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Results for “balancing selection”

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PubMed1996

The role of microfixation in malar fractures: a quantitative biophysical study.

Microfixation and wire fixation techniques were used in combination with miniplates in the stabilization of simulated simple zygoma fractures in four fresh human cadaver heads. An orthogonal conveyer and rigid steel test frame were used to test rotational stability after deforming forces were applied. After testing multiple combinations at an initial deforming force of 5 kg, selected combinations were tested over a range of 2 to 22 kg. Evaluation of force-displacement data revealed that three-point fixation with miniplates was superior to all other methods, in agreement with previous studies. The combination of lateral buttress miniplate fixation in conjunction with microfixation at the zygomaticofrontal and infraorbital rim regions exhibited stable characteristics over the range of forces applied. Miniplate-microplate combinations exhibited greater stability than corresponding miniplate-wire combinations. The combination of miniplate-microplate fixation clinically allows a balance between stability and aesthetics in selected zygoma fractures.

Biomechanical Phenomena↗

PubMed2004

Natural selection drives altitudinal divergence at the albumin locus in deer mice, Peromyscus maniculatus.

In populations that are distributed across steep environmental gradients, the potential for local adaptation is largely determined by the spatial scale of fitness variation relative to dispersal distance. Since altitudinal gradients are generally characterized by dramatic ecological transitions over relatively short linear distances, adaptive divergence across such gradients will typically require especially strong selection to counterbalance the homogenizing effect of gene flow. Here we report the results of a study that was designed to test for evidence of adaptive divergence across an altitudinal gradient in a natural population of deer mice, Peromyscus maniculatus. We conducted a multilocus survey of allozyme variation across a steep altitudinal gradient in the southern Rocky Mountains that spanned several distinct biomes, from prairie grassland to alpine tundra. As a control for the effects of altitude, we also surveyed the same loci in mice sampled along a latitudinal transect through the prairie grassland that ran perpendicular to the east-west altitudinal transect. We used a coalescent-based simulation model to identify loci that deviated from neutral expectations, and we then assessed whether locus-specific patterns of variation were nonrandom with respect to altitude. Results indicated that the albumin locus (Alb) reflects a history of diversifying selection across the altitudinal gradient. This conclusion is supported by two main lines of evidence: (1) Alb was characterized by levels of divergence across the altitudinal transect that exceeded neutral expectations in two consecutive years of sampling (in contrast to the spatial pattern of variation across the latitudinal transect), and (2) levels of divergence at the Alb locus exhibited a positive association with altitudinal distance in both years (in contrast to the pattern observed at unlinked loci). We conclude that clinal variation at the Alb locus reflects a balance between gene flow and diversifying selection that results from elevational changes in fitness rankings among alternative genotypes.

Adaptation, Physiological↗

PubMed2005

Yin-yang: balancing act of prostaglandins with opposing functions to regulate inflammation.

For many years, cyclooxygenase-2 (COX-2), a critical enzyme for PG production, has been the favorite target for anti-inflammatory drug development. However, recent revelations regarding the adverse effects of selective COX-2 inhibitors have stimulated intense debate. Interestingly, in the early phase of inflammation, COX-2 facilitates inflammatory PG production while in the late phase it has anti-inflammatory effects. Moreover, although some PGs are proinflammatory, others have anti-inflammatory effects. Thus, it is likely that PGs with opposing effects maintain homeostasis, although the molecular mechanism(s) remains unclear. We report here that an inflammatory PG, PGD2, via its receptor, mediates the activation of NF-kappaB stimulating COX-2 gene expression. Most interestingly, an anti-inflammatory PG (PGA1) suppresses NF-kappaB activation and inhibits COX-2 gene expression. We propose that while pro- and anti-inflammatory PGs counteract each other to maintain homeostasis, selective COX-2 inhibitors may disrupt this balance, thereby resulting in reported adverse effects.

Animals↗

PubMed1989

Genetic variation and microevolution of dengue 2 virus in Southeast Asia.

Dengue 2 (DEN 2) virus strains collected from dengue hemorrhagic fever (DHF) patients and Aedes aegypti mosquitoes in Thailand, Burma, and Vietnam over a 25-year period have been analyzed by computer assisted T1-RNase-resistant oligonucleotide fingerprinting. Fifty-seven DEN 2 virus strains of the Thailand topotype were separated into four major clusters by phylogenetic analysis of 97 unique oligonucleotides identified in a common well-resolved region of the fingerprints. Similarities in the 57 fingerprints indicated that DEN 2 virus of a single, continually evolving genetic population has been involved in endemic transmission of the disease. Virus isolates from DHF cases and mosquitoes are genetically very similar, indicating that different genetic topotypes are not selectively the cause of severe DEN disease in Thailand. Microevolution of the DEN 2 virus genome from 1962-1986 was gradual with detectable changes in the pattern of oligonucleotides through time. Segregation of the DEN 2 virus fingerprints into the three decades (1960s, 1970s, and 1980s) revealed the rate of genetic change to be one consensus oligonucleotide per year. Based on average association coefficient (Sab) values between the consensus fingerprints for each decade, the similarity between the consensus fingerprints decreased by 1.4% per year. Genetic variation during each of the three decades was found to be essentially the same (0.866 +/- 0.053). Constancy in the microevolutionary rate and genetic variability suggests that a balance of genetic drift and natural selection acting on the viral population did not significantly change throughout the 25-year period.

Aedes↗

PubMed1989

Investigation of the effects of paralysis by pancuronium on heart rate variability, blood pressure and fluid balance.

The effects of pancuronium bromide on the cardiovascular system and fluid balance in preterm ventilated neonates was investigated. Infants were selectively paralysed if actively expiring. Their results were compared to a control group of similar gestational age, ventilated during the same study period, but who received no paralysing agent. There was no significant difference in the blood pressure of the two groups. Treatment with pancuronium was not associated with differences in blood pressure variability. All paralysed infants showed a significant reduction in heart rate variability which persisted during treatment. This was not present in the control infants. Paralysed infants, despite fluid restriction, had evidence of fluid retention, being significantly heavier than the control babies from day 3 onwards and above their birthweight by day 7. No paralysed or control infant developed a pneumothorax or renal failure. We conclude that selective treatment with pancuronium is without adverse effects on blood pressure but strict attention to fluid balance is essential.

Blood Pressure↗

PubMed2005

Aza-bicyclic amino acid carboxamides as alpha4beta1/alpha4beta7 integrin receptor antagonists.

A series of N-carboxy, N-alkyl, and N-carboxamido azabicyclo[2.2.2]octane carboxamides were prepared and assayed for inhibition of alpha4beta1-VCAM-1 and alpha4beta7-MAdCAM-1 interactions. Potency and alpha4beta1/alpha4beta7 selectivity were sensitive to the substituent R1-R3 in the structures 6, 7, and 8. Several compounds demonstrated low nanomolar balanced alpha4beta1/alpha4beta7 in vitro activity. Two compounds were selected for in vivo leukocytosis studies and demonstrated increases in circulating lymphocytes up to 250% over control.

Amino Acids, Cyclic↗

PubMed2003

Serum urea concentration as a predictor of dietary lysine requirement in selected lines of pigs.

Serum urea concentrations were measured in Large White pigs from lines divergently selected for components of efficient lean growth rate and performance tested over three 14-d test periods starting at 30, 50, and 75 kg. Two methods of performance testing were used. Phase-fed pigs were fed to appetite isoenergetic diets differing in total lysine:energy ratio (0.58, 0.69, 0.81, 0.91, 1.01, 1.12, and 1.23 g/MJ of digestible energy), whereas diet-choice pigs were offered a choice of the 0.69 and 1.12 lysine:energy diets. Between test periods, all animals were fed one diet: 0.91 g of lysine/MJ of digestible energy. The study consisted of 230 boars and gilts with 150 pigs performance tested on phase-feeding and 80 pigs on diet-choice. The line selected for high lean food conversion had lower urea concentrations on each diet than the line selected for high lean growth rate, despite similar predicted lysine balances. Efficiency of lean growth rather than the rate of lean growth may be a better selection strategy in the context of nitrogen excretion. Urea concentrations at the end of each test period were correlated with lysine intake (0.33, 0.48 and 0.65; standard error, 0.08) and predicted lysine balance (0.39,0.44, and 0.64), but were uncorrelated with predicted lysine for protein deposition (0.01, 0.08, and 0.08) and maintenance. Urea concentration at the end of a test period was not a useful predictor of protein deposition, even after accounting for pretest variation in urea concentration and food intake during test. The expected response pattern of serum urea concentration to diets differing in total lysine:energy would be nonlinear, with the point of inflection occurring at the required dietary total lysine:energy for each genotype. However, there was no evidence of such an inflection point such that the prediction of lysine requirement from urea concentration was not possible for the selection lines in the study.

Animal Feed↗

PubMed1983

Density dependent selection incorporating intraspecific competition 1. A haploid model.

A haploid model is introduced and analyzed in which intraspecific competition is incorporated within a density dependent framework. It is assumed that each genotype has a unique carrying capacity corresponding to the equilibrium population size when fixed for that type. Each genotypic fitness at a single multi-allelic locus is a function of a distinctive effective population size formed by adding the numbers of each genotype present, weighted by an intraspecific competition coefficient. As a result, the fitnesses depend upon the relative frequencies of the various genotypes as well as the total population size. Intergenotypic interactions can have a profound effect upon the outcome of the population. In particular, when the density effect of one individual upon another depends upon their respective genotypes, a unique stable interior equilibrium is possible in which all alleles are present. This stands in contrast to the purely density dependent haploid system in which the only possible stable state corresponds to fixation for the type with the highest carrying capacity. In the present model selective advantage is determined by a balance between carrying capacity and sensitivity to density pressures from other genotypes. Fixation for the genotype with the highest carrying capacity, for instance, will not be stable if it exerts a sufficiently weak competitive effect upon the other genotypes. In the diallelic case, maintenance of both alleles at a stable equilibrium requires that the net intragenotypic competition between individuals of like genotype be stronger than that between unlike types. As for purely density regulated systems, there may be no stable equilibria and/or regular and chaotic cycling may occur. The results may also be interpreted in terms of a discrete time model of interspecific competition with each haplotype representing a different species.

Animals↗

PubMedDate not supplied

A performance test protocol and scoring scale for the evaluation of ankle injuries.

The aim of the study was to introduce and evaluate a standardized test protocol and scoring scale for evaluation of ankle injuries. After evaluation of 11 different functional ankle tests, questionnaire answers, and results of clinical ankle examination, the final test protocol consisted of 3 simple questions describing the subjective assessment of the injured ankle, 2 clinical measurements (range of motion in dorsiflexion, laxity of the ankle joint), 1 ankle test measuring functional stability (walking down a staircase), 2 tests measuring muscle strength (rising on heels and toes), and 1 test measuring balance (balancing on a square beam). Each selected test showed excellent reproducibility when tested with a reference group of 100 uninjured persons. According to the test results of a population of 148 patients with an operatively treated grade III lateral ligament injury of the ankle, each test could significantly differentiate healthy controls and patients with excellent overall healing from those with poor or fair recovery. The final total test score correlated significantly with the isokinetic strength results of the ankle, subjective opinion about the recovery, and subjective-functional assessment. The scale presented is recommended for studies evaluating functional recovery after ankle injury.

Adult↗

PubMed2004

A balanced expression of two chains of heterodimer protein, the human interleukin-12, improves high-level expression of the protein in CHO cells.

Interleukin-12 (IL-12) comprises of p40 and p35 subunits that are encoded by genes on separate chromosomes and form p70 heterodimer, a bioactive protein, and free p40, an antagonist of IL-12. Balance expression of two subunits within cells would be the key for high-level of production of bioactive IL-12. Thinking about different expression efficiencies of two genes (p40 gene with higher efficiency), we selected two expression vectors with different efficiencies and inserted genes of p40 and p35 into them separately and co-transfected them into Chinese hamster ovary (CHO) cells. The high-level expression of IL-12 was obtained when p40 cDNA was inserted into pcDNA3 (lower expression vector) and p35 cDNA was inserted into pEE14 (higher expression vector), but using pEE14 for p40 cDNA and pcDNA3 for p35 cDNA, which was opposite to the optimal design, or pEE14 or pcDNA3 for both p35 cDNA and p40 cDNA did not obtain high-level of production of p70 heterodimer, the bioactive IL-12. We also observed that using two chemical reagents in combination, as a pressure selection method or amplification for the two vectors, markedly enhanced the IL-12 production, when compared with any one selection chemical. Our results indicated that the balance expressions of two chains of hetrodimer protein, such as p40 and p35 of IL-12, would be a better choice to obtain high-level of production of the proteins.

Animals↗

PubMed2003

Nutrient balancing in grasshoppers: behavioural and physiological correlates of dietary breadth.

We examined correlates of nutrient balancing with dietary range by comparing diet selection and ingestive, post-ingestive and performance-related responses to macronutrient imbalance in two species of grasshopper. One of the two species, Locusta migratoria (the African migratory locust), is a specialist grass-feeder, while the other, Schistocerca gregaria (the desert locust), is a generalist herbivore that includes both grasses and forbs in its diet. In ad libitum conditions, both species composed a balanced intake of the two macronutrients protein and carbohydrate from nutritionally complementary synthetic foods, but the composition of the selected diet differed, with the generalist selecting more protein, but not carbohydrate, than the grass-specialist. The grass-specialist, by contrast, retained ingested nitrogen more efficiently on the ad libitum diets. When confined to nutritionally imbalanced foods, both species regulated ingestion in such a way as to mitigate excesses as well as deficits of the two nutrients. The responses were, however, distinct in the two species, with the generalist feeder ingesting greater excesses of protein than the specialist. The species also differed in their post-ingestive responses to ingested excesses of nutrient, with the generalist but not the specialist using protein-derived carbon as an energy source when fed carbohydrate-deficient foods. The generalist also retained a higher level of body protein when confined to protein-deficient diets. The data suggested one functional reason why the generalist species selected a diet with higher protein content in the ad libitum treatment because, when confined to the nutritionally imbalanced foods, development rate peaked on higher protein foods for the generalist compared with the specialist. Many aspects of these data agree with the prediction that generalist-feeding animals should show greater behavioural and physiological flexibility in their responses to nutrient imbalance than do specialists.

Animal Nutritional Physiological Phenomena↗

PubMedDate not supplied

PLUMS: a program for the rapid optimization of focused libraries.

PLUMS is a new method to perform rational monomer selection for combinatorial chemistry libraries. The algorithm has been developed to optimize focused libraries with specific two-dimensional and/or three-dimensional properties. A preliminary step is the identification of those molecules in the initial virtual library which satisfy the imposed property constraints; we define these molecules as the virtual hits. From the virtual hits, PLUMS generates a starting library, which is the true combinatorial library that includes all the virtual hits. Monomers are then removed in an iterative fashion, thus reducing the size of the library. At each iteration, the worst monomer is removed. Each sublibrary is selected using a global scoring function, which balances effectiveness and efficiency. The iterative process continues until one is left with a library that consists entirely of virtual hits. The optimal library, which is the best compromise between effectiveness and efficiency, can then be selected according to the score. During the iterative process, equivalent solutions may well occur and are taken into account by the algorithm, according to a user-defined parameter. The number of monomers for each substitution site and the size of the library are parameters that can be either optimized or used to constrain the selection. The results obtained on two test libraries are presented. PLUMS was compared with genetic algorithms (GA) and monomer frequency analysis (MFA), which are widely used for monomer selection. For the two test libraries, PLUMS and GA gave equivalent results. MFA is the fastest method, but it can give misleading solutions. Possible advantages and disadvantages of the different methods are discussed.

Journal Article↗

PubMedDate not supplied

Effects of balance training in elderly evaluated by clinical tests and dynamic posturography.

All persons aged 70 through 75 years (N = 457) in a Swedish community were invited to participate in a 9 week balance training study. Out of 55 interested subjects, 15 were chosen at random for a study group; 15 matched controls were also selected. Before and after the investigation period the balance function was assessed by clinical balance tests and dynamic posturography. In the clinical balance tests, the training group significantly improved their balance standing on one leg with eyes closed as well as standing on one leg while shaking the head; they also walked 15 m back and forth faster. In the dynamic posturography the training group significantly improved their equilibrium scores in the 3 most difficult test conditions. The results of the control group were unchanged except for one test condition in the dynamic posturography. The differences in one-leg standing with head shaking, walking 2 x 15 m, and the equilibrium score using sway-referenced platform in dynamic posturography were proved to be attributable to the training. The first investigation in all 29 subjects formed normative dynamic posturography data for the age group 70 through 75 years. The normative posturographic data of this age group differed from previously obtained data in the age groups 20 through 59 and 60 through 69 years. It is concluded that elderly may improve their balance by regular balance training exercises for as short a period as 9 weeks. This might prove to be of great value in improving balance and thereby preventing accidental falls and subsequent fractures in elderly.

Aged↗

PubMed2006

Selective digestive tract decontamination--will it prevent infection with multidrug-resistant gram-negative pathogens but still be applicable in institutions where methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci are endemic?

The purposes of selective decontamination of the digestive tract are to treat infections that may be incubating at the time a patient is admitted to an intensive care unit (ICU), by intravenous administration of antibiotics during the first days of a stay in the ICU, and to prevent ICU-acquired infections, by topical application of antibiotics in the oropharynx and the gastrointestinal tract. Despite multiple trials in which a considerable reduction in the incidence of ventilator-associated pneumonia was demonstrated, major objections against the routine use of selective decontamination of the digestive tract have included a lack of demonstrated reductions in mortality rates and in length of stay (in individual trials), a lack of cost-efficacy data, and the threat of selection of multidrug-resistant bacteria. Recently, 2 controlled, randomized studies reported significant reductions in mortality rates among patients in ICUs who underwent selective decontamination of the digestive tract in combination with reduced selection of antibiotic-resistant pathogens. However, those studies were performed in settings where levels of antibiotic resistance are low, and some methodological issues remain unresolved. If these beneficial results are confirmed, the question of how to balance these benefits against the expected enhanced selection of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and, possibly, multidrug-resistant gram-negative bacteria will emerge.

Anti-Bacterial Agents↗

PubMed2003

Mutually antagonistic signals regulate selection of the T cell repertoire.

The sensitivity of T cells to agonist-induced death during development contrasts with their proliferative responses after agonist challenge in the periphery. The means by which TCR engagement results in these distinct outcomes is incompletely understood. It has been previously hypothesized that glucocorticoids (GC) modulate the threshold for thymocyte activation by blunting the consequences of TCR engagement. In support of this possibility, inhibition of GC production in fetal thymic organ culture was shown to result in CD4(+)CD8(+) thymocyte apoptosis. This was dependent upon MHC diversity, implying that endogenous GC might regulate antigen-specific selection. Similarly, mice expressing reduced GC receptor (GR) levels due to the presence of an antisense transgene have fewer CD4(+)CD8(+) thymocytes, which was due to an impaired transition from CD4(-)CD8(-) precursors and increased apoptosis. Here we ask how manipulating peptide diversity in the context of reduced GC signaling might affect T cell development and function. In mice with impaired GR expression there was a rescue of thymocyte cellularity and proportions as the diversity of peptides presented by self-MHC was reduced. Furthermore, whereas more CD4(+) T cells survived the selection process in mice expressing single-peptide-MHC class II complexes and reduced GR levels, these cells largely failed to recognize the same MHC molecules bound with foreign peptides. Together, these results support a role for endogenous GC in balancing TCR-mediated signals during thymic selection.

Animals↗

PubMed1997

Effect of interleukin-10 on dendritic cell maturation and function.

The main function of dendritic cells (DC) is to induce the differentiation of naive T lymphocytes into helper cells producing a large array of lymphokines, including interleukin (IL)-2; interferon-gamma (IFN-gamma), IL-4, IL-5 and IL-10. The potent immunostimulatory properties of DC develop during a process of maturation that occurs spontaneously in vitro. Since IL-10 has been shown to inhibit Th1 responses, we determined its effect on DC maturation and accessory function. Our data show that DC that have undergone maturation in vitro in the presence of IL-10, have an impaired capacity to induce a Th1-type response in vivo, leading to the development of Th2 lymphocytes. Their inability to promote the synthesis of IFN-gamma seems to correlate with a decreased production of IL-12, an heterodimeric cytokine necessary for optimal generation of Th1-type cells. These results suggest that IL-10 skews the Th1/Th2 balance to Th2 in vivo by selectively blocking IL-12 synthesis by the antigen-presenting cells that play a role of adjuvant of the primary immune response. The cytokines present in the environment at the presentation step may, therefore, determine the class of the immune response induced by DC in vivo, i.e. Th0, Th1 and/or Th2.

Animals↗

PubMed1981

Coexistence of myeloid and lymphoid neoplastic subpopulations in chronic myelogenous leukemia.

Serial cytogenetic studies have been performed on a child with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) and correlated with clinical, morphologic, and cytochemical data in an attempt to elucidate further the natural history of leukemia progression observed in this disease. Once the initial blast crisis had occurred, two genetically different leukemic clones of cells, one presumably having arisen from the other, coexisted throughout the remainder of the patient's course. The initial clone comprised differentiating myeloid cells, while the second clone appeared on morphologic and cytochemical grounds to be lymphoid and blastic. A dynamic equilibrium existed between these two populations of cells, with the balance altered by chemotherapy and/or other selective pressures. The leukemic progression demonstrated in this case is consistent with the concept of clonal evolution of malignant cell populations. In planning therapy, it may be necessary to consider each of these coexistent clones and their different therapeutic requirements.

Child, Preschool↗

PubMed1999

Water temperature influences the shoaling decisions of guppies, Poecilia reticulata, under predation threat.

In previous experiments, we found antipredator behaviours in female Trinidadian guppies to be influenced by water temperature. To distinguish between hypotheses suggested to explain these observations, we examined the effect of an increase in water temperature on the choice of shoal size of individual female guppies, in the absence and presence of predation threat from a confined cichlid. At 22 degrees C, guppies showed no significant preference for either of two shoal sizes of female guppies, although other responses indicated a reaction to the threat. At 26 degrees C, females chose to shoal with the smaller group when the predator was absent, but, once threatened, switched to a strong preference for the larger group. Variation in preference between individuals was quite high in all treatments, and was somewhat lower for guppies under threat in warmer water, although not significantly so. Our evidence indicates that guppies in warmer water behave as if they are at greater risk of predation, but only when under threat. Temperature-dependent increases in predation risk from ectothermic piscivores could result from less efficient escape responses and from greater vulnerability because of increased foraging activity. We suggest that selection favouring guppies displaying an optimal balance between foraging and antipredator behaviours should act more strongly at higher temperature. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗