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PubMed2001

Phenotypic plasticity of Senecio vulgaris from contrasting habitat types: growth and pyrrolizidine alkaloid formation.

The growth-differentiation balance hypothesis (GDB), which postulates a physiological trade-off between growth and differentiation (morphological and chemical), has been tested almost exclusively for carbon-based secondary metabolites. Little attention has been paid to N-based compounds. In this study we aimed to test the predictions of the GDB hypothesis under field conditions for growth and pyrrolizidine alkaloid (PA) formation in Senecio vulgaris. We conducted a reciprocal transplant experiment at two sites differing widely in their nutrient supply. These included a conventionally managed vineyard (V) and a strip of local wild flowers between crop fields, which was established to promote species diversity in agroecosystems (C). No fertilizer or pesticides are allowed in such ecological compensation areas. In C, we expected lower growth but higher PA formation than in V. Due to differentiated selection regimes in the two habitat types with regard to nutrient (nitrogen) availability in the soil, we also expected different N-allocation patterns for the genotypes of the two collection sites. Plants of V produced more biomass and were taller than the plants of C. The relatively poor nitrogen conditions in C favored an earlier differentiation towards generative organs. In plants of C, higher concentrations of PAs were found than in plants of V. There exists a close negative correlation between growth and PA formation, indicating a trade-off. The origin of the plant material had only a little effect on PA formation. The observed phenotypic reaction of PA formation in S. vulgaris in the two habitats fits quite well the predictions of GDB theory. It is shown that this general response is overlaid by physiological factors leading to a pattern of PA accumulation, which is not readily predictable by nonmechanistic theories.

Analysis of Variance↗
PubMed2005

Correlation between gene expression levels and limitations of the empirical bayes methodology for finding differentially expressed genes.

Stochastic dependence between gene expression levels in microarray data is of critical importance for the methods of statistical inference that resort to pooling test statistics across genes. The empirical Bayes methodology in the nonparametric and parametric formulations, as well as closely related methods employing a two-component mixture model, represent typical examples. It is frequently assumed that dependence between gene expressions (or associated test statistics) is sufficiently weak to justify the application of such methods for selecting differentially expressed genes. By applying resampling techniques to simulated and real biological data sets, we have studied a potential impact of the correlation between gene expression levels on the statistical inference based on the empirical Bayes methodology. We report evidence from these analyses that this impact may be quite strong, leading to a high variance of the number of differentially expressed genes. This study also pinpoints specific components of the empirical Bayes method where the reported effect manifests itself.

Journal Article↗
PubMed1996

A chance-selection model for cell differentiation.

A chance-selection model is proposed to explain cell differentiation. It is based on the general idea that stochasticity at the molecular level generates diversity in cell types whereas cell interactions impose a characteristic order on the developing embryo. In this model, gene expression depends on stochastic molecular interactions between transcriptional regulators and DNA. Random diffusion of these regulators along DNA causes differential gene expression in differentiating cells.The role of phosphorylation or dephosphorylation of transcriptional regulators, triggered by cell interactions, is to control their random diffusion and to stabilize stochastic gene expression in differentiated cells. This model is based on well documented phenomena: random diffusion of DNA binding molecules along DNA, phosphorylation or dephosphorylation of transcription factors by protein kinases or phosphatases and control of DNA binding of transcription factors through this latter process. The different explanatory powers of deterministic and stochastic models are discussed.

Journal Article↗
PubMed2000

A comparative study of the chromatographic selectivity of polystyrene-coated zirconia and related reversed-phase materials.

The chromatographic selectivities of polystyrene-coated zirconia (PS-ZrO2) have been investigated in detail by means of homologue series retention studies and studies of a variety of nonpolar aromatic positional isomers. This material has been compared to polybutadiene-coated zirconia, octadecyl- and phenyl-bonded silica, and polymer-based reversed phases. In addition, the separations of a wide variety of compound classes on PS-ZrO2 were compared with those on other aromatic and aliphatic RPLC phases. The PS-ZrO2 material exhibits substantial differences in selectivity toward nonpolar and polar analytes as compared to other phases, especially with respect to polybutadiene-coated zirconia (PBD-ZrO2). On PS-ZrO2, polynuclear aromatic hydrocarbons (PAHs) are retained much more than are alkylbenzenes, whereas on PBD-ZrO2 the opposite is observed. In addition, PS-ZrO2 has much greater selectivity than does PBD-ZrO2 for the separation of structural isomers which differ in the position of phenyl groups. In general, even though the carbon content of PS-ZrO2 is much lower than that of conventional reversed-phase materials, such as octadecyl-bonded silica (C18-SiO2), polar analytes exhibit sufficient retention and differential selectivity on PS-ZrO2 that resolution comparable to that on C18-SiO2 can be obtained but with substantially improved analysis times.

Chromatography, Liquid↗
PubMed2005

Gene transfer of the Runx2 transcription factor enhances osteogenic activity of bone marrow stromal cells in vitro and in vivo.

Marrow stromal cells (MSCs) have the potential to differentiate into multiple mesenchymal cell types. To harness the power of MSCs for bone regeneration, methods must be developed to direct their differentiation selectively to the osteoblast lineage. The objective of this study was to examine the feasibility of using ex vivo Runx2 gene transfer to enhance the osteogenic activity of MSCs. Primary MSCs isolated from C57BL6 mice were transduced with adenoviral vectors encoding beta-galactosidase or Runx2. Cells transduced with Ad-Runx2 expressed Runx2 protein and underwent osteoblast differentiation as measured by increases in alkaline phosphatase activity and mineralization. Time-course studies revealed that Runx2 protein was highest 1 day after transduction and declined below the limits of detection by 15 days. Osteoblast marker mRNA expression paralleled Runx2 levels. In contrast, Runx2-dependent mineralization persisted for the duration of the experiment. To assess in vivo osteogenic activity, Ad-Runx2-transduced and control MSCs were adsorbed to two different carrier scaffolds and subcutaneously implanted into C57BL6 mice. In both cases, MSCs expressing Runx2 formed substantially more bone than cells transduced with control virus. Taken together, these studies indicate that Runx2 gene transfer may be an effective route to enhance the osteogenic potential of MSCs.

Adenoviridae↗
PubMed1983

Incidence of colourblindness in different Indian populations: further example of selection relaxation hypothesis.

Incidence of colourblindness among 1154 males belonging to seven endogamous groups viz. Brahmins, Rajputs and Shilpkars of Pithoragarh (Uttar Pradesh), Brahmins and Rajputs of Simla (Himachal Pradesh) and Kolis and Rajputs of panchmahal [Gujarat] has been reported. The frequency of colourblindness varies from 1.74% in Shilpkars to 5.0% in Kolis. Further, Indian male population data have been divided into three categories on the basis of their mode of life and habitat to test Post, Pickford and Neel and Post's hypothesis of differential selection for colourblindness.

Adolescent↗
PubMed2006

Messenger-specific role for nicotinic acid adenine dinucleotide phosphate in neuronal differentiation.

Cells possess several Ca2+-mobilizing messengers, which couple stimulation at the cell surface by a multitude of extracellular cues to the regulation of intracellular Ca2+-sensitive targets. Recent studies suggest that agonists differentially select from this molecular palette to generate their characteristic Ca2+ signals but it is still unclear whether different messengers mediate different functions or whether they act in a redundant fashion. In this study, we compared the effects of nicotinic acid adenine dinucleotide phosphate (NAADP), a novel Ca2+-mobilizing messenger, with that of the prototypical messenger inositol trisphosphate on cytosolic Ca2+ levels and differentiation status of PC12 cells. We demonstrate that liposomal delivery of NAADP mediated release of Ca2+ from acidic Ca2+ stores and that this stimulus was sufficient to drive differentiation of the cells to a neuronal-like phenotype. In sharp contrast, cell fate was unaffected by more transient Ca2+ signals generated by inositol trisphosphate-evoked release of endoplasmic reticulum Ca2+ stores. Our data establish for the first time (i) the presence of novel NAADP-sensitive Ca2+ stores in PC12 cells, (ii) a role for NAADP in differentiation, and (iii) that Ca2+-dependent function can be messenger-specific. Thus, differential recruitment of intracellular Ca2+-mobilizing messengers and their target Ca2+ stores may represent a robust means of maintaining stimulus fidelity in the control of Ca2+-dependent cell function.

Animals↗
PubMed2002

[Heterozygosity and selective value: the case of the marine fish, Diplodus sargus (Linné, 1758)].

A total of 842 white sea bream (Diplodus sargus), sampled in Banyuls-sur-Mer, were analysed to test 'genotype-phenotype' relationship for various characters related to the fitness. The results show significant differences (MLH and FIS) for the age according to the sex between females carrying out and not carrying out sexual inversion. This suggests an overdominance for old females and a genetic sex determination. The individuals laying very early during the period of reproduction are also differentiated from the individuals reproducing later in the season. These results suggest either a stable calendar of laying in time separating the individuals genetically reproducing precociously from the others and this by differential selection and/or genetic drift either a Wahlund effect among cohorts.

Animals↗
PubMed2006

Characterization of a collection of Enterobacter sakazakii isolates from environmental and food sources.

Enterobacter sakazakii has emerged as a rare cause of neonatal meningitis, septicemia and enterocolitis. Contaminated infant milk formula (IMF) has been identified as one infection route. A small number of clinical outbreaks have been epidemiologically linked to IMF contaminated post-pasteurization during manufacture and/or mishandled when reconstituted. Currently no agreed standardized typing protocol has been developed to trace E. sakazakii. The objectives of this study were to apply biochemical and genetic methods to characterize 51 environmental and food E. sakazakii isolates and 6 E. sakazakii type strains. Isolates were presumptively identified using biochemical profiles based on API 20E and ID32E methods and by culture on differential selective Druggan Forsythe Iversen (DFI) agar. Identification was subsequently confirmed by real time polymerase chain reaction (PCR). All but one of the isolates was identified as E. sakazakii by biochemical profiling. One isolate was identified as Escherichia vulneris by ID 32E and as Pantoea agglomerans by API 20E. All isolates produced green/blue colonies on DFI medium characteristic of this organism. Real time PCR could differentiate between E. sakazakii, Enterobacter spp. and other Enterobacteriacae. Analysis of RAPD banding patterns revealed 3 major clusters of E. sakazakii. There was a large degree of diversity noted amongst the remaining isolates. Our findings indicate that RAPD may be applied as a useful and reliable tool for direct comparison of E. sakazakii isolates providing traceability through the infant formula food chain.

Cluster Analysis↗
PubMed1998

Differential expression of c-fos and hsp72 mRNA in focal cerebral ischemia of mice.

The heterogeneity of c-fos and hsp72 mRNA expression during focal ischemia was studied in mice by combining in situ hybridization with metabolic imaging. Focal ischemia was produced by middle cerebral artery occlusion for 3 h. The infarct core and the penumbra were differentiated by regional ATP and cerebral protein synthesis (CPS) imaging. hsp72 mRNA expression was restricted to the ischemic penumbra, as defined by the dissociation between preserved ATP and suppressed CPS. c-fos mRNA was expressed not only in the penumbra but also in the peri-ischemic normal brain tissue in which both ATP and CPS were preserved. These data demonstrate a highly selective differential expression of immediate-early and stress-related genes in the peri-infarct surrounding which is explained by different mechanisms of gene induction.

Adenosine Triphosphate↗
PubMed1994

The paradigm of biologically closed electric circuits (BCEC) and the formation of an International Association (IABC) for BCEC systems.

Matter is condensed energy. Matter derived from electromagnetic energy, supplied with the electrically powered BCEC systems (biologically closed electric circuits) inherits prerequisites to become biological matter. This is possible because mechanisms of BCEC systems contain the capacity to initiate structuring and functioning of matter. The principle of BCEC systems, their actual and potential importance for structure and function in biology and medicine, has been presented only in the form of a survey. Only few examples of the impact of the BCEC systems have been described. For detailed information, the reader is advised to take part of the original background articles by means of the reference list, which extends beyond the selected descriptions. Thereby it is hoped that the reader may get an understanding of the central biological role of the BCEC systems. They represent in this partial theory of the biological evolution a key mechanism which may provide the important primary steps that are necessary for the transfer of non-biological into biological matter. Second, also other factors are evidently contributing to biological differentiation, including for instance the principle of differential selection of species. Due to their basic role, the BCEC systems can nevertheless be recognized to be involved in the majority of structural and functional expressions in biology. This rests on the fact that our physical world once developed from energy and specifically its representation of electric energy. It has also been emphasised that electric energy is equivalent to the remarkable Oriental concept of Qi ("life energy"). Differences are predominantly a matter of semantics.

Animals↗
PubMed2005

Detecting differentially expressed genes by relative entropy.

DNA microarray experiments have generated large amount of gene expression measurements across different conditions. One crucial step in the analysis of these data is to detect differentially expressed genes. Some parametric methods, including the two-sample t-test (T-test) and variations of it, have been used. Alternatively, a class of non-parametric algorithms, such as the Wilcoxon rank sum test (WRST), significance analysis of microarrays (SAM) of Tusher et al. (2001), the empirical Bayesian (EB) method of Efron et al. (2001), etc., have been proposed. Most available popular methods are based on t-statistic. Due to the quality of the statistic that they used to describe the difference between groups of data, there are situations when these methods are inefficient, especially when the data follows multi-modal distributions. For example, some genes may display different expression patterns in the same cell type, say, tumor or normal, to form some subtypes. Most available methods are likely to miss these genes. We developed a new non-parametric method for selecting differentially expressed genes by relative entropy, called SDEGRE, to detect differentially expressed genes by combining relative entropy and kernel density estimation, which can detect all types of differences between two groups of samples. The significance of whether a gene is differentially expressed or not can be estimated by resampling-based permutations. We illustrate our method on two data sets from Golub et al. (1999) and Alon et al. (1999). Comparing the results with those of the T-test, the WRST and the SAM, we identified novel differentially expressed genes which are of biological significance through previous biological studies while they were not detected by the other three methods. The results also show that the genes selected by SDEGRE have a better capability to distinguish the two cell types.

Acute Disease↗
PubMed2005

Ambient particulate matter and health effects: publication bias in studies of short-term associations.

BACKGROUND: Time-series studies have shown short-term temporal associations between low levels of ambient particulate air pollution and adverse health effects. It is not known whether or to what extent this literature is affected by publication bias. METHODS: We obtained effect estimates from time-series studies published up to January 2002. These were summarized and examined for funnel plot asymmetry. We compared summary estimates between single-city and prospective multicity studies. Using 1 multicity study, we examined the sensitivity of summary estimates to alternative lag selection policies. RESULTS: We found evidence for publication bias among single-city studies of daily mortality, hospital admissions for chronic obstructive lung disease (COPD), and incidence of cough symptom, but not for studies of lung function. Statistical correction for this bias reduced summary relative risk estimates for a 10 microg/m increment of particulate matter less than 10 microm aerodynamic diameter (PM10) as follows: daily mortality from 1.006 to 1.005 and admissions for COPD from 1.013 to 1.011; and odds ratio for cough from 1.025 to 1.015. Analysis of results from a large multicity study suggested that selection of positive estimates from a range of lags could increase summary estimates for PM10 and daily mortality by up to 130% above those based on nondirectional approaches. CONCLUSION: We conclude that publication bias is present in single-city time-series studies of ambient particles. However, after correcting for publication bias statistically, associations between particles and adverse health effects remained positive and precisely estimated. Differential selection of positive lags may also inflate estimates.

Air Pollutants↗
PubMed1985

Selection practices and genetic and phenotypic trends estimated from Nebraska SPF swine field records.

Records collected during 1971 through 1979 from 101,606 pigs raised in 18 herds that were members of the Nebraska SPF Swine Accrediting Association were evaluated for phenotypic trends and predicted and observed genetic trends. Traits considered were backfat at 100 kg (BF) and weight at 140 d of age (WT). Phenotypic change on average was beneficial for BF (-.05 mm/yr) but undesirable for WT (-.2 kg/yr). However, the average observed genetic trend was nil for BF and .6 kg/yr for WT. An average, predicted response based on observed selection differentials and estimates of within herd-sex genetic parameters was in good agreement with observed response for BF, but was three times higher for WT.

Adipose Tissue↗
PubMed2000

Dose-dependent selective priming of Th1 and Th2 immune responses is achieved only by an antigen with an affinity over a certain threshold level.

Helper CD4+ T lymphocytes can be divided into two subsets, Th1 and Th2. The types of Th subsets activated during the adaptive immune response inductiondetermine the efficacy of immune responses against thee antigens introduced. Selective differentiation of subsets of CD4+ T lymphocytes has been known to be influenced by several factors, such as the cytokine environment around the T cells, the specificity of antigen recognition bythe T cell receptor, the expression of costimulatory molecules, and/ or the dose of the antigen applied to stimulate the T cells. In this study, we tried to determine the influence of the antigen dose on the selective priming of T lymphocytes when an inefficient antigen was applied since all the conclusions drawn from previous experiments were based on experiments with immune systems which responded well against the antigens introduced. When the recombinant hen egg-white lysozyme (HEL) was used too stimulate immune responses in HEL low-responder C57B3L/6 mice, dose-dependent selective priming of immune responses was not observed. However, when the variant antigen, which had been characterized as an efficientantigen in anti-HEL immune response induction in the low-responder mice, was applied, dose-dependent selective priming of Th immune responses was clearly demonstrated. These results suggested that dose-dependent selective priming of Th immune responses could be achieved only by the antigens with an affinity over a certain level.

Animals↗
PubMed2003

Sexual variation in heritability and genetic correlations of morphological traits in house sparrow (Passer domesticus).

Estimates of genetic components are important for our understanding of how individual characteristics are transferred between generations. We show that the level of heritability varies between 0.12 and 0.68 in six morphological traits in house sparrows (Passer domesticus L.) in northern Norway. Positive and negative genetic correlations were present among traits, suggesting evolutionary constraints on the evolution of some of these characters. A sexual difference in the amount of heritable genetic variation was found in tarsus length, wing length, bill depth and body condition index, with generally higher heritability in females. In addition, the structure of the genetic variance-covariance matrix for the traits differed between the sexes. Genetic correlations between males and females for the morphological traits were however large and not significantly different from one, indicating that sex-specific responses to selection will be influenced by intersexual differences in selection differentials. Despite this, some traits had heritability above 0.1 in females, even after conditioning on the additive genetic covariance between sexes and the additive genetic variances in males. Moreover, a meta-analysis indicated that higher heritability in females than in males may be common in birds. Thus, this indicates sexual differences in the genetic architecture of birds. Consequently, as in house sparrows, the evolutionary responses to selection will often be larger in females than males. Hence, our results suggest that sex-specific additive genetic variances and covariances, although ignored in most studies, should be included when making predictions of evolutionary changes from standard quantitative genetic models.

Animals↗
PubMed1984

Differential ventilation and selective PEEP during anaesthesia in the lateral decubitus posture.

The potential of differential ventilation (DV) with selective positive end-expiratory pressure (PEEP) has been tested versus conventional ventilation with and without general PEEP. Gas exchange and central haemodynamics were studied in 15 subjects with no clinical or radiological signs of pulmonary disease. The rationale of the method was to ensure ventilation of the well-perfused dependent lung and to counteract airway closure within that lung. The subjects were intubated with a double-lumen catheter prior to scheduled abdominal surgery. During general anaesthesia in the lateral posture, they were given DV. The mean inspired oxygen fraction was 0.32. Fifty per cent ("even" tidal volume (VT) distribution) or 70% ("inverted" VT distribution) of the inspired volume was administered to the dependent lung. Two synchronized ventilators were used. In eight subjects DV was also combined with PEEP applied solely to the dependent lung (selective PEEP). The major findings were that DV with even VT distribution reduced venous admixture by 26% (P less than 0.05) and the alveolo-arterial oxygen tension gradient (P(A-a)o2) by 30% (P less than 0.05) in comparison with conventional ventilation in the lateral position. The addition of selective PEEP further reduced the P(A-a)o2 by 13%. P(A-a)o2 was consequently 43% lower than during conventional ventilation without PEEP in the lateral posture (P less than 0.01). Selective PEEP also had less impact on cardiac output than general PEEP (P less than 0.05). It is concluded that DV with even distribution of VT and selective PEEP can reduce the P(A-a)o2 in anaesthetized lung-healthy subjects in the lateral position.

Adult↗
PubMed1989

Selective amidation of carboxyl groups of the intermolecular contact regions of hemoglobin S: structural aspects.

Carboxyl groups of HbS are readily activated by water-soluble carbodiimide at pH 6.0 and room temperature. These o-acylurea intermediates (activated carboxyl) are accessible for nucleophilic attack by amines. With glycine ethyl ester, the amidation is very selective for the gamma-carboxyl of Glu-43(beta) and more than 65% of the glycine ethyl ester incorporated is on this carboxyl group. In contrast, glucosamine derivatizes the gamma-carboxyl group of Glu-22(beta) as well as that of Glu-43(beta) to nearly the same degree. However, the total amidation of HbS by glucosamine is lower than that with glycine ethyl ester. The differential selectivity of the two amines is apparently related to the differences in the microenvironment of the gamma-carboxyl groups of Glu-22(beta) and Glu-43(beta), which either facilitates or refracts the aminolysis of the activated carboxyl with the two amines to different degrees. The carboxyl groups of isolated beta-chain exhibit a higher reactivity for amidation with glycine ethyl ester than does the tetramer. The carboxyl groups of Glu-22(beta) and Glu-43(beta) and that of Asp-47(beta) are all activated by carbodiimide suggesting that the higher pKa of these carboxyl groups (facilitating the activation) is a property of tertiary interaction of the polypeptide chain. The interaction of the beta-chain with alpha-chain, i.e., generation of the quaternary interactions, reduces overall reactivity of the carboxyl groups of the protein. The higher selectivity of hemoglobin S for amidation at Glu-43(beta) with glycine ethyl ester compared with that of isolated beta-chain appears to be primarily a consequence of decreased amidation at sites other than at Glu-43(beta).

Amides↗