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https://www.readbyqxmd.com/read/29117955/alzheimer-s-disease-related-dementias-summit-2016-national-research-priorities
#1
REVIEW
Roderick A Corriveau, Walter J Koroshetz, Jordan T Gladman, Sophia Jeon, Debra Babcock, David A Bennett, S Thomas Carmichael, Susan L-J Dickinson, Dennis W Dickson, Marian Emr, Howard Fillit, Steven M Greenberg, Michael L Hutton, David S Knopman, Jennifer J Manly, Karen S Marder, Claudia S Moy, Creighton H Phelps, Paul A Scott, William W Seeley, Beth-Anne Sieber, Nina B Silverberg, Margaret L Sutherland, Angela Taylor, Christine L Torborg, Salina P Waddy, Amelie K Gubitz, David M Holtzman
Goal 1 of the National Plan to Address Alzheimer's Disease is to prevent and effectively treat Alzheimer disease and Alzheimer disease-related dementias by 2025. To help inform the research agenda toward achieving this goal, the NIH hosts periodic summits that set and refine relevant research priorities for the subsequent 5 to 10 years. This proceedings article summarizes the 2016 Alzheimer's Disease-Related Dementias Summit, including discussion of scientific progress, challenges, and opportunities in major areas of dementia research, including mixed-etiology dementias, Lewy body dementia, frontotemporal degeneration, vascular contributions to cognitive impairment and dementia, dementia disparities, and dementia nomenclature...
November 8, 2017: Neurology
https://www.readbyqxmd.com/read/29053860/clinicopathological-correlations-in-behavioural-variant-frontotemporal-dementia
#2
David C Perry, Jesse A Brown, Katherine L Possin, Samir Datta, Andrew Trujillo, Anneliese Radke, Anna Karydas, John Kornak, Ana C Sias, Gil D Rabinovici, Maria Luisa Gorno-Tempini, Adam L Boxer, Mary De May, Katherine P Rankin, Virginia E Sturm, Suzee E Lee, Brandy R Matthews, Aimee W Kao, Keith A Vossel, Maria Carmela Tartaglia, Zachary A Miller, Sang Won Seo, Manu Sidhu, Stephanie E Gaus, Alissa L Nana, Jose Norberto S Vargas, Ji-Hye L Hwang, Rik Ossenkoppele, Alainna B Brown, Eric J Huang, Giovanni Coppola, Howard J Rosen, Daniel Geschwind, John Q Trojanowski, Lea T Grinberg, Joel H Kramer, Bruce L Miller, William W Seeley
Accurately predicting the underlying neuropathological diagnosis in patients with behavioural variant frontotemporal dementia (bvFTD) poses a daunting challenge for clinicians but will be critical for the success of disease-modifying therapies. We sought to improve pathological prediction by exploring clinicopathological correlations in a large bvFTD cohort. Among 438 patients in whom bvFTD was either the top or an alternative possible clinical diagnosis, 117 had available autopsy data, including 98 with a primary pathological diagnosis of frontotemporal lobar degeneration (FTLD), 15 with Alzheimer's disease, and four with amyotrophic lateral sclerosis who lacked neurodegenerative disease-related pathology outside of the motor system...
October 6, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29053832/reward-deficits-in-behavioural-variant-frontotemporal-dementia-include-insensitivity-to-negative-stimuli
#3
David C Perry, Samir Datta, Virginia E Sturm, Kristie A Wood, Jessica Zakrzewski, William W Seeley, Bruce L Miller, Joel H Kramer, Howard J Rosen
During reward processing individuals weigh positive and negative features of a stimulus to determine whether they will pursue or avoid it. Though patients with behavioural variant frontotemporal dementia display changes in their pursuit of rewards, such as food, alcohol, money, and sex, the basis for these shifts is not clearly established. In particular, it is unknown whether patients' behaviour results from excessive focus on rewards, insensitivity to punishment, or to dysfunction in a particular stage of reward processing, such as anticipation, consumption, or action selection...
October 7, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29031088/probing-the-correlation-of-neuronal-loss-neurofibrillary-tangles-and-cell-death-markers-across-the-alzheimer-s-disease-braak-stages-a-quantitative-study-in-humans
#4
Panos Theofilas, Alexander J Ehrenberg, Austin Nguy, Julia M Thackrey, Sara Dunlop, Maria B Mejia, Ana T Alho, Renata Elaine Paraizo Leite, Roberta Diehl Rodriguez, Claudia K Suemoto, Camila F Nascimento, Marcus Chin, Daniel Medina-Cleghorn, Ana Maria Cuervo, Michelle Arkin, William W Seeley, Bruce L Miller, Ricardo Nitrini, Carlos Augusto Pasqualucci, Wilson Jacob Filho, Udo Rueb, John Neuhaus, Helmut Heinsen, Lea T Grinberg
Clarifying the mechanisms connecting neurofibrillary tangle (NFT) neurotoxicity to neuronal dysfunction in humans is likely to be pivotal for developing effective treatments for Alzheimer's disease (AD). To model the temporal progression of AD in humans, we used a collection of brains with controls and individuals from each Braak stage to quantitatively investigate the correlation between intraneuronal caspase activation or macroautophagy markers, NFT burden, and neuronal loss, in the dorsal raphe nucleus and locus coeruleus, the earliest vulnerable areas to NFT accumulation...
September 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28980714/-18-f-flortaucipir-tau-positron-emission-tomography-distinguishes-established-progressive-supranuclear-palsy-from-controls-and-parkinson-disease-a-multicenter-study
#5
MULTICENTER STUDY
Daniel R Schonhaut, Corey T McMillan, Salvatore Spina, Bradford C Dickerson, Andrew Siderowf, Michael D Devous, Richard Tsai, Joseph Winer, David S Russell, Irene Litvan, Erik D Roberson, William W Seeley, Lea T Grinberg, Joel H Kramer, Bruce L Miller, Peter Pressman, Ilya Nasrallah, Suzanne L Baker, Stephen N Gomperts, Keith A Johnson, Murray Grossman, William J Jagust, Adam L Boxer, Gil D Rabinovici
OBJECTIVE: (18) F-flortaucipir (formerly (18) F-AV1451 or (18) F-T807) binds to neurofibrillary tangles in Alzheimer disease, but tissue studies assessing binding to tau aggregates in progressive supranuclear palsy (PSP) have yielded mixed results. We compared in vivo (18) F-flortaucipir uptake in patients meeting clinical research criteria for PSP (n = 33) to normal controls (n = 46) and patients meeting criteria for Parkinson disease (PD; n = 26). METHODS: Participants underwent magnetic resonance imaging and positron emission tomography for amyloid-β ((11) C-PiB or (18) F-florbetapir) and tau ((18) F-flortaucipir)...
October 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28959956/apoe4-markedly-exacerbates-tau-mediated-neurodegeneration-in-a-mouse-model-of-tauopathy
#6
Yang Shi, Kaoru Yamada, Shane Antony Liddelow, Scott T Smith, Lingzhi Zhao, Wenjie Luo, Richard M Tsai, Salvatore Spina, Lea T Grinberg, Julio C Rojas, Gilbert Gallardo, Kairuo Wang, Joseph Roh, Grace Robinson, Mary Beth Finn, Hong Jiang, Patrick M Sullivan, Caroline Baufeld, Michael W Wood, Courtney Sutphen, Lena McCue, Chengjie Xiong, Jorge L Del-Aguila, John C Morris, Carlos Cruchaga, Anne M Fagan, Bruce L Miller, Adam L Boxer, William W Seeley, Oleg Butovsky, Ben A Barres, Steven M Paul, David M Holtzman
APOE4 is the strongest genetic risk factor for late-onset Alzheimer disease. ApoE4 increases brain amyloid-β pathology relative to other ApoE isoforms. However, whether APOE independently influences tau pathology, the other major proteinopathy of Alzheimer disease and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human ApoE knock-in (KI) or ApoE knockout (KO) background, here we show that P301S/E4 mice have significantly higher tau levels in the brain and a greater extent of somatodendritic tau redistribution by three months of age compared with P301S/E2, P301S/E3, and P301S/EKO mice...
September 28, 2017: Nature
https://www.readbyqxmd.com/read/28951832/advancing-functional-dysconnectivity-and-atrophy-in-progressive-supranuclear-palsy
#7
Jesse A Brown, Alice Y Hua, Andrew Trujllo, Suneth Attygalle, Richard J Binney, Salvatore Spina, Suzee E Lee, Joel H Kramer, Bruce L Miller, Howard J Rosen, Adam L Boxer, William W Seeley
Progressive supranuclear palsy syndrome (PSP-S) results from neurodegeneration within a network of brainstem, subcortical, frontal and parietal cortical brain regions. It is unclear how network dysfunction progresses and relates to longitudinal atrophy and clinical decline. In this study, we evaluated patients with PSP-S (n = 12) and healthy control subjects (n = 20) at baseline and 6 months later. Subjects underwent structural MRI and task-free functional MRI (tf-fMRI) scans and clinical evaluations at both time points...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28898979/obesity-pathogenesis-an-endocrine-society-scientific-statement
#8
Michael W Schwartz, Randy J Seeley, Lori M Zeltser, Adam Drewnowski, Eric Ravussin, Leanne M Redman, Rudolph L Leibel
Obesity is among the most common and costly chronic disorders worldwide. Estimates suggest that in the United States obesity affects one-third of adults, accounts for up to one-third of total mortality, is concentrated among lower income groups, and increasingly affects children as well as adults. A lack of effective options for long-term weight reduction magnifies the enormity of this problem; individuals who successfully complete behavioral and dietary weight-loss programs eventually regain most of the lost weight...
August 1, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28854673/peculiar-citric-acid-cycle-of-hydrothermal-vent-chemolithoautotroph-hydrogenovibrio-crunogenus-and-insights-into-carbon-metabolism-by-obligate-autotrophs
#9
Ishtiaque Quasem, Alexandra N Achille, Brittany A Caddick, Travis A Carter, Camille Daniels, Jennifer A Delaney, Vedad Delic, Kimberly A Denton, Martina C Duran, Marianne K Fatica, Christopher M Ference, Julie P Galkiewicz, Ana M Garcia, Jacqueline D Hendrick, Steven A Horton, Mey S Kun, Phoebe W Koch, Tien Min Lee, Christie R McCabe, Sean McHale, Lauren D McDaniel, Damian M Menning, Kristy J Menning, Hamed Mirzaei-Souderjani, Salina Mostajabian, David A Nicholson, Courtney K Nugent, Nicholas P Osman, Desiree I Pappas, Andrea M Rocha, Karyna Rosario, Haydn Rubelmann, Julie A Schwartz, Kent W Seeley, Christopher M Staley, Elizabeth M Wallace, Terianne M Wong, Brian L Zielinski, Thomas E Hanson, Kathleen M Scott
The genome sequence of the obligate chemolithoautotroph Hydrogenovibrio crunogenus paradoxically predicts a complete oxidative citric acid cycle (CAC). This prediction was tested by multiple approaches including whole cell carbon assimilation to verify obligate autotrophy, phylogenetic analysis of CAC enzyme sequences and enzyme assays. Hydrogenovibrio crunogenus did not assimilate any of the organic compounds provided (acetate, succinate, glucose, yeast extract, tryptone). Enzyme activities confirmed that its CAC is mostly uncoupled from the NADH pool...
August 1, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28818053/the-impact-of-self-interviews-on-response-patterns-for-sensitive-topics-a-randomized-trial-of-electronic-delivery-methods-for-a-sexual-behaviour-questionnaire-in-rural-south-africa
#10
Guy Harling, Dumile Gumede, Tinofa Mutevedzi, Nuala McGrath, Janet Seeley, Deenan Pillay, Till W Bärnighausen, Abraham J Herbst
BACKGROUND: Self-interviews, where the respondent rather than the interviewer enters answers to questions, have been proposed as a way to reduce social desirability bias associated with interviewer-led interviews. Computer-assisted self-interviews (CASI) are commonly proposed since the computer programme can guide respondents; however they require both language and computer literacy. We evaluated the feasibility and acceptability of using electronic methods to administer quantitative sexual behaviour questionnaires in the Somkhele demographic surveillance area (DSA) in rural KwaZulu-Natal, South Africa...
August 17, 2017: BMC Medical Research Methodology
https://www.readbyqxmd.com/read/28776676/consistency-of-elemental-and-isotope-ratio-patterns-across-multiple-scales-from-individual-fish
#11
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
#12
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...
September 2017: Nature Genetics
https://www.readbyqxmd.com/read/28611041/an-immunosuppressive-dendritic-cell-subset-accumulates-at-secondary-sites-and-promotes-metastasis-in-pancreatic-cancer
#13
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
#14
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
#15
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.
September 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
#16
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...
November 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
#17
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
#18
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
#19
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
#20
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
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