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Results for “differential selection”

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PubMed1999

Uterine and postnatal maternal effects in mice selected for differential rate of early development.

A series of mouse lines was produced by long-term restricted index selection for divergent rate of growth during early and late postnatal development. The selection program was based on the following treatments: E(+) and E(-) lines were selected to alter birth to 10-day weight gain while holding late gain for both lines constant and a control line was established via random selection. Using embryo transfer and crossfostering methodology, we partitioned postnatal growth for E(+), E(-), and C lines into progeny genetic, uterine maternal, and nurse maternal components. Selection for differential early growth resulted in correlated response in uterine and nurse maternal effects on body weights, with significant genetic-by-environment interactions. Significant uterine effects were also observed in tail length measurements. Direct uterine effects on body weight were relatively small and resulted in growth rate differences early in development. Nurse effects were large, resulting in modification of progeny growth trajectory especially during early postnatal development. Genetic-by-uterine interactions were large and demonstrate progeny-specific effects of the prenatal uterine environment.

Analysis of Variance↗
PubMed1988

Relationship of plasma growth hormone to growth within and between turkey lines selected for differential growth rates.

The ontogeny of plasma growth hormone (GH) was determined within and between genetically-related turkey lines selected for differential growth rates. Blood samples were obtained at weekly intervals from hatching through 195 days of age from male and female poults of a slow-growing, randombred line (RBC-2), representing the base population, and a fast-growing line selected over 20 generations from RBC-2 for increased 16-wk body weight (F). Growth rate of the F line exceeded that of RBC-2 during the very early (0 to 14 day) posthatch period (P less than .05), but was not different from that of the RBC-2 line by 77 to 195 days of age. Males of both lines were larger than females at all ages (P less than .05). Plasma GH increased from hatching until 2 wk of age and declined thereafter in both lines. Differences between overall plasma GH concentrations of the lines were not observed during the 0 to 14 day period, but concentrations were higher (P less than .05) in RBC-2 than F birds thereafter (21 to 195 days of age). Plasma GH concentrations initially (0 to 14 days) were higher in females than in males for both lines (P less than .05), but thereafter (21 to 195 days) declined more rapidly and averaged lower overall in females than in males (P less than .05). Correlations between measures of GH and growth rate within lines over age were strongly positive (r = .83 to .93; P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

The geographic mosaic in predispersal interactions and selection on Helleborus foetidus (Ranunculaceae).

We examine the hierarchical geographic structure of the interaction between a plant, Helleborus foetidus, and its floral herbivores and pollinators (interactors). Six populations from three distant regions of the Iberian Peninsula were used to examine intra- and inter-regional variation in plant traits, interactors and plant fecundity, and to compare, through selection gradient and path analyses, which traits were under selection, and which interactors were responsible for differential selection. Geographic and temporal congruency in interactor-mediated selection was further tested using a recent analytical approach based on multi-group comparison in Structural Equation Models. Most plant traits, interactors and fecundity differed among regions but not between populations. Similarly, the identity of the traits under selection, the selection gradients (strength and/or the direction of the selection) and the path coefficients (identifying the ecological basis for selection) varied inter- but not intra-regionally. Results show a selection mosaic at the broad scale and, for some traits, a link of differential selection to trait differentiation.

Ecosystem↗
PubMed1998

Differentiation: the selective potentiation of chromatin domains.

Potentiation is requisite for the expression of our genome. It is the mechanism of opening chromatin domains to render genes accessible to tissue-specific and ubiquitous transacting-factors that enables transcription. The results presented in this study demonstrate that modulation of stage- and cell-type-specific gene expression during mammalian spermatogenesis involves selective potentiation of testis-expressed genes that reverses their repressive state when present in the spermatogonial stem cell. This directly contrasts hematopoiesis, which acts to selectively restrict lineage potential during differentiation from its permissive stem cell. These results are key to understanding how differentiative pathways are controlled and cellular phenotypes determined. A window to their modulation is presented.

Aging↗
PubMed2004

Identification of amino acid residues that direct differential ligand selectivity of mammalian and nonmammalian V1a type receptors for arginine vasopressin and vasotocin. Insights into molecular coevolution of V1a type receptors and their ligands.

Arginine vasotocin (VT) is the ortholog in all nonmammalian vertebrates of arginine vasopressin (AVP) in mammals. We have previously cloned an amphibian V1atype vasotocin receptor (VT1R) that exhibited higher sensitivity for VT than AVP, while the mammalian V1a type receptor (V1aR) responded better to AVP than VT. In the present study, we identified the amino acid residues that confer differential ligand selectivity for AVP and VT between rat V1aR and bullfrog VT1R (bfVT1R). A chimeric rat V1aR having transmembrane domain (TMD) VI to the carboxyl-terminal tail (C-tail) of bfVT1R showed a reverse ligand preference for AVP and VT, whereas a chimeric VT1R with TMD VI to the C-tail of rat V1aR showed a great increase in sensitivity for AVP. A single mutation (Ile(315(6.53)) to Thr) in TMD VI of V1aR increased the sensitivity for VT, while a single mutation (Phe(313(6.51)) to Tyr or Pro(334(7.33)) to Thr) reduced sensitivity toward AVP. Interestingly the triple mutation (Phe(313(6.51)) to Tyr, Ile(6.53) to Thr, and Pro(7.33) to Thr) of V1aR increased sensitivity to VT but greatly reduced sensitivity to AVP, behaving like bfVT1R. Further, like V1aR, a double mutant (Tyr(306(6.51)) to Phe and Thr(327(7.33)) to Pro) of bfVT1R showed an increased sensitivity to AVP. These results suggest that Phe/Tyr(6.51), Ile/Thr(6.53), and Pro/Thr(7.33) are responsible for the differential ligand selectivity between rat V1aR and bfVT1R. This information regarding the molecular interaction of VT/AVP with their receptors may have important implications for the development of novel AVP analogs.

Amino Acid Sequence↗
PubMed1984

A selective and differential agar for anaerobic comma-shaped bacteria recovered from patients having motile rods and non-specific vaginosis.

A selective and differential agar for optimal growth of the large curved motile anaerobic rods isolated from patients having non-specific vaginosis (NSV) was developed. A basal medium of Columbia CNA agar was used with colony growth found to be optimal by the addition of 7% fetal calf serum and 5% rabbit blood (CNARS). Beta-Haemolysis was found to be demonstrated most readily on a bilayer plate with a basal layer consisting of CNA agar with fetal calf serum, overlaid with a layer of CNA agar containing fetal calf serum and rabbit blood. Optimal growth was found by anaerobic incubation at 37 degrees C, after 5 days.

Agar↗
PubMed1995

Asymmetric signaling requirements for thymocyte commitment to the CD4+ versus CD8+ T cell lineages: a new perspective on thymic commitment and selection.

Differentiation of immature CD4+ CD8+ thymocytes into mature CD4+ CD8- and CD4-CD8+ T cells requires that synthesis of one or the other coreceptor molecule be terminated, a process referred to as lineage commitment. The present study has utilized a novel coreceptor reexpression assay to identify lineage commitment in immature thymocytes and has found that the MHC recognition requirements for CD4 commitment and CD8 commitment fundamentally differ from one another. Remarkably, we found that thymocyte commitment to the CD8+ lineage requires MHC class I-dependent instructional signals, whereas thymocyte commitment to the CD4+ lineage is MHC independent and may occur by default. In addition, an unanticipated relationship between lineage commitment and surface phenotype has been identified. These results are incompatible with current concepts and require a new perspective on lineage commitment and positive selection, which we refer to as asymmetric commitment.

Animals↗
PubMed1995

Early molecular events induced by T cell receptor (TCR) signaling in immature CD4+ CD8+ thymocytes: increased synthesis of TCR-alpha protein is an early response to TCR signaling that compensates for TCR-alpha instability, improves TCR assembly, and parallels other indicators of positive selection.

Differentiation of immature CD4+ CD8+ thymocytes into mature CD4+ or CD8+ T cells occurs within the thymus and is dependent upon expression of antigen receptor complexes (T cell receptor [TCR]) containing clonotypic alpha/beta proteins. We have recently found that CD4+ CD8+ thymocytes express low levels of surface TCR because of limitations placed on TCR assembly by the instability of nascent TCR-alpha proteins within the endoplasmic reticulum (ER) of immature thymocytes. Because TCR-alpha/beta expression increases during development, a molecular mechanism must exist for increasing the number of assembled TCR complexes present in immature CD4+ CD8+ thymocytes that have been signaled to differentiate into mature T cells, although no such mechanism has yet been described. In the current report we have examined the molecular consequences of intracellular signals generated by engagement of surface TCR complexes on immature CD4+ CD8+ thymocytes. Isolated TCR engagement generated signals that increased TCR-alpha RNA levels and increased synthesis of TCR-alpha proteins, which, in turn, significantly increased assembly of complete TCR-alpha/beta complexes in CD4+ CD8+ thymocytes. Increased TCR-alpha protein levels in TCR-signaled CD4+ CD8+ thymocytes was the result of increased synthesis and not increased stability of TCR-alpha proteins, indicating that TCR engagement compensates for, but does not correct, the inherent instability of TCR-alpha proteins in the ER of immature thymocytes. Consistent with the delivery by TCR engagement of a positive selection signal, TCR engagement also increased CD5 expression, decreased RAG-1 expression, and decreased CD4/CD8 coreceptor expression in immature CD4+ CD8+ thymocytes. These data identify amplified TCR-alpha expression as an initial response of immature CD4+ CD8+ thymocytes to TCR-mediated positive selection signals and provide a molecular basis for increased surface TCR density on developing thymocytes undergoing selection events within the thymus.

Animals↗
PubMed1997

A method for assessing age-time disease incidence using serial prevalence data.

This paper considers nonparametric estimation of age- and time-specific trends in disease incidence using serial prevalence data collected from multiple cross-sectional samples of a population over time. The methodology accounts for differential selection of diseased and undiseased individuals resulting, for example, from differences in mortality. It is shown that when a log-linear incidence odds model is adopted, an EM algorithm provides a convenient method for carrying out maximum likelihood estimation, primarily using existing generalized linear models software. The procedure is quite general, allowing a range of age-time incidence models to be fitted under the same framework. Furthermore, by making use of existing software for fitting generalized additive models, the procedure can be generalized with virtually no extra complexity to allow maximization of a penalized likelihood for smooth nonparametric estimation. Automatic choice of smoothing level for the penalized likelihood estimates is discussed, using generalized cross-validation. The method is applied to a data set on serial toxoplasmosis prevalence, which has previously been analyzed under the assumption of nondifferential selection. A variety of age-time incidence models are fitted, and the sensitivity to plausible differential selection patterns is considered. It is found that nonmultiplicative models are unnecessary and that qualitative incidence trends are fairly robust to differential selection.

Algorithms↗
PubMed2005

Role for Runx1 in the proliferation and neuronal differentiation of selected progenitor cells in the mammalian nervous system.

Neurogenesis requires factors that regulate the decision of dividing progenitors to leave the cell cycle and activate the neuronal differentiation program. It is shown here that the murine runt-related gene Runx1 is expressed in proliferating cells on the basal side of the olfactory epithelium. These include both Mash1+ olfactory receptor neuron (ORN) progenitors and NeuroD+ ORN precursors. Disruption of Runx1 function in vivo does not cause a change in Mash1 expression but leads to a decrease in the number of NeuroD+ neuronal precursors and an increase in differentiated ORNs. These effects result in premature and ectopic ORN differentiation. It is shown further that exogenous Runx1 expression in cultured olfactory neural progenitors causes an expansion of the mitotic cell population. In agreement with these findings, exogenous Runx1 expression also promotes cortical neural progenitor cell proliferation without inhibiting neuronal differentiation. These effects are phenocopied by a chimeric protein containing ETO, the eight twenty one transcriptional repressor, fused to the Runx1 DNA-binding domain, which suggests the involvement of transcription repression mechanisms. Consistent with this possibility, Runx1 represses transcription driven by the promoter of the cell cycle inhibitor p21Cip 1 in cortical progenitors. Together, these findings suggest a previously unrecognized role for Runx1 in coordinating the proliferation and neuronal differentiation of selected populations of neural progenitors.

Amino Acid Substitution↗
PubMed1996

Development and evaluation of a selective and differential medium for the primary isolation of Peptostreptococcus micros.

Peptostreptococcus micros, an anaerobic gram-positive coccus, has been associated with periodontal and endodontic lesions, including those refractory to treatment, as well as many human polymicrobial infections in other body locations. A selective and differential medium for the primary isolation of P. micros was developed and evaluated. Columbia CNA agar, a selective medium for gram-positive cocci, was supplemented with glutathione and lead acetate (P. micros medium: PMM). P. micros has a characteristic of rapidly utilizing the reduced form of glutathione to form hydrogen sulfide, which reacts with lead acetate producing a black precipitate in the medium. When grown on PMM, P. micros can be easily identified by its typical colonial morphology and the presence of a black precipitate directly under the colony. PMM was compared for the growth of P. micros with phenylethyl alcohol agar (PEA) and Columbia base medium (CBM) with 80 strains of P. micros and 30 strains of other gram-positive cocci. All P. micros isolates tested grew and showed the typical morphology of P. micros on PMM. Using colony counts on CBM as controls, there was an average 81.8% recovery in the number of P. micros colonies on PMM, in contrast to an average 6.1% recovery on PEA. Subgingival plaque and tongue samples from 12 adult periodontitis and 6 early-onset periodontitis patients were cultured onto PMM for the isolation of P. micros. P. micros was isolated on PMM and identified biochemically and enzymatically from both adult periodontitis and early-onset periodontitis patients with higher percentages isolated from the diseased periodontal pockets of adult periodontitis patients; furthermore, this is the first isolation of P. micros from tongue samples taken from periodontally diseased patients. This medium in cultural studies will further our understanding and assist future investigations of P. micros involved in disease processes.

Agar↗
PubMed1979

Selective and differential medium for isolation of Clostridium difficile.

Clostridium difficile is a recognized cause of pseudomembranous (antimicrobial agent-associated) colitis and may be one of the causes of antimicrobial agent-induced diarrhea. A selective and differential agar medium that contains cycloserine, cefoxitin, fructose, and egg yolk (CCFA) was developed to facilitate the isolation of C. difficile from fecal specimens. Quantitative cultures of 16 stock strains of C. difficile on this medium (and on a medium containing cycloserine, fructose, and egg yolk) yielded counts equivalent to those obtained on blood agar; other media selective for clostridia, including Clostrisel agar, reinforced clostridial agar plus 0.2% para-cresol, and egg yolk-neomycin agar (the latter was inoculated with cultures subjected to prior heat shocking), were also tested and found to be inhibitory to the growth of C. difficile. Of 28 fecal or colostomy effluent specimens cultured on the above media, 14 yielded C. difficile. CCFA was found to be the most sensitive and selective of these media for the recovery of C. difficile. Colonies of C. difficile growing on CCFA had distinctive morphological and fluorescent properties which were sufficient for presumptive identification. CCFA should provide a rapid method for the screening of fecal specimens from patients with antimicrobial agent-associated diarrhea or colitis for C. difficile.

Animals↗
PubMed2006

Selection of differentially expressed genes in microarray data analysis.

One common objective in microarray experiments is to identify a subset of genes that express differentially among different experimental conditions, for example, between drug treatment and no drug treatment. Often, the goal is to determine the underlying relationship between poor versus good gene signatures for identifying biological functions or predicting specific therapeutic outcomes. Because of the complexity in studying hundreds or thousands of genes in an experiment, selection of a subset of genes to enhance relationships among the underlying biological structures or to improve prediction accuracy of clinical outcomes has been an important issue in microarray data analysis. Selection of differentially expressed genes is a two-step process. The first step is to select an appropriate test statistic and compute the P-value. The genes are ranked according to their P-values as evidence of differential expression. The second step is to assign a significance level, that is, to determine a cutoff threshold from the P-values in accordance with the study objective. In this paper, we consider four commonly used statistics, t-, S- (SAM), U-(Mann-Whitney) and M-statistics to compute the P-values for gene ranking. We consider the family-wise error and false discovery rate false-positive error-controlled procedures to select a limited number of genes, and a receiver-operating characteristic (ROC) approach to select a larger number of genes for assigning the significance level. The ROC approach is particularly useful in genomic/genetic profiling studies. The well-known colon cancer data containing 22 normal and 40 tumor tissues are used to illustrate different gene ranking and significance level assignment methods for applications to genomic/genetic profiling studies. The P-values computed from the t-, U- and M-statistics are very similar. We discuss the common practice that uses the P-value, false-positive error probability, as the primary criterion, and then uses the fold-change as a surrogate measure of biological significance for gene selection. The P-value and the fold-change can be pictorially shown simultaneously in a volcano plot. We also address several issues on gene selection.

Data Interpretation, Statistical↗
PubMed1989

Effect of GABAergic drugs on motor impairment from ethanol, barbital and lorazepam in rat lines selected for differential sensitivity to ethanol.

The effect of GABAergic drugs on the motor-impairing effects of ethanol, barbital, and lorazepam were studied in the ethanol-sensitive ANT (Alcohol Nontolerant) and ethanol-insensitive AT (Alcohol Tolerant) rat lines, selected for differential ethanol-induced motor impairment on the tilting plane. The basic population from which these rat lines were derived, the mixed (M) line, was also included in the study. The ANT rats were more sensitive to the intoxicating effects of ethanol, barbital, and lorazepam than the AT and M rats at the dose ranges tested. Picrotoxin antagonized motor impairment from all three drugs. Flumazenil (Ro 15-1788) antagonized only the effects of lorazepam, and isoniazid did not modify motor impairment induced by any of the three drugs. These results confirm that the selection of AT and ANT lines has not been specific to ethanol, and that it has increased sensitivity to ethanol, barbital, and lorazepam in the ANT rats rather than decreasing it in the AT rats relative to the M rats. The finding that picrotoxin counteracted motor impairment from ethanol, barbital, and lorazepam support the view that the GABAA receptor complex is important in mediating the intoxicating effects of these drugs. These results also suggest that the genetically-determined difference in sensitivity to ethanol between the rat lines involves GABAergic mechanisms, but it remains to be determined whether any part of the GABAA receptor itself has been affected by the selection program.

Animals↗
PubMed2006

Renewed selection for heat loss in mice: direct responses and correlated responses in feed intake, body weight, litter size, and conception rate.

Divergent selection in mice was renewed in 3 independent replicates for high (MH) and low (ML) heat loss. An unselected control (MC) was maintained in all replicates. Heat loss was measured for individual male mice for 15 h, overnight in direct calorimeters. After 16 initial generations of selection followed by 26 generations of relaxed selection, divergent selection resumed for 9 generations. The realized selection applied was very close to the maximum possible selection according to the criteria and protocol. Selection differentials were greater for high than for low selection due to greater variation in the MH line. When corrected for SD, standardized selection differentials were similar for MH and ML selection. Unintended selection in MC was negligible. Realized heritability for divergence was 0.14 +/- 0.01, which was considerably less than that realized during the initial generations of selection (0.28 +/- 0.03). Realized heritabilities for MH selection (0.16 +/- 0.05) and for ML selection (0.07 +/- 0.06) were less, especially for ML selection, than were observed in the earlier generations. The difference in heat loss between MH and ML males was 55.7% of the MC mean at generation 51, compared with a difference of 53.6% in generation 15; this difference had decreased to 34.4% at the end of the relaxed selection (generation 42). For feed intake between 8 and 11 wk, MH and ML males differed by 34.0% of the MC mean by the end of the selection process. Body weight at 12 wk for MH and ML males was less than for MC males. Litter size response was positively related to the heat loss response. Conception rate was poorer in MH matings than in MC and ML matings.

Animals↗
PubMed1991

Effect of neurotransmitter-selective drugs in mice selected for differential sensitivity to the hypothermic actions of ethanol.

Mice selectively bred for resistance (HOT) and sensitivity (COLD) to the hypothermic effect of EtOH were tested for their hypothermic response to neurotransmitter-specific drugs and for the effect of such drugs on EtOH induced hypothermia (HT). The drugs administered were the opiate drugs morphine, levorphanol and U50488H, the dopamine agonists apomorphine, LY171535 and SKF38393, the dopamine antagonist chlorpromazine, the alpha adrenergic agonist St587, the cholinergic agonist nicotine and amphetamine, which increases the release of catecholamines. All of the drugs tested, with the exception of SKF38393 and amphetamine, induced a hypothermic response in HOT and COLD mice. SKF38393 had no effect on body temperature or HT produced by EtOH. Amphetamine caused HT at low doses and hyperthermia at high doses. COLD mice were more sensitive than HOT mice to the hypothermic effect of morphine and levorphanol, mu-opiate agonists, and U50488H, a relatively specific kappa agonist. All of the other drugs tested were approximately equally potent in HOT and COLD mice. These results suggest that the differential sensitivity of HOT and COLD mice to EtOH-induced HT may be partially mediated through genetic changes in opiate mechanisms.

Animals↗
PubMed1997

Propofol-induced ataxia and hypnosis in rat lines selected for differential alcohol sensitivity.

An alcohol-sensitive rat line, selectively bred for high sensitivity to ethanol-induced motor impairment, also exhibits greater sensitivity to gamma-aminobutyric acid type A (GABAA) receptor agonists, such as benzodiazepines and barbiturates, than an alcohol-insensitive rat line. We have investigated whether this difference was also maintained for the most recent intravenous anaesthetic, propofol. Propofol (100 mg/kg, intraperitoneally) induced similar sleep times and produced identical plasma propofol concentrations in alcohol-sensitive and alcohol-insensitive rat lines. At lower doses (50 and 75, but not 25 mg/kg), propofol produced a greater motor impairment in a tilting plane test in alcohol-sensitive than alcohol-insensitive rats shortly after the injection. Binding of a convulsant, [35S]t-butylbicyclophosphorothionate, to cerebellar and cerebrocortical GABAA receptors in the presence of 2 microM GABA was similarly affected by low micromolar propofol concentrations in both rat lines, while in the absence of GABA, propofol was slightly less potent in the alcohol-sensitive than alcohol-insensitive line. These data indicate that alcohol-sensitive rats show transiently enhanced sensitivity to an ataxic, but not to a hypnotic dose of propofol, which cannot be explained by sensitivity differences to propofol in GABAA receptors determined in a binding assay using brain membrane homogenates.

Alcohol Drinking↗
PubMed1999

Endrin inhibits adipocyte differentiation by selectively altering expression pattern of CCAAT/enhancer binding protein-alpha in 3T3-L1 cells.

The effects of selected chlorinated cyclodiene pesticides on the adipocyte differentiation process were examined using the 3T3-L1 adipocyte model in vitro. Endrin was found to cause a dose-dependent inhibition of adipocyte differentiation in 3T3-L1 cells. Aldrin and dieldrin were less potent than endrin in interfering with the adipogenic process. Endrin's inhibitory effect was effective only when the pesticide was present in the medium during the first 48 h after exposure of 3T3-L1 cells to adipogenic inducers. Immunoblots analysis revealed that endrin caused a dose-dependent, selective inhibition of the intracellular levels of CCAAT enhancer binding protein (C/EBP)alpha without altering the expression patterns of C/EBPbeta or C/EBPdelta along the differentiation. Supershift analysis showed that DNA-binding capacity of C/EBPalpha was affected most by endrin treatment. Endrin also caused a decrease in the elevation of the adipogenic factor peroxisome proliferator-activated receptor (PPAR)gamma elicited by the adipogenic inducers. However, the cotreatment with troglitazone, a thiazolidinedione known to activate PPARgamma, did not suppress the antiadipogenic action of endrin, indicating that its direct action site is not PPARgamma receptor. Endrin also altered the pattern of activation of nuclear factor-kappaB, a factor activated by 12-O-tetradecanoylphorbol-13-acetate and tumor necrosis factor-alpha, which are known to interfere with adipocyte differentiation. Thus, endrin inhibited the normal decrease in nuclear factor-kappaB-DNA binding observed as cells are acquiring the adipocyte phenotype at a late stage of differentiation. Our results suggest that endrin inhibits adipocyte differentiation through the specific suppression of C/EBPalpha.

3T3 Cells↗