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PubMed1981

Social class and psychological disorder in natives and immigrants to Britain.

An examination is made of various hypotheses which have been developed to account for the frequently observed inverse relationship between social class and psychological disturbance. Two of these explanations--the social selection and social causation hypotheses--are tested in a study designed to enable an assessment of their relative power to be made. Quasi-random samples of 200 Indian-born, 200 Pakistani-born and 240 native-born residents of England were interviewed and measures of social class, psychological symptoms and other relevant variables made. The results failed to support either of the two hypotheses as the expected social class gradient in psychological disorder only emerged in the native group. Indian immigrants in fact showed a reversal with higher status individuals, especially women, having higher symptom levels. Overall Indian immigrants had significantly fewer symptoms than either of the other groups. The findings are discussed in terms of differential selection for migration and the varying experiences of immigrants after arrival in Britain.

Adult↗
PubMed1992

Correlated responses in reproductive and carcass traits to selection for 200-day weight in Duroc swine.

Correlated responses in reproductive and carcass traits from a line of Duroc pigs selected for increased 200-d weight along with a randomly selected control line were studied in 189 litters (116 select, 73 control) and 191 pigs (106 select, 85 control), respectively. Reproductive and maternal traits studied included litter sizes born, born alive, and alive at 21 d and litter weight at birth and at 21 d. Carcass traits studied were carcass length, longissimus muscle area, average backfat thickness, 10th rib backfat thickness, specific gravity, weights of closely trimmed ham, loin, and shoulder, belly weight, subjective scoring of the longissimus muscle for color and marbling, estimated percentage of muscle and lean gain per day. Total weighted cumulative selection differential for 200-d weight was 81.7 kg. The realized heritability for 200-d weight was .18 +/- .08, and the change in 200-d weight was 2.5 +/- 1.2 kg per generation. The regression coefficient of litter size born on generation was -.29 +/- .12 (P less than .10) pigs per generation. None of the other regression coefficients for the reproductive traits differed from zero. Average backfat thickness, 10th rib backfat thickness, and belly weight increased by .093 +/- .016 cm, .122 +/- .029 cm, and .089 +/- .040 kg, respectively, per generation. Specific gravity, ham weight, shoulder weight, color score, and percentage of muscle decreased -.00086 +/- .00024, -.165 +/- .013 kg, -.104 +/- .011 kg, -.035 +/- .015 points, and -.47 +/- .12%, respectively, per generation in response to the selection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1981

Differential glycosylation of murine B cell and spleen adherent cell Ia antigens.

Examination of I-A and I-E molecules from purified B cells and splenic adherent cells from various haplotypes revealed a consistent difference in isoelectric focusing (IEF) that has been localized to the alpha-chain. alpa-Chains from B cells appeared heterogeneous and contained acidic IEF bands absent from the adherent cell I-A molecules. No difference in Ia beta-chain or H-2 IEF patterns was observed when B cell and adherent cell preparatios were compared when B cell and adherent cell preparations were compared. I-A alpha-chain preparations from the 2 cell sources showed no differences in 3H-leucine-labeled tryptic peptides separated by reverse-phase high-pressure liquid chromatography. Digestion with neuraminidase, kinetics of labeling, and subcellular distribution indicated that the extra acidic IEF bands in B cell Ia represent a mature, more heavily sialated form of alpha-chain that is not present in adherent cells. The selective differential glycosylation of B cell and adherent cell Ia could have some relation to the function of those cell types or to cell type-specific recognition of those cells.

Animals↗
PubMed1994

Cost and intensity of care in case managers' referrals to psychiatric day programs.

OBJECTIVE: The purpose of the study was to determine whether case managers referred clients with different needs to programs with different goals and levels of intensity, and thus with different costs. METHOD: A total of 150 case managers were asked to select one of three day programs--day treatment, clubhouse, or supported employment--for four hypothetical clients described in case vignettes. They also were asked to choose any or all of three types of concurrent services for these clients, including a medication clinic, outpatient counseling, and a social club. They listed the five most important criteria for making their decisions. RESULTS: The 70 case managers who responded to the survey consistently referred the most functionally impaired clients to day treatment programs and recommended fewer support services for those clients. The least impaired clients were referred to clubhouse or supported employment programs, and many support services were recommended. The most important decision-making criteria cited were clients' motivation, problem-solving ability, and history. CONCLUSIONS: Case managers differentially select day programs based on clients' functional ability. Clients referred to vocationally oriented programs are also referred to concurrent services that increase the cost of the total service package.

Adult↗
PubMed2000

A performance-dependent adjustment of the retention interval in a delayed non-matching-to-position paradigm differentiates effects of amnestic drugs in rats.

Operant delayed non-matching-to-position (delayed non-matching-to-position) tasks have been widely used as tests of working memory in rats, but have suffered some loss in sensitivity to differentiating selective mnemonic from non-mnemonic deficits due to floor and ceiling effects. To circumvent this problem, a novel delayed non-matching-to-position was developed in which the retention interval was adjusted on a trial-by-trial basis to hold performance accuracy at an intermediate value. The present study assessed the effects of three amnestic drugs in this delayed non-matching-to-position. Rats were administered (i.p.) NMDA receptor antagonist ((5R,10S)-(+)-5-Methyl-10, 11-dihydro-5H-dibenzo[a,d,] cyclohepten-5,10-imine (Dizocilpine or MK-801), muscarinic receptor antagonist (-)-scopolamine hydrobromide (scopolamine), or cannabinoid receptor agonist ((R)-(+)-[2, 3-Dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1, 4-benzoxazin-6-yl]-1-naphthalenylmethanone) (WIN 55, 212-2). At high doses, both MK-801 (0.12-0.25 mg/kg) and scopolamine (0.25 mg/kg) produced deficits not selective to working memory. At low doses, scopolamine (0.06-0.12 mg/kg) and MK-801 (0.06 mg/kg) produced no deficits in any mnemonic or secondary measures. WIN 55, 212-2 produced deficits at 2.0 mg/kg that were consistent with a specific impairment of working memory. Using this particular delayed non-matching-to-position revealed that consistent changes in performance accuracy at the short retention interval were evident for scopolamine and MK-801, at times in the absence of changes in response tendency, which are consistent with an interpretation that these drugs produce general deficits in reference or procedural memory. In contrast, cannabinoid-induced deficits in choice accuracy support previous reports of delay-dependent deficits. Together, these data suggest that this delayed non-matching-to-position task is able to differentiate deficit patterns of amnestic drugs, and isolate the effects of motivational side effects of drugs from working memory measurement.

Amnesia↗
PubMed1976

Response to selection for time interval between ovipositions in the hen.

Data were collected from seven generations of selection for reduced time interval between oviposition in a line of Single Comb White Leghorns. This study involved 151 sires, 539 dams, and 2100 female progeny. Oviposition time was measured from 174 to 280 days of age. The only deliberate selection practiced was for reduced oviposition time interval. The mating system was random with the restriction of full or half sib matings. The reduction in oviposition time interval has been 73 minutes or 4.8 percent. There were no significant changes for total egg number, body weight or age at first egg. Rate of lay after reaching 50 percent production to 280 days has increased (P less than .07). Egg weight has declined five percent. Heritability estimates for intra-clutch time interval from correlations were .33 +/- .08, .36 +/- .09 and .35 +/- .15 by sire, dam, and combined components, respectively, .36 +/- .15 by regression of offspring on dam and .39 for realized. The magnitude of the selection differential decreased, over time. The genetic correlation of time interval with early production (280 days) was --.43 +/- .13, and with total egg production (500 days) was .20 +/- .27. The genetic correlations of time interval with egg weight and age at first egg were high and positive; and with body weight, it was negative. The increase in clutch size and the days between clutches during the time of this study were both highly significant.

Animals↗
PubMed2002

Specificity of memapsin 1 and its implications on the design of memapsin 2 (beta-secretase) inhibitor selectivity.

Memapsin 1 is closely homologous to memapsin 2 (BACE), or beta-secretase, whose action on beta-amyloid precursor protein (APP) leads to the production of beta-amyloid (A beta) peptide and the progression of Alzheimer's disease. Memapsin 2 is a current target for the development of inhibitor drugs to treat Alzheimer's disease. Although memapsin 1 hydrolyzes the beta-secretase site of APP, it is not significantly present in the brain, and no direct evidence links it to Alzheimer's disease. We report here the residue specificity of eight memapsin 1 subsites. In substrate positions P(4), P(3), P(2), P(1), P(1)', P(2)', P(3)', and P(4)', the most preferred residues are Glu, Leu, Asn, Phe, Met, Ile, Phe, and Trp, respectively, while the second preferred residues are Gln, Ile, Asp, Leu, Leu, Val, Trp, and Phe, respectively. Other less preferred residues can also be accommodated in these subsites of memapsin 1. Despite the broad specificity, these residue preferences are strikingly similar to those of human memapsin 2 [Turner et al. (2001) Biochemistry 40, 10001-10006] and thus pose a serious problem to the design of differentially selective inhibitors capable of inhibiting memapsin 2. This difficulty was confirmed by the finding that several potent memapsin 2 inhibitors effectively inhibited memapsin 1 as well. Several possible approaches to overcome this problem are discussed.

Amino Acid Sequence↗
PubMed2006

Differential modulation by the GABAB receptor allosteric potentiator 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)-phenol (CGP7930) of synaptic transmission in the rat hippocampal CA1 area.

The recently discovered GABAB receptor-positive allosteric modulators enhanced the potency and efficacy of GABAB receptor agonists in in vitro experiments. These GABAB modulators also attenuated reward and anxiety in behavioral experiments without causing the untoward side effects associated with GABAB receptor activation by agonist administration and hence exhibited potential therapeutic utility. However, the underlying molecular mechanisms enabling the GABAB allosteric modulators to dissociate from the GABAB agonistic side effects remain elusive. To address this question, we have examined the effects of a typical GABAB modulator, 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)-phenol (CGP7930), on GABAB receptor-mediated modulations of both the excitatory and the delayed inhibitory components of hippocampal CA1 synaptic transmission. Using baclofen as an agonist and a multielectrode recording system, we recorded GABAB receptor-mediated modulations of both the field excitatory postsynaptic potentials and the population spikes simultaneously, as well as the paired-pulse inhibition of the population spike. We found that CGP7930 selectively enhanced the baclofen-induced modulation of synaptic inhibition without having any significant effects on the synaptic excitation. Our experiments have therefore revealed a pathway-selective differential modulation of synaptic transmission by CGP7930. This finding provides a synaptic mechanism to support the hypothesis that GABAB potentiators may be a better therapeutic alternative than GABAB agonists for central nervous system disorders.

Action Potentials↗
PubMed2005

"Matched/mismatched" diastereomeric dirhodium(II) carboxamidate catalyst pairs. Structure-selectivity correlations in diazo decomposition and hetero-Diels-Alder reactions.

Homo-ligated dirhodium(II) carboxamidates provide well-defined structural frameworks with which to investigate catalyst-controlled multiple asymmetric induction ("match/mismatch" effects). Diastereomeric pairs of methyl 2-oxoimidazolidine-4(S)-carboxylate ligands containing 2-phenylcyclopropane (4S,2'S,3'S-HMCPIM and 4S,2'R,3'R-HMCPIM) and N-benzenesulfonylproline (4S,2'S-HBSPIM and 4S,2'R-HBSPIM) attachments at the 1-N-acyl site have been prepared; the resulting (cis-2,2)-Rh(2)L(4) compounds have been produced in good yields, and the X-ray crystal structure of each dirhodium(II) compound has been obtained. The incorporation of additional stereocenters into the dirhodium(II) ligands leads to recognizable levels of double asymmetric induction for C-H insertion, cyclopropanation, and hetero-Diels-Alder cycloaddition applications. The configurationally "matched" cases provide modest increases in enantioselectivity for intramolecular C-H insertion reactions relative to the model catalyst Rh(2)(MPPIM)(4), but applications of the configurationally mismatched catalysts result in significant lowering of enantioselectivity. The Rh(2)(BSPIM)(4) catalysts show the highest degree of differential selectivity. Hetero-Diels-Alder reactions show inverse behavior from the configurationally matched and mismatched Rh(2)L(4) catalysts to that found in the metal carbene transformations.

Catalysis↗
PubMed1990

Lack of response to family selection for directional asymmetry in Drosophila melanogaster: left and right are not distinguished in development.

Family selection for directional asymmetry in the expression of the Drosophila melanogaster mutant scute had no result. Fluctuating asymmetry did not show a selection differential correlated with directional asymmetry. The unfolding of bilateral symmetry in embryogenesis can be used to explain the lack of genetic variation for directional asymmetry. Directional asymmetry provides a well-understood example of a developmental constraint in evolution. It is proposed that as no evidence is available for an independent left-right gradient in the embryo, quantitative traits can only be expressed variably along an existing gradient of positional information or a morphogen.

Animals↗
PubMed2001

2-(2-Piperidyl)- and 2-(2-pyrrolidyl)chromans as nicotine agonists: synthesis and preliminary pharmacological characterization.

As part of an effort to develop a new class of subtype selective nicotine agonists, we have synthesized and tested a group of 12 hydroxylated 2-(2-piperidyl)- and 2-(2-pyrrolidyl)chromans. In rat brain membranes, all 12 compounds displayed poor affinity for [(125)I]-alpha-bunagarotoxin binding sites. In contrast, three compounds, 17c, 24, and 26, displayed moderate to high affinity for [(3)H]cytisine binding sites, while three (17b, 18b,c) and six (17a,d,e and 18a,d,e) compounds showed weak and poor affinity, respectively, for these same sites. In subsequent studies, compounds 17a and 17c were found to stimulate the efflux of (86)Rb(+) from rat cortical synaptosomes, an indication of agonist activity. Further, both 17c and 26 displayed high intrinsic activity in stimulating the release of [(3)H]dopamine from striatal synaptosomes; however, only 17c was effective at stimulating the release of [(3)H]acetylcholine from cortical synaptosomes, suggesting differential selectivity. In cloned human nicotinic acetylcholine receptors (nAChR) expressed in Xenopus oocytes, both 17c and 26 activated alpha7 and alpha3beta2 receptor subtypes in a dose-dependent manner, but 26 was clearly the more potent agonist. Last, neither compound displayed dose-dependent activation of alpha4beta2 nAChRs. We conclude that 2-(2-azacyclic)chromans appear to be a promising new class of nicotine agonists.

Acetylcholine↗
PubMed2006

Good genes sexual selection in nature.

Whether the mate sampling and choice performed by females in nature influences offspring performance is a controversial issue in theory and an open empirical question. Pronghorn (Antilocapra americana) females engage in an obvious and energetically expensive mate sampling process to identify vigorous males. Although individual females sample independently, their choices converge on a small proportion of males that sire most young. Offspring of attractive males were more likely to survive to weaning and to age classes as late as 5 years, resulting in a selection differential, calculated by expected differences in lifetime number of offspring weaned, of 0.32 against random mating. Enhanced survival to weaning appeared to be accomplished by faster growth rates. Females compensated for matings with a less attractive mate by elevating rates of milk delivery to their young. Because pronghorn males do not have costly ornaments, we conclude that female choice for good genes can exist in the absence of ornaments. Furthermore, female choice may be important and unrecognized as a force that can lower population genetic load.

Animals↗
PubMed1970

Polymyxin-coagulase-mannitol-agar. I. A selective isolation medium for coagulase-positive Staphylococci.

A selective, differential plating medium was developed for the isolation and identification of coagulase-positive and mannitol-fermenting staphylococci. Coagulase produced by growing Staphylococcus aureus caused an opaque zone of fibrin to form around each colony. Several strains of S. aureus produced a visible coagulase reaction by 8 hr, and all strains gave a positive reaction before 12 hr. Mannitol fermentation was usually observed between 12 and 36 hr. Rabbit serum was filtered through Sephadex G-100 to obtain plasmin- and plasminogen-free coagulase-reacting factor (CRF). False-negative reactions, caused by staphylokinase and staphylococcal Müller factor action on plasminogen, were eliminated when this CRF was used. False-positive reactions by lipolytic, coagulase-negative staphylococci were reduced, since gel filtration removed the serum lipoprotein which served as a primary source of opacity. The addition of 75 mug of polymyxin B per ml selectively retarded the growth of S. epidermidis and minimized false-positive reactions caused by citrate-utilizing gram-negative rods. The preparation, characteristics, and use of the medium are presented.

Agar↗
PubMed1991

Thymic nurse cells: differentiation of thymocytes within complexes.

Thymic nurse cell complexes (TNC-c) were isolated from thymuses of BDF1 mice at pre-determined intervals during the 12-week latency period that precedes the development of leukemias. T-cell leukemias were induced by a single i.v. injection of 50 mg/kg of methylnitrosourea (MNU). In order to clarify processes taking place in TNC-c, the complexes of mice after MNU injection were compared with TNC-c of age-matched control mice, with respect to their number per thymus, the distribution of TNC-c according to their size (the number of intra-TNC thymocytes reflects the type of TNC-c), the number of intra-TNC thymocytes that undergo DNA synthesis, and the phenotype of thymocytes inside TNC-c. During the latency period of leukemogenesis, the effects of MNU were shown to involve, in addition to changes in number of TNC-c, a decrease in the number of thymocytes incorporating labeled thymidine, viz., the number of dividing cells, thus affecting the size distribution of TNC-c types. Intra-TNC thymocytes of control mice were heterogeneous in their phenotype and represented cells at varying stages of their maturation cycle. MNU administration was followed by selective differentiation of thymocytes within TNC-c to Lyt 1-thymocytes in some and to Lyt 2-thymocytes in others. Lyt 1 and Lyt 2 being specific antigens expressed by thymocytes.

Animals↗
PubMed2004

The molecular population genetics of HIV-1 group O.

HIV-1 group O originated through cross-species transmission of SIV from chimpanzees to humans and has established a relatively low prevalence in Central Africa. Here, we infer the population genetics and epidemic history of HIV-1 group O from viral gene sequence data and evaluate the effect of variable evolutionary rates and recombination on our estimates. First, model selection tools were used to specify suitable evolutionary and coalescent models for HIV group O. Second, divergence times and population genetic parameters were estimated in a Bayesian framework using Markov chain Monte Carlo sampling, under both strict and relaxed molecular clock methods. Our results date the origin of the group O radiation to around 1920 (1890-1940), a time frame similar to that estimated for HIV-1 group M. However, group O infections, which remain almost wholly restricted to Cameroon, show a slower rate of exponential growth during the twentieth century, explaining their lower current prevalence. To explore the effect of recombination, the Bayesian framework is extended to incorporate multiple unlinked loci. Although recombination can bias estimates of the time to the most recent common ancestor, this effect does not appear to be important for HIV-1 group O. In addition, we show that evolutionary rate estimates for different HIV genes accurately reflect differential selective constraints along the HIV genome.

Bayes Theorem↗
PubMed1988

Temperature-dependent genotypic selection and embryonic survival of rainbow trout.

The survival of rainbow trout (Salmo gairdneri) with different developmental rates and genotypes at eight polymorphic loci was compared in two experiments. The embryos were reared at temperatures colder (5 and 8 degrees C) and warmer (12 degrees C) than normally experienced by the strain (9.5 degrees C). Embryo survival in five different hatching groups (representing the sequential order of hatching) was compared at 8 and 12 degrees C. Embryos in the center of the hatching distribution (groups 2, 3, and 4) showed a greater survival to yolk sac resorption than those in the extremes (groups 1 and 5). These differences are significant in the embryos reared at 12 degrees C in both experiments. Embryo survival from hatching to yolk sac resorption was poorer at 12 compared to 8 degrees C. In the one experiment where it was examined, significantly fewer embryos hatched at 5 and 12 than at 8 degrees C. Significant deviations from genotypic expectations (based upon parental allele frequencies) were detected in the progeny (23 of 34 cases). In contrast, few deviations from Hardy-Weinberg expectations were detected (5 of 34 cases) when progeny allele frequencies are used. Few significant differences in genotype frequencies were detected among the progeny reared at the different temperatures. This suggests that nonequal contributions of parental gametes rather than differential selection of genotypes account for the deviations from expectations in the progeny.

Acclimatization↗
PubMed1994

Ten generations of selection for predicted weight of testes in swine: direct response and correlated response in body weight, backfat, age at puberty, and ovulation rate.

Selection for predicted weight of testes at 150 d of age (PWT) was practiced for 10 generations to determine the effect on reproductive and growth traits in swine. Mass selection among boars (line TS) or random selection (line C) was practiced beginning with the F3 generation of a Large White x Landrace composite population. Population size in each line was 40 to 45 litters by 15 sires per generation. Responses were estimated by regressions on cumulative selection differentials for PWT and on generation number and by mixed-model derivative-free REML procedures. The realized heritability of PWT was .35 +/- .02 and the response per generation was 19 g (P < .01). Correlated responses in body weight were .95 +/- .37 (140 d) and 1.13 +/- .42 kg (160 d) per generation for boars and .70 +/- .32 (130 d) and .64 +/- .46 kg (180 d) per generation for gilts. Response in backfat was .08 +/- .14 mm per generation in boars and .16 +/- .14 mm in gilts. Negative genetic trends occurred in age at puberty in both lines, but the difference between lines was not significant. At Generation 10, ovulation rate was .76 +/- .43 eggs more for gilts of the TS line than for C gilts. Genetic correlations of PWT with other traits are presented. Heritability of PWT was moderately high and its phenotypic variance was large; therefore, a high rate of response of 5.5% per generation occurred. Selection for PWT was not effective in decreasing age at puberty or increasing ovulation rate of daughters.

Adipose Tissue↗
PubMed2005

Does habitat fragmentation affect temperature-related life-history traits? A laboratory test with a woodland butterfly.

Habitat fragmentation may change local climatic conditions leading to altered selection regimes for life-history traits in small ectotherms, including several insects. We investigated temperature-related performance in terms of fitness among populations of the woodland butterfly Pararge aegeria (L.) originating from populations of a closed, continuous woodland landscape versus populations of an open, highly fragmented agricultural landscape in central Belgium. Female fecundity and longevity were evaluated in a temperature-gradient experiment. As predicted, females of woodland landscape origin reached higher maximum daily fecundity and lifetime number of eggs than did agricultural landscape females at low ambient temperatures, but this reversed at high ambient temperature. Egg weight decreased with temperature, and eggs of woodland butterflies were smaller. Contrary to what is generally assumed, remaining thorax mass was a better predictor of lifetime reproductive output than was abdomen mass. Since we used the F2 generation from wild-caught females reared under common garden conditions, the observed effects are likely to rely on intrinsic, heritable variation. Our results suggest that differential selection regimes associated with different landscapes intervene by intraspecific variation in the response of a butterfly to variation in ambient temperature, and may thus be helpful when making predictions of future impacts on how wild populations respond to environmental conditions under a global change scenario, with increasing temperatures and fragmented landscapes.

Adaptation, Physiological↗