1,281 research outputs found

    Synthesis of pH stable, blue light-emitting diode-excited, fluorescent silica nanoparticles and effects on cell behavior

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    Shin-Woo Ha,1 Jin-Kyu Lee,2 George R Beck Jr1,3,4 1Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA, USA; 2Department of Chemistry, Seoul National University, Seoul, South Korea; 3The Atlanta Department of Veterans Affairs Medical Center, Decatur, 4The Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA Abstract: To date, delivery of light-emitting diode (LED)-activated compounds to cells and tissue remains a challenge. Silica-based materials possess good biocompatibility and have advantages of control of size and shape. Fluorescent silica nanoparticles (NPs) have been synthesized and used for applications such as cell tracking and tumor identification. Here, we report the synthesis and optimization of fluorescent silica NPs, which incorporate a naphthalimide dye with triethoxysilanes that are excited by the blue LED wavelength (LEDex NPs). The NPs can be imaged in the 420–470 nm wavelength, demonstrate a high quantum yield, are stable in a range of pH, and are taken into the cells. Therefore, these NPs represent a novel imaging technology for biomedical applications. Keywords: naphthalimide, imaging, bone marrow stromal cell migration, reduced toxicity&nbsp

    Modulation of GR transcriptional signalling by HIV-1 Vpr insights into regulation by progestins

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    Includes bibliographical references.It has been 30 years since HIV was first discovered, yet the molecular mechanisms whereby the virus mediates its pathogenic effects have not yet been completely elucidated. The glucocorticoid receptor (GR) is a ligand-activated host transcription factor, which mediates anti-inflammatory effects in response to stimulation with glucocorticoids (GC). One of the HIV-1 accessory proteins, Vpr, is highly immunosuppressive and contributes to suppression of the immune system thereby creating an environment favourable for viral proliferation. Vpr has been previously reported to act as a GR co-activator on glucocorticoid response element (GRE) containing promoters. Thus, the GR appears likely to play a role in HIV-1 pathogenesis. Contraceptive usage is also likely to affect HIV-1 pathogenesis as some hormonal contraceptives can bind to and activate the GR. Progesterone (P4) regulates the female reproductive system and the synthetic progestins medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-A) are extensively used as injectable contraceptives. MPA has been shown to act as a partial or full GR agonist and recent evidence indicates that injectable MPA increases HIV-1 acquisition and transmission. The molecular mechanisms of this remain unclear, but may involve decreasing the thickness of the vaginal epithelium as well as actions via the GR that affect gene expression in the cervo-vaginal environment and/or elsewhere. This study aims to investigate the actions of GC's, P4, MPA and NET-A via the GR in the absence and presence of Vpr protein towards gaining some insight into the potential interplay between the host GR, contraceptive use, HIV-1 pathogenesis, and the mechanisms thereof

    Porcine stress syndrome: an animal model for the neuroleptic malignant syndrome?

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    The porcine stress syndrome is a genetic disorder of swine which, like neuroleptic malignant syndrome, is characterized by hyperthermia, muscle rigidity, and autonomic dysfunction. We investigated the porcine stress syndrome as a possible animal model for neuroleptic malignant syndrome in two ways. First, we administered haloperidol and lithium carbonate, alone and in combination, to susceptible and resistant swine. Second, we attempted to prevent the syndrome by pretreating animals with bromocriptine. Porcine stress syndrome was induced in 2 of 3 susceptible and 1 of 3 resistant swine by combined treatment with lithium and haloperidol, but was not triggered by treatment with lithium or haloperidol alone. Pretreatment with bromocriptine conferred no protection against the syndrome.LR: 20061115; PUBM: Print; GR: MH-31154/MH/NIMH; GR: MH-36224/MH/NIMH; JID: 0213264; 0 (Receptors, Dopamine); 151-67-7 (Halothane); 25614-03-3 (Bromocriptine); 52-86-8 (Haloperidol); 554-13-2 (Lithium Carbonate); 7439-93-2 (Lithium); ppublishSource type: Electronic(1

    An examination of some proposed correlates of depressive illness

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    Ten depressed subjects, ten recovered subjects and ten control subjects were assessed by the use of the Beck Depression Inventory, the Hostility Direction of Hostility Questionnaire, the Rotter Internal-External Control Scale and the Bene Anthony Family Relations Test. The depressed subjects differed significantly from the recovered and control group in the amount of hostility shown, and from the control group in the direction of hostility. Depressives did not differ significantly from the other two groups in their scores of the amount of internal control, nor in the way they perceived family relations in childhood. The results were seen to support Freud's and Bibring's theories concerning amount and direction of hostility. Rotter's internal-external control hypothesis could not be demonstrated. Nor did family feelings in childhood contribute to Bibring's theory of helplessness. The Family Relations Test was not able to distinguish between family relations of depressives and non- depressives

    Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders

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    Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets

    Food consumption frequency and perceived stress and depressive symptoms among students in three European countries

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    Mikolajczyk RT, El Ansari W, Maxwell AE. Food consumption frequency and perceived stress and depressive symptoms among students in three European countries. Nutrition Journal. 2009;8(1):31.Background: Certain foods might be more frequently eaten under stress or when higher levels of depressive symptoms are experienced. We examined whether poor nutritional habits are associated with stress and depressive symptoms and whether the relationships differ by country and gender in a sample from three European countries collected as part of a Cross National Student Health Survey. Methods: A cross-sectional survey was conducted among first-year students in Germany (N = 696), Poland (N = 489) and Bulgaria (N = 654). Self-administered questionnaires included a 12-item food frequency questionnaire, Cohen's Perceived Stress Scale, and a modified Beck Depression Index. Linear regression analyses were conducted for two outcomes, perceived stress and depressive symptoms. Results: Food consumption frequencies differed by country and gender, as did depressive symptoms and perceived stress. For male students, none of the food consumption groups were associated with perceived stress or depressive symptoms. In females, perceived stress was associated with more frequent consumption of sweets/fast foods and less frequent consumption of fruits/vegetables. Additionally, depressive symptoms were associated with less frequent consumption of fruits/vegetables and meat. Conclusion: Our data show consistent associations between unhealthy food consumption and depressive symptoms and perceived stress among female students from three European countries, but not among male students. This suggests that efforts to reduce depressive symptoms and stress among female students may also lead to the consumption of healthier foods and/or vice-versa

    Bioinformatics' approaches to detect genetic variation in whole genome sequencing data

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    Current genetic marker repositories are not sufficient or even are completely lacking for most farm animals. However, genetic markers are essential for the development of a research tool facilitating discovery of genetic factors that contribute to resistance to disease and the overall welfare and performance in farm animals. By large scale identification of Single Nucleotide Polymorphisms (SNPs) and Structural Variants (SVs) we aimed to contribute to the development of a repository of genetic variants for farm animals. For this purpose bioinformatics data pipelines were designed and validated to address the challenge of the cost effective identification of genetic markers in DNA sequencing data even in absence of a fully sequenced reference genome. To find SNPs in pig, we analysed publicly available whole genome shotgun sequencing datasets by sequence alignment and clustering. Sequence clusters were assigned to genomic locations using publicly available BAC sequencing and BAC mapping data. Within the sequence clusters thousands of SNPs were detected of which the genomic location is roughly known. For turkey and duck, species that both were lacking a sufficient sequence data repository for variant discovery, we applied next-generation sequencing (NGS) on a reduced genome representation of a pooled DNA sample. For turkey a genome reference was reconstructed from our sequencing data and available public sequencing data whereas in duck the reference genome constructed by a (NGS) project was used. SNPs obtained by our cost-effective SNP detection procedure still turned out to cover, at intervals, the whole turkey and duck genomes and are of sufficient quality to be used in genotyping studies. Allele frequencies, obtained by genotyping animal panels with a subset our SNPs, correlated well with those observed during SNP detection. The availability of two external duck SNP datasets allowed for the construction of a subset of SNPs which we had in common with these sets. Genotyping turned out that this subset was of outstanding quality and can be used for benchmarking other SNPs that we identified within duck. Ongoing developments in (NGS) allowed for paired end sequencing which is an extension on sequencing analysis that provides information about which pair of reads are coming from the outer ends of one sequenced DNA fragment. We applied this technique on a reduced genome representation of four chicken breeds to detect SVs. Paired end reads were mapped to the chicken reference genome and SVs were identified as abnormally aligned read pairs that have orientation or span sizes discordant from the reference genome. SV detection parameters, to distinguish true structural variants from false positives, were designed and optimized by validation of a small representative sample of SVs using PCR and traditional capillary sequencing. To conclude: we developed SNP repositories which fulfils a requirement for SNPs to perform linkage analysis, comparative genomics QTL studies and ultimately GWA studies in a range of farm animals. We also set the first step in developing a repository for SVs in chicken, a relatively new genetic marker in animal sciences. <br/

    Molecular cloning and characterization of the corticoid receptors from the American alligator

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    Steroid hormones are essential for health in vertebrates. Corticosteroids, for example, have a regulatory role in many physiological functions, such as osmoregulation, respiration, immune responses, stress responses, reproduction, growth, and metabolism. Although extensively studied in mammals and some non-mammalian species, the molecular mechanisms of corticosteroid hormone (glucocorticoids and mineralocorticoids) action are poorly understood in reptiles. Here, we have evaluated hormone receptor-ligand interactions in the American alligator (Alligator mississippiensis), following the isolation of cDNAs encoding a glucocorticoid receptor (GR) and a mineralocorticoid receptor (MR). The full-length alligator GR (aGR) and aMR cDNAs were obtained using 5' and 3' rapid amplification cDNA ends (RACE). The deduced amino acid sequences exhibited high identity to the chicken orthologs (aGR: 83%; aMR: 90%). Using transient transfection assays of mammalian cells, both aGR and aMR proteins displayed corticosteroid-dependent activation of transcription from keto-steroid hormone responsive, murine mammary tumor virus promoters. We further compared the ligand-specifity of human, chicken, Xenopus, and zebrafish GR and MR. We found that the alligator and chicken GR/MR have very similar amino acid sequences, and this translates to very similar ligand specificity. This is the first report of the full-coding regions of a reptilian GR and MR, and the examination of their transactivation by steroid hormones

    A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms

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    We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms (SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds (a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines--in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases

    Population and Poverty: A Review of the Links, Evidence and Implications for the Philippines

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    The article reviews trends in population and poverty, compares population and development between the Philippines and Thailand over the last 40 years, discusses the theoretical links between population and poverty as well as the empirical evidence, and finally its implications for policy. The author emphasizes the primacy of growth as a development strategy in reducing poverty and perhaps inequality, as well as better fertility management--particularly among the poor--aimed at the potential development benefits arising from demography.poverty, population, inequality, demographic changes
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