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PubMed2001

Effects of malnutrition during early lactation on development and feeding behavior under the self-selection paradigm.

Selection of food can be affected by several factors, and with the method of self-selection, qualitative changes in nutritional balance may be detected. The goal of the present study was to evaluate feeding preferences in weaning rats using three macronutrients (protein, carbohydrate, and fat), through a free-choice method, evaluating the alteration in their feeding patterns as compared with the previous nutritional status during the early lactation period. We analyzed the effects of protein restriction during lactation over the nitrogen balance after the weaning. The dams were assigned to one of two diet conditions (nourished or malnourished). At weaning, two pups from each litter were housed individually in metabolic cages, and they were maintained on self-selection under a free-choice paradigm and were provided with separate sources of macronutrients. The parameter for evaluating the nutritional effectiveness of the diets was nitrogen balance. We observed that protein intake tended to increase and consumption of carbohydrate and fat tended to decrease progressively during the 3 wk of experiment. In selecting their own food, growing rats and malnourished rats consumed a larger amount of protein than the other rats. Nourished rats selecting their diet had a larger nitrogen balance than nourished rats receiving a composed diet; no nitrogen balance difference was found between the self-selecting groups. Rats can choose an adaptive form when recovering from protein malnutrition.

Animals↗

PubMed1997

Synthesis and dihydrofolate reductase inhibitory activities of 2,4-diamino-5-deaza and 2,4-diamino-5,10-dideaza lipophilic antifolates.

Two series of nonclassical antifolates (2,4-diamino-5-deaza compounds 2-5 and 5,10-dideaza compounds 6-13) were synthesized as inhibitors of dihydrofolate reductase (DHFR) from Pneumocystis carinii (pc) and Toxoplasma gondii (tg) organisms that are responsible for fatal opportunistic infections in AIDS patients. Rat liver (rl) DHFR served as the mammalian reference enzyme to determine selectivity. Syntheses of the target 5-deaza compounds were achieved by initial construction of the pivaloyl-protected 2,4-diamino-6-bromopyrido[2,3-d]-pyrimidine 17 via a cyclocondensation of 2,4,6-triaminopyrimidine with bromomalonaldehyde. Sequential Heck coupling of 17 with styrene followed by ozonolysis afforded the 6-formyl derivative 19. Reductive amination of 19 with 3,4,5-trimethoxyaniline afforded the N10-H analog. The N10-Me and N10-Et analogs were synthesized by nucleophilic displacement of the 6-bromomethyl derivative 22 (obtained from the 6-formyl derivative 19 by reduction and bromination) with the appropriate N-alkylaniline. The trans-5,10-dideaza analogs 6-8 were synthesized via a Heck coupling of the appropriate methoxystyrene with 17, and selective reduction of the resulting 9,10-double bond afforded target compounds 9-11. Further reduction to the tetrahydro derivatives afforded analogs 12 and 13. The 5-deaza N10-Me 3,4,5-trimethoxy analog 3 maintained the best balance of potency and selectivity against both tgDHFR and pcDHFR. Compared to trimethoprim, compound 3 was only slightly less selective but was 300-fold more potent against tgDHFR. The 5,10-dideaza analogs were generally less potent and selective than the 5-deaza compounds.

AIDS-Related Opportunistic Infections↗

PubMed1999

The physiological basis for faster growth in the Sydney rock oyster, Saccostrea commercialis

Sydney rock oysters were sampled from a mass selection experiment for growth (the "selected" category) and from a control ("not selected") population and held in the laboratory at three ration levels. We evaluated three models to explain faster rates of growth by selected oysters. Selection resulted in oysters feeding at up to twice the rate and with greater metabolic efficiency than controls. A field experiment confirmed that selection leads to faster rates of feeding across a wide range of food concentrations. Selected oysters also grew more efficiently, at a smaller cost of growth (Cg): mean values for Cg were 0.43 J x J(-1) in selected individuals and 0.81 J x J(-1) in the controls. In contrast, oysters in both categories showed similar metabolic rates at maintenance, i.e., at a ration supporting zero growth. There was no evidence that differential energy allocation affected the balance between total metabolic requirements above and below zero net energy balance. By experimenting with selected and control oysters of different sizes and ages, then standardizing the data for size, we found no effects of age on the differences due to selection. Faster-growing oysters feed more rapidly; invest more energy per joule ingested; show a higher net growth efficiency; and are able to allocate less energy per unit of tissue growth, than slower-growing individuals.

Journal Article↗

PubMed2004

Branch site haplotypes that control alternative splicing.

We show that the allele-dependent expression of transcripts encoding soluble HLA-DQbeta chains is determined by branchpoint sequence (BPS) haplotypes in DQB1 intron 3. BPS RNAs associated with low inclusion of the transmembrane exon in mature transcripts showed impaired binding to splicing factor 1 (SF1), indicating that alternative splicing of DQB1 is controlled by differential BPS recognition early during spliceosome assembly. We also demonstrate that naturally occurring human BPS point mutations that alter splicing and lead to recognizable phenotypes cluster in BP and in position -2 relative to BP, implicating impaired SF1-BPS interactions in disease-associated BPS substitutions. Coding DNA variants produced smaller fluctuations of exon inclusion levels than random exonic substitutions, consistent with a selection against coding mutations that alter their own exonization. Finally, proximal splicing in this multi-allelic reporter system was promoted by at least seven SR proteins and repressed by hnRNPs F, H and I, supporting an extensive antagonism of factors balancing the splice site selection. These results provide the molecular basis for the haplotype-specific expression of soluble DQbeta, improve prediction of intronic point mutations and indicate how extraordinary, selection-driven DNA variability in HLA affects pre-mRNA splicing.

Alternative Splicing↗

PubMed1994

Microsurgical thumb reconstruction with toe transfer: selection of various techniques.

Microsurgical toe transfer is an established method for reconstruction of missing thumbs. However, there is little agreement on which of the various techniques represents the ideal transfer. Basically, selection of technique requires balancing the patient's functional needs, appearance of the reconstructed thumb, and donor-site cosmesis. Based on our experience with 103 toe-to-thumb transfers performed over the past 9 years, this paper attempts to provide guidelines for appropriate selection among the four most commonly employed toe transfer techniques (e.g., second toe, total great toe, great toe wrap-around, trimmed great toe) so that optimal results and patient's acceptance can both be achieved.

Adolescent↗

PubMed1998

Preimplantation genetic analysis of translocations: case-specific probes for interphase cell analysis.

Carriers of balanced translocations show an increased risk of infertility and spontaneous abortions, because of errors in gametogenesis, and constitute a significant fraction of patients seeking assisted reproduction. The objective of this study was to design approaches for preimplantation diagnosis of chromosome translocations and to apply such techniques to the selection of chromosomally normal or balanced embryos prior to their transfer to the mother's womb. Three slightly different approaches were assessed by means of chromosome-specific, non-isotopically labeled DNA probes and an assay based on fluorescence in situ hybridization- to score and characterize chromosomes in single blastomeres biopsied from embryos on their third day of development. The three approaches were used for preimplantation genetic diagnosis involving four couples who had enrolled in our IVF program and in which one of the partners was a carrier of one of the following translocations: 46,XX,t(12;20)(p 13.1 ;q 13.3), 46,XY,t(3;4) (p24;p15), 45,XY,der(14;15)(10q;10q), and 46,XY,t(6;11) (p22.1;p15.3). A total of 33 embryos were analyzed, of which 25 (75.8%) were found to be either unbalanced or otherwise chromosomally abnormal. Only a single embryo could be transferred to patients A and D, whereas three embryos were transferred to patient B in a total of two IVF cycles. Transfer of two embryos to patient C resulted in an ongoing pregnancy. Re-analysis of non-transferred embryos with additional probes confirmed the initial results in 95% (20/21) of the cases. In conclusion, case-specific translocation tests can be applied to any translocation carrier for the selection of normal or chromosomally balanced embryos prior to embryo transfer. This is expected significantly to increase the success rates in IVF cycles of translocation carriers, while preventing the spontaneous abortion or birth of abnormal offspring.

Adult↗

PubMed2005

Clinical elements that predict outcome after traumatic brain injury: a prospective multicenter recursive partitioning (decision-tree) analysis.

Traumatic brain injury (TBI) often presents clinicians with a complex combination of clinical elements that can confound treatment and make outcome prediction challenging. Predictive models have commonly used acute physiological variables and gross clinical measures to predict mortality and basic outcome endpoints. The primary goal of this study was to consider all clinical elements available concerning a survivor of TBI admitted for inpatient rehabilitation, and identify those factors that predict disability, need for supervision, and productive activity one year after injury. The Traumatic Brain Injury Model Systems (TBIMS) database was used for decision tree analysis using recursive partitioning (n = 3463). Outcome measures included the Functional Independence Measure(), the Disability Rating Scale, the Supervision Rating Scale, and a measure of productive activity. Predictor variables included all physical examination elements, measures of injury severity (initial Glasgow Coma Scale score, duration of post-traumatic amnesia [PTA], length of coma, CT scan pathology), gender, age, and years of education. The duration of PTA, age, and most elements of the physical examination were predictive of early disability. The duration of PTA alone was selected to predict late disability and independent living. The duration of PTA, age, sitting balance, and limb strength were selected to predict productive activity at 1 year. The duration of PTA was the best predictor of outcome selected in this model for all endpoints and elements of the physical examination provided additional predictive value. Valid and reliable measures of PTA and physical impairment after TBI are important for accurate outcome prediction.

Activities of Daily Living↗

PubMed2000

What is balance?

Balance is a term frequently used by health professionals working in a wide variety of clinical specialities. There is no universally accepted definition of human balance, or related terms. This article identifies mechanical definitions of balance and introduces clinical definitions of balance and postural control. Postural control is defined as the act of maintaining, achieving or restoring a state of balance during any posture or activity. Postural control strategies may be either predictive or reactive, and may involve either a fixed-support or a change-in-support response. Clinical tests of balance assess different components of balance ability. Health professionals should select clinical assessments based on a sound knowledge and understanding of the classification of balance and postural control strategies.

Gravity Sensing↗

PubMed2006

Parasite local adaptation in a geographic mosaic.

A central prediction of the geographic mosaic theory of coevolution is that coevolving interspecific interactions will show varying degrees of local maladaptation. According to the theory, much of this local maladaptation is driven by selection mosaics and spatially intermingled coevolutionary hot and cold spots, rather than a simple balance between gene flow and selection. Here I develop a genetic model of host-parasite coevolution that is sufficiently general to incorporate selection mosaics, coevolutionary hot and cold spots, and a diverse array of genetic systems of infection/resistance. Results from this model show that the selection mosaics experienced by the interacting species are an important determinant of the sign and magnitude of local maladaptation. In some cases, this effect may be stronger than a previously described effect of relative rates of parasite and host gene flow. These results provide the first theoretical evidence that selection mosaics and coevolutionary hot and cold spots per se determine the magnitude and sign of local maladaptation. At the same time, however, these results demonstrate that coevolution in a geographic mosaic can lead to virtually any pattern of local adaptation or local maladaptation. Consequently, empirical studies that describe only patterns of local adaptation or maladaptation do not provide evidence either for or against the theory.

Adaptation, Physiological↗

PubMed2002

The influence of commercial-grade carpet on postural sway and balance strategy among older adults.

PURPOSE: The purpose of this research study was to examine the effect of a selected commercial-grade carpet on the static balance of healthy, older adults who had not fallen more than twice in the last 6 months. DESIGN AND METHODS: We tested a total of 45 participants. Each participant stood on a computerized balance machine and was subjected to a carpeted versus a noncarpeted condition while exposed to various sensory limitations. We measured both postural sway and balance strategy. RESULTS: The selected commercial-grade carpet did not affect postural sway. The participants were able to adapt to the sensory limitations regardless of whether they were standing on the carpet. Although balance strategy scores were significantly lower during the carpeted conditions, the clinical significance was questionable as the difference between the means was small for practical purposes. IMPLICATIONS: Healthy, older adults did not have difficulty maintaining static balance on the carpeted surface; however, the results could be different if participants who had a history of falling had been included. The results from this study are important and provide a basis of comparison for those individuals who have experienced more than two falls in the last 6 months or who have a history of falling.

Accidental Falls↗

PubMed1999

The effect of overdominance on characterizing deleterious mutations in large natural populations.

Alternatives to the mutation-accumulation approach have been developed to characterize deleterious genomic mutations. However, they all depend on the assumption that the standing genetic variation in natural populations is solely due to mutation-selection (M-S) balance and therefore that overdominance does not contribute to heterosis. Despite tremendous efforts, the extent to which this assumption is valid is unknown. With different degrees of violation of the M-S balance assumption in large equilibrium populations, we investigated the statistical properties and the robustness of these alternative methods in the presence of overdominance. We found that for dominant mutations, estimates for U (genomic mutation rate) will be biased upward and those for h (mean dominance coefficient) and s (mean selection coefficient), biased downward when additional overdominant mutations are present. However, the degree of bias is generally moderate and depends largely on the magnitude of the contribution of overdominant mutations to heterosis or genetic variation. This renders the estimates of U and s not always biased under variable mutation effects that, when working alone, cause U and s to be underestimated. The contributions to heterosis and genetic variation from overdominant mutations are monotonic but not linearly proportional to each other. Our results not only provide a basis for the correct inference of deleterious mutation parameters from natural populations, but also alleviate the biggest concern in applying the new approaches, thus paving the way for reliably estimating properties of deleterious mutations.

Animals↗

PubMed2002

Contact chemoreception in feeding by phytophagous insects.

Gustatory receptors associated with feeding in phytophagous insects are broadly categorized as phagostimulatory or deterrent. No phytophagous insect is known that tastes all its essential nutrients, and the ability to discriminate between nutrients is limited. The insects acquire a nutritional balance largely "adventitiously" because leaves have an appropriate chemical composition. Sugars are the most important phagostimulants. Plant secondary compounds are most often deterrent but stimulate phagostimulatory cells if they serve as host-indicating sign stimuli, or if they are sequestered for defense or used as pheromone precursors. The stimulating effects of chemicals are greatly affected by other chemicals in mixtures like those to which the sensilla are normally exposed. Host plant selection depends on the balance of phagostimulatory and deterrent inputs with, in some oligophagous and monophagous species, a dominating role of a host-related chemical. Evolution of phytophagy has probably involved a change in emphasis in the gustatory system, not fundamentally new developments. The precise role of the gustatory systems remains unclear. In grasshoppers, it probably governs food selection and the amounts eaten, but in caterpillars there is some evidence that central feedbacks are also involved in regulating the amount eaten.

Animals↗

PubMed1998

A therapeutic trial of acupuncture in neurogenic bladder of spinal cord injured patients--a preliminary report.

Eighty patients with spinal cord injury (SCI) and neurogenic bladder were studied. Among them, 28 (70%) cases in the control group and 32 (80%) cases in the electroacupuncture group achieved ultimately balanced voiding and were selected for further analysis. The acupuncture group received electroacupuncture at four acupoints: Chung Chi (Conception Vessel CV3), Kuan Yuan (CV4), and bilateral Tzu Liao (Urinary Bladder UB32), in addition to conventional intermittent catheterization program (ICP). Whereas the control group underwent conventional bladder training program with ICP only. The results revealed that the time of achieving balanced voiding was statistically significantly shorter with electroacupuncture than in the control group: 57.1 +/- 22.6 vs 85.2 +/- 27.4 days (P < 0.005) for upper motor neuron lesions, and 55.4 +/- 22.6 vs 83.4 +/- 26.1 days (P < 0.01) for lower motor neuron lesions. However, there was almost no difference between upper motor neuron lesions and lower motor neuron lesions. When acupuncture commenced was alos a factor to influence the results. Those who received acupuncture within 3 weeks after injury had significantly shortened the total days to achieve a balanced bladder, as compared to those who received acupuncture 3 weeks after injury (46.6 +/- 13.2 vs 65.8 +/- 15.4 days, P < 0.005). Our study implied that acupuncture might be beneficial in the management of neurogenic bladder of SCI, and the earlier the patient received electro-acupuncture therapy, the sooner the bladder balanced. On the other hand, we also found that complete spinal cord injury, either with pronounced detrusor-sphincter dyssynergia in upper motor neuron lesion or with persistent areflexic bladder in lower motor neuron-lesion, was not affected by acupuncture.

Acupuncture Therapy↗

PubMed2000

[Equilibrium and orthognathodontic surgery: correlations in a group of patients undergoing treatment].

BACKGROUND: The aim of this study was to evaluate the main parameters provided by the static stabilometric test (mean X, mean Y, mean velocity, length of tracing, standard deviation of velocity, ellipse area) in the follow-up of patients suffering from skeletal occlusive pathology undergoing orthognathodontic surgery to confirm the re-establishment of postural equilibrium. METHODS: Fifteen patients with skeletal dysgnathia were correlated with a group of 10 healthy subjects. The same parameters were analysed in the dysgnathic subjects at 6 and 12 months after surgical correction. The patients enrolled in this study underwent surgery at the Division of Maxillofacial surgery of Turin University. Student's "t"-test and multivariate statistical analysis (Cox regression) were used for the statistical analysis of results. RESULTS: A significant variability was noted in some of the main parameters analysed (mean X, mean Y, tracing length) between the two populations (healthy and dysgnathic) compared to visual signs (eyes opened-closed). The change in stabilometric values within the group of dysgnathic patients was highly significant 6 and 12 months after surgery, not only in terms of visual signs but also the cervical component (retroflexion of the head), above all the value of mean Y (p = 0.001). CONCLUSIONS: An analysis of these results shows that static stabilometry can be a valuable aid both during the preoperative evaluation and during the follow-up in patients undergoing jaw surgery since it can quantify the improvement of body balance.

Adolescent↗

PubMed1998

Modular augments in revision total knee arthroplasty.

Modularity in total knee arthroplasty is extremely helpful in the management of patients with complex primary and revision total knee arthroplasties. Modularity allows selective augmentation to deal with bone deficiencies on the distal and posterior femur. The ability to selectively augment the femur is very helpful in balancing the soft tissues and providing stability. Selective augmentation of the femur allows restoration of the joint line and more normal patellar and collateral ligament kinematics. Selective modular augments on the tibia allow dealing with bone deficiency without the concerns of bone graft incorporation. Modular extended intramedullary stems allow the option of either press-fit or cement fixation of the stem, entailing the stem diameter length to the given patient.

Arthroplasty, Replacement, Knee↗

PubMed2002

The impact of message mutation on the fitness of a genetic code.

The Standard Genetic Code is organized such that similar codons encode similar amino acids. One explanation suggested that the Standard Code is the result of natural selection to reduce the fitness "load" that derives from the mutation and mistranslation of protein-coding genes. We review the arguments against the mutational load-minimizing hypothesis and argue that they need to be reassessed. We review recent analyses of the organization of the Standard Code and conclude that under cautious interpretation they support the mutational load-minimizing hypothesis. We then present a deterministic asexual model with which we study the mode of selection for load minimization. In this model, individual fitness is determined by a protein phenotype resulting from the translation of a mutable set of protein-coding genes. We show that an equilibrium fitness may be associated with a population with the same genetic code and that genetic codes that assign similar codons to similar amino acids have a higher fitness. We also show that the number of mutant codons in each individual at equilibrium, which determines the strength of selection for load minimization, reflects a long-term evolutionary balance between mutations in messages and selection on proteins, rather than the number of mutations that occur in a single generation, as has been assumed by previous authors. We thereby establish that selection for mutational load minimization acts at the level of an individual in a single generation. We conclude with comments on the shortcomings and advantages of load minimization over other hypotheses for the origin of the Standard Code.

Amino Acids↗

PubMed2003

A two-locus gene conversion model with selection and its application to the human RHCE and RHD genes.

A two-locus gene conversion model with selection is developed. Under the joint action of selection, mutation, gene conversion, recombination, and random genetic drift, approximate formulas for the expectations of the moments of allele frequencies and the expected amounts of variation within and between two loci are obtained by a diffusion method assuming relatively strong selection. It is shown that the pattern of allelic variation is mainly determined by the balance between gene conversion and selection, because these two mechanisms act in opposite directions. As an application of the theoretical results, the human RHCE and RHD genes are considered. The very high level of amino acid divergence between the two genes is observed only in a short region around exon 7. It is known that exon 7 encodes amino acids that characterize the difference between the RHCE and RHD antigens. The observed pattern of DNA variation in this region is consistent with the selection model developed in this article, suggesting that strong selection might be working to maintain the RHCE/RHD antigen variation in the two-locus system. The selection intensity is estimated on the basis of the theoretical result.

Alleles↗

PubMedDate not supplied

Sexual selection as a cause of human skin colour variation: Darwin's hypothesis revisited.

The dark skin of tropical peoples is likely to be an adaptation to the strong ultraviolet (UV) radiation near the equator, perhaps protecting against sunburn or degradation of folate. By contrast, the adaptive value of light skin is questionable. In particular, the relevance of vitamin D deficiency rickets as a selective factor has been cogently criticized. Population genetic studies on the melanocortin 1 receptor (MC1R) gene (one of the genes responsible for normal human skin colour variation) also cast doubt on the role of positive natural selection in the evolution of light skin. Natural selection may favour dark skin everywhere, though to a lesser extent at higher latitudes. Darwin believed that racial differences in skin colour were caused by sexual selection. Available evidence suggests that in each society a lighter-than-average skin colour is preferred in a sexual partner. Such a preference would generate sexual selection for light skin that counteracts natural selection for dark skin. The observed latitudinal gradient in skin colour may result from the balance between natural and sexual selection.

Cross-Cultural Comparison↗