PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “balancing selection”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,135 records · Page 63Linked to original sources
PubMed2004

Targets of programmed destruction: a primer to regulatory proteolysis in yeast.

Proteasome-mediated proteolysis of defined target proteins is an important regulatory mechanism, which contributes to control of various essential pathways and programs of the eukaryotic cell. Here, I describe basic principles and mechanisms of regulatory proteolysis as observed in a prominent model cell, the yeast Saccharomyces cerevisiae. Selective proteolysis is important for balancing of a cell's proteins. It is used to directly limit or neutralize enzymes in response to defined signals. Proteasome-mediated degradation is also crucial for the regulation of gene transcription. Elimination of transcription factors as well as mobilization of transcriptional activators by limited proteolysis is involved in negative and positive control of transcription. Moreover, recent data indicate that the proteasomal degradation system may be spatially linked to the transcription machinery. Selective proteolytic destruction of regulators and structural proteins is an essential regulatory mechanism ideally designed for the regulation and correct execution of unidirectional processes as are the cell division cycle or the program of apoptotic cell death. Here the proteasomal degradation system acts on various levels.

Adenosine Triphosphatases↗
PubMed2001

Somatic generation of antigen-receptor diversity: a reprise.

Thirty years ago, in his inaugural article entitled 'The somatic generation of immune recognition', Niels Jerne put forward the hypothesis that the primary antigen (Ag)-receptor repertoire must be restricted towards self-Ags before Ag-mediated selection. The subsequent discovery that Ag receptors are encoded by random rearrangements between discontinuous gene segments was, apparently, at odds with this hypothesis. However, recent findings have begun to reconcile these two concepts. The recombination process is, in fact, relatively precise, exhibiting marked preferences for some gene segments over others, even among members of the same gene family. The result is an intricately patterned primary repertoire that accommodates both sets of predictions, ensuring a balance between the efficiency of selection (requiring limited diversity) and the complexity of the repertoire (requiring maximum diversity).

Animals↗
PubMedDate not supplied

New adjuvants for parenteral and mucosal vaccines.

Developing efficient adjuvants for human vaccines, in order to elicit broad and sustained immune responses at systemic or mucosal levels, remains a challenge for the vaccine industry. Conventional approaches in the past have been largely empirical and partially successful. Selection was based on the balance between toxicity and adjuvanticity, first in an animal model, and then in clinical trials. The advent of improved biochemical techniques has allowed for the purification or construction of new and well characterised adjuvants. In addition, recent advances in our understanding of the immune system, most particularly with respect to early proinflammatory signals, have led to the identification of new biological targets for vaccine adjuvants. In particular, one can now choose adjuvants able to selectively induce T helper (Th)-1 and/or Th2 responses, according to the vaccine target and the desired immune response. As our knowledge of the cell types and cytokines interacting in the immune responses increases, so does our understanding of the mode of action of adjuvants, as well as the way in which they produce adverse effects.

Adjuvants, Immunologic↗
PubMed1989

Fisherian and Wrightian theories of speciation.

Fisher's theory of sexual selection, Wright's shifting-balance theory, and recent models based on them are reviewed as mechanisms of animal speciation. The joint evolution of mating preferences and secondary sexual characters can cause rapid nonadaptive phenotypic divergence and premating isolation between geographically separated populations, or along a cline. Extensive comparative data on Drosophila species support the suggestion of R. A. Fisher and T. Dobzhansky that the evolution of mating preferences can reinforce partial postmating isolation between sympatric populations. The interaction of natural selection and random genetic drift in local populations with a small effective size can produce a rapid transition between relatively stable phenotypes separated by an adaptive valley, or between chromosomal rearrangements with a heterozygote disadvantage. Large demographic fluctuations, such as frequent random local extinction and colonization, are required for the rapid spread of new adaptations (or karyotypes) when intermediate phenotypes (or rearrangement heterozygotes) are selected against.

Animals↗
PubMed2005

Modeling masticatory muscle force in finite element analysis: sensitivity analysis using principal coordinates analysis.

Our work on a finite element model of the skull of Macaca aims to investigate the functional significance of specific features of primate skulls and to determine to which of the input variables (elastic properties, muscle forces) the model behavior is most sensitive. Estimates of muscle forces acting on the model are derived from estimates of physiological cross-sectional areas (PCSAs) of the jaw muscles scaled by relative electromyographic (EMG) amplitudes recorded in vivo. In this study, the behavior of the model was measured under different assumptions regarding the PCSAs of the jaw muscles and the latency between EMG activity in those muscles and the resulting force production. Thirty-six different loading regimes were applied to the model using four different PCSA sets and nine different PCSA scaling parameters. The four PCSA sets were derived from three different macaque species and one genus average, and the scaling parameters were either EMGs from 10, 20, 30, 40, 50 and 60 msec prior to peak bite force, or simply 100%, 50%, or 25% of peak muscle force. Principal coordinates analysis was used to compare the deformations of the model produced by the 36 loading regimes. Strain data from selected sites on the model were also compared with in vivo bone strain data. The results revealed that when varying the external muscle forces within these boundaries, the majority of the variation in model behavior is attributable to variation in the overall magnitude rather than the relative amount of muscle force generated by each muscle. Once this magnitude-related variation in model deformation was accounted for, significant variation was attributable to differences in relative muscle recruitment between working and balancing sides. Strain orientations at selected sites showed little variation across loading experiments compared with variation documented in vivo. These data suggest that in order to create an accurate and valid finite element model of the behavior of the primate skull at a particular instant during feeding, it is important to include estimates of the relative recruitment levels of the masticatory muscles. However, a lot can be learned about patterns of skull deformation, in fossil species for example, by applying external forces proportional to the estimated relative PCSAs of the jaw adductors.

Animals↗
PubMedDate not supplied

Regulation of alternative RNA splicing by exon definition and exon sequences in viral and mammalian gene expression.

Intron removal from a pre-mRNA by RNA splicing was once thought to be controlled mainly by intron splicing signals. However, viral and other eukaryotic RNA exon sequences have recently been found to regulate RNA splicing, polyadenylation, export, and nonsense-mediated RNA decay in addition to their coding function. Regulation of alternative RNA splicing by exon sequences is largely attributable to the presence of two major cis-acting elements in the regulated exons, the exonic splicing enhancer (ESE) and the suppressor or silencer (ESS). Two types of ESEs have been verified from more than 50 genes or exons: purine-rich ESEs, which are the more common, and non-purine-rich ESEs. In contrast, the sequences of ESSs identified in approximately 20 genes or exons are highly diverse and show little similarity to each other. Through interactions with cellular splicing factors, an ESE or ESS determines whether or not a regulated splice site, usually an upstream 3' splice site, will be used for RNA splicing. However, how these elements function precisely in selecting a regulated splice site is only partially understood. The balance between positive and negative regulation of splice site selection likely depends on the cis-element's identity and changes in cellular splicing factors under physiological or pathological conditions.

Alternative Splicing↗
PubMed2002

Energy balance profiles for the first three lactations of dairy cows estimated using random regression.

Daily animal solutions were predicted using random regression analysis for feed intake, milk yield, live weight, and condition score recorded on 189 cows at the Langhill Dairy Cattle Research Centre. All cows had three successive lactations. Energy balance for days 1 to 305 of each of the three lactations was calculated both from daily measures of feed intake and milk output and from weekly measures of live weight and condition score. Cows returned to positive energy balance at days 72, 75, and 95 in lactations 1, 2, and 3, respectively, based on energy balance calculated from feed intake and milk output records (EB1), and at days 77, 83, and 73 based on energy balance calculated from body energy state changes (EB2). Correlations between energy balance at the same time in successive lactations ranged from 0.01 to 0.66 depending on the method of calculation and the stage of lactation. Energy balance over three lactations was modelled using sinusoidal functions which were associated with individual cows and allowed to vary between cows. The parameters of these curves are potentially useful since they have a biological interpretation. The phase relates to the period from calving to return to positive energy balance, and the amplitude relates to the degree of body energy loss (and recovery). The sinusoidal functions fitted to the curve removed a significant proportion of the variation, but accounted for only 45% and 40% of the variation in EB1 and EB2, respectively. The relationship between energy balance in the first three lactations is likely to be more complex than a simple linear function, but the profile of energy balance over the first three lactations may be a useful selection criteria in a multi-trait index. Energy balance profile over lactations one to three can be modelled with moderate accuracy using sinusoidal functions, and this warrants further research.

Animals↗
PubMed1975

Intrahemispheric response competition between vocal and unimanual performances in normam adult human males.

Subjects balanced a dowel rod vertically on the left and right index finger singly and while simultaneously repeating phrases. With right-handed subjects who had no left-handed relatives, concurrent verbalization shortened right- but not left-handed balancing. Increased phonetic difficulty of the phrases produced an increased decrement on right-handed balancing, but left-handed balancing was unchanged; it also produced more verbalization errors on trials with the right hand, but not with the left. Concurrent verbalization shortened balancing duration with both hands of left-handers. Right-handers with left-handed relatives produced variable results. Concurrent humming also selectively interfered with right-handed balancing. It was concluded that the results conform to an interpretation based on intrahemispheric interference between incompatible, simultaneously produced sets of responses.

Adult↗
PubMed1989

Self-serving biases in causal attributions as a function of altered activation asymmetry.

The method of induced lateral orientation of attention was selectively used to alter the balance of activation of the brain toward one cerebral hemisphere or the other. The goal was to extend earlier research which showed greater personal optimism for future events during left hemisphere activation to the related phenomenon of causal attributions. As predicted, there was significantly greater self-serving bias (attribution of internal, stable, and global causes for positive events and external, unstable, and specific causes for negative events) during left hemisphere than during right hemisphere relative activation. This was true for achievement but not for affiliation events. These effects were explained in terms of the increased positive affect which correlates with greater left hemisphere activation. Selective activation of the left hemisphere as a means temporarily to alter attributional style was discussed as a possible tool in the treatment of learned helplessness and depression.

Adolescent↗
PubMed1999

Safety issues in ultrasound-assisted large-volume lipoplasty.

Ultrasound-assisted large volume lipoplasty is controversial because of the potential for increased morbidity and mortality. The plastic surgeon must pay attention to details in patient selection, anesthesia considerations, intraoperative fluid balance, and the technical aspects of ultrasound-assisted lipoplasty to be consistently successful. The avoidance or early detection of complications such as intracavitary penetrations, fluid overload, hypovolemia, deep venous thrombosis, and lidocaine toxicity requires frequent examination by the surgeon. When properly executed, large volume lipoplasty can be gratifying to both patient and surgeon.

Adipose Tissue↗
PubMed2006

Sergliflozin, a novel selective inhibitor of low-affinity sodium glucose cotransporter (SGLT2), validates the critical role of SGLT2 in renal glucose reabsorption and modulates plasma glucose level.

The low-affinity sodium glucose cotransporter (SGLT2), which is expressed specifically in the kidney, plays a major role in renal glucose reabsorption in the proximal tubule. We have discovered sergliflozin, a prodrug of a novel selective SGLT2 inhibitor, based on benzylphenol glucoside. In structure, it belongs to a new category of SGLT2 inhibitors and its skeleton differs from that of phlorizin, a nonselective SGLT inhibitor. We investigated its pharmacological properties and potencies in vitro and in vivo. By examining a Chinese hamster ovary-K1 cell line stably expressing either human SGLT2 or human high-affinity sodium glucose cotransporter (SGLT1), we found sergliflozin-A (active form) to be a highly selective and potent inhibitor of human SGLT2. At pharmacological doses, sergliflozin, sergliflozin-A, and its aglycon had no effects on facilitative glucose transporter 1 activity, which was inhibited by phloretin (the aglycon of phlorizin). The transport maximum for glucose in the kidney was reduced by sergliflozin-A in normal rats. As a result of this effect, orally administered sergliflozin increased urinary glucose excretion in mice, rats, and dogs in a dose-dependent manner. In an oral glucose tolerance test in diabetic rats, sergliflozin exhibited glucose-lowering effects independently of insulin secretion. Any glucose excretion induced by sergliflozin did not affect normoglycemia or electrolyte balance. These data indicate that selective inhibition of SGLT2 increases urinary glucose excretion by inhibiting renal glucose reabsorption. As a representative of a new category of antidiabetic drugs, sergliflozin may provide a new and unique approach to the treatment of diabetes mellitus.

Absorption↗
PubMed1999

Population structure of pathogens: the role of immune selection.

Sunetra Gupta and Roy Anderson discuss how the balance between host immune responses against conserved and variable antigens shapes the population structure of pathogens. At one extreme, immune selection against polymorphic determinants can cause pathogen populations to self-organize spontaneously into discrete antigenic types that may either be maintained over long periods or undergo cyclical or chaotic fluctuations. At the other extreme, diversity may be drastically reduced by competition induced by a strong immune response against a conserved determinant. Where does each pathogen lie along this continuum? How would this knowledge influence our attempts to control an infectious disease?

Alleles↗
PubMed2000

Nutritional composition and micronutrient status of home made and commercial weaning foods consumed in Tanzania.

About 50% of young children in Tanzania suffer from protein-energy undernutrition (PEU) while more than 45% of children under the age of five suffer from various micronutrient deficiency disorders. The immediate cause of these conditions is inadequate intake and poor utilization of nutrients, which begins in the weaning period and amplifies in the subsequent years. This study was conducted to assess the potential of some home made and commercial weaning foods commonly consumed in Tanzania to supply adequate amounts of both macro- and micronutrients as recommended in the Tanzania and FAO/WHO Codex Alimentarius Standards for cereal/milk-based weaning foods. Six types of home made weaning foods, maize, cassava, millet, sorghum and millet-sardine-peanut composite gruels and plantain pap, and four types of commercial weaning foods, Cerelac- 1, Cerelac-2, Lactogen-1 and Lactogen-2, popularly consumed in Tanzania, were chemically assayed for proximate composition, energy and mineral density. Results of the study indicated that, both the home made and commercial weaning foods were good sources of macro- and micronutrients. When compared with the Codex Alimentarius and Tanzania Bureau of Standards specifications for weaning foods, both home made and commercial weaning foods had some shortcomings in terms of nutrient composition and energy balance. Many of the foods were low in fat. Fe, Ca, Zn and P but high in crude fiber, carbohydrate and magnesium. Ca, Fe and Zn were the most common deficient macro/micronutrients in the home made weaning foods. In spite of these shortcomings, most of the home made and commercial weaning foods were nutritionally sound since they could provide reasonable percentages of the recommended daily allowances for macro/micronutrients and energy. It is suggested that, more efforts must be directed towards increasing the concentration of Ca, Fe and Zn in the home made weaning foods through supplementation of the starchy staples with mineral rich foods. Meanwhile, the parents, caretakers and health workers should be educated on the selection and preparation of nutritious, balanced weaning foods and good weaning practices.

Animals↗
PubMed1986

Some trends in medical populations genetics.

Five topics concerning medical population genetics have been selected for discussion: in the field of population cytogenetics, the frequency of chromosomal aberrations and the roles of mutation and selection in the maintenance of balanced rearrangements are studied; the long term genetic effects of treatment and prevention of genetic diseases are reviewed; the relationships between malaria and the sickle-cell trait are discussed; some recent works concerning human DNA polymorphisms in the field of population genetics are presented, and finally, some methods of genetic epidemiology are described.

Anemia, Sickle Cell↗
PubMed2003

Nonrandom intragenic variations in patterns of codon bias implicate a sequential interplay between transitional genetic drift and functional amino acid selection.

Although most codon third bases appear to be functionless, the synonymous codons so defined exhibit a strikingly nonrandom distribution (codon bias) within human and other genes. To examine this phenomenon further, we generated a database of DNA sequences encoding human transmembrane cell-surface receptor proteins. Using this database we show here that the guanine and cytosine content of codon third bases (GC3) varies intragenically with the nature of the specified receptor domains (transmembrane > extracellular > intracellular domains; p < 0.001), the phenotype of the encoded amino acids (hydrophobic > hydrophilic > neutral amino acids; p < 0.001), and the receptor affiliation of the transmembrane (G-protein-coupled receptors > receptor tyrosine kinases; p < 0.001). Within gene regions specifying transmembrane domains, GC3 declines as domain functionality becomes redundant with increasing hydrophobicity (p < 0.001). Codons containing the second-base cytosine (XCZ, which encodes neutral amino acids) are selectively depleted of third-base adenine content (A3: XCA codons) when encoding transmembrane domain residues, consistent with positive selection for transitional mutation of XCG to XTG (which encodes hydrophobic amino acids) rather than to the synonymous XCA. Supporting this XCG --> XTG mechanism of codon bias, the G3:A3 ratio of codons specifying the transmembrane amino acid glycine (GGZ) is intermediate between that of its functional homolog alanine (GCZ) and that of hydrophobic valine (GTZ), even though the C3:T3 ratios are similar. Conversely, nearest-neighbor analysis of third bases 5' to codons specifying valine and leucine (CTZ) confirms a significant difference in C3:T3 but not G3:A3 ratios (i.e., C3/G1 --> T3/G1 > C3/A1; p < 0.001), consistent with the functionally advantageous retention of hydrophobic residues. These data raise the possibility that patterns of intragenic codon bias reflect a balance between negative and positive selection, suggesting in turn that analysis of codon third-base usage may help to predict the functional significance of encoded products.

Amino Acids↗
PubMed1998

[Absorptive pattern of individual fatty acids and total fat in full term babies. Its stability in the absence of lactose].

OBJECTIVE: Lactose absence implies a decrease in calcium absorption. If not absorbed, calcium soaps can be produced with the intestinal fatty acids. Absorption and retention of total fat, individual fatty acids, calcium, magnesium and phosphate have been compared between two groups of children, one fed with lactose free formula and higher levels of calcium (FSL) and the other with standard starting formula (FI). None of them had additional arachidonic or docosahexaenoic acids. PATIENTS AND METHODS: A randomized prospective study was made on 19 term newborn babies by means of metabolic balance measurement during an 8 day period (four days of a stabilization period on the formula, 3 days of the balance period and the final day for feces collection). Both groups were selected following the same criteria for gestational age, balance age, and weight and length at both time periods. Aliquos from the formula were collected daily, as well as all feces and urine during the balance period. Calcium and magnesium quantification of the corresponding ashed products was performed by means of atomic absorption, while Pi was with a colorimetric assay. Total fat was extracted by organic solvents and quantified by gravimetry. Lipid phase fatty acids were methylated, extracted and quantified by means of gas chromatography with a detector of flame ionization. RESULTS: Total fat content and the percentages of each fatty acid did not differ, only calcium concentration in FSL was slightly higher (64.9 +/- 6.9 vs 58.9 +/- 7.0 mg/100 g). No differences were found between groups in relation to ingestion, excretion and retention. The percentages of calcium and total fat retention, however, were slightly superior in the FI in relation to the FSL group. Ca: 68 +/- 22 mg/kg/d, 49 +/- 14% vs 56 +/- 23 mg/kg/d, 48 +/- 17% and total fat: 6.6 +/- 1.2 g/kg/d, 92 +/- 8% vs 6.8 +/- 1.5 g/kg/d, 90 +/- 9%. Absorption of MC fatty acids was 99% for C8. Linoleic and alfalinolenic acid showed an absorption of around 90% despite the big differences in their intake (10/1). Net retention of linoleic acid was 933 +/- 168 mg/kg/d (FI) and 963 +/- 190 mg/kg/d (FSL) and the amount of alpha-linolenic acid was 95 +/- 16 (FI) and 100 +/- 22 mg/kg/d (FSL). No correlation could be found between the amount of excreted calcium and the total amount of fat in feces or with any of the fatty acids studied. This was true for each group studied separately or when considered as a single group. CONCLUSIONS: The absorptive pattern of fatty acids in full term babies, when quantified did not show any conspicous alterations in relation to the accepted values of other ages. The absence of lactose (FSL) in a formula does not make any change in the absorption of total fat and the individual fatty acids when compared to lactose containing formula (FI), when these are present in the same proportions. Supplemented calcium in the formula without lactose could compensate for its lower absorbtion. The absorptive pattern of fatty acid in full term babies did not show any conspicuos alterations in relationship to the accepted values of other ages.

Absorption↗