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Selection with restriction in a poultry breeding scheme with different selection procedures in both sexes: direct responses.

1. A selection experiment with two lines of White Leghorns originating from a common base population was carried out over 5 generations with the aims of maintaining an unchanged egg weight, reducing age at first egg and reducing adult body weight. Each line consisted of 14 male and 42 female breeders. 2. Males were mass selected for low body weight at 20 weeks of age. To compensate for the expected correlated loss in egg weight, hens were selected according to an index which counteracted this undesirable change while also reducing age at first egg and reducing body weight. 3. An index value was calculated for each individual hen from average egg weight, age at first egg and body weight at 20 weeks. Index weights had to be calculated for each generation and line in accordance with the expected change in egg weight due to male selection on body weight. 4. For control matings hens with an index near the population average were mated either to males with body weight near the population average (control C1) or to the selected males within lines (control C2). 5. Expected and observed total responses agreed well for all traits in line 1 and for body weight in line 2. 6. Phenotypic variances and covariances showed little change during the experiment. However, genetic variances and covariances estimated at the end of the experiment showed some differences, both between lines and compared to the parameters used for index construction.

Animals↗

Selection with partial selfing. I. Mass selection.

The expected responses to mass selection carried out before or after reproduction in a population whose members all have a fixed probability of self pollination (s) are formulated using covariances of relatives and their component quadratic functions for a model with arbitrary additive and dominance effects. The response measured in the first generation offspring after selection (immediate gain) can differ from that retained when the population has regained equilibrium (permanent gain). The population mean behaves in a predictable manner during the return to equilibrium, and its value at any time can be predicted from earlier generations. The permanent gain from selection after reproduction is always (1 + s)/2 times as large as that from selection before reproduction, but the relationship of the immediate gains depends on the genetic model assumed. Numerical analysis applied to a model with two alleles per locus and varying allele frequencies, dominance ratios and numbers of loci showed that the proportion of the immediate gain retained at equilibrium was reduced with the large inbreeding depression associated with increasing dominance levels and numbers of loci and was generally lower for selection after reproduction than before. In the absence of information as to the magnitude of genetic variances and inbreeding depression in species reproducing by partial selfing, the importance of this phenomenon is unknown.

Genetic Variation↗

Effects of population size and selection intensity on correlated responses to selection for postweaning gain in mice.

Correlated responses to selection for postweaning gain in mice were studied to determine the influence of population size and selection intensity. Correlated traits measured were three-, six- and eight-week body weights, litter size, twelve-day litter weight, proportion infertile matings and two indexes of reproductive performance. In general, the results agreed with observations made on direct response: correlated responses in the body weight traits and litter size increased as (1) selection intensity increased and (2) effective population size increased. Correlated responses in the body weight traits and litter size were positive in the large population size lines (16 pairs), as expected from the positive genetic correlation between these traits and postweaning gain. However, several negative correlated responses were observed at small population sizes (one and two pairs). Within each level of selection intensity, traits generally associated with fitness tended to decline most in the very small populations (one and two pairs) and in the large populations (16 pairs) for apparently different reasons. The fitness decline at the small effective population sizes was attributable to inbreeding depression. In contrast, it was postulated that the fitness decline at the large effective population size was due to selection moving the population mean for body weight and a trait positively correlated genetically with body weight (i.e., percent body fat) away from an optimum.

Age Factors↗

The effects of disruptive and stabilizing selection on body size in Drosophila melanogaster. II. Analysis of responses in the thorax selection lines.

An analysis was made of changes in mean and variance in some thorax selection lines. The decrease of mean thorax length in the stabilizing selection lines (S) was a consequence of a directional selection component, caused by the skewness of the frequency distributions. The slight or temporary increase of the phenotypic variance and the large increase of the mean value in the disruptive selection lines with random mating (D(R)) could be attributed to differences in reproduction between small and large flies (egg production and mating success). Phenotypic variability was high in two disruptive selection lines with compulsory mating of opposite extremes (D(-)). The mechanism of the change in variability was different in these replicate lines. In D(-)-1 the change was obtained by an increase of the environmental and the nonadditive genetic components of the variance. In D(-)-2 almost exclusively an increase of additive genetic variance occurred.

Analysis of Variance↗

Selection for plasmid post-segregational killing depends on multiple infection: evidence for the selection of more virulent parasites through parasite-level competition.

Is the virulence of parasites an outcome of optimized infection? Virulence has often been considered an inevitable consequence of parasite reproduction when the cost incurred by the parasite in reducing the fitness of its current host is offset by increased infection of new hosts. More recent models have focused on how competition occurring between parasites during co-infection might effect selection of virulence. For example, if co-infection was common, parasites with higher intrinsic growth rates might be selected, even at the expense of being optimally adapted to infect new hosts. If growth rate is positively correlated with virulence, then competition would select increased virulence. We tested these models using a plasmid-encoded virulence determinant. The virulence determinant did not contribute to the plasmid's reproduction within or between hosts. Despite this, virulent plasmids were more successful than avirulent derivatives during selection in an environment allowing within-host competition. To explain these findings we propose and test a model in which virulent parasites are selected by reducing the reproduction of competitors.

Animals↗

Bidirectional selective breeding for ethanol effects on locomotor activity: characterization of FAST and SLOW mice through selection generation 35.

Increased recognition of the advantages of genetic animal models has led to heightened interest in their use and development. A replicated bidirectional selective breeding project has produced lines of mice that differ in their locomotor responses to 2.0 g/kg ethanol. FAST-1 and FAST-2 mice are highly stimulated by ethanol (EtOH), whereas SLOW-1 and SLOW-2 mice are either not affected or respond with locomotor depression. Current heritability estimates indicate that approximately 6-8% of the response variance in the FAST lines and 2-10% of the response variance in the SLOW lines is of additive genetic origin. Little systematic response to selection has occurred in recent generations, which implies that the limits of selection have been reached. Analysis of saline activity over 35 generations of selection indicates that baseline activities have not changed during the course of selection in three of the lines, whereas baseline activity of FAST-1 mice has increased slightly. In EtOH dose-response studies (0.5-3.0 g/kg), FAST mice had biphasic dose-response curves, whereas the locomotor activity of SLOW mice was either unaffected or depressed by all doses of EtOH. In addition, FAST mice spent more time in motion, traveled farther per movement, traversed greater distances in the center of the test chamber, and ambulated more quickly than SLOW mice when given EtOH. FAST and SLOW mice differed in EtOH clearance rates; however, the differences were slight relative to the large difference in locomotor response. We encourage the use of FAST and SLOW mice to investigate neurophysiological factors underlying sensitivity to the behavioral effects of EtOH, with a view to further testing of the postulated homology between locomotor stimulant effects and addiction potential of drugs of abuse.

Alcohol Drinking↗

Estimation of phenotypic selection differentials for predicting genetic responses to ratio-based selection.

Ratios of the phenotypic values of two traits may be used as selection criteria in animal and plant breeding to improve the ratio traits themselves or to effect changes in their two component (numerator and denominator) traits. Prediction of genetic responses to ratio-based selection would facilitate quantitative analysis and evaluation of selection based on ratios. Methods for predicting such responses are derived and presented here. They employ expressions for the truncation value of a ratio and for the phenotypic selection differentials of the numerator and denominator traits. The derivation of these expressions is based upon the assumption that the phenotypic values of each of these traits are normally distributed. Worked examples relating to livestock and crop improvement are included to demonstrate how responses to selection for ratios may be predicted.

Agriculture↗

Detecting amino acid sites under positive selection and purifying selection.

An excess of nonsynonymous over synonymous substitution at individual amino acid sites is an important indicator that positive selection has affected the evolution of a protein between the extant sequences under study and their most recent common ancestor. Several methods exist to detect the presence, and sometimes location, of positively selected sites in alignments of protein-coding sequences. This article describes the "sitewise likelihood-ratio" (SLR) method for detecting nonneutral evolution, a statistical test that can identify sites that are unusually conserved as well as those that are unusually variable. We show that the SLR method can be more powerful than currently published methods for detecting the location of positive selection, especially in difficult cases where the strength of selection is low. The increase in power is achieved while relaxing assumptions about how the strength of selection varies over sites and without elevated rates of false-positive results that have been reported with some other methods. We also show that the SLR method performs well even under circumstances where the results from some previous methods can be misleading.

Amino Acids↗

Selection for weaning weight and postweaning gain in Hereford cattle. II. Response to selection.

Single trait selection was practiced in three lines of Hereford cattle at two locations. Bulls were selected within sire families for increased weaning weight (WW) in the WW line (WWL), for postweaning gain (PG) in the PG line (PGL) and at random in the control line (CTL). Data include the performance of 2,467 calves produced from 1967 to 1981. Environmental effects were estimated from CTL (method I) and from multiple regression procedures (method II). Phenotypic and environmental time trends were negative for WW and generally were positive for PG. Estimated genetic gains for WW in WWL were 1.07 +/- .51 kg/yr in bulls and .62 +/- .36 kg/yr in heifers using method I and .50 +/- .31 kg/yr in bulls and .10 +/- .17 kg/yr in heifers using method II. Corresponding values for PG in PGL were .85 +/- .40 and 1.03 +/- .24 kg/yr in bulls and .30 +/- .28 and .37 +/- .12 kg in heifers. Correlated genetic gains for WW in PGL were larger than direct WW gains, whereas genetic gains for PG in WWL were smaller than direct PG gains. From method I, estimates of realized heritability (h2R) for WW were .31 +/- .18 in bulls and .22 +/- .13 in heifers. For PG, h2R was .31 +/- .13 in bulls and .06 +/- .12 in heifers. Using method II, h2R for WW was .09 +/- .08 in bulls and .02 +/- .07 in heifers. Corresponding values for PG were .29 +/- .10 and .11 +/- .08. Joint estimates of the realized genetic correlation between WW and PG were .69 +/- .18 and .46 +/- .31 for methods I and II, respectively. Variation in selection response was evaluated using quasi-replicates. Results of this study indicate that selection for PG improved both WW and PG faster than selection for WW.

Animals↗

[Selected plateau during long-term selection in experimental populations of Drosophila].

Drosophila subpopulations which did not any more response to the artificial selection effect were obtained as the result of long-term selection for the number of abdominal bristles and thorax length. Study on selection lines has shown that genetic variability may both decrease in the process of selection and increase temporarily. Not always does fixation of alleles controlling a quantitative character occur when the selection limits are achieved.

Alleles↗

The importance of patient selection for adjunctive postoperative radiation therapy for cancer of the rectum. Patient selection in adjunctive therapy.

BACKGROUND: Clinical stage of disease is an important selection criterion for choice of primary treatment and strategies for adjunctive therapy for most cancers. For adenocarcinoma of the rectum, strategies for adjuvant treatment are based primarily on pathologic stage alone, without consideration of presenting clinical factors. This analysis was undertaken to assess the effect of patient selection on results of adjunctive therapy. METHODS: Three groups of patients with Astler-Coller Stage B2 and C rectal cancer were compared to assess the effect of patient selection factors on outcome of treatment after adjuvant postoperative radiation. Thirty-two patients in Group 1 received only 5 Gy preoperatively; 54 patients in Group 2 received low-dose (5 Gy) preoperative and high-dose (45 Gy) postoperative radiation; and 53 patients in Group 3 received high-dose (45 Gy) postoperative radiation. All patients have a minimum follow-up of 5 years. Whereas Group 1 and Group 2 patients were similar in distribution by clinical tumor characteristics, Group 3 had more patients with poor clinical features: higher median age, more men, and a higher proportion of tumors in the distal rectum. Group 3 also had a slightly higher percentage of C2 tumors compared with the other two groups. RESULTS: Treatment was well tolerated with minimal side effects. Patients in Group 1 had no long-term complications. Four percent of patients (2 of 54) in Group 2 and 6% of patients (3 of 53) in Group 3 experienced major small bowel complications. The incidence of local recurrence was 34% (11 of 32) in Group 1, 9% (5 of 54) in Group 2, and 21% (11 of 53) in Group 3. The incidence of distant metastasis was 28% (9 of 32), 22% (12 of 54), and 38% (20 of 53), respectively. Absolute 5-year survival rates were 54%, 72%, and 41% in these three groups, respectively. CONCLUSIONS: Low-dose preoperative adjunctive radiation alone (Group 1) resulted in a high incidence of local recurrence and poor survival compared with patients treated more appropriately with low-dose preoperative plus adjunctive postoperative irradiation (Group 2). In spite of postoperative radiation, patients with clinically unfavorable rectal cancer (Group 3) did worse than carefully selected patients, although both were nominally Stage B2 and C. Careful patient selection before surgery, histopathologic stage of disease postsurgery, and adequate adjunctive therapy are all important factors in obtaining the best results from adjunctive therapy.

Adenocarcinoma↗

Prophylactic versus selective use of surfactant for preventing morbidity and mortality in preterm infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To compare the effect of prophylactic surfactant administration to surfactant treatment of established respiratory distress syndrome in premature infants. SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: pulmonary surfactant; limits: age groups, newborn infants), previous reviews including cross-references, abstracts, conference and symposia proceedings, expert informants, and journal handsearching in the English language. SELECTION CRITERIA: Randomized controlled trials which compared the effects of prophylactic surfactant administration to surfactant treatment of established respiratory distress syndrome in premature infants were included in the analysis. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including the incidence of pneumothorax, pulmonary interstitial emphysema, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage (any grade and severe intraventricular hemorrhage), bronchopulmonary dysplasia, mortality, bronchopulmonary dysplasia or death, and retinopathy of prematurity were excerpted from the reports of the clinical trials by the reviewers. Data analysis was done in accordance with the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: The majority of included studies noted an initial improvement in the respiratory status and a decrease in the incidence of respiratory distress syndrome in infants who received prophylactic surfactant. The meta-analysis supports a decrease in the incidence of pneumothorax, a decrease in the incidence of pulmonary interstitial emphysema, a decrease in the incidence of mortality and a decrease in the incidence of bronchopulmonary dysplasia or death associated with prophylactic administration of surfactant. No significant untoward effects of prophylactic surfactant administration are noted. REVIEWER'S CONCLUSIONS: Prophylactic surfactant administration to infants judged to be at risk of developing respiratory distress syndrome (intubated infants less than 30-32 weeks gestation) has been demonstrated to improve clinical outcome. Infants who receive prophylactic surfactant have a decreased incidence of pneumothorax, a decreased incidence of pulmonary interstitial emphysema and a decreased incidence of mortality. However, it remains unclear exactly which criteria should be used to judge "at risk" infants who would require prophylactic surfactant administration.

Humans↗

B cell positive selection by self antigens and counter-selection of dual B cell receptor cells in the peripheral B cell pools.

The presence of B cells expressing two B cell receptors (BCR), described in BCR-transgenic, gene-targeted and normal mice, may represent an autoimmune hazard. We generated RAG-2-deficient mice bearing two complete rearranged immunoglobulin transgenes. In these mice most mature resting B cells express chains from the two transgenes. We studied selection of these dual receptor B cells in the presence of self antigens. In spite of the reduced surface density of the anti-self receptor, self-reactive B cells are deleted in the presence of membrane-bound self antigens. In contrast, the presence of soluble self antigen positively selects single receptor B cells expressing the self-reactive receptor. At the periphery these positively selected B cells down-regulate surface IgM expression and become unresponsive. A few dual receptor cells, however, escape tolerance induction. We examined the peripheral fate of the dual receptor B cells and showed that they are poorly selected into the activated B cell compartment and show a poor competitive capacity when in presence of populations of single receptor B cells. These results indicate that peripheral selection contributes to the very low frequencies of dual receptor B cells in normal mice and that multiple safeguard mechanisms operate to minimize the autoimmune hazard that allelically included B cells could represent.

Animals↗

Slice-selective fat saturation in MR angiography using spatial-spectral selective prepulses.

Presaturation of fat signals by frequency-selective radiofrequency (RF) pulses is often applied in MR angiography to improve the visualization of the blood vessels. Unfortunately, standard fat saturation methods might cause a considerable reduction of the blood signal in the measured slices. This effect is caused by an attenuation of blood magnetization in remote tissue regions with water protons showing a similar Larmor frequency as the fat protons in the recorded slice. The affected blood water protons subsequently flow into the recorded slice and provide low signal intensity. Suitable spatial-spectral selective methods for slice-selective fat saturation were developed to avoid this unwanted effect. A spatial-spectral fat saturation technique was compared with a corresponding only spectrally selective approach. Both saturation techniques were included in a standard two-dimensional (2D) cine sequence and applied in angiographic examinations of the thighs. The results indicate that spatial-spectral saturation (acting slice selectively) leads to a clearly higher blood signal intensity in fat-suppressed MR angiography compared with standard techniques, especially in measurements performed during the systolic phase of the cardiac cycle.

Adipose Tissue↗

Quantitative structure-selectivity relationships: selective drug design.

The concept of complex selectivity (Scn) permits the investigation of quantitative structure--selectivity relationships in the presence of n side effects; Scn permits differentiation of the most selective molecules rather than the most active ones in a congener series. Selectivity quantification in the presence of n side effects facilitates molecular comparisons. The information provided by Scn and its changes with increasing n is discussed. The proposed mathematical model is applied to the study of the selectivity of some antibiotics and antibacterial agents.

Chemistry, Pharmaceutical↗

MUSIC, selective pulses, and tuned delays: amino acid type-selective (1)H-(15)N correlations, II.

Amino acid type-selective experiments help to remove ambiguities in either manual or automated assignment procedures. Here we present modified triple-resonance experiments that yield amino acid type-selective (1)H-(15)N correlations. They are based on the MUSIC coherence transfer scheme which replaces the initial INEPT transfer and is selective for XH(2) or XH(3) (where X is either (15)N or (13)C). Signals of the desired amino acid types are thus selected based on the topology of the side chain. MUSIC is combined with selective pulses and carefully tuned delays to create experiments for Ser (S-HSQC); Val, Ile, and Ala (VIA-HSQC); Leu and Ala (LA-HSQC); Asp, Asn, and Gly (DNG-HSQC), as well as Glu, Gln, and Gly (EQG-HSQC). The new experiments are recorded as two-dimensional spectra and their performance is demonstrated by their application to two protein domains of 83 and 115 residues.

Algorithms↗

In vitro selection for different mutational patterns in the HIV-1 reverse transcriptase using high and low selective pressure of the nonnucleoside reverse transcriptase inhibitor HBY 097.

In vitro resistance of HIV-1 against high levels of HBY 097 ((S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3, 4-dihydro-quinoxaline-2(1H)-thione) and other quinoxaline nonnucleoside reverse transcriptase inhibitors (NNRTIs) is characterized by a specific amino acid substitution in the reverse transcriptase (RT), Gly 190Glu. This change results in decreased RT polymerase activity and in reduced growth properties of the corresponding viral variant. Here we show that the appearance of the crippling mutation at codon 190 can be prevented by lowering the selective pressure exerted by HBY 097. Under low selective pressure an accumulation of other NNRTI-specific mutations is observed. Up to five NNRTI-specific substitutions were detected in some of these virus lineages. In addition, we report novel RT amino acid changes which were not observed previously, including Val106lle, Val106Leu, and Gly190Thr. HBY 097 selects for different mutational patterns under high and low selective pressure conditions, respectively. Thus, the type of mutations which appear in HIV-infected patients undergoing therapy may be determined by the levels of the selecting drug.

Antiviral Agents↗

The design of selective and non-selective combination therapy for acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is an unique subtype of acute myeloid leukemia typically carrying a specific reciprocal chromosome translocation, t(15;17), leading to the expression of a leukemia-generating fusion protein, PML-RARalpha. APL patients are responsive to APL-selective reagents such as all-trans retinoic acid (ATRA) or arsenic trioxide and non-selective cytotoxic chemotherapy. Nearly all de novo APL patients undergo clinical remission when treated with ATRA plus chemotherapy or with the combinational selective therapy, ATRA plus As2O3. Combining ATRA with As2O3 as an induction followed by chemotherapy consolidation results in more profound clinical remissions compared to treatment with any agent alone or any of the other possible combinations. The mechanism of action of each of these agents differs. ATRA induces APL cell differentiation and PML-RARalpha proteolysis. As2O3 induces APL cell partial differentiation, PML-RARalpha proteolysis, and apoptosis. Chemotherapy, mainly using anthracyclines, induces APL cell death. The combined effects of selective APL therapy (ATRA and As2O3) and/or non-selective chemotherapy in APL cells in vitro and their mechanisms in relation to clinical protocol design are discussed.

Anthracyclines↗