

Stochastic correlative firing for figure-ground segregation.

Segregation of sensory inputs into separate objects is a central aspect of perception and arises in all sensory modalities. The figure-ground segregation problem requires identifying an object of interest in a complex scene, in many cases given binaural auditory or binocular visual observations. The computations required for visual and auditory figure-ground segregation share many common features and can be cast within a unified framework. Sensory perception can be viewed as a problem of optimizing information transmission. Here we suggest a stochastic correlative firing mechanism and an associative learning rule for figure-ground segregation in several classic sensory perception tasks, including the cocktail party problem in binaural hearing, binocular fusion of stereo images, and Gestalt grouping in motion perception.

Acoustic Stimulation↗

Using a kinetic model that considers cell segregation to optimize hEGF expression in fed-batch cultures of recombinant Escherichia coli.

Growth inhibition of recombinant Escherichia coli during the expression of human epidermal growth factor was observed. The recombinant cells could be segregated into three populations based on their cell division and plasmid maintenance abilities: dividing and plasmid-bearing cells, dividing and plasmid-free cells, and viable-but-non-culturable (VBNC) cells. Fed-batch fermentations were performed to investigate the effect of cell segregation on the kinetics of growth and foreign protein production. The results showed that a low concentration of inducer caused weak induction, whereas high levels cause strong induction, resulting in cells segregating into VBNC bacteria and producing a low foreign protein yield. A kinetic model for cell segregation was proposed and its predictions correlated well with experimental data for cell growth and protein expression. The optimal induction strategy could then be predicted by the model, and this prediction was then verified by experimentally deriving the conditions necessary for maximum expression of recombinant protein.

Epidermal Growth Factor↗