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Rheumatic fever susceptibility in four ascertainments: regressive segregation on a geometric ascertainment pattern.

On resolving the ascertainment biases of the observed data in the geometric continuum vaffected-1 x P(sibship), where 0 less than v----infinity, four published ascertainments of rheumatic fever show excellent conformation with Mendelian recessive segregation, even in multiplex sibships. In two surveys in which ascertainment bias is near or a little above random sampling (v = 1), this conclusion is further corroborated by classical segregation analysis. The other two surveys have bias trends declining (v less than 1) very much below random sampling. Such levels of ascertainment bias, if defined through the ascertainment probability parameter pi, would be out of range because the range is from single ascertainment, where pi----0 to random sampling where pi = 1 and probability cannot exceed unity. Highly successful antimicrobial measures that would reduce the number of diseased sibs independent of the distribution of susceptible sibs could produce a dissociation of the gene-to-"rheumatic" relationship and thus explains the declining ascertainment bias.

Adult↗

The number of segregating sites in expanding human populations, with implications for estimates of demographic parameters.

The frequency distribution of pairwise differences between sequences of mtDNA has recently been used to estimate the size of human populations before and after a hypothetical episode of rapid population growth and the time at which the population grew. To test the internal consistency of this method, we used three different sets of human mtDNA data and the corresponding demographic parameters estimated from the distribution of pairwise differences to determine by simulation the expected number of segregating sites, S, and its empirical distribution. The results indicate that the observed values of S are significantly lower than expected in two of three cases under the assumption of the infinite-sites model. Further simulations in which mutations were allowed to occur more than once at the same site and in which there was variation in mutation rate among sites show that the expected number of segregating sites can be much lower than under the infinite-site assumption. Nevertheless, the observed value of S is still significantly different from the value expected under the expansion hypothesis in two of three cases.

Animals↗

Bayesian segregation analysis of production traits in two strains of laying chickens.

A bayesian marker-free segregation analysis was applied to search for evidence of segregating genes affecting production traits in two strains of laying hens under long-term selection. The study used data from 6 generations of Leghorn (H77) and New Hampshire (N88) breeding nuclei. Estimation of marginal posterior means of variance components and parameters of a single autosomal locus was performed by use of the Gibbs sampler. The results showed evidence for a mixed major gene: -polygenic inheritance of BW and age at sexual maturity (ASM) in both strains. Single genes affecting BW and ASM explained one-third of the genetic variance. For ASM large overdominance effect at single locus was estimated. Initial egg production (IEP) and average egg weight (EW) showed a polygenic model of inheritance. The polygenic heritability estimates for BW, ASM, IEP, and EW were 0.32, 0.25, 0.23, and 0.08 in Strain H77 and 0.25, 0.24, 0.11, and 0.38 in Strain N88, respectively.

Age Factors↗

Segregation of the pathways leading to cortical reaction and cell cycle activation in the rat egg.

At fertilization of the mammalian egg, resumption of the cell cycle and the cortical reaction are two events of egg activation, correlated with an increase in intracellular Ca2+ concentration and activation of protein kinase C. To evaluate the pathways leading to both events, rat eggs were parthenogenetically activated by the calcium ionophore ionomycin, or by the protein kinase C activators 12-O-tetradecanoyl phorbol-13-acetate (TPA) or 1-oleoyl-2-acetylglycerol (OAG). Cortical granule exudate was visualized by the lectin Lens culinaris and Texas Red streptavidin, using a confocal microscope. Resumption of meiosis was detected by Hoechst dye, and intracellular Ca2+ concentration by fura-2. Ionomycin triggered both a cortical reaction and resumption of meiosis, while chelation of intracellular Ca2+ rise by BAPTA-AM (1,2-bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester) revealed a segregation between these two events. A low Ca2+ transient (approximately 150 nM) induced a partial cortical reaction in half of the eggs, but the meiotic status was not affected. TPA triggered a cortical reaction with neither resumption of meiosis nor intracellular Ca2+ rise, while OAG induced both aspects of activation, as well as a significant intracellular Ca2+ rise. We conclude that in the cascade of events leading to egg activation, the initial Ca2+ rise is followed by a segregation in the pathway. A relatively low Ca2+ rise is sufficient to induce a partial cortical reaction. However, a higher level of Ca2+ is required to complete the cortical reaction and resumption of meiosis. The activation of the cell cycle is Ca2+-dependent, but protein kinase C-independent.

Animals↗

Tissue segregation enhances calvarial osteogenesis in adult primates.

Calvarial defects of adult mammals have a limited potential for regeneration. Osteogenesis may be impaired by the intrusion within the defect of nonosteogenic tissues during healing, which inhibits centripetal bone deposition from the margins of the defects. Using a primate model, we evaluated bone regeneration in calvarial defects treated with demineralized bone matrix versus defects treated according to the strategy of guided tissue regeneration. Sixty-four defects, 25 mm in diameter, were prepared in 16 adult male baboons (Papio ursinus). In each animal, 2 contralateral defects were covered with a template of porous polymer, 35 mm in diameter. Templates were positioned over the calvarial margins to prevent penetration of the pericranium and the temporalis muscle within the defects, thus maintaining tissue segregation during healing. The third defect was implanted with allogeneic demineralized bone matrix, as positive control. The fourth defect was left untreated and was used as negative control. Undecalcified bone sections (7 microns thick) were prepared from the harvested specimens 3 and 6 months after surgery. Although untreated defects showed limited osteogenesis after fusion of the pericranium with the dura, defects covered with the polymeric template often showed extensive bone deposition extending centripetally from the margins of the craniotomies. Histomorphometry demonstrated that defects treated with demineralized bone matrix and defects covered with the polymeric template had greater amounts of bone and osteoid when compared with untreated defects (p < 0.01). At 6 months, greater amounts of bone formed in demineralized bone matrix-treated defects when compared with defects covered with the polymeric template (p < 0.01). The results of this study show that calvarial membranous bones of adult primates retain the potential to regenerate when segregation between the different tissue components participating in the healing of the wound is maintained. In the same model, however, implantation of allogeneic demineralized bone matrix, used as a positive control provided the most effective treatment for the defects.

Age Factors↗

Magno- and parvocellular pathways are segregated in the human optic tract.

There is abundant psychophysical evidence in humans suggesting the existence of parallel pathways subserving different aspects of vision. However, there is little direct proof of the neural structures underlying the two pathways. We present direct anatomical evidence that in the normal human optic tract fibres are segregated according to size. Large axons, likely to correspond to the magnocellular pathway of non-human primates, take a more ventral and superficial course than the smaller axons belonging to the parvocellular pathway. This anatomical segregation not only reinforces the hypothesis of parallel pathways but, more importantly, offers a unique opportunity for studying the psychophysical effects of selective damage to one or the other fibre contingent.

Aged↗

Segregated distribution of TH-immunoreactivity in olfactory glomeruli.

Atypical and typical olfactory glomeruli differ in their primary afferents, centrifugal control and in some chemically identified subpopulations of interneurones. The distribution of tyrosine hydroxylase (TH)-immunopositive neurones in the periglomerular region of both typical and atypical glomeruli has been studied using a double histochemical-immunohistochemical method. A segregated distribution of TH-immunopositive cells was found among both types of glomeruli. TH-immunolabelled cells were more abundant (p < 0.05) in the atypical glomeruli. These data suggest that some neuronal subpopulations are related to specific properties of the glomerular physiology and they have a segregated distribution in different subsets of glomeruli. Thus, catecholamines might be involved in the processing of specific olfactory cues in atypical glomeruli. This study presents new differences in the cellular composition of typical and atypical glomeruli.

Acetylcholinesterase↗

Evidence for fusion and segregation induced by 21 Hz multiple-digit stimulation in humans.

Subjects were trained to detect changes in the frequency of 21 Hz tactile stimulation applied to digits 2 + 3 + 4 (fusion group) or 2 + 4 (segregation group) of the right hand. The 21 Hz steady-state response for digit 3 was measured by 64 channel EEG on mapping trials before and after training. Discrimination improved over 3 days, confirming that subjects attended to the training stimuli. The 21 Hz response was larger on training than on mapping trials, indicating sensitivity of the response to the strength of cortical activation. Under these conditions the 21 Hz response for digit 3 decreased after training in both groups on day 1. On day 3 this effect reversed in a subset of fusion subjects while segregation continued to yield decreases. The findings suggest that somatosensory representations are dynamically modified by the sensory input experienced on a task.

Adult↗

Segregation and linkage analyses of Tourette's syndrome and related disorders.

Segregation and linkage analyses were performed with data from a large Tourette's syndrome (TS) multigenerational kindred. Results of segregation analyses were remarkably similar to some reported earlier and suggest that the mode of transmission is consistent with autosomal dominant inheritance. The analyses were done using three diagnostic schemes to specify affected family members (TS only; TS or chronic tics [CT]; and TS, CT or obsessive compulsive disorder [OCD]). The estimates of penetrance for the genotypes AA, Aa and aa (A denotes the susceptibility allele) in the analyses including relatives with TS, CT or OCD were 0.99, 0.99 and 0.00, respectively, for males and 0.70, 0.70 and 0.00 for females. Pairwise linkage analyses with 140 marker loci failed to identify a linked marker. However, approximately 30 percent of the genome was excluded as the site of the hypothesized locus for TS.

Child↗

Differential brain atrial natriuretic peptide expression co-segregates with occurrence of early stroke in the stroke-prone phenotype of the spontaneously hypertensive rat.

OBJECTIVE: To determine how the downregulation of atrial natriuretic peptide (ANP) gene expression, previously demonstrated to occur only in the brain of the stroke-prone spontaneously hypertensive rat (SHRsp), in contrast to the stroke-resistant SHR (SHRsr), co-segregates with stroke occurrence in SHRsp/SHRsr F2 descendants in order to study the 'protective' role towards stroke previously demonstrated in SHRsp for the quantitative trait locus STR2 that also carries the ANP gene. DESIGN AND METHODS: Eight male SHRsp, eight male SHRsr and 16 male SHRsp/SHRsr F2-intercross animals (progeny of brother/sister mated F1 hybrids from an original cross between F0 SHRsp and SHRsr) were selected for this study. All rats were exposed to a stroke-permissive Japanese-style diet starting at the age of 6 weeks. Half of the F2 animals had early strokes; the remainder had late strokes. Blood pressure was measured before sacrifice. Analysis of brain ANP expression using an RNase protection assay was performed in all animals. RESULTS: Downregulation of brain ANP in the stroke-prone phenotype was found to co-segregate with the occurrence of early strokes in the F2 rats independently of blood pressure levels. CONCLUSIONS: The observed lower expression of ANP in the brains of stroke-prone rats appears to be the result of an inhibitory effect by another gene or genes. It seems unlikely that this specific trait represents a primary protective mechanism.

Animals↗

Swim test immobility co-segregates with serotonergic but not cholinergic sensitivity in cross-breeds of Flinders Line rats.

The Flinders Sensitive Line (FSL) rat, a genetic animal model of depression, was cross-bred with its normal control, the Flinders Resistant Line (FRL) rat, in order to investigate the relationship between cholinergic sensitivity, the selected variable, and two apparent genetically correlated variables, serotonergic sensitivity and swim test immobility. Cross-breeding established F1, F2 and back-cross progeny, with at least 20 rats of each sex for each group. Cholinergic sensitivity was assessed as the hypothermic response to oxotremorine (0.2 mg/kg) in 30 day old rats. Serotonergic sensitivity was assessed as the hypothermic response to 8-OH-DPAT, a serotonin (5-HT)-1A agonist, in 35-40 day old rats. Immobility was assessed as the time spent immobile in a 5 min swim test in 60-70 day old rats. For each variable, there were highly significant group differences, with the parental FSL and FRL groups being at the extremes. The segregating populations tended to be intermediate between the parental lines and were generally significantly different from both FSL and FRL groups. However, the crosses more closely resembled the FRL parent for only the cholinergic responses, the distributions for 8-OH-DPAT and immobility suggesting predominantly additive genetics. Statistical analyses with chi square to compare response distributions and regression to quantify the association between variables in the segregating populations confirmed that cholinergic sensitivity was different from serotonergic sensitivity and immobility, which were significantly correlated with each other.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Moving from spatially segregated to transparent motion: A modelling approach.

Motion transparency, in which patterns of moving elements group together to give the impression of lacy overlapping surfaces, provides an important challenge to models of motion perception. It has been suggested that we perceive transparent motion when the shape of the velocity histogram of the stimulus is bimodal. To investigate this further, random-dot kinematogram motion sequences were created to simulate segregated (perceptually spatially separated) and transparent (perceptually overlapping) motion. The motion sequences were analysed using the multi-channel gradient model (McGM) to obtain the speed and direction at every pixel of each frame of the motion sequences. The velocity histograms obtained were found to be quantitatively similar and all were bimodal. However, the spatial and temporal properties of the velocity field differed between segregated and transparent stimuli. Transparent stimuli produced patches of rightward and leftward motion that varied in location over time. This demonstrates that we can successfully differentiate between these two types of motion on the basis of the time varying local velocity field. However, the percept of motion transparency cannot be based simply on the presence of a bimodal velocity histogram.

Models, Theoretical↗

Adaptive significance of a circadian clock: temporal segregation of activities reduces intrinsic competitive inferiority in Drosophila parasitoids.

Most organisms show self-sustained circadian oscillations or biological clocks which control their daily fluctuations in behavioural and physiological activities. While extensive progress has been made in understanding the molecular mechanisms of biological clocks, there have been few clear demonstrations of the fitness value of endogenous rhythms. This study investigated the adaptive significance of circadian rhythms in a Drosophila parasitoid community. The activity rhythms of three sympatric Drosophila parasitoids are out of phase, the competitively inferior parasitoid species being active earlier than the superior competitor. This temporal segregation appears at least partially determined by endogenous periods of the clock which also vary between species and which correlate the time of activity. This earlier activity of the inferior competitor significantly reduces its intrinsic competitive disadvantage when multiparasitism occurs, thus suggesting that natural selection acting on the phase of the rhythm could substantially deviate the endogenous period from the optimal ca. 24 h period. This study demonstrates that temporal segregation of competing species could be endogenously controlled, which undoubtedly favours their coexistence in nature and also shows how natural selection can act on biological clocks to shape daily activity patterns.

Adaptation, Physiological↗

Further studies in genetic resistance of fowl to RSV(RAV O): evidence for interaction between independently segregating tumour virus b and tumour virus e genes.

The segregation of resistant and susceptible phenotypes in response to infection by RSV(RAV 2), RSV(RAV 50) and RSV(RAV 0), of avian RNA tumour virus subgroups B, D and E, respectively, was analysed in several test-crosses using chickens from the RPRL line 7-2, HPRS-synthetic line E and the Reaseheath line C. The results were fully consistent with out view reported previously that the genes at the tve and tvb loci segregate independently and recombine under the Mendelian second law of independent assortment. The dominant susceptibility es gene is expressed phenotypically when associated with the dominant susceptibility bs gene, but its expression is suppressed when associated with two doses of the recessive br gene. Genetic causes such as lack of penetration, recessive epistasis, and/or complementary intereaction between the tvb and tve genes have been discussed to account for the modified phenotypic expression of brbreses cells, i.e. resistance to subgroup E virus. Also, as reported previously, it was observed in this study that the tvb genes control the cellular response to subgroup D virus.

Animals↗

Segregation of proteinase-negative mutants from heterozygous Candida albicans.

The extracellular acidic proteinase (EC 3.4.23.6) produced by Candida albicans has been reported to be a virulence factor. In studying the role of this proteinase in human disease, we determined the optimum conditions for stimulating proteinase production in order to isolate proteinase-negative (Prt-) mutants. We found that in liquid medium containing bovine serum albumin (BSA) as the sole nitrogen source, at pH 4 and 27 degrees C, the sensitivity of proteinase detection was considerably greater than when assayed on BSA agar at 37 degrees C. This observation is due, in part, to temperature sensitivity of proteinase induction. Nitrogen starvation did not induce proteinase. Proteinase production on agar was increased by adding 0.01% yeast extract (YE) to BSA medium. Using BSA + YE agar to isolate mutants, it was discovered that C. albicans ATCC 28366 was heterozygous for a Prt- mutation. Spontaneous Prt- mutants occurred at a frequency of 2 x 10(-3). Ultraviolet light increased the mitotic segregation of Prt- cells to a frequency of 1 x 10(-2). The Prt- phenotype showed a large inoculum effect, Prt- segregants reverted with a high frequency, and the revertants were unstable.

Aspartic Acid Endopeptidases↗

Missense mutations in the 3' end of the Escherichia coli dnaG gene do not abolish primase activity but do confer the chromosome-segregation-defective (par) phenotype.

Isogenic dnaG strains of Escherichia coli with the parB and dnaG2903 alleles in the MG1655 chromosomal background displayed the classic par phenotype at the nonpermissive temperature of 42 degrees C. These strains synthesized DNA at 42 degrees C, but remained chromosome segregation defective as determined by cytology. A strain with the dnaG2903 allele was tested for its ability to support DNA replication of a primase-dependent G4ori(c)-containing M13 phage derivative by quantitative competitive PCR (QC-PCR). The dnaG2903 strain converted the single-stranded DNA into double-stranded replicative form DNA at 42 degrees C. These results indicate that DnaG2903 retains primase activity at the restrictive temperature. Nucleoids remained unsegregated in the central region of cell filaments at 42 degrees C. The observed suppression of cell filamentation in dnaG sfiA or dnaG lexA double mutants suggests that the SOS response is induced at the restrictive temperature in parB and dnaG2903 strains but fails to account entirely for the cell filamentation phenotype. ParB and DnaG2903 presumably can synthesize primer RNA for DNA replication, but may be defective in their interactions with DNA replication proteins, cell cycle regulatory factors, or the chromosome segregation apparatus itself.

Alleles↗

The mother-daughter mating type switching asymmetry of budding yeast is not conferred by the segregation of parental HO gene DNA strands.

The Saccharomyces cerevisiae HO gene, which encodes a site-specific endonuclease, is transcribed in the parent (mother) cell but not in the daughter (bud) cell. Consequently mother cells can switch their mating type whereas bud cells cannot. Whether or not the different capabilities of these cells are due to a nonrandom segregation of parental HO gene DNA strands to progeny cells is tested here by assaying the pattern of switching in cells where the HO gene is inverted in the chromosome. In an inverted HO strain, as is the case with the normal HO arrangement strains, only the mother cells were found to switch. Thus, the possibility of asymmetric segregation of parental HO gene DNA strands does not regulate the mother-daughter asymmetry of switching.

Cell Cycle↗

Synapsis and chiasma formation in Caenorhabditis elegans require HIM-3, a meiotic chromosome core component that functions in chromosome segregation.

Meiotic chromosomes are organized about a proteinaceous core that forms between replicated sister chromatids. We have isolated a Caenorhabditis elegans gene, him-3, which encodes a meiosis-specific component of chromosome cores with some similarity to the yeast lateral element protein Hop1p. Antibodies raised against HIM-3 localize the protein to condensing chromosomes in early prophase I and to the cores of both synapsed and desynapsed chromosomes. In RNA interference experiments, chromosomes appear to condense normally in the absence of detectable protein but fail to synapse and form chiasmata, indicating that HIM-3 is essential for these processes. Hypomorphs of him-3, although being synapsis proficient, show severe reductions in the frequency of crossing-over, demonstrating that HIM-3 has a role in establishing normal levels of interhomolog exchange. Him-3 mutants also show defects in meiotic chromosome segregation and the persistence of the protein at the chromosome core until the metaphase I-anaphase I transition suggests that HIM-3 may play a role in sister chromatid cohesion. The analysis of him-3 provides the first functional description of a chromosome core component in a multicellular organism and suggests that a mechanistic link exists between the early meiotic events of synapsis and recombination, and later events such as segregation.

Animals↗