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Results for “differential selection”

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PubMed2005

Locomotor activity detects subunit-selective effects of agonists and decahydroisoquinoline antagonists at AMPA/kainic acid ionotropic glutamate receptors in adult rats.

RATIONALE: In vitro studies have identified a series of decahydroisoquinoline compounds with differential selectivity for the subunits that comprise AMPA/kainic acid receptors. Compounds have been identified that have preferential activity at AMPA receptors (LY302679), whereas others (LY377770) have affinity for GluR5-kainic acid preferring subunit, which is activated by ATPA and kainic acid. OBJECTIVES: These studies set out to determine if locomotor activity could differentiate these profiles in vivo. METHODS: Locomotor activity was assessed in photocell drums in male Lister Hooded rats. RESULTS: AMPA, kainic acid and the GluR5 selective agonist ATPA, all suppressed spontaneous locomotor activity (SLA) in rats at doses of 1.0, 5.0 and 20 mg/kg resp. All three agonists achieve micromolar concentrations measured in whole brain after dosing with 10 mg/kg SC. The decahydroisoquinoline antagonist compounds, LY302679 (GluR2), LY293558 (GluR2, 5) and LY377770 (GluR5) all decreased SLA in rats (ED(min) 2.5, 5.0 and 20 mg/kg respectively). The rank order of potency at GluR2 subunits (LY302679>LY293558>LY377770) was reflected in the same rank order of activity for suppression of SLA. LY293558 reversed the suppression of SLA induced by all three agonists (0.62--2.5 mg/kg). LY377770 reversed the effects of ATPA only (ED(min) 1.0 mg/kg), LY302679 (ED(min) 2.5 mg/kg) attenuated the effect of kainic acid but was ineffective against AMPA and ATPA. CONCLUSIONS: Both agonist and antagonist suppression of SLA is associated with greater affinity for the GluR2 subunit, while compounds with affinity for the GluR5 subunit were less potent in suppressing SLA.

Animals↗
PubMedDate not supplied

Membrane introduction mass spectrometry: trends and applications.

Recent advances in membrane introduction mass spectrometry (MIMS) are reviewed. On-line monitoring is treated by focusing on critical variables, including the nature and dimensions of the membrane, and the analyte vapor pressure, diffusivity, and solubility in the membrane barrier. Sample introduction by MIMS is applied in (i) on-line monitoring of chemical and biological reactors, (ii) analysis of volatile organic compounds in environmental matrices, including air, water and soil, and (iii) in more fundamental studies, such as measurements of thermochemical properties, reaction mechanisms, and kinetics. New semipermeable membranes are discussed, including those consisting of thin polymers, low vapor pressure liquids, and zeolites. These membranes have been used to monitor polar compounds, selectively differentiate compounds through affinity-binding, and provide isomer differentiation based on molecular size. Measurements at high spatial resolution, for example, using silicone-capped hypodermic needle inlets, are also covered, as is electrically driven sampling through microporous membranes. Other variations on the basic MIMS experiment include analyte preconcentration through cryotrapping (CT-MIMS) or trapping in the membrane (trap-and-release), as well as differential thermal release methods and reverse phase (i.e., organic solvent) MIMS. Method limitations center on semivolatile compounds and complex mixture analysis, and novel solutions are discussed. Semivolatile compounds have been monitored with thermally assisted desorption, ultrathin membranes and derivatization techniques. Taking advantage of the differences in time of membrane permeation, mixtures of structurally similar compounds have been differentiated by using sample modulation techniques and by temperature-programmed desorption from a membrane interface. Selective ionization techniques that increase instrument sensitivity towards polar compounds are also described, and comparisons are made with other direct sampling (nonchromatographic) methods that are useful in mixture analysis.

Bioreactors↗
PubMed1996

Selection for egg shell strength in laying hens using shell membrane characteristics.

1. Divergent selection for attachment strength between the shell membrane and the calcium shell was performed in a White Leghorn strain. Multivariate analysis was used to estimate genetic parameters for shell membrane measurements and shell thickness. The aim was to investigate the possibility of improving shell strength in laying hens by selecting for increased attachment strength. 2. A significant direct selection response for attachment strength was achieved. There was a favourable correlated selection differential in the frequency of cracked eggs which resulted in a nonsignificant but favourable, correlated response. Selection for a strong attachment resulted in a thinner egg shell, and vice versa. Heritabilities were all relatively high (0.30 to 0.70). Most of the genetic correlations were in agreement with the achieved correlated responses. 3. Two factors that probably contributed to the responses in egg shell thickness were an unfavourable genetic correlation between attachment strength and shell thickness, and natural selection against changes in attachment strength, in the form of increased mortality during incubation and hatching. Problems connected with breeding for increased shell strength are discussed.

Animals↗
PubMed2005

Evolutionary dynamics of human retroviruses investigated through full-genome scanning.

To test hypotheses on the differences in retroviral genetic diversity, we compared the evolutionary dynamics of the human immunodeficiency virus type 1 (HIV-1) group M and the primate T-cell lymphotropic virus (PTLV) using a full-genome analysis. Evolutionary rates and nonsynonymous/synonymous substitution rate ratios were estimated across the genome using a maximum likelihood sliding window approach, and molecular clock properties were investigated. We confirm a remarkable difference in genetic stability and selective pressure at the interhost level. While there is evidence for adaptive evolution in HIV-1, the evolution of PTLV is almost exclusively characterized by negative selection or nearly neutral processes. For both retroviruses, evolutionary rate estimates across the genome reflect the differential selective constraints. However, based on the relationship between evolutionary rate and selective pressure and based on the comparison of synonymous substitution rates, the differences in rate between HIV-1 and PTLV cannot be explained by selective forces only. Several evolutionary and statistical assumptions, examined using a Bayesian coalescent method, were shown to have little influence on our inference.

Bayes Theorem↗
PubMed2005

Rapid evolutionary change in a secondary sexual character linked to climatic change.

The ability of organisms to respond evolutionarily to rapid climatic change is poorly known. Secondary sexual characters show the potential for rapid evolutionary change, as evidenced by strong divergence among species and high evolvability. Here we show that the length of the outermost tail feathers of males of the socially monogamous barn swallow Hirundo rustica, feathers that provide a mating advantage to males, has increased by more than 1 standard deviation during the period from 1984 to 2003. Barn swallows from the Danish population studied here migrate through the Iberian Peninsula to South Africa in fall, and return along the same route in spring. Environmental conditions on the spring staging grounds in Algeria, as indexed by the Normalized Difference Vegetation Index, predicted tail length and change in tail length across generations. However, conditions in the winter quarters and at the breeding grounds did not predict change in tail length. Environmental conditions in Algeria in spring showed a temporal deterioration during the study period, associated with a reduction in annual survival rate of male barn swallows. Phenotypic plasticity in tail length of males, estimated as the increase in tail length from the age of 1 to 2 years, decreased during the course of the study. Estimates of directional selection differentials for male tail length with respect to mating success, breeding date, fecundity, survival and total selection showed temporal variation, with the intensity of breeding date selection, survival selection and total selection declining during the study. Response to selection as estimated from the product of heritability and total selection was very similar to the observed temporal change in tail length. These findings provide evidence of rapid micro-evolutionary change in a secondary sexual character during a very short time period, which is associated with a rapid change in environmental conditions.

Algeria↗
PubMed1991

On the complexity of self.

Self peptides bound to self major histocompatibility complex (MHC) molecules have been implicated both in positive and in negative selection of T cells during intrathymic development. We report here that the novel MHC-restricted monoclonal antibody Y-Ae detects the MHC class II bound form of a major self peptide. Y-Ae binds approximately 12% of the relevant MHC class II molecules on self antigen presenting cells. The peptide detected by Y-Ae is one of several major peptides eluted from the MHC molecule. These data suggest that self peptides presented by self MHC class II molecules at densities sufficient to signal a CD4 T cell are of very limited complexity. Furthermore, as Y-Ae stains antigen presenting cells that mediate negative selection but not thymic cortical epithelial cells that drive positive selection, differential expression of self peptide:self MHC class II complexes may be a key feature of intrathymic selection.

Amino Acid Sequence↗
PubMed2000

The evolution of the G matrix: selection or drift?

The evolution of quantitative characters can be described by the equation Deltaz=GP-1S where Deltaz is the vector of mean responses, G is the matrix of additive genetic variances and covariances, P is the matrix of phenotypic variances and covariances and S is the vector of selection differentials. This equation can be used to predict changes in trait values or to retrospectively estimate the selection gradient and is thus a central equation of evolutionary quantitative genetics. Genetic variances and covariances will be reduced by stabilizing selection, directional selection and drift, and increased by mutation. Changes in trait values resulting from directional selection that are comparable with differences observed among species are readily obtainable in short geological time spans (<5000 generations) with selection intensities so small that they would have an insignificant effect on the G matrix (of course it is possible that such changes came about by strong selection over a few generations, followed by long periods of stasis; there is insufficient evidence to presently distinguish these two possibilities). On the other hand, observed effective population sizes are sufficiently small that considerable changes in G can be expected from drift alone. The action of drift can be distinguished from selection because the former produces a proportional change in G whereas the latter, in general, will not. A survey of studies examining variation in G suggests that the null hypothesis that most of the variation can be attributed to drift rather than selection cannot be rejected. However, more research on the predicted statistical distribution of G as a result of selection and/or drift is required and further development of statistical tests to distinguish these two forces needs to be made.

Animals↗
PubMedDate not supplied

Intraperitoneal transplantation of pancreatic anlagen.

To determine whether embryonic pancreatic anlagen transplanted to an intraperitoneal site in adult hosts grow, differentiate, and function, we implanted pancreas from embryonic day (E) 12.5 Lewis rat embryos into the omentum of adult Lewis rats or C57Bl/6J mice. E12.5 pancreatic anlagen were relatively undifferentiated except for the presence of condensing tubuloacinar cords. By 2 weeks after implantation, pancreatic anlagen transplanted into rats had enlarged and differentiated such that islets of Langerhans that stained positive for insulin could be delineated. Continued differentiation, as reflected by the presence of "ductal" islets connected to the duct epithelium, was observed at 6 weeks after implantation. At 15 weeks after implantation, "mature" islets had separated from the ducts. Electron microscopy showed eccentric dense bodies within clear vacuoles consistent with insulin granules. Little or no acinar tissue was present in developed anlagen. Within 5 weeks of pancreatic anlagen transplantation, levels of glucose in rats rendered diabetic by an injection of streptozotocin were normalized compared with levels in nontransplanted diabetic controls. Rat pancreatic anlagen underwent growth and development in the peritoneum of C57Bl/61 mice that received costimulatory blocking agents but not in the absence of costimulatory blockade. We concluded that whole E12.5 pancreatic anlagen undergo growth, differentiation, and function after intraperitoneal placement. Implantation of the embryonic pancreas, a "cellular" transplant, is followed by selective differentiation of islet compared with acinar components.

Animals↗
PubMed2006

Detection of differential gene expression in brown adipose tissue of hibernating arctic ground squirrels with mouse microarrays.

Hibernation is an energy-saving strategy adopted by a wide range of mammals to survive highly seasonal or unpredictable environments. Arctic ground squirrels living in Alaska provide an extreme example, with 6- to 9-mo-long hibernation seasons when body temperature alternates between levels near 0 degrees C during torpor and 37 degrees C during arousal episodes. Heat production during hibernation is provided, in part, by nonshivering thermogenesis that occurs in large deposits of brown adipose tissue (BAT). BAT is active at tissue temperatures from 0 to 37 degrees C during rewarming and continuously at near 0 degrees C during torpor in subfreezing conditions. Despite its crucial role in hibernation, the global gene expression patterns in BAT during hibernation compared with the nonhibernation season remain largely unknown. We report a large-scale study of differential gene expression in BAT between winter hibernating and summer active arctic ground squirrels using mouse microarrays. Selected differentially expressed genes identified on the arrays were validated by quantitative real-time PCR using ground squirrel specific primers. Our results show that the mRNA levels of the genes involved in nearly every step of the biochemical pathway leading to nonshivering thermogenesis are significantly increased in BAT during hibernation, whereas those of genes involved in protein biosynthesis are significantly decreased compared with summer active animals in August. Surprisingly, the differentially expressed genes also include adipocyte differentiation-related protein or adipophilin (Adfp), gap junction protein 1 (Gja1), and secreted protein acidic and cysteine-rich (Sparc), which may play a role in enhancing thermogenesis at low tissue temperatures in BAT.

Adipose Tissue, Brown↗
PubMed1999

Contrasting effects of selective T- and L-type calcium channel blockade on glomerular damage in DOCA hypertensive rats.

Mibefradil and amlodipine are calcium antagonists with different channel selectivities. Mibefradil blocks both L- and T-type calcium channels; although in the usual pharmacological doses, it predominantly blocks the T-type channels. In contrast, amlodipine selectively blocks L-type channels. The goal of the present study was to assess whether this differential selectivity would result in different effects on end-organ damage in experimental hypertension. For this purpose, deoxycorticosterone acetate (DOCA)-salt hypertensive rats were treated either with equipotent doses of mibefradil or amlodipine (30 mg. kg(-1). d(-1) as food admix). Despite the fact that both drugs decreased systolic arterial pressure to the same extent (140+/-5 mm Hg in the mibefradil group and 144+/-3 mm Hg in the amlodipine group versus 225+/-5 mm Hg in the untreated-DOCA group), only mibefradil decreased proteinuria (35. 5+/-6.5 versus 103.3+/-14.1 mg/24 h in untreated DOCA-salt animals) and prevented glomerular lesions. Both drugs, however, prevented the occurrence of vascular renal lesions. To elucidate the mechanism responsible for this difference, we evaluated in an additional series of experiments the effects of mibefradil and amlodipine on plasma and renal renin concentrations, as well as the effects of the addition of enalapril, an ACE inhibitor, given on top of both drugs on proteinuria. Amlodipine, in contrast to mibefradil, markedly stimulated the plasma (17.8+/-2.6 ng Ang I. mL(-1). h(-1) in the amlodipine group versus 3.9+/-0.4 ng Ang I. mL(-1). h(-1) in the mibefradil group and 3.2+/-0.3 ng Ang I. mL(-1). h(-1) in the untreated-DOCA group) and renal (2.42+/-0.37 ng Ang I. mL(-1). h(-1) in the amlodipine group versus 0.36+/-0.04 ng Ang I. mL(-1). h(-1) in the mibefradil group and 0.26+/-0.08 ng Ang I. mL(-1). h(-1) in the untreated-DOCA group) renin concentrations. Stimulation of the renin-angiotensin system could explain the absence of a renal protective effect of amlodipine. This was also suggested by the fact that enalapril given in addition to amlodipine could decrease proteinuria. In conclusion, T-type channel blockade by mibefradil decreases blood pressure without stimulation of the renin-angiotensin system and therefore prevents most of the glomerular damage in DOCA hypertensive rats.

Amlodipine↗
PubMed1992

Predicting lean growth while accounting for correlated traits.

Lean tissue growth rate is usually estimated from indirect measurements including growth rate. A procedure to determine prediction equations for lean tissue growth rate is proposed. The procedure restricts the regression of fat growth rate on predicted lean growth rate to be equal to the regression of fat growth rate on actual lean growth rate. The restriction can be phenotypic or genetic if suitable parameter estimates are available. When applied phenotypically, selection on predicted lean tissue growth rate will result in selection differentials for both fat and lean tissue growth rates that are proportional to those obtained by direct selection for lean tissue growth rate. This restriction is desirable because expected correlated changes in fat are used to justify selection for lean tissue growth. Conventional prediction procedures have ignored correlated changes and obscured the original intent of using lean tissue growth rate as a biological selection criterion. When using conventional procedures to predict a biological selection criterion from indirect measurements, changes in important correlated traits may depend more on the choice of indirect measurements than on the choice of selection criterion.

Adipose Tissue↗
PubMed1985

Heterogeneity's ruses: some surprising effects of selection on population dynamics.

"As a cohort of people, animals, or machines ages, the individuals at highest risk tend to die or exit first. This differential selection can produce patterns of mortality for the population as a whole that are surprisingly different from the patterns for subpopulations or individuals. Naive acceptance of observed population patterns may lead to erroneous policy recommendations if an intervention depends on the response of individuals. Furthermore, because patterns at the individual level may be simpler than composite population patterns, both theoretical and empirical research may be unnecessarily complicated by failure to recognize the effects of heterogeneity."

Cohort Studies↗
PubMed1996

[ERG diagnosis and differential diagnosis: results of examination over 6 years].

PURPOSE: This study reviews the patient material first from the point of view of referral diagnosis. Secondly, we focus on difficulties in selective differential diagnoses. PATIENTS AND METHOD: 1501 patients underwent electroretinographic (ERG) testing from 1989 to 1994, amounting to 1815 ERG recordings, including follow-up examinations. The technique applied is full-field, single flash ERG with selective stimulation of the rod- and of the cone-systems. In 3.8% (57 cases) the ERG was performed under general anesthesia in outpatients. RESULTS: Tapetoretinal degenerations, toxic retinal side effects, inflammatory disease and ocular trauma represented, in this order, the major groups of referral diagnoses aside from unclear visual loss. The documentation or the exclusion of tapetoretinal degeneration represented the largest share (57%) of the application of the diagnostic procedure. 171 cases of isolated retinitis pigmentosa (RP) and 33 cases of syndromic RP were identified. Frequent and rare diagnostic entities and their differential diagnoses within this group are discussed. Inevitably, a number of diagnostic decisions remain problematic, in particular at the first examination. These diagnostic difficulties are addressed also and include the differentiation between RP sine pigmento and congenital amaurosis Leber in infants, RP with macular involvement vs. cone-rod degeneration, unilateral RP vs. postinflammatory conditions, and progressive cone dystrophy vs. achromatopsia, cone-rod degeneration or Stargardt's disease. CONCLUSIONS: Frequent and meaningful indications for ERG recording and difficult diagnostic decisions arise from this review of a relatively large group of patients. A number of diagnoses can hardly, if not at all be established without ERG testing. These include retinal cause of visual loss in infants, congenital amaurosis Leber, RP sine pigmento, early stages of RP, carrier status in XL RP and in choroideremia, progressive cone dystrophy, toxic retinopathy without fundus changes, retinal involvement in uveitis with opaque media, and incomplete CSNB.

Adult↗
PubMed2006

Characterization of genes associated with different phenotypes of human bladder cancer cells.

To identify genes associated with morphological phenotypes of human bladder transitional cell carcinoma, we used suppression subtractive hybridization (SSH) to create a subtractive cDNA library of two established cell lines, BLZ-211 and BLS-211, derived from a patient with transitional cell carcinoma of the bladder, then to screen for differentially expressed genes. Real-time reverse transcription-polymerase chain reaction was used to further confirm the selected differentially expressed genes. Forward and reverse subtractive cDNA libraries yielded 168 and 305 putative clones, and among them more than 90% contained the inserts. After differential screening, 36 different transcripts were obtained from 64 cDNA clones of a forward and reverse subtraction library. Among them, 17 were identified as known genes by homology, for example, Vimentin, Keratin7, DDH and UCH-L1. The remaining 19 were unknown expressed genes, and were collected as new expressed sequence tags by the GenBank dbEST database. Their function will be studied further. Thus, SSH appears to be a useful technique for identifying differentially expressed genes between cell lines or clones. Our results, as revealed by SSH, also suggest that differences in gene expression of cytoskeletal proteins might contribute to the different morphologies in BLZ-211 and BLS-211 cells.

Base Sequence↗
PubMed1992

Identification of a new brain-specific transcription factor, NURR1.

We have identified and cloned a novel member of the nuclear receptor superfamily. The cDNA was isolated from a mouse brain cDNA library and encodes a protein 598 amino acids in length with a predicted mol wt of 66 kilodaltons. The amino acid sequence of the protein is closely related to an additional family member and immediate early gene product, Nur77, and the novel factor is referred to as Nurr1 (Nur-related factor 1). The relationship between Nurr1 and Nur77 suggests that these proteins constitute an additional subfamily within the nuclear receptor superfamily. Like Nur77, the expression of Nurr1 is induced by membrane depolarization of PC12 cells. However, while Nur77 shows an early transcriptional response to nerve growth factor stimulation, the failure of Nurr1 to respond to this agent suggests a differential selectivity of the two proteins in terms of their transcriptional responses to specific stimuli. Finally, both proteins are differentially expressed during development and in tissues of the adult mouse. Unlike Nur77, Nurr1 appears to be predominantly located in brain tissue, suggesting a primary role for this putative transcription factor in regulation of gene expression in the central nervous system.

Action Potentials↗
PubMed1990

[Quantitative evaluation of growth-promoting properties of selected culture media used for isolation of Salmonella and Shigella strains].

Growth promoting properties and selectivity of 11 commercially produced media recommended for Salmonella and Shigella isolation were evaluated. The following media were tested: EMB (Eosin methylene blue agar), Endo, Płoskiriew, MacConkey, DC (Deoxycholate citrate agar), SS (Salmonella-Shigella agar), BS (Bismuth sulfite agar) and Mueller-Hinton as a medium with no selective properties. The media were produced in Czechoslovakia, East Germany, West Germany, Poland, and Soviet Union. Quantitative studies were performed on 71 strains representing 8 genera of Enterobacteriaceae family; both reference and wild newly + isolated from clinical material strains were included. It was found that none of DC and BS media provided suitable growth conditions for Shigella strains and in particular for S. dysenteriae, S. boydii, and S. flexneri. It was also found that the same medium (name and content) but derived from different producer can vary significantly in respect to growth promotion and selectivity especially for Shigella strains. All media with selective, differentiating properties for Salmonella and Shigella isolation should not be used without previous quantitative control test for their selective and growth promoting properties checked by user. The need for such a control performed both on reference and freshly isolated strains was shown in this study. In the set of control strains all species of Shigella should be represented.

Agar↗
PubMed1987

Genetic differentiation among cottontails from isolated playa basins.

Protein variation in 182 Sylvilagus floridanus from 19 playa basins in Castro Co., Texas was examined using starch-gel electrophoresis. Heterozygote deficiencies were noted for all populations. This heterozygote deficiency may be due to differential selection against heterozygous individuals over the winter months. Results of F-statistics indicated a significant degree of population differentiation at six loci. Nei's genetic distance between populations ranged from 0.20 to 0.388 and a significant association between genetic distance and linear geographic distance among playas was found. These results suggest that genetic exchange and long-distance dispersal may be hindered by expanses of unsuitable habitat.

Animals↗
PubMed1985

Involvement of acyl exchange between acyl-CoA and phosphatidylcholine in the remodelling of phosphatidylcholine in microsomal preparations of rat lung.

Microsomal membrane preparations from rat lung catalyse the incorporation of radioactive linolenic acid from [14C]linolenoyl-CoA into position 2 of sn-phosphatidylcholine. The incorporation was stimulated by bovine serum albumin and free CoA. Free fatty acids in the incubation mixtures were not utilised in the incorporation into complex lipids. Fatty acids were transferred to the acyl-CoA pool during the incorporation of linolenic acid into phosphatidylcholine. An increase in lysophosphatidylcholine occurred in incubations containing both bovine serum albumin and free CoA and in the absence of acyl-CoA. The results were consistent with an acyl-CoA: lysophosphatidylcholine acyltransferase operating in both a forwards and backwards direction and thus catalysing the acyl exchange between acyl-CoA and position 2 of sn-phosphatidylcholine. In incubations with mixed species of acyl-CoAs, palmitic acid was the major fatty acid substrate transferred to phosphatidylcholine in acyl exchange, whereas this acid was completely selected against in the acylation of added lysophosphatidylcholine. The selectivity for palmitoyl-CoA was particularly enhanced when the mixed acyl-CoA substrate was presented to the microsomes in molar concentrations equivalent to the molar ratios of the fatty acids in position 2 of sn-phosphatidylcholine. During acyl exchange, the predominant fatty acid transferred to phosphatidylcholine from acyl-CoA was palmitic acid, whereas arachidonic acid was particularly selected for in the reverse reaction from phosphatidylcholine to acyl-CoA. A hypothesis is presented to explain the differential selectivity for acyl species between the forward and backward reactions of the acyltransferase that is based upon different affinities of the enzyme for substrates at high and low concentrations of acyl donor. Acyl exchange between acyl-CoA and phosphatidylcholine offers, therefore, a possible mechanism for the acyl-remodelling of phosphatidylcholine for the production of lung surfactant.

Acyl Coenzyme A↗