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At least 199 records · Page 11Linked to original sources
PubMed2007

3D computation modelling of the influence of cytokine secretion on Th-cell development suggests that negative selection (inhibition of Th1 cells) is more effective than positive selection by IL-4 for Th2 cell dominance.

Th-cell development has been suggested to include selective mechanisms in which certain cytokines select either Th1 or Th2 cells to proliferate and grow. The selective theory is based on the observation that Th2 cells secrete IL-4, a cytokine that promotes Th2 development, whereas Th1 cells secrete interferon-gamma (IFN-gamma) that favours Th1 development, and both positive and negative selective influences have been suggested to operate. In this study, we investigate the role of autocrine secretion and utilization of IL-4 by Th2 cells and address the question of whether an activated Th2 cell can be positively selected by IL-4 secreted from other Th2 cells. We present a spatial three dimensional (3D) modelling approach to simulate the interaction between the IL-4 ligand and its IL-4 receptors expressed on discrete IL-4 secreting cells. The simulations, based on existing experimental data on the IL-4 receptor-ligand system, illustrate how Th-cell development is highly dependent on the distance between cells that are communicating. The model suggests that a single Th2 cell is likely to communicate with possible target cells within a range of approximately 100 microm and that an activated Th2 cell manages to fill most of its own IL-4 receptors, even at a low secretion rate. The predictions made by the model suggest that negative selection against Th1 cells is more effective than positive selection by IL-4 for promoting Th2 dominance.

Animals↗
PubMed2004

Evolving potassium channels by means of yeast selection reveals structural elements important for selectivity.

Potassium channels are widely distributed. To serve their physiological functions, such as neuronal signaling, control of insulin release, and regulation of heart rate and blood flow, it is essential that K+ channels allow K+ but not the smaller and more abundant Na+ ions to go through. The narrowest part of the channel pore, the selectivity filter formed by backbone carbonyls of the GYG-containing K+ channel signature sequence, approximates the hydration shell of K+ ions. However, the K+ channel signature sequence is not sufficient for K+ selectivity. To identify structural elements important for K+ selectivity, we randomly mutagenized the G protein-coupled inwardly rectifying potassium channel 3.2 (GIRK2) bearing the S177W mutation on the second transmembrane segment. This mutation confers constitutive channel activity but abolishes K+ selectivity and hence the channel's ability to complement the K+ transport deficiency of Deltatrk1Deltatrk2 mutant yeast. S177W-containing GIRK2 mutants that support yeast growth in low-K+ medium contain multiple suppressors, each partially restoring K+ selectivity to S177W-containing double mutants. These suppressors include mutations in the first transmembrane segment and the pore helix, likely exerting long-range actions to restore K+ selectivity, as well as a mutation of a second transmembrane segment residue facing the cytoplasmic half of the pore, below the selectivity filter. Some of these suppressors also affected channel gating (channel open time and opening frequency determined in single-channel analyses), revealing intriguing interplay between ion permeation and channel gating.

Amino Acid Substitution↗
PubMed1981

Trade-off between r-selection and K-selection in Drosophila populations.

Density-dependent genetic evolution was tested in experimental populations of Drosophila melanogaster subject for eight generations to natural selection under high (K-selection) or low (r-selection) population density regimes. The test consisted of determining at high and at low densities the per capita rate of population growth of the selected populations. At high densities, the K-selected populations showed a higher per capita rate of population growth than did r-selected populations, but the reverse was true at low densities. These results corroborate the predictions derived from formal models of density-dependent selection. However, no evidence of a trade-off in per capita rate of growth was observed in 25 populations of D. melanogaster, each homozygous for a different second chromosome sampled from a natural population.

Journal Article↗
PubMed2006

Mechanism of Cl- selection by a glutamate-gated chloride (GluCl) receptor revealed through mutations in the selectivity filter.

To learn about the mechanism of ion charge selectivity by invertebrate glutamate-gated chloride (GluCl) channels, we swapped segments between the GluClbeta receptor of Caenorhabditis elegans and the vertebrate cationic alpha7-acetylcholine receptor and monitored anionic/cationic permeability ratios. Complete conversion of the ion charge selectivity in a set of receptor microchimeras indicates that the selectivity filter of the GluClbeta receptor is created by a sequence connecting the first with the second transmembrane segments. A single substitution of a negatively charged residue within this sequence converted the selectivity of the GluClbeta receptor's pore from anionic to cationic. Unexpectedly, elimination of the charge of each basic residue of the selectivity filter, one at a time or concomitantly, moderately reduced the P(Cl)/P(Na) ratios, but the GluClbeta receptor's mutants retained high capacity to select Cl(-) over Na(+). These results indicate that, unlike the proposed case of anionic Gly- and gamma-aminobutyric acid-gated ion channels, positively charged residues do not play the key role in the selection of ionic charge by the GluClbeta receptor. Taken together with measurements of the effective open pore diameter and with structural modeling, the study presented here collectively indicates that in the most constricted part of the open GluClbeta receptor's channel, Cl(-) interacts with backbone amides, where it undergoes partial dehydration necessary for traversing the pore.

Amino Acid Sequence↗
PubMed1996

Predicted response in food conversion ratio for growth by selection on the ratio or on linear component traits, in a (sequential) selection programme.

1. Direct versus indirect selection for food conversion ratio of growth (FCR) after selection for live body weight (LWT), a sequential scheme often applied in broilers, was considered. In the present study loss of response in either FCR or aggregate genotype (H) when LWT was included was investigated under selection on a linear index of ratio component traits (and LWT) or FCR (and LWT) by selection index methodology. 2. Relative responses in FCR and H were generally very similar under single-step and sequential selection. Without LWT in H, selection for linear index or ratio gave similar responses in FCR when heritabilities of components were equal. With large differences in heritabilities (0.2 compared with 0.5) or genetic and environmental correlation (> 0.6) significant differences in response (5 to 12%) in FCR emerged. Therefore, whether additional costs are justified for parameter and breeding value estimation when using a linear index in place of selection for the ratio depends on the difference in heritabilities and correlations of the ration component traits. With LWT in H, loss of response in FCR was partially or entirely offset by response in LWT. 3. The non-normality of FCR and consequences for (co)variance component estimation were studied in terms of the coefficients of variation of the component traits of FCR. Restricted Maximum Likelihood (REML) estimation of (co) variance components for both FCR and logarithm transformed FCR (closer to normality) showed the robustness of REML to such deviations from normality.

Animal Feed↗
PubMed2005

Selection strategy for a seedling seed orchard design based on trait selection index and genomic analysis by molecular markers: a case study for Eucalyptus dunnii.

Molecular genetic analysis was applied to 162 individuals of 37 half-sib selected families belonging to six provenances of Eucalyptus dunnii Maiden in a provenance/family trial. The individuals were selected by a trait selection index and genetic diversity criteria were later applied for designing seedling seed orchards. Genetic diversity and its distribution, as well as relationships among individuals, were assessed on the basis of nine microsatellite loci and 243 amplified fragment length polymorphism markers. High diversity was found with both kinds of markers. Clear-cut genomic patterns of identification (fingerprinting) were obtained for each individual. Genetic differentiation estimates consistently showed low differentiation among provenances (R(ST1) = 0.069, theta(P) = 0.026 and F(CT) = 0.035) and great differentiation among families (R(ST2) = 0.223, theta(S) = 0.174 and F(SC) = 0.164). A high proportion of the total variation was observed within families (around 80% by both marker analyses), suggesting that orchard design should be based on individual or family selection rather than on provenance selection, and that individual ranking by both trait selection index and molecular genetic diversity criteria should be considered. A selection procedure for a seedling seed orchard design is proposed.

DNA Fingerprinting↗
PubMed1999

Growth of starved Escherichia coli O157 cells in selective and non-selective media.

Escherichia coli O157 strains starved in sterile deionized water (SDW) and filter-sterilized natural river water (SRW) were investigated with specific reference to their culturability in selective and non-selective media. Growth of the strains starved in both SDW and SRW were markedly suppressed with time in selective liquid media such as modified trypticase soy broth supplemented with novobiocin (mTSB+n) and modified E. coli broth supplemented with novobiocin (mEC+n). This suppression was more pronounced when incubated at 42 C than at 37 C, especially with mEC+n. By contrast, such growth suppression was seldom observed when cultured at 37 C in non-selective liquid media such as trypticase soy broth (TSB) and buffered peptone water. In mEC+n at 42 C, the non-starved cells from overnight cultures with an initial density of less than 10(3) colony-forming units (CFU)/ml grew to the density of over 10(7) CFU/ml after 24 hr incubation, whereas those starved for 6 weeks in SRW were only to maintain their initial density or died off after 24 hr incubation under the same culturing conditions. These results indicated that the isolation of starved cells of E. coli O157 from water samples would be most difficult with selective enrichment or direct plating on the selective plate media. It is thus highly recommended that a "resuscitation" of the cells with non-selective enrichment should be performed as a routine practice for maximum recovery of E. coli O157 from water systems.

Animals↗
PubMed1989

Within-channel selection and event-related potentials during selective auditory attention.

Event-related potentials were recorded from subjects who listened selectively to stimuli in one of two input channels (ears). The stimuli were random sequences of five vowels and a tone pip. In separate experimental runs, the difficulty of within-channel selection was manipulated by designating either tone (T), one vowel (1V), or two vowels (2V) as targets. An attention-related negativity (Nd) was observed for attended nontarget vowels irrespective of the target difficulty, but the early, centrally maximal phase of Nd was substantial only for the one-vowel and two-vowel conditions. The Nd between its early and late peaks was significantly larger for the two-vowel condition than for the one-vowel and tone conditions. The 2V minus 1V difference in Nd had a closely similar distribution to the early Nd. These target difficulty effects were interpreted as suggesting that the early Nd recorded in two-selection tasks can be related to a within-channel selection process as well as a between-channel selection process. The more anteriorly distributed, later phase of Nd was suggested to be rather insensitive to the difficulty of the within-channel selection. The nature of the within-channel selection underlying the early Nd was discussed in relation to controlled memory search operations.

Adult↗
PubMed1972

Incidence of dumping after truncal and selective vagotomy with pyloroplasty and highly selective vagotomy without drainage procedure.

The incidence of dumping after truncal or selective vagotomy with pyloroplasty and highly selective vagotomy without a drainage procedure was assessed both clinically and experimentally. At a gastric follow-up clinic dumping was found to be significantly less frequent in patients who had undergone highly selective vagotomy without a drainage procedure than in patients who had undergone truncal or selective vagotomy with pyloroplasty (P < 0.05 or < 0.001, respectively). Hypertonic glucose given by mouth provoked the onset of dumping in 20% of patients with duodenal ulcer before operation, in 73% after truncal vagotomy and pyloroplasty, in 80% after selective vagotomy and pyloroplasty, and in 47% after highly selective vagotomy. The test meal also produced significantly greater decreases in blood pressure and increases in pulse rate in patients who had undergone vagotomy with pyloroplasty than in patients who had undergone highly selective vagotomy.

Blood Pressure↗
PubMed2003

Reversal of charge selectivity in cation or anion-selective epithelial lines by expression of different claudins.

Tight junctions (TJ) regulate paracellular ionic charge selectivity and conductance across epithelial tissues and cell lines. These properties vary among epithelia, and recent evidence implicates the claudins, a family of TJ transmembrane proteins, as important determinants of both characteristics. To test the hypothesis that each claudin contributes a characteristic charge discrimination to the TJ, we expressed claudins-2, -4, -11, and -15 in both cation-selective Madin-Darby canine kidney (MDCK) II cells and in anion-selective LLC-PK1 cells and examined changes in transepithelial electrical resistance (TER) and paracellular charge selectivity. Regulated expression and localization were verified by immunoblot analysis and immunofluorescence microscopy, respectively. Expression of claudin-4 increased TER in both cell lines, whereas effects of the others on TER were variable. Claudin-4 and -11 decreased paracellular permeability for Na+ in MDCK II cells, whereas neither claudin-2 nor -15 had an effect. Conversely, in LLC-PK1 cells, claudin-2 and -15 increased the permeability for Na+, whereas claudin-4 and -11 were without effect. We conclude that the contribution of each claudin is most easily detectable when it reverses the direction of monolayer charge selectivity. These results are consistent with a model in which exogenous claudins add new charge-selective pores, leading to a physiological phenotype that combines endogenous and exogenous contributions. Additionally, it is possible to rationalize the direction of charge selectivity conferred by the individual claudins on the basis of electrostatic effects of the charged amino acids in their first extracellular loops.

Amino Acid Sequence↗
PubMed1990

Alternative methods of selection for litter size in mice: II. Response to thirteen generations of selection.

Selection was conducted on an index of components of litter size (I = 1.21 x ovulation rate + 9.05 x ova success; ovulation rate measured by number of corpora lutea and ova success measured as number of pups born + number of corpora lutea), on uterine capacity (measured as number of pups born to unilaterally ovariectomized dams) and on litter size concurrent with an unselected control for 13 generations. Selection criteria (IX = index, UT = uterine capacity, LS = litter size and LC = control) were applied in each of three replicates. In an evaluation after five generations, IX and LS each exceeded LC by about .5 pups, with no response in UT. After 13 generations, mean ovulation rate, ova success and litter size (measured as number of fetuses at 17 d gestation in intact females) were, for IX, 14.25, .84, 11.95; for LS, 14.15, .82, 11.64; for UT, 12.61, .86, 10.77; and for LC, 12.27, .82, 9.98. The regression of number born (litter size in IX, LS and LC; uterine capacity with only a functional left uterine horn in UT) on cumulative selection differential across 13 generations was .12 +/- .01, .09 +/- .02 and .08 +/- .02 for IX, LS and UT, respectively. The regression of breeding value for litter size on each selection criterion, estimated as response in the generation-13 evaluation divided by cumulative selection differential, was .11 +/- .02, .08 +/- .01 and .05 +/- .03 for IX, LS and UT, respectively. Regression of response in number born on generation number was .17 +/- .01, .15 +/- .04 and .10 +/- .02 for IX, LS and UT, respectively. Selection in IX was promising relative to LS, and selection in UT changed number born.

Animals↗
PubMed1992

Effect of culling on selection response using phenotypic selection or best linear unbiased prediction of breeding values in small, closed herds of swine.

Records from 7,200 separate closed herds with either 12 or 25 sows that were mated to either four or eight boars per year were simulated by computer. Effects of selection method, herd size, and contemporary group variability on average genetic change, genetic variance, and inbreeding over 10 yr of selection were analyzed for traits with heritabilities of .1, .3, and .6. Selection of replacement animals was on individual phenotype or BLUP of breeding value using a reduced animal model. For both of these selection methods, two culling schemes were imposed: 1) based only on involuntary culling because of losses due to conception rate and age and 2) when an available replacement animal was projected to be superior to an existing breeding animal in the herd in addition to the involuntary culling. The contemporary group standard deviation was set at either .1 or .5 of a phenotypic standard deviation. Selection with BLUP gave 72, 36, and 12% more genetic improvement for heritabilities of .1, .3, and .6, respectively, than selection on individual phenotype after 10 yr. However, inbreeding increased 20 to 52% more rapidly and there was a decrease in genetic variance. Culling based on Scheme 2 increased genetic improvement over Scheme 1 by about 75% with coincident increases in inbreeding level and decreases in genetic variance. The largest changes in inbreeding and genetic variance were associated with culling on BLUP. Culling when a superior animal was available with individual phenotype had little effect on inbreeding and genetic variance. Use of four boars rather than eight boars and 25 rather than 12 sows per herd increased genetic response. Use of four boars also increased inbreeding and decreased genetic variance. Genetic variance was higher in herds with 25 sows, but the size of the sow herd had little effect on inbreeding. Contemporary group variation influenced only the genetic response of individual phenotypic selection with culling.

Animals↗
PubMed1999

Progeny testing sires selected by independent culling levels for below-average birth weight and high yearling weight or by mass selection for high yearling weight.

Breeding values of sires resulting from selection either for reduced birth weight and increased yearling weight (YB, n = 8) or for increased yearling weight alone (YW, n = 9) were compared with each other and with sires representative of the population before selection began (BS, n = 12) using progeny testing. Reference sires (n = 6) connected these Line 1 sires with the Hereford international genetic evaluation. Thirty-five sires produced 525 progeny that were evaluated through weaning. After weaning, 225 steer progeny were individually fed, slaughtered, and carcass data collected. Data were analyzed using restricted maximum likelihood procedures for multiple traits to estimate breeding values for traits measured on the top-cross progeny while simultaneously accounting for selection of the sires. Results of the progeny test substantiate within-line results for traits upon which sires were selected. Breeding values for gestation length were greater in YB sires than in YW sires and were unchanged relative to BS sires. Breeding values for growth rate and feed intake for the YB and YW sires were greater than for BS sires. Predicted breeding values for indicators of fat deposition tended to be greater in YB sires and less in YW sires relative to BS sires, although YB and YW sires had similar breeding values for marbling score. Selection based on easily and routinely measured growth traits, although achieving the intended direct responses, may not favorably affect all components of production efficiency. Further, divergence of selection lines may not be easily anticipated from preexisting parameter estimates, particularly when selection is based on more than one trait.

Animals↗
PubMed2006

Selective attention versus selection for action: negative priming is not the result of distractors being unattended.

Using a novel referent size-selection task, MacDonald, Joordens, and Seergobin (1999; MacDonald & Joordens, 2000) found that negative priming persisted even when participants were encouraged to attend to distractors before selectively responding to targets. This finding suggested that negative priming is not caused by processes that operate on stimuli that are to be ignored in the traditional selective attention sense. Mackintosh, Mathews, and Holden's (2002) attempt to replicate the MacDonald et al. study resulted in the discovery of possible artifacts in the referent size-selection task, thereby making the implications with respect to the role of attention less clear. In the present study, we describe a different method for directing attention to distractors in a negative priming context, one that does not suffer from the same potential artifacts as the referent size-selection task. Our results are consistent with those found by MacDonald et al., in that negative priming persisted even when participants were explicitly encouraged to attend to distractors. Implications are discussed in the context of the related concepts of selective attention (e.g., Broadbent, 1965) versus selection for action (e.g., Allport, 1987).

Affect↗
PubMed1995

Visual selection mediated by location: selecting successive visual objects.

In these experiments, each stimulus consists of a series of frames, each containing a target digit of one color and a distractor digit of another color. The task is to name the highest digit of the target color. Subjects make fewer errors when successive targets appear at the same location than when they appear at different locations, apparently because they select target objects by using a mechanism that is based on location. When successive targets appear at the same location, there is no need to "move" the selection mechanism to a new location, leaving more time to identify the stimuli. These experiments show that location-based selection is used even though selection by color would be more direct. They also demonstrated a method of measuring location-based selection that can be applied to a variety of visual tasks. Further experiments reveal that although location-based selection is used to identify a digit in the presence of a digit distractor, it is not used to identify a digit in the presence of a letter distractor, suggesting that this selection mechanism is not used in this situation to prevent interference among the basic features making up letters and digits, but to inhibit responses associated with the distractors.

Adult↗
PubMedDate not supplied

The outcome of non-selective vs selective nitric oxide synthase inhibition in lipopolysaccharide treated rats.

UNLABELLED: Nitric oxide (NO), generated by inducible nitric oxide synthase (NOS) following lipopolysaccharide (LPS) administration, produces renal failure through autoinhibition of glomerular endothelial NOS activity. Preadministration of selective iNOS inhibitors abolishes this effect. Although nonselective NOS inhibitors further decrease GFR, current clinical trials investigate the effect of nonselective NOS inhibition in septic patients. The goals of our study were to determine whether treatment with selective NOS inhibitors can reverse the decrease in GFR in LPS treated rats with already established renal failure and to define the outcome of LPS treated rats following nonselective NOS inhibition. Four hours following the administration of LPS (4 mg/kg), we measured creatinine clearance (CrCl) before and after the administration of either L-NIL (selective iNOS inhibitor, 3 mg every 20 minutes) or saline. Selective iNOS inhibition attenuated the decrease in blood pressure [ CONTROLS: 105 +/- 6 to 98 +/- 5, LPS: 92 +/- 5* to 83 +/- 4*, LPS + L-NIL: 88 +/- 6* to 94 +/- 6 mm Hg; *p < 0.05, vs controls (n = 6)], and reversed the decrease in GFR after LPS [ CONTROLS: 2.21 +/- 0.13 to 2.07 +/- 0.11, LPS: 0.82 +/- 0.18* to 0.66 +/- 0.22*, LPS + L-NIL: 0.76 +/- 0.15* to 1.86 +/- 0.15 ml/min; *p < 0.05 vs controls (n = 6)]. We next studied the effect of complete non-selective NOS inhibition (L-NAME 200 mg, 2 hours after LPS) on LPS treated rats. All (6/6) animals treated with both LPS and L-NAME died within 2 hours following LPS, while rats treated with either LPS, L-NAME, or LPS + L-NIL survived. Histologic studies performed in all experimental groups were unremarkable. Overnight mortality was studied using smaller doses of L-NAME. All LPS + L-NAME (10/10) and 1/10 LPS treated rats died. L-NAME, control, and LPS + L-NIL animals survived. The characteristic histologic findings in LPS + L-NAME rats were diffuse ischemic changes, most importantly acute myocardial infarction. IN CONCLUSION: Selective iN-OS inhibition might prove to have clinical application as it prevents the decrease in GFR following LPS, even after renal failure is established. Treatment with a non selective NOS inhibitor in septic patients should be reconsidered.

Analysis of Variance↗
PubMed1992

Selective association between MHC class I-restricted T cell receptors, CDS, and activated tyrosine kinases on thymocytes undergoing positive selection.

Developing T cells undergo distinct selection processes that determine the TCR repertoire. Positive selection involves the differentiation of immature thymocytes capable of recognizing antigens complexed with self-MHC molecules to mature T cells. Besides the central role of TCR engagement by MHC in triggering selection; the interaction of CD8 and CD4 with MHC class I and class II, respectively; is thought to be important in regulating the selection process. To study potential mechanisms involved in positive selection of CD8+ cells, we have analyzed mice expressing a unique transgenic TCR. The transgenic receptor recognizes the HY male Ag in the context of the MHC class I molecule, H2-Db. We describe that CD8 and the TCR are selectively associated in thymocytes of mice expressing the restricting MHC, but not in thymocytes of mice expressing a nonrestricting MHC. pp56lck and pp59fyn, the tyrosine kinases associated with CD8 and TCR, respectively, were found to be present in this complex in an activated form. No comparable TCR-CD4 complex formation was found in thymuses undergoing positive selection to CD8+ cells. The formation of a multimolecular complex between CD8 and TCR, in which pp56lck and pp59fyn are activated, may initiate specific signaling programs involved in the maturation of CD8+ cells.

Animals↗
PubMed1994

Antinociception induced by intrathecal coadministration of selective adenosine receptor and selective opioid receptor agonists in mice.

Intrathecal administration of adenosine or adenosine analogs causes antinociception. In addition, opioid-induced antinociception is mediated, in part, by spinal adenosine release. Recent investigations from our laboratory suggest the significance of adenosine in opioid-mediated actions varies between different pharmacologic effects of opioid agonists and may vary after selective activation of different opioid receptor subtypes. A series of investigations using isobolographic analysis were designed to examine the functional significance of adenosine in antinociception induced by opioid receptor-selective agonists in the mouse tail-flick assay. Combinations of A1 or A2 adenosine receptor-selective agonists were coadminstered in a constant dose ratio with mu, delta or kappa opioid receptor-selective agonists. Additive interactions were observed for adenosine agonists coadministered with mu opioid receptor selective agonists. Synergism was generally observed after coadministration of adenosine receptor agonists with agonists selective for either delta-1 or delta-2 opioid receptors. A synergistic interaction was also observed after coadministration of an A1 adenosine receptor agonist with a kappa opioid receptor agonist. Observations reported with mu opioid receptor selective agonists are consistent with earlier reports demonstrating opiod-mediated adenosine release as one mechanism of opioid-induced antinociception. Results with combinations of adenosine agonists and delta or kappa opioid receptor agonists appear inconsistent with delta or kappa opioid receptor-mediated release of adenosine, and suggest a more complex functional interaction between adenosine and delta or kappa opioid spinal system.

Adenosine↗