4,120 research outputs found

    The analysis of quantitative variation in natural populations with isofemale strains

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    Isofemale strains are having an increasing role in the analysis of variability of ecological and behavioural traits in natural populations. This paper therefore considers the association between heritability and phenotypic variation within and between isofemale strains. Heritability from an isofemale strain analysis approximates narrow heritability over a wide range of dominance values, particularly when genes contributing to variation in a trait are at intermediate frequencies. Meaningful heritability estimates require that isofemale strains are maintained at a population size greater than 50 and tested within 5 generations after establishment. Values of heritabilities for morphological traits in Drosophila melanogaster were similar to those estimated from a conventional sib analysis. Published data on isofemale strains can therefore be put into a theoretical framework. The contribution of isofemale strain analyses to the debate about the number of loci affection variation in quantitative traits is briefly discussed

    Geographic Analysis of Blood Lead Levels in New York State Children Born 1994–1997

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    We examined the geographic distribution of the blood lead levels (BLLs) of 677,112 children born between 1994 and 1997 in New York State and screened before 2 years of age. Five percent of the children screened had BLLs higher than the current Centers for Disease Control and Prevention action level of 10 μg/dL. Rates were higher in upstate cities than in the New York City area. We modeled the relationship between BLLs and housing and socioeconomic characteristics at the ZIP code level. Older housing stock, a lower proportion of high school graduates, and a higher percentage of births to African-American mothers were the community characteristics most associated with elevated BLLs. Although the prevalence of children with elevated BLLs declined 44% between those born in 1994 and those born in 1997, the rate of improvement may be slowing down. Lead remains an environmental health problem in inner-city neighborhoods, particularly in upstate New York. We identified areas having a high prevalence of children with elevated BLLs. These communities can be targeted for educational and remediation programs. The model locates areas with a higher or lower prevalence of elevated BLLs than expected. These communities can be studied further at the individual level to better characterize the factors that contribute to these differences

    Childhood Correlates of Blood Lead Levels in Mumbai and Delhi

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    BACKGROUND: Lead exposure has previously been associated with intellectual impairment in children in a number of international studies. In India, it has been reported that nearly half of the children have elevated blood lead levels (BLLs). However, little is known about risk factors for these elevated BLLs. METHODS: We conducted a retrospective cross-sectional analysis of data from the Indian National Family Health Survey, a population-based study conducted in 1998–1999. We assessed potential correlates of BLLs in 1,081 children who were < 3 years of age and living in Mumbai or Delhi, India. We examined factors such as age, sex, religion, caste, mother’s education, standard of living, breast-feeding, and weight/height percentile. RESULTS: Most children (76%) had BLLs between 5 and 20 μg/dL. Age, standard of living, weight/height percentile, and total number of children ever born to the mother were significantly associated with BLLs (log transformed) in multivariate regression models. Compared with children ≤3 months of age, children 4–11 and 12–23 month of age had 84 and 146% higher BLLs, respectively (p < 0.001). A low standard of living correlated with a 32.3% increase in BLLs (p = 0.02). Children greater than the 95th percentile for their weight/height had 31% (p = 0.03) higher BLLs compared with those who were below the 5th percentile for their weight/height. CONCLUSIONS: Our study found various factors correlated with elevated BLLs in children. The correlation between greater than the 95th percentile weight/height and higher BLL may reflect an impact of lead exposure on body habitus. Our study may help in targeting susceptible populations and identifying correctable factors for elevated BLLs in Mumbai and Delhi

    Sociological and Communication-Theoretical Perspectives on the Commercialization of the Sciences

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    Both self-organization and organization are important for the further development of the sciences: the two dynamics condition and enable each other. Commercial and public considerations can interact and "interpenetrate" in historical organization; different codes of communication are then "recombined." However, self-organization in the symbolically generalized codes of communication can be expected to operate at the global level. The Triple Helix model allows for both a neo-institutional appreciation in terms of historical networks of university-industry-government relations and a neo-evolutionary interpretation in terms of three functions: (i) novelty production, (i) wealth generation, and (iii) political control. Using this model, one can appreciate both subdynamics. The mutual information in three dimensions enables us to measure the trade-off between organization and self-organization as a possible synergy. The question of optimization between commercial and public interests in the different sciences can thus be made empirical.Comment: Science & Education (forthcoming

    Correction to: The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson's disease.

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    Following publication of the original article [1], the author identified an error in Fig. 4E. The data and statistics were correct, but the synaptophysin blot was incorrect. The incorrect (Fig. 1) and correct figure (Fig. 2) are shown in this correction article. (Figure presented.)

    The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson's disease

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    Elevated iron in the SNpc may play a key role in Parkinson's disease (PD) neurodegeneration since drug candidates with high iron affinity rescue PD animal models, and one candidate, deferirpone, has shown efficacy recently in a phase two clinical trial. However, strong iron chelators may perturb essential iron metabolism, and it is not yet known whether the damage associated with iron is mediated by a tightly bound (eg ferritin) or lower-affinity, labile, iron pool. Here we report the preclinical characterization of PBT434, a novel quinazolinone compound bearing a moderate affinity metal-binding motif, which is in development for Parkinsonian conditions. In vitro, PBT434 was far less potent than deferiprone or deferoxamine at lowering cellular iron levels, yet was found to inhibit iron-mediated redox activity and iron-mediated aggregation of α-synuclein, a protein that aggregates in the neuropathology. In vivo, PBT434 did not deplete tissue iron stores in normal rodents, yet prevented loss of substantia nigra pars compacta neurons (SNpc), lowered nigral α-synuclein accumulation, and rescued motor performance in mice exposed to the Parkinsonian toxins 6-OHDA and MPTP, and in a transgenic animal model (hA53T α-synuclein) of PD. These improvements were associated with reduced markers of oxidative damage, and increased levels of ferroportin (an iron exporter) and DJ-1. We conclude that compounds designed to target a pool of pathological iron that is not held in high-affinity complexes in the tissue can maintain the survival of SNpc neurons and could be disease-modifying in PD

    Genetic and biochemical analyses of chromosome and plasmid gene homologues encoding ICL and ArCP domains in Vibrioanguillarum strain 775

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    Anguibactin, the siderophore produced by Vibrio anguillarum 775 is synthesized from 2,3-dihydroxybenzoic acid (DHBA), cysteine and hydroxyhistamine via a nonribosomal peptide synthetase (NRPS) mechanism. Most of the genes encoding anguibactin biosynthetic proteins are harbored by the pJM1 plasmid. In this work we report the identification of a homologue of the plasmid-encoded angB on the chromosome of strain 775. The product of both genes harbor an isochorismate lyase (ICL) domain that converts isochorismic acid to 2,3-dihydro-2,3-dihydroxybenzoic acid, one of the steps of DHBA synthesis. We show in this work that both ICL domains are functional in the production of DHBA in V. anguillarum as well as in E. coli. Substitution by alanine of the aspartic acid residue in the active site of both ICL domains completely abolishes their isochorismate lyase activity in vivo. The two proteins also carry an aryl carrier protein (ArCP) domain. In contrast with the ICL domains only the plasmid encoded ArCP can participate in anguibactin production as determined by complementation analyses and site-directed mutagenesis in the active site of the plasmid encoded protein, S248A. The site-directed mutants, D37A in the ICL domain and S248A in the ArCP domain of the plasmid encoded AngB were also tested in vitro and clearly show the importance of each residue for the domain function and that each domain operates independently.
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