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PubMed1994

Restraint, fear, and distress in Japanese quail genetically selected for long or short tonic immobility reactions.

Japanese quail genetically selected for long (LTI) rather than short (STI) tonic immobility reactions showed more pronounced overt fear-responses in a number of putatively frightening situations. Greater fear has also been found in Japanese quail selected, in an independent program, for exaggerated (HS, high stress) rather than reduced (LS, low stress) plasma corticosterone response to brief mechanical restraint. The present study examined tonic immobility (TI) and adrenocortical responses in male and female quail of the LTI, STI and CON (control) lines which had either remained undisturbed or had been briefly exposed to a mechanical restraint stressor similar to that used for selection of the HS and LS lines. Behavioral strategies during restraint differed across lines, i.e., struggling followed the pattern STI > CON > LTI. The LTI quail showed more pronounced TI reactions than did CON and STI birds. Mechanical restraint prolonged subsequent TI responses and markedly elevated plasma corticosterone concentrations in all lines, but there were no line x treatment interactions. The results are discussed in terms of the parallels between the four selected lines and of the likelihood that the independent selection programs may have affected the same intervening variable.

Animals↗
PubMed1990

Ontogeny of social behavior of pups of laboratory rats genetically selected for activity level.

In pups of Wistar laboratory rats genetically selected for high (+A) and low (-A) locomotor activity in an open field social behavior was tested in a situation of paired interactions in a novel environment. Tests were performed on postnatal Days 16, 19, 23, and 27. They consisted of four five-minute trials with 50 min, intertrial intervals. Duration of active contacts, passive contacts, mutual grooming, following (chasing), and playful fighting was recorded. In pups of the +A line total duration of all social interactions increased between Days 16 and 23, while in the -A pairs preweaning maximum in most types of social activities was achieved already on Day 16, after this day the time spent in mutual contacts decreased. Analysis of dynamics of social behavior over trials in the -A line showed the tendency to habituate, maximum duration of paired interactions appeared in the first trial contrary to +A groups, in which duration of social contacts tended to increase with repeated trials. In both lines, duration of following responses increased from Day 16 to Day 27. In +A pairs following often led to playful fighting, while in -A pairs fighting was practically absent. The experiment demonstrated that differences between lines +A and -A appeared in those social contacts which required higher energy expenditure and which realized themselves in the larger space of the testing box.

Animals↗
PubMed1999

Genetic selection of peptide inhibitors of biological pathways.

Genetic selections were used to find peptides that inhibit biological pathways in budding yeast. The peptides were presented inside cells as peptamers, surface loops on a highly expressed and biologically inert carrier protein, a catalytically inactive derivative of staphylococcal nuclease. Peptamers that inhibited the pheromone signaling pathway, transcriptional silencing, and the spindle checkpoint were isolated. Putative targets for the inhibitors were identified by a combination of two-hybrid analysis and genetic dissection of the target pathways. This analysis identified Ydr517w as a component of the spindle checkpoint and reinforced earlier indications that Ste50 has both positive and negative roles in pheromone signaling. Analysis of transcript arrays showed that the peptamers were highly specific in their effects, which suggests that they may be useful reagents in organisms that lack sophisticated genetics as well as for identifying components of existing biological pathways that are potential targets for drug discovery.

Amino Acid Sequence↗
PubMed1995

Response to dietary fat and cholesterol in young adult boars genetically selected for high or low plasma cholesterol.

Twenty-eight young adult boars (age 7 to 8 mo) genetically selected for four generations for high (HG) or low (LG) plasma cholesterol were studied to assess dietary and genetic effects and their interactions on cholesterol metabolism. Boars within a genetic group were paired according to their plasma cholesterol concentration at 8 wk of age and were fed for 15 wk (2.7 kg/d) one of two diets (16.5% fat and 1,156 mg of cholesterol/kg diet, HD; or 3.1% fat and 0 cholesterol diet, LD) in a 2 x 2 factorial arrangement. Plasma total cholesterol (P < .01) and HDL-cholesterol (P < .01) concentrations were higher in boars fed HS (P < .01) and in HG boars (P < .01). There was a trend toward a diet x genotype interaction for plasma HDL-cholesterol (P < .06). Plasma insulin concentration tended to be lower in boars fed HD (P < .09) or HG boars (P < .10). There was a diet x genotype interaction for plasma glucagon (P < .04) concentration and a trend toward an interaction for insulin (P < .07). After 15 wk, all boars were killed by electrocution and exsanguination and measurements were taken. Backfat thickness was greater (P < .01) and carcass length (P < .01) and weights of the four lean cuts (P < .02) were lower in LG than in HG boars. No microscopic atherosclerotic plaques were observed in aorta or coronary arteries. Cholesterol concentration in subcutaneous fat was lower (P < .04) in LG boars, suggesting that cholesterol content of depot fat can be reduced by genetic selection in swine.

Adipose Tissue↗
PubMed2002

Development of a genetic selection for catalytic antibodies.

The design and evaluation of a new genetic selection system for evolving catalytic antibodies with aldolase activity are described. Through a series of model selections, we have identified selection conditions where expression of a catalytically active antibody confers a growth advantage to Escherichia coli. In addition, we provide evidence that the growth advantage is a direct result of catalytic activity.

Antibodies, Catalytic↗
PubMed1987

Spontaneous wheel running in laboratory rats genetically selected for activity level in a novel environment.

Wistar rats were genetically selected for either high (+A) or low (-A) locomotor activity level in a new environment. The response to the novelty was tested in all filial generations at the age between 75-80 days of life. Groups of 15 +A male rats selected from the 11th and 12th generations were placed in the individual cages connected with rotation wheels at the age 149 +/- 9 days. For a period of 32 days, the spontaneous wheel running activity was recorded for the time intervals 0.00-6.00 a.m., 6.00-12.00, 12.00-18.00, and 18.00-24.00 h. The -A group exhibited a generally low level of running activity over the entire experimental period, whereas the time of running in the +A tended to increase. Inside the +A group, homogeneous as to the short- term activity level, there gradually differentiated two sub-groups, one with relatively constant medium values and the other which showed an enormous prolongation of the time spent with running. The +A and -A groups differed also in their daily activity rhythm. Whereas the +A rats reached maximum of their activity between 18-24 h., followed by a rapid decrease in the morning hours, the -A animals showed a tendency to a later onset of night-type activity, and a higher level continued to morning hours.

Animals↗
PubMed1977

Genetic selection of mice for quantitative responsiveness of lymphocytes to phytohemagglutinin.

A two-way selection was performed in mice according to the quantitative in vitro response of lymph node lymphocytes to the mitogenic activity of phytohemagglutinin (PHA). The foundation population was composed of outbred mice produced by reciprocal mating of equal numbers of mice from four different colonies. The selective breeding was carried out by mating of mice at each generation giving the best or the lowest response, respectively. The progressive interline separation produced by 6 generations of selective breeding demonstrates that responsiveness to PHA is submitted to polygenic regulation. The heritability of the character investigated is 0.28 +/- 0.08. The interline separation is also found with another T mitogen, concanavalin A (Con A). In spleen cells PHA and Con A produce a similar interline difference. In contrast, the purified protein derivative of tuberculin (PPD) stimulated both lines equally, and E. coli lipopolysaccharide gave only a slightly higher response in high line. This finding implies that our selection based upon response to PHA did not influence B cell function.

Animals↗
PubMed1995

A new genetic selection identifies essential residues in SecG, a component of the Escherichia coli protein export machinery.

The signal sequence of the murine serine protease inhibitor PAI-2 promotes alkaline phosphatase export to the E. coli periplasm. However, high level expression of this chimeric protein interferes with cell growth. Since most suppressors of this toxic phenotype map to secA and secY, growth arrest results from a defective interaction of the chimeric protein with the export machinery. We have characterized suppressors which map in secG, a newly defined gene of the export machinery. All single amino acid substitutions map to three adjacent codons. These secG mutants have a weak Sec phenotype, as determined by their effect on export mediated by wild-type and mutant signal sequences. Whilst a secG disruption allele also confers a weak Sec phenotype, it does not suppress the toxicity of the chimeric protein. This difference results from a selective effect of the secG suppressors on the kinetics of export mediated by the PAI-2 signal sequence. Using a malE signal sequence mutant, which has a Mal-phenotype in secG mutant strains, we have isolated extragenic Mal+ suppressors. Most suppressors map to secY, and several are allele-specific. Finally, SecG overexpression accelerates the kinetics of protein export, suggesting that there are two types of functional translocation complexes: with or without SecG.

ATP-Binding Cassette Transporters↗
PubMed1993

Differential effects of ethanol in mouse lines genetically selected for high and low antibody production.

There is considerable evidence of a relationship between the central nervous system and the immune system, and that several drugs with primary action at the central nervous system can affect different immune responses. In an attempt to obtain a better understanding of the interaction between ethanol's effects and immune functions, we used two mouse lines selected according to their high (HGP) or low (LGP) antibody production. These animals were injected with ethanol (20% w/v, 3.6 g/kg, ip); the latency for the loss of the righting reflex (LORR) and the time for the recovery of the righting reflex (RORR) were measured. Body temperature of both lines was also recorded before the injections and at RORR. Blood samples were taken at RORR to determine blood ethanol concentration. The results showed that the HGP mice presented shorter latency for sleep, longer sleeping time, and lower blood ethanol levels than the LGP mice. These data suggest that the HGP line is more sensitive to the effects of ethanol, and provide an additional approach for studying interactions between the immune and the central nervous systems.

Animals↗
PubMed1992

Fear and distress in Japanese quail chicks of two lines genetically selected for low or high adrenocortical response to immobilization stress.

Behavioral and adrenocortical reactivity to stressful stimulation was examined in 12- and 13-day-old chicks of two lines of Japanese quail selected over several generations for exaggerated (HS: high stress) or reduced (LS: low stress) plasma corticosterone (B) response to brief immobilization stress. Plasma B concentrations and tonic immobility (TI) fear reactions were measured in unstressed (control) and stressed (overnight cooping) chicks of both lines. The stress treatment was applied over a period of 12-20 hr and it involved capture by the experimenter, inescapable exposure to an unfamiliar environment and to strange conspecifics, reductions in ambient temperature and floor space, and the deprivation of food and water. Chicks of the HS line were more susceptible to the induction of TI and they remained immobile longer than did LS chicks. Therefore HS chicks were considered to be more fearful than their LS counterparts. Stress treatment elicited a marked adrenocortical response that was more pronounced in HS than in LS chicks. Stress treatment also increased susceptibility to TI but did not significantly affect the duration of immobility. These findings suggest that selecting the quail for differential corticosterone response to a particular stressor had exerted an unconscious and concomitant effect on underlying fearfulness as well as on their adrenocortical reactivity to several other stressful situations. The results are further discussed in terms of a putative relationship between adrenocortical activation and fearfulness.

Adrenal Cortex↗
PubMed1984

Effects of chronically elevated intake of different concentrations of saccharin on morphine tolerance in genetically selected rats.

Sixty-four LC2-Hi and LC2-Lo female rats were chronically supplied with either water or a solution of 1, 3 or 30 mM of sodium-saccharin. Pain sensitivity, as well as its reduction by a 2.5 mg/kg morphine injection, were measured in a hot-plate test. High saccharin consuming LC2-Hi rats did not exhibit significant morphine-induced analgesia (MIA) compared to baseline, after 38 days of drinking of saccharin, irrespective of concentration. MIA of those rats were maintained on water was significant. In contrast, the low consuming LC2-Lo animals maintained either on water or on 1 and 30 mM saccharin showed significant MIA compared to baseline, following the same exposure period. The findings demonstrate that chronically elevated saccharin intake, activates an endogenous opiate system leading ultimately to cross-tolerance to the analgetic effects of morphine.

Animals↗
PubMed1993

Responses to isolation in Japanese quail genetically selected for high or low sociality.

The adrenocortical, behavioral, and leucocytic responses to isolation, for 1, 3, or 72 h, of 7-10-day-old Japanese quail chicks, of lines selected for high (HSR) or low (LSR) levels of social reinstatement (SR) behavior, were studied. Isolation had no effect on plasma corticosterone levels of heterophil/lymphocyte measures in LSR line chicks. Conversely, circulating corticosterone levels were increased after 1 h of isolation in the HSR line, although they fell to control levels thereafter. Heterophil/lymphocyte ratios of HSR line chicks were also increased after 3 h of isolation but decreased to control levels thereafter. Isolated HSR line chicks were consistently more active and showed more peeping and jumping than LSR line chicks in which sitting and lying were more frequent. However, no such behavioral divergence was observed when HSR and LSR line chicks were housed in same-line groups. These results indicate that selection for SR behavior has influenced both underlying social motivation and responses to short-term isolation. Social separation appeared to be more stressful for HSR than LSR line chicks.

Animals↗