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PubMed2004

Convergence and segregation of the multiple rod pathways in mammalian retina.

Using a multidisciplinary approach, we demonstrate that three different pathways are responsible for the transmission of rod signals across the mouse retina. Each pathway serves a primarily nonoverlapping range of stimulus intensities, with ganglion cells receiving either segregated or convergent inputs. For both on-center (ON) and off-center (OFF) ganglion cells, the primary rod pathway carries signals with the lowest threshold, whereas the secondary rod pathway is less sensitive by approximately 1 log unit. In addition, OFF signaling uses a tertiary rod pathway that is approximately 1 log unit less sensitive than the secondary. Although some ganglion cells received rod inputs exclusively from one of the pathways, others showed convergent inputs. Using pharmacological and genetic approaches, we defined classes of ON and OFF ganglion cells for which the scotopic inputs derive only from the primary pathway or from both primary and secondary pathways. In addition, we observed a class of OFF ganglion cell receiving mixed input from primary and tertiary pathways. Interestingly, OFF ganglion cells receiving convergent inputs from all three rod pathways or from the secondary and tertiary pathways together were never observed. Overall, our data show a complex arrangement of convergence and segregation of rod inputs to ganglion cells in the mammalian retina.

Action Potentials↗
PubMed2005

Thalamic neuronal activity in dopamine-depleted primates: evidence for a loss of functional segregation within basal ganglia circuits.

Different analyses of neuronal activity in primate models of Parkinson's disease (PD) have resulted in two different views on the effects of dopamine depletion. The first is based on the higher firing rate and bursty firing pattern, and assumes that dopamine depletion results in a hyperactivity of basal ganglia (BG) output structures. The second is based on the less-specific responses to passive joint manipulation and the excessive correlations between neuronal discharges, and assumes that dopamine depletion results in a loss of functional segregation in cortico-BG circuits. The aim of the present study was to test out the predictions of these two different views on thalamic neuronal activity. Three male vervet monkeys (Cercopithecus aethiops) were progressively intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neuronal activities were characterized using standard analyses (firing rates and patterns, receptive fields, and cross-correlations) and compared between the normal, asymptomatic (before the stabilization of motor symptoms), and parkinsonian (with persistent akinesia and rigidity) stages of MPTP intoxication. The pallidonigral thalamus (receiving projections from the BG) was characterized in both the asymptomatic and parkinsonian states by (1) an unchanged firing rate and pattern and (2) a proliferation of nonspecific neurons and correlated pairs. In contrast, the cerebellar thalamus (receiving projections from the cerebellum), was characterized by no change (asymptomatic state) or minor changes (symptomatic state). Thus the major dysfunction after dopamine depletion appeared to be the loss of functional segregation within cortico-BG circuits, which could also be at the heart of parkinsonian pathophysiology.

Action Potentials↗
PubMed2006

Ligand detection and discrimination by spatial relocalization: A kinase-phosphatase segregation model of TCR activation.

We develop a model of tyrosine phosphorylation and activation of the T-cell receptor (TCR) by localization to regions of close membrane-membrane proximity (close contact) that physically exclude tyrosine phosphatases such as CD45. Phosphatase exclusion generates regions of low phosphatase and high kinase activity and thus our model provides a framework to examine the kinetic segregation model of TCR activation. We incorporate a sequence of activation steps modeling the construction of the signalosome with a final sequestered, or high-stability, signaling state. The residence time of unbound TCRs in tyrosine kinase-rich domains is shown to be too short for accumulation of activation steps, whereas binding to an agonist lengthens the localization time and leads to generation of fully active TCRs. Agonist detection depends only on this localization, and therefore kinetic segregation represents a viable ligand detection mechanism, or signal transduction mechanism across membranes, distinct from receptor oligomerization and conformational change. We examine the degree of discrimination of agonists from a background of null (self) peptides, and from weak agonists achievable by this mechanism.

Animals↗
PubMed2004

Naturally segregating quantitative trait loci affecting wing shape of Drosophila melanogaster.

Variation in vein position and wing shape of Drosophila melanogaster depends on many genes. In the following, we report the results of a QTL analysis of wing shape in D. melanogaster. We identified QTL responsible for natural variation for wing shape and analyzed their interactions with developmental genetic signaling pathways important for vein positioning. The QTL analysis indicated that the total number of QTL segregating in this population is likely to be very large. The locations of putative QTL identified in this study were compared to those identified in previous studies and, while there is more correspondence across studies than expected by chance on the third chromosome, the studies appear to have identified different QTL. Using a complementation design, we tested for interactions among these QTL with the Hedgehog and Decapentaplegic signaling pathways, which are important for the development and position of vein pairs L3-L4 and L2-L5. Three QTL showed strong interactions with these two pathways, supporting the hypothesis that these QTL are involved in these pathways. Naturally segregating variation can therefore act through known signaling pathways to produce variation in vein position.

Animals↗
PubMed2005

Genetical genomics analysis of a yeast segregant population for transcription network inference.

Genetic analysis of gene expression in a segregating population, which is expression profiled and genotyped at DNA markers throughout the genome, can reveal regulatory networks of polymorphic genes. We propose an analysis strategy with several steps: (1) genome-wide QTL analysis of all expression profiles to identify eQTL confidence regions, followed by fine mapping of identified eQTL; (2) identification of regulatory candidate genes in each eQTL region; (3) correlation analysis of the expression profiles of the candidates in any eQTL region with the gene affected by the eQTL to reduce the number of candidates; (4) drawing directional links from retained regulatory candidate genes to genes affected by the eQTL and joining links to form networks; and (5) statistical validation and refinement of the inferred network structure. Here, we apply an initial implementation of this strategy to a segregating yeast population. In 65, 7, and 28% of the identified eQTL regions, a single candidate regulatory gene, no gene, or more than one gene was retained in step 3, respectively. Overall, 768 putative regulatory links were retained, 331 of which are the strongest candidate links, as they were retained in the expression correlation analysis and were located within or near an eQTL subregion identified by a multimarker analysis separating multiple linked QTL. One or several biological processes were statistically significantly overrepresented in independent network structures or in highly interconnected subnetworks. Most of the transcription factors found in the inferred network had a putative regulatory link to only one other gene or exhibited cis-regulation.

DNA↗
PubMed2005

Systematic segregation to mutant mitochondrial DNA and accompanying loss of mitochondrial DNA in human NT2 teratocarcinoma Cybrids.

In this study a well-characterized pathological mutation at nucleotide position 3243 of human mitochondrial DNA was introduced into human rho(0) teratocarcinoma (NT2) cells. In cloned and mixed populations of NT2 cells heteroplasmic for the mutation, mitotic segregation toward increasing levels of mutant mitochondrial DNA always occurred. Rapid segregation was frequently followed by complete loss of mitochondrial DNA. These findings support the idea that pathological mitochondrial DNA mutations are particularly deleterious in specific cell types, which can explain some of the tissue-specific aspects of mitochondrial DNA diseases. Moreover, these findings suggest that mitochondrial DNA depletion may be an important and widespread feature of mitochondrial DNA disease.

Cell Line, Tumor↗
PubMed2005

The evolution of cytoplasmic incompatibility types: integrating segregation, inbreeding and outbreeding.

Cytoplasmic incompatibility (CI) is a reproductive incompatibility induced by maternally transmitted bacteria of the genera Wolbachia and Cardinium. In the simplest form of CI, offspring from infected males and uninfected females suffer from increased mortality. However, it has been noted that crosses between males and females carrying different strains of infection are often also incompatible. The evolutionary processes leading to the emergence of new CI-compatibility types are still not resolved. Here, we develop a model that extends previous theoretical approaches by including segregation of bacterial strains during transmission as well as a continuum of breeding systems ranging from inbreeding (complete sib mating) to outbreeding (complete sib-mating avoidance). Our results demonstrate that (1) with segregation of strains, evolution is unlikely to lead to new CI types that co-occur as a double infection with the preexisting one, (2) inbreeding substantially hampers the evolution of new CI types, and (3) outbreeding facilitates the evolution of new CI types. Our model also provides a hypothesis on the evolutionary origin of CI.

Bacteria↗
PubMed2004

Heritability and segregation analysis of deafness in U.S. Dalmatians.

Hereditary loss of hearing affects many breeds of the domestic dog, but the Dalmatian has the highest prevalence. Approximately 30% are affected in the United States (U.S.) population. It is widely accepted that a relationship exists between deafness and pigmentation in the dog and also in other animals. While the Dalmatian exemplifies this relationship, the genetic origin and mode of inheritance of deafness in this breed are unknown. The goals of this study were to: (1) estimate the heritability of deafness in an extended kindred of U.S. Dalmatians and (2) determine, through complex segregation analysis, whether there is a major segregating locus that has a large effect on the expression of deafness. A kindred of 266 Dalmatians was assembled, of which 199 had been diagnosed using the brainstem auditory evoked response to determine auditory status. Of these, 74.4% (N = 148) had normal hearing, 18.1% (N = 36) were unilaterally deaf, and 7.5% (N = 15) were bilaterally deaf. A heritability of 0.73 was estimated considering deafness a dichotomous trait and 0.75 considering it as a trichotomous trait. Although deafness in the Dalmatian is clearly heritable, the evidence for the presence of a single major gene affecting the disorder is not persuasive.

Animals↗
PubMed2003

The first international leprosy conference, Berlin, 1897: the politics of segregation.

The present paper examines the first attempts to internationalize the problem of leprosy, a subject hitherto overlooked by historians of imperialism and disease. The last decade of the nineteenth century saw many in the 'civilized countries' of the imperialist West gripped by a paranoia about an invasion of leprosy via germ-laden immigrants and returning expatriates who had acquired the infection in leprosy-endemic colonial possessions. Such alarmists clamoured for the adoption of vigorous leper segregation policies in such colonies. But the contagiousness of leprosy did not go unquestioned by other westerners. The convocation in Berlin of the first international meeting on leprosy revealed the interplay of differing and sometimes incompatible views about the containment of leprosy by segregation. The roles of officials from several countries, as well as the roles of five protagonists (Albert Ashmead, Jules Goldschmidt, Edvard Ehlers, Armauer Hansen, and Phineas Abraham) in the shaping of the Berlin Conference are here examined.

Colonialism↗
PubMed1982

Is smoker/nonsmoker segregation effective in reducing passive inhalation among nonsmokers?

Using expired carbon monoxide (CO) and a test of coordination as measures of tobacco smoke exposure in a natural environmental setting where smokers and nonsmokers were segregated, results indicate that by comparison to a control group, subjects seated in adjacent smoking/ nonsmoking environments were not only exposed to similar ambient levels of CO, but also show similar physical and physiological reactions to their exposure in the form of coordination test scores, expired CO, and blood carboxyhemoglobin. While the results may not be generalized to other tobacco smoke constituents or other environmental settings, they raise questions about the health benefits of smoker segregation which future research must address.

Adult↗
PubMed1996

Trends in US urban black infant mortality, by degree of residential segregation.

Trends in Black infant mortality rates from 1982 through 1991 in large US metropolitan statistical areas were examined. In some least-segregated areas, the total Black infant mortality rate reached a low of 13 per 1000 live births in 1985; it increased sharply after 1985 in the West but not in the South. The explanation for these trends is unknown, but variation in regional trends in Black postneonatal infant mortality rates suggested that social and medical-care differences among Blacks should be examined. A high Black infant mortality rate for a group of most-segregated metropolitan statistical areas persisted and contributed to the rising Black-White ratio of rates.

Black or African American↗
PubMed2000

Complex segregation analysis of deafness in Dalmatians.

OBJECTIVE: To use pedigree analysis to evaluate the feasibility of a major locus model for deafness in Dalmatians. ANIMALS: 605 purebred Dalmatians from 42 families. PROCEDURE: Hearing loss was evaluated through the brainstem auditory-evoked response. Dogs were classified into mutually exclusive categories: normal hearing, unilaterally deaf, or bilaterally deaf. Information was collected on sex, coat color, presence or absence of a color patch at birth, and eye color. Statistical analyses were performed by use of regressive logistic models designed for complex segregation analysis. Genetic correlations among eye color, deafness, and color patch were estimated. RESULTS: Prevalence of hearing loss was 11% for dogs classified as unilaterally deaf and 5% for dogs that were bilaterally deaf. Complex segregation analysis detected statistical evidence of a single allele with an expected frequency of 0.21 that had an effect on the prevalence of deafness. Results of analyses suggested that this locus cannot completely explain the inheritance and incidence of deafness in Dalmatians. Genetic correlation estimates among deafness, eye color, and color patch revealed strong interrelationships among these characteristics. CONCLUSIONS AND CLINICAL RELEVANCE: To reduce the incidence of hearing loss in Dalmatians, unilaterally deaf, blue-eyed dogs should not be considered as potential parents.

Alleles↗
PubMed1999

Individual differences in textural segregation.

Dimensional interactions of width and orientation stimuli in early visual processing were assessed in a texture-segregation paradigm. The basis for detecting a discrepant quadrant in 6 x 6 arrays of objects was varied in accordance with Garner's Control, Correlated, and Orthogonal conditions. Individual differences as measured by Witkin's Group Embedded Figures Task differentiated performance patterns on the texture-segregation task. Individuals with high scores on the Embedded Figures Test, termed Field-independent, exhibited redundancy gains in the Correlated condition and no interference in the Orthogonal condition whereas those scoring low, termed Field-dependent, demonstrated no redundancy gains and no interference effects. Results support recent findings that individual differences in field dependence-independence are associated with differences in low-level visual mechanisms and suggest that individual differences in attentional flexibility exist in early visual processing.

Attention↗
PubMed1995

The effect of dietary methionine and its relationship to lysine on growth performance of the segregated early-weaned pig.

Two experiments were conducted to determine the dietary methionine requirement and the appropriate methionine:lysine for the segregated early weaned-weaned pig. In Exp. 1, 435 crossbred pigs (9.5 +/- 4 d of age and 3.5 kg BW) were fed diets (1.8% lysine, .62% cystine) containing 10% spray-dried plasma protein (SDPP) and 1.75% spray-dried blood meal (SDBM) from day 0 to 21 postweaning. Pigs were feed one of six dietary treatments from .36% to .56% total dietary methionine (.317 to .517% apparent digestible methionine). From d 0 to 7 and d 0 to 21 postweaning, ADG and gain:feed ratio (G/F) increased (linear, P < .01, P < .05, respectively) as dietary methionine increased. In Exp. 2, 350 crossbred pigs (9.0 +/- 2 d of age and 3.8 kg BW) were used to determine the appropriate methionine:lysine ratio for the segregated early-weaned pig in a 2 x 5 factorial arrangement. Two lysine levels (1.8 and 1.4%) and five methionine levels within each lysine level were used to obtain methionine:lysine ratios ranging from 21.5 to 33.5%. From d 0 to 21 postweaning, pigs were assigned to one of 10 dietary treatments containing 25% dried whey, 12% lactose, 7.5% SDPP, 6.0% select menhaden fish meal, and 1.75% SDBM. No methionine x lysine interactions were observed (P > .10). From d 0 to 7 postweaning, increasing dietary methionine improved (quadratic, P < .01) ADG and ADFI regardless of dietary lysine. From d 0 to 14 postweaning, increasing dietary methionine improved ADG (quadratic, P < .01), ADFI quadratic, P =.02), and G/F (quadratic, P < .10). Inflection point analysis projected maximum ADG at methionine:lysine ratios of 27 and 27.5% for pigs fed 1.4 and 1.8% lysine, respectively. Cumulative (d 0 to 21 postweaning) ADG, ADFI, and G/F were improved (quadratic, P < .05) by increasing dietary methionine. Increasing dietary lysine improved (P < .01) ADG and G/F from d 0 to 7, from d 0 to 14, and for the overall experiment. In conclusion, a diet with 1.8% total lysine that includes spray-dried blood products must contain .48 to .52% total dietary methionine (.437 to .477% apparent digestible) or 27.5% of total lysine to maximize growth performance of pigs from d 0 to 21 postweaning (3.5 to 12 kg BW).

Aging↗
PubMed1999

Effect of segregated early weaning on postweaning small intestinal development in pigs.

The effect of segregated early weaning (SEW) on postweaning small intestinal development was investigated in SEW and control (CON) pigs. Small intestines were collected from a total of 15 pigs killed at 11 (preweaning), 15 (3 d postweaning), and 34 d of age. At 3 d postweaning, the SEW and CON pigs had shorter villi (P<.01), deeper crypts (P<.01), and reduced (P<.01) ratios of villus height:crypt depth (V:C) compared with preweaning. Weaning also reduced specific activities of lactase (P<.01) in duodenum and ileum and alkaline phosphatase (ALP) (P<.05) in duodenum and jejunum. Sucrase activity in the three regions of the small intestine marginally decreased in both groups at 3 d postweaning. The mucosal protein:DNA ratio in duodenum and jejunum increased (P<.05) in SEW and CON pigs at 3 d postweaning compared with preweaning pigs. The SEW and CON treatments resulted in differences in postweaning gut development. At 15 d of age in SEW pigs, the mucosal protein:DNA ratio in duodenum and jejunum were 20 and 25.5% (P<.05) less, respectively, than those in CON pigs. However, at 34 d, these ratios in duodenum, jejunum, and ileum were 43.5 (P<.05), 24.3, and 32.9% (P<.05) greater, respectively, in SEW pigs than in CON pigs. Longer villi, shorter crypts (P<.01), and higher V:C ratios (P<.01) in jejunum and ileum were observed in SEW pigs vs CON pigs at 34 d of age. The specific activities of lactase in duodenum (P<.01) and jejunum (P<.05) and of ALP in duodenum (P<.01) were higher in SEW pigs. Sucrase activity in duodenum, jejunum, and ileum was 21.7, 46.3 (P<.05), and 11.2% greater in SEW pigs at 34 d of age. These results demonstrate differences in postweaning gut development between SEW and CON pigs. Furthermore, the number of intraepithelial lymphocytes in jejunum was greater (P<.001) in 34-d-old SEW pigs compared with CON pigs. Microscopy revealed a thick mucus coating over epithelial cells in the ileum of 34-d-old CON pigs that was not apparent in the SEW pigs. These observations are consistent with reduced pathogen exposure associated with SEW. We suggest that segregated early weaning advances postweaning gut maturation, which is consistent with improved growth and feed efficiency observed in SEW pigs.

Animals↗
PubMed2001

Bayesian segregation analysis of somatic cell scores of Ontario Holstein cattle.

Bayesian segregation analysis using a Gibbs sampling approach was applied to four sets of simulated data and one set of field data to detect evidence of major genes affecting the evaluated trait. The substitution effect of a major gene and its allelic frequency were estimated for each set of data. For two datasets simulated with a model with no major gene effect, the resulting estimates of polygenic variance and heritability agreed with the simulated values and tests for the presence of a major gene were not significant. Analyses of two sets of data simulated with a major gene produced posterior distributions that gave significant evidence of major gene effects but underestimated the substitution values of the major gene. The segregation analysis of field data suggested that a major gene significantly affected somatic cell score (SCS) in the population of Ontario Holstein cattle. The estimated heritability of SCS was approximately 0.16. The major gene variance accounted for about 17% of the total genetic variance and the point estimate of the frequency of the allele having a positive effect on SCS was 0.30. However, the precision of these estimates is questionable based on the simulation results. The effect of the major gene may be underestimated.

Animals↗
PubMed1995

Segregation by color and stereoscopic depth in three-dimensional visual space.

Two experiments were conducted to investigate how color and stereoscopic depth information are used to segregate objects for visual search in three-dimensional (3-D) visual space. Eight observers were asked to indicate the alphanumeric category (letter or digit) of the target which had its unique color and unique depth plane. In Experiment 1, distractors sharing a common depth plane or a common color appeared in spatial contiguity in the xy plane. The results suggest that visual search for the target involves examination of kernels formed by homogeneous items sharing the same color and depth. In Experiment 2, the xy contiguity of distractors sharing a common color or a common depth plane was varied. The results showed that when target-distractor distinction becomes more difficult on one dimension, the other dimension becomes more important in performing visual search, as indicated by a larger effect on search time. This suggests that observers can make optimal use of the information available. Finally, color had a larger effect on search time than did stereoscopic depth. Overall, the results support models of visual processing which maintain that perceptual segregation and selective attention are determined by similarity among objects in 3-D visual space on both spatial and nonspatial stimulus dimensions.

Color Perception↗
PubMed1999

Attention-based texture segregation.

Luminance- or color-defined +/- 45 degrees-oriented bars were arranged to yield single-feature or double-conjunction texture pairs. In the former, the global edge between two regions is formed by differences in one attribute (orientation, or color, or luminance). In the color/orientation double-conjunction pair, one region has +45 degrees red and -45 degrees green textels, the other -45 degrees red and +45 degrees green textels (the luminance/orientation double-conjunction pair is similar); such a pair contains a single-feature orientation edge in the subset of red (or green) textels, and a color edge in the subset of +45 degrees (or -45 degrees) textels. We studied whether edge detection improved when observers were instructed to attend to such subsets. Two groups of observers participated: in the test group, the stimulus construction was explained to observers, and they were cued to attend to one subset. The control group ran through the same total number of sessions without explanations/cues. The effect of cuing was week but statistically significant. Feature cuing was more effective for color/orientation than for luminance/orientation conjunctions. Within each stimulus category, performance was nearly the same no matter which subset was attended to. On average, a global performance improvement occurred over time even without cuing, but some observers did not improve with either cuing or practice. We discuss these results in the context of one-versus two-stage segregation theories, as well as by reference to signal enhancement versus noise suppression. We conclude that texture segregation can be improved by attentional strategies aimed to isolate specific stimulus features.

Adolescent↗