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At least 613 records · Page 34Linked to original sources
PubMed1994

MHC control of the naive TCR alpha-chain repertoire.

The naive T cell repertoire is shaped by interactions between developing thymocytes and thymic stroma. Both positive and negative selection involve the clonotypic TCR and MHC molecules carrying self-peptides. Except for the MHC-dependent effects of superantigens on TCR V beta usage; there has been little evidence that the TCR structure of naive T cell varies with the selecting MHC products. To examine this point from another angle, in particular the TCR alpha-chain, we have analyzed alpha-chain usage in a system in which the vast majority of T cells express a transgene-encoded TCR beta-chain, compatible with efficient T cell development on a wide range of MHC haplotypes. Endogenous TCR alpha-chains are thus selected without interference from the forces known to act on TCR-beta, permitting us to observe MHC influences on alpha-chain selection. We have used V alpha-specific Abs to quantitate alpha-chain usage in MHC congenic, MHC recombinant, and MHC transgenic mice and provide evidence that the naive TCR alpha-chain repertoire is under MHC control. The data demonstrate a direct impact of known MHC class II products but also reflect more complex influences, apparently involving other gene products within the MHC. Sequence analysis of differentially selected TCR suggests that selection acts on the entire alpha-chain, including V alpha, J alpha, and the junctional region.

Amino Acid Sequence↗
PubMed1988

Selection of Japanese quail for contrasting blood corticosterone response to immobilization.

Japanese quail (Coturnix coturnix japonica) were divergently selected for 12 generations for increased (high stress, HS) and decreased (low stress, LS) blood corticosterone (B) response to unfamiliar environments. Response lines were selected initially on the basis of wild-type quail B response to albino (ALB) quail intrusion (S1 to S3) and subsequently on B response to immobilization (IMB) (S4 to S12). Using ALB intruders as stressors proved unsuccessful, therefore the practice was abandoned in favor of using IMB, which proved successful. Across nine generations of selection, using the IMB stressor, the HS line exhibited a mean serum B response that was approximately 58% greater than that of the random-bred (control stress, CS) line, whereas the LS line had a mean response approximately 23% less than that of the CS line. Selection differentials were approximately three-fold greater in the HS than in the LS line whereas realized heritabilities (h2) were approximately two-fold greater in the HS than in the LS line.

Animals↗
PubMed2003

Antibody repertoire development in fetal and neonatal piglets. VI. B cell lymphogenesis occurs at multiple sites with differences in the frequency of in-frame rearrangements.

B cell lymphogenesis in mammals occurs in various tissues during development but it is generally accepted that it operates by the same mechanism in all tissues. We show that in swine, the frequency of in-frame (IF) VDJ rearrangements differs among yolk sac, fetal liver, spleen, early thymus, bone marrow, and late thymus. All VDJ rearrangements recovered and analyzed on the 20th day of gestation (DG20) from the yolk sac were 100% IF. Those recovered at DG30 in the fetal liver were >90% IF, and this predominance of cells with apparently a single IF rearrangement continued in all organs until approximately DG45, which corresponds to the time when lymphopoiesis begins in the bone marrow. Thereafter, the proportion of IF rearrangements drops to approximately 71%, i.e., the value predicted whether VDJ rearrangement is random and both chromosomes were involved. Unlike other tissues, VDJs recovered from thymus after DG50 display a pattern suggesting no selection for IF rearrangements. Regardless of differences in the proportion of IF rearrangements, we observed no significant age- or tissue-dependent changes in CDR3 diversity, N region additions, or other characteristics of fetal VDJs during ontogeny. These findings indicate there are multiple sites of B cell lymphogenesis in fetal piglets and differences in the frequency of productive VDJ rearrangements at various sites. We propose the latter to result from differential selection or a developmentally dependent change in the intrinsic mechanism of VDJ rearrangement.

Aging↗
PubMed1990

[Ethnogenetics: adaptive structure of the gene pool of the mankind from the data on human polymorphic genetic markers].

The mean FST value as a characteristic of gene frequency changes in a random sample of polymorphic genes from population gene pool provides the best indirect estimation of selectively neutral level of genetic variability. The set of test criteria, including chi 2, F and t, can be used in order to compare F1 with F and subdivide gene sample into three subgroups, or classes of genes which are differing from each other by the degree of variation of allelic frequencies. These three classes comprise the adaptive structure of gene pool and consist of the genes which are, respectively, under stabilizing and differentiating selection pressures or neutral ones. Adaptive structures of gene pools of aboriginal human populations at the main 9 geographical regions of the World, taken together, reveal statistically significantly correlation with adaptive structure of the total gene pool of the Mankind. But the correlation is rather small and therefore, the adaptive structure of human gene pool reveals between adaptive structures, the highest is for the USSR and the lowest are for the East-Asiatic and Australian regions. The proportion of neutral to non-neutral genes is about 50% in the average, with the range of variation 40-60% in different regions. But none of the polymorphic genes so far studied reveals constant neutrality in all regional conditions of environment and at different times of evolution history of human gene pool. Its adaptive structure underwent essential transformation from the Palaeolithic till the Postpalaeolithic times, but nevertheless, among the main features of contemporary adaptive structure of human gene pool, those predominate which are of the Palaeolithic origin.

Alleles↗
PubMed2004

Selection, proliferation and differentiation of bone marrow-derived liver stem cells with a culture system containing cholestatic serum in vitro.

AIM: To explore the feasibility of direct separation, selective proliferation and differentiation of the bone marrow-derived liver stem cells (BDLSC) from bone marrow cells with a culture system containing cholestatic serum in vitro. METHODS: Whole bone marrow cells of rats cultured in routine medium were replaced with conditioning selection media containing 20 mL/L, 50 mL/L, 70 mL/L, and 100 mL/L cholestatic sera, respectively, after they attached to the plates. The optimal concentration of cholestatic serum was determined according to the outcome of the selected cultures. Then the selected BDLSC were induced to proliferate and differentiate with the addition of hepatocyte growth factor (HGF). The morphology and phenotypic markers of BDLSC were characterized using immunohistochemistry, RT-PCR and electron microscopy. The metabolic functions of differentiated cells were also determined by glycogen staining and urea assay. RESULTS: Bone marrow cells formed fibroblast-like but not hepatocyte-like colonies in the presence of 20 mL/L cholestatic serum. In 70 mL/L cholestatic serum, BDLSC colonies could be selected but could not maintain good growth status. In 100 mL/L cholestatic serum, all of the bone marrow cells were unable to survive. A 50 mL/L cholestatic serum was the optimal concentration for the selection of BDLSC at which BDLSC could survive while the other populations of the bone marrow cells could not. The selected BDLSC proliferated and differentiated after HGF was added. Hepatocyte-like colony-forming units (H-CFU) then were formed. H-CFU expressed markers of embryonic hepatocytes (AFP, albumin and cytokeratin 8/18), biliary cells (cytokeratin 19), hepatocyte functional proteins (transthyretin and cytochrome P450-2b1), and hepatocyte nuclear factors (HNF-1alpha and HNF-3beta). They also had glycogen storage and urea synthesis functions, two of the critical features of hepatocytes. CONCLUSION: The selected medium containing cholestatic serum can select BDLSC from whole bone marrow cells. It will be a new way to provide a readily available alternate source of cells for clinical hepatocyte therapy.

Animals↗
PubMed1990

[Influence of sociodemographic variables in the enrollment of subjects in a population case-control study].

Selection in representation of the study base was quantified in a case-control study of laryngeal cancer among residents of the City of Torino, Italy. Two-hundred-ninety-nine out of 408 eligible cases (73.3%) and 608 out of 1104 (55.1%) eligible controls were interviewed. All interviewed and non interviewed subjects were compared in a logistic regression model with respect to age, sex, educational level, civil status and area of birth. No large differential selection with respect to these variables was found between interviewed and non interviewed cases. Lower proportions of interviewed subjects were found among older controls and controls with lower education. These results suggest the possibility of selection bias in this case-control study. In particular, biased measures of effects might be estimated when analyzing variables related to educational level.

Adult↗
PubMed1984

Apomorphine effects on behavioral response to ethanol in mice selectively bred for differential sensitivity to ethanol.

Two lines of mice selectively bred for differences in response to a hypnotic dose of ethanol were administered apomorphine alone or in combination with ethanol. When administered by itself, apomorphine produced similar dose-dependent depression of locomotor activity and increases in stereotypy in the two lines. Doses of apomorphine (0.5 microM/kg and 2 microM/kg) thought to bind only presynaptic dopamine receptors blocked the slight locomotor activation to 1.5 g/kg ethanol in the ethanol-sensitive Long-Sleep (LS) mice; in the ethanol-insensitive Short-Sleep (SS) mice which show marked activation to all subhypnotic doses of ethanol, these doses of apomorphine only attenuated the activation. A higher apomorphine dose (8 microM/kg) antagonized the locomotor depressant effects of 2.0 and 2.5 g/kg of ethanol in LS mice but did not alter the shape of the SS ethanol dose response curve for locomotor activity. Apomorphine (2 and 8 microM/kg) potentiated ethanol-induced loss of the righting reflex in LS mice in a dose dependent fashion, but did not alter this soporific effect of ethanol in SS mice. These findings extend the data base suggesting a role for dopamine both in the mechanism(s) differentiating the LS and SS mice and the stimulant and intoxicating properties of ethanol.

Animals↗
PubMed2006

Differentiation of hippocampal stem cells into functional neurons: evolving our understanding of monoamine oxidase-A inhibition.

Depression affects many millions of people worldwide and much is still unknown with respect to the mode of action of antidepressant drugs. The hippocampus has been associated with many psychiatric disorders, including clinical depression. Recently, stem cells have also been shown to reside within discrete regions of the hippocampus and can differentiate under a variety of conditions into neural cells. In this issue, Chiou et al. have elegantly demonstrated that cells isolated from the rat hippocampus, and treated with the antidepressant moclobemide, may be differentiated in vitro into neural cells exhibiting features to those of serotoninergic neurons. They have also suggested that this process was mediated, in part, through the expression of specific antiapoptotic genes (Bcl-2 and Bcl-XL) and via activation of extracellular-regulated kinase. This work raises the attractive possibility that the use of antidepressants, such as moclobemide, may exert neuroprotective and potentially neurogenerative effects not just in vitro, but also in vivo, through the selected differentiation of stem cells into functional neurons. The exact mechanisms by which such antidepressants differentiate neural stem cells still remains to be fully elucidated.

Animals↗
PubMed2004

Construction and differential screening of a cDNA library specific to osmotic stress of Haloxylon ammodendron seedlings.

A subtracted cDNA library specific to osmotic stress of Haloxylon ammodendron (Mey.) Bge seedlings was constructed by suppression subtractive hybridization (SSH) and T/A cloning. SSH was performed between two groups of H. ammodendron seedlings, one was cultivated in Hoagland (H) solution as a driver and the other group was treated with osmotic stress of the Hoagland solution by the addition of 400 mM mannitol (M), as a tester. The library consisted of about 400 recombinant clones, with the average size being of 500 bp, ranging from 300 bp to 1500 bp. Using a PCR-select differential screening kit, 100 recombinant clones were randomly chosen from the subtracted cDNA library and hybridized with forward, reverse subtracted and unsubtracted probes for two rounds. As a result, 21 positive clones specific to osmotic stress were obtained and some of them were verified by Northern blot analysis. The sequencing analysis of 6 positive clones and the following homology comparison to GenBank [blastx] non-redundant databases characterized that two sequences obtained in this experiment may contribute to novel drought-related genes.

Amaranthaceae↗
PubMed2005

Classification analysis of the transcriptosome of nonlesional cultured dermal fibroblasts from systemic sclerosis patients with early disease.

OBJECTIVE: To compare the transcriptosome of early-passage nonlesional dermal fibroblasts from systemic sclerosis (SSc) patients with diffuse disease and matched normal controls in order to gain further understanding of the gene activation patterns that occur in early disease. METHODS: Total RNA was isolated from early-passage fibroblasts obtained from nonlesional skin biopsy specimens from 21 patients with diffuse SSc (disease duration <5 years in all but 1) and 18 healthy controls who were matched to the cases by age (+/-5 years), sex, and race. Array experiments were performed on a 16,659-oligonucleotide microarray utilizing a reference experimental design. Supervised methods were used to select differentially expressed genes. Quantitative polymerase chain reaction (PCR) was used to independently validate the array results. RESULTS: Of the 8,324 genes that passed filtering criteria, classification analysis revealed that <5% were differentially expressed between SSc and normal fibroblasts. Individually, differentially expressed genes included COL7A1, COL18A1 (endostatin), DAF, COMP, and VEGFB. Using the panel of genes discovered through classification analysis, a set of model predictors that achieved reasonably high predictive accuracy was developed. Analysis of 1,297 gene ontology (GO) classes revealed 35 classes that were significantly dysregulated in SSc fibroblasts. These GO classes included anchoring collagen (30934), extracellular matrix structural constituent (5201), and complement activation (6958, 6956). Validation by quantitative PCR demonstrated that 7 of 7 genes selected were concordant with the array results. CONCLUSION: Fibroblasts cultured from nonlesional skin of patients with SSc already have detectable abnormalities in a variety of genes and cellular processes, including those involved in extracellular matrix formation, fibrillogenesis, complement activation, and angiogenesis.

Dermis↗
PubMed1978

Altruism: its characteristics and evolution.

Altruism is a group phenomenon in which some genes or individuals, which must be presumed to be selfish, benefit others at cost to themselves. The presumption of selfishness and the fact of altruism are reconciled by kin-group selection and by reciprocal altruism. Kin-group selection is clearly visible only in special cases; its role even among social insects may be overestimated; it is probably usually inhibited by competition. However, reciprocal altruism is ubiquitous. All altruism is: (i) potentially reciprocal; (ii) potentially profitable to altruists as well as to recipients; (iii) environmentally determined, usually by position of individuals in group or environmental situations; and (iv) a net-gain lottery. These generalizations are illustrated by four idealized cases; the difficulty of applying them to real cases is illustrated by alarm-calling in groups of birds. Although altruism is a group phenomenon, it evolves by individual selection, by processes equivalent to co-evolutions. Its evolution is: (i) opposed by competition; (ii) costly, complex, and slow, and tending to produce an imprecise flexible altruism rather than a precisely detailed one; and (iii) supplemented by group selection (differential extinction of groups). That altruism in human beings conforms to these generalizations is a good working hypothesis. However, analysis does not "take the altruism out of (human) altruism." Humans do not calculate it, but behave altruistically because they have human altruistic emotions.

Altruism↗
PubMed1973

Inheritance of plasma cholesterol levels in mice.

Mean plasma cholesterol levels were determined at two ages in mice from eight unrelated inbred strains (BALB/cJ, BDP/J, CBA/J, C57BL/6J, LP/J, RF/J, SJL/J, and 129/J). Significant strain, sex, and age differences were observed. Estimates of the degree of genetic determination of the trait obtained from an analysis of the strain data averaged 58 +/- 4% for the males and 54 +/- 8% for the females.-Selection for high and low plasma cholesterol levels produced two significantly different and distinct lines. Selection was initiated in a genetically heterogeneous population derived from an eight-way cross of the inbred strains listed above. After five generations of selection the divergence of the high and low lines amounted to 4 phenotypic standard deviations of the foundation population. Realized heritability estimated from the regression of divergence on the combined cumulative selection differential was 51 +/- 5% for the males and 50 +/- 3% for the females. The results indicate that genetic factors are important in controlling plasma cholesterol levels in the mouse and that the majority of these factors act additively.

Aging↗
PubMed1984

2'Fluoro-5-iodo-arabinosyl-cytosine: a new agent for herpes infections in the immunosuppressed patient.

Concurrent with our increased understanding of mechanisms of viral replication, new antiviral agents were developed with greater selectivity and sensitivity. Acyclovir was the first of these. We now present the initial compound of a series of 2'-Fluoro pyrimidine nucleosides with potent antiviral activity. This agent demonstrates both potency and sensitivity in vitro and in vivo against herpes simplex virus types I and II, and varicella zoster virus and is selective in vitro against cytomegalovirus. Initial clinical trials show the drug to be well tolerated and to be more effective than adenine arabinoside against varicella zoster in the immunosuppressed patient. Future developmental plans with the drug are outlined. FIAC (2'-Fluoro-5-iodo-aracytosine) is still at an early stage of clinical development and any comparison with acyclovir is premature; rather, therapy of severe viral infections in the future should consider combinations of such agents that show differential selectivity at multiple sites of action.

Antiviral Agents↗
PubMed1995

Genetics of the interval from weaning to estrus in first-litter sows: distribution of data, direct response of selection, and heritability.

A selection experiment with a selection and a control line maintained for eight generations was set up to study efficacy of selection for a short interval from weaning to estrus after weaning the first litter and to estimate genetic variation in the Dutch Landrace population. Intervals were recorded without truncation (i.e., intervals up to 234 d were observed). A mating scheme with 10 mating groups was used to avoid inbreeding. Distribution of intervals from weaning to estrus was described by a mixture of a normal and an exponential distribution. Between lines, both underlying distributions were similar, but the contribution to the total distribution was different. From generation 4 onward, intervals were significantly shorter in the selection line than in the control line. Variances within lines, generations, and mating groups varied to a large extent. Response per unit selection differential was calculated for original data and three sets of transformed data, both with and without correction for unequal subclass numbers. Standardized responses were more precise and linear, when data were log-transformed, and when corrected for unequal subclass numbers. The assumed best estimate of the realized heritability was .17. The heritability in the foundation population was estimated at .36 +/- .05, using an animal model including all genetic relationships in the data. It was concluded that genetic selection decreases the average interval from weaning to estrus by reducing the number of sows with a record in the exponential part of the distribution.

Algorithms↗
PubMed2001

Comparative study of the two more frequent HFE mutations (C282Y and H63D): significant different allelic frequencies between the North and South of Portugal.

An earlier study of reference values of iron parameters in Portugal showed significant differences between populations from northern and southern villages. This study addresses the question of the geographical distribution in Portugal of the two main mutations (C282Y and H63D) of the hereditary hemochromatosis gene, HFE. For that purpose, a stratified sample of 640 anonymous dried blood spot samples was randomly selected from the major regions of Portugal: North, Center, Lisbon and the Tagus Valley, Alentejo and Algarve. Differences in the geographical distribution of these two mutations were observed thus confirming the presumed differences between the age of the two mutations which is compatible with the postulated Celtic/Nordic origin of the C282Y mutation. The finding of a significantly higher allelic frequency of the C282Y mutation in the North (0.058) than in the South (0.009) could also point to an effect of differential selective forces acting in the different geographical areas of the country. Data on archaeological, ethnographic and linguistic records and on the North/South distribution of Portuguese cattle breeds of European or African origin have also been reported. In addition to their interest for population genetics, the results represent a reminder of the need to take into account regional differences in the design of strategies for population screening of hereditary hemochromatosis.

DNA↗
PubMed1991

Mass selection for increased 200-day weight in a closed line of Duroc pigs.

Mass selection for increased weight at 200 d of age was conducted for six generations in a line of Duroc pigs. A randomly selected contemporary control line was maintained. Our objectives were to observe the response in 200-d weight, to measure correlated responses in weights at earlier ages, daily gains and ultrasound backfat thickness and to compare three methods for estimating responses to selection. Inbreeding coefficients averaged .213 and .202 for the select- and control-line pigs and .200 and .173 for the select- and control-line dams in the sixth generation, respectively. A total of 1,866 pigs were farrowed; 200-d weights were collected on 798 of them. These pigs were sired by 89 boars and were out of 193 sows. Twelve traits were studied: weights at birth and at 21, 35, 70, 154 and 200 d of age, daily gains from birth to 35 d, 35 d to 70 d, 70 d to 154 d and 154 d to 200 d, ultrasound backfat thickness at 200 d and ultrasound backfat thickness adjusted for 200-d weight. Three methods for estimating responses to selection gave similar results; therefore, the estimates were averaged. Total weighted cumulative selection differential for 200-d weight was 81.7 kg with a response in 200-d weight of 2.5 +/- 1.2 kg/generation. This response corresponds to a realized heritability for 200-d weight of .18 +/- .08. Increased weight at 200 d was the result of more rapid growth in the 154- to 200-d period, with decreased growth in the period from birth to 35 d. Growth at other periods was not changed significantly. Ultrasound backfat thickness at 200 d increased in the select line compared to the control line, but not when adjusted for 200-d weight.

Adipose Tissue↗
PubMed1992

P element transposition contributes substantial new variation for a quantitative trait in Drosophila melanogaster.

The P-M system of transposition in Drosophila melanogaster is a powerful mutator for many visible and lethal loci. Experiments using crosses between unrelated P and M stocks to assess the importance of transposition-mediated mutations affecting quantitative loci and response to selection have yielded unrepeatable or ambiguous results. In a different approach, we have used a P stock produced by microinjection of the ry506 M stock. Selection responses were compared between transposition lines that were initiated by crossing M strain females with males from the "co-isogenic" P strain, and ry506 M control lines. Unlike previous attempts to quantify the effects of P element transposition, there is no possibility of P transposition in the controls. During 10 generations of selection for the quantitative trait abdominal bristle number, none of the four control lines showed any response to selection, indicative of isogenicity for those loci affecting abdominal bristle number. In contrast, three of the four transposition lines showed substantial response, with regression of cumulative response on cumulative selection differential ranging from 15% to 25%. Transposition of P elements has produced new additive genetic variance at a rate which is more than 30 times greater than the rate expected from spontaneous mutation.

Animals↗
PubMed1980

Divergent selection in Japanese quail for the plasma cholesterol response to ACTH.

Two lines of Japanese quail were divergently selected for high and low plasma cholesterol levels after three daily injections with 2 IU of adrenocorticotropen (ACTH)/100 g of body weight. Plasma cholesterols were obtained at 31 days of age, just before the first injection, and at 34 days of age, after the last injection. After eight generations of selection, the plasma cholesterol level after ACTH injections in the high line was 34% greater than the level in the control line, whereas the low line level was approximately 14% less than that in the control. Selection differentials were significantly greater in the high line than in the low line. The realized heritability for plasma cholesterol before ACTH treatment calculated by regression of progeny on mid-parent was .25 in the high line and .16 in the low line.

Adrenocorticotropic Hormone↗