946 research outputs found

    Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma

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    Background: Identifying genetic determinants for lung function is important in providing insight into the pathophysiology of asthma. Signal transducer and activator of transcription 3 is a transcription factor latent in the cytoplasm; the gene (STAT3) is activated by a wide range of cytokines, and may play a role in lung development and asthma pathogenesis. Methods: We genotyped six single nucleotide polymorphisms (SNPs) in the STAT3 gene in a cohort of 401 Caucasian adult asthmatics. The associations between each SNP and forced expiratory volume in 1 second (FEV1), as a percent of predicted, at the baseline exam were tested using multiple linear regression models. Longitudinal analyses involving repeated measures of FEV1 were conducted with mixed linear models. Haplotype analyses were conducted using imputed haplotypes. We completed a second association study by genotyping the same six polymorphisms in a cohort of 652 Caucasian children with asthma. Results: We found that three polymorphisms were significantly associated with baseline FEV1: homozygotes for the minor alleles of each polymorphism had lower FEV1 than homozygotes for the major alleles. Moreover, these associations persisted when we performed an analysis on repeated measures of FEV1 over 8 weeks. A haplotypic analysis based on the six polymorphisms indicated that two haplotypes were associated with baseline FEV1. Among the childhood asthmatics, one polymorphism was associated with both baseline FEV1 and the repeated measures of FEV1 over 4 years. Conclusion: Our results indicate that genetic variants in STAT3, independent of asthma treatment, are determinants of FEV1 in both adults and children with asthma, and suggest that STAT3 may participate in inflammatory pathways that have an impact on level of lung function.National Heart, Lung, and Blood Institut

    Effects of vocal registration training on the vocal range and perceived comfort of the adolescent male singer:

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    The purpose of this study was to investigate adolescent male vocal registers and repertoire selection for middle school choirs. Subjects included seventh and eighth grade boys (N = 48) enrolled in elective mixed choirs at a single middle school in Northern New Jersey. The study was designed to determine (a) the vocal range of subjects before and after vocal registration training, (b) the perceived comfort level of subjects before and after vocal registration training, and (c) the preferences of subjects toward 3-part and SATB arrangements. Data were collected on the dependent variables of (a) lowest pitch sung, (b) highest pitch sung, and (c) total range sung. Subjects sang 3-part (Treatment 1) and SATB (Treatment 2) choral literature and rated the comfort of each. A concluding attitudinal survey was used to investigate attitudes regarding 3-part mixed and SATB repertoire. Analysis of variance (ANOVA) revealed a significant increase in total range (p < .001). A significant difference in the lowest pitch was observed (p < .05) in addition to a significant difference in highest pitch (p < .001). No significant differences were found between the two treatment periods on a measure of vocal comfort. Survey responses revealed a significant preference toward SATB music (p < .001). Results replicated Emge (1996), suggesting that seventh and eighth grade boys are capable of singing a wider range than commonly thought possible. Subjects sang both 3 and 4-part arrangements with a general sense of vocal comfort.D.M.A.Includes bibliographical references (p. 70-76)by Stacey L. Sass

    A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

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    We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

    FROM PARSING TO ALIGNING REWARD: MULTIMETHOD MEASUREMENT OF REWARD CONSTRUCTS IN SUBSTANCE USE DISORDERS

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    Substance Use Disorders are characterized by increased reward sensitivity to drugs and a decreased reward sensitivity to substance-free reward. Research has utilized neurobiological and self-report measures to capture reward pathology, yet it is unclear whether these measures are aligned in SUDs. This study tested the relationship between self-report and neural indices of substance-free reward anticipation and response in SUDs. N=31 treatment-seeking adults with SUDs underwent functional neuroimaging during a money-incentivized reward task. Neural indices of reward anticipation and response were collected via BOLD signal and self-report indices of reward anticipation and response were collected via research assistant administration and Qualtrics. Self-reported reward anticipation had a small positive effect (f2 = .10) on neural reward anticipation, and self-reported reward response had a negative effect (f2 = -.18) on neural reward response. Further research is needed on the relationship between multi-method measurement of reward sensitivity to inform clinical utility of these measures.Master of Art

    <b>O inescapável conto do homem <i>tomahawk

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    De acordo com a crítica literária contemporânea, O homem que fora consumido (1982, [1839]) representa uma das mais significativas sátiras de Edgar Allan Poe. Esse burlesque sugere muitas referências aos efeitos do contexto dos magazines na literatura da primeira metade do século XIX. O objetivo deste estudo é descrever, de forma breve, a influência da carreira de periodista de Poe no campo da ficção, precisamente nesse conto, segundo estudos de J. Gerald Kennedy, Jonathan Auerbach, Leonard Cassuto e Stacey Margolis, dentre outros.  

    Efficient preservation of young terrestrial organic carbon in sandy turbidity-current deposits

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    © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Hage, S., Galy, V. V., Cartigny, M. J. B., Acikalin, S., Clare, M. A., Grocke, D. R., Hilton, R. G., Hunt, J. E., Lintern, D. G., McGhee, C. A., Parsons, D. R., Stacey, C. D., Sumner, E. J., & Talling, P. J. Efficient preservation of young terrestrial organic carbon in sandy turbidity-current deposits. Geology, 48(9), (2020): 882-887, doi:10.1130/G47320.1.Burial of terrestrial biospheric particulate organic carbon in marine sediments removes CO2 from the atmosphere, regulating climate over geologic time scales. Rivers deliver terrestrial organic carbon to the sea, while turbidity currents transport river sediment further offshore. Previous studies have suggested that most organic carbon resides in muddy marine sediment. However, turbidity currents can carry a significant component of coarser sediment, which is commonly assumed to be organic carbon poor. Here, using data from a Canadian fjord, we show that young woody debris can be rapidly buried in sandy layers of turbidity current deposits (turbidites). These layers have organic carbon contents 10× higher than the overlying mud layer, and overall, woody debris makes up >70% of the organic carbon preserved in the deposits. Burial of woody debris in sands overlain by mud caps reduces their exposure to oxygen, increasing organic carbon burial efficiency. Sandy turbidity current channels are common in fjords and the deep sea; hence we suggest that previous global organic carbon burial budgets may have been underestimated.We thank C. Johnson, M. Lardie, A. Gagnon, A. McNichol, and the NOSAMS (National Ocean Sciences Accelerator Mass Spectrometry) team (Woods Hole Oceanographic Institution [WHOI], Massachusetts, USA) for their help with ramped oxidation system and isotopes. We thank the captain and crew of CCGS Vector. Support was provided by UK Natural Environment Research Council (NERC) grants NE/M007138/1 (to Cartigny) and NE/L013142/1 (to Talling), NE/P005780/1 and NE/P009190/1 (to Clare); a Royal Society Research Fellowship (to Cartigny); an International Association of Sedimentologists Postgraduate Grant and National Oceanography Centre Southampton–WHOI exchange program funds (to Hage); an independent study award from WHOI (to Galy); the Climate Linked Atlantic Sector Science (CLASS) program (NERC grant NE/R015953/1); and the European Research Council under the European Union’s Horizon 2020 research and innovation program (Grant 725955, to Parsons). We thank François Baudin, Xingqian Cui, editor James Schmitt, and three anonymous reviewers

    The effect of probiotics and organic acids on Shiga-toxin 2 gene expression in enterohemorrhagic Escherichia coli O157:H7

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    Probiotics are known to have an inhibitory effect against the growth of various foodborne pathogens, however, the specific role of probiotics in Shiga-toxin-producing Escherichia coli (STEC) virulence gene expression has not been well defined. Shiga toxins are members of a family of highly potent bacterial toxins and are the main virulence marker for STEC. Shiga toxins inhibit protein synthesis in eukaryotic cells and play a role in hemorrhagic colitis and hemolytic uremic syndrome. STEC possesses Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2), both of which have A and B subunits. Although STEC containing both Stx1 and Stx2 has been isolated from patients with hemorrhagic colitis, Stx2 is more frequently associated with human disease complications. Thus, the effect of Lactobacillus, Pediococcus, and Bifidobacterium strains on stx2A expression levels in STEC was investigated. Lactic acid bacteria and bifidobacteria were isolated from farm animals, dairy, and human sources and included L. rhamnosus GG, L. curvatus, L. plantarum, L. jensenii, L. acidophilus, L. casei, L. reuteri, P. acidilactici, P. cerevisiae, P. pentosaceus, B. thermophilum, B. boum, B. suis and B. animalis. E. coli O157:H7 (EDL 933) was coincubated with sub-lethal concentrations of each probiotic strain. Following RNA extraction and cDNA synthesis, relative stx2A mRNA levels were determined according to a comparative critical threshold (Ct) real-time PCR. Data were normalized to the endogenous control glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the level of stx2A expression between treated and untreated STEC was compared. Observed for all probiotic strains tested, stx2A was down-regulated, when compared to the control culture. Probiotic production of organic acids, as demonstrated by a decrease in pH, influenced stx2A gene expression

    Investigating the Impact of Chronic Stress on Anhedonia Via Alterations in Striatal Dopamine & Reward Circuitry Functioning

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    In preclinical and human studies, long-term exposure to chronic stress causes distinctive changes in neurobiological systems, including alterations in striatal dopamine (DA) functioning and functional brain reward circuitry (i.e., mesolimbic) that mediate hedonic functioning. However, most of the research linking alterations in brain reward circuitry and anhedonia has been in depressed populations. This is the first study of striatal dopamine functioning and reward circuitry in a transdiagnostic sample of adults with anhedonia, ranging in exposure to chronic stress. Participants completed a reward-processing task during simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging with the D2/D3 receptor antagonist, [11C]raclopride, which selectively binds to striatal DA receptors. Results presented here provide evidence for reduced striatal DA functioning during reward processing and decreased mesocorticolimbic network functional connectivity in a transdiagnostic sample with clinically significant anhedonia. This research has the potential to advance our understanding of conditions marked by dysfunctional reward processing, including depression, addiction, and schizophrenia.Master of Art
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