26 research outputs found

    Season of birth and Alzheimer's disease: a population-based study in Saguenay-Lac-St-Jean/Québec (IMAGE Project)

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    The birth distribution of 399 cases of Alzheimer's disease (AD) identified in the region of Saguenay-Lac-St-Jean (Québec) was compared with that of: (a) the population currently living in the area; and (b) the population born during the same period in the area. AD cases have been recruited since 1986 by the IMAGE Project. Cases and controls were grouped according to the month of birth and according to the day of birth using density estimation. Analyses showed a significant deficit of births in the month of May. We believe these preliminary results deserve further attention and we suggest two possible explanations that could lead to a deficit of AD births at specific periods during the year

    Mapping circumstellar magnetic fields of late-type evolved stars with the Goldreich-Kylafis effect: CARMA observations at λ1.3\lambda 1.3 mm of R Crt and R Leo

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    Mapping magnetic fields is the key to resolving what remains an unclear physical picture of circumstellar magnetic fields in late-type evolved stars. Observations of linearly polarized emission from thermal molecular line transitions due to the Goldreich-Kylafis (G-K) effect provides valuable insight into the magnetic field geometry in these sources that is complementary to other key studies. In this paper, we present the detection of spectral-line polarization from both the thermal J=2−1J=2-1 CO line and the v=1,J=5−4v=1, J=5-4 SiO maser line toward two thermal-pulsating (TP-) AGB stars, R Crt and R Leo. The observed fractional linear polarization in the CO emission is measured as ml∌3.1%m_l\sim 3.1\% and ml∌9.7%m_l\sim9.7\% for R Crt and R Leo respectively. A circumstellar envelope (CSE) model profile and the associated parameters are estimated and used as input to a more detailed modeling of the predicted linear polarization expected from the G-K effect. The observed thermal line polarization level is consistent with the predicted results from the G-K model for R Crt; additional effects need to be considered for R Leo

    Regional variability in peatland burning at mid- to high-latitudes during the Holocene

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    Acknowledgements This work developed from the PAGES (Past Global Changes) C-PEAT (Carbon in Peat on EArth through Time) working group. PAGES has been supported by the US National Science Foundation, Swiss National Science Foundation, Swiss Academy of Sciences and Chinese Academy of Sciences. We acknowledge the following financial support: UK Natural Environment Research Council Training Grants NE/L002574/1 (T.G.S.) and NE/S007458/1 (R.E.F.); Dutch Foundation for the Conservation of Irish Bogs, Quaternary Research Association and Leverhulme Trust RPG-2021-354 (G.T.S); the Academy of Finland (M.V); PAI/SIA 80002 and FONDECYT IniciaciĂłn 11220705 - ANID, Chile (C.A.M.); R20F0002 (PATSER) ANID Chile (R.D.M.); Swedish Strategic Research Area (SRA) MERGE (ModElling the Regional and Global Earth system) (M.J.G.); Polish National Science Centre Grant number NCN 2018/29/B/ST10/00120 (K.A.); Russian Science Foundation Grant No. 19-14-00102 (Y.A.M.); University of Latvia Grant No. AAp2016/B041/Zd2016/AZ03 and the Estonian Science Council grant PRG323 (TrackLag) (N.S. and A.M.); U.S. Geological Survey Land Change Science/Climate Research & Development Program (M.J., L.A., and D.W.); German Research Foundation (DFG), grant MA 8083/2-1 (P.M.) and grant BL 563/19-1 (K.H.K.); German Academic Exchange Service (DAAD), grant no. 57044554, Faculty of Geosciences, University of MĂŒnster, and Bavarian University Centre for Latin America (BAYLAT) (K.H.K). Records from the Global Charcoal Database supplemented this work and therefore we would like to thank the contributors and managers of this open-source resource. We also thank Annica Greisman, Jennifer Shiller, Fredrik Olsson and Simon van Bellen for contributing charcoal data to our analyses. Any use of trade, firm, or product name is for descriptive purposes only and does not imply endorsement by the U.S. Government.Peer reviewedPostprin

    Seven transmembrane receptor core signaling complexes are assembled prior to plasma membrane trafficking

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    Much is known about beta(2)-adrenergic receptor trafficking and internalization following prolonged agonist stimulation. However, less is known about outward trafficking of the beta(2)-adrenergic receptor to the plasma membrane or the role that trafficking might play in the assembly of receptor signaling complexes, important for targeting, specificity, and rapidity of subsequent signaling events. Here, by using a combination of bioluminescence resonance energy transfer, bimolecular fluorescence complementation, and confocal microscopy, we evaluated the steps in the formation of the core receptor-G protein heterotrimer complex. By using dominant negative Rab and Sar GTPase constructs, we demonstrate that receptor dimers and receptor-G beta gamma complexes initially associate in the endoplasmic reticulum, whereas G alpha subunits are added to the complex during endoplasmic reticulum-Golgi transit. We also observed that G protein heterotrimers adopt different trafficking itineraries when expressed alone or with stoichiometric co-expression with receptor. Furthermore, deliberate mistargeting of specific components of these complexes leads to diversion of other members from their normal subcellular localization, confirming the role of these early interactions in targeting and formation of specific signaling complexes

    Novel, gel-free proteomics approach identifies RNF5 and JAMP as modulators of GPCR stability

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    The maturation and folding of G protein-coupled receptors are governed by mechanisms that remain poorly understood. In an effort to characterize these biological events, we optimized a novel, gel-free proteomic approach to identify partners of the beta(2)-adrenergic receptor (beta(2)AR). In addition to a number of known interacting proteins such as heterotrimeric G protein subunits, this allowed us to identify proteins involved in endoplasmic reticulum (ER) QC of the receptor. Among beta(2)AR-associated proteins is Ring finger protein 5 (RNF5), an E3 ubiquitin ligase anchored to the outer membrane of the ER. Coimmunoprecipitation assays confirmed, in a cellular context, the interaction between RNF5 and the beta(2)AR as well as the prostaglandin D-2 receptor (DP). Confocal microscopy revealed that DP colocalized with RNF5 at the ER. Coexpression of RNF5 with either receptor increased levels of their expression, whereas small interfering RNA-mediated knockdown of endogenous RNF5 promoted the opposite. RNF5 did not modulate the ubiquitination state of beta(2)AR or DP. Instead, RNF5 ubiquitinated JNK-associated membrane protein (JAMP), a protein that recruits the proteasome to the ER membrane and that is negatively regulated by RNF5-mediated ubiquitination. JAMP coimmunoprecipitated with both beta(2)AR and DP and decreased total receptor protein levels through proteasomal degradation. Expression of DP, a receptor largely retained in the ER, promoted proteasome recruitment by JAMP. Degradation of both receptors via JAMP was increased when RNF5 was depleted. Our data suggest that RNF5 regulates the turnover of specific G protein-coupled receptors by ubiquitinating JAMP and preventing proteasome recruitment

    GÎČÎł is a negative regulator of AP-1 mediated transcription

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    Following stimulation of G protein-coupled receptors (GPCRs) at the cell surface, heterotrimeric G proteins are activated. Both G alpha and G beta gamma subunits regulate specific effectors to transmit signals received by the receptor. Recent data suggest potential nuclear localization or translocation of the G beta gamma subunit. Here, we show that co-expression of the G beta gamma dimer decreased phorbol 12-myristate 13-acetate (PMA)-stimulated AP-1 gene reporter activity in HEK293 cells as well as the AP-1 dependent gonadotropin-releasing hormone-stimulated human follicle-stimulating hormone beta reporter activity in L beta T2 gonadotrope cells. Further, we identify Fos transcription factors as novel interactors of the G beta 1 subunit, using protein fragment complementation assays, as well as co-immunoprecipitation in vivo and in vitro. Fos proteins dimerize with Jun proteins to form activator protein-1 (AP-1) transcription factor complexes, which regulate target gene expression. G beta gamma did not interfere with the dimerization of Fos and Jun or their ability to bind DNA. Rather, G beta gamma co-localized with the AP-1 complex in the nucleus and recruited histone deacetylases (HDACs) to inhibit AP-1 transcriptional activity. Our data indicate a novel role for G beta gamma subunits as transcriptional regulators. (C) 2010 Elsevier Inc. All rights reserved
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