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Heterogeneous Population (heterogeneous + population)
Selected AbstractsTHE DIFFUSIVE SPREAD OF ALLELES IN HETEROGENEOUS POPULATIONSEVOLUTION, Issue 3 2004Garrick T. Skalski Abstract The spread of genes and individuals through space in populations is relevant in many biological contexts. I study, via systems of reaction-diffusion equations, the spatial spread of advantageous alleles through structured populations. The results show that the temporally asymptotic rate of spread of an advantageous allele, a kind of invasion speed, can be approximated for a class of linear partial differential equations via a relatively simple formula, c= 2,rD, that is reminiscent of a classic formula attributed to R. A. Fisher. The parameters r and D, represent an asymptotic growth rate and an average diffusion rate, respectively, and can be interpreted in terms of eigenvalues and eigenvectors that depend on the population's demographic structure. The results can be applied, under certain conditions, to a wide class of nonlinear partial differential equations that are relevant to a variety of ecological and evolutionary scenarios in population biology. I illustrate the approach for computing invasion speed with three examples that allow for heterogeneous dispersal rates among different classes of individuals within model populations. [source] THE ADAPTIVE DYNAMICS OF ALTRUISM IN SPATIALLY HETEROGENEOUS POPULATIONSEVOLUTION, Issue 1 2003JEAN-FRANÇOIS LE GALLIARD Abstract., We study the spatial adaptive dynamics of a continuous trait that measures individual investment in altruism. Our study is based on an ecological model of a spatially heterogeneous population from which we derive an appropriate measure of fitness. The analysis of this fitness measure uncovers three different selective processes controlling the evolution of altruism: the direct physiological cost, the indirect genetic benefits of cooperative interactions, and the indirect genetic costs of competition for space. In our model, habitat structure and a continuous life cycle makes the cost of competing for space with relatives negligible. Our study yields a classification of adaptive patterns of altruism according to the shape of the costs of altruism (with decelerating, linear, or accelerating dependence on the investment in altruism). The invasion of altruism occurs readily in species with accelerating costs, but large mutations are critical for altruism to evolve in selfish species with decelerating costs. Strict selfishness is maintained by natural selection only under very restricted conditions. In species with rapidly accelerating costs, adaptation leads to an evolutionarily stable rate of investment in altruism that decreases smoothly with the level of mobility. A rather different adaptive pattern emerges in species with slowly accelerating costs: high altruism evolves at low mobility, whereas a quasi-selfish state is promoted in more mobile species. The high adaptive level of altruism can be predicted solely from habitat connectedness and physiological parameters that characterize the pattern of cost. We also show that environmental changes that cause increased mobility in those highly altruistic species can beget selection-driven self-extinction, which may contribute to the rarity of social species. [source] THE USE OF AGGREGATE DATA TO ESTIMATE GOMPERTZ-TYPE OLD-AGE MORTALITY IN HETEROGENEOUS POPULATIONSAUSTRALIAN & NEW ZEALAND JOURNAL OF STATISTICS, Issue 4 2009Christopher R. Heathcote Summary We consider two related aspects of the study of old-age mortality. One is the estimation of a parameterized hazard function from grouped data, and the other is its possible deceleration at extreme old age owing to heterogeneity described by a mixture of distinct sub-populations. The first is treated by half of a logistic transform, which is known to be free of discretization bias at older ages, and also preserves the increasing slope of the log hazard in the Gompertz case. It is assumed that data are available in the form published by official statistical agencies, that is, as aggregated frequencies in discrete time. Local polynomial modelling and weighted least squares are applied to cause-of-death mortality counts. The second, related, problem is to discover what conditions are necessary for population mortality to exhibit deceleration for a mixture of Gompertz sub-populations. The general problem remains open but, in the case of three groups, we demonstrate that heterogeneity may be such that it is possible for a population to show decelerating mortality and then return to a Gompertz-like increase at a later age. This implies that there are situations, depending on the extent of heterogeneity, in which there is at least one age interval in which the hazard function decreases before increasing again. [source] Welfare Comparisons: Sequential Procedures for Heterogeneous PopulationsECONOMICA, Issue 276 2002Peter J. Lambert Some analysts use sequential dominance criteria, and others use equivalence scales in combination with non-sequential dominance tests, to make welfare comparisons of joint distributions of income and needs. In this paper we present a new sequential procedure which copes with situations in which sequential dominance fails. We also demonstrate that the recommendations deriving from the sequential approach are valid for distributions of equivalent income whatever equivalence scale the analyst might adopt. Thus, the paper marries together the sequential and equivalizing approaches, seen as alternatives in much previous literature. All results are specified in forms that allow for demographic differences in the populations being compared. [source] Adaptation of the Fungal Parasite Zygorhizidium planktonicum During 200 Generations of Growth on Homogeneous and Heterogeneous Populations of Its Host, the Diatom Asterionella formosa,THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 2 2008ARNOUT DE BRUIN ABSTRACT. We followed adaptation of the chytrid parasite Zygorhizidium planktonicum during 200 generations of growth on its host, the freshwater diatom Asterionella formosa, in a serial passage experiment. Evolution of parasite fitness was assessed both on a homogenous and heterogeneous host population, consisting of respectively a single new and ten different new host strains. These 10 host strains were genetically different and also varied in their initial susceptibility to the parasite. Parasite fitness increased significantly and rapidly on the new, genetically homogenous host population, but remained unaltered during 200 generations of growth on the heterogeneous host population. Enhanced parasite fitness was the result of faster and more efficient transmission, resulting in higher values of R0 (number of secondary infections). Consequently, parasites that evolved within the uniclonal host population infected significantly more of these hosts than did their ancestors. We thus provide experimental evidence for the widely held view that host genetic diversity restricts evolution of parasites and moderates their harmful effects. Genetically uniform host populations are not only at increased risk from fungal epidemics because they all share the same susceptibility, but also because new parasite strains are able to adapt quickly to new host environments and to improve their fitness. [source] Primary mesenchyme cell-ring pattern formation in 2D-embryos of the sea urchinDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 1 2000Hideki Katow Primary mesenchyme cell (PMC) migration during PMC-ring pattern formation was analyzed using computer-assisted time-lapse video microscopy in spread embryos (2D-embryo) of the sea urchin, Mespilia globulus, and a computer simulation. The PMC formed a near normal ring pattern in the 2D-embryos, which were shown to be an excellent model for the examination of cell behavior in vivo by time-lapse computer analysis. The average migration distance of the ventro-lateral PMC aggregate-forming cells (AFC) and that of the dorso-ventral PMC cable-forming cells (CFC) showed no significant difference. All PMC took a rather straightforward migration path to their destinations with little lag time after ingression. This in vivo cell behavior fitted well to a computer simulation with a non-diffusable chemotaxis factor in the cyber-cell migration field. This simulation suggests that PMC recognize their destination from a very early moment of cell migration from the vegetal plate, and implicates that a chemoattractive region is necessary for making the PMC migration pattern. The left- and right-lateral AFC and dorso and ventral CFC were each derived from an unequally divided one-quarter segment of the vegetal plate. This suggests that AFC and CFC have a distinctive ancestor in the vegetal plate, and the PMC are a heterogeneous population at least in terms of their destination in the PMC-ring pattern. [source] The islet autoantibody titres: their clinical relevance in latent autoimmune diabetes in adults (LADA) and the classification of diabetes mellitusDIABETIC MEDICINE, Issue 2 2008A. W. Van Deutekom Abstract Latent autoimmune diabetes in the adult (LADA) is a slowly progressive form of autoimmune diabetes, characterized by diabetes-associated autoantibody positivity. A recent hypothesis proposes that LADA consists of a heterogeneous population, wherein several subgroups can be identified based on their autoimmune status. A systematic review of the literature was carried out to appraise whether the clinical characteristics of LADA patients correlate with the titre and numbers of diabetes-associated autoantibodies. We found that the simultaneous presence of multiple autoantibodies and/or a high-titre anti-glutamic acid decarboxylase (GAD),compared with single and low-titre autoantibody,is associated with an early age of onset, low fasting C-peptide values as a marker of reduced pancreatic B-cell function, a high predictive value for future insulin requirement, the presence of other autoimmune disorders, a low prevalence of markers of the metabolic syndrome including high body mass index, hypertension and dyslipidaemia, and a high prevalence of the genotype known to increase the risk of Type 1 diabetes. We propose a more continuous classification of diabetes mellitus, based on the finding that the clinical characteristics gradually change from classic Type 1 diabetes to LADA and finally to Type 2 diabetes. Future studies should focus on determining optimal cut-off points of anti-GAD for differentiating clinically relevant diabetes mellitus subgroups. [source] Measurements in the Addictions for Triage and Evaluation (MATE): an instrument based on the World Health Organization family of international classificationsADDICTION, Issue 5 2010Gerard M. Schippers ABSTRACT Aims To present and evaluate a measurement tool for assessing characteristics of people with drug and/or alcohol problems for triage and evaluation in treatment. Measurements in the Addictions for Triage and Evaluation (MATE) is composed of 10 modules, selected on the basis of a detailed set of specifications. Conceptually, the MATE was constructed according to the ICD and International Classification of Functioning (ICF) in the World Health Organization (WHO) classification system. Two of the ICF-related modules were newly designed. Design Monitoring feasibility and field-testing in a treatment-seeking population with researcher and clinician-administered test,retest interviews, construct validation with related instruments and evaluation of the dimensional structure of the ICF-related modules. Setting The research was conducted in a large, regional substance abuse treatment centre in the Netherlands and at the Municipal Health Service of Amsterdam. Participants A total of 945 treatment-seeking patients were recruited during routine intakes, 159 of whom were interviewed twice; 32 problem drug users were also recruited from the Amsterdam cohort studies among problem drug users. Findings Completion time was reasonably short, and there were relatively few missing data. The factor structure of the ICF-related modules revealed a three-factor model with an acceptable fit. Inter-rater reliability ranged between 0.75 and 0.92 and was satisfactory, but interviewer reliability ranged between 0.34 and 0.73, indicating that some of subscales need to be improved. Concurrent validity was indicated by significant correlations (>0.50) between the ICF-related modules and the WHO Disability Assessment Schedule II (WHODAS II) and WHO Quality of Life brief version (WHOQOL-BREF). Conclusions The MATE can be used to allocate patients to substance abuse treatment. Because it is a comprehensive but flexible measurement tool that is also practical to use, the MATE is well suited for use in a heterogeneous population. [source] Cellular microparticles: new players in the field of vascular disease?EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2004M. Diamant Abstract Microparticles are small membrane vesicles that are released from cells upon activation or during apoptosis. Cellular microparticles in body fluids constitute a heterogeneous population, differing in cellular origin, numbers, size, antigenic composition and functional properties. Microparticles support coagulation by exposure of negatively charged phospholipids and sometimes tissue factor, the initiator of coagulation in vivo. Microparticles may transfer bioactive molecules to other cells or microparticles, thereby stimulating cells to produce cytokines, cell-adhesion molecules, growth factors and tissue factor, and modulate endothelial functions. Microparticles derived from various cells, most notably platelets but also leucocytes, lymphocytes, erythrocytes and endothelial cells, are present in the circulation of healthy subjects. Rare hereditary syndromes with disturbances in membrane vesiculation leading to a decreased numbers of microparticles clinically present with a bleeding tendency. In contrast, elevated numbers of microparticles are encountered in patients with a great variety of diseases with vascular involvement and hypercoagulability, including disseminated intravascular coagulation, acute coronary syndromes, peripheral arterial disease, diabetes mellitus and systemic inflammatory disease. Finally, microparticles are a major component of human atherosclerotic plaques. In view of their functional properties, cell-derived microparticles may be an important intermediate in the cascade of cellular and plasmatic dysfunctions underlying the process of atherogenesis. [source] Effects of nicotine in the dopaminergic system of mice lacking the alpha4 subunit of neuronal nicotinic acetylcholine receptorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2003L. M. Marubio Abstract The mesostriatal dopaminergic system influences locomotor activity and the reinforcing properties of many drugs of abuse including nicotine. Here we investigate the role of the ,4 nicotinic acetylcholine receptor (nAChR) subunit in mediating the effects of nicotine in the mesolimbic dopamine system in mice lacking the ,4 subunit. We show that there are two distinct populations of receptors in the substantia nigra and striatum by using autoradiographic labelling with 125I ,-conotoxin MII. These receptors are comprised of the ,4, ,2 and ,6 nAChR subunits and non-,4, ,2, and ,6 nAChR subunits. Non-,4 subunit-containing nAChRs are located on dopaminergic neurons, are functional and respond to nicotine as demonstrated by patch clamp recordings. In vivo microdialysis performed in awake, freely moving mice reveal that mutant mice have basal striatal dopamine levels which are twice as high as those observed in wild-type mice. Despite the fact that both wild-type and ,4 null mutant mice show a similar increase in dopamine release in response to intrastriatal KCl perfusion, a nicotine-elicited increase in dopamine levels is not observed in mutant mice. Locomotor activity experiments show that there is no difference between wild-type and mutant mice in basal activity in both habituated and non-habituated environments. Interestingly, mutant mice sustain an increase in cocaine-elicited locomotor activity longer than wild-type mice. In addition, mutant mice recover from depressant locomotor activity in response to nicotine at a faster rate. Our results indicate that ,4-containing nAChRs exert a tonic control on striatal basal dopamine release, which is mediated by a heterogeneous population of nAChRs. [source] THE ADAPTIVE DYNAMICS OF ALTRUISM IN SPATIALLY HETEROGENEOUS POPULATIONSEVOLUTION, Issue 1 2003JEAN-FRANÇOIS LE GALLIARD Abstract., We study the spatial adaptive dynamics of a continuous trait that measures individual investment in altruism. Our study is based on an ecological model of a spatially heterogeneous population from which we derive an appropriate measure of fitness. The analysis of this fitness measure uncovers three different selective processes controlling the evolution of altruism: the direct physiological cost, the indirect genetic benefits of cooperative interactions, and the indirect genetic costs of competition for space. In our model, habitat structure and a continuous life cycle makes the cost of competing for space with relatives negligible. Our study yields a classification of adaptive patterns of altruism according to the shape of the costs of altruism (with decelerating, linear, or accelerating dependence on the investment in altruism). The invasion of altruism occurs readily in species with accelerating costs, but large mutations are critical for altruism to evolve in selfish species with decelerating costs. Strict selfishness is maintained by natural selection only under very restricted conditions. In species with rapidly accelerating costs, adaptation leads to an evolutionarily stable rate of investment in altruism that decreases smoothly with the level of mobility. A rather different adaptive pattern emerges in species with slowly accelerating costs: high altruism evolves at low mobility, whereas a quasi-selfish state is promoted in more mobile species. The high adaptive level of altruism can be predicted solely from habitat connectedness and physiological parameters that characterize the pattern of cost. We also show that environmental changes that cause increased mobility in those highly altruistic species can beget selection-driven self-extinction, which may contribute to the rarity of social species. [source] Mass spectrometry study of ecto-5,-nucleotidase from bull seminal plasmaFEBS JOURNAL, Issue 16 2000Carlo Fini The structure of ecto-5,-nucleotidase from bull seminal plasma, containing a glycosyl-phosphatidylinositol anchor, was studied using mass spectrometry. MALDI-MS analysis of intact protein indicated a mass of 65 568.2 Da for the monomeric form, and it also showed a heterogeneous population of glycoforms with the glycosidic moiety accounting for ,,6000 Da. MALDI-MS analysis showed that Asn53, Asn311, Asn333 and Asn403 were four sites of N -glycosylation. GC-MS analysis provided information on the glycosidic structures linked to the four asparagines. Asn53, Asn311 and Asn333 were linked to high-mannose saccharide chains, whereas the glycan chains linked to Asn403 contained a heterogeneous mixture of oligosaccharides, the high-mannose type structure being the most abundant and hybrid or complex type glycans being minor components. By combining enzymatic and/or chemical hydrolysis with GC-MS analysis, detailed characterization of the glycosyl-phpsphatidylinositol anchor was obtained. MALDI spectral analysis indicated that the glycosyl-phosphatidylinositol core contained EtN(P)Man3GlcNH2 -myo-inositol(P)-glycerol, principally modified by stearoyl and palmitoyl residues or by stearoyl and myristoyl residues to a minor extent. Moreover, 1-palmitoylglycerol and 1-stearoylglycerol outweighed 2-palmitoylglycerol and 2-stearoylglycerol. The combination of chemical and enzymatic digestions of the protein with the mass spectral analysis yielded a complete pattern of S,S bridges. The protein does not contain free thiols and its eight cysteines are linked by intramolecular disulfide bonds, the pairs being: Cys51,Cys57, Cys353,Cys358, Cys365,Cys387 and Cys476,Cys479. This work resolves details of the structure of ecto-5,-nucleotidase, with particular regard to the localization and composition of the glycidic moiety, number and localization of the disulfide bridges and characterization of the glycosyl-phosphatidylinositol anchor. [source] In vivo investigation of CD133 as a putative marker of cancer stem cells in Hep-2 cell lineHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 1 2009Xu Dong Wei PhD Abstract Background Mounting evidence suggests that most tumors consist of a heterogeneous population of cells with a subset population that has the exclusive tumorigenic ability. They are called cancer stem cells (CSCs). CSCs can self-renew to generate additional CSCs and also differentiate to generate phenotypically diverse cancer cells with limited proliferative potential. They have been identified in a variety of tumors. In this study, we identify the marker of CSCs in the established human laryngeal tumor Hep-2 cell line in vivo. Our in vitro experiment shown as CD133, a 5-transmembrane glycoprotein expressed in Hep-2 cell line. CD133 was supposed as a candidate of CSC in laryngeal carcinoma. In this study, the expression of CD133 was detected in a Hep-2 cell line. Applying the magnetic cell sorting (MACS) technology, we reported the results of purifying CD133 positive cells from a Hep-2 cell line. Three-type cells' tumor-forming ability was examined in vivo to identify the marker of CSCs in Hep-2 cell line. Methods CD133 was selected as a putative marker of CSC in laryngeal carcinoma, Hep-2 cell lines. Flow cytometry was used to detect the expression of CD133 in the Hep-2 cell line. Immunomagnetic beads were applied to purify CD133-positive cells. CD133(+), CD133(,) tumor cells, and unsorted Hep-2 cells were injected into severe combined immune deficiency (SCID) mice individually to observe tumor-forming ability. Results Only a small proportion (3.15% ± 0.83%) of cells in the Hep-2 cell line express the CD133 marker. In comparison with CD133(,) tumor cells and unsorted cells, CD133(+) cells possess a marked capacity for tumor formation in vivo (p <.05). Conclusion CD133 is 1 of the markers for CSCs in human laryngeal tumors of the Hep-2 cell line. Work on the characterization of these cells provides a powerful tool to investigate the tumorigenic process in the larynx and to develop therapies targeting the CSC. © 2008 Wiley Periodicals, Inc. Head Neck, 2009 [source] Measurement of informal care: an empirical study into the valid measurement of time spent on informal caregivingHEALTH ECONOMICS, Issue 5 2006Bernard van den Berg Abstract The incorporation of informal care into economic evaluations of health care is troublesome. The debate focuses on the valuation of time spent on informal caregiving, while time measurement, a related and may be even a more important issue, tends to be neglected. Valid time measurement is a necessary condition for the valuation of informal care. In this paper, two methods of time measurement are compared and evaluated: the diary, which is considered the gold standard, and the recall method, which is applied more often. The main objective of this comparison is to explore the validity of the measurement of time spent on providing informal care. In addition, this paper gives empirical evidence regarding the measurement of joint production and the separation between ,normal' housework and additional housework due to the care demands of the care recipients. Finally, the test,retest stability for the recall method is assessed. A total of 199 persons giving informal care to a heterogeneous population of care recipients completed the diary and the recall questionnaire. Corrected for joint production, informal caregivers spent almost 5.8 h a day on providing informal care. If one assumes that respondents take into account joint production when completing the recall questionnaire, the recall method is a valid instrument to measure time spent on providing informal care compared to the diary. Otherwise, the recall method is likely to overestimate the time spent on providing informal care. Moreover, the recall method proves to be unstable over time. This could be due to learning effects from completing a diary. Copyright © 2005 John Wiley & Sons, Ltd. [source] Molecular characterisation of GSD III subjects and identification of six novel mutations in AGL,,HUMAN MUTATION, Issue 6 2002S. Lucchiari Abstract Deficiency of amylo-1,6-glucosidase, 4-,-glucanotransferase enzyme (AGL or glycogen debranching enzyme) is causative of Glycogen Storage Disease type III, a rare autosomal recessive disorder of glycogen metabolism. The disease has been demonstrated to show clinical and biochemical heterogeneity, reflecting the genotype-phenotype heterogeneity among different subjects. The aim of this study was the molecular characterisation of eight unrelated patients from an ethnically heterogeneous population (six Italians, one from India and another one from Tunisia). We describe six novel mutations responsible for the disease (C234R, R675W, 2547delG, T38A, W1327X, IVS6 +3 A>G) and the presence in two Italian subjects of a splice variant (IVS21+1 G>A) already described elsewhere. This last one is confirmed to be the most frequent mutation among the Italian patients come to our observation, accounting for 28% of 21 patients. One subject was found to be a compound heterozygous. Our data confirm the substantial genetic heterogeneity of this disease. Consequently, the strategy of mutation finding based on screening of recurrent common mutations is limited, as far as regards Italian GSD III patients, to check for the presence of IVS21+1 G>A. © 2002 Wiley-Liss, Inc. [source] Cardiomyocyte precursors and telocytes in epicardial stem cell niche: electron microscope imagesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2010Mihaela Gherghiceanu Abstract A highly heterogeneous population of stem and progenitor cells has been described by light immunohistochemistry in the mammalian adult heart, but the ultrastructural identity of cardiac stem cells remains unknown. Using electron microscopy, we demonstrate the presence of cells with stem features in the adult mouse heart. These putative cardiac stem cells are small (6,10 ,m), round cells, with an irregular shaped nucleus, large nucleolus, few endoplasmic reticulum cisternae and mitochondria, but numerous ribosomes. Stem cells located in the epicardial stem cell niche undergo mitosis and apoptosis. Cells with intermediate features between stem cells and cardiomyocyte progenitors have also been seen. Moreover, electron microscopy showed that cardiomyocyte progenitors were added to the peripheral working cardiomyocytes. Telocytes make a supportive interstitial network for stem cells and progenitors in the stem cell niche. This study enhances the hypothesis of a unique type of cardiac stem cell and progenitors in different stages of differentiation. In our opinion, stem cells, cardiomyocyte progenitors and telocytes sustain a continuous cardiac renewal process in the adult mammalian heart. [source] Tropical forest tree mortality, recruitment and turnover rates: calculation, interpretation and comparison when census intervals varyJOURNAL OF ECOLOGY, Issue 6 2004SIMON L. LEWIS Summary 1Mathematical proofs show that rate estimates, for example of mortality and recruitment, will decrease with increasing census interval when obtained from censuses of non-homogeneous populations. This census interval effect could be confounding or perhaps even driving conclusions from comparative studies involving such rate estimates. 2We quantify this artefact for tropical forest trees, develop correction methods and re-assess some previously published conclusions about forest dynamics. 3Mortality rates of > 50 species at each of seven sites in Africa, Latin America, Asia and Australia were used as subpopulations to simulate stand-level mortality rates in a heterogeneous population when census intervals varied: all sites showed decreasing stand mortality rates with increasing census interval length. 4Stand-level mortality rates from 14 multicensus long-term forest plots from Africa, Latin America, Asia and Australia also showed that, on average, mortality rates decreased with increasing census interval length. 5Mortality, recruitment or turnover rates with differing census interval lengths can be compared using the mean rate of decline from the 14 long-term plots to standardize estimates to a common census length using ,corr = , × t0.08, where , is the rate and t is time between censuses in years. This simple general correction should reduce the bias associated with census interval variation, where it is unavoidable. 6Re-analysis of published results shows that the pan-tropical increase in stem turnover rates over the late 20th century cannot be attributed to combining data with differing census intervals. In addition, after correction, Old World tropical forests do not have significantly lower turnover rates than New World sites, as previously reported. Our pan-tropical best estimate adjusted stem turnover rate is 1.81 ± 0.16% a,1 (mean ± 95% CI, n = 65). 7As differing census intervals affect comparisons of mortality, recruitment and turnover rates, and can lead to erroneous conclusions, standardized field methods, the calculation of local correction factors at sites where adequate data are available, or the use of our general standardizing formula to take account of sample intervals, are to be recommended. [source] The zinc-finger protein ZFR is critical for Staufen 2 isoform specific nucleocytoplasmic shuttling in neuronsJOURNAL OF NEUROCHEMISTRY, Issue 1 2006George Elvira Abstract In mammalian neurons, transport and translation of mRNA to individual potentiated synapses is believed to occur via a heterogeneous population of RNA granules. To identify components of Staufen2-containing granules, we used the yeast two-hybrid system. A mouse fetal cDNA library was screened with the N-terminal fragment of Staufen2 as bait. ZFR, a three zinc finger protein, was identified as an interacting protein. Confocal microscopy showed that ZFR, although mainly nuclear, was also found in the somatodendritic compartment of primary hippocampal neurons where it localized as granule-like structures. Co-localization with Staufen2 was observed in several granules. Biochemical analyses (immunoprecipitation, cell fractionation) further confirmed the ZFR/Staufen2 association. ZFR was shown to interact with at least the Staufen262 isoform, but not with Staufen1. ZFR also co-fractionated with ribosomes and Staufen259 and Staufen252 in a sucrose gradient. Interestingly, knockdown expression of ZFR through RNA interference in neurons relocated specifically the Staufen262, but not the Staufen259, isoform to the nucleus. Our results demonstrate that ZFR is a native component of Staufen2-containing granules and likely plays its role during early steps of RNA transport and localization. They also suggest that one of these roles may be linked to Staufen262 -containing RNA granule formation in the nucleus and/or to their nucleo-cytoplasmic shuttling. [source] Cyclic acetal hydroxyapatite composites and endogenous osteogenic gene expression of rat marrow stromal cellsJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 6 2010Minal Patel Abstract In this study, bone marrow stromal cells (BMSCs) were differentiated on cyclic acetal composites containing hydroxyapatite (HA) particles (110 or 550 nm). These composites were evaluated for their role in influencing osteogenic signalling by encapsulated BMSCs. While a number of factors exert influence on osteogenic signalling during the production of an osteogenic matrix, we hypothesize that HA particles may upregulate bone growth factor expression due to enhanced BMSC adhesion. To this end, fluorescence-activated cell sorting (FACS) analysis was performed for the evaluation of BMSC surface marker expression after culture on two-dimensional (2D) cyclic acetal/HA composites. Three-dimensional (3D) composites were then fabricated by incorporating 110 or 550 nm HA particles at 5, 10 and 50 ng/ml concentrations. Bone growth factor molecules (TGF,1, FGF-2 and PDGFa), bone biomarker molecules (ALP, OC, OPN and OCN) and extracellular matrix-related molecules (FN, MMP-13, Dmp1 and aggrecan) were selected for evaluation of osteogenic signalling mechanisms when in presence of these composites. FACS results at day 0 demonstrated that BMSCs were a heterogeneous population with a small percentage of cells staining positive for CD29, CD90 and CD51/61, while staining negative for CD34 and CD45. At day 3, a significant enrichment of cells staining strongly for CD29, CD90 and CD51/61 was achieved. Gene expression patterns for bone growth factors and extracellular matrix molecules were found to be largely dependent upon the size of HA particles. Bone marker molecules, except OCN, had unaltered expression patterns in response to the varied size of HA particles. Overall, the results indicate that larger-sized HA particles upregulate PDGF and these groups were also associated with the most significant increase in osteodifferentiation markers, particularly ALP. Our results suggest that endogenous signalling is dependent upon material properties. Furthermore, we propose that studying gene expression patterns induced by the surrounding biomaterials environment is a fundamental step in the creation of engineered tissues. Copyright © 2010 John Wiley & Sons, Ltd. [source] Differential Mortality and the Design of the Italian System of Public PensionsLABOUR, Issue 2003Graziella Caselli After reviewing the secular trends in elderly mortality in Italy, and the evolution of regional differences in survival over the last three decades, we evaluate the impact, on the conversion factors introduced by the Dini reform, of a further decline in elderly mortality over the next few decades. We compute the conversion factors using a close approximation to the unknown formula employed in the Dini reform but allowing for gender- and region-specific survival probabilities. Our results leave no doubt about the importance of frequently updating the conversion factors in the light of the rapid increase in elderly survival. The paper also quantifies to what extent gender- and region-specific conversion factors may differ from their currently legislated values, that only vary by age. Finally, we recognize that the actuarial fairness of the system introduced by the recent reform can only be guaranteed on average and that, in the presence of a heterogeneous population of individuals that differ considerably in their mortality prospects, the current system implies a substantial degree of redistribution from high-mortality groups (typically characterized by low income and low wealth) to low-mortality groups (typically characterized by high income and high wealth). [source] Allergic rhinitis: prevalence and possible risk factors in a Gulf Arab populationALLERGY, Issue 2 2010S. Alsowaidi To cite this article: Alsowaidi S, Abdulle A, Shehab A, Zuberbier T, Bernsen R. Allergic rhinitis: prevalence and possible risk factors in a Gulf Arab population. Allergy 2010; 65: 208,212 DOI: 10.1111/j.1398-9995.2009.02123.x. Abstract Background:, Epidemiological studies mainly from Europe, the USA and Asia indicate a high prevalence of allergic rhinitis (AR) in modern societies. However, little is known about AR among the heterogeneous population of the United Arab Emirates (UAE). Objectives: To estimate the prevalence of AR and its independent risk factors in Al-Ain City, UAE. Methods:, We used a validated, self-administered questionnaire modified from the ISAAC study to collect data from a two stage randomly selected sample of 10 000 school children. Overall, 7550 subjects (aged 13 years and above, siblings, and their parents) responded. We assessed the prevalence of AR (both crude and standardized prevalence of previous 12 months) as well as the independent relationship of AR with age, gender, education, nationality and family history by means of logistic regression. Results:, The response rate was 76%. A total of 6543 subjects (median age 30 years) were included in the final analysis. Self-reported prevalence of AR (having symptoms in the past 12 months) was 36%, while adjusted values for sex/age yielded a prevalence of 32%. Regression analysis revealed that AR was independently associated with family history, Arab origin, younger age, female gender and higher education. Conclusions:, The relatively high prevalence of AR found in this study may be attributable to modernization and genetic factors. Further studies on the impact of rapid environmental and cultural changes on AR in the Arab countries are needed and currently planned in conjunction with GA2LEN (Global Allergy and Asthma European Network). [source] Endotoxin-Induced Myeloid-Derived Suppressor Cells Inhibit Alloimmune Responses via Heme Oxygenase-1AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009V. De Wilde Inflammation and cancer are associated with impairment of T-cell responses by a heterogeneous population of myeloid-derived suppressor cells (MDSCs) coexpressing CD11b and GR-1 antigens. MDSCs have been recently implicated in costimulation blockade-induced transplantation tolerance in rats, which was under the control of inducible NO synthase (iNOS). Herein, we describe CD11b+GR-1+MDSC-compatible cells appearing after repetitive injections of lipopolysaccharide (LPS) using a unique mechanism of suppression. These cells suppressed T-cell proliferation and Th1 and Th2 cytokine production in both mixed lymphocyte reaction and polyclonal stimulation assays. Transfer of CD11b+ cells from LPS-treated mice in untreated recipients significantly prolonged skin allograft survival. They produced large amounts of IL-10 and expressed heme oxygenase-1 (HO-1), a stress-responsive enzyme endowed with immunoregulatory and cytoprotective properties not previously associated with MDSC activity. HO-1 inhibition by the specific inhibitor, SnPP, completely abolished T-cell suppression and IL-10 production. In contrast, neither iNOS nor arginase 1 inhibition did affect suppression. Importantly, HO-1 inhibition before CD11b+ cell transfer prevented the delay of allograft rejection revealing a new MDSC-associated suppressor mechanism relevant for transplantation. [source] The Cocaine- and Amphetamine-regulated Transcript (CART) Immunoreactivity in the Amygdala of the PigANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2010M. Równiak With 5 figures and 1 table Summary The distribution and morphology of neurons containing cocaine- and amphetamine-regulated transcript (CART) was investigated in the pig amygdala. CART- immunoreactive (CART-IR) cell bodies were rarely observed in the pig amygdala and most often they were present in the posterior (small-celled) parts of the basolateral and basomedial nuclei. In all other subdivisions only a small number of randomly scattered pericarya were present. In every region studied the CART-IR neurons formed a heterogeneous population consisting mostly of small, rounded or slightly elongated cell bodies, with a few poorly branched, smooth dendrites. In general, the morphological features of these cells clearly resembled non-pyramidal Golgi type II interneurons. Some randomly scattered CART-IR cell bodies were significantly larger and they demonstrated features of pyramidal-like Golgi type I projecting neurons. The highest densities of CART-IR fibres were evident within the central and medial nuclei. Moderate to high expression was found within the large-celled part of the basolateral nucleus and moderate to low levels in the lateral, basomedial and cortical nuclei. The routine double-labelling studies with antisera directed against CART and somatostatin (SOM), or neuropeptide Y (NPY), or cholecystokinin (CCK), or vasoactive intestinal peptide (VIP), or substance P (SP) demonstrated that, in general, these peptides do not co-exist in the CART-IR neurons. However, small subpopulations of the CART-IR fibres contained SOM, CCK, VIP or SP together. [source] Locally advanced prostate cancer: the role of surgical managementBJU INTERNATIONAL, Issue 4 2009Kelly L. Stratton Among the heterogeneous population of patients with prostate cancer, a high-risk group with locally advanced prostate cancer (LAPC) present a diagnostic and therapeutic dilemma. Although the incidence of LAPC has decreased with screening since the introduction of prostate-specific antigen (PSA) testing, significantly many patients are still diagnosed with LAPC. These patients are by definition at higher risk of metastatic disease and worse outcomes. The role of radical prostatectomy (RP) in this population has been debated, as the combination of radiotherapy and hormonal therapy is becoming used more frequently for LAPC. Unfortunately, the clinical staging and evaluation of LAPC is a challenge that results in possibly understaging or overstaging these patients. This further complicates therapeutic decision-making, and as a result no established standard treatment has been proposed. Like other patients with prostate cancer, individualized therapeutic choices are essential and depend on a multitude of factors. Herein we examine the role of RP for managing LAPC and attempt to emphasize how the risk of distant disease and difficulty with clinical staging might favour incorporating a surgical approach as part of the therapy for patients with LAPC. [source] Caring for people with learning disability: a survey of general practitioners' attitudes in Southampton and South-west HampshireBRITISH JOURNAL OF LEARNING DISABILITIES, Issue 1 2000Ken SteinArticle first published online: 24 DEC 200 The aim of the present paper was to examine general practitioners' (GPs') beliefs about: the demands made on the primary care team by people with learning disability; their confidence in meeting health care needs and perceived training requirements; attitudes towards specialist or generic health service provision, and current contact with specialist teams; and attitudes towards screening in people with learning disability. A postal questionnaire was sent to a randomly selected partner from 95% of the practices in the Southampton and South-west Hampshire Health District. Forty-eight (75%) GPs responded and few were undecided about the demands placed on primary care teams, but beliefs were mixed. Most GPs were confident in dealing with the medical care needs of people with learning disability and the majority felt that training courses would not be worthwhile, except to learn more about specialist services where contact was very low and a ,link worker' scheme had had little apparent impact. Most respondents agreed that GPs should meet the medical needs of people with learning disability as part of general medical services and approximately half had a positive attitude towards providing regular health checks. Respondents were cautious about offering cervical cancer screening to women with learning disability. A small minority suggested that they would take no action to follow up a non-attendance for mammography. As a heterogeneous population, it is not surprising that GPs' attitudes vary widely. Further research is required to establish the nature and scale of demands made on primary health care teams, and to evaluate systematic means of addressing health care needs of people with learning disability. [source] Heterogeneity of the neuropeptide Y (NPY) contractile and relaxing receptors in horse penile small arteriesBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2004Dolores Prieto The distribution of neuropeptide Y (NPY)-immunorective nerves and the receptors involved in the effects of NPY upon electrical field stimulation (EFS)- and noradrenaline (NA)-elicited contractions were investigated in horse penile small arteries. NPY-immunoreactive nerves were widely distributed in the erectile tissues with a particularly high density around penile intracavernous small arteries. In small arteries isolated from the proximal part of the corpora cavernosa, NPY (30 nM) produced a variable modest enhancement of the contractions elicited by both EFS and NA. At the same concentration, the NPY Y1 receptor agonist, [Leu31, Pro34]NPY, markedly potentiated responses to EFS and NA, whereas the NPY Y2 receptor agonist, NPY(13,36), enhanced exogenous NA-induced contractions. In arteries precontracted with NA, NPY, peptide YY (PYY), [Leu31, Pro34]NPY and the NPY Y2 receptor agonists, N - acetyl[Leu28,31]NPY (24,36) and NPY(13,36), elicited concentration-dependent contractile responses. Human pancreatic polypeptide (hPP) evoked a biphasic response consisting of a relaxation followed by contraction. NPY(3,36), the compound 1229U91 (Ile-Glu-Pro-Dapa-Tyr-Arg-Leu-Arg-Tyr-NH2, cyclic(2,4,)diamide) and eventually NPY(13,36) relaxed penile small arteries. The selective NPY Y1 receptor antagonist BIBP3226 ((R)- N2 -(diphenacetyl)- N -[(4-hydroxyphenyl)methyl]D -arginineamide) (0.3 ,M) shifted to the right the concentration,response curves to both NPY and [Leu31, Pro34]NPY and inhibited the contractions induced by the highest concentrations of hPP but not the relaxations observed at lower doses. In the presence of the selective NPY Y2 receptor antagonist BIIE0246 ((S)- N2-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b,e]azepin-11-y1]-1-piperazinyl]-2-oxoethyl]cyclo-pentyl- N -[2-[1,2-dihydro,3,5 (4H)-dioxo-1,2-diphenyl-3H -1,2, 4-triazol-4-yl]ethyl]-argininamide) (0.3 ,M), the Y2 receptor agonists NPY(13,36) and N - acetyl[Leu28,31]NPY (24,36) evoked potent slow relaxations in NA-precontracted arteries, under conditions of nitric oxide (NO) synthase blockade. Mechanical removal of the endothelium markedly enhanced contractions of NPY on NA-precontracted arteries, whereas blockade of the neuronal voltage-dependent Ca2+ channels did not alter NPY responses. These results demonstrate that NPY can elicit dual contractile/relaxing responses in penile small arteries through a heterogeneous population of postjunctional NPY receptors. Potentiation of the contractions evoked by NA involve both NPY Y1 and NPY Y2 receptors. An NO-independent relaxation probably mediated by an atypical endothelial NPY receptor is also shown and unmasked in the presence of selective antagonists of the NPY contractile receptors. British Journal of Pharmacology (2004) 143, 976,986. doi:10.1038/sj.bjp.0706005 [source] Neoplastic stem cells: A novel therapeutic target in clinical oncologyCANCER, Issue 10 2006Axel Schulenburg MD Abstract Cancer is among the leading causes of morbidity and mortality in the Western world. Despite recent advances, most therapeutic approaches fail to eradicate the entire neoplastic clone. The remaining cells often develop metastasis and/or recurrences and therefore may represent attractive targets of therapy. A new exciting concept in this regard suggests that each neoplasm represents a heterogeneous population of cells that pertain to long-term tumor growth both in vivo in the natural host and in experimental animals. This concept postulates the existence of small fractions of ,tumor stem cells' that exhibit a capacity for self-renewal and unlimited growth and therefore are distinct from their progeny. Based on these hypotheses, the targeting of neoplastic stem cells is considered indispensable for eradication of the entire clone and for the development of curative treatment approaches. However, tumor stem cells often may be quiescent cells and may express a different profile of targets compared with ,more mature' tumor cells. Therefore, current efforts have attempted to characterize target expression profiles in cancer stem cells in various malignancies. In the this review, the authors have provided a brief summary of the current knowledge of neoplastic stem cells and the application of respective concepts in translational oncology with the ultimate objective of improving anticancer therapy. Cancer 2006. © 2006 American Cancer Society. [source] The Study of Protein Folding and Dynamics by Determination of Intramolecular Distance Distributions and Their Fluctuations Using Ensemble and Single-Molecule FRET Measurements,CHEMPHYSCHEM, Issue 5 2005Elisha Haas Prof. Abstract The folding and dynamics of globular proteins is a multidimensional problem. The structures of the heterogeneous population of refolding protein molecules are characterized by multiple distances and time constants. Deciphering the mechanism of folding depends on studies of the processes rather than the folded structures alone. Spectroscopy is indispensable for these sorts of studies. Herein, it is shown that the determination of intramolecular distance distributions by ensemble and single-molecule FRET experiments enable the exploration of partially folded states of refolding protein molecules. [source] Splenic stromal cells mediate IL-7 independent adult lymphoid tissue inducer cell survivalEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2010Tie Zheng Hou Abstract Lymphoid tissue inducer cells (LTi) play an important role in the development of lymphoid tissue in embryos. Adult CD4+CD3, LTi-like cells present a similar phenotype and gene expression to their embryonic counterpart and have important roles in CD4+ T-cell memory and lymphoid tissue recovery following viral infection. However, adult LTi-like cells are heterogeneous populations and the factors that regulate their survival and accumulation within secondary lymphoid organs remain unclear, in particular whether the T-zone stroma is involved. Here we report the identification and characterization of a distinct subset of podoplanin+ murine splenic stromal cells that support adult LTi-like cell survival. We have identified and isolated CD45,podoplanin+ stromal cell populations which have a similar but distinct phenotype to T-zone reticular cells in LN. CD45,podoplanin+ fibroblast-like cells mediate LTi-like cell survival in vitro; surprisingly this was not dependent upon IL-7 as revealed through blocking Ab experiments and studies using LTi-like cells unable to respond to , chain cytokines. Our findings show that adult LTi-like cells require extrinsic signals from podoplanin+ splenic stromal cells to survive and suggest that IL-7 is not necessary to mediate their survival in the adult spleen. [source] A critical evaluation of genomic control methods for genetic association studiesGENETIC EPIDEMIOLOGY, Issue 4 2009Tony Dadd Abstract Population stratification is an important potential confounder of genetic case-control association studies. For replication studies, limited availability of samples may lead to imbalanced sampling from heterogeneous populations. Genomic control (GC) can be used to correct ,2 test statistics which are presumed to be inflated by a factor ,; this may be estimated by a summary ,2 value (,median or ,mean) from a set of unlinked markers. Many studies applying GC methods have used fewer than 50 unlinked markers and an important question is whether this can adequately correct for population stratification. We assess the behavior of GC methods in imbalanced case-control studies using simulation. SNPs are sampled from two subpopulations with intra-continental levels of FST (,0.005) and sampling schemata ranging from balanced to completely imbalanced between subpopulations. The sampling properties of ,median and ,mean are explored using 6,1,600 unlinked markers to estimate Type 1 error and power empirically. GC corrections based on the ,2 -distribution (GCmedian or GCmean) can be anti-conservative even when more than 100 single nucleotide polymorphisms (SNPs) are genotyped and realistic levels of population stratification exist. The GCF procedure performs well over a wider range of conditions, only becoming anti-conservative at low levels of , and with fewer than 25 SNPs genotyped. A substantial loss of power can arise when population stratification is present, but this is largely independent of the number of SNPs used. A literature survey shows that most studies applying GC have used GCmedian or GCmean, rather than GCF, which is the most appropriate GC correction method. Genet. Epidemiol. 2009. © 2008 Wiley Liss, Inc. [source] | |||||||||||||||||||||||||||||||