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Psychiatric morbidity in sentenced segregated HIV-positive prisoners.

In this comparative study with a control group of prisoners, psychiatric morbidity was measured in two groups of sentenced prisoners, each group completing the GHQ-30 and 21-item Beck Depression Inventory (BDI). Group 1 consisted of 40 segregated HIV-positive prisoners and group 2 a matched control group in the main prison who had no history of HIV seropositivity. All members of group 1 had a history of intravenous drug abuse. The mean GHQ-30 and BDI scores were significantly higher in group 1, and 90% of group 1 were psychiatric 'cases' compared with just over 42% of group 2. Levels of psychiatric morbidity present in a third group, consisting of HIV-positive prisoners who had not been segregated (prison authorities were unaware of their seropositivity) are an interesting pointer for further research.

Adult↗

Does occupational gender segregation influence the association of effort-reward imbalance with myocardial infarction in the SHEEP study?

The objective of this study was to investigate whether occupational gender segregation moderates the association between job stress in terms of effort-reward imbalance and the risk of myocardial infarction. This analysis was conducted in 1,381 cases and 1,697 referents of the Swedish SHEEP case control study aged 45-70 years. Information on myocardial infarction and biological coronary risk factors (e.g. hypertension, blood lipids) was achieved from clinical screenings. Information on socio-demographic variables, effort-reward imbalance, behavioral coronary risk factors (e.g., smoking), and additional coronary risk factors (e.g., diabetes, family history of coronary heart disease) was derived from well-tested standardized questionnaires. After adjustment for confounders the strongest association between overcommitment (the intrinsic component of effort-reward imbalance) and risk of belonging to the myocardial infarction group was found among women in male-dominated jobs (odds ratio [OR] = 2.71, 95% CI = 1.13-6.52) as compared to the remaining group (OR = 1.52, 95% CI = 1.01-2.31). Moreover, a significant interaction between pronounced overcommitment and male domination in relation to myocardial infarction was observed among women (OR = 2.44, 95% CI = 1.05-5.67). In men, an association between the ratio of effort and reward (the extrinsic component of the model) and risk of myocardial infarction was found for the majority, that is the group not working in women-dominated jobs (OR = 1.39, 95% CI = 1.04-1.86). Despite methodological limitations, this study gives preliminary evidence of a moderating effect of occupational gender segregation on the association of effort-reward imbalance (i.e., the intrinsic model component overcommitment) with acute myocardial infarction risk among women, but not among men.

Adult↗

Complex segregation analysis of dystonia pedigrees suggests autosomal dominant inheritance.

We reanalyzed data collected in a large family study of idiopathic torsion dystonia (ITD) using complex segregation analysis. Previous investigators concluded that the mode of inheritance of ITD differed between Jews and non-Jews. The results from our segregation analyses suggest that ITD is inherited as an autosomal dominant trait, with low penetrance (0.255 to 0.333), regardless of ethnic origin. The low penetrance implies that, although a major gene is important for the expression of the illness, other factors also contribute to the manifestations of ITD.

Dystonia↗

Segregation of telencephalic and eye-field identities inside the zebrafish forebrain territory is controlled by Rx3.

Anteroposterior patterning of the vertebrate forebrain during gastrulation involves graded Wnt signaling, which segregates anterior fields (telencephalon and eye) from the diencephalon. How the telencephalic and retinal primordia are subsequently subdivided remains largely unknown. We demonstrate that at late gastrulation the Paired-like homeodomain transcription factor Rx3 biases cell specification choices towards the retinal fate within a population of bipotential precursors of the anterior forebrain: direct cell tracing demonstrates that retinal precursors acquire a telencephalic fate in embryos homozygous for the rx3-null allele ckh(ne2611), characterized by an enlarged telencephalon and a lack of eyes. Chimera analyses further indicate that this function of Rx3 is cell autonomous. Transfating of the eye field in the absence of Rx3 function correlates with a substantial posterior expansion of expression of the Wnt antagonist Tlc and the winged-helix transcription factor Foxg1. These results suggest that the process segregating the telencephalic and eye fields is isolated from diencephalic patterning, and is mediated by Rx3.

Amino Acid Sequence↗

Cranial paraxial mesoderm and neural crest cells of the mouse embryo: co-distribution in the craniofacial mesenchyme but distinct segregation in branchial arches.

The spatial distribution of the cranial paraxial mesoderm and the neural crest cells during craniofacial morphogenesis of the mouse embryo was studied by micromanipulative cell grafting and cell labelling. Results of this study show that the paraxial mesoderm and neural crest cells arising at the same segmental position share common destinations. Mesodermal cells from somitomeres I, III, IV and VI were distributed to the same craniofacial tissues as neural crest cells of the forebrain, the caudal midbrain, and the rostral, middle and caudal hindbrains found respectively next to these mesodermal segments. This finding suggests that a basic meristic pattern is established globally in the neural plate ectoderm and paraxial mesoderm during early mouse development. Cells from these two sources mixed extensively in the peri-ocular, facial, periotic and cervical mesenchyme. However, within the branchial arches a distinct segregation of these two cell populations was discovered. Neural crest cells colonised the periphery of the branchial arches and enveloped the somitomere-derived core tissues on the rostral, lateral and caudal sides of the arch. Such segregation of cell populations in the first three branchial arches is apparent at least until the 10.5-day hindlimb bud stage and could be important for the patterning of the skeletal and myogenic derivatives of the arches.

Animals↗

Segregation of germ granules in living Caenorhabditis elegans embryos: cell-type-specific mechanisms for cytoplasmic localisation.

Germ granules are ribonucleoprotein particles that are thought to function in germline specification in invertebrates and possibly in vertebrates. In Caenorhabditis elegans, these structures, termed P granules, are partitioned to the germline P cells during the early embryonic divisions. By injecting a fluorescently labelled anti-P-granule antibody into the C. elegans germline syncitium, we followed P-granule segregation in live embryos using laser-scanning confocal microscopy. We show that, in early P cells (P0 and P1), P-granule partitioning is achieved primarily by their migration through the cytoplasm towards the site of formation of the germline daughter cell. A different mechanism appears to operate in later P cells (P2 and P3): P granules associate with the nucleus and move with it toward the site of formation of the germline daughter cell, where they are then deposited. At each division, there is also disassembly or degradation of those P granules that remain in the cytoplasm destined for the somatic daughter cell. Microfilaments, microtubules and the product of the gene mes-1 are required for the normal pattern of P-granule segregation in P2.

Actin Cytoskeleton↗

Drosophila Klp67A is required for proper chromosome congression and segregation during meiosis I.

Drosophila Klp67A belongs to the Kip3 subfamily of Kinesin-type microtubule catastrophe factors. In primary spermatocytes, loss of klp67A leads to defects in karyokinesis and cytokinesis. We show that these cells formed disorganised, bipolar spindles that contained increased numbers of microtubules. The kinetochore fibres were wavy and bent, whereas astral microtubules appeared abnormally robust and formed cortical bundles. Time-lapse studies revealed that during biorientation, the chromosomes in klp67A mutant cells continued to reorient for about twice as long as those in control cells. Metaphase plates were poorly defined in the mutants and often formed at non-equatorial positions. Consistent with the above abnormalities in chromosome congression, we found that in wild-type cells Klp67A associated with prometaphase/metaphase kinetochores before redistributing to the central spindle at anaphase onset. Although the timing of this redistribution of kinetochores argues against a role in anaphase chromosome segregation, dyads in the mutants disjoined but exhibited greatly diminished poleward velocities. They travelled on average at approximately 34% of the velocity of their wild-type counterparts and often decondensed at non-polar locations. Hypomorphic mutations of klp67A may lead to segregation defects.

Animals↗

Activation of the pheromone-responsive MAP kinase drives haploid cells to undergo ectopic meiosis with normal telomere clustering and sister chromatid segregation in fission yeast.

Meiosis is a process of importance for sexually reproducing eukaryotic organisms. In the fission yeast Schizosaccharomyces pombe, meiosis normally proceeds in a diploid zygote which is produced by conjugation of haploid cells of opposite mating types. We demonstrate that activation of the pheromone-responsive MAPK, Spk1, by the ectopic expression of a constitutively active form of Byr1 (MAPKK for Spk1) induced the cells to undergo meiosis while in the haploid state. Moreover, the induction of meiosis required Mei2 (a key positive regulator of meiosis), but did not require Mei3; Mei3 is normally required to inactivate the Pat1 kinase (a negative regulator of Mei2) thereby allowing Mei2 to drive meiosis. Therefore, expression of a constitutively active form of Byr1 activates Mei2 without the need of Mei3. In cells induced to undergo meiosis by activating the Spk1 MAPK signaling pathway, telomeres clustered at the spindle pole body (SPB) and centromeres detached normally from the SPB during meiotic prophase, and the cells showed the correct segregation of sister chromatids during meiotic divisions. In contrast, in meiosis induced by inactivation of Pat1, sister chromatids segregate precociously during the first meiotic division. Thus, these results suggest that activation of Spk1 drives meiosis in S. pombe.

Binding Sites↗

Calmodulin localizes to the spindle pole body of Schizosaccharomyces pombe and performs an essential function in chromosome segregation.

The essential calmodulin genes in both Saccharomyces cerevisiae and Schizosaccharomyces pombe were precisely replaced with genes encoding fusions between calmodulin and the green fluorescent protein (GFP). In living budding yeast the GFP-calmodulin fusion protein (GFP-Cmd1p) localized simultaneously to sites of cell growth and to the spindle pole body (SPB), the yeast analog of the centrosome. Having demonstrated proper localization of GFP-calmodulin in budding yeast, we examined the localization of a fusion between GFP and calmodulin (GFP-Camlp) in fission yeast, where calmodulin had not been localized by any method. We find GFP-Camlp also localizes both to sites of polarized cell growth and to the fission yeast SPB. The localization of calmodulin to the SPB by GFP fusion was confirmed by indirect immunofluorescence. Antiserum to S. pombe calmodulin labeled the ends of the mitotic spindle stained with anti-tubulin antiserum. This pattern was identical to that seen using antiserum to Sad1p, a known SPB component. We then characterized the defects in a temperature-sensitive S. pombe calmodulin mutant. Mutant cam1-E14 cells synchronized in S phase completed DNA synthesis, but lost viability during transit of mitosis. Severe defects in chromosome segregation, including hypercondensation, fragmentation, and unequal allocation of chromosomal material were observed. Immunofluorescence analysis of tubulin revealed a population of cells containing either broken or mislocalized mitotic spindles, which were never observed in wild-type cells. Taken together with the subcellular localization of calmodulin, the observed spindle and chromosome segregation defects suggest that calmodulin performs an essential role during mitosis at the fission yeast SPB.

Calmodulin↗

COPI-coated ER-to-Golgi transport complexes segregate from COPII in close proximity to ER exit sites.

Transport of proteins between the endoplasmic reticulum and Golgi apparatus is mediated by two distinct membrane coat complexes, COPI and COPII. Genetic, biochemical and morphological data have accumulated into a model which suggests a sequential mode of action with COPII mediating the selection of cargo and formation of transport vesicles at the ER membrane for ER-to-Golgi transport and COPI mediating recycling of the transport machinery from post-ER membranes. To test this transport model directly in vivo, and to study the precise temporal sequence of COPI and COPII action in ER-to-Golgi transport, we have used time lapse microscopy of living cells to visualise simultaneously the dynamics of COPII and COPI, as well as COPII and GFP tagged secretory markers in living cells. The majority of COPII labelling appears tightly associated with ER membranes that move only within a limited area (less than 2 microm). Secretory cargo segregates from these sites and is then transported to the Golgi apparatus without any apparent association with COPII. COPI-coated transport complexes are seen to form adjacent to the COPII sites on the ER before segregating and moving directionally towards the Golgi apparatus. COPII is not present on these transport complexes and remains associated with the ER. These data demonstrate for the first time directly in vivo that ER-to-Golgi transport is organised in two steps characterised by a sequential mode of action of COPII and COPI.

Animals↗

Three dimensional configuration of the secretory pathway and segregation of secretion granules in the yeast Saccharomyces cerevisiae.

The structural elements of the secretory pathway in the budding yeast Saccharomyces cerevisiae were analyzed by 3D stereo-electron microscopy using relatively thick sections in which membranes were selectively impregnated. In a wild-type strain, tubular networks of various sizes and staining properties were distributed throughout the cytoplasm. As a rule, wide-meshed, lightly stained polygonal networks were connected to more or less fenestrated sheets of endoplasmic reticulum (ER). Some of these networks were continuous with more intensely stained networks and narrower meshes that displayed at their intersections nodular dilations that progressively increased in size and staining properties to reach those of secretion granules. Such networks presumably corresponded to Golgi elements. Indeed, stacked cisternae typical of the mammalian Golgi apparatus are rarely found in wild-type cells. However, if it is assumed that the Golgi apparatus plays a key role in the segregation and maturation of secretion granules, then tubular networks with nodular dilations should be equivalent to parts of this organelle. In correlation with the increase in size and density of the nodules there was a decrease in diameter and staining intensity of the interconnecting tubules. These results parallel observations on the formation of secretory granules in mammalian cells and suggest that the segregation of secretory material is concomitant with the progressive perforation and tubulization of previously unperforated sheets. When the sec21-3 thermosensitive mutant was examined at the nonpermissive temperature (37 degrees C), the secretory pathway was blocked at exit from the ER, which started to accumulate as clusters of narrow, anastomosed, unperforated ribbon-like elements. When the block was released by shifting down to permissive temperature (24 degrees C), tubular networks of various sizes and caliber, presumably Golgi in nature, formed as soon as 5 minutes after release of the block. At later time intervals, granules of various sizes and densities appeared to be released by rupture of these tubular networks or even to form at the edges of ER fenestrae. These observations support a dynamic maturation process in which the formation of secretion granules occurs by means of an oriented series of membrane transformations starting at the ER and culminating with the liberation of secretion granules from Golgi networks.

Biological Transport, Active↗

Segregation of modified bacteriorhodopsin aggregations in reconstituted vesicle membrane induced by the change of thermodynamical parameters.

It was clearly shown that the change in thermodynamical parameters could cause the segregation of membrane protein aggregations in the phospholipid membrane. At first, reconstituted vesicles were prepared with a membrane protein, bacteriorhodopsin and a constituent phospholipid of biomembranes, L-alpha-dimyristoyl phosphatidylcholine. When the temperature of the suspension was decreased or the osmotic pressure was increased by adding poly(ethylene glycol) to this vesicle suspension at 23 degrees, the circular dichroism spectra showed a typical band indicating bacteriorhodopsin trimer formation implying their aggregation. This suggests that the aggregation of trimers proceeded by adding poly(ethylene glycol) into vesicle suspension, just as it proceeded by decreasing the temperature. Next, vesicles were prepared with fluorescein isothiocyanate-labeled bacteriorhodopsin, photoemissive bacteriorhodopsin and L-alpha-dimyristoyl phosphatidylcholine. The excitation energy transfer between the two modified proteins was measured by fluorescence spectroscopy. In this case, however, when poly(ethylene glycol) was added into the suspension, the yield of the excitation energy transfer decreased. This result indicates that modified proteins aggregate separately in a segregated form in the vesicle membrane.

Bacteriorhodopsins↗

Development of the KVL segregating inbred strain of the Syrian hamster (Mesocricetus auratus).

A new colony of a single segregating inbred strain of the Syrian hamster (Mesocricetus auratus), designated KVL, has recently been developed at the Royal Veterinary and Agricultural University, Copenhagen, Denmark. The segregation occurs with respect to coat colour (pied gray/pied brown) as a result of inbreeding with forced heterozygosity. After 20 generations average litter size was 6.7 at birth and 5.57 at weaning. Mean generation interval was 89.4 days. An initially significant decrease in productivity (inbreeding depression) levelled out with further generations and has now stabilized. The colony is being maintained.

Animals↗

Segregation and black/white differences in exposure to air toxics in 1990.

I examined non-Hispanic Black and non-Hispanic White differences in exposure to noncriteria air pollutants in 44 U.S. Census Bureau-defined metropolitan areas with populations greater than one million, using data on air toxics concentrations prepared for the U.S. Environmental Protection Agency as part of its Cumulative Exposure Project combined with U.S. census data. I measured differences in exposure to air toxics through the calculation of a net difference score, which is a statistical measure used in income inequality analysis to measure inequality over the whole range of exposures. The scores ranged from 11.52 to 83.60. In every metropolitan area, non-Hispanic Blacks are more likely than non-Hispanic Whites to be living in tracts with higher total modeled air toxics concentrations. To assess potential reasons for such a wide variation in exposure differences, I performed a multiple regression analysis with the net difference score as the dependent variable. Independent variables initially included were as follows: the dissimilarity index (to measure segregation), Black poverty/White poverty (to control for Black/White economic differences), population density and percentage of persons traveling to work who drive to work (alone and in car pools), and percentage of workforce employed in manufacturing (factors affecting air quality). After an initial analysis I eliminated from the model the measures of density and the persons driving to work because they were statistically insignificant, they did not add to the predictive power of the model, and their deletion did not affect the other variables. The final model had an R(2) of 0.56. Increased segregation is associated with increased disparity in potential exposure to air pollution.

Air Pollutants↗

Proximal chiasma localization within an interstitial chromosome segment, a likely correlate of adjacent-2 segregation of translocation causing multivalents in the mouse.

Two T7OH/+ translocation-carrying male mice were used in an investigation into the relation between the segregation pattern of the translocation caused multivalent at anaphase I and the position of the only chiasma in a long interstitial segment. Moreover, the relation between meiotic stage (from early diakinesis to metaphase I) and chiasma movement was assessed. It appeared that pronounced movement of a chiasma within the multivalent was linked with chiasma terminalization in an adjacent segment, either on the same side of the translocation breakpoint or on the other side. On summing the CIV and CIII+I configurations (making up 97.9% of all configurations found) and focusing on the multivalents from late meiotic cells, 41.3% had a proximal chiasma in the long interstitial segment of the multivalent. In total, a percentage of 33.5% of all secondary spermatocytes were characteristic of adjacent-2 segregation (i.e., homologous centromeres move to the same pole at anaphase I). Results obtained with T7OH translocation trisomics, which are briefly discussed in this paper, confirm the tendency of proximal chiasma frequencies in late meiotic cells to coincide with the frequency of absence of homologous centromere separation within the T7OH translocation multivalent. The importance of this phenomenon for normal bivalent behavior during anaphase I is considered.

Anaphase↗

Complex segregation analysis of the radiographic phalanges bone mineral density and their age-related changes.

The complex segregation analyses performed in our previous studies revealed a significant major gene (MG) effect on the age-adjusted cortical and cancellous bone mineral density (BMD) in two ethnically different populations, Chuvasha and Turkmenians. The aim of the present study was to test the hypothesis of pleiotropic MG control of three components of bone aging, that is, the baseline level of BMD (mu(gs)), the age at onset of the bone mass loss (T(gs)), and the rate of this loss over the years (alpha(gs)). Nuclear and more complex pedigrees from the same two ethnic samples were assessed for hand phalangeal BMD (Chuvasha, 1208 individuals, and Turkmenians, 643 individuals), and complex segregational analysis incorporating age and sex effects directly into MG penetrance function was carried out. The results of the present analysis clearly confirmed the existence of the putative MG and showed that the proportion of BMD variation attributable to this MG effect within the sex was remarkably similar in both populations and ranged between 34.7% and 35.2%. The most parsimonious model for BMD transmission in Chuvasha pedigrees additionally indicated significant residual correlation between siblings and clear sex differences in the annual rates of bone loss alpha(gs). The latter was more than twice as high in females than that in males (0.086 SD vs. 0.033 SD per year). In Turkmenian pedigrees the most parsimonious model presented obvious evidence of the MG control of BMD baseline levels in both sexes with significantly lower baseline levels and younger age at onset (T(gs)) in females. No clear MG effects were inferred on T(gs) and/or alpha(gs) in either sample, either in males or in females. That is, the present study does not suggest MG x SEX x AGE interaction. We suppose that if the rate of age-related changes in phalangeal BMD is genetically determined, then these are not the same genes as those affecting the BMD baseline levels.

Adolescent↗

Texture segregation by chromatic and achromatic visual pathways: an analogy with motion processing.

We present results to show that texture segregation can be obtained through the so-called coherent spatial grouping of local shape (orientation) and of local color under both nonequiluminant and equiluminant conditions. Color grouping entails texture segregation independent of orientation grouping, while the reverse is not true under equiluminant conditions. The experiments permit the isolation of chromatic- and luminance-oriented mechanisms, as well as of chromatic nonoriented mechanisms, all of which contribute to texture discrimination. As a general rule, the present results (including the asymmetry between color and orientation grouping) are similar to those obtained by us in a series of motion-perception experiments. This similarity suggests that the perceptual rules governing spatial grouping are analogous (if not identical) to those governing spatiotemporal grouping. As in the case of directional discrimination, texture-discrimination performances may be accounted for by the activation of higher-order units receiving inputs from subunits, all of which display similar tuning properties within a multidimensional space.

Color Perception↗

Chemical segregation and reduction of Raman background interference using drop coating deposition.

A new application of the recently described drop coating deposition Raman (DCDR) method facilitates the segregation and independent spectral characterization of mixture components. The quality of the normal (un-enhanced) Raman spectra are significantly improved as a result of reduced spectral interference from fluorescent impurities and buffer compounds. Fluorescence of commercial amino acid (O-phospho-L-serine) and protein (myoglobin) samples is reduced by over an order of magnitude using DCDR, more effectively than prolonged photo-bleaching. Furthermore, DCDR is used to obtain high-quality Raman spectra of proteins, lysozyme, and insulin, derived from solutions with up to 1000-fold excess buffer concentration. Possible thermodynamic and kinetic contributions to the observed segregation phenomena are discussed.

Amino Acids↗