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https://www.readbyqxmd.com/read/28488187/erratum-to-interhemispheric-gene-expression-differences-in-the-cerebral-cortex-of-humans-and-macaque-monkeys
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
https://www.readbyqxmd.com/read/28040670/focal-temporal-pole-atrophy-and-network-degeneration-in-semantic-variant-primary-progressive-aphasia
#17
MULTICENTER STUDY
Jessica A Collins, Victor Montal, Daisy Hochberg, Megan Quimby, Maria Luisa Mandelli, Nikos Makris, William W Seeley, Maria Luisa Gorno-Tempini, Bradford C Dickerson
A wealth of neuroimaging research has associated semantic variant primary progressive aphasia with distributed cortical atrophy that is most prominent in the left anterior temporal cortex; however, there is little consensus regarding which region within the anterior temporal cortex is most prominently damaged, which may indicate the putative origin of neurodegeneration. In this study, we localized the most prominent and consistent region of atrophy in semantic variant primary progressive aphasia using cortical thickness analysis in two independent patient samples (n = 16 and 28, respectively) relative to age-matched controls (n = 30)...
February 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28035008/regulator-of-g-protein-signaling-6-protects-the-heart-from-ischemic-injury
#18
Boyd R Rorabaugh, Bandana Chakravarti, Nathaniel W Mabe, Sarah L Seeley, Albert D Bui, Jianqi Yang, Stephanie W Watts, Richard R Neubig, Rory A Fisher
Gαi-coupled receptors play important roles in protecting the heart from ischemic injury. Regulator of G protein signaling (RGS) proteins suppress Gαi signaling by accelerating the GTPase activity of Gαi subunits. However, the roles of individual RGS proteins in modulating ischemic injury are unknown. In this study, we investigated the effect of RGS6 deletion on myocardial sensitivity to ischemic injury. Hearts from RGS6 knockout (RGS6(-/-)) and RGS6 wild-type (RGS6(+/+)) mice were subjected to 30 minutes of ischemia and 2 hours of reperfusion on a Langendorff heart apparatus...
March 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27981028/regional-correlations-between-11-c-pib-pet-and-post-mortem-burden-of-amyloid-beta-pathology-in-a-diverse-neuropathological-cohort
#19
Sang Won Seo, Nagehan Ayakta, Lea T Grinberg, Sylvia Villeneuve, Manja Lehmann, Bruce Reed, Charles DeCarli, Bruce L Miller, Howard J Rosen, Adam L Boxer, James P O'Neil, Lee-Way Jin, William W Seeley, William J Jagust, Gil D Rabinovici
Imaging-pathological correlation studies show that in vivo amyloid-β (Aβ) positron emission tomography (PET) strongly predicts the presence of significant Aβ pathology at autopsy. We sought to determine whether regional PiB-PET uptake would improve sensitivity for amyloid detection in comparison with global measures (experiment 1), and to estimate the relative contributions of different Aβ aggregates to in vivo PET signal (experiment 2). In experiment 1, 54 subjects with [(11)C] PiB-PET during life and postmortem neuropathologic examination (85...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/27913432/von-economo-neurons-and-fork-cells-a-neurochemical-signature-linked-to-monoaminergic-function
#20
Anke A Dijkstra, Li-Chun Lin, Alissa L Nana, Stephanie E Gaus, William W Seeley
The human anterior cingulate and frontoinsular cortices are distinguished by 2 unique Layer 5 neuronal morphotypes, the von Economo neurons (VENs) and fork cells, whose biological identity remains mysterious. Insights could impact research on diverse neuropsychiatric diseases to which these cells have been linked. Here, we leveraged the Allen Brain Atlas to evaluate mRNA expression of 176 neurotransmitter-related genes and identified vesicular monoamine transporter 2 (VMAT2), gamma-aminobutyric acid (GABA) receptor subunit θ (GABRQ), and adrenoreceptor α-1A (ADRA1A) expression in human VENs, fork cells, and a minority of neighboring Layer 5 neurons...
December 1, 2016: Cerebral Cortex
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