What Do Experimental Studies Tell Us about Group Selection in Nature?
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evolution↗
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Results for “balancing selection”
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Gene flow and the geographical distribution of a molecular polymorphism in Drosophila pseudoobscura.
This paper discusses the relation between the geographical distribution of an enzyme polymorphism and population structure in Drosophila pseudoobscura. California populations of this species living in very different montane and lowland habitats separated by several kilometers are similar to each other in the frequency of an esterase allele. Previous estimates suggest that gene flow is too limited to account for this homogeneity of genetic structure, so that it must reflect some balancing force of natural selection. We slow, however, that dispersal over unfavorable habitats is much greater than earlier supposed. Isolated populations of D. pseudoobscura separated by 15 km from other populations are subject to large amounts of immigration. This is shown by changes in the seasonal abundance of this species and in the annual pattern of lethal alleles in such populations. The genetic structure of an experimentally perturbed isolated population in an oasis returned to normal within a single year, suggesting that such populations are ephemeral and that the oasis is subject to annual recolonization by distant migrants. Direct assessment of marked flies shows that they can move at least 10 10 km in 24 hours over a desert. Such extensive gene flow may help explain the distribution of the esterase allele, and is relevant to the high level of molecular polymorphism and its general lack of geographic differentiation throughout the range of D. pseudoobscura.
Alleles↗
Tandem repeat polymorphism and heteroplasmy in the mitochondrial control region of redfishes (Sebastes: Scorpaenidae).
Three species of redfish (Sebastes) share a common pattern of mitochondrial DNA tandem repeat polymorphism and heteroplasmy in the northwest Atlantic Ocean. All three species exhibit 9-17 copies of an approximately 275 base pair (bp) tandem repeat situated within the 3' domain of the control region. Sequence analysis of cloned mtDNA from S. mentella revealed that the tandem array is adjacent to the tRNA(phe) gene, and that the repeat shares 53% identity with the tRNA(phe) gene and part of the 12S rRNA gene. These features, as well as potential secondary structure assumed by the repeat, are consistent with previously proposed models explaining tandem duplications in the 3' end of the control region. In a sample comprising 36 S. fasciatus, 52 S. mentella, and 13 S. marinus taken near Newfoundland, neither the mean number of repeats per fish (12.2-12.7) nor the frequency of heteroplasmy varied significantly among species. A total of 42% of the redfishes were heteroplasmic, bearing either two or three repeat variants (33% and 9%, respectively). The similarity of the frequency distributions of tandem repeat variants in the three species suggests either a common balance between mutation and selection in the three species, or mitochondrial gene flow between them.
Animals↗
Esmolol potentiates reduction of minimum alveolar isoflurane concentration by alfentanil.
UNLABELLED: Esmolol, a short-acting beta1-receptor antagonist, decreases anesthetic requirements during propofol/N2O/morphine anesthesia. This study was designed to determine whether esmolol affects the volatile anesthetic (isoflurane) required to prevent movement to skin incision in 50% patients (minimum alveolar anesthetic concentration [MAC]) with or without an additional opioid (alfentanil). One hundred consenting adult patients were randomly divided into five treatment groups: isoflurane alone (I), I with continuous large-dose (250 microg x kg(-1) x min(-1)) esmolol (E), I with alfentanil (effect site target of 50 ng/mL) via a continuous computer-controlled infusion (A), A plus continuous small-dose (50 microg x kg(-1) x min(-1)) esmolol (A1), or A plus large-dose esmolol (A2). Anesthesia was induced via a face mask, and steady-state target end-tidal isoflurane concentrations were maintained before incision. The MAC of isoflurane alone was 1.28% +/- 0.13%. Large-dose esmolol did not significantly alter the isoflurane MAC (1.23% +/- 0.14%). Alfentanil alone significantly decreased isoflurane MAC by 25% (0.96% +/-0.09%). Adding small-dose esmolol did not further decrease MAC with alfentanil (0.96% +/- 0.13%). However, large-dose esmolol significantly decreased isoflurane MAC with alfentanil (0.74% +/- 0.09%). Esmolol and alfentanil both significantly reduced the increases in heart rate and mean arterial pressure associated with endotracheal intubation and incision. The mechanism of this effect is unknown. IMPLICATIONS: Most anesthetic techniques rely on a balance of several highly selective medications. The current results define a new anesthetic-sparing effect when volatile anesthetic, analgesic, and beta-adrenergic blocking drugs are combined.
Adolescent↗
Why aren't there more women leaders in academic medicine? the views of clinical department chairs.
PURPOSE: A scarcity of women in leadership positions in academic medicine has persisted despite their increasing numbers in medical training. To understand the barriers confronting women and potential remedies, clinical department chairs with extensive leadership experience were interviewed. METHOD: In 1998-99, open-ended interviews averaging 80 minutes in length were conducted with 34 chairs and two division chiefs in five specialties. Individuals were selected to achieve a balance for gender, geographic locale, longevity in their positions, and sponsorship and research intensity of their institutions. The interviews were audiotaped and fully transcribed, and the themes reported emerged from inductive analysis of the responses using standard qualitative techniques. RESULTS: The chairs' responses centered on the constraints of traditional gender roles, manifestations of sexism in the medical environment, and lack of effective mentors. Their strategies for addressing these barriers ranged from individual or one-on-one interventions (e.g., counseling, confronting instances of bias, and arranging for appropriate mentors) to institutional changes (e.g., extending tenure probationary periods, instituting mechanisms for responding to unprofessional behavior, establishing mentoring networks across the university). CONCLUSION: The chairs universally acknowledged the existence of barriers to the advancement of women and proposed a spectrum of approaches to address them. Individual interventions, while adapting faculty to requirements, also tend to preserve existing institutional arrangements, including those that may have adverse effects on all faculty. Departmental or school-level changes address these shortcomings and have a greater likelihood of achieving enduring impact.
Attitude of Health Personnel↗
Positive inotropy contributes to the hemodynamic mechanism of action of flosequinan (BTS 49465) in the intact dog.
Flosequinan (BTS 49465) is a putative, selective direct-acting balanced vasodilator currently undergoing evaluation for the treatment of congestive heart failure (CHF) and hypertension. We examined the pharmacologic action of flosequinan and compared it to milrinone and nitroprusside (SNP). In ferret papillary muscle, in vitro, flosequinan (1-100 microM) increased the rate of force development up to 116%. The effect was not blocked by nadolol (10 microM). Flosequinan was less effective than milrinone and SNP as a relaxant of canine renal and coronary arteries, in vitro, since 100 microM of flosequinan produced less than 50% relaxation of the arteries, whereas milrinone or SNP (100 microM) produced between 85 and 125% relaxation of the precontracted arteries. Flosequinan, SNP, and milrinone (100 microM) completely relaxed precontracted canine mesenteric veins. Fifteen minutes after intraduodenal administration (i.d.) of flosequinan (0.3, 1.0, and 3.0 mg/kg) to anesthetized dogs (n = 7), mean left ventricular (LV) dP/dT increased by 11, 27, and 54%, respectively, whereas total peripheral resistance (TPR) decreased by 4, 4, and 13%, and mean arterial pressure (MAP) decreased by 7, 14, and 23%, respectively. flosequinan was 4.6 times more potent as a positive inotrope than as a vasodilator. The hemodynamic profile of milrinone was similar to that of flosequinan, except milrinone produced greater increases in LV dP/dT and decreases in MAP and TPR. In contrast, SNP (1, 3, and 10 micrograms/kg/min i.v.) decreased TPR (7, 18, and 34%, respectively) and MAP (14, 32, and 41%, respectively) without any increase in LV dP/dT. In dogs with propranolol-induced heart failure (PIHF), flosequinan (1.0 and 3.0 mg/kg, i.d.) increased mean myocardial dP/dT by 54 and 84% (n = 5) and MAP, but decreased TPR. The data show that (a) the hemodynamic effects of flosequinan in the normal and PIHF dogs were primarily due to positive inotropy rather than to arterial vasodilation and (b) the positive inotropic effect of flosequinan is independent of catecholamines, since it occurred in dogs with PIHF. The beneficial effect of flosequinan in patients with CHF may not be mediated by balanced vasodilation.
Animals↗
The angiotensin II receptor blocker candesartan improves survival and mesenteric perfusion in an acute porcine endotoxin model.
BACKGROUND: Blockade of the angiotensin II type 1 (AT1) receptor has been demonstrated to ameliorate splanchnic hypoperfusion in acute experimental circulatory failure. This study focused on hemodynamic changes and survival in pigs treated with AT1 blockade prior to or during acute endotoxinemia. METHODS: Escherichia coli lipopolysaccharide endotoxin was infused in anesthetized and mechanically ventilated pigs. Systemic, renal, mesenteric and jejunal mucosal perfusion as well as systemic oxygen and acid-base balance were monitored. The selective AT1 receptor blocker candesartan was administered prior to as well as during endotoxinemia. Control animals received the saline vehicle. RESULTS: Pre-treatment with candesartan resulted in higher survival rate (83%, 10 out of 12 animals) compared with 50% (6 of 12) in control animals and 27% (3 of 11) in animals treated during endotoxinemia. Pre-treatment with candesartan resulted in higher cardiac output, mixed venous oxygen saturation, arterial standard base-excess, portal venous blood flow during endotoxin infusion compared with controls and animals treated during endotoxinemia. No adverse effects were found on neither systemic nor renal circulation. CONCLUSION: The favorable results of AT1 receptor blockade prior to endotoxinemia are lost when blockade is established during endotoxinemia demonstrating the importance of the renin-angiotensin system and its dynamic involvement in acute endotoxinemic shock.
Acute Disease↗
Phenotypic divergence despite high levels of gene flow in Galápagos lava lizards (Microlophus albemarlensis).
The extent of evolutionary divergence of phenotypes between habitats is predominantly the result of the balance of differential natural selection and gene flow. Lava lizards (Microlophus albemarlensis) on the small island of Plaza Sur in the Galápagos archipelago inhabit contrasting habitats: dense vegetation on the western end of the island thins rapidly in a transitional area, before becoming absent on the eastern half. Associated with these habitats are phenotypic differences in traits linked to predator avoidance (increased wariness, sprint speed, and endurance in lizards from the sparsely vegetated habitat). This population provides an opportunity to test the hypothesis that reduced gene flow is necessary for phenotypic differentiation. There was no evidence of any differences among habitats in allele frequencies at six out of seven microsatellite loci examined, nor was there any indication of congruence between patterns of genetic variability and the change in vegetation regime. We infer that gene flow between the habitats on Plaza Sur must be sufficiently high to overcome genetic drift within habitats but that it does not preclude phenotypic differentiation.
Analysis of Variance↗
Effect of increased myocardial cyclic GMP induced by cyclic GMP-phosphodiesterase inhibition on oxygen consumption and supply of rabbit hearts.
1. We tested the hypothesis that increasing myocardial cyclic GMP levels would reduce myocardial O2 consumption and areas of low O2 supply/consumption balance, using zaprinast, a selective cyclic GMP-phosphodiesterase inhibitor. 2. The study was conducted in three groups (vehicle, 10(-3) and 3 x 10(-3) mol/L zaprinast) of anaesthetized open-chest New Zealand white rabbits (n = 24). Coronary blood flow (radioactive microspheres), arterial and venous O2 saturation (microspectrophotometry), O2 consumption, cyclic GMP content (competitive binding) and cyclic GMP-phosphodiesterase activity (conversion of 3H-cyclic GMP to 3H-GMP) were determined. 3. Agents were applied to a patch on the myocardial surface and did not cause significant haemodynamic changes, except for bradycardia in the vehicle and low dose group. 4. The total myocardial cyclic GMP-phosphodiesterase activity was 148 +/- 14 while the zaprinast (10 mumol/L) inhibitable activity averaged 63 +/- 8 pmol/mg protein per min. Cyclic GMP content was increased with increasing doses of zaprinast (vehicle, 4.308 +/- 0.349 pmol/g; low dose zaprinast, 4.803 +/- 0.279 and high dose zaprinast, 7.938 +/- 1.304 pmol/g). 5. Coronary blood flow was not different after treatment (198 +/- 11, 209 +/- 10 and 153 +/- 9 mL/min per 100 g for the vehicle, low and high dose zaprinast, respectively). 6. Under control conditions, 48% of the small veins had O2 saturations below 50%. With zaprinast, this value was reduced to 19% for the low and 24% for the high dose. 7. Average venous O2 saturation increased with zaprinast (49 +/- 2%, 61 +/- 3% and 59 +/- 1%).(ABSTRACT TRUNCATED AT 250 WORDS)
3',5'-Cyclic-GMP Phosphodiesterases↗
The influence of surface properties on uptake of oil into complex coacervate microcapsules.
A range of surfactants with different hydrophile-lipophile balance (HLB) values was selected to investigate the influence of interfacial properties on the uptake of oil droplets into complex coacervate microcapsules. The well characterized gelatin/acacia complex coacervate system was used in this study and the encapsulation of squalane, and oleic acid was investigated. The surfactants investigated were Span 85, Span 80, Span 40, egg yolk lecithin, and Tween 80. Combinations of surfactants were utilized to obtain intermediate HLB values. The percentage oil encapsulated was determined gravimetrically, based on the initial concentration and the amount extracted from the microcapsules. The aqueous interfacial tension values of the oils and oil/surfactant systems were measured using the Wilhelmy plate method. The interfacial properties were correlated to the percentage oil uptake by the coacervate phase. The relative hydrophobicity/lipophilicity of the oil influenced its uptake by complex coacervate droplets. The presence of surfactant affected oil uptake, depending on the HLB value of the surfactant or surfactant mixture. Uptake of squalane by the gelatin/acacia coacervates was found to be optimized by the addition of surfactants with HLB values in the range 2.5-6. The percentage uptake of oil decreased rapidly for systems prepared containing surfactants with HLB values outside this range. No correlation was observed between oil uptake by the coacervate phase and the interfacial tension of the oil and oil/surfactant systems with double-distilled deionized water.
Capsules↗
Evidence of lactate dehydrogenase-B allozyme effects in the teleost, Fundulus heteroclitus.
The evolutionary significance of protein polymorphisms has long been debated. Exponents of the balanced theory advocate that selection operates to maintain polymorphisms, whereas the neoclassical school argues that most genetic variation is neutral. Some studies have suggested that protein polymorphisms are not neutral, but their significance has been questioned because one cannot eliminate the possibility that linked loci were responsible for the observed differences. Evidence is presented that an enzymatic phenotype can affect carbon flow through a metabolic pathway. Glucose flux differences between lactate dehydrogenase-B phenotypes of Fundulus heteroclitus were reversed by substituting the Ldh-B gene product of one homozygous genotype with that of another.
Animals↗
Anaerobic biodegradation of eleven aromatic compounds to methane.
A range of 11 simple aromatic lignin derivatives are biodegradable to methane and carbon dioxide under strict anaerobic conditions. A serum-bottle modification of the Hungate technique for growing anaerobes was used for methanogenic enrichments on vanillin, vanillic acid, ferulic acid, cinnamic acid, benzoic acid, catechol, protocatechuic acid, phenol, p-hydroxybenzoic acid, syringic acid, and syringaldehyde. Microbial populations acclimated to a particular aromatic substrate can be simultaneously acclimated to other selected aromatic substrates. Carbon balance measurements made on vanillic and ferulic acids indicate that the aromatic ring was cleaved and that the amount of methane produced from these substrates closely agrees with calculated stoichiometric values. These data suggest that more than half of the organic carbon of these aromatic compounds potentially can be converted to methane gas and that this type of methanogenic conversion of simple aromatics may not be uncommon.
Journal Article↗
Recent advances in the MOBJ algorithm for training artificial neural networks.
This paper presents a new scheme for training MLPs which employs a relaxation method for multi-objective optimization. The algorithm works by obtaining a reduced set of solutions, from which the one with the best generalization is selected. This approach allows balancing between the training error and norm of network weight vectors, which are the two objective functions of the multi-objective optimization problem. The method is applied to classification and regression problems and compared with Weight Decay (WD), Support Vector Machines (SVMs) and standard Backpropagation (BP). It is shown that the systematic procedure for training proposed results on good generalization neural models, and outperforms traditional methods.
Algorithms↗
Renal assimilation of oligopeptides: physiological mechanisms and metabolic importance.
Assimilation of systemic oligopeptides (di- and tripeptides) is largely a function of kidneys. The most specific and unique mechanism utilized for the performance of this renal function is transport, followed by intracellular hydrolysis and then release of constituent amino acids to the systemic circulation. Among tissues examined (liver, kidney, intestine, and muscle), kidney is the only tissue capable of accumulating dipeptides in concentrations that are greater than their plasma concentrations. Kidney also is the tissue with the highest cytoplasmic dipeptidase activity. Intracellular accumulation is mediated by two transporters (Pept-1 and Pept-2), both of which have been recently cloned. These transporters use dipeptides and tripeptides as substrates and rely on protons and membrane potential for their driving force. Pept-1 is a low-affinity, high-capacity transporter, and Pept-2 is a high-affinity, low-capacity transporter. The nutritional and metabolic regulation of renal assimilation of oligopeptides is suggested by the selective decrease in dipeptide balance across the kidneys of starved human subjects and by the insulin stimulation of dipeptide transport by a renal cell line. Peptiduria has been observed in a variety of diseases, but the mechanism, except in genetic diseases affecting hydrolysis of oligopeptides, is not known. Finally, the capacity for active transport of oligopeptides and peptidomimetic drugs enables kidneys to play major roles in nutritional and pharmacological therapies.
Animals↗
Estimating entropy rates with Bayesian confidence intervals.
The entropy rate quantifies the amount of uncertainty or disorder produced by any dynamical system. In a spiking neuron, this uncertainty translates into the amount of information potentially encoded and thus the subject of intense theoretical and experimental investigation. Estimating this quantity in observed, experimental data is difficult and requires a judicious selection of probabilistic models, balancing between two opposing biases. We use a model weighting principle originally developed for lossless data compression, following the minimum description length principle. This weighting yields a direct estimator of the entropy rate, which, compared to existing methods, exhibits significantly less bias and converges faster in simulation. With Monte Carlo techinques, we estimate a Bayesian confidence interval for the entropy rate. In related work, we apply these ideas to estimate the information rates between sensory stimuli and neural responses in experimental data (Shlens, Kennel, Abarbanel, & Chichilnisky, in preparation).
Bayes Theorem↗
Glycoprotein 130 regulates bone turnover and bone size by distinct downstream signaling pathways.
The gp130-dependent cytokines, which signal through at least two intracellular pathways, regulate osteoclast and osteoblast formation. To define their roles in regulating bone mass, we analyzed mice in which gp130 signaling via either the signal transducer and activator of transcription (STAT) 1/3 (gp130(DeltaSTAT/DeltaSTAT)) or SHP2/ras/MAPK (gp130(Y757F/Y757F)) pathway was attenuated. In gp130(DeltaSTAT/DeltaSTAT) mice, trabecular bone volume (BV/TV) and turnover were normal, but bone length was reduced by premature growth plate closure, indicating an essential role for gp130-STAT1/3 signaling in chondrocyte differentiation. In contrast, while bone size was normal in gp130(Y757F/Y757F) mice, BV/TV was reduced due to high bone turnover, indicated by high osteoclast surface/bone surface (OcS/BS) and osteoblast surface/bone surface (ObS/BS). Furthermore, generation of functional osteoclasts from bone marrow of gp130(Y757F/Y757F) mice was elevated, revealing that while gp130 family cytokines stimulate osteoclastogenesis through the osteoblast lineage, gp130, via SHP2/Ras/MAPK, inhibits osteoclastogenesis in a cell lineage-autonomous manner. Genetic ablation of IL-6 in gp130(Y757F/Y757F) mice exacerbated this osteopenia by reducing ObS/BS without affecting OcS/BS. Thus, while IL-6 is critical for high bone formation in gp130(Y757F/Y757F) mice, it is not involved in the increased osteoclastogenesis. In conclusion, gp130 is essential for normal bone growth and trabecular bone mass, with balanced regulation depending on selective activation of STAT1/3 and SHP2/ras/MAPK, respectively. Furthermore, the latter pathway can directly inhibit osteoclastogenesis in vivo.
Animals↗
The Physical Performance Test as a predictor of frequent fallers: a prospective community-based cohort study.
OBJECTIVE: To construct a risk model in order to identify elderly individuals at risk of frequent falling. DESIGN: Prospective community-based cohort study over 12 months. SETTING: Baseline measures were performed at a local community centre. SUBJECTS: Two hundred and sixty-three community-dwelling elderly people (mean age 72 years). MEASUREMENTS: A variety of variables were evaluated, including medical, psychological, sensory, physical and postural control measurements. Fall incidence was monitored retrospectively and during one-year follow-up. RESULTS: Logistic regression analysis showed that polypharmacia was the most prominent medical fall predictor with an odds ratio (OR) of 1.29 (P= 0.005), poor visual acuity the best sensory predictor (OR = 0.84; P= 0.009) and general fear of falling the most crucial psychological predictor (OR = 3.25; P< 0.001). Increased postural sway in near-tandem stance with eyes open was selected as the best balance predictor for falls (OR = 5.60; P= 0.010), followed by delayed anteroposterior movement velocity during rhythmic weight shifts (OR = 0.42; P= 0.004). The best physical predictor was a low score on the Physical Performance Test (OR =4.16; P< 0.001), followed by decreased maximal handgrip strength (OR = 0.87; P< 0.001) and increased timed chair-stands (OR = 1.13; P= 0.003). Step-by-step regression analysis revealed a risk model for the prediction of future falls, as a combination of the Physical Performance Test and maximal handgrip strength. CONCLUSION: This study confirms the multicausality of falls, since medical, psychological, sensory, postural control as well as physical variables provides a predictive value. The composed fall risk model was mainly physically oriented.
Accidental Falls↗
Recombinant human thyroid peroxidase generated in eukaryotic cells: a source of specific antigen for the immunological assay of antimicrosomal antibodies in the sera of patients with autoimmune thyroid disease.
Recombinant, enzymatically active human thyroid peroxidase (hTPO) generated in nonthyroidal eukaryotic cells was compared with Graves' thyroid microsomes as a source of antigen for the immunological detection of antimicrosomal/anti-hTPO antibodies. Enzyme-linked immunosorbent assay of 51 sera, selected to produce a balanced distribution of antimicrosomal antibody (anti-MSA) levels, revealed (at 1:100 serum dilution) a moderately good correlation between anti-MSA and anti-hTPO antibody levels (r = 0.668; P less than 0.001). However, a number of sera with high anti-MSA levels yielded markedly discordant values between the two assays. A much lower correlation was observed between antithyroglobulin and anti-hTPO antibody levels (r = 0.315; P less than 0.05). At higher serum dilutions (1:1,000 and 1:10,000), at which low affinity, high capacity binding reactions will be reduced, the correlation between anti-MSA and anti-hTPO antibody values was greatly improved (r = 0.906 and 0.902, respectively; P less than 0.001), and there were no longer widely discrepant values between the two assays. In summary, the present study indicates that recombinant hTPO expressed in nonthyroidal cells provides an unlimited source of human TPO of unvarying quality for anti-hTPO antibody assays. This material offers increased specificity over standard anti-MSA assays that use thyroid cell microsomes as antigen.
Antigen-Antibody Reactions↗