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PubMed2002

Sexual dimorphism in lizard body shape: the roles of sexual selection and fecundity selection.

Sexual dimorphism is widespread in lizards, with the most consistently dimorphic traits being head size (males have larger heads) and trunk length (the distance between the front and hind legs is greater in females). These dimorphisms have generally been interpreted as follows: (1) large heads in males evolve through male-male rivalry (sexual selection); and (2) larger interlimb lengths in females provide space for more eggs (fecundity selection). In an Australian lizard (the snow skink, Niveoscincus microlepidotus), we found no evidence for ongoing selection on head size. Trunk length, however, was under positive fecundity selection in females and under negative sexual selection in males. Thus, fecundity selection and sexual selection work in concert to drive the evolution of sexual dimorphism in trunk length in snow skinks.

Animals↗
PubMed2004

The close relationship between estimated divergent selection and observed differentiation supports the selective origin of a marine snail hybrid zone.

To study the role of divergent selection in the differentiation of the two morphs in a hybrid zone of the intertidal snail Littorina saxatilis, we compared the strength of the divergent selection acting on a series of shell characters (as estimated by the viability of snails in a reciprocal transplant experiment) with the contribution of these characters to the phenotypic differences between the morphs. We found a close correlation between selection and differentiation, which suggests a cause-effect relationship, i.e. that all present differentiation is the result of past divergent selection. In addition, divergent selection was a very important component of the total natural selection acting on shell measures. These novel results support previous evidence, based on allozyme analysis, of a parapatric origin for this hybrid zone. We discuss possible limitations of this interpretation and the circumstances under which allopatric differentiation would produce the same results. Phenotypic analysis of divergent selection may be a useful method of investigating the evolutionary mechanisms involved in differentiation processes.

Animals↗
PubMedDate not supplied

A comparison of two methods for prediction of response and rates of inbreeding in selected populations with the results obtained in two selection experiments.

Selection programmes are mainly concerned with increasing genetic gain. However, short-term progress should not be obtained at the expense of the within-population genetic variability. Different prediction models for the evolution within a small population of the genetic mean of a selected trait, its genetic variance and its inbreeding have been developed but have mainly been validated through Monte Carlo simulation studies. The purpose of this study was to compare theoretical predictions to experimental results. Two deterministic methods were considered, both grounded on a polygenic additive model. Differences between theoretical predictions and experimental results arise from differences between the true and the assumed genetic model, and from mathematical simplifications applied in the prediction methods. Two sets of experimental lines of chickens were used in this study: the Dutch lines undergoing true truncation mass selection, the other lines (French) undergoing mass selection with a restriction on the representation of the different families. This study confirmed, on an experimental basis, that modelling is an efficient approach to make useful predictions of the evolution of selected populations although the basic assumptions considered in the models (polygenic additive model, normality of the distribution, base population at the equilibrium, etc.) are not met in reality. The two deterministic methods compared yielded results that were close to those observed in real data, especially when the selection scheme followed the rules of strict mass selection: for instance, both predictions overestimated the genetic gain in the French experiment, whereas both predictions were close to the observed values in the Dutch experiment.

Animals↗
PubMed2005

The mean and variance of the selection differential after top-down selection from a mixture of normal samples.

A procedure is presented for determining the mean and variance of the selection differential for top-down selections in which the candidates come from populations that have a different average score on the selection measure. Although the procedure is based on the same stochastic model and requires identical data to the currently available method for estimating the mean selection differential, it has the advantage that the resulting expressions are valid for finite-sample selection decisions and that the variance of the selection differential can also be assessed. The difference between the two procedures is illustrated by means of an example application, and it is shown how the present results are particularly helpful in determining the expected utility of personnel selection decisions.

Analysis of Variance↗
PubMed2000

Elective versus selective caesarean section for delivery of the small baby.

BACKGROUND: Elective caesarean delivery for women in preterm labour might reduce the chances of fetal or neonatal death, but it might also increase the risk of maternal morbidity. OBJECTIVES: The objective of this review was to assess the effects of a policy of elective caesarean delivery versus selective caesarean delivery for women in preterm labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register was searched. SELECTION CRITERIA: Randomised trials comparing a policy of elective caesarean delivery with expectant management with recourse to caesarean section. DATA COLLECTION AND ANALYSIS: One reviewer assessed eligibility and trial quality. MAIN RESULTS: Five studies involving 104 women were included. All trials reported recruiting difficulties. No significant differences between elective and selective policies for caesarean delivery were found for fetal, neonatal or maternal outcomes. REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate the use of a policy for elective caesarean delivery for small babies. Randomised trials in this area are likely to continue to experience recruitment problems. However it still may be possible to investigate elective caesarean delivery in preterm babies presenting cephalically.

Cesarean Section↗
PubMed2001

The effects of slice-selective excitation/refocusing in localized spectral editing with gradient-selected double-quantum coherence transfer.

Spectral editing using gradient-selected double-quantum filtering (DQF) with PRESS localization has been used for selective observation of metabolites in vivo. In previous studies using localized DQF sequences, it is generally assumed that the slice-selective pulses used in the sequence have no roles in coherence transfer, and do not interfere with DQF. To validate this assumption, the effects of slice-selective excitation/refocusing on DQF were investigated in DQF lactate editing sequences combined with PRESS localization. Contrary to the previous assumption, the results show that, due to chemical shift displacement artifact and J coupling, slice selection in DQF does interfere with coherence transfer, affecting both the accuracy of spatial localization and the detection sensitivity adversely. In the case of lactate editing, the effects of this interference can be accounted for simply by adjusting the strength of the slice-selection gradients and by using narrowband slice-selective refocusing pulses.

Calibration↗
PubMed1989

Bias in correlations from selected samples of relatives: the effects of soft selection.

Martin and Wilson (1982) describe two forms of sampling bias in twin studies. One is "hard selection," where individuals above a threshold participate, and those below do not. The second is "soft selection," where the probability of including a pair of relatives varies over the range of the character. We present an alternative model of soft selection which has strikingly different consequences for the resemblance between relatives. In general, the softer the threshold, the more the correlation resembles that in the underlying population. Results are presented where the probability of selection equals the cumulative distribution function of a normal distribution with 10% of the variance of the selected variable. In these circumstances, soft selection usually leads to less severely attenuated correlations than truncate selection.

Genetics, Behavioral↗
PubMed2006

Comparative effects of selective and non-selective nitric oxide synthase inhibition in gentamicin-induced rat nephrotoxicity.

Different nitric oxide synthase (NOS) isoforms are found in the kidney. Some studies provided evidences that increased endothelial NOS (eNOS) activity leads to restoration of renal function after injury, but activation of inducible NOS (iNOS) aggravates renal failure. In the present study, the beneficial effects of selective iNOS blockade in gentamicin (GM) induced nephrotoxicity have been investigated. Four groups of rats were studied. Untreated control rats received saline. In GM group, GM was injected (IV, 4 mg kg(-1)). In GM + L-NAME group rats received L-NAME (N-omega-L-arginine methyl ester, a non-selective NOS inhibitor) simultaneously with GM (IV, 30 mg kg(-1)). Additional doses of L-NAME were administered 2 and 4 h after GM (IP, 30 mg kg(-1)). In GM + L-NIL group rats were treated by N-imino-ethyl lysine (L-NIL, a selective iNOS inhibitor). First dose (IV, 3 mg kg(-1)) administrated simultaneously with GM. Next doses (IP, 3 mg kg(-1)) were administered 2 and 4 h after GM. In all groups, serum and urine creatinine levels were measured. Creatinine clearance was calculated and considered as an estimation of glomerular filtration rate (GFR). Urine N-acetyl-b-D-glucose aminidase (NAG) activities were also determined. After experiments, kidney sections were histologically studied. Selective iNOS inhibition by L-NIL prevented the GM-induced decrease in GFR and increase in creatinine levels, while complete non-selective NOS inhibition by L-NAME aggravated the GFR reduction, elevation of creatinine levels and enzyme release (P < 0.05). Histological studies showed that GM-treated kidneys had evidences of tubular damages and these damages were less evident by the administration of L-NIL. In conclusion, selective inhibition of iNOS may prevent GM-induced nephrotoxicity, whereas non-selective inhibition of NOS aggravates it.

Acetylglucosaminidase↗
PubMed1991

Attitudes on the ethics of abortion, sex selection, and selective pregnancy termination among health care professionals, ethicists, and clergy likely to encounter such situations.

The ethical attitudes of health care providers toward abortion, sex selection, and selective termination of normal and anomalous fetuses in singleton or multiple pregnancies were evaluated by questionnaires distributed to members of the American Society of Human Genetics, the International Fetal Medicine and Surgery Society, the Society of Perinatal Obstetricians, ethicists, and clergy. Demographic characteristics of respondents exhibited a preponderance of men (76%), age greater than 40 (68%), and of United States residents (82%). Seventy-nine percent of respondents were in the medical profession. Approximately half of the respondents were Protestant, the rest being evenly distributed among Catholic, Jewish, and other religions. Acceptance of abortion for social indication varied by religion and gestational age but not by religious conviction, age, country, or gender of respondent. First-trimester abortion of a normal singleton pregnancy was considered more acceptable than selective termination of normal fetuses in multifetal gestations. Sex selection was considered unethical by most respondents. Selective termination was deemed ethically appropriate in quadruplets or multifetal gestations of more than five fetuses and in multiple pregnancies bearing one anomalous fetus. In the latter situation, acceptance increased with the severity of fetal anomalies and decreased from the first to the third trimester. The medical specialty of respondents was the only independent factor strongly associated with acceptance of selective termination by trimester, indication, and number of fetuses. Acceptance of selective termination among health care professionals appears to reflect not only perceptions of procedure-related risks and benefits in the index pregnancy but also individual training and religious beliefs.

Abortion, Induced↗
PubMed1993

The interaction of selective and non-selective antagonists with pre- and postjunctional muscarinic receptor subtypes in the guinea pig trachea.

Muscarinic receptor antagonists were used to study prejunctional M2 and postjunctional M3 receptors in the isolated guinea pig trachea. The effects of four M2-selective muscarinic receptor antagonists (gallamine, methoctramine, AQ-RA 741 and AF-DX 116) were studied on twitch contractions, elicited by electrical field stimulation, of tracheal ring preparations. M1-selective (pirenzepine, (+)- and (-)-telenzepine), M3-selective (4-DAMP-methobromide and UH-AH 371) and non-selective (atropine and ipratropium) muscarinic receptor antagonists were also used. The clear potentiation of the twitch contractions and the subsequent strong inhibition observed with M2-selective antagonists demonstrate antagonism at prejunctional M2 and postjunctional M3 muscarinic receptors, respectively. The maximal potentiation correlated well with the M2/M3-selectivity known from binding experiments: gallamine > methoctramine > AQ-RA 741 > AF-DX 116. Strong correlations were also found between the pEC20 values for potentiation of the twitch response and the pKi values for bovine cardiac M2 muscarinic receptors and between the pIC50 values for inhibition of the twitch response and the pA2 values for M3 muscarinic receptors as determined on non-stimulated methacholine-contracted tracheal smooth muscle preparations. Thus, study of the effects of a wide concentration range of putative M2-selective muscarinic receptor antagonists on the twitch contractions of single tracheal rings induced by low-intensity electrical field stimulation yields information about M2/M3 receptor selectivity and about prejunctional M2 and postjunctional M3 receptor affinity within the same experiment.

Animals↗
PubMed2006

In vivo cholesteryl ester selective uptake of mildly and standardly oxidized LDL occurs by both parenchymal and nonparenchymal mouse hepatic cells but SR-BI is only responsible for standardly oxidized LDL selective uptake by nonparenchymal cells.

In blood circulation, low density lipoproteins (LDL) can undergo modification, such as oxidation, and become key factors in the development of atherosclerosis. Although the liver is the major organ involved in the elimination of oxidized LDL (oxLDL), the identity of the receptor(s) involved remains to be defined. Our work aims to clarify the role of the scavenger receptor class B type I (SR-BI) in the hepatic metabolism of mildly and standardly oxLDL as well as the relative contribution of parenchymal (hepatocytes) and nonparenchymal liver cells with a special emphasis on CE-selective uptake. The association of native LDL and mildly or standardly oxLDL labeled either in proteins or in cholesteryl esters (CE) was measured on primary cultures of mouse hepatocytes from normal and SR-BI knock-out (KO) mice. These in vitro assays demonstrated that hepatocytes are able to mediate CE-selective uptake from both LDL and oxLDL and that SR-BI KO hepatocytes have a 60% reduced ability to selectively take CE from LDL but not towards mildly or standardly oxLDL. When lipoproteins were injected in the mouse inferior vena cava, parenchymal and nonparenchymal liver cells accumulated more CE than proteins from native, mildly and standardly oxLDL, indicating that selective uptake of CE from these lipoproteins occurs in vivo in these two cell types. The parenchymal cells contribute near 90% of the LDL-CE selective uptake and SR-BI for 60% of this pathway. Nonparenchymal cells capture mainly standardly oxLDL while parenchymal and nonparenchymal cells equally take up mildly oxLDL. An 82% reduction of standardly oxLDL-CE selective uptake by the nonparenchymal cells of SR-BI KO mice allowed emphasizing the contribution of SR-BI in hepatic metabolism of standardly oxLDL. However, SR-BI is not responsible for mildly oxLDL metabolism. Thus, SR-BI is involved in LDL- and standardly oxLDL-CE selective uptake in parenchymal and nonparenchymal cells, respectively.

Animals↗
PubMed1996

A comparison of the yield of positive antenatal group B Streptococcus cultures with direct inoculation in selective growth medium versus primary inoculation in transport medium followed by delayed inoculation in selective growth medium.

OBJECTIVE: Our purpose was to compare the yield of positive group B Streptococcus cultures with standard medium for transport of culture swabs compared with use of selective medium during transport. STUDY DESIGN: Cultures of introitus, perineum, and rectum were obtained on prenatal patients; one was placed in standard transport medium, and the other directly in selective growth medium. Swabs in standard transport medium were plated for routine culture and then transferred to selective growth medium, Todd-Hewitt broth, in the laboratory. RESULTS: A total of 307 of 1222 (25.1%) patients had a positive result by any method. With direct inoculation into selective growth medium at the time of sampling, 4.6% of positive cultures were missed. With delayed inoculation into selective growth medium, 16.3% were missed (p < 0.001). Without use of selective media (routine culture), 31.9% were missed (p < 0.001). CONCLUSIONS: Use of standard transport medium with subsequent transfer into selective growth medium results in a significantly decreased yield of positive group B Streptococcus cultures.

Bacteriological Techniques↗
PubMed2003

Achieving selectivity between highly homologous tyrosine kinases: a novel selective erbB2 inhibitor.

The discovery of small molecule kinase inhibitors for use as drugs is a promising approach for the treatment of cancer and other diseases, but the discovery of highly specific agents is challenging because over 850 kinases are expressed in mammalian cells. Systematic modification of the 4-anilino functionality of a selective quinazoline inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase can invert selectivity to favor inhibition of the highly homologous erbB2 tyrosine kinase. The selectivity pattern was demonstrated in assays of recombinant kinases and recapitulated in measures of kinase activity in intact cells. The most potent and selective erbB2 inhibitor of the analog series has anti-proliferative activity against an erbB2-overexpressing cell line that was lacking in the original EGFR-selective compound. Subtle changes to the molecular structure of ATP-competitive small molecule inhibitors of tyrosine kinases can yield dramatic changes in potency and selectivity. These results suggest that the discovery of highly selective small molecule inhibitors of very homologous kinases is achievable.

Adenosine Triphosphate↗
PubMed2003

Conversion of delta-, kappa- and mu-receptor selective opioid peptide agonists into delta-, kappa- and mu-selective antagonists.

2',6'-Dimethyl substitution of the Tyr(1) residue of opioid agonist peptides and deletion of the positively charged N-terminal amino group or its replacement with a methyl group has recently been shown to represent a general structural modification to convert opioid peptide agonists into antagonists. This conversion requires the syntheses of opioid peptide analogues containing either 3-(2,6-dimethyl-4-hydroxyphenyl)propanoic acid (Dhp) or (2S)-2-methyl-3-(2,6-dimethyl-4-hydroxyphenyl)propanoic acid [(2S)-Mdp] in place of Tyr(1). Using this approach, delta-, kappa- and mu-selective opioid peptide agonist peptides were successfully converted into corresponding delta-, kappa- and mu-selective antagonists, whereby receptor selectivity was often maintained or even improved. Thus, two (2S)-Mdp(1)-analogues of the delta-selective cyclic enkephalin analogue H-Tyr-c[D-Pen-Gly-Phe(pF)-Pen]-Phe-OH turned out to be potent and selective delta antagonists. Most successful was the development of kappa antagonists derived from dynorphin A (Dyn A), including the highly potent and selective kappa-antagonist [(2S)-Mdp(1)]Dyn A(1-11)-NH(2) (dynantin) and the enzymatically stable octapeptide analogue [(2S)-Mdp(1),MeArg(7),D-Leu(8)]Dyn A(1-8)-NH(2). The (2S)-Mdp(1)-analogues of dynorphin B and alpha-neoendorphin also were kappa antagonists and may be useful as pharmacological tools in studies of kappa receptor subtypes. Finally, the Dhp(1)-analogues of the mu-selective cyclic enkephalin analogue H-Tyr-c[N(epsilon ),N(beta)-carbonyl-D-Lys(2),Dap(5)]enkephalinamide and of endomorphin-2 were moderately potent mu opioid antagonists.

Animals↗
PubMed1999

A method for evaluating chemical selectivity of agonists for glutamate receptor channels incorporated in liposomes based on an agonist-induced ion flux measured by ion-selective electrodes.

A new method for evaluating chemical selectivity of agonists for the NMDA subtype of glutamate receptor (GluR) channels is described. The method is based on the magnitude of Ca2+ release from GluR-incorporated liposomes, which is measured by a Ca2+ ion-selective electrode with a thin-layer mode. The partially purified GluRs from rat whole brain were reconstituted into Ca2+-loaded liposomes. Small aliquots (each 50 microl) of the proteoliposomes, in the presence of an antagonist DNQX for blocking non-NMDA subtype, were subjected to potentiometric measurements of Ca2+ release under stimulation by three kinds of agonists, i.e. NMDA, L-glutamate and L-CCG-IV. The amount of the Ca2+ ion flux through the GluR channel induced by the agonists was found to increase in the order of NMDA < L-glutamate < L-CCG-IV, which was consistent with that of binding affinity of the agonists toward the NMDA subtype. However, the range of selectivity of the relevant agonists was much smaller compared with results based on binding affinities. The present method provides physiologically more relevant values for the agonist selectivity of GluRs as compared to that of the conventional binding assay in the sense that the selectivity is based on the very magnitude of Ca2+ flux through the NMDA receptor, i.e. the extent of signal transduction by a given agonist. The evaluation of agonist selectivity based on Na+ release was also investigated by using a Na+ ion-selective electrode, but agonist-induced Na+ release was not detected, because of low permeability of Na+ through the NMDA subtype.

Amino Acids, Dicarboxylic↗
PubMed1993

Hypoxia-selective antitumor agents. 7. Metal complexes of aliphatic mustards as a new class of hypoxia-selective cytotoxins. Synthesis and evaluation of cobalt(III) complexes of bidentate mustards.

Nitrogen mustards coordinated to Co(III) are potential hypoxia-selective cytotoxins, since one-electron reduction to the Co(II) complexes greatly labilizes the Co-N bonds, causing the release of activated aliphatic mustards which can act as diffusible cytotoxins. Two series of Co(III) complexes of the bidentate bisalkylating nitrogen mustard ligands N,N'-bis(2-chloroethyl)-ethylenediamine (BCE) and N,N-bis(2-chloroethyl)ethylenediamine (DCE) have been synthesized and evaluated for their hypoxia-selective cytotoxicity against AA8 cells in vitro. The complexes also bear two 3-alkylpentane-2,4-dionato (acac) auxiliary ligands; cyclic voltammetry studies show that variation of the alkyl group in the auxiliary ligands alters the reduction potentials of the complexes (within a series) over a range of about 150 mV. In both series, the patterns of cytotoxicities of the cobalt complexes were broadly similar to those of the respective free ligands, suggesting that the cytotoxicity of these compounds is due to release of the free ligands. The nonsymmetrical ligand DCE and its cobalt complexes were 1 order of magnitude more cytotoxic than the corresponding BCE compounds. Although the unsubstituted acac/DCE complex showed no hypoxic selectivity against repair-deficient UV4 cells in a stirred suspension culture assay, the methyl and ethyl analogues showed substantial selectivity. The results may indicate a narrow range of acceptable reduction potential, with an optimum close to that for the methyl analogue (E1/2 = -305 mV). The methyl analogue also shows hypoxic selectivity against repair-proficient cell lines (e.g., AA8 and EMT6) and has high activity against EMT6 cells in intact spheroids, suggesting that the released DCE is capable of back-diffusion from the hypoxic core of the spheroid. This work shows that metal complexes of nitrogen mustards have significant hypoxia-selective cytotoxicity toward mammalian cells in cell culture and are a new general class of hypoxia-selective cytotoxins.

Animals↗
PubMed1992

Hypoxia-selective antitumor agents. 5. Synthesis of water-soluble nitroaniline mustards with selective cytotoxicity for hypoxic mammalian cells.

Nitroaniline mustards have potential as hypoxia-selective cytotoxic agents, with reductive metabolism activating the nitrogen mustard by converting the electron-withdrawing nitro group to an electron-donating hydroxylamine or amine. However, the parent compounds have poor aqueous solubility, and their potencies are limited by low reduction potentials (E1/2 ca. -600 mV versus the normal hydrogen electrode) and corresponding slow rates of nitro reduction. To address these limitations, a series of 4-nitroaniline mustards bearing hydrophilic side chains attached via an electron-withdrawing carboxamide group was prepared and evaluated for hypoxia-selective cytotoxicity against Chinese hamster cell lines. The N-[(N,N-dimethylamino)ethyl]carboxamide derivatives proved to have excellent aqueous solubility and improved cytotoxic potency, but their reduction potentials, while higher than the non-carboxamide compounds, were still low and little selectivity for hypoxic cells were observed. A series of carboxamides of 2,4-dinitroaniline mustard was also prepared. These compounds had reduction potentials in the desired range (E1/2 ca. -450 mV by cyclic voltammetry) and were more toxic to hypoxic than aerobic UV4 cells. The most selective compounds were 5-[N,N-bis(2-chloroethyl)amino]-2,4-dinitrobenzamide (20, SN 23862) and its water-soluble N-[(N,N-dimethylamino)ethyl]carboxamide analogue. These showed selectivities of 60- to 70-fold for hypoxic UV4 cells. The selectivity of 20 was much superior to that of its aziridine analogue (23, CB 1954), which was only 3.6-fold more toxic to hypoxic than oxic cells in the same system. Compound 20 is a much less efficient substrate than CB 1954 for the major aerobic nitroreductase from rat Walker tumor cells, NAD(P)H:quinone oxidoreductase (DT diaphorase). Lack of aerobic bioactivation of 20 by DT diaphorases may be responsible for its higher hypoxic selectivity than that of 23.

Aniline Compounds↗
PubMed2004

Sex selection, child welfare and risk: a critique of the HFEA's recommendations on sex selection.

This paper will examine the recent Human Fertilisation and Embryology Authority public consultation on sex selection. It will review the current regulation on sex selection in the United Kingdom and critically examine the outcomes of the HFEA consultation. The paper will argue that the current ban on embryo sex selection for social reasons and a proposed ban on sperm selection are not justified. There is no evidence for sex selection causing an increase in sex discrimination; creating a slippery slope towards selection for other non-disease characteristics; or promoting a consunmerist attitude towards children. The HFEA recommendations to prohibit social sex selection techniques rely upon an unwarranted concern about the risk of the procedures used. Reproductive technologies should be made available to peoptle unless a substantial risk of harm--to the child, the parents or to society--can be identified. There is no such evidence of harm in this case.

Advisory Committees↗