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PubMed1997

Effects of oxygenation during selective lobar versus total lung collapse with or without continuous positive airway pressure.

UNLABELLED: Hypoxemia is common during anesthesia with one-lung ventilation (OLV). This study tested the hypothesis that selective lobar blockade would result in higher PaO2 values compared with those found with total lung collapse independent of continuous positive airway pressure (CPAP) application. Thirty patients undergoing lobectomy were randomly assigned to one of four groups with the following maneuvers during OLV: Group 1 (n = 8) total lung collapse (TLC) plus 5 cm H2O of CPAP to the nonventilated operative lung for 15 mins, followed by selective lobe collapse plus 5 cm H2O of CPAP (during selective collapse only the surgical lobe was collapsed and the rest of that lung was ventilated); Group 2 (n = 6) selective lobar collapse plus 5 cm H2O of CPAP to the operative lung, followed by TLC plus 5 cm H2O of CPAP; Group 3 (n = 8) total lung collapse without CPAP, followed by selective lobe collapse and no CPAP; Group 4 (n = 8) selective lobe collapse without CPAP, followed by TLC and no CPAP. To obtain selective lobe collapse, the bronchial blocker of the Univent (Vitaid, Lewiston, NY) endotracheal tube was guided into the operative bronchus with the aid of a fiberoptic bronchoscope. Blood pressure, heart rate, and arterial blood gas measurements were obtained during the following times: Time 1--while the patient was awake; Time 2--two-lung ventilation (2LV) in the supine position; Time 3--after 30 min of OLV in the lateral decubitus position (no CPAP or selective blockade); Time 4 and Time 5--during maneuvers described above (see group description); Time 6--2LV resumed; Time 7--30 min after extubation. Twenty-eight patients completed the study. There were no differences among groups with regard to arterial blood pressure, heart rate, or arterial oxygen saturation during the experimental maneuvers. All four groups showed a decrease in PaO2 from 2LV to OLV (P < 0.05). Both with and without CPAP application, oxygenation was improved with selective lobe collapse compared with TLC. When selective lobe collapse with 5 cm H2O of CPAP followed TLC (group 1), PaO2 values increased to values similar to those found for 2LV (PaO2 449 +/- 122 vs 394 +/- 105 mm Hg). This study indicates that by using a bronchial blocker, changing from total lung collapse to selective lobar blockade improves PaO2 during lung surgery. IMPLICATIONS: This study examines how oxygen tension in arterial blood can be higher during one-lung ventilation. The use of a bronchial blocker, which changes a total lung collapse to selective lobar blockade, improves oxygenation during lung surgery.

Adult↗
PubMed2002

Population variation in sexual selection and its effect on size allometry in two dung fly species with contrasting sexual size dimorphism.

Body size is one of the most important quantitative traits under evolutionary scrutiny. Sexual size dimorphism (SSD) in a given species is expected to result if opposing selection forces equilibrate differently in both sexes. We document variation in the intensity of sexual and fecundity selection, male and female body size, and thus SSD among 31 and 27 populations of the two dung fly species, Scathophaga stercoraria and Sepsis cynipsea, across Switzerland. Whereas in S. cynipsea females are larger, the SSD is reversed in S. stercoraria. We comprehensively evaluated Fairbairn and Preziosi's (1994) general, three-tiered scenario, hypothesizing that sexual selection for large male size is the major driving force of SSD allometry within these two species. Sexual selection intensity on male size in the yellow dung fly, S. stercoraria, was overall positive, greater, and more variable among populations than fecundity selection on females. Also, sexual selection intensity in a given population correlated positively with mean male body size of that population for both the field-caught fathers and their laboratory-reared sons, indicating a response to selection. In S. cvnipsea, sexual selection intensity on males was lower overall and significantly positive, about equal in magnitude, but more variable than fecundity selection on females. However, there was no correlation between the intensity of sexual selection and mean male body size among populations. In both species, the laboratory-reared offspring indicate genetic differentiation among populations in body size. Despite fulfillment of all key prerequisites, at least in S. stercoraria, we did not find hypoallometry for SSD (Rensch's rule, i.e., greater evolutionary divergence in male size than female size) for the field-caught parents or the laboratory-reared offspring: Female size was isometric to male size in both species. We conclude that S. cynipsea does not fit some major requirements of Fairbairn and Preziosi's (1994) scenario, whereas for S. stercoraria we found partial support for it. Failure to support Rensch's rule within the latter species may be due to phylogenetic or other constraints, power limitations, erroneous estimates of sexual selection, insufficient genetic isolation of populations, or sex differences in viability selection against large size.

Animals↗
PubMed1997

Altered pHi regulation in 3T3/CFTR clones and their chemotherapeutic drug-selected derivatives.

Recently (L. Y. Wei, M. J. Stutts, M. M. Hoffman, and P. D. Roepe. Biophys. J. 69: 883-895, 1996), 3T3 cells overexpressing the cystic fibrosis transmembrane conductance regulator (CFTR) were found to exhibit chemotherapeutic drug resistance and other traits of multidrug resistant (MDR) cells. In the present work, NIH 3T3/CFTR clones were selected with either doxorubicin or vincristine in incremental fashion to generate series of stable MDR cell lines that exhibit increasing levels of drug resistance. Thus C3D6 (grown in the presence of 600 nM doxorubicin) was selected from C3D4 (grown in the presence of 400 nM doxorubicin), which was selected from C3D1 (grown in the presence of 100 nM doxorubicin), which was in turn selected from the original 3T3/CFTR clone C3 (M. J. Stutts, S. E. Gabriel, J. C. Olsen, J. T. Gatzy, T. L. O'Connell, E. M. Price, and R. C. Boucher. J. Biol. Chem. 268: 20653-20658, 1993), which was not grown in the presence of chemotherapeutic drug. A similar series was generated via selection with vincristine. In both series, as well as series derived from a different CFTR clone, initial low-level drug selection increases CFTR expression without promoting MDR 1 or multidrug resistance-associated protein expression. On continued selection at higher drug concentrations, CFTR mRNA levels decrease while MDR 1 mRNA levels concomitantly increase. At each incremental step of selection, intracellular pH (pHi) increases (e.g., pHi of C3D6 > C3D4 > C3D1 > C3). Cl-/HCO3- exchange activity is significantly reduced in the drug-selected derivatives overexpressing MDR 1 but not the parental CFTR clones. The apparent set point of Na+/H+ exchange activity is significantly lower for the non-drug-selected 3T3/CFTR clones, relative to controls, but it increases on initial selection with chemotherapeutic drug. Overexpression of MDR 1 in the higher-level selectants does not appear to further perturb apparent Na+/H+ exchange. These data further describe how CFTR and MDR proteins may affect pHi regulation.

3T3 Cells↗
PubMed2000

Selectivity for the shape, size, and orientation of objects for grasping in neurons of monkey parietal area AIP.

In this study, we mainly investigated the visual selectivity of hand-manipulation-related neurons in the anterior intraparietal area (area AIP) while the animal was grasping or fixating on three-dimensional (3D) objects of different geometric shapes, sizes, and orientations. We studied the activity of 132 task-related neurons during the hand-manipulation tasks in the light and in the dark, as well as during object fixation. Seventy-seven percent (101/132) of the hand-manipulation-related neurons were visually responsive, showing either lesser activity during manipulation in the dark than during that in the light (visual-motor neurons) or no activation in the dark (visual-dominant neurons). Of these visually responsive neurons, more than half (n = 66) responded during the object-fixation task (object-type). Among these, 55 were tested for their shape selectivity during the object-fixation task, and many (n = 25) were highly selective, preferring one particular shape of the six different shapes presented (ring, cube, cylinder, cone, sphere, and square plate). For 28 moderately selective object-type neurons, we performed multidimensional scaling (MDS) to examine how the neurons encode the similarity of objects. The results suggest that some moderately selective neurons responded preferentially to common geometric features shared by similar objects (flat, round, elongated, etc.). Moderately selective nonobject-type visually responsive neurons, which did not respond during object fixation, were found by MDS to be more closely related to the handgrip than to the object shape. We found a similar selectivity for handgrip in motor-dominant neurons that did not show any visual response. With regard to the size of the objects, 16 of 26 object-type neurons tested were selective for both size and shape, whereas 9 object-type neurons were selective for shape but not for size. Seven of 12 nonobject-type and all (8/8) of the motor-dominant neurons examined were selective for size, and almost all of them were also selective for objects. Many hand-manipulation-related neurons that preferred the plate and/or ring were selective for the orientation of the objects (17/20). These results suggest that the visual responses of object-type neurons represent the shape, size, and/or orientation of 3D objects, whereas those of the nonobject-type neurons probably represent the shape of the handgrip, grip size, or hand-orientation. The activity of motor-dominant neurons was also, in part, likely to represent these parameters of hand movement. This suggests that the dorsal visual pathway is concerned with the aspect of form, orientation, and/or size perception that is relevant for the visual control of movements.

Animals↗
PubMed2002

Orientation selectivity is reduced by monocular deprivation in combination with PKA inhibitors.

We have previously shown that the protein kinase A (PKA) inhibitor, 8-chloroadenosine-3',5'-monophosphorothioate (Rp-8-Cl-cAMPS), abolishes ocular dominance plasticity in the cat visual cortex. Here we investigate the effect of this inhibitor on orientation selectivity. The inhibitor reduces orientation selectivity in monocularly deprived animals but not in normal animals. In other words, PKA inhibitors by themselves do not affect orientation selectivity, nor does monocular deprivation by itself, but monocular deprivation in combination with a PKA inhibitor does affect orientation selectivity. This result is found for the receptive fields in both deprived and nondeprived eyes. Although there is a tendency for the orientation selectivity in the nondeprived eye to be higher than the orientation selectivity in the deprived eye, the orientation selectivity in both eyes is considerably less than normal. The result is striking in animals at 4 wk of age. The effect of the monocular deprivation on orientation selectivity is reduced at 6 wk of age and absent at 9 wk of age, while the effect on ocular dominance shifts is less changed in agreement with previous results showing that the critical period for orientation/direction selectivity ends earlier than the critical period for ocular dominance. We conclude that closure of one eye in combination with inhibition of PKA reduces orientation selectivity during the period that orientation selectivity is still mutable and that the reduction in orientation selectivity is transferred to the nondeprived eye.

Animals↗
PubMed2004

Topical colchicine selection of keratinocytes transduced with the multidrug resistance gene (MDR1) can sustain and enhance transgene expression in vivo.

In gene therapy, a clinically relevant therapeutic effect requires long-term expression of the desired gene at a level sufficient to correct or at least alleviate the underlying gene defect. One approach to achieve persistent as well as high-level transgene expression in a significant percentage of target cells would be to select cells expressing both the desired transgene and a linked selectable gene--such as the human multi-drug resistance (MDR1) gene--in a bicistronic vector. Because of its accessibility, the skin is a very attractive target tissue to select genetically modified cells, allowing topical application of a selecting agent, thus minimizing potential toxic side effects. Among the potential selecting drugs, agents that block cell division, such as colchicine, are of particular interest because the use of anti-mitotic drugs takes advantage of the rapid keratinocyte (KC) turnover in the epidermis and the need for continued proliferation to substitute the KC lost due to selection. Before assessing the therapeutic benefit of such an approach, several key questions need to be answered in preclinical models: (1) Does topical colchicine application achieve the desired in vivo effect by blocking KC mitosis without eliciting unwanted toxic side effects? (2) Are MDR-transduced (MDR+) human KC still able to proliferate and differentiate when treated with colchicine? (3) Can MDR+ KC be enriched by topical selection? (4) Does topical selection result in persistent transgene expression by selecting KC stem cells expressing MDR? To answer these questions and to test the feasibility of such an approach both an in vitro skin equivalent and an in vivo human skin graft model were developed in which MDR+ KC were treated with different dosages of colchicine. Quantitative and qualitative analyses of MDR expression in human KC showed that topical colchicine treatment selects high-level transgene expression in a high percentage of KC. Moreover, determination of transgene copy numbers demonstrated that MDR+ KC progenitor cells were enriched by topical selection resulting in long-term expression of the transgene in the skin. Thus, in summary, these models demonstrate that topical selection of MDR+ KC is a safe approach to efficiently enhance long-term gene expression in the skin and holds future promise for clinical gene therapy applications.

Administration, Topical↗
PubMed2001

An algorithm for mapping positively selected members of quasispecies-type viruses.

BACKGROUND: Many RNA viruses do not have a single, representative genome but instead form a set of related variants that has been called a quasispecies. The sequence variability of such viruses presents a significant bioinformatics challenge. In order for the sequence information to be understood, the complete mutational spectrum needs to be distilled to a biologically relevant and analyzable representation. RESULTS: Here, we develop a "selection mapping" algorithm--QUASI--that identifies the positively selected variants of viral proteins. The key to the selection mapping algorithm is the identification of particular replacement mutations that are overabundant relative to silent mutations at each codon (e.g., threonine at hemagglutinin position 262). Selection mapping identifies such replacement mutations as positively selected. Conversely, selection mapping recognizes negatively selected variants as mutational "noise" (e.g., serine at hemagglutinin position 262). CONCLUSION: Selection mapping is a fundamental improvement over earlier methods (e.g., dN/dS) that identify positive selection at codons but do not identify which amino acids at these codons confer selective advantage. Using QUASI's selection maps, we characterize the selected mutational landscapes of influenza A H3 hemagglutinin, HIV-1 reverse transcriptase, and HIV-1 gp120.

Algorithms↗
PubMed2001

Toward automated nucleic acid enzyme selection.

Methods for automation of nucleic acid selections are being developed. The selection of aptamers has been successfully automated using a Biomek 2000 workstation. Several binding species with nanomolar affinities were isolated from diverse populations. Automation of a deoxyribozyme ligase selection is in progress. The process requires eleven times more robotic manipulations than an aptamer selection. The random sequence pool contained a 5' iodine residue and the ligation substrate contained a 3' phosphorothioate. Initially, a manual deoxyribozyme ligase selection was performed. Thirteen rounds of selection yielded ligators with a 400-fold increase in activity over the initial pool. Several difficulties were encountered during the automation of DNA catalyst selection, including effectively washing bead-bound DNA, pipetting 50% glycerol solutions, purifying single strand DNA, and monitoring the progress of the selection as it is performed. Nonetheless, automated selection experiments for deoxyribozyme ligases were carried out starting from either a naive pool or round eight of the manually selected pool. In both instances, the first round of selection revealed an increase in ligase activity. However, this activity was lost in subsequent rounds. A possible cause could be mispriming during the unmonitored PCR reactions. Potential solutions include pool redesign, fewer PCR cycles, and integration of a fluorescence microtiter plate reader to allow robotic 'observation' of the selections as they progress.

Automation↗
PubMed1996

Impact of selective financing of drugs on pharmaceutical expenditure control in the province of Valladolid, Spain.

In July 1993, public financing for 1692 drug specialities was stopped in Spain (a drug speciality is a medicine with a defined composition, particular pharmaceutical form and dosage, prepared for immediate use, ready and packaged for dispatching to the public, with uniform name, packaging and labelling which has been granted authorisation by the State Administration and registered in the Pharmaceutical Specialities Register). We designed a study to assess the repercussions of this so-called 'selective financing' on expenditure control. The aims of the study were 2-fold: first, to forecast the consumption of drug specialities that are reimbursable on the Spanish National Health Service, had selective financing not been applied; and, secondly, to estimate the impact of selective financing on drug consumption. For short- and medium-term forecast estimates, time-series analysis was used, and was applied to monthly consumption data. The measures of consumption used were the number of prescriptions per 1000 patients, and cost [in Spanish pesetas (Pta; $US1 = Pta123.9, February 1996)] per 1000 patients. Data were analysed from January 1986 up to the introduction of selective financing. We found that drug specialities excluded by selective financing showed, overall, a negative increase (i.e. the consumption of drugs that were excluded under selective financing decreased). The repercussion forecast, both in terms of prescription numbers and cost, of the 13 excluded drug specialities that had the highest pre-selective financing consumption is decreasing compared with total consumption. The assessment of the repercussions of selective financing up to December 1994 was made by calculating the difference between actual expenditures and forecast expenditures in the absence of selective financing. This repercussion, in prescriptions, was lower than the percentage of the 1692 excluded drug specialities relating to total consumption in 1992. The repercussion in cost, nevertheless, was greater than expected during the first year of selective financing application. This could be attributable to average price containment of drug specialities due to causes other than selective financing itself. The economic impact of selective financing after 1 year of application was reduced because of accommodation phenomena.

Cost Control↗
PubMed2002

Improving metal ion specificity during in vitro selection of catalytic DNA.

Metal ions play important roles in both the structure and function of catalytic DNA and RNA. While most natural catalytic RNA molecules (ribozymes) are active in solutions containing Mg(2+), in vitro selection makes it possible to search for new catalytic DNA/RNA that are specific for other metal ions. However, previous studies have indicated that the in vitro selection protocols often resulted in catalytic DNA/RNA that were equally active or sometimes even more active with metal ions other than the metal ion of choice. To improve the metal ion specificity during the in vitro selection process, we implemented a negative selection strategy where the nucleic acid pool was subjected to a solution containing competing metal ions. As a result, those nucleic acids that were active with those metal ions are discarded. To demonstrate the effectiveness of the negative selection strategy, we carried out two parallel in vitro selections of Co(2+)-dependent catalytic DNA. When no negative selection was used in the selection process, the resulting catalytic DNA molecules were more active in solutions of Zn(2+) and Pb(2+) than in Co(2+). On the other hand, when the negative selection steps were inserted between the normal positive selection steps, the resulting catalytic DNA molecules were much more active with Co(2+) than in other metal ions including Zn(2+) and Pb(2+). These results suggest strongly that in vitro selection can be used to obtain highly active and specific transition metal ion-dependent catalytic DNA/RNA, which hold great promise as versatile and efficient endonucleases as well as sensitive and selective metal ion sensors.

Base Sequence↗
PubMed1991

Selection within and across populations in livestock improvement.

Genetic evaluations within and across populations (countries, breeds, herds) allow ranking on estimated genetic merit and selecting breeding individuals across populations. Selection within and across populations (combined selection) should by definition always be as good as, or better than, within-population selection, the limiting case. The advantage depends on the sizes of the populations, the number of populations, the initial genetic means, and the correspondence of the breeding objectives in the different populations, as measured by the genetic correlation for economic merit. The advantages of combined selection are evaluated deterministically for a simple case of selecting the best males for use across populations by using a common truncation line over the distributions of EBV for the different populations. Combined selection increases overall response rates in the cooperating populations. Where the initial genetic means are the same, small populations (100 males tested) benefit greatly from combined selection. Large populations (500 to 1,000 males tested) also benefit, but less. The results depend on the increased selection response to scale, response being approximately linear with the logarithm of the number tested. When the initial means differ, the genetically poorer population can catch up in three to five generations and then contribute to the increased responses with combined selection. When breeding objectives differ, selection usually gradually pulls the populations apart and they make less and less contribution to each other and finally become separate. These results have implications for breeding strategies. Their application would affect structures of populations and rates of genetic change possible by selection.

Animals↗
PubMed1993

Efficiency of visual selection in duplex and conjunction conditions in partial report.

Factors that determine the efficiency of visual selection were investigated in two precued partial-report experiments. There were four selection conditions: a color condition (e.g., selecting purple letters among blue letters), a class condition (e.g., selecting letters among digits), a duplex condition (e.g., selecting purple letters among blue digits; that is, the targets differed from the distractors both in color and in alphanumeric class), and a conjunction condition (e.g., selecting purple letters among blue letters and purple digits; that is, the targets differed from the distractors either in color or in alphanumeric class). The efficiency of visual selection was highest in the duplex condition and lowest in the conjunction condition. The difference in performance across the different selection conditions within subjects was accounted for by variation in the value of a single parameter of the fixed-capacity independent race model (FIRM) proposed by Shibuya and Bundesen (1988), which assumes independent parallel processing, limitations in both processing capacity and storage capacity, and time-invariant selectivity. By assuming that the factors that determine the efficiency of selection in the color and class conditions also underlie the efficiency of selection in the duplex and conjunction conditions, an extension of FIRM, FIRM+, accounted for the relationship with respect to efficiency of selection among the different conditions.

Adolescent↗
PubMed2003

Phenotypic versus marker-assisted selection for stalk strength and second-generation European corn borer resistance in maize.

Maize ( Zea mays L.) stalk lodging is breakage of the stalk at or below the ear, which may result in loss of the ear at harvest. Stalk lodging is often intensified by the stalk tunneling action of the second-generation of the European corn borer (2-ECB) [Ostrinia nubilalis (Hübner)]. Rind penetrometer resistance (RPR) has been used to measure stalk strength and improve stalk lodging resistance, and quantitative trait loci (QTL) have been identified for both RPR and 2-ECB damage. Phenotypic recurrent selection (PS) increases the frequency of favorable alleles over cycles of selection. Several studies have indicated that marker-assisted selection (MAS) is also a potentially valuable selection tool. The objective of this study was to compare the efficiency of PS versus MAS for RPR and 2-ECB. Marker-assisted selection for high and low RPR was effective in the three populations studied. Phenotypic selection for both high and low RPR was more effective than MAS in two of the populations. However, in a third population, MAS for high RPR using QTL effects from the same population was more effective than PS, and using QTL effects from a separate population was just as effective as PS. Marker-assisted selection for resistance and susceptibility to 2-ECB using QTL effects from the same population was effective in increasing susceptibility, but not in increasing resistance. Marker-assisted selection using QTL effects from a separate population was effective in both directions of selection. Thus, MAS was effective in selecting for both resistance and susceptibility to 2-ECB. These results demonstrated that MAS can be an effective selection tool for both RPR and 2-ECB resistance. These results also validate the locations and effects of QTL for RPR and 2-ECB resistance identified in earlier studies.

Alleles↗
PubMed2006

Phenotypic selection on leaf water use efficiency and related ecophysiological traits for natural populations of desert sunflowers.

Plant water-use efficiency (WUE) is expected to affect plant fitness and thus be under natural selection in arid habitats. Although many natural population studies have assessed plant WUE, only a few related WUE to fitness. The further determination of whether selection on WUE is direct or indirect through functionally related traits has yielded no consistent results. For natural populations of two desert annual sunflowers, Helianthus anomalus and H. deserticola, we used phenotypic selection analysis with vegetative biomass as the proxy for fitness to test (1) whether there was direct and indirect selection on WUE (carbon isotope ratio) and related traits (leaf N, area, succulence) and (2) whether direct selection was consistent with hypothesized drought/dehydration escape and avoidance strategies. There was direct selection for lower WUE in mesic and dry H. anomalus populations, consistent with dehydration escape, even though it is the longer lived of the two species. For mesic H. anomalus, direct selection favored lower WUE and higher N, suggesting that plants may be "wasting water" to increase N delivery via the transpiration stream. For the shorter lived H. deserticola in the direr habitat, there was indirect selection for lower WUE, inconsistent with drought escape. There was also direct selection for higher leaf N, succulence and leaf size. There was no direct selection for higher WUE consistent with dehydration avoidance in either species. Thus, in these natural populations of two desert dune species higher fitness was associated with some combination direct and indirect selection for lower WUE, higher leaf N and larger leaf size. Our understanding of the adaptive value of plant ecophysiological traits will benefit from further consideration of related traits such as leaf nitrogen and more tests in natural populations.

Desert Climate↗
PubMed1995

A signal strength hypothesis of thymic selection: preliminary considerations.

During their differentiation, thymocytes are subjected to two rounds of selection. First, CD4-8- double-negative (DN) thymocytes with a functional TCR-beta chain express a alpha-beta+ CD3 complex on their surface and, as a consequence, are selected to mature to the CD4+8+ double-positive (DP) stage. This round ends after the initial proliferation of young DP thymocytes and is termed beta-chain selection. Second, DP thymocytes are selected on the basis of their alpha+beta+ CD3 complex. This is termed repertoire selection and the cells are given three choices: death by neglect selection, death by positive selection, or deletion by negative selection. Using anti-CD3 epsilon mAb as invariant ligand, signals for beta-chain selection of DN cells including proliferation of DP cells do not require a Ca2+ response, are independent of CD3 zeta, and are only slightly impaired in the absence of p56lck (lck). Signals that induce positive selection of DP thymocytes require a partial Ca2+ response and CD3 zeta but are independent of lck. Deletion of DP thymocytes requires a full-blown Ca2+ response and both, CD3 zeta and lck. Thymic selection thus appears to be governed by a gradient of signal intensities.

CD3 Complex↗
PubMed1990

Effects of genetic selection on growth rate and intestinal structure in the domestic fowl (Gallus domesticus).

1. Pieces of small intestine taken from chickens subjected previously to continuous selection, relaxed selection or no selection for rapid growth were used to estimate villus surface area and microvillus development to determine what effects genetic selection might have on factors controlling intestinal function. 2. Crypt size and the rates at which enterocytes migrated out of crypts were also measured, after injection of tritiated thymidine, to determine the time course of microvillus elongation. 3. Differences in growth rates measured between highly selected, relaxed selected or unselected birds were found to be correlated with parallel changes in villus surface area. Selection for growth did not change the density, dimensions or pattern of development of enterocyte microvilli. Microvilli did, however, produce a maximal 20-fold increase in villus surface area under all conditions. 4. Crypt size and enterocyte migration rates did not vary significantly between tissue taken from unselected and relaxed selected chickens. Tissue taken from highly selected birds had a crypt size and enterocyte migration rate 40% higher than values found for the other two groups of chickens. 5. The possibility that early genetic selection increased growth potential by uncoupling diet-induced changes on crypt hyperplasia from secondary effects on villus structure, and that later selection increased growth potential by increasing appetite, is discussed.

Animals↗
PubMed2005

Background selection and population differentiation.

A general analytical formula is derived, which predicts the effects of background selection on population differentiation at a neutral locus as a result of its linkage with selected loci of deleterious mutations. The theory is based on the assumptions of random mating, multiplicative fitness, and weak selection in hermaphrodite plants in the island model of population structure. The analytical results show that Fst at the neutral locus increases as a result of the effects of background selection, regardless of the dependence or independence among linked background selective loci. The increment in Fst is closely related to the magnitude of linkage disequilibria between the neutral locus and selected loci, and can be estimated by the ratio of Fst with background selection to Fst without background selection minus one. The steady-state linkage disequilibrium between a neutral locus and a selected locus in subpopulations, primarily attained by gene flow, decreases with the recombination rate, and can be enhanced when there are dependence among linked selected loci. Monte Carlo computer simulations with two- and three-locus models show that the analytical formulae perform well under general conditions. Application of the present theory may aid in analyzing the genome-wide mapping of the effect of background selection in terms of Fst.

Computer Simulation↗
PubMed2003

Sperm competition games: sperm selection by females.

We analyse a co-evolutionary sexual conflict game, in which males compete for fertilizations (sperm competition) and females operate sperm selection against unfavourable ejaculates (cryptic female choice). For simplicity, each female mates with two males per reproductive event, and the competing ejaculates are of two types, favourable (having high viability or success) or unfavourable (where progeny are less successful). Over evolutionary time, females can increase their level of sperm selection (measured as the proportion of unfavourable sperm eliminated) by paying a fecundity cost. Males can regulate sperm allocations depending on whether they will be favoured or disfavoured, but increasing sperm allocation reduces their mating rate. The resolution of this game depends on whether males are equal, or unequal. Males could be equal: each is favoured with probability, p, reflecting the proportion of females in the population that favour his ejaculate (the 'random-roles' model); different males are favoured by different sets of females. Alternatively, males could be unequal: given males are perceived consistently by all females as two distinct types, favoured and disfavoured, where p is now the frequency of the favoured male type in the population (the 'constant-types' model). In both cases, the evolutionarily stable strategy (ESS) is for females initially to increase sperm selection from zero as the viability of offspring from unfavourable ejaculates falls below that of favourable ejaculates. But in the random-roles model, sperm selection decreases again towards zero as the unfavourable ejaculates become disastrous (i.e. as their progeny viability decreases towards zero). This occurs because males avoid expenditure in unfavourable matings, to conserve sperm for matings in the favoured role where their offspring have high viability, thus allowing females to relax sperm selection. If sperm selection is costly to females, ESS sperm selection is high across a region of intermediate viabilities. If it is uncostly, there is no ESS in this region unless sperm limitation (i.e. some eggs fail to be fertilized because sperm numbers are too low) is included into the model. In the constant-types model, no relaxation of sperm selection occurs at very low viabilities of disfavoured male progeny. If sperm selection is sufficiently costly, ESS sperm selection increases as progeny viability decreases down towards zero; but if it is uncostly, there is no ESS at the lowest viabilities, and unlike the random-roles model, this cannot be stabilized by including sperm limitation. Sperm allocations in the ESS regions differ between the two models. With random roles, males always allocate more sperm in the favoured role. With constant types, the male type that is favoured allocates less sperm than the disfavoured type. These results suggests that empiricists studying cryptic female choice and sperm allocation patterns need to determine whether sperm selection is applied differently, or consistently, on given males by different females in the same population.

Animals↗