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At least 865 records · Page 48Linked to original sources
PubMed1993

Restriction selection cloning: a simple general method for the selection of recombinant DNA.

It is well known that the ligation of two DNA fragments which are the product of digestion from different restriction enzymes will not lead to the regeneration of either of the original blunt end or cohesive end restriction sites. This property of sequence incompatibility for the original restriction enzyme can be exploited in a general cloning procedure for both PCR products and restricted DNAs. Restriction selection is particularly useful when cloning low abundance polymerase chain reaction (PCR) products and when cloning blunt ended DNA into reporter vectors that lack a method for the selection of recombinants.

Base Sequence↗
PubMed1993

Premedication with non-selective and M1-selective muscarinic antagonists before ECT.

Atropine treatment before electroconvulsive therapy (ECT) is used for two main reasons: a) to prevent transient post-ictal bradyarrhythmias due to excessive vagal tone; b) to minimize secretions within the respiratory tract. In the present study we have compared the effects of premedication using atropine, a non-selective muscarinic antagonist, with biperiden, an M1-selective muscarinic antagonist. Cardiac rate and other cardiac parameters and respiratory tract secretions after ECT were compared in order to determine whether atropine effects following ECT involve central or peripheral antagonistic effects. Our results show that in preventing excessive sialorrhea following ECT, atropine works antagonistically through peripheral glandular M2 receptors whereas biperiden antagonizing M1 receptors fails to prevent sialorrhea. Our results are not conclusive concerning cardiac protective effects of atropine following ECT. None of the patients, whether premedicated by atropine or biperiden, displayed bradyarrhythmias following ECT. No significant differences were found in any of the measured cardiac parameters following ECT between atropine and biperiden premedications. Thus, the question whether atropine exerts its protective cardiac effects following ECT through central (probably M1) or peripheral M2 receptors remains open.

Adult↗
PubMed1996

Attentional selection and word processing in Stroop and word search tasks: the role of selection for action.

The time course of visual word processing was investigated in two tasks differing in whether words were "selected for action" (Allport, 1989). Using identical displays in which a square color patch appeared at fixation with either 2, 4, or 8 flanking words appearing at any of the 8 sides and corners, subjects performed either a Stroop color-naming task or a word search task requiring detection of a color name among the flanking words by either a manual presence/absence response (Experiment 1) or a vocal naming response (Experiment 2). The color-naming task produced Stroop effects indicating parallel word processing in multiword displays, whereas the word search task produced evidence consistent with serial, self-terminating search requiring allocation of spatial attention. The differences in word processing across tasks are reconciled using Allport's concept of selection for action and extended to neuropsychological evidence on attention.

Attention↗
PubMed1996

Isoenzyme-selective inhibition of glutathione conjugation in vivo: selective inhibition of the conjugation of S-2-Bromoisovalerylurea in the rat.

Glutathione S-transferases (GSTs) play a major role in the (de-)toxification of many endogenous and xenobiotic substrates. To assess their contribution in (de-)toxification, specific in vivo inhibitors that ideally are selective for a single isoenzyme of GST are required. In the present study, selective inhibition of the alpha class GST by the glutathione analog (R)-5-ethyloxycarbonyl-2-gamma-(S)-glutamylamino-N-2-hept ylpentamide (Et-R-Hep) was studied. In rat liver cytosol and in isolated rat hepatocytes, only the conjugation of the (S)-enantiomer of (RS)-2-bromoisovalerylurea (BIU), which is conjugated mainly by alpha class GST 2-2 (Te Koppele et al., Biochem. J. 252:137-142, 1988), was inhibited by Et-R-hep. The conjugation of (R)-BIU, which is mainly catalyzed by mu class GSTs 3-3 and 4-4, was unaffected. In anesthetized rats to which an infusion of (RS)-BIU was administered, the biliary excretion of the glutathione conjugate of (S)-BIU was inhibited by up to 67% after administration of Et-R-hep (an i.v. bolus dose of 200 mu mol/kg followed by an infusion of 6.7 mu mol/min/kg for 30 min). The extent of inhibition decreased gradually to reach 40% at the end of the experiment (4 hr after administration of the inhibitor). The conjugation of (R)-BIU was unaffected. Thus, the inhibitor Et-R-Hep shows preferential inhibition of the alpha-GST substrate (S)-BIU. Although Et-R-Hep is not specific for alpha class GST, it may be used to assess the role of this class of GST in (de)-toxification and conjugation in vivo.

Animals↗
PubMed1995

A novel screening system for construction and selection of active ribozymes using DHFR (dihydrofolate reductase) gene as selection marker.

Ribozyme is thought to be a powerful tool for suppression of specific gene expression, but there are many failure cases in their applications in vivo. One reason may be that there are many cellular proteins in vivo which may inhibit the catalytic activity of ribozymes. Such being the case, many researchers have made efforts to increase the activity of ribozymes. Here we have developed a new screening system for active ribozymes using DHFR (dihydrofolate reductase) gene as a selection marker. In our system, we set the ribozyme target site not to the DHFR gene itself but to the interspace between two ATG codons. One of which is the original initiation codon, ATG, for DHFR gene itself, and the second one locates upstream of the former. The upstream ATG has an ability to cause frame shift for DHFR gene. Since the upstream ATG is preferentially used during translation, unless it is removed, production of DHFR is negligible. By setting the ribozyme target site between the two ATGs, we can make this screening system as positive selection. To our best knowledge, this is the first successful screening system in vivo.

Base Sequence↗
PubMed1997

Selection of S18326 as a new potent and selective boronic acid direct thrombin inhibitor.

Using enzymatic microassays, the potency of a series of new boroarginine tripeptides was determined versus thrombin and a panel of serine-proteases implicated in the coagulation and fibrinolysis pathways. The inhibition of the serine-protease complement factor I was also studied. Factor I regulates the alternate pathway of the complement and its inhibition appears to be responsible for the toxic effects of the orally available thrombin inhibitor Ac-D-Phe-Pro-boroArg (DuP-714). The structure of the new boronic acid derivatives tested was modified from that of DuP-714 by replacing the proline in the P2 position by N-cycloalkyl-glycine residues of increasing size (S18989: cyclopropyl; S18563: cyclobutyl; S18326: cyclopentyl; S18229: cyclohexyl). All compounds were found to be slow-tight binding inhibitors of thrombin versus purified human fibrinogen. Replacement of proline by N-cycloalkyl-glycines did not decrease the anti-thrombin potency of the substances up to the cyclopentyl size and this result was confirmed by classical coagulation assays with human plasma in vitro. In contrast, the inhibitory activities of the four new boronic acids were found to be lower than those of DuP-714 versus plasmin, urokinase (u-PA), plasmatic kallikrein, activated protein C (aPC) and complement factor I. The cyclopentyl derivative S18326 is a slightly more active inhibitor of thrombin than DuP-714 (initial IC50 values 3.99 +/- 0.18 nM versus 4.73 +/- 0.27 nM, respectively). Moreover S18326 was identified as the most selective compound of the series with relative potencies being 2 to 29 fold higher than that of DuP-714 versus the panel of serine-proteases tested; the rank order of potency versus the other serine-proteases for S18326 was t-PA>kallikrein>aPC>factor I>plasmin>fXa>u-PA. These results indicate that the size of the thrombin hydrophobic pocket S2 is sufficient to accept larger residues than proline in the P2 position of Ac-D-Phe-X-boroArg derivatives while this is not the case for other important serine-proteases of the fibrinolysis, coagulation and complement pathways. The N-cyclopentyl glycine containing derivative S 18326, which is the most potent and the most selective anti-thrombin compound of the series, currently undergoes major preclinical testing.

Anticoagulants↗
PubMed2000

Fundamental theorem of natural selection and frequency-dependent selection: analysis of the matrix game diploid model.

Following Ewens' interpretation about Fisher's fundamental theorem of natural selection, the matrix game model for diploid populations undergoing non-overlapping, discrete generations is investigated. The total genetic variance is decomposed and it is shown that the partial change in the mean fitness, which is equal to the additive genetic variance over the mean fitness, can be thought of as a change due only to the partial changes in the phenotypic frequencies.

Animals↗
PubMed1994

Variable selectivity of the Hitachi chemistry analyzer chloride ion-selective electrode toward interfering ions.

Chloride measurements by ion-selective electrodes are vulnerable to interference by anions such as iodide, thiocyanate, nitrate, and bromide. We have found that the degree of interference of these anions on the Hitachi chemistry analyzer chloride electrode varies from electrode to electrode and this variation can even occur within the same lot of membrane. This variation is not dependent upon the length of time the cartridge has been in the analyzer because no correlation existed between the usage time and the electrode response to interfering ions. Neither is this variation due to the deterioration of the electrode because all electrodes tested had calibration slopes within the manufacturer's specification. Our study, however, showed that even after repeated exposure to a plasma sample containing 2 mM thiocyanate, the chloride electrode was still able to accurately measure the chloride in plasma without thiocyanate, thus confirming that a carryover effect does not exist from a previous thiocyanate-containing sample.

Anions↗
PubMed2006

From selective to highly selective SSRIs: a comparison of the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram.

Most Serotonin Selective Reuptake Inhibitors (SSRIs) have been found to possess secondary binding properties, while citalopram and its S-enantiomer (escitalopram) have been reconfirmed "purest SSRIs". Using the mouse model of acute pain hotplate analgesia meter, we evaluated the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram, injected i.p. Fluvoxamine induced a dose-dependent clear antinociceptive effect (with an ED(50) value of 6.4 mg/kg). Both fluoxetine and citalopram induced (separately) only a weak antinociceptive effect with an inverse "U" shape curve. All three drug's effects were not abolished by naloxone. Escitalopram did not elicit any effect at quasi-equipotent doses. These findings show that fluoxetine, fluvoxamine and citalopram given i.p. are weak antinociceptors, (not mediated through opioid mechanisms), while escitalopram possesses no antinociceptive properties when injected i.p. This difference between citalopram and escitalopram calls for further studies in order to assess the various differences between the two enantiomers of citalopram, and between each enantiomer and the racemic mixture.

Analgesics↗
PubMed2005

Do mice genetically selected for resistance to oral tolerance provide selective advantage for Schistosoma mansoni infection?

A highly evolved relationship exists between the parasitic flatworm Schistosoma mansoni and its vertebrate hosts that include the use of host immune signals by parasites. The S. mansoni infection was studied in two strains of mice genetically selected, over 18 generations of assortative mating, for extreme phenotypes of susceptibility (TS) and resistance (TR) to immunological tolerance. The objective was to observe whether the different host genetic backgrounds affected the outcome of experimental schistosomiasis. Fecal egg excretion, tissue egg count, worm recovery, and adult worm morphology and morphometry were monitored throughout the period of infection. TR mice presented total fecal egg excretion and thickness of tegument in adult male worms significantly higher than TS mice. Therefore, the comparative analysis of mice with extreme phenotypes of immunological response turns out to be useful in host-parasite relationship studies. Our results suggest that the TR mouse immunological profile provides a more favorable environment for the development of S. mansoni.

Animals↗
PubMed2005

Exposure assessment and microcosm fate of selected selective serotonin reuptake inhibitors.

The exposure and fate of selective serotonin reuptake inhibitors (SSRIs) was evaluated using modeled predicted environmental concentrations (PECs) according to the U.S. and the European Union (EU) guidelines and microcosm model ecosystems. According to the U.S. guidance, crude environmental introduction concentrations, the only SSRI that would require environmental assessment would be sertraline. However, the more conservative EU draft guidance PEC would require further assessment of all five SSRIs. Refined PECs developed using the U.S. and the EU guidelines along with estimates of removal by sewage treatment and receiving water dilution factors indicate that the U.S. methodology corresponds better to MEC data determined in the U.S. and Canada. Worst-case (99th centile) PECs for citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline were 30, 19, 30, 65, and 122 ng/L, respectively, using the U.S. methodology and 142, 182, 841, 144, and 575 ng/L, respectively, using the EU draft methodology. The dissipation of fluoxetine and fluvoxamine from the water column in aquatic microcosms was best described using a two-compartment model while sertraline followed a one-compartment model. Fluoxetine and fluvoxamine water concentrations initially dissipated with first phase half-lives of 3.8 and 1.8 days, respectively, but levelled off at concentrations around 10 microg/L with second phase half-lives of 76.7 and 59.3 days, respectively, not including those estimated as infinity. Sertraline dissipation tended toward the detection limit with a half-life of 3.4 days. Fluoxetine was found to be the most persistent followed by fluvoxamine and sertraline. Estimated log(K(OC)) values for all SSRIs were >4.3 indicating that SSRIs are expected to adsorb to sediment or sludge. Partitioning into other environmental compartments such as this may act as a reservoir from which SSRIs may be re-released into surface waters and indicates the potential susceptibility of benthos.

Environmental Exposure↗
PubMed2006

Discriminative stimulus properties of the selective norepinephrine reuptake inhibitor, reboxetine, in rats: a characterization with alpha/beta-adrenoceptor subtype selective ligands, antidepressants, and antagonists at neuropeptide receptors.

Although little information is available concerning discriminative stimulus (DS) properties of antidepressants, rats can be trained to recognize the selective norepinephrine (NE) reuptake inhibitor, reboxetine (2.5 mg/kg i.p.). By analogy to reboxetine (effective dose50, 1.1), 'full' (80%) substitution dose50 was obtained with the NE reuptake inhibitors, nisoxetine (4.9), nomifensine (0.5) and BW1555,U88 (1.0). Full substitution was also attained with the NE/serotonin (5-HT) reuptake inhibitors, S33005 (0.3), venlafaxine (4.8) and duloxetine (26.8), and the tricyclics, imipramine (2.5) and clomipramine (2.9). In contrast, the 5-HT reuptake inhibitors, citalopram, sertraline and paroxetine (all >2.5), and the 5-HT reuptake inhibitors/5-HT2 receptor antagonists, nefazodone and trazodone (both >10.0), did not substitute for reboxetine. The 'atypical' antidepressants, mirtazapine (>10.0) and mianserin (>2.5), similarly failed to substitute. DS properties of reboxetine were dose-dependently blocked by the alpha1-adrenoceptor (AR) antagonists, prazosin (inhibitory dose50, 0.3) and WB4101 (0.5), but resistant to the alpha2-AR antagonists, atipamezole (>0.63), idazoxan (>2.5) and RX821,002 (>0.08), and to the beta1-AR and beta2-AR antagonists, betaxolol (>2.5) and ICI118,551 (>10.0). Interestingly, the neurokinin-1 receptor antagonist, GR205,171, stereospecifically substituted for reboxetine (1.1) compared to its less active isomer, GR226,206 (>10.0). The corticotrophin-releasing factor-1 antagonists, DMP695 (>40), CP154,526 (>10.0) and SN003 (>40.0), and the melanin-concentrating hormone-1 antagonist, SNAP-7941 (>40.0), failed to substitute for reboxetine. In conclusion, DS properties of reboxetine are mimicked by antidepressants recognizing NE transporters, and require functionally intact alpha1-ARs for their expression. The neurokinin-1 antagonist, GR205,171, mimics the interoceptive properties of reboxetine, possibly reflecting its elevation of extracellular levels of NE in corticolimbic structures.

Adrenergic Uptake Inhibitors↗
PubMed1984

Components of selection in X chromosome lines of Drosophila melanogaster: sex ratio modification by meiotic drive and viability selection.

Selection coefficients and segregation parameters have been estimated in 18 randomly chosen lines carrying wild X chromosomes on the cn bw genetic background. Each line was studied in replicated crosses of four types, with approximately 100 replications per line per cross. Crosses in which male X chromosomes differed exhibited significant sex ratio heterogeneity. Maximum likelihood estimation of segregation parameters revealed two lines in which the proportion of X-bearing gametes produced by males was significantly different from Mendelian expectations. These observations suggest that segregation distortion is a common feature of naturally occurring genetic variation. Non-Mendelian segregation has important evolutionary implications.

Animals↗
PubMed1976

Selection in reference to biological groups. VI. Use of extreme forms of nonrandom groups to increase selection efficiency.

The strategy of using non-random groups to increase the efficiency of truncation selection is discussed. The present study, which considers extreme forms of non-rnadom groups, complements a previous study involving full-sib groups. It is shown that of the two kinds of non-randomness, i.e. that due to homozygosity or that due to homogeneity (as represented by cloning), the latter is the most effective. This suggests that with those plant crops in which intense competition among plants exists, use of clonal propagation to produce non-random groups should be investigated.

Genetics, Population↗
PubMed2004

Behavioral and physiological features of chickens diversely selected for resistance to Avian Disease. 1. Selected inbred lines differ in behavioral and physical responses to social stress.

To test the hypothesis that genetic variations in response to social stress modulate susceptibility to disease in poultry, aggressive behaviors induced by social stress were measured in chickens of different inbred lines selected for disease resistance (line 63) or susceptibility (lines 72 and 15I5), as well as 2 recombinant congenic strains (B and X). At 15 wk of age, roosters from each genetic line or strain were randomly assigned to pairs for intraline male-male aggression tests (n = 8 per line). Based on the results of the intraline aggression tests, the roosters were divided into 2 groups, winners and losers. At 16 wk of age, the roosters were randomly paired as winners vs. winners and losers vs. losers for interline aggression tests, i.e., line 63 vs. 72 and 15I5; line 73 vs. line 15I5; and strain X vs. strain B. Similarly, at 17 wk of age, line 63 vs. strains X and B, and line 72 vs. strains X and B were tested. The tests were conducted in a novel cage that was similar to their home cages, to provide a neutral space for both roosters being tested. Each pair was videotaped for 15 min. Male-male interaction-induced aggressive behaviors were markedly different among the genetic lines. Compared with roosters of lines 15I5 and 72, line 63 roosters generally showed fewer aggressive behaviors, including aggressive pecks and fights, as well as durations (P < 0.05). Roosters of the recombinant congenic strains X and B, each possessing a unique random 87.5% genome of line 63, exhibited low aggressive behaviors, which were similar or equal to the level of line 63 in both intraline and interline aggression tests (P = 0.05). These results may indicate that some of the gene(s) commonly carried between strains X and B as well as line 63 likely played an important role in governing their lower levels of aggression. The present chicken lines may be used as animal models for investigation of the cellular mechanisms of genetic-environmental interactions on disease resistance and stress responses.

Aggression↗
PubMed2006

Maximum aerobic performance in lines of Mus selected for high wheel-running activity: effects of selection, oxygen availability and the mini-muscle phenotype.

We compared maximum aerobic capacity during forced exercise (VO2max) in hypoxia (PO2=14% O2), normoxia (21%) and hyperoxia (30%) of lines of house mice selectively bred for high voluntary wheel running (S lines) with their four unselected control (C) lines. We also tested for pleiotropic effects of the ;mighty mini-muscle' allele, a Mendelian recessive that causes a 50% reduction in hind limb muscle but a doubling of mass-specific aerobic enzyme activity, among other pleiotropic effects. VO2max of female mice was measured during forced exercise on a motorized treadmill enclosed in a metabolic chamber that allowed altered PO2. Individual variation in VO2max was highly repeatable within each PO2, and values were also significantly correlated across PO2. Analysis of covariance showed that S mice had higher body-mass-adjusted VO2max than C at all PO2, ranging from +10.7% in hypoxia to +20.8% in hyperoxia. VO2max of S lines increased practically linearly with PO2, whereas that of C lines plateaued from normoxia to hyperoxia, and respiratory exchange ratio (=CO2 production/VO2max) was lower for S lines. These results suggest that the physiological underpinnings of VO2max differ between the S and C lines. Apparently, at least in S lines, peripheral tissues may sustain higher rates of oxidative metabolism if central organs provide more O2. Although the existence of central limitations in S lines cannot be excluded based solely on the present data, we have previously reported that both S and C lines can attain considerably higher VO2max during cold exposure in a He-O2 atmosphere, suggesting that limitations on VO2max depend on interactions between the central and peripheral organs involved. In addition, mini-muscle individuals had higher VO2max than did those with normal muscles, suggesting that the former might have higher hypoxia tolerance. This would imply that the mini-muscle phenotype could be a good model to test how exercise performance and hypoxia tolerance could evolve in a correlated fashion, as previous researchers have suggested.

Analysis of Variance↗
PubMed2005

Selected topics in personnel selection: primarily in the early to mid-years of the 20th century.

A brief historical review is presented of the events in the USA relating to personnel selection in business and industry from 1903 to 2003. Emphasis is placed on the early periods of the century through the midyears. Involved in these events have been applied psychologists, the American Psychological Association, Government Agencies, Federal, Circuit Courts of Appeals, and the Supreme Court.

Advertising↗
PubMed1999

Selective estrogen receptor modulators: tissue selectivity and differential uterine effects.

Selective estrogen receptor modulators (SERMs) are compounds that bind to estrogen receptors and produce estrogen-like (agonist) effects in some tissues and estrogen-blocking (antagonist) effects in other tissues. One of the goals of SERM research has been to develop compounds that provide the potential benefits of estrogen in the skeleton and cardiovascular system, but avoid the negative effects of estrogen in other tissues. Estrogen therapy has been consistently associated with endometrial stimulation, including glandular proliferation, hyperplasia and cancer. In contrast, the presence or degree of endometrial stimulation observed with SERMs varies by compound. The purpose of this review is to differentiate the endometrial effects of compounds that display a SERM-like profile. Molecular mechanisms involving SERM binding to estrogen receptors, preclinical uterine effects in both tissue culture and animal models, and endometrial findings in clinical experience are discussed. There are several SERMs commercially available or in development. The favorable safety profile of raloxifene in the uterus differentiates it from the others. Future SERM development will continue to focus on finding compounds that exhibit minimal endometrial stimulation.

Animals↗