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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

Effect of variability in response to superovulation on donor cow selection differentials in nucleus breeding schemes.

The effectiveness of nucleus breeding schemes based on multiple ovulation and embryo transfer in practice is highly dependent upon the achieved reproductive rate. This study quantifies the effects of donor cow variability in response to superovulation (random and phenotypically correlated with milk yield) and failure rates (proportion of selected cows producing no transferable embryos) on the mean and variance of realized female selection differentials as affected by herd size, average embryo yield, and the coefficient of variation for embryo yield. Results show that differences in failure rates (0 to 40%) reduced realized female selection differentials up to 64%. The existence of a negative phenotypic correlation (-.3) between donor cow embryo yield and milk yield caused smaller reductions (up to 19%). Variability in realized female selection differentials is largest for small nucleus units and should not be neglected when planning the establishment of a nucleus breeding unit. The use of multiple flushes rather than a single flush per cow to produce the same average number of transferable embryos can reduce the variability in realized selection differentials but increases generation interval. Variability in response to superovulation will also affect inbreeding rates and the average accuracy of selection. Simulation studies are needed to quantify the total effect of variability in response to superovulation on the genetic responses possible in nucleus breeding schemes relying on multiple ovulation and embryo transfer.

Analysis of Variance

Reduction of selection differentials in finite populations with a nested full-half sib family structure.

The effect of family structure is of increasing importance in modern breeding schemes, because increased intraclass correlations between relatives due to improved breeding value estimation methods use all family information, and increased family sizes are possible with improved reproduction rates. In addition, reduction of the generation intervals in modern breeding schemes leads to increased intraclass (family) correlations, because young animals have little information on individual or on progeny performance. This paper derives an approximation for the selection differential in a population divided into families. The result is then extended to an approximation for the selection differentials in populations that are divided into full sib families within paternal half sib families. The approximation is compared with Monte Carlo results, from which it is concluded that the approximation is satisfactory (i.e., rarely more than 5% in error). In some practical situations the approximation is shown to be not more than 2% in error. With high intraclass correlations and few animals selected, the reduction of the selection differentials is maximal. When breeding values are based on family information and the family structure is not accounted for, overestimation of the selection differentials can be up to 61%.

Animal Husbandry

Variances of selection differentials in normal samples.

Standardized variances of selection differentials are defined in general and then considered in detail for the case of directional selection on the basis of normally distributed test scores. Symmetry properties, bounds and asymptotic values for the variances are derived. The results are used to investigate the variance of response to selection.

Mathematics

New, simple medium for selective, differential recovery of Klebsiella spp.

A highly selective, differential medium for the enumeration and isolation of Klebsiella spp. was developed. With pure cultures, 100% recovery of Klebsiella spp. was observed. Recovery of Klebsiella spp. on MacConkey-inositol-potassium tellurite (MCIK) agar was as good as or better than on MacConkey-inositol-carbenicillin agar either with pure cultures or environmental samples. Recovery and percent colony confirmation with MCIK agar were greater and easier to obtain than for other proposed Klebsiella selective media.

Bacteria

Interleukin 7 receptor engagement stimulates tyrosine phosphorylation, inositol phospholipid turnover, proliferation, and selective differentiation to the CD4 lineage by human fetal thymocytes.

The purposes of this study were to elucidate the effects of recombinant human interleukin 7 (rhIL-7) on proliferation as well as differentiation of human fetal thymocytes and to analyze the biochemical nature of the IL-7 receptor-linked transmembrane signal. In the absence of costimulants, rhIL-7 stimulated the in vitro proliferation and colony formation of CD4+CD8+ double-positive immature fetal thymocytes. Furthermore, rhIL-7 promoted partial differentiation of immature thymocytes with a selective advantage for the development of CD4+CD8- single-positive thymocytes. Our observations suggest that IL-7 likely has an important regulatory role during the earliest stages of human T-cell ontogeny. Stimulation of fetal thymocytes with rhIL-7 resulted in enhanced tyrosine phosphorylation of three distinct phosphoproteins with molecular masses of 72, 98, 123, and 190 kDa and induced a rapid and biphasic increase in the production of inositol 1,4,5-trisphosphate, which was inhibitable by the tyrosine protein kinase inhibitor genistein. Thus, the transmembrane signal triggered by engagement of the IL-7 receptor is intimately linked to a functional tyrosine protein kinase pathway and stimulates the inositol phospholipid turnover and proliferation, as well as selective differentiation to the CD4 lineage, by human fetal thymocytes.

Antibodies, Monoclonal

Regions of stable equilibria for models of differential selection in the two sexes under random mating.

The equilibrium structure of models of differential selection in the sexes is investigated. It is shown that opposing additive selection leads to stable polymorphic equilibria for only a restricted set of selection intensities, and that for weak selection intensities must be of approximately the same magnitude in the sexes. General models of opposing directional selection, with arbitrary dominance, are investigated by considering simultaneously the stability properties of the trivial equilibria and the curve along which multiple roots appear. Numerical calculations lead us to infer that the average degree of dominance determines the equilibrium characteristics of models of opposing selection. It appears that if the favored alleles are, on the average, recessive, there may be multiple polymorphic equilibria, whereas only a single polymorphic equilibrium can occur when the favored alleles are, on the average, dominant. The principle that the average degree of dominance controls equilibrium behavior is then extended to models allowing directional selection in one sex with overdominance in the other sex, by showing that polymorphism is maintained if and only if the average fitness in heterozygotes exceeds one.

Animals

Myeloproliferative disorders with selective differentiation toward megakaryocytic cells. A clinicopathological study of three autopsy cases.

Three autopsy cases of myeloproliferative disorders with selective differentiation toward megakaryocytic cells were reported with a clinicopathological analysis. All of these cases had some common distinctive features; (1) patients, adult of more than 40 years of age, (2) relatively acute fatal course (about 20 to 100 days), (3) continued pancytopenia in the peripheral blood, (4) so-called blast cells, occasionally showing accumulation, according to the length of total duration, in addition to overwhelming predominance of atypical megakaryocytic cells in the bone marrow, and (5) an increased tendency of fibrillosis in the interstitium of the bone marrow corresponding to the more or less prolonged duration of the course. From these facts, they should be compatible with so-called megakaryocytic myelosis. Some relationship between this disorder and myelogenous leukemia, and infiltrative tendency of megakaryocytic cells in the extramedullary organs had also been discussed shortly.

Adult

The dogfish peptides scyliorhinin I and scyliorhinin II bind with differential selectivity to mammalian tachykinin receptors.

The dogfish intestinal, linear tachykinin scyliorhinin I (SCYI) and cyclic tachykinin scyliorhinin II (SCYII) bound with differential selectivity to mammalian tachykinin, membrane receptor sites. SCYI bound with highest affinity to NK-1 sites in rat submandibular gland (KI = 0.9 nM) and to NK-2 sites in hamster urinary bladder (KI = 2 nM) whereas SCYII bound with highest affinity to NK-3 sites in rat cerebral cortex (KI = 2.5 nM). These results suggest that SCYI is a dual NK-1/NK-2 tachykinin receptor agonist while SCYII is an NK-3 selective tachykinin receptor agonist.

Animals

Different stromal cell lines support lineage-selective differentiation of the multipotential bone marrow stem cell clone LyD9.

An interleukin 3-dependent multipotential stem cell clone, LyD9, has been shown to generate mature B lymphocytes, macrophages, and neutrophils by coculture with primary bone marrow stromal cells. We report here that coculture with the cloned stromal cell lines PA6 and ST2 can support differentiation of LyD9 cells predominantly into granulocyte/macrophage colony-stimulating factor (GM-CSF)- and granulocyte (G)-CSF-responsive cells, respectively. However, these stromal cell lines were unable to support lymphopoiesis of LyD9 cells. The GM-CSF-dependent line, L-GM, which was derived from LyD9 cells cocultured with PA6 stromal cells, could differentiate into macrophages and granulocytes in the presence of GM-CSF. The L-GM line can further differentiate predominantly into neutrophils by coculture with ST2 stromal cells. The G-CSF-dependent line, L-G, which was derived from LyD9 cells cocultured with ST2 stromal cells, differentiated into neutrophils in response to G-CSF. Although the stromal cell-supported differentiation of LyD9 cells required the direct contact between LyD9 and stromal cells, a small fraction of LyD9 cells that were pretreated with 5-azacytidine could differentiate into neutrophils and macrophages without direct contact with stromal cells. These results indicate that different stromal cell lines support lineage-selective differentiation of the LyD9 stem cell and that 5-azacytidine treatment can bypass the requirement of direct contact with stromal cells, albeit with a lower frequency.

Animals

Selective differentiation and proliferation of hematopoietic cells induced by recombinant human interleukins.

Effects of recombinant human interleukins on hematopoiesis were explored by using suspension cultures of mononuclear cells of human umbilical-cord blood and bone marrow. The results showed that interleukin 5 induced the selective differentiation and proliferation of eosinophils. After 3 weeks in culture with interleukin 5, essentially all nonadherent cells in both bone marrow and cord blood cell cultures became eosinophilic myelocytes. Culture of the same cells with interleukin 4 resulted in the selective growth of OKT3+ lymphocytes. However, OKT3+ cells did not develop if the bone marrow cells were depleted of OKT3+/OKT11+ cells prior to the culture, indicating that interleukin 4 induced the proliferation of a subpopulation of resting T cells present in cord blood and bone marrow cell preparations. In suspension cultures of bone marrow cells and cord blood cells grown in the presence of interleukin 3, basophilic, eosinophilic, and neutrophilic myelocytes and macrophages developed within 2 weeks. By 3 weeks, however, the majority of nonadherent cells became eosinophilic myelocytes. In contrast to mouse bone marrow cell cultures, neither interleukin 3 nor a combination of interleukins 3 and 4 induced the differentiation of mast cells in human bone marrow or cord blood cell cultures.

Bone Marrow Cells

Unusual anodic migrating isoamylase differentiates selected malignant from nonmalignant ascites.

Ascitic fluid from nine patients with nonmalignant ascites and nine patients with malignant ascites was subjected to isoamylase analysis. Unusual isoamylase bands that migrate to the anode were demonstrated in seven of eight patients with ovarian carcinoma and in one patient with gastric carcinoma. In no case of nonmalignant ascites was anodic isoamylase found, despite the presence of normal amylase in all samples. This is the first report of anodic isoamylase from ascitic fluid in gastric carcinoma and the first series comparing isoamylase patterns in malignant and nonmalignant ascites. Anodic isoamylase on electrophoresis of ascitic fluid may prove to be useful as a tumor marker in differentiating selected malignancies from nonmalignant ascites.

Amylases

Graduated resistance to G418 leads to differential selection of cultured mammalian cells expressing the neo gene.

The effects of Geneticin (G418) selection on the growth and survival of cultured mammalian cells expressing the neomycin-resistance gene (neo) were studied by the analysis of cell clones from two retroviral neo vector-infected populations. We found a correlation between the neo expression level and growth rates in medium containing varying G418 concentrations. This relationship permits the use of differential selection schemes for the isolation of rare cells with increased expression. Comparison, by clone sampling, of vector-positive populations before and after selection with a G418 concentration in the range usually used for selection, showed different expression level and vector copy number distributions for the population infected with the vector of lower LTR activity, but not for the other. Such biasing effects of G418 selection may be important when selected cells are used for quantitative studies of gene expression.

Animals

Apparent differential selection at an isozyme locus between queens and workers of the ant Aphaenogaster rudis.

The frequencies of two alleles at a cathodal malate dehydrogenase locus in populations of A. rudis were studied in 47 colonies from three localities in Georgia and one in New Jersey. The male gene frequencies of the New Jersey and one Georgia locality differ significantly. All the queens at one Georgia locality were heterozygotes. This genotypic distribution differs strongly from that of the workers, in which approximately equal numbers of heterozygotes and homozygotes were found. The heterozygote excess among queens but not their worker progeny suggests differential selection between these castes. This study also shows that rudis colonies consist of a single, once-mated queen and her worker progeny.

Alleles

Differential selectivity of endothelium-derived relaxing factor and nitric oxide in smooth muscle.

The selectivity of endothelium-derived relaxing factor (EDRF) and nitric oxide (NO) on smooth muscle relaxation was examined and compared. EDRF released from was examined and compared. EDRF released from bovine pulmonary arterial endothelium (BPAE) in culture and NO were superfused over vascular, tracheal, gastrointestinal and uterine smooth muscle. EDRF relaxed vascular smooth muscle but not tracheal, gastrointestinal or uterine smooth muscle. NO relaxed vascular and gastrointestinal smooth muscle but not tracheal or uterine smooth muscle. There was a differential selectivity between the relaxant effect of EDRF and NO on smooth muscle.

Animals

Phylogeny, chromosomal mapping and expression analyses of wheat CLAVATA pathway components suggest differential selection on receptor-like kinases, CLEs and T3 WOXes.

Ensuring continuous global food security is a major challenge of the 21st century. Wheat contributes approximately 20% of the total calories consumed by humans, and an estimated 60% increase in production will be required by 2050 to meet forecast global demand. In cereals like wheat, inflorescence (ear) size and branching patterns determine the number of flowers (florets) and grains produced, and these aspects of plant architecture are regulated by the activity of stem cells in the growing shoot tips. CLAVATA peptide and receptor-like kinase signalling regulates angiosperm stem cell activity, and as changes in CLAVATA function can improve crop yields, CLAVATA is a key target for reverse engineering. Here, we identify components of the wheat CLAVATA pathway using genome searches against Triticum aestivum and its wild relatives Triticum turgidum ssp. durum, Triticum turgidum ssp. dicoccoides, Triticum urartu and Aegilops tauschii. Using phylogenetic and synteny analysis, we determine the relationship between homoeologues and infer patterns of gene family evolution. Whilst CLAVATA1, BARELY ANY MERISTEM, RECEPTOR-LIKE PROTEIN KINASE 2, CORYNE and CLAVATA2 receptor-like kinase homologues are mainly present as single genome copies as in other grasses, CLAVATA3-like but not TRACHEARY ELEMENT DIFFERENTIATION FACTOR (TDIF)-like peptide encoding genes and WUSCHEL-LIKE HOMEOBOX (WOX) genes have expanded copy numbers with many gene gains and losses during evolution. Our results highlight wheat CLAVATA pathway components for reverse genetic analysis and indicate potential differential selection on wheat receptor-like kinases, their peptide ligands and WOXes.

Triticum

Antiproliferative effect of IFN-gamma in immune regulation. III. Differential selection of TH1 and TH2 murine helper T lymphocyte clones using recombinant IL-2 and recombinant IFN-gamma.

Supernatants collected after primary or secondary stimulation of spleen cells contain different arrays of lymphokines. Primary supernatants from spleen cells stimulated with Con A or allogeneic spleen cells (MLC-SF) contain IL-2 but little IL-4 or IGN-gamma; in contrast, secondary MLC-SF contains IL-2 as well as substantial IL-4 and IFN-gamma. Our laboratory previously had always used secondary MLC-SF for cloning T cells, and had routinely obtained TH1 helper T lymphocyte clones. In the present study, when primary Con A-SF was used as source of growth factors, TH2 and not TH1 clones were preferentially derived. Considering the possibility that IFN-gamma may be one important factor in determining whether TH1 or TH2 clones are preferentially obtained, clone derivation was then performed either in the presence of rIL-2 or rIL-2 plus rIFN-gamma. The majority of clones derived using rIL-2 alone were TH2 cells, whereas the majority of clones derived using rIL-2 plus rIFN-gamma were TH1 cells. Using either procedure, some clones were obtained that produced IL-2, IL-4, and IFN-gamma. These data are consistent with our previous observations that IFN-gamma inhibits the proliferation of TH2 but not TH1 clones, and suggest that the presence of IFN-gamma during an immune response would result in the preferential expansion of helper T lymphocytes of the TH1 phenotype. Our procedure for the differential selection of TH1 and TH2 clones reactive with the same Ag should be useful for designing in vitro systems for studying the function of these cell subsets in specific immune responses.

Animals