2,158 research outputs found

    Hypothalamic actions of neuromedin U.

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    The central nervous system and gut peptide neuromedin U (NMU) inhibits feeding after intracerebroventricular injection. This study explored the hypothalamic actions of NMU on feeding and the hypothalamo-pituitary-adrenal axis. Intraparaventricular nucleus (intra-PVN) NMU dose-dependently inhibited food intake, with a minimum effective dose of 0.1 nmol and a robust effect at 0.3 nmol. Feeding inhibition was mapped by NMU injection into eight hypothalamic areas. NMU (0.3 nmol) inhibited food intake in the PVN (0-1 h, 59 ± 6.9% of the control value; P < 0.001) and arcuate nucleus (0-1 h, 76 ± 10.4% of the control value; P < 0.05). Intra-PVN NMU markedly increased grooming and locomotor behavior and dose-dependently increased plasma ACTH (0.3 nmol NMU, 24.8 ± 1.9 pg/ml; saline, 11.4 ± 1.0; P < 0.001) and corticosterone (0.3 nmol NMU, 275.4 ± 40.5 ng/ml; saline, 129.4 ± 25.0; P < 0.01). Using hypothalamic explants in vitro, NMU stimulated CRH (100 nM NMU, 5.9 ± 0.95 pmol/explant; basal, 3.8 ± 0.39; P < 0.01) and arginine vasopressin release (100 nM NMU, 124.5 ± 21.8 fmol/explant; basal, 74.5 ± 7.6; P < 0.01). Leptin stimulated NMU release (141.9 ± 20.4 fmol/explant; basal, 92.9 ± 9.4; P < 0.01). Thus, we describe a novel role for NMU in the PVN to stimulate the hypothalamo-pituitary-adrenal axis and locomotor and grooming behavior and to inhibit feeding

    Neuromedin U partially mediates leptin-induced hypothalamo-pituitary adrenal (HPA) stimulation and has a physiological role in the regulation of the HPA axis in the rat.

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    Intracerebroventricular (ICV) administration of the hypothalamic neuropeptide neuromedin U (NMU) or the adipostat hormone leptin increases plasma ACTH and corticosterone. The relationship between leptin and NMU in the regulation of the hypothalamo-pituitary adrenal (HPA) axis is currently unknown. In this study, leptin (1 nM) significantly increased the release of CRH from ex vivo hypothalamic explants by 207 ± 8.4% (P < 0.05 vs. basal), an effect blocked by the administration of anti-NMU IgG. The ICV administration of leptin (10 μg, 0.625 nmol) increased plasma ACTH and corticosterone 20 min after injection [plasma ACTH (picograms per milliliter): vehicle, 63 ± 20, leptin, 135 ± 36, P < 0.05; plasma corticosterone (nanograms per milliliter): vehicle, 285 ± 39, leptin, 452 ± 44, P < 0.01]. These effects were partially attenuated by the prior administration of anti-NMU IgG. Peripheral leptin also stimulated ACTH release, an effect attenuated by prior ICV administration of anti-NMU IgG. We examined the diurnal pattern of hypothalamic NMU mRNA expression and peptide content, plasma leptin, and plasma corticosterone. The diurnal changes in hypothalamic NMU mRNA expression were positively correlated with hypothalamic NMU peptide content, plasma corticosterone, and plasma leptin. The ICV administration of anti-NMU IgG significantly attenuated the dark phase rise in corticosterone [corticosterone (nanograms per milliliter): vehicle, 493 ± 38; NMU IgG, 342 ± 47 (P < 0.05)]. These studies suggest that NMU may play a role in the regulation of the HPA axis and partially mediate leptin-induced HPA stimulation. Copyright © 2006 by The Endocrine Society

    Misregulation of cell cycle-dependent methylation of budding yeast CENP-A contributes to chromosomal instability.

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    Centromere (CEN) identity is specified epigenetically by specialized nucleosomes containing evolutionarily conserved CEN-specific histone H3 variant CENP-A (Cse4 in Saccharomyces cerevisiae, CENP-A in humans), which is essential for faithful chromosome segregation. However, the epigenetic mechanisms that regulate Cse4 function have not been fully defined. In this study, we show that cell cycle-dependent methylation of Cse4-R37 regulates kinetochore function and high-fidelity chromosome segregation. We generated a custom antibody that specifically recognizes methylated Cse4-R37 and showed that methylation of Cse4 is cell cycle regulated with maximum levels of methylated Cse4-R37 and its enrichment at the CEN chromatin occur in the mitotic cells. Methyl-mimic cse4-R37F mutant exhibits synthetic lethality with kinetochore mutants, reduced levels of CEN-associated kinetochore proteins and chromosome instability (CIN), suggesting that mimicking the methylation of Cse4-R37 throughout the cell cycle is detrimental to faithful chromosome segregation. Our results showed that SPOUT methyltransferase Upa1 contributes to methylation of Cse4-R37 and overexpression of UPA1 leads to CIN phenotype. In summary, our studies have defined a role for cell cycle-regulated methylation of Cse4 in high-fidelity chromosome segregation and highlight an important role of epigenetic modifications such as methylation of kinetochore proteins in preventing CIN, an important hallmark of human cancers

    Active Membrane Fluctuations Studied by Micropipet Aspiration

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    We present a detailed analysis of the micropipet experiments recently reported in J-B. Manneville et al., Phys. Rev. Lett. 82, 4356--4359 (1999), including a derivation of the expected behaviour of the membrane tension as a function of the areal strain in the case of an active membrane, i.e., containing a nonequilibrium noise source. We give a general expression, which takes into account the effect of active centers both directly on the membrane, and on the embedding fluid dynamics, keeping track of the coupling between the density of active centers and the membrane curvature. The data of the micropipet experiments are well reproduced by the new expressions. In particular, we show that a natural choice of the parameters quantifying the strength of the active noise explains both the large amplitude of the observed effects and its remarkable insensitivity to the active-center density in the investigated range. [Submitted to Phys Rev E, 22 March 2001]Comment: 14 pages, 5 encapsulated Postscript figure

    The Spectroscopic Classification and Explosion Properties of SN2009nz Associated with GRB091127 at z=0.490

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    We present spectroscopic observations of GRB091127 (z=0.490) at the peak of the putative associated supernova, SN2009nz. Subtracting a late-time spectrum of the host galaxy, we isolate the contribution of SN2009nz and uncover broad features typical of nearby GRB-SNe. This establishes unambiguously that GRB091127 was accompanied by a broad-lined Type Ic SN, and links a cosmological long burst with a standard energy release (E_gamma,iso ~ 1.1e52 erg) to a massive star progenitor. The spectrum of SN2009nz closely resembles that of SN2006aj, with SN2003dh also providing an acceptable match, but has significantly narrower features than SNe 1998bw and 2010bh, indicative of a lower expansion velocity. The photospheric velocity inferred from the SiII 6355 absorption feature, v_ph ~ 17,000 km/s, is indeed closer to that of SNe 2006aj and 2003dh than to the other GRB-SNe. Combining the measured velocity with the light curve peak brightness and width, we estimate the following explosion parameters: M_Ni ~ 0.35 M_sun, E_K ~ 2.3e51 erg, and M_ej ~ 1.4 M_sun, similar to those of SN2006aj. These properties indicate that SN2009nz follows a trend of lower M_Ni for GRB-SNe with lower E_K and M_ej. Equally important, since GRB091127 is a typical cosmological burst, the similarity of SN2009nz to SN2006aj either casts doubt on the claim that XRF060218/SN2006aj was powered by a neutron star, or indicates that the nature of the central engine is encoded in the SN properties but not in the prompt emission. Future spectra of GRB-SNe at z > 0.3, including proper subtraction of the host galaxy contribution, will shed light on the full dispersion of SN properties for standard long GRBs, on the relation between SNe associated with sub-energetic and standard GRBs, and on a potential dispersion in the associated SN types.Comment: Submitted to ApJ; 11 pages; 2 tables; 4 figures; emulateapj styl

    Impact of the California Lead Ammunition Ban on Reducing Lead Exposure in Golden Eagles and Turkey Vultures

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    Predatory and scavenging birds may be exposed to high levels of lead when they ingest shot or bullet fragments embedded in the tissues of animals injured or killed with lead ammunition. Lead poisoning was a contributing factor in the decline of the endangered California condor population in the 1980s, and remains one of the primary factors threatening species recovery. In response to this threat, a ban on the use of lead ammunition for most hunting activities in the range of the condor in California was implemented in 2008. Monitoring of lead exposure in predatory and scavenging birds is essential for assessing the effectiveness of the lead ammunition ban in reducing lead exposure in these species. In this study, we assessed the effectiveness of the regulation in decreasing blood lead concentration in two avian sentinels, golden eagles and turkey vultures, within the condor range in California. We compared blood lead concentration in golden eagles and turkey vultures prior to the lead ammunition ban and one year following implementation of the ban. Lead exposure in both golden eagles and turkey vultures declined significantly post-ban. Our findings provide evidence that hunter compliance with lead ammunition regulations was sufficient to reduce lead exposure in predatory and scavenging birds at our study sites

    Observational Constraints on the Angular and Spectral Distributions of Photons in Gamma-Ray Burst Sources

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    The typical spectra of gamma-ray bursts (GRBs) are discussed in the context of the compactness problem for GRB sources and how it is resolved in the popular fireball model. In particular, observational (model-independent) constraints on the collimation of the gamma-rays and the dependence of the collimation angle on the photon energy are considered. The fact that the threshold for the creation of ee+e^{-}e^{+} pairs depends on the angle between the momenta of the annihilating photons in the GRB source provides an alternative solution to the compactness problem. A new approach to explaining GRBs, taking into account the angular dependence for pair creation, is proposed, and the main features of a scenario describing a GRB source with a total (photon) energy smaller or of the order of 104910^{49} erg are laid out. Thus, we are dealing with an alternative to an ultra-relativistic fireball, if it turns out (as follows from observations) that all "long" GRBs are associated with normal (not peculiar) core-collapse supernovae. The effects of radiation pressure and the formation of jets as a consequence of even a small amount of anisotropy in the total radiation field in a (compact) GRB source are examined in this alternative model. Possible energy release mechanisms acting in regions smaller or of the order of 10810^{8} cm in size (a compact model for a GRB) are discussed. New observational evidence for such compact energy release in the burst source is considered.Comment: 15 pages, no figures, no table

    Obesity and poor breast cancer prognosis: an illusion because of hormone replacement therapy?

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    High body mass index (BMI) and use of hormone replacement therapy (HRT) increase the risk of postmenopausal breast cancer. It has been shown that BMI modifies the effect of HRT, as its influence is most pronounced in lean women. We investigated the influence of BMI and HRT on prognosis in 2640 postmenopausal women diagnosed with breast cancer in Sweden in 1993–1995, taking into account HRT and mammography before diagnosis. Logistic and Cox regression were used. In non-users of HRT, obese women (BMI >30) compared with normal weight women (BMI <25) had a similar prognosis (hazard ratio (HR) 1.1, 95% confidence interval (CI) 0.8–1.6), despite larger tumours found in obese women. Obese HRT users had less favourable tumour characteristics and poorer prognosis compared with normal weight women (HR 3.7, 95% CI 1.9–7.2). The influence of BMI on breast cancer prognosis was similar whether diagnosed by mammographic screening or not. We found a similar prognosis of postmenopausal breast cancer-specific death regardless of BMI in non-users of HRT, but among HRT users obesity was associated with a poorer breast cancer prognosis

    A sociological dilemma: race, segregation, and US sociology

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    US sociology has been historically segregated in that, at least until the 1960s, there were two distinct institutionally organized traditions of sociological thought – one black and one white. For the most part, however, dominant historiographies have been silent on that segregation and, at best, reproduce it when addressing the US sociological tradition. This is evident in the rarity with which scholars such as WEB Du Bois, E Franklin Frazier, Oliver Cromwell Cox, or other ‘African American Pioneers of Sociology’, as Saint-Arnaud calls them, are presented as core sociological voices within histories of the discipline. This article addresses the absence of African American sociologists from the US sociological canon and, further, discusses the implications of this absence for our understanding of core sociological concepts. With regard to the latter, the article focuses in particular on the debates around equality and emancipation and discusses the ways in which our understanding of these concepts could be extended by taking into account the work of African American sociologists and their different interpretations of core themes

    Tobacco use and caries risk among adolescents - a longitudinal study in Sweden

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    Background: Smoking and the use of smokeless tobacco have a detrimental impact on general and oral health. The relationship to dental caries is however still unclear. As caries is a multi-factorial disease with clear life-style, socio-economic and socio-demographic gradients, the tobacco use may be a co-variable in this complex rather than a direct etiological factor. Our aim was to analyze the impact of tobacco use on caries incidence among adolescents, with consideration to socio-economic variables by residency, using epidemiological data from a longitudinal study in the region of Halland, Sweden. Methods: The study population consisted of 10,068 adolescents between 16-19 years of age from whom yearly data on caries and tobacco use (cigarette smoking and use of smokeless tobacco) were obtained during the period 2006-2012. Reported DMFS increment between 16 and 19 years of age (Delta DMFS) for an individual was considered as the primary caries outcome. The outcome data were compared for self-reported never vs. ever users of tobacco, with consideration to neighborhood-level socio-economy (4 strata), baseline (i.e., 16 years of age) DMFS and sex. The region consists of 65 parishes with various socio-economic conditions and each study individual was geo-coded with respect to his/her residence parish. Neighborhood (parish-level) socio-economy was assessed by proportion of residing families with low household purchasing power. Results:Delta DMFS differed evidently between ever and never users of tobacco (mean values: 1.8 vs. 1.2; proportion with Delta DMFS > 0: 54.2% vs. 40.5%; p < 0.0001). Significant differences were observed in each neighborhood-level socio-economic stratum. Even after controlling for baseline DMFS and sex, Delta DMFS differed highly significantly between the ever and never users of tobacco (overall p < 0.0001). Conclusion: Tobacco use was clearly associated with increased caries increment during adolescence. Hence, this factor is relevant to consider in the clinical caries risk assessment of the individual patient as well as for community health plans dealing with oral health
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