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Eleven susceptibility loci for late-onset Alzheimer’s disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer’s disease cases and 37,154 controls. In stage 2,11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer’s disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer’s disease.
Jean-Charles Lambert,1,2,3,145 Carla A Ibrahim-Verbaas,4,5,145 Denise Harold,6,145 Adam C Naj,7,8,145 Rebecca Sims,6 Celine Bellenguez,1,2,3 Gyungah Jun,9,10,11 Anita L DeStefano,11 Joshua C Bis,12 Gary W Beecham,13,14 Benjamin Grenier-Boley,1,2,3 Giancarlo Russo,15 Tricia A Thornton-Wells,16 Nicola Jones,6 Albert V Smith,17,18 Vincent Chouraki,1,2,3 Charlene Thomas,6 M Arfan Ikram,4,5,19,20 Diana Zelenika,21 Badri N Vardarajan,9 Yoichiro Kamatani,22 Chiao-Feng Lin,23 Amy Gerrish,6 Helena Schmidt,24 Brian Kunkle,13 Melanie L Dunstan,6 Agustin Ruiz,25 Marie-Therese Bihoreau,21 Seung-Hoan Choi,11 Christiane Reitz,26,27 Florence Pasquier,2,28 Paul Hollingworth,6 Alfredo Ramirez,29,30 Olivier Hanon,31 Annette L Fitzpatrick,12,32,33 Joseph D Buxbaum,34,35,36 Dominique Campion,37 Paul K Crane,38 Clinton Baldwin,9 Tim Becker,39,40 Vilmundur Gudnason,17,18 Carlos Cruchaga,41,42 David Craig,43 Najaf Amin,5 Claudine Berr,44 Oscar L Lopez,45 Philip L De Jager,46,47 Vincent Deramecourt,2,28 Janet A Johnston,43 Denis Evans,48 Simon Lovestone,49 Luc Letenneur,50 Francisco J Moron,51 David C Rubinsztein,52 Gudny Eiriksdottir,18 Kristel Sleegers,53,54 Alison M Goate,41,42 Nathalie Fievet,1,3 Matthew J Huentelman,55 Michael Gill,56 Kristelle Brown,57 M Ilyas Kamboh,58,59 Lina Keller,60 Pascale Barberger-Gateau,50 Bernadette McGuinness,43 Eric B Larson,38,61 Robert Green,62 Amanda J Myers,63 Carole Dufouil,50 Stephen Todd,43 David Wallon,37 Seth Love,64 Ekaterina Rogaeva,65 John Gallacher,66 Peter St George-Hyslop,52,65,67 Jordi Clarimon,68,69 Alberto Lleo,68,69 Anthony Bayer,66 Debby W Tsuang,70 Lei Yu,71 Magda Tsolaki,72 Paola Bossù,73 Gianfranco Spalletta,73 Petroula Proitsi,49 John Collinge,74 Sandro Sorbi,75,76 Florentino Sanchez-Garcia,77 Nick C Fox,78 John Hardy,79,80 Maria Candida Deniz Naranjo,77 Paolo Bosco,81 Robert Clarke,82 Carol Brayne,83 Daniela Galimberti,84 Michelangelo Mancuso,85 Fiona Matthews,86 European Alzheimer’s disease Initiative (EADI),87 Genetic and Environmental Risk in Alzheimer’s Disease (GERAD),87 Alzheimer’s Disease Genetic Consortium (ADGC),87 Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE),87 Susanne Moebus,88 Patrizia Mecocci,89 Maria Del Zompo,90 Wolfgang Maier,29,39 Harald Hampel,91,92 Alberto Pilotto,93 Maria Bullido,94,95,96 Francesco Panza,97 Paolo Caffarra,98,99 Benedetta Nacmias,75,76 John R Gilbert,13,14 Manuel Mayhaus,100 Lars Lannfelt,101 Hakon Hakonarson,102 Sabrina Pichler,100 Minerva M Carrasquillo,103 Martin Ingelsson,101 Duane Beekly,104 Victoria Alvarez,105 Fanggeng Zou,103 Otto Valladares,23 Steven G Younkin,103 Eliecer Coto,105 Kara L Hamilton-Nelson,13 Wei Gu,100 Cristina Razquin,106 Pau Pastor,106,107 Ignacio Mateo,108,109 Michael J Owen,6 Kelley M Faber,110 Palmi V Jonsson,17,111 Onofre Combarros,108,109 Michael C O’Donovan,6 Laura B Cantwell,23 Hilkka Soininen,112,113 Deborah Blacker,114,115 Simon Mead,74 Thomas H Mosley, Jr,116 David A Bennett,71,117 Tamara B Harris,12 Laura Fratiglioni,60,118 Clive Holmes,119 Renee F A G de Bruijn,4,5,20 Peter Passmore,43 Thomas J Montine,120 Karolien Bettens,53,54 Jerome I Rotter,121 Alexis Brice,122,123 Kevin Morgan,57 Tatiana M Foroud,110 Walter A Kukull,32 Didier Hannequin,37 John F Powell,49 Michael A Nalls,124 Karen Ritchie,44,125 Kathryn L Lunetta,11 John S K Kauwe,126 Eric Boerwinkle,127,128,129 Matthias Riemenschneider,100 Merce Boada,25,130 Mikko Hiltunen,112,113 Eden R Martin,13,14 Reinhold Schmidt,131 Dan Rujescu,132 Li-san Wang,23 Jean-Francois Dartigues,50,133 Richard Mayeux,26,27 Christophe Tzourio,134 Albert Hofman,5,20 Markus M Nothen,135 Caroline Graff,117,136 Bruce M Psaty,12,32,61,137 Lesley Jones,6 Jonathan L Haines,16,138 Peter A Holmans,6 Mark Lathrop,21,22,139 Margaret A Pericak-Vance,13,14 Lenore J Launer,140 Lindsay A Farrer,9,10,11,141,142 Cornelia M van Duijn,5,20,143 Christine Van Broeckhoven,53,54 Valentina Moskvina,6 Sudha Seshadri,142,145,146 Julie Williams,6,145,146 Gerard D Schellenberg,23,145,146 and Philippe Amouyel1,2,3,28,144,145,146
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease
2014 Jun 1.
The aim was to investigate the vision of all 90 dentally qualified staff at a dental school.
Materials and Methods:
Ethical approval was obtained and a questionnaire-based survey conducted. Data were screened and analysed using Stata 13.1. The χ2 and Fisher’s Exact tests were used to test for significance with an alpha level of 0.05.
The participation rate was 95.6%. Most of the teachers (92%) considered their eyesight was satisfactory to practice dentistry. Of the 97% who had been tested at some stage, 15% had their eye examination due to sight deterioration with 22% needing correction. Almost two-thirds were myopic and a third were hyperopic. Forty-nine per cent wore spectacles only, with about a quarter of this group alternating between spectacles and contact lenses. Of those with corrected vision, 80% followed their optometrist’s recall advice. Four participants reported that they were colour blind. While 4% had had laser-eye surgery, a further 27% were interested in this. Magnification was used by 72% with no significant differences between genders, age of staff member, place of qualification or registration status. Most of the staff (81%) thought that screening of dental student’s eyesight should be mandatory, and regular eye examinations as a condition of dental practice was supported by 67%.
The number of teachers reporting recent vision tests was encouraging; nevertheless, a worrying 8% surveyed were unsure if their eyesight was satisfactory for work. The commonest vision problem was myopia, with almost half of the teachers wearing spectacles. It is clear that visual standards for dentistry would be helpful. Magnification use was high, with many non-users indicating their intention to buy loupes.
Within the limits of this study the teachers were conscientious regarding their eye care, irrespective of their training and age. There was strong support for the mandatory testing of vision for all dentists and especially dental students.
Nicholas P Chandler,1,* Andrew R Gray,2 and Colleen M Murray1
Nicholas P Chandler,1,* Andrew R Gray,2 and Colleen M Murray1
Long-term memory requires activity-dependent synthesis of plasticity-related proteins (PRPs) to strengthen synaptic efficacy and consequently consolidate memory. Cytoplasmic polyadenylation element binding protein (CPEB)3 is a sequence-specific RNA-binding protein that regulates translation of several PRP RNAs in neurons. To understand whether CPEB3 plays a part in learning and memory, we generated CPEB3 knock-out (KO) mice and found that the null mice exhibited enhanced hippocampus-dependent, short-term fear memory in the contextual fear conditioning test and long-term spatial memory in the Morris water maze. The basal synaptic transmission of Schaffer collateral-CA1 neurons was normal but long-term depression evoked by paired-pulse low-frequency stimulation was modestly facilitated in the juvenile KO mice. Molecular and cellular characterizations revealed several molecules in regulating plasticity of glutamatergic synapses are translationally elevated in the CPEB3 KO neurons, including the scaffolding protein PSD95 and the NMDA receptors along with the known CPEB3 target, GluA1. Together, CPEB3 functions as a negative regulator to confine the strength of glutamatergic synapses by downregulating the expression of multiple PRPs and plays a role underlying certain forms of hippocampus-dependent memories.
Deletion of CPEB3 Enhances Hippocampus-Dependent Memory via Increasing Expressions of PSD95 and NMDA Receptors
Hsu-Wen Chao,1,* Li-Yun Tsai,1,* Yi-Ling Lu,1 Pei-Yi Lin,1 Wen-Hsuan Huang,1 Hsin-Jung Chou,1 Wen-Hsin Lu,1,2 Hsiu-Chen Lin,1 Ping-Tao Lee,1 and Yi-Shuian Huangcorresponding author1,2
2013 Oct 23;