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PubMed1995

Segregation of mitochondrial DNAs carrying a pathogenic point mutation (tRNA(leu3243)) in cybrid cells.

To investigate the mechanism of segregation of mitochondrial DNAs (mtDNAs) carrying a pathogenic point mutation in the tRNA(leu(UUR)) gene (A to G at position 3243) cytoplasts, derived from a heteroplasmic myoblast clone, were fused to rhoo cells to create cybrid cells carrying different proportions of mutant and wild-type mtDNAs. Although the individual myoblasts used as fusion partners contained predominantly mutant mtDNAs (mean proportion 0.77, range 0.46-0.94), the majority (56%) of the cybrid clones isolated after growth in selective medium were homoplasmic wild-type, indicating preferential replication of wild-type mtDNAs. Long-term culture of heteroplasmic cybrid clones in non-selective medium produced no change in the mean proportion of wild-type mtDNAs but an increase in population variance, consistent with a purely stochastic segregation mechanism. These results are at variance with a previous report suggesting a replicative advantage for mtDNAs carrying the tRNA(leu3243) point mutation.

Adenine↗
PubMed2001

Immature granules are not major sites for segregation of constitutively secreted granule content proteins in NIT-1 insulinoma cells.

Immature secretory granules (ISG's) are sites of segregation of proteins destined for secretion by unregulated pathways from those stored in mature secretory granules in endocrine cells. To determine whether significant soluble protein sorting occurs in ISG's, the secretion of soluble versions of the pancreatic protein GP2 (GP2-GPI(-)) and placental alkaline phosphatase (SEAP) was analyzed in NIT-1 cells. By immunofluorescence microscopy, neither protein localized to SG's in transfected cells. Their secretion was secretagogue-independent in pulse-chase radiolabeling experiments even at early times of chase, while a small increase in the secretion of amylase, which is known to enter ISG's, could be detected. Finally, in sucrose gradient fractionation experiments, SEAP was present in light density fractions. We conclude that while some proteins, such as amylase, have a limited intrinsic capacity to enter ISG's, the segregation of proteins secreted via the constitutive pathway from SG content proteins occurs primarily in the trans Golgi network.

Alkaline Phosphatase↗
PubMed1996

Inhibition, contextual segregation, and subject strategies in list method directed forgetting.

This experiment tested alternative explanations of list method directed forgetting effects. Two word lists were studied by 135 subjects. Between lists, subjects were instructed to remember both lists (remember group), remember both lists as well as in which list words were studied (segregate group), or to forget the first list and remember the second (forget group). All subjects took both recall and recognition tests with test order varied between subjects. Among subjects who took the recall test first, the forget group showed a directed forgetting effect (poorer performance on List 1 than List 2) with both recall accuracy, recall typing time, and recognition reaction time measures. Contextual segregation of List 1 words by forget subjects was ruled out as a sufficient cause of the effect. Limited support was obtained for a differential rehearsal explanation of the effect. Within-group comparisons and findings of release from directed forgetting support inhibitory processes as the major cause of the directed forgetting effect.

Adult↗
PubMed1994

Beyond visible persistence: an alternative account of temporal integration and segregation in visual processing.

When processing sequences of rapidly varying stimuli, the visual system must satisfy two conflicting requirements. To maintain perceptual continuity, sequential stimuli must be integrated into a single, unified percept. On the other hand, to detect rapid changes, sequential stimuli must be segregated from each other. We propose that these conflicting demands are reconciled by a process that codes the temporal relationship between contiguous stimuli: Stimuli that are coded as co-extensive are integrated and those that are coded as disjoint are segregated. This approach represents a conceptual departure from the more traditional "intrinsic persistence" view of temporal integration. The approach provides a parsimonious account of the results of two temporal-integration tasks in which the durations of the leading and trailing displays were varied over a broad range. The data were accurately fit by a quantitative model in which temporal codes were determined by the correlation in time between the visual responses to the leading and trailing displays.

Adult↗
PubMed1995

A maternal RNA localized in the yellow crescent is segregated to the larval muscle cells during ascidian development.

A cDNA library prepared from one-cell zygotes of the ascidian Styela clava was screened with probes from isolated cellular fractions to identify clones encoding RNAs localized in the yellow crescent or myoplasm, a cytoskeletal domain with multiple developmental roles. The differential screen yielded five overlapping cDNA (Styela clava yellow crescent or ScYC) clones encoding a 1.2-kb polyadenylated RNA (yellow crescent or YC RNA) which is present throughout embryonic development. In situ hybridization confirmed that YC RNA is localized in the yellow crescent. Antisense probes containing the 3' region of YC RNA hybridize with multiple maternal and zygotic RNAs, suggesting sequence homologies with other transcripts. YC RNA was first detected during oogenesis when transcripts accumulate in the perinuclear region of vitellogenic oocytes and are gradually translocated to the cortex. The YC transcripts are localized in the cortex of unfertilized eggs but after fertilization segregate with the myoplasm to the yellow crescent. During cleavage most YC transcripts enter the primary muscle cell lineage. YC RNA is also present in the secondary muscle cells. The YC transcripts are retained in the myoplasm of oocytes and eggs extracted with the non-ionic detergent Triton X-100, suggesting that they are associated with the cytoskeleton. The nucleotide sequence of the longest ScYC clone contains a short open reading frame (ORF). The YC ORF would encode a putative polypeptide of 49 amino acids, which shows no significant homology to known proteins. Several features of the YC RNA, however, suggest that it functions as an RNA rather than as a protein coding molecule. We conclude that the myoplasm contains a novel maternal RNA which is associated with the cytoskeleton and segregated to the muscle cells during ascidian embryogenesis. The YC RNA may be a new member of a growing family of noncoding RNAs that play important roles in growth and development.

Amino Acid Sequence↗
PubMed2000

In situ and in vitro study of colocalization and segregation of alpha-synuclein, ubiquitin, and lipids in Lewy bodies.

alpha-Synuclein and ubiquitin are two Lewy body protein components that may play antagonistic roles in the pathogenesis of Lewy bodies. We examined the relationship between alpha-synuclein, ubiquitin, and lipids in Lewy bodies of fixed brain sections or isolated from cortical tissues of dementia with Lewy bodies. Lewy bodies exhibited a range of labeling patterns for alpha-synuclein and ubiquitin, from a homogeneous pattern in which alpha-synuclein and ubiquitin were evenly distributed and overlapped across the inclusion body to a concentric pattern in which alpha-synuclein and ubiquitin were partially segregated, with alpha-synuclein labeling concentrated in the peripheral domain and ubiquitin in the central domain of the Lewy body. Lipids represented a significant component in both homogeneous and concentric Lewy bodies. These results suggest that Lewy bodies are heterogeneous in their subregional composition. The segregation of alpha-synuclein to Lewy body peripheral domain is consistent with the hypothesis that alpha-synuclein is continually deposited onto Lewy bodies.

Aged↗
PubMed1995

Two-dimensional DNA typing of human pedigrees: spot pattern characterization and segregation.

By two-dimensional (2-D) genome typing, i.e., electrophoretic separation of restriction enzyme-digested genomic DNA on the basis of both size and sequence in denaturing gradient gels followed by hybridization analysis, several hundred alleles (spots) can be analyzed in parallel, using a micro- or minisatellite core probe. We studied the segregation of 213 and 214 spots detected by microsatellite core probe (CAC)n and minisatellite core probe 33.6, respectively, in two three-generation human pedigrees. Reproducibility of the spot patterns was such that particular spot variants could be scored in both pedigrees. Between 73 and 74% of the spots scored were variant and were transmitted in a Mendelian manner. Very little cosegregation among the 2-D spots themselves was observed, suggesting a random distribution over the genome. Several pairs of spots that appeared to contain both alleles from single loci were identified. The few spots detected by both probes (overlapping spots) showed different segregation patterns, indicating that each probe detects independent sets of genetically informative loci. These results provide a firm basis for using 2-D DNA typing to identify disease loci and for constructing a 2-D spot genetic linkage map of the human genome.

Alleles↗
PubMed2001

Object recognition and object segregation in infancy: historical perspective, theoretical significance, "kinds" of knowledge, and relation to object categorization.

Needham (2001, this issue) reports that 4.5-month-old infants can use a short-term familiarization experience with a single object to facilitate the segregation of a visual display consisting of a configurally similar object and a configurally dissimilar adjacent object. We reflect on this finding in the larger context of Needham's systematic research on the development of object perception, a program that has included (1) a series of empirical studies designed to identify the different cues that infants use for object segregation and (2) a theoretical framework in which infants are presumed to integrate these cues to form interpretations of complex visual displays.

Child Development↗
PubMed2001

Infant object segregation implies information integration.

Researchers, including Needham (2001, this issue), have found that infants as young as 4.5 months of age have the ability to use featural information to segregate objects. However, considerable research on infants' perception of color, shape, size, orientation, and so on has shown that infants younger than 4.5 months are capable of using these featural cues to discriminate between objects or other test items. Infants as young as 2 months of age also can perceive a moving object as unified. In this article, we argue for an information processing explanation of these results, which centers on the development of infants' ability to integrate both featural and object information. The proposed explanation is based upon L. B. Cohen's (1991, 1998) information processing propositions and is consistent with the evidence on object segregation as well as evidence from our laboratory and others' on infant perception and cognition.

Child Development↗
PubMed1995

Cellular segregation and engulfment simulations using the cell programming language.

In developmental biology, modeling and simulation play an important role in understanding cellular interactions. In this paper a simple language, the Cell Programming Language (CPL), is suggested for writing programs that describe this behavior. Using these programs, it is possible to simulate and visualize intercellular behavior. CPL is used to model cellular segregation based upon the differential adhesion hypothesis. Results indicate that a high degree of segregation can be produced in a mixture of cells by allowing random motion. The engulfment of a tissue by a less adhesive tissue is also observed when the two tissues are placed in contact. Both these simulations utilize only local interactions and random motion of cells. Earlier simulations used long-range interactions to observe similar effects. The present simulations prove that random motion of cells can produce long-range effects.

Animals↗
PubMed1997

Segregation of rhombomeres by differential chemoaffinity.

The developing hindbrain is transiently subdivided into structural repeat units, rhombomeres, whose formation is matched by both differential regulatory gene expression and a metameric pattern of early neuronal differentiation and axogenesis. Individual rhombomeres are polyclonal cell lineage restriction units; once defined by transverse interrhombomere interfaces, cells are confined within the territory of a single rhombomere. In order to assess the relevance of this restriction to hindbrain development. It is necessary to understand the underlying mechanism. One possibility is that cells of adjacent rhombomeres acquire differential affinities or adhesive properties. To explore this possibility, we isolated rhombomere cells, mixed them together in short-term aggregation cultures, and assessed the composition of the resulting aggregates. We found that rhombomeres do differ in their affinity: cells from even-numbered rhombomeres sort out from cells of odd-numbered rhombomeres. They also segregate from cells of other even-numbered rhombomeres but to a much lesser extent. This selective cell affinity operates from the time of rhombomere formation until late stages in development. The region-specific segregation was abolished when Ca(2+)-dependent adhesion molecules were inactivated but not when Ca(2+)-independent adhesion molecules were inactivated. These findings suggest that distinct cell affinity restricts cell mixing between adjacent rhombomeres and may be involved in establishing the series of discrete compartments, thereby maintaining anteroposterior positional information during hindbrain development. These results support a general role for cell adhesion molecules in subdividing CNS territories.

Animals↗
PubMed2001

Selection and segregation distortion in a sex-differentiated population.

We extend the classical model for selection at an autosomal locus in a sex-differentiated population to include segregation distortion. The equations remain the same, but the fitness parameters are interpreted differently and refer to alleles instead of genotypes. We derive conditions for internal and external stability of the equilibria, i.e., stability with respect to perturbations of alleles that are already present at equilibrium and stability with respect to invasion attempts by newly arising alleles. We show that, in a sex-differentiated population, external stability of an equilibrium can be judged on the basis of Shaw--Mohler criteria. Throughout, we compare the situation in populations with and without sex differentiation. Interestingly, internal stability is more difficult to achieve in a population without sex differentiation than in a population in which selection and segregation distortion are restricted to one sex. In a companion paper we show how the general results of the present paper can lead to new insights into specific systems such as the t complex of the house mouse.

Alleles↗
PubMed1995

Onset of chromosome segregation at the metaphase to anaphase transition of the cell cycle.

Chromosome segregation is one of the most important acts in the life of the cell. Unequal inheritance of chromosomes (aneuploidy) is a cause of a number of disorders, particularly in humans, even though eukaryotic cells can arrest or delay the transition from metaphase to anaphase if an event critical to the completion of metaphase is impaired. In this report, we review recent advances in our knowledge of how the complex process of chromosome segregation is coupled with cell cycle progression, and starts at onset of anaphase with sister chromatids separation of the replicated chromosomes.

Anaphase↗
PubMed1992

Partner choice in heterologous chromosome segregation of the Y chromosome in competitive situations in the oocyte of Drosophila melanogaster.

Heterologous segregation of the Y chromosome and secondary non-disjunction of the X chromosomes in female meiosis of Drosophila melanogaster was investigated in ten different crosses where different constellations of translocation/inversion or translocation/translocation systems of the large autosomes were present in the female parent. It appeared that the Y chromosome always segregates from the shortest of the possible heterologous pairing partners. This may be due to size-dependent mechanism of so-called 'distributive disjunction' or to the possibility that the shorter the chromosome element is, the more easily it moves in the nucleus of the oocyte. Secondary non-disjunction of the X chromosomes appeared to be lower the more possible autosomal pairing partners the Y chromosome had, suggesting that the autosomes effectively compete with the X chromosomes for pairing with the Y chromosome. An alternative explanation is that, due to interchromosomal effect on recombination, crossing over in the X chromosomes was different in different experiments.

Animals↗
PubMed1994

Projections of the olfactory bulb in an elasmobranch fish, Sphyrna tiburo: segregation of inputs in the telencephalon.

We have previously shown that the morphological compartmentalization of the elasmobranch olfactory bulb is accompanied by a topographical arrangement of the primary olfactory projections onto the bulb. If this spatial arrangement is significant for the processing of the information, one would expect it to be preserved in the secondary olfactory centers of the telencephalon. In this paper, we describe the elasmobranch secondary projections from the olfactory bulb to the telencephalon, focusing on their spatial arrangements within the forebrain. Results show that the olfactory input onto the telencephalon are segregated. The medial olfactory tract projects rostrally onto the superficial layer of the dorsal pallium and onto the lateral pallium. The lateral olfactory tract projects caudally onto the lateral pallium, the striatum and the area superficialis basalis. Thus, the secondary olfactory projections are segregated within the telencephalon, with an overlapping of the secondary fibers in the main projection area, the lateral pallium.

Animals↗
PubMed1993

A genetic analysis of human minor histocompatibility antigens demonstrates Mendelian segregation independent of HLA.

An analysis of the genetic traits of human minor histocompatibility (mH) antigens is, unlike with inbred mice, rather complicated. Moreover, the fact that mH antigens are recognized in the context of MHC molecules creates an additional complication for reliable segregation analysis. To gain insight into the mode of inheritance of the mH antigens, we relied upon a series of HLA-A2-restricted cytotoxic T-cell (CTL) clones specific for four mH antigens. To perform segregation analysis independent of HLA-A2, we transfected HLA-A2-negative cells with the HLA-A2 gene: this results in the cell surface expression of the HLA-A2 gene product and, if present, mH antigen recognition. The mode of inheritance of the HLA-A2-restricted mH antigens HA-1, -2, -4, and -5 was analyzed in 25 families whose members either naturally expressed HLA-A2 or were experimentally rendered HLA-A2-positive. Analysis of distribution of the mH antigens in the parent population among the mating types, together with their inheritance patterns in the families, demonstrated that the four mH antigens behaved as Mendelian traits, whereby each can be considered a product of a gene with two alleles, one expressing and one not expressing the detected specificity. We also showed that the loci encoding the HA-1 and HA-2 antigens are not closely linked to HLA (lod scores Z (0 = 0.05) <-4.0). Some indication was obtained that the HA-4- and HA-5-encoding loci may be closely linked to HLA. While we are aware of the limited results of this nonetheless comprehensive study, we feel the similarity in immunogenetic traits between human and mouse mH antigens is at least striking.

Alleles↗
PubMed1990

Amplification of the COL2A1 3' variable region used for segregation analysis in a family with the Stickler syndrome.

Amplification of a variable region 3' to the human type II collagen gene (COL2A1) has permitted segregation analysis in a three generation Stickler syndrome pedigree. This family had previously proved uninformative for the known restriction fragment length dimorphisms. Amplification of the variable region revealed five distinguishable alleles, of which three were segregating in this family. The lod score in favour of linkage was 2.86 at zero recombination.

Abnormalities, Multiple↗
PubMed1992

The segregation of a translocation t(1;4) in two male carriers heterozygous for the translocation.

We examined the meiotic segregation pattern of a t(1;4)(p36.2;q31.3) reciprocal translocation in two male cousins heterozygous for the translocation. The wife of subject 1 had four recognized spontaneous abortions and two carrier daughters, and the wife of subject 2 had three recognized spontaneous abortions and no live-born children. The results showed that subject 1 had an imbalance rate of 54% and subject 2 had an imbalance rate of 61% with respect to the translocation. This was not statistically different (P = 0.3174) and the 95% confidence intervals overlapped for each segregation type. The sex ratio of X- and Y-bearing sperm was not statistically different than the expected 50%. The rate of structural abnormalities was 11.3% in subject 1 and 17.8% in subject 2. Both of these values were above the range of control subjects in our lab, but only subject 2's value fell outside the 95% confidence interval for the control population.

Abortion, Habitual↗