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https://www.readbyqxmd.com/read/28776676/consistency-of-elemental-and-isotope-ratio-patterns-across-multiple-scales-from-individual-fish
#1
M E Seeley, W K Logan, B D Walther
Assays of elemental and stable-isotope ratios across growth increments of scales have the potential to provide a non-lethal alternative to otolith chemistry for identifying migration and ontogenetic trophic shifts. A central assumption when employing scales as otolith analogues is that any scale from an individual will provide equivalent information about the chemical history of that fish. This assumption was investigated with multiple scales from wild and captive euryhaline Atlantic tarpon Megalops atlanticus from the north-west Gulf of Mexico...
August 3, 2017: Journal of Fish Biology
https://www.readbyqxmd.com/read/28714976/rare-coding-variants-in-plcg2-abi3-and-trem2-implicate-microglial-mediated-innate-immunity-in-alzheimer-s-disease
#2
Rebecca Sims, Sven J van der Lee, Adam C Naj, Céline Bellenguez, Nandini Badarinarayan, Johanna Jakobsdottir, Brian W Kunkle, Anne Boland, Rachel Raybould, Joshua C Bis, Eden R Martin, Benjamin Grenier-Boley, Stefanie Heilmann-Heimbach, Vincent Chouraki, Amanda B Kuzma, Kristel Sleegers, Maria Vronskaya, Agustin Ruiz, Robert R Graham, Robert Olaso, Per Hoffmann, Megan L Grove, Badri N Vardarajan, Mikko Hiltunen, Markus M Nöthen, Charles C White, Kara L Hamilton-Nelson, Jacques Epelbaum, Wolfgang Maier, Seung-Hoan Choi, Gary W Beecham, Cécile Dulary, Stefan Herms, Albert V Smith, Cory C Funk, Céline Derbois, Andreas J Forstner, Shahzad Ahmad, Hongdong Li, Delphine Bacq, Denise Harold, Claudia L Satizabal, Otto Valladares, Alessio Squassina, Rhodri Thomas, Jennifer A Brody, Liming Qu, Pascual Sánchez-Juan, Taniesha Morgan, Frank J Wolters, Yi Zhao, Florentino Sanchez Garcia, Nicola Denning, Myriam Fornage, John Malamon, Maria Candida Deniz Naranjo, Elisa Majounie, Thomas H Mosley, Beth Dombroski, David Wallon, Michelle K Lupton, Josée Dupuis, Patrice Whitehead, Laura Fratiglioni, Christopher Medway, Xueqiu Jian, Shubhabrata Mukherjee, Lina Keller, Kristelle Brown, Honghuang Lin, Laura B Cantwell, Francesco Panza, Bernadette McGuinness, Sonia Moreno-Grau, Jeremy D Burgess, Vincenzo Solfrizzi, Petra Proitsi, Hieab H Adams, Mariet Allen, Davide Seripa, Pau Pastor, L Adrienne Cupples, Nathan D Price, Didier Hannequin, Ana Frank-García, Daniel Levy, Paramita Chakrabarty, Paolo Caffarra, Ina Giegling, Alexa S Beiser, Vilmantas Giedraitis, Harald Hampel, Melissa E Garcia, Xue Wang, Lars Lannfelt, Patrizia Mecocci, Gudny Eiriksdottir, Paul K Crane, Florence Pasquier, Virginia Boccardi, Isabel Henández, Robert C Barber, Martin Scherer, Lluis Tarraga, Perrie M Adams, Markus Leber, Yuning Chen, Marilyn S Albert, Steffi Riedel-Heller, Valur Emilsson, Duane Beekly, Anne Braae, Reinhold Schmidt, Deborah Blacker, Carlo Masullo, Helena Schmidt, Rachelle S Doody, Gianfranco Spalletta, W T Longstreth Jr, Thomas J Fairchild, Paola Bossù, Oscar L Lopez, Matthew P Frosch, Eleonora Sacchinelli, Bernardino Ghetti, Qiong Yang, Ryan M Huebinger, Frank Jessen, Shuo Li, M Ilyas Kamboh, John Morris, Oscar Sotolongo-Grau, Mindy J Katz, Chris Corcoran, Melanie Dunstan, Amy Braddel, Charlene Thomas, Alun Meggy, Rachel Marshall, Amy Gerrish, Jade Chapman, Miquel Aguilar, Sarah Taylor, Matt Hill, Mònica Díez Fairén, Angela Hodges, Bruno Vellas, Hilkka Soininen, Iwona Kloszewska, Makrina Daniilidou, James Uphill, Yogen Patel, Joseph T Hughes, Jenny Lord, James Turton, Annette M Hartmann, Roberta Cecchetti, Chiara Fenoglio, Maria Serpente, Marina Arcaro, Carlo Caltagirone, Maria Donata Orfei, Antonio Ciaramella, Sabrina Pichler, Manuel Mayhaus, Wei Gu, Alberto Lleó, Juan Fortea, Rafael Blesa, Imelda S Barber, Keeley Brookes, Chiara Cupidi, Raffaele Giovanni Maletta, David Carrell, Sandro Sorbi, Susanne Moebus, Maria Urbano, Alberto Pilotto, Johannes Kornhuber, Paolo Bosco, Stephen Todd, David Craig, Janet Johnston, Michael Gill, Brian Lawlor, Aoibhinn Lynch, Nick C Fox, John Hardy, Roger L Albin, Liana G Apostolova, Steven E Arnold, Sanjay Asthana, Craig S Atwood, Clinton T Baldwin, Lisa L Barnes, Sandra Barral, Thomas G Beach, James T Becker, Eileen H Bigio, Thomas D Bird, Bradley F Boeve, James D Bowen, Adam Boxer, James R Burke, Jeffrey M Burns, Joseph D Buxbaum, Nigel J Cairns, Chuanhai Cao, Chris S Carlson, Cynthia M Carlsson, Regina M Carney, Minerva M Carrasquillo, Steven L Carroll, Carolina Ceballos Diaz, Helena C Chui, David G Clark, David H Cribbs, Elizabeth A Crocco, Charles DeCarli, Malcolm Dick, Ranjan Duara, Denis A Evans, Kelley M Faber, Kenneth B Fallon, David W Fardo, Martin R Farlow, Steven Ferris, Tatiana M Foroud, Douglas R Galasko, Marla Gearing, Daniel H Geschwind, John R Gilbert, Neill R Graff-Radford, Robert C Green, John H Growdon, Ronald L Hamilton, Lindy E Harrell, Lawrence S Honig, Matthew J Huentelman, Christine M Hulette, Bradley T Hyman, Gail P Jarvik, Erin Abner, Lee-Way Jin, Gyungah Jun, Anna Karydas, Jeffrey A Kaye, Ronald Kim, Neil W Kowall, Joel H Kramer, Frank M LaFerla, James J Lah, James B Leverenz, Allan I Levey, Ge Li, Andrew P Lieberman, Kathryn L Lunetta, Constantine G Lyketsos, Daniel C Marson, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Wayne C McCormick, Susan M McCurry, Andrew N McDavid, Ann C McKee, Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, John C Morris, Jill R Murrell, Amanda J Myers, Sid O'Bryant, John M Olichney, Vernon S Pankratz, Joseph E Parisi, Henry L Paulson, William Perry, Elaine Peskind, Aimee Pierce, Wayne W Poon, Huntington Potter, Joseph F Quinn, Ashok Raj, Murray Raskind, Barry Reisberg, Christiane Reitz, John M Ringman, Erik D Roberson, Ekaterina Rogaeva, Howard J Rosen, Roger N Rosenberg, Mark A Sager, Andrew J Saykin, Julie A Schneider, Lon S Schneider, William W Seeley, Amanda G Smith, Joshua A Sonnen, Salvatore Spina, Robert A Stern, Russell H Swerdlow, Rudolph E Tanzi, Tricia A Thornton-Wells, John Q Trojanowski, Juan C Troncoso, Vivianna M Van Deerlin, Linda J Van Eldik, Harry V Vinters, Jean Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Kirk C Wilhelmsen, Jennifer Williamson, Thomas S Wingo, Randall L Woltjer, Clinton B Wright, Chang-En Yu, Lei Yu, Fabienne Garzia, Feroze Golamaully, Gislain Septier, Sebastien Engelborghs, Rik Vandenberghe, Peter P De Deyn, Carmen Muñoz Fernadez, Yoland Aladro Benito, Hakan Thonberg, Charlotte Forsell, Lena Lilius, Anne Kinhult-Stählbom, Lena Kilander, RoseMarie Brundin, Letizia Concari, Seppo Helisalmi, Anne Maria Koivisto, Annakaisa Haapasalo, Vincent Dermecourt, Nathalie Fievet, Olivier Hanon, Carole Dufouil, Alexis Brice, Karen Ritchie, Bruno Dubois, Jayanadra J Himali, C Dirk Keene, JoAnn Tschanz, Annette L Fitzpatrick, Walter A Kukull, Maria Norton, Thor Aspelund, Eric B Larson, Ron Munger, Jerome I Rotter, Richard B Lipton, María J Bullido, Albert Hofman, Thomas J Montine, Eliecer Coto, Eric Boerwinkle, Ronald C Petersen, Victoria Alvarez, Fernando Rivadeneira, Eric M Reiman, Maura Gallo, Christopher J O'Donnell, Joan S Reisch, Amalia Cecilia Bruni, Donald R Royall, Martin Dichgans, Mary Sano, Daniela Galimberti, Peter St George-Hyslop, Elio Scarpini, Debby W Tsuang, Michelangelo Mancuso, Ubaldo Bonuccelli, Ashley R Winslow, Antonio Daniele, Chuang-Kuo Wu, Oliver Peters, Benedetta Nacmias, Matthias Riemenschneider, Reinhard Heun, Carol Brayne, David C Rubinsztein, Jose Bras, Rita Guerreiro, Ammar Al-Chalabi, Christopher E Shaw, John Collinge, David Mann, Magda Tsolaki, Jordi Clarimón, Rebecca Sussams, Simon Lovestone, Michael C O'Donovan, Michael J Owen, Timothy W Behrens, Simon Mead, Alison M Goate, Andre G Uitterlinden, Clive Holmes, Carlos Cruchaga, Martin Ingelsson, David A Bennett, John Powell, Todd E Golde, Caroline Graff, Philip L De Jager, Kevin Morgan, Nilufer Ertekin-Taner, Onofre Combarros, Bruce M Psaty, Peter Passmore, Steven G Younkin, Claudine Berr, Vilmundur Gudnason, Dan Rujescu, Dennis W Dickson, Jean-François Dartigues, Anita L DeStefano, Sara Ortega-Cubero, Hakon Hakonarson, Dominique Campion, Merce Boada, John Keoni Kauwe, Lindsay A Farrer, Christine Van Broeckhoven, M Arfan Ikram, Lesley Jones, Jonathan L Haines, Christophe Tzourio, Lenore J Launer, Valentina Escott-Price, Richard Mayeux, Jean-François Deleuze, Najaf Amin, Peter A Holmans, Margaret A Pericak-Vance, Philippe Amouyel, Cornelia M van Duijn, Alfredo Ramirez, Li-San Wang, Jean-Charles Lambert, Sudha Seshadri, Julie Williams, Gerard D Schellenberg
We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10(-4)) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10(-8)) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p...
July 17, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28611041/an-immunosuppressive-dendritic-cell-subset-accumulates-at-secondary-sites-and-promotes-metastasis-in-pancreatic-cancer
#3
Justin A Kenkel, William W Tseng, Matthew G Davidson, Lorna L Tolentino, Okmi Choi, Nupur Bhattacharya, E Scott Seeley, Daniel A Winer, Nathan E Reticker-Flynn, Edgar G Engleman
Pancreatic ductal adenocarcinoma (PDAC) after complete surgical resection is often followed by distant metastatic relapse for reasons that remain unclear. In this study, we investigated how the immune response at secondary sites affects tumor spread in murine models of metastatic PDAC. Early metastases were associated with dense networks of CD11b(+)CD11c(+)MHC-II(+)CD24(+)CD64(low)F4/80(low) dendritic cells (DC), which developed from monocytes in response to tumor-released GM-CSF. These cells uniquely expressed MGL2 and PD-L2 in the metastatic microenvironment and preferentially induced the expansion of T regulatory cells (Treg) in vitro and in vivo Targeted depletion of this DC population in Mgl2(DTR) hosts activated cytotoxic lymphocytes, reduced Tregs, and inhibited metastasis development...
August 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28541286/impaired-prosaposin-lysosomal-trafficking-in-frontotemporal-lobar-degeneration-due-to-progranulin-mutations
#4
Xiaolai Zhou, Lirong Sun, Oliver Bracko, Ji Whae Choi, Yan Jia, Alissa L Nana, Owen Adam Brady, Jean C Cruz Hernandez, Nozomi Nishimura, William W Seeley, Fenghua Hu
Haploinsufficiency of progranulin (PGRN) due to mutations in the granulin (GRN) gene causes frontotemporal lobar degeneration (FTLD), and complete loss of PGRN leads to a lysosomal storage disorder, neuronal ceroid lipofuscinosis (NCL). Accumulating evidence suggests that PGRN is essential for proper lysosomal function, but the precise mechanisms involved are not known. Here, we show that PGRN facilitates neuronal uptake and lysosomal delivery of prosaposin (PSAP), the precursor of saposin peptides that are essential for lysosomal glycosphingolipid degradation...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28488187/erratum-to-interhemispheric-gene-expression-differences-in-the-cerebral-cortex-of-humans-and-macaque-monkeys
#5
Gerard Muntané, Gabriel Santpere, Andrey Verendeev, William W Seeley, Bob Jacobs, William D Hopkins, Arcadi Navarro, Chet C Sherwood
No abstract text is available yet for this article.
May 9, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28470587/a-randomized-controlled-trial-of-a-long-term-professional-mentoring-program-for-children-at-risk-outcomes-across-the-first-5-years
#6
J Mark Eddy, Charles R Martinez, Jean Baldwin Grossman, Jennifer J Cearley, Danita Herrera, Alice C Wheeler, Jeff S Rempel, Dana Foney, Jeff M Gau, Bert O Burraston, Tracy W Harachi, Kevin P Haggerty, John R Seeley
Child outcomes due to a paid professional mentoring program, Friends of the Children (FOTC), were investigated across the first 5 years of an ongoing multi-site randomized controlled trial. Participants were 278 children attending kindergarten or first grade who were identified as "at risk" for adjustment problems during adolescence. The program was delivered through established nonprofit community-based organizations. Mentors were hired to work full time and were provided training, supervision, and support to work individually with small numbers of children...
May 3, 2017: Prevention Science: the Official Journal of the Society for Prevention Research
https://www.readbyqxmd.com/read/28404863/individuals-with-progranulin-haploinsufficiency-exhibit-features-of-neuronal-ceroid-lipofuscinosis
#7
Michael E Ward, Robert Chen, Hsin-Yi Huang, Connor Ludwig, Maria Telpoukhovskaia, Ali Taubes, Helene Boudin, Sakura S Minami, Meredith Reichert, Philipp Albrecht, Jeffrey M Gelfand, Andres Cruz-Herranz, Christian Cordano, Marcel V Alavi, Shannon Leslie, William W Seeley, Bruce L Miller, Eileen Bigio, Marek-Marsel Mesulam, Matthew S Bogyo, Ian R Mackenzie, John F Staropoli, Susan L Cotman, Eric J Huang, Li Gan, Ari J Green
Heterozygous mutations in the GRN gene lead to progranulin (PGRN) haploinsufficiency and cause frontotemporal dementia (FTD), a neurodegenerative syndrome of older adults. Homozygous GRN mutations, on the other hand, lead to complete PGRN loss and cause neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease usually seen in children. Given that the predominant clinical and pathological features of FTD and NCL are distinct, it is controversial whether the disease mechanisms associated with complete and partial PGRN loss are similar or distinct...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28377871/weight-loss-independent-changes-in-adipose-tissue-macrophage-and-t-cell-populations-after-sleeve-gastrectomy-in-mice
#8
Henriette Frikke-Schmidt, Brian F Zamarron, Robert W O'Rourke, Darleen A Sandoval, Carey N Lumeng, Randy J Seeley
OBJECTIVE: In addition to adipocytes, adipose tissue contains large numbers of immune cells. A wide range of evidence links the activity of these cells to regulation of adipocyte and systemic metabolic function. Bariatric surgery improves several aspects of metabolic derangements and at least some of these effects occur in a weight-loss independent manner. We sought to investigate the impact of vertical sleeve gastrectomy (VSG) on adipose immune cell frequencies. METHODS: We analyzed the frequencies of immune cells within distinct adipose tissue depots in obese mice that had VSG or sham surgery with a portion of the latter group pair-fed such that their body mass was matched to the VSG animals...
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28376190/effects-of-ctgf-blockade-on-attenuation-and-reversal-of-radiation-induced-pulmonary-fibrosis
#9
Sebastian Bickelhaupt, Christian Erbel, Carmen Timke, Ute Wirkner, Monika Dadrich, Paul Flechsig, Alexandra Tietz, Johanna Pföhler, Wolfgang Gross, Peter Peschke, Line Hoeltgen, Hugo A Katus, Hermann-Josef Gröne, Nils H Nicolay, Rainer Saffrich, Jürgen Debus, Mark D Sternlicht, Todd W Seeley, Kenneth E Lipson, Peter E Huber
Background: Radiotherapy is a mainstay for the treatment of lung cancer that can induce pneumonitis or pulmonary fibrosis. The matricellular protein connective tissue growth factor (CTGF) is a central mediator of tissue remodeling. Methods: A radiation-induced mouse model of pulmonary fibrosis was used to determine if transient administration of a human antibody to CTGF (FG-3019) started at different times before or after 20 Gy thoracic irradiation reduced acute and chronic radiation toxicity...
August 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28337409/network-degeneration-and-dysfunction-in-presymptomatic-c9orf72-expansion-carriers
#10
Suzee E Lee, Ana C Sias, Maria Luisa Mandelli, Jesse A Brown, Alainna B Brown, Anna M Khazenzon, Anna A Vidovszky, Theodore P Zanto, Anna M Karydas, Mochtar Pribadi, Deepika Dokuru, Giovanni Coppola, Dan H Geschwind, Rosa Rademakers, Maria Luisa Gorno-Tempini, Howard J Rosen, Bruce L Miller, William W Seeley
Hexanucleotide repeat expansions in C9ORF72 are the most common known genetic cause of familial and sporadic frontotemporal dementia and amyotrophic lateral sclerosis. Previous work has shown that patients with behavioral variant frontotemporal dementia due to C9ORF72 show salience and sensorimotor network disruptions comparable to those seen in sporadic behavioral variant frontotemporal dementia, but it remains unknown how early in the lifespan these and other changes in brain structure and function arise...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28331872/induction-of-erythropoiesis-by-hypoxia-inducible-factor-prolyl-hydroxylase-inhibitors-without-promotion-of-tumor-initiation-progression-or-metastasis-in-a-vegf-sensitive-model-of-spontaneous-breast-cancer
#11
Todd W Seeley, Mark D Sternlicht, Stephen J Klaus, Thomas B Neff, David Y Liu
The effects of pharmacological hypoxia-inducible factor (HIF) stabilization were investigated in the MMTV-Neu(ndl)-YD5 (NeuYD) mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF), using bigenic NeuYD;MMTV-VEGF-25 mice. Tumor initiation was dramatically accelerated in bigenic animals. Bigenic tumors were also more aggressive, with shortened doubling times and increased lung metastasis as compared to NeuYD controls. In separate studies, NeuYD mice were treated three times weekly from 7 weeks of age until study end with two different HIF prolyl hydroxylase inhibitors (HIF-PHIs), FG-4497 or roxadustat (FG-4592)...
2017: Hypoxia
https://www.readbyqxmd.com/read/28317062/interhemispheric-gene-expression-differences-in-the-cerebral-cortex-of-humans-and-macaque-monkeys
#12
Gerard Muntané, Gabriel Santpere, Andrey Verendeev, William W Seeley, Bob Jacobs, William D Hopkins, Arcadi Navarro, Chet C Sherwood
Handedness and language are two well-studied examples of asymmetrical brain function in humans. Approximately 90% of humans exhibit a right-hand preference, and the vast majority shows left-hemisphere dominance for language function. Although genetic models of human handedness and language have been proposed, the actual gene expression differences between cerebral hemispheres in humans remain to be fully defined. In the present study, gene expression profiles were examined in both hemispheres of three cortical regions involved in handedness and language in humans and their homologues in rhesus macaques: ventrolateral prefrontal cortex, posterior superior temporal cortex (STC), and primary motor cortex...
March 19, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28289062/mapping-neurodegenerative-disease-onset-and-progression
#13
William W Seeley
Brain networks have been of long-standing interest to neurodegeneration researchers, including but not limited to investigators focusing on conventional prion diseases, which are known to propagate along neural pathways. Tools for human network mapping, however, remained inadequate, limiting our understanding of human brain network architecture and preventing clinical research applications. Until recently, neuropathological studies were the only viable approach to mapping disease onset and progression in humans but required large autopsy cohorts and laborious methods for whole-brain sectioning and staining...
March 13, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28271184/shared-genetic-risk-between-corticobasal-degeneration-progressive-supranuclear-palsy-and-frontotemporal-dementia
#14
Jennifer S Yokoyama, Celeste M Karch, Chun C Fan, Luke W Bonham, Naomi Kouri, Owen A Ross, Rosa Rademakers, Jungsu Kim, Yunpeng Wang, Günter U Höglinger, Ulrich Müller, Raffaele Ferrari, John Hardy, Parastoo Momeni, Leo P Sugrue, Christopher P Hess, A James Barkovich, Adam L Boxer, William W Seeley, Gil D Rabinovici, Howard J Rosen, Bruce L Miller, Nicholas J Schmansky, Bruce Fischl, Bradley T Hyman, Dennis W Dickson, Gerard D Schellenberg, Ole A Andreassen, Anders M Dale, Rahul S Desikan
Corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and a subset of frontotemporal dementia (FTD) are neurodegenerative disorders characterized by tau inclusions in neurons and glia (tauopathies). Although clinical, pathological and genetic evidence suggests overlapping pathobiology between CBD, PSP, and FTD, the relationship between these disorders is still not well understood. Using summary statistics (odds ratios and p values) from large genome-wide association studies (total n = 14,286 cases and controls) and recently established genetic methods, we investigated the genetic overlap between CBD and PSP and CBD and FTD...
May 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28264087/precipitous-deterioration-of-motor-function-cognition-and-behavior
#15
Mireya Fernández-Fournier, David C Perry, Maria Carmela Tartaglia, Mary de May, Adam Boxer, Giovanni Coppola, Chadwick W Christine, Eric J Huang, William W Seeley, Bruce L Miller, Steven J DeArmond, Lea T Grinberg, Michael D Geschwind
A 72-year-old woman developed new-onset depression, sustained an unexplained fall, and started walking cautiously. After 1 year, her depression resolved but she developed a dry cough. One year later, she experienced a more rapid decline in her gait with parkinsonism, visual difficulties with restricted vertical gaze, slowed horizontal and vertical saccades, dysphagia, apathy, and progressive cognitive decline, which led to her death 2 years later. The differential diagnosis, neuroimaging, and pathological findings are discussed, as well as their public health implications...
May 1, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28133816/typical-and-atypical-pathology-in-primary-progressive-aphasia-variants
#16
Edoardo G Spinelli, Maria Luisa Mandelli, Zachary A Miller, Miguel A Santos-Santos, Stephen M Wilson, Federica Agosta, Lea T Grinberg, Eric J Huang, John Q Trojanowski, Marita Meyer, Maya L Henry, Giancarlo Comi, Gil Rabinovici, Howard J Rosen, Massimo Filippi, Bruce L Miller, William W Seeley, Maria Luisa Gorno-Tempini
OBJECTIVE: To characterize in vivo signatures of pathological diagnosis in a large cohort of patients with primary progressive aphasia (PPA) variants defined by current diagnostic classification. METHODS: Extensive clinical, cognitive, neuroimaging, and neuropathological data were collected from 69 patients with sporadic PPA, divided into 29 semantic (svPPA), 25 nonfluent (nfvPPA), 11 logopenic (lvPPA), and 4 mixed PPA. Patterns of gray matter (GM) and white matter (WM) atrophy at presentation were assessed and tested as predictors of pathological diagnosis using support vector machine (SVM) algorithms...
March 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28130473/frontotemporal-dementia-with-the-v337m-mapt-mutation-tau-pet-and-pathology-correlations
#17
Salvatore Spina, Daniel R Schonhaut, Bradley F Boeve, William W Seeley, Rik Ossenkoppele, James P O'Neil, Andreas Lazaris, Howard J Rosen, Adam L Boxer, David C Perry, Bruce L Miller, Dennis W Dickson, Joseph E Parisi, William J Jagust, Melissa E Murray, Gil D Rabinovici
OBJECTIVE: To assess the efficacy of [(18)F]AV1451 PET in visualizing tau pathology in vivo in a patient with frontotemporal dementia (FTD) associated with the V337M microtubule-associated protein tau (MAPT) mutation. METHODS: MAPT mutations are associated with the deposition of hyperphosphorylated tau protein in neurons and glia. The PET tracer [(18)F]AV1451 binds with high affinity to paired helical filaments tau that comprises neurofibrillary tangles in Alzheimer disease (AD), while postmortem studies suggest lower or absent binding to the tau filaments of the majority of non-AD tauopathies...
February 21, 2017: Neurology
https://www.readbyqxmd.com/read/28117917/quantifying-the-accretion-of-hyperphosphorylated-tau-in-the-locus-coeruleus-and-dorsal-raphe-nucleus-the-pathological-building-blocks-of-early-alzheimer-s-disease
#18
A J Ehrenberg, A K Nguy, P Theofilas, S Dunlop, C K Suemoto, A T Di Lorenzo Alho, R P Leite, R Diehl Rodriguez, M B Mejia, U Rüb, J M Farfel, R E de Lucena Ferretti-Rebustini, C F Nascimento, R Nitrini, C A Pasquallucci, W Jacob-Filho, B Miller, W W Seeley, H Heinsen, L T Grinberg
AIMS: Hyperphosphorylated tau neuronal cytoplasmic inclusions (ht-NCI) are the best protein correlate of clinical decline in Alzheimer's disease (AD). Qualitative evidence identifies ht-NCI accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht-NCI burden in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages. METHODS: We utilized unbiased stereology in a sample of 48 well-characterized subjects enriched for controls and early AD stages...
January 24, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28113724/brain-modulyzer-interactive-visual-analysis-of-functional-brain-connectivity
#19
Sugeerth Murugesan, Kristofer Bouchard, Jesse A Brown, Bernd Hamann, William W Seeley, Andrew Trujillo, Gunther H Weber
We present Brain Modulyzer, an interactive visual exploration tool for functional magnetic resonance imaging (fMRI) brain scans, aimed at analyzing the correlation between different brain regions when resting or when performing mental tasks. Brain Modulyzer combines multiple coordinated views-such as heat maps, node link diagrams and anatomical views-using brushing and linking to provide an anatomical context for brain connectivity data. Integrating methods from graph theory and analysis, e.g., community detection and derived graph measures, makes it possible to explore the modular and hierarchical organization of functional brain networks...
May 9, 2016: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28072389/suppression-of-c9orf72-rna-repeat-induced-neurotoxicity-by-the-als-associated-rna-binding-protein-zfp106
#20
Barbara Celona, John von Dollen, Sarat C Vatsavayai, Risa Kashima, Jeffrey R Johnson, Amy A Tang, Akiko Hata, Bruce L Miller, Eric J Huang, Nevan J Krogan, William W Seeley, Brian L Black
Expanded GGGGCC repeats in the first intron of the C9orf72 gene represent the most common cause of familial amyotrophic lateral sclerosis (ALS), but the mechanisms underlying repeat-induced disease remain incompletely resolved. One proposed gain-of-function mechanism is that repeat-containing RNA forms aggregates that sequester RNA binding proteins, leading to altered RNA metabolism in motor neurons. Here, we identify the zinc finger protein Zfp106 as a specific GGGGCC RNA repeat-binding protein, and using affinity purification-mass spectrometry, we show that Zfp106 interacts with multiple other RNA binding proteins, including the ALS-associated factors TDP-43 and FUS...
January 10, 2017: ELife
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