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Paul Edison

Zhen Fan, Melanie Dani, Grazia D Femminella, Melanie Wood, Valeria Calsolaro, Mattia Veronese, Federico Turkheimer, Steve Gentleman, David J Brooks, Rainer Hinz, Paul Edison
PURPOSE: Neuroinflammation and microglial activation play an important role in amnestic mild cognitive impairment (MCI) and Alzheimer's disease. In this study, we investigated the spatial distribution of neuroinflammation in MCI subjects, using spectral analysis (SA) to generate parametric maps and quantify11 C-PBR28 PET, and compared these with compartmental and other kinetic models of quantification. METHODS: Thirteen MCI and nine healthy controls were enrolled in this study...
March 9, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Cornelius K Donat, Nazanin Mirzaei, Sac-Pharm Tang, Paul Edison, Magdalena Sastre
Deficits in neuronal function and synaptic plasticity in Alzheimer's disease (AD) are believed to be linked to microglial activation. A hallmark of reactive microglia is the upregulation of mitochondrial translocator protein (TSPO) expression. Positron emission tomography (PET) is a nuclear imaging technique that measures the distribution of trace doses of radiolabeled compounds in the body over time. PET imaging using the 2nd generation TSPO tracer [11 C]PBR28 provides an opportunity for accurate visualization and quantification of changes in microglial density in transgenic mouse models of Alzheimer's disease (AD)...
2018: Methods in Molecular Biology
Vidushi Neergheen-Bhujun, Almas Taj Awan, Yusuf Baran, Nils Bunnefeld, Kit Chan, Thomas Edison Dela Cruz, Dilfuza Egamberdieva, Simon Elsässer, Mari-Vaughn V Johnson, Shoji Komai, Andrey L Konevega, John H Malone, Paul Mason, Rothsophal Nguon, Ross Piper, Uttam Babu Shrestha, Milica Pešić, Alexander Kagansky
No abstract text is available yet for this article.
December 2017: Journal of Global Health
Nicholas A Willis, Richard L Frock, Francesca Menghi, Erin E Duffey, Arvind Panday, Virginia Camacho, E Paul Hasty, Edison T Liu, Frederick W Alt, Ralph Scully
Small, approximately 10-kilobase microhomology-mediated tandem duplications are abundant in the genomes of BRCA1-linked but not BRCA2-linked breast cancer. Here we define the mechanism underlying this rearrangement signature. We show that, in primary mammalian cells, BRCA1, but not BRCA2, suppresses the formation of tandem duplications at a site-specific chromosomal replication fork barrier imposed by the binding of Tus proteins to an array of Ter sites. BRCA1 has no equivalent role at chromosomal double-stranded DNA breaks, indicating that tandem duplications form specifically at stalled forks...
November 30, 2017: Nature
Marc Mulet-Gas, Laura Abella, Maira R Cerón, Edison Castro, Alan G Marshall, Antonio Rodríguez-Fortea, Luis Echegoyen, Josep M Poblet, Paul W Dunk
An ultimate goal in carbon nanoscience is to decipher formation mechanisms of highly ordered systems. Here, we disclose chemical processes that result in formation of high-symmetry clusterfullerenes, which attract interest for use in applications that span biomedicine to molecular electronics. The conversion of doped graphite into a C80 cage is shown to occur through bottom-up self-assembly reactions. Unlike conventional forms of fullerene, the iconic Buckminsterfullerene cage, I h-C60, is entirely avoided in the bottom-up formation mechanism to afford synthesis of group 3-based metallic nitride clusterfullerenes...
October 31, 2017: Nature Communications
Andre Lopes, Jessica St Louis, Marcelo Luiz Balancin, Angelica Nogueira-Rodrigues, Luana C F F Silva, Eduardo Paulino, Bianca Silveira Sá, Alexandra Bukowski, Edison Mantovani Barbosa, Ronaldo Lúcio Rangel Costa, Paul E Goss
No abstract text is available yet for this article.
June 23, 2017: Clinical Breast Cancer
Grazia Daniela Femminella, Leonardo Bencivenga, Laura Petraglia, Lucia Visaggi, Lucia Gioia, Fabrizio Vincenzo Grieco, Claudio de Lucia, Klara Komici, Graziamaria Corbi, Paul Edison, Giuseppe Rengo, Nicola Ferrara
Diabetes mellitus (DM) and Alzheimer's disease (AD) are two highly prevalent conditions in the elderly population and major public health burden. In the past decades, a pathophysiological link between DM and AD has emerged and central nervous system insulin resistance might play a significant role as a common mechanism; however, other factors such as inflammation and oxidative stress seem to contribute to the shared pathophysiological link. Both preclinical and clinical studies have evaluated the possible neuroprotective mechanisms of different classes of antidiabetic medications in AD, with some promising results...
2017: Journal of Diabetes Research
Edison S Zuniga, Aaron Korkegian, Steven Mullen, Erik J Hembre, Paul L Ornstein, Guillermo Cortez, Kallolmay Biswas, Naresh Kumar, Jeffrey Cramer, Thierry Masquelin, Philip A Hipskind, Joshua Odingo, Tanya Parish
We identified a di-substituted triazolopyrimidine with anti-tubercular activity against Mycobacterium tuberculosis. Three segments of the scaffold were examined rationally to establish a structure-activity relationship with the goal of improving potency and maintaining good physicochemical properties. A number of compounds displayed sub-micromolar activity against Mycobacterium tuberculosis with no cytotoxicity against eukaryotic cells. Non-substituted aromatic rings at C5 and a two-carbon chain connecting a terminal aromatic at C7 were preferred features; the presence of NH at C7 and a lack of substituent at C2 were essential for potency...
August 1, 2017: Bioorganic & Medicinal Chemistry
Peter Parbo, Rola Ismail, Kim V Hansen, Ali Amidi, Frederik H Mårup, Hanne Gottrup, Hans Brændgaard, Bengt O Eriksson, Simon F Eskildsen, Torben E Lund, Anna Tietze, Paul Edison, Nicola Pavese, Morten G Stokholm, Per Borghammer, Rainer Hinz, Joel Aanerud, David J Brooks
See Kreisl (doi:10.1093/awx151) for a scientific commentary on this article.Subjects with mild cognitive impairment associated with cortical amyloid-β have a greatly increased risk of progressing to Alzheimer's disease. We hypothesized that neuroinflammation occurs early in Alzheimer's disease and would be present in most amyloid-positive mild cognitive impairment cases. 11C-Pittsburgh compound B and 11C-(R)-PK11195 positron emission tomography was used to determine the amyloid load and detect the extent of neuroinflammation (microglial activation) in 42 mild cognitive impairment cases...
July 1, 2017: Brain: a Journal of Neurology
Zhen Fan, David J Brooks, Aren Okello, Paul Edison
Amyloid-β deposition, neuroinflammation and tau tangle formation all play a significant role in Alzheimer's disease. We hypothesized that there is microglial activation early on in Alzheimer's disease trajectory, where in the initial phase, microglia may be trying to repair the damage, while later on in the disease these microglia could be ineffective and produce proinflammatory cytokines leading to progressive neuronal damage. In this longitudinal study, we have evaluated the temporal profile of microglial activation and its relationship between fibrillar amyloid load at baseline and follow-up in subjects with mild cognitive impairment, and this was compared with subjects with Alzheimer's disease...
March 1, 2017: Brain: a Journal of Neurology
Jansen de Araujo, Michael K Lo, Azaibi Tamin, Tatiana L Ometto, Luciano M Thomazelli, Marcello S Nardi, Renata F Hurtado, Alessandra Nava, Christina F Spiropoulou, Paul A Rota, Edison L Durigon
Bats are reservoir hosts for many paramyxoviruses, some of which cause human and zoonotic diseases of public health importance. We developed a Nipah virus nucleoprotein enzyme-linked immunosorbent assay to detect cross-reactive antibodies in serum samples from several bat species in Brazil. Our results warrant further investigation of henipa-like virus reservoirs in the Western hemisphere.
April 2017: Vector Borne and Zoonotic Diseases
Maira R Cerón, Edison Castro, Venkata S Pavan K Neti, Paul W Dunk, Luis A Echegoyen
A β-4-β' C70 bis-adduct regioisomer and an uncommon mono-adduct β-malonate C70 derivative were synthesized by using a Diels-Alder cycloaddition followed by an addition-elimination of bromo-ethylmalonate and a retro-Diels-Alder cycloaddition reaction. We also report the regioselective synthesis and spectroscopic characterization of Cs-symmetric tris- and C2v-symmetric tetra-adducts of C70, which are the precursors of the mono- and bis-adduct final products.
January 20, 2017: Journal of Organic Chemistry
Valeria Calsolaro, Paul Edison
BACKGROUND: Alzheimer's disease (AD) is the most frequent type of dementia in people over 65 years of age; type 2 diabetes mellitus is a metabolic condition affecting 382 million of adults worldwide. Glucose is the main substrate for energy for the brain, which consumes 25% of the body's glucose. Glucose metabolism, evaluated using Positron Emission Tomography (PET) scanning using 18F-fluorodeoxyglucose ([18F]-FDG) is commonly used for diagnosis and follow up in AD. Epidemiological and pathophysiological studies showed a link between AD and diabetes, particularly in relation to insulin resistance...
2016: Recent Patents on Endocrine, Metabolic & Immune Drug Discovery
Marie Alexandra Edison, Megan Eaton, Siba Prosad Paul
No abstract text is available yet for this article.
March 2016: Journal of Family Health
Zhen Fan, Valeria Calsolaro, Rebecca A Atkinson, Grazia D Femminella, Adam Waldman, Christopher Buckley, William Trigg, David J Brooks, Rainer Hinz, Paul Edison
Neuroinflammation is associated with neurodegenerative disease. PET radioligands targeting the 18-kDa translocator protein (TSPO) have been used as in vivo markers of neuroinflammation, but there is an urgent need for novel probes with improved signal-to-noise ratio. Flutriciclamide ((18)F-GE180) is a recently developed third-generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modeling strategies for (18)F-GE180 PET in (older) healthy controls. METHODS: Ten healthy controls, 6 TSPO high-affinity binders, and 4 mixed-affinity binders were recruited...
November 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Valeria Calsolaro, Paul Edison
Several attempts have been made to treat Alzheimer's disease (AD) using anti-amyloid strategies with disappointing results. It is clear that the "amyloid cascade hypothesis" alone cannot fully explain the neuronal damage in AD, as evidenced both by autopsy and imaging studies. Neuroinflammation plays a significant role in neurodegenerative diseases, whereas the debate is ongoing about its precise role, whether it is protective or harmful. In this review, we focus on the potential mechanism of glial activation and how local and systemic factors influence disease progression...
June 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Grazia D Femminella, Siddharth Ninan, Rebecca Atkinson, Zhen Fan, David J Brooks, Paul Edison
BACKGROUND: The influence of neuroinflammation on neuronal function and hippocampal atrophy in Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) is still unclear. OBJECTIVES: Here we investigated whether microglial activation measured by [11C]PK11195 PET is associated with neuronal function measured by cerebral glucose metabolic rate (rCMRGlc) using FDG-PET and hippocampal volume measurements. METHODS: We enrolled 25 subjects (9 PDD, 8 AD, and 8 controls) who underwent PET scans with [11C](R)PK11195, [18F]FDG, and volumetric MRI scanning...
2016: Journal of Alzheimer's Disease: JAD
Gregory Scott, Anil F Ramlackhansingh, Paul Edison, Peter Hellyer, James Cole, Mattia Veronese, Rob Leech, Richard J Greenwood, Federico E Turkheimer, Steve M Gentleman, Rolf A Heckemann, Paul M Matthews, David J Brooks, David J Sharp
OBJECTIVE: To image β-amyloid (Aβ) plaque burden in long-term survivors of traumatic brain injury (TBI), test whether traumatic axonal injury and Aβ are correlated, and compare the spatial distribution of Aβ to Alzheimer disease (AD). METHODS: Patients 11 months to 17 years after moderate-severe TBI underwent (11)C-Pittsburgh compound B ((11)C-PiB)-PET, structural and diffusion MRI, and neuropsychological examination. Healthy aged controls and patients with AD underwent PET and structural MRI...
March 1, 2016: Neurology
Zhonghui Tang, Oscar Junhong Luo, Xingwang Li, Meizhen Zheng, Jacqueline Jufen Zhu, Przemyslaw Szalaj, Pawel Trzaskoma, Adriana Magalska, Jakub Wlodarczyk, Blazej Ruszczycki, Paul Michalski, Emaly Piecuch, Ping Wang, Danjuan Wang, Simon Zhongyuan Tian, May Penrad-Mobayed, Laurent M Sachs, Xiaoan Ruan, Chia-Lin Wei, Edison T Liu, Grzegorz M Wilczynski, Dariusz Plewczynski, Guoliang Li, Yijun Ruan
Spatial genome organization and its effect on transcription remains a fundamental question. We applied an advanced chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) strategy to comprehensively map higher-order chromosome folding and specific chromatin interactions mediated by CCCTC-binding factor (CTCF) and RNA polymerase II (RNAPII) with haplotype specificity and nucleotide resolution in different human cell lineages. We find that CTCF/cohesin-mediated interaction anchors serve as structural foci for spatial organization of constitutive genes concordant with CTCF-motif orientation, whereas RNAPII interacts within these structures by selectively drawing cell-type-specific genes toward CTCF foci for coordinated transcription...
December 17, 2015: Cell
Valeria Calsolaro, Paul Edison
The link between diabetes mellitus and Alzheimer's disease (AD) has been known for the last few decades. Since insulin and insulin receptors are known to be present in the brain, the downstream signalling as well as the effect of hyperinsulinemia have been extensively studied in both AD and Parkinson's disease. Glucagon-like peptide-1 (GLP-1) is a hormone belonging to the incretin family, and its receptors (GLP-1Rs) can be found in pancreatic cells and in vascular endothelium. Interestingly, GLP-1Rs are found in the neuronal cell body and dendrites in the central nervous system (CNS), in particular in the hypothalamus, hippocampus, cerebral cortex and olfactory bulb...
December 2015: CNS Drugs
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