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Normal X chromosome induced reversion in the direction of chromosome segregation in mouse-Chinese hamster somatic cell hybrids.

The effect of a normal mouse X chromosome on the chromosome segregation of mouse-Chinese hamster somatic cell hybrids was determined by (i) producing hybrids between the mouse sarcoma line CMS4 and a microcell hybrid (mfe4) of the hamster line E36, containing a mouse X chromosome from a normal cell; (ii) isolating hybrids between CMS4 and a 6-thioguanine selected (X minus) mfe4 subpopulation; (iii) comparing the direction of segregation in the two sets of hybrids. It was found that the normal X chromosome, like the X chromosomes from two MCA-transformed sarcoma lines reported previously [9], has the ability to switch the chromosome segregation of mouse-Chinese hamster somatic cell hybrids. We conclude that the reversal in chromosome segregation is mediated by factors located on the X chromosome. We designate these genetic elements as segregation reversal genes or sr genes.

Animals↗

Different effects from spatial frequency masking in texture segregation and texton detection tasks.

The paper reports psychophysical experiments set up to study the visual cues used in texture discrimination. In particular, the special role of "textons", i.e. distinct visual features such as blobs of different size, lines at different orientation, line intersections ("crossings") and line ends ("terminators") which have been proposed to provide the basis of perceptual segregation of texture areas, has been investigated. Texture pairs were briefly presented and simultaneously masked with two-dimensional visual noise at various spatial frequency bands. In different tasks on similar patterns, observers had to estimate the orientation of globally dissecting texture areas ("texture segregation") and to identify and distinguish the texture elements themselves ("texton detection"). Differential masking effects between these tasks indicate that texture segregation is often based on visual cues different from the supposed texton features. The segregation of crossing or terminator differences is also achieved from associated differences in the spatial frequency composition, that of differences in blob size from associated differences in mean luminance. Only differences in line orientation revealed similar masking curves in texture segregation and texton detection tasks.

Adult↗

Nonlinear processes in spatial-frequency channel models of perceived texture segregation: effects of sign and amount of contrast.

Observers rated the degree of segregation between two textures, each composed of the same two element types but in differing arrangements (a checkerboard arrangement in the middle region of the pattern and a striped arrangement in the top and bottom regions). The two element types in a given pattern were either both solid squares or both center-surround elements. In center-surround elements the average luminance equaled the background luminance. The two elements types were identical in size but differed in sign and/or amount of contrast. Discrepancies between the observers' ratings of perceived segregation and the predictions of simple (linear) spatial-frequency and orientation channels models of texture segregation suggested adding nonlinear processes to the model. Complex channels (a rectification-type nonlinearity between two linear-filtering stages) can explain why some patterns made of center-surround elements segregate even though there is little energy at the spatial frequencies that differentiate the two textures. Complex channels cannot, however, explain the very poor segregation of "same-sign-of-contrast" patterns (where the luminances of the two element types were both far above or both far below the background). This second result might arise from a local nonlinearity preceding the channels and might be ascribed to retinal light adaptation except that it occurs at contrasts less than or equal to 25%! Alternatively, it might arise from normalization, which may result from intracortical inhibition. Some preliminary quantitative predictions were computed from two models, one incorporating complex channels and an early local nonlinearity, the other complex channels and normalization. With suitable choices of parameters, either model could account for the results.

Contrast Sensitivity↗

Evidence for functional hemizygosity at the Emtr locus in CHO cells through segregation analysis.

The hypothesis of functional hemizygostiy at the emetine-resistant (Emtr, a non-X-linked recessive marker) locus in Chinese hamster ovary (CHO) cells has been examined by segregation analysis. The frequencies and the rates of segregation of the Emtr and Thgr (thioguanine-resistant, an X-linked recessive mutation) markers were determined from hybrids constructed between an Emtr-Thgr CHO cell line and various other Chinese hamster lines (V79, M3-1, CHO, GM7S, CHW and CHL). Thgr segregants were obtained at similar frequencies (10(-2)-10(-3)) from all the hybrids. The frequency of segregation of the Emtr marker, however, was similar to that of Thgr only in the CHO x CHO hybrids and was much lower (10(-4)-10(-6)) than the CHO x other Chinese hamster hybrids. Similar results were obtained when the segregation rates for the two markers from various hybrids were determined. These results are consistent with the hypothesis that in CHO cells, the gene responsible for Emtr is present in a single (functional) copy, whereas two copies of this gene are present in other Chinese hamster lines examined.

Cell Line↗

A role for recombination junctions in the segregation of mitochondrial DNA in yeast.

In S. cerevisiae, mitochondrial DNA (mtDNA) molecules, in spite of their high copy number, segregate as if there were a small number of heritable units. The rapid segregation of mitochondrial genomes can be analyzed using mtDNA deletion variants. These small, amplified genomes segregate preferentially from mixed zygotes relative to wild-type mtDNA. This segregation advantage is abolished by mutations in a gene, MGT1, that encodes a recombination junction-resolving enzyme. We show here that resolvase deficiency causes a larger proportion of molecules to be linked together by recombination junctions, resulting in the aggregation of mtDNA into a small number of cytological structures. This change in mtDNA structure can account for the increased mitotic loss of mtDNA and the altered pattern of mtDNA segregation from zygotes. We propose that the level of unresolved recombination junctions influences the number of heritable units of mtDNA.

Cytoplasm↗

Tests which distinguish induced crossing-over and aneuploidy from secondary segregation in Aspergillus treated with chloral hydrate or gamma-rays.

A system of tests with the ascomycete Aspergillus nidulans was devised that can detect 3 primary effects of genotoxic agents: (1) increases in mitotic crossing-over; (2) induced aneuploidy; and (3) clastogenic effects which cause chromosomal imbalance. Conidia of a new diploid tester strain, heterozygous for 4 recessive markers which alter conidial color, are treated and plated onto nonselective media. In cases of induced crossing-over, large color segments are found in normal green colonies, frequently adjacent to reciprocal twin segments. In contrast, both malsegregation and chromosome breakage produce unbalanced types which grow poorly and segregate further. Cases with yellow segregants are replated and their secondary diploid sectors tested for markers which are located on both chromosome arms in coupling with yA. Induced aneuploidy can be distinguished from chromosome breakage by the pattern of marker segregation. Any aneuploid type will produce euploid sectors solely by segregation of whole chromosomes; trisomic colonies (yA / yA / +) will show 1:2 ratios for yellow (homozygous yA) to parental green (yA/+) sectors and have characteristic phenotypes. Other induced unbalanced types, if heterozygous for deletions or aberrations may produce yellow diploid sectors by secondary crossing-over as well as by nondisjunction and such cases show unique patterns of genetic segregation and non- predictable phenotypes. As a complementary test, haploid strains are treated and induced abnormally growing types are replated and classified by phenotype. Aneuploids are unstable and produce many normal sectors, and some of these disomic or trisomic types can be visually identified.In contrast, induced deletions are lethal, and duplications or 'morphological' mutants show much more stable abnormal phenotypes. This test system was used to characterize the primary effects of gamma-rays and chloral hydrate. Results and evidence were as follows: (1) A dose-dependent increase of color segments resulting from reciprocal crossing-over was found after treatment of dividing nuclei in germinating diploid conidia with gamma-rays, but not with chloral hydrate. (2) Highly aneuploid and polyploid types were induced in diploid and haploid germinating conidia by chloral hydrate but not to any significant extent by gamma-rays. (3) gamma-Rays caused a dose- dependent increase off abnormally growing colonies when dormant or germinating diploid conidia were treated. These colonies produced secondary euploid sectors by spontaneous nondisjunction and frequently also by crossing-over, which provided evidence for induced semidominant and recessive lethal mutations of many types.

Alleles↗

Disruptive effects of ethyl alcohol on mitotic chromosome segregation in diploid and haploid strains of Aspergillus nidulans.

To identify, with certainty, the primary genotoxic effects of ethanol, condidia from diploid strains of Aspergillus nidulans were treated during early germination with ethyl alcohol, and all the resulting segregants from large samples were analysed in detail. Results were identical whether technical grade (95%), or highly purified 'absolute', alcohol was diluted to obtain the effective low levels of ethanol (3-6%). This makes it unlikely that trace contaminants, rather than ethanol itself, caused the observed induced segregation. At the most effective concentrations survival was about 50%, but over half of the colonies were abnormal and showed sectoring phenotypes. Higher concentrations were too inhibitory for growth. In practically all cases, when 'abnormals' were replated, aneuploids of various types were recovered. Most aneuploids were hyperdiploid, including a fraction of simple trisomics, and some were even polyploid types. All showed chromosomal-type segregation in diploid sectors, often segregating for genetic markers of many different chromosomes. Mitotic crossing-over was slightly increased, but probably not induced, since an equally high spontaneous frequency was observed among replated aneuploid types. To eliminate conclusively the possibility that chromosome breakage was the primary effect of ethanol, which might indirectly produce aneuploid-like types, haploid conidia were also treated. Up to 8% abnormals, mainly hyperhaploids, were obtained (at about 20-50% survival). When diploid and haploid strains were treated identically with ethanol in liquid media after a few hours of pregermination, frequencies of abnormals were similar for short treatments, but higher in diploid strains for longer ones (10-20% aneuploids). The abnormal colonies from the haploid strain were replated and visually identified: about 2/3 were typical n + 1 hyperhaploids, and most others were n + 2 or 3 or more, including a few 2n + 1 trisomics. It is concluded that as a primary effect, alcohol interferes with, and probably arrests, mitotic segregation, and causes chromosome missegregation and nondisjunction. In most cases, the resulting nuclei contain increased numbers of chromosomes and show high frequencies of chromosome loss.

Aspergillus nidulans↗

Cytoplasmic segregation and cytoskeletal organization in the electric catfish giant electromotoneuron with special reference to the axon hillock region.

The cytoplasm of the highly polarized nerve cell is permanently segregated into domains with differing organellar composition. The mechanisms maintaining this segregation are largely unknown. In order to elucidate the potential role of cytoskeletal elements in this process we compared the cytoplasmic segregation within the giant electromotoneuron of the electric catfish (Malapterurus electricus) with the distribution of binding sites for antibodies against elements of the cytoskeleton. Most prominent cytoplasmic segregations include the formation of a subplasmalemmal cortical structure free of Nissl bodies and Golgi cisternae, the separation within the soma of domains containing rough endoplasmic reticulum and filament-rich domains, and the soma-axon transition. The cytoplasmic transition at the axon hillock forms a distinct borderline where Nissl bodies, Golgi cisternae and the bulk of lysosomes abruptly terminate and are excluded from the axoplasm. Synaptic vesicles and mitochondria are free to pass compartmental borders. Tropomyosin, spectrin, and alpha-actinin reveal a rather homogeneous immunofluorescence throughout the neuron. In contrast, neurofilament protein and tubulin display a distinctly increased immunofluorescence in the subplasmalemmal cortical layer, in dendrites as well as in the axon. The increase in immunofluorescence at the axon hillock exactly depicts the small transition zone from the somatic cytoplasm rich in Nissl bodies, Golgi cisternae and lysosomes to the differently structured axoplasm. The picture is similar for beta-tubulin, tyrosinylated and detyrosinylated alpha-tubulin. Detyrosinylated tubulin (glu-tubulin, which is contained in microtubules of increased stability) shows the most prominent enrichment in the axon. The distribution of myosin is comparable to that of neurofilament protein but there is less difference in immunofluorescence between the domains. Our results would be compatible with a role of microtubules together with (the closely associated) neurofilaments in the segregation of neuronal cytoplasmic domains. Active transport as well as stable binding to the somatic cytoskeleton might counteract a homogeneous cytoplasmic distribution of the various classes of organelles by diffusion.

Actinin↗

Auditory stream segregation in an insect.

Auditory stream segregation is the perceptual grouping of the acoustic mixture reaching the ear into coherent representations of sound sources. It has been described in a variety of vertebrates and underlies auditory scene analysis or auditory image formation. Here we describe a phenomenon in an invertebrate that bears an intriguing resemblance to auditory stream segregation observed in vertebrates: in Neoconocephalus retusus (Orthoptera, Tettigoniidae) an auditory interneuron segregates information about bat echolocation calls from background male advertisement songs. This process utilizes differences between the temporal and spectral characteristics of the two stimuli, a mechanism which is similar to those of auditory stream segregation in vertebrates. This similarity suggests that auditory stream segregation is a fundamental feature of auditory perception, widespread from invertebrates to humans.

Acoustic Stimulation↗

Racial residential segregation and weight status among US adults.

While the segmentation of residential areas by race is well known to affect the social and economic well-being of the segregated minority group in the United States, the relationship between segregation and health has received less attention. This study examines the association between racial residential segregation, as measured by the isolation index, and individual weight status in US metropolitan areas. Multi-level, nationally representative data are used to consider the central hypothesis that segregation is positively associated with weight status among African Americans, a group that is hyper-segregated and disproportionately affected by unhealthy weight outcomes. Results show that among non-Hispanic blacks, higher racial isolation is positively associated with both a higher body mass index (BMI) and greater odds of being overweight, adjusting for multiple covariates, including measures of individual socioeconomic status. An increase of one standard deviation in the isolation index is associated with a 0.423 unit increase in BMI (p < 0.01), and a 14% increase in the odds of being overweight (p < 0.01). Among whites, there is no significant association between the isolation index and weight status. These findings suggest that in addition to differences among people, differences among places and, in particular, differences in the spatial organization of persons may be relevant to health policy and promotion efforts.

Adolescent↗

Simulation of consumer exposure to deoxynivalenol according to wheat crop management and grain segregation: case studies and methodological considerations.

We combined agronomic data and a model simulating exposure based on consumption data to assess the impact of crop management and grain segregation procedures on consumer exposure to deoxynivalenol. We used three scenarios of soil tillage at a regional scale and three scenarios of grain segregation for a supply area. The soil tillage scenarios were applied to a range of mean crop contamination levels, with various coefficients representing the degree of tillage. The grain segregation scenarios were applied to two real datasets of DON content distributions. We found that the increase in consumer exposure in response to increases in "risky" crop management practices such as direct-drilling depends largely on mean contamination and on the value of the tillage coefficient. The results for grain segregation procedures showed that exposure was most strongly affected by contamination distributions as the segregation procedure minimising risk differed for the two datasets.

Agriculture↗

Differential segregation in a cell-cell contact interface: the dynamics of the immunological synapse.

Receptor-ligand couples in the cell-cell contact interface between a T cell and an antigen-presenting cell form distinct geometric patterns and undergo spatial rearrangement within the contact interface. Spatial segregation of the antigen and adhesion receptors occurs within seconds of contact, central aggregation of the antigen receptor then occurring over 1-5 min. This structure, called the immunological synapse, is becoming a paradigm for localized signaling. However, the mechanisms driving its formation, in particular spatial segregation, are currently not understood. With a reaction diffusion model incorporating thermodynamics, elasticity, and reaction kinetics, we examine the hypothesis that differing bond lengths (extracellular domain size) is the driving force behind molecular segregation. We derive two key conditions necessary for segregation: a thermodynamic criterion on the effective bond elasticity and a requirement for the seeding/nucleation of domains. Domains have a minimum length scale and will only spontaneously coalesce/aggregate if the contact area is small or the membrane relaxation distance large. Otherwise, differential attachment of receptors to the cytoskeleton is required for central aggregation. Our analysis indicates that differential bond lengths have a significant effect on synapse dynamics, i.e., there is a significant contribution to the free energy of the interaction, suggesting that segregation by differential bond length is important in cell-cell contact interfaces and the immunological synapse.

Animals↗

Segregation of the photosystems in higher plant thylakoids and short- and long-term regulation by a mesoscopic approach.

In this paper we consider the relationship between the lateral segregation of photosystems I and II in the grana and characteristics of the short- and long-term regulation in thylakoids following the mesoscopic approach. Our study is thermodynamic; it is based on the Flory-Huggins theory for binary mixtures and the McMillan-Mayer theory of heterogeneous solutions. We demonstrate that state transitions promote rearrangement of photosystems by either favoring their mixing after LHCII phosphorylation or enhancing their segregation after LHCII dephosphorylation. This regulation influences the entire system properties locally. We also demonstrate that the variations of the photosystem ratio promote rearrangement of the photosystems preserving their segregation. This regulation influences the entire system properties globally. The studies presented are another indication of the importance of the segregation of the photosystems in the grana thylakoids of higher plants. Segregation of PSIs and PSIIs is a signature of the spinodal decomposition, which is a fine regulatory mechanism, related to both the short- and long-term adaptations of the photosynthetic apparatus in higher plant thylakoids.

Models, Biological↗

Analysis of chromosome segregation by means of fluorescence in situ hybridization: application to cytokinesis-blocked human lymphocytes.

The application of methods based on in situ hybridization to centromeric regions to cytokinesis-blocked cells provides a convenient way for the analysis of chromosome segregation in interphase cells. In this way, the reciprocal segregation patterns in daughter nuclei can be visualized and most of the problems related to the artefactual loss or gain of chromosomes which flaw other methods are avoided. In this work, the methodology has been applied to human lymphocytes to investigate the influence of donor age on spontaneous malsegregation rates, the occurrence of multiple malsegregation events, and the effect of the cytokinesis-blocking agent cytochalasin B (Cyt B) on spontaneous and induced chromosome malsegregation. The results obtained with 14 male donors, aged 22-57 years, demonstrated a significant (p < 0.001) increase in the frequency of micronuclei and X chromosome missegregation (both non-disjunction and chromosome loss) with the increasing age of the donors. Moreover, a similar association was observed with cultures hybridized with either chromosome 8 or 18 centromere probes, suggesting that the age-related loss of fidelity in chromosome segregation in vitro may be a general trait. The investigation of the distribution of multiple malsegregation events in cultured lymphocytes of eight male and nine female donors, with the simultaneous hybridization with pairs of centromeric probes (for chromosomes X and 8 or X and 18), demonstrated a large excess of multiple events with respect to that expected by random segregation. This fact may highlight the existence of cellular subpopulation(s) prone to malsegregate, or indicate that the malsegregation of one chromosome is able to affect the fidelity of segregation of the other chromosomes. Finally, the possible influence of Cyt B on chemically induced malsegregation has been investigated with the analysis of chromosomes X and 8 signals in nuclei of lymphocyte cultures treated with vinblastine (2.5-20 ng/ml) in the presence and absence of 6 micrograms/ml Cyt B. Vinblastine induced a small increase in hyperploidy of either chromosome X or 8 at 10 ng/ml in cultures treated with Cyt B. Without Cyt B, a significant increase of hyperploidy was only observed at the highest dose assayed (20 ng/ml). This vinblastine dosage had a severe inhibitory effect on cultures treated with Cyt B, where no binucleated cells were detected. At all doses, a relatively greater mitotic index was observed in cultures with Cyt B, suggesting a synergistic effect of this drug with vinblastine. Most notably, at the two highest vinblastine dosages (10 and 20 ng/ml), a large incidence of polyploid nuclei was observed in cytokinesis-blocked cultures, whereas none or far lower increases of polyploidy were found in the absence or Cyt. B. This results provides direct evidence of the potential of Cyt B to indirectly interfere with chromosome misdistribution induced by a spindle poison, to be considered before drawing firm conclusions from kinesis-blocked systems.

Adult↗

Summation of texture segregation across orientation and spatial frequency: electrophysiological and psychophysical findings.

Objects are usually segregated from ground by several visual dimensions. We studied texture segregation in checkerboards defined by gradients in spatial frequency, orientation or both frequency and orientation, using Gabor-filtered noise patterns. Saliency was measured electrophysiologically using the visual evoked potential (VEP) associated with texture segregation ('tsVEP') (an associated component in the visual evoked potential), and psychophysically by a 2AFC task. Spatial frequency and orientation stimuli evoked percepts of texture segregation and tsVEPs in all 11 subjects. The tsVEPs to combined stimuli were larger than those to each dimension alone, but smaller (74%) than the algebraic sum of tsVEPs to both individual dimensions. Psychophysical detection rates differed significantly between all conditions (P < 0.001), with highest rates for the combined stimuli. The findings suggest that segregation based on a combination of 'orientation' and 'spatial frequency' is more salient than that based on either of these alone. The significant deviation from full additivity in the tsVEPs suggests that simultaneous contrasts in spatial frequency and orientation have a common processing stage.

Evoked Potentials, Visual↗

Temporal resolution of orientation-based texture segregation.

We analysed the temporal-frequency characteristics of two functional processes involved in orientation-based texture segregation: local orientation coding and subsequent orientation-contrast coding. Two texture images, in which each micropattern was rotated by 90 degrees, were alternated at various temporal frequencies. A micropattern was a second-derivative (D2) of a Gaussian that loses orientation information when temporally fused with the orthogonal D2 pattern. We measured the upper temporal-frequency limits for localising the target region whose mean orientation differed from the background by 90 degrees or by 45 degrees. If the temporal limit of the texture perception is determined by the most sluggish processing stage, the temporal limit for the 90 degrees texture should be determined by local orientation coding or by orientation-contrast coding, depending on which stage has the lower temporal precision. On the other hand, the 45 degrees texture should always be segregated below the temporal limit of local orientation coding regardless of the temporal limit of orientation-contrast coding. We found that the temporal limit for the 90 degrees texture was slightly higher than that for the 45 degrees texture under spatial conditions appropriate for texture segregation. Moreover, an orientation-noise analysis of segregation performance for a wide range of temporal frequencies revealed that the temporal-frequency sensitivities for the two textures were nearly identical. These results imply that the temporal limit for orientation-based texture segregation depends only on that of local orientation coding. This conclusion further suggests that the potential temporal resolution of orientation-contrast coding is not lower than that of local orientation coding, which would imply that the orientation-contrast coding is unlikely to be mediated by sluggish neural processes.

Contrast Sensitivity↗

Stereoscopic segregation of transparent surfaces and the effect of motion contrast.

Stereoscopic segregation in depth was studied using two superimposed frontoparallel surfaces displayed in dynamic random dot stereograms. The two patterns were positioned symmetrically in front of and behind a binocular fixation point. They were either stationary, or they could move relative to each other. Sensitivity for segregation was established by adding gaussian distributed disparity noise to the disparities specifying the two planes, and finding the noise amplitude that gave threshold segregation performance. Observers easily segregate the two surfaces for disparity differences between approximately 6 and 30-40 arcmin. Motion contrast, which by itself provides no cue to perform the task, greatly improves sensitivity for segregation. Noise tolerance rises by a factor of two or more when the patterns move at different speeds, or in different (frontoparallel) directions. The effect increases with directional difference, but the optimal directional difference deviated from 180 deg. The optimal speed varies with disparity difference. Thus, motion and disparity must interact in order to resolve the two transparent planes.

Depth Perception↗

Residential segregation and mortality in New York City.

The objective of this research was to determine the effect of residential racial segregation on all-cause and cardiovascular disease mortality in New York City. A cross-sectional study of residents in New York City was conducted linking mortality records from 1988 through 1994, to the 1990 United States Census data stratified by zipcode. All-cause and cardiovascular disease mortality rates for non-Hispanic blacks and whites were estimated by zipcode. Zipcodes were aggregated according to the degree of residential segregation (predominantly (> or = 75%) white and black areas) and mortality rates were compared. Multiple regression analysis was used to associate population characteristics with mortality. In New York City, although overall mortality rates of blacks exceed whites, these rates varied substantially by locality according to the pattern of racial segregation. Whites living in the higher (mainly white) socioeconomic areas had lower mortality rates than whites living in predominantly black areas (1473.7 vs 1934.1 for males, and 909.9 vs 1414.7 for females for all-cause mortality). This was true for all age groups. By contrast, elderly blacks living in black areas, despite their less favorable socioeconomic status, had lower mortality rates for all-cause, total cardiovascular disease, and coronary heart disease, than did those living in white areas, even after adjusting for available socioeconomic variables. Racial segregation in residence is independently associated with mortality. Within racially segregated areas, members of the dominant group, for all age, among whites and elderly blacks, enjoy outcomes superior both to members of the minority racial group of their community, and to members of the same race residing in other areas, where they are in the minority, independent of socio-economic status.

Adult↗