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A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis.

Martina Absinta, Dragan Maric, Marjan Gharagozloo, Thomas Garton, Matthew D Smith, Jing Jin, Kathryn C Fitzgerald, Anya Song, Poching Liu, Jing-Ping Lin, Tianxia Wu, Kory R Johnson, Dorian B McGavern, Dorothy P Schafer, Peter A Calabresi, Daniel S Reich,

Multiple sclerosis (MS) lesions that do not resolve in the months after they form harbour ongoing demyelination and axon degeneration, and are identifiable in vivo by their paramagnetic rims on MRI scans<sup>1-3</sup>. Here, to define mechanisms underlying this disabling, progressive neurodegenerative state<sup>4-6</sup> and foster development of new therapeutic agents, we ... Read more >>

Nature (Nature)
[2021, 597(7878):709-714]

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Longitudinal peripheral tissue RNA-Seq transcriptomic profiling, hyperalgesia, and wound healing in the rat plantar surgical incision model.

Taichi Goto, Matthew R Sapio, Dragan Maric, Jeffrey M Robinson, Anthony F Domenichiello, Leorey N Saligan, Andrew J Mannes, Michael J Iadarola,

Postoperative pain and delayed healing in surgical wounds, which require complex management strategies have understudied complicated mechanisms. Here we investigated temporal changes in behavior, tissue structure, and transcriptomic profiles in a rat model of a surgical incision, using hyperalgesic behavioral tests, histological analyses, and next-generation RNA sequencing, respectively. The most ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(10):e21852]

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Inhibiting protein phosphatase 2A increases the antitumor effect of protein arginine methyltransferase 5 inhibition in models of glioblastoma.

Yoshihiro Otani, Hannah P Sur, Guruprasad Rachaiah, Sriya Namagiri, Ashis Chowdhury, Cole T Lewis, Toshihiko Shimizu, Arunakumar Gangaplara, Xiang Wang, Amélie Vézina, Dragan Maric, Sadhana Jackson, Yuanqing Yan, Zhuang Zhengping, Abhik Ray-Chaudhury, Sachin Kumar, Leomar Y Ballester, Prashant Chittiboina, Ji Young Yoo, John Heiss, Balveen Kaur, Yeshavanth Kumar Banasavadi-Siddegowda,

<h4>Background</h4>Despite multi-model therapy of maximal surgical resection, radiation, chemotherapy, and tumor-treating fields, the median survival of glioblastoma (GBM) patients is less than 15 months. Protein arginine methyltransferase 5 (PRMT5) catalyzes the symmetric dimethylation of arginine residues and is overexpressed in GBM. Inhibition of PRMT5 causes senescence in stem-like GBM tumor ... Read more >>

Neuro Oncol (Neuro-oncology)
[2021, 23(9):1481-1493]

Cited: 2 times

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NMDARs Drive the Expression of Neuropsychiatric Disorder Risk Genes Within GABAergic Interneuron Subtypes in the Juvenile Brain.

Vivek Mahadevan, Apratim Mitra, Yajun Zhang, Xiaoqing Yuan, Areg Peltekian, Ramesh Chittajallu, Caroline Esnault, Dragan Maric, Christopher Rhodes, Kenneth A Pelkey, Ryan Dale, Timothy J Petros, Chris J McBain,

Medial ganglionic eminence (MGE)-derived parvalbumin (PV)+, somatostatin (SST)+and Neurogliaform (NGFC)-type cortical and hippocampal interneurons, have distinct molecular, anatomical, and physiological properties. However, the molecular mechanisms regulating their maturation remain poorly understood. Here, via single-cell transcriptomics, we show that the obligate NMDA-type glutamate receptor (NMDAR) subunit gene <i>Grin1</i> mediates transcriptional regulation ... Read more >>

Front Mol Neurosci (Frontiers in molecular neuroscience)
[2021, 14:712609]

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Lipid peroxidation and pathological disruption of the ApoE/Reelin-ApoER2-DAB1 axis in sporadic Alzheimer’s disease

Christopher Ramsden, Gregory Keyes, Elizabeth Calzada, Mark Horowitz, Jahandar Jahanipour, Fred Indig, Daisy Zamora, Andrea Sedlock, Ruin Moaddel, Dimitrios Kapogiannis, Dragan Maric,

The strong genetic link between Apolipoprotein E (ApoE) and sporadic Alzheimer’s disease (AD) and the marked increase in brain lipid peroxidation observed in early AD suggest that dysfunctional lipid metabolism plays a central role in AD pathogenesis. However, specific mechanisms and targets linking ApoE and lipid peroxidation to AD are ... Read more >>

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Transcriptional heterogeneity of ventricular zone cells throughout the embryonic mouse forebrain

Dongjin Lee, Christopher Rhodes, Apratim Mitra, Yajun Zhang, Dragan Maric, Ryan Dale, Timothy Petros,

<h4>SUMMARY</h4> The ventricular zone (VZ) of the nervous system contains radial glia cells that were originally considered relatively homogenous in their gene expression. However, a detailed characterization of transcriptional diversity in these VZ cells has not been reported. Here, we performed single-cell RNA sequencing to characterize transcriptional heterogeneity of neural ... Read more >>

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OTME-4. IDH mutated gliomas promote epileptogenesis via D-2-hydroxyglutarate dependent mTOR hyperactivation

Armin Mortazavi, Islam Fayed, Muzna Bachani, Dragan Maric, Tyrone Dowdy, Mioara Larion, Alexander Ksendzovsky, Kareem Zaghloul,

Abstract Epilepsy in the context of brain tumors provides a great burden in these patients, yet mechanisms underlying this process are poorly understood. It has been demonstrated that isocitrate dehydrogenase (IDH) mutations are an independent factor in epileptogenesis in patients with low grade gliomas. Here, using electrographically sorted human cortical ... Read more >>

Neurooncol Adv (Neuro-oncology advances)
[2021, 3(Suppl 2):ii14-ii14]

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Longitudinal in vivo imaging of acute neuropathology in a monkey model of Ebola virus infection.

William Schreiber-Stainthorp, Jeffrey Solomon, Ji Hyun Lee, Marcelo Castro, Swati Shah, Neysha Martinez-Orengo, Rebecca Reeder, Dragan Maric, Robin Gross, Jing Qin, Katie R Hagen, Reed F Johnson, Dima A Hammoud,

Ebola virus (EBOV) causes neurological symptoms yet its effects on the central nervous system (CNS) are not well-described. Here, we longitudinally assess the acute effects of EBOV on the brain, using quantitative MR-relaxometry, 18F-Fluorodeoxyglucose PET and immunohistochemistry in a monkey model. We report blood-brain barrier disruption, likely related to high ... Read more >>

Nat Commun (Nature communications)
[2021, 12(1):2855]

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VPS13D promotes peroxisome biogenesis.

Heather A Baldwin, Chunxin Wang, Gil Kanfer, Hetal V Shah, Antonio Velayos-Baeza, Marija Dulovic-Mahlow, Norbert Brüggemann, Allyson Anding, Eric H Baehrecke, Dragan Maric, William A Prinz, Richard J Youle,

The VPS13 gene family consists of VPS13A-D in mammals. Although all four genes have been linked to human diseases, their cellular functions are poorly understood, particularly those of VPS13D. We generated and characterized knockouts of each VPS13 gene in HeLa cells. Among the individual knockouts, only VPS13D-KO cells exhibit abnormal ... Read more >>

J Cell Biol (The Journal of cell biology)
[2021, 220(5):]

Cited: 7 times

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A Single Cell Atlas of Spared Tissue Below a Spinal Cord Injury Reveals Cellular Mechanisms of Repair

Kaya J.E. Matson, Daniel Russ, Claudia Kathe, Dragan Maric, Isabelle Hua, Jonathan Krynitsky, Randall Pursley, Anupama Sathyamurthy, Jordan Squair, Gregoire Courtine, Ariel Levine,

After spinal cord injury (SCI), the “spared” tissue below the lesion contains undamaged cells that could support or augment recovery, but targeting these cells requires a clearer understanding of their injury responses and capacity for repair. Here, we used single nucleus sequencing to profile how each cell type in the ... Read more >>

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DDRE-27. IDH MUTATED GLIOMAS PROMOTE EPILEPTOGENESIS VIA D-2-HYDROXYGLUTARATE DEPENDENT MTOR HYPERACTIVATION

Armin Mortazavi, Islam Fayed, Muzna Bachani, Tyrone Dowdy, Joseph Steiner, Dragan Maric, Chun Zhang Yang, Mioara Larion, Alexander Ksendzovsky, Kareem Zaghloul,

Abstract <h4>INTRODUCTION</h4> Epileptic seizures in patients with low-grade, isocitrate dehydrogenase (IDH) mutated gliomas reach 90%, a major source of morbidity for these patients. Albeit there are multiple features that contribute to tumor related epileptogenesis, IDH mutations are determined to be an independent factor, although the pathogenesis remains poorly understood. We ... Read more >>

Neurooncol Adv (Neuro-oncology advances)
[2021, 3(Suppl 1):i12-i12]

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The Persistent Pain Transcriptome: Identification of Cells and Molecules Activated by Hyperalgesia.

Matthew R Sapio, Jenny J Kim, Amelia J Loydpierson, Dragan Maric, Taichi Goto, Fernando A Vazquez, Mary K Dougherty, Radhika Narasimhan, Wallis T Muhly, Michael J Iadarola, Andrew J Mannes,

During persistent pain, the dorsal spinal cord responds to painful inputs from the site of injury, but the molecular modulatory processes have not been comprehensively examined. Using transcriptomics and multiplex in situ hybridization, we identified the most highly regulated receptors and signaling molecules in rat dorsal spinal cord in peripheral ... Read more >>

J Pain (The journal of pain)
[2021, 22(10):1146-1179]

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Identification of circulating CD31+CD45+ cell populations with the potential to differentiate into erythroid cells.

Maria Chiara G Monaco, Dragan Maric, Ombretta Salvucci, Cristina Antonetti Lamorgese Passeri, Patrizia Accorsi, Eugene O Major, Anna Concetta Berardi,

Erythro-myeloid progenitors (EMP) are found in a population of cells expressing CD31 and CD45 markers (CD31<sup>+</sup>CD45<sup>+</sup>). A recent study indicated that EMPs persist until adulthood and can be a source of endothelial cells. We identified two sub-populations of EMP cells, CD31<sup>low</sup>CD45<sup>low</sup> and CD31<sup>high</sup>CD45<sup>+</sup>, from peripheral blood that can differentiate into ... Read more >>

Stem Cell Res Ther (Stem cell research & therapy)
[2021, 12(1):236]

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Whole-brain tissue mapping toolkit using large-scale highly multiplexed immunofluorescence imaging and deep neural networks.

Dragan Maric, Jahandar Jahanipour, Xiaoyang Rebecca Li, Aditi Singh, Aryan Mobiny, Hien Van Nguyen, Andrea Sedlock, Kedar Grama, Badrinath Roysam,

Mapping biological processes in brain tissues requires piecing together numerous histological observations of multiple tissue samples. We present a direct method that generates readouts for a comprehensive panel of biomarkers from serial whole-brain slices, characterizing all major brain cell types, at scales ranging from subcellular compartments, individual cells, local multi-cellular ... Read more >>

Nat Commun (Nature communications)
[2021, 12(1):1550]

Cited: 2 times

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Mt-Keima detects PINK1-PRKN mitophagy in vivo with greater sensitivity than mito-QC.

Yi-Ting Liu, Danielle A Sliter, Mario K Shammas, Xiaoping Huang, Chunxin Wang, Hannah Calvelli, Dragan S Maric, Derek P Narendra,

PINK1 and PRKN, which cause Parkinson disease when mutated, form a quality control mitophagy pathway that is well-characterized in cultured cells. The extent to which the PINK1-PRKN pathway contributes to mitophagy <i>in vivo</i>, however, is controversial. This is due in large part to conflicting results from studies using one of ... Read more >>

Autophagy (Autophagy)
[2021, :1-10]

Cited: 1 time

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Comparative Analysis of Dorsal Root, Nodose and Sympathetic Ganglia for the Development of New Analgesics.

Matthew R Sapio, Fernando A Vazquez, Amelia J Loydpierson, Dragan Maric, Jenny J Kim, Danielle M LaPaglia, Henry L Puhl, Van B Lu, Stephen R Ikeda, Andrew J Mannes, Michael J Iadarola,

Interoceptive and exteroceptive signals, and the corresponding coordinated control of internal organs and sensory functions, including pain, are received and orchestrated by multiple neurons within the peripheral, central and autonomic nervous systems. A central aim of the present report is to obtain a molecularly informed basis for analgesic drug development ... Read more >>

Front Neurosci (Frontiers in neuroscience)
[2020, 14:615362]

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Commentary on Winzeler et al 'Low arginine vasopressin levels in patients with diabetes insipidus are not associated with anaemia'.

Balázs Mayer, Krisztián Németh, Miklós Krepuska, Vamsee D Myneni, Dragan Maric, John F Tisdale, Matthew M Hsieh, Naoya Uchida, Heon-Jin Lee, Michael J Nemeth, Kenn Holmbeck, Constance Tom Noguchi, Heather Rogers, Soumyadeep Dey, Arne Hansen, Jeffrey Hong, Ian Chow, Sharon Key, Ildikó Szalayova, Jerome Pagani, Károly Markó, Ian MacClain-Caldwell, Lynn Vitale-Cross, W Scott Young, Michael J Brownstein, Éva Mezey,

Clin Endocrinol (Oxf) (Clinical endocrinology)
[2021, 94(5):888-890]

Cited: 0 times

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Microvascular Injury in the Brains of Patients with Covid-19.

Myoung-Hwa Lee, Daniel P Perl, Govind Nair, Wenxue Li, Dragan Maric, Helen Murray, Stephen J Dodd, Alan P Koretsky, Jason A Watts, Vivian Cheung, Eliezer Masliah, Iren Horkayne-Szakaly, Robert Jones, Michelle N Stram, Joel Moncur, Marco Hefti, Rebecca D Folkerth, Avindra Nath,

N Engl J Med (The New England journal of medicine)
[2021, 384(5):481-483]

Cited: 76 times

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Longitudinal Transcriptomic Profiling in Carrageenan-Induced Rat Hind Paw Peripheral Inflammation and Hyperalgesia Reveals Progressive Recruitment of Innate Immune System Components.

Taichi Goto, Matthew R Sapio, Dragan Maric, Jeffrey M Robinson, Leorey N Saligan, Andrew J Mannes, Michael J Iadarola,

Pain is a common but potentially debilitating symptom, often requiring complex management strategies. To understand the molecular dynamics of peripheral inflammation and nociceptive pain, we investigated longitudinal changes in behavior, tissue structure, and transcriptomic profiles in the rat carrageenan-induced peripheral inflammation model. Sequential changes in the number of differentially expressed ... Read more >>

J Pain (The journal of pain)
[2021, 22(3):322-343]

Cited: 1 time

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Molecular Pathways Linking Oxylipins to Nociception in Rats.

Anthony F Domenichiello, Matthew R Sapio, Amelia J Loydpierson, Dragan Maric, Taichi Goto, Mark S Horowitz, Gregory S Keyes, Zhi-Xin Yuan, Sharon F Majchrzak-Hong, Andrew J Mannes, Michael J Iadarola, Christopher E Ramsden,

Oxylipins are lipid peroxidation products that participate in nociceptive, inflammatory, and vascular responses to injury. Effects of oxylipins depend on tissue-specific differences in accumulation of precursor polyunsaturated fatty acids and the expression of specific enzymes to transform the precursors. The study of oxylipins in nociception has presented technical challenges leading ... Read more >>

J Pain (The journal of pain)
[2021, 22(3):275-299]

Cited: 2 times

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GL261 luciferase-expressing cells elicit an anti-tumor immune response: an evaluation of murine glioma models.

Victoria E Sanchez, John P Lynes, Stuart Walbridge, Xiang Wang, Nancy A Edwards, Anthony K Nwankwo, Hannah P Sur, Gifty A Dominah, Arnold Obungu, Nicholas Adamstein, Pradeep K Dagur, Dragan Maric, Jeeva Munasinghe, John D Heiss, Edjah K Nduom,

Preclinical models that reliably recapitulate the immunosuppressive properties of human gliomas are essential to assess immune-based therapies. GL261 murine glioma cells are widely used as a syngeneic animal model of glioma, however, it has become common practice to transfect these cells with luciferase for fluorescent tumor tracking. The aim of ... Read more >>

Sci Rep (Scientific reports)
[2020, 10(1):11003]

Cited: 4 times

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NMDAR-mediated transcriptional control of gene expression during the development of medial ganglionic eminence-derived interneurons

Vivek Mahadevan, Apratim Mitra, Yajun Zhang, Xiaoqing Yuan, Areg Peltekian, Ramesh Chittajallu, Caroline Esnault, Dragan Maric, Christopher Rhodes, Kenneth Pelkey, Kenneth Pelkey, Ryan Dale, Timothy Petros, Chris McBain,

<h4>ABSTRACT</h4> Medial ganglionic eminence (MGE)-derived parvalbumin (PV)+, somatostatin (SST)+ and Neurogliaform (NGFC)-type cortical and hippocampal interneurons, have distinct molecular, anatomical and physiological properties. However, the molecular mechanisms regulating their diversity remain poorly understood. Here, via single-cell transcriptomics, we show that the obligate NMDA-type glutamate receptor (NMDAR) subunit gene Grin1 mediates ... Read more >>

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Overexpression of fibroblast growth factor-21 (FGF-21) protects mesenchymal stem cells against caspase-dependent apoptosis induced by oxidative stress and inflammation.

Gabriel R Linares, Yan Leng, Dragan Maric, De-Maw Chuang,

The clinical application of stem cells offers great promise as a potential avenue for therapeutic use in neurodegenerative diseases. However, cell loss after transplantation remains a major challenge, which currently plagues the field. On the basis of our previous findings that fibroblast growth factor 21 (FGF-21) protected neurons from glutamate ... Read more >>

Cell Biol Int (Cell biology international)
[2020, 44(10):2163-2169]

Cited: 4 times

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CD8+ T cells target cerebrovasculature in children with cerebral malaria.

Brittany A Riggle, Monica Manglani, Dragan Maric, Kory R Johnson, Myoung-Hwa Lee, Osorio Lopes Abath Neto, Terrie E Taylor, Karl B Seydel, Avindra Nath, Louis H Miller, Dorian B McGavern, Susan K Pierce,

BACKGROUNDCerebral malaria (CM) accounts for nearly 400,000 deaths annually in African children. Current dogma suggests that CM results from infected RBC (iRBC) sequestration in the brain microvasculature and resulting sequelae. Therapies targeting these events have been unsuccessful; findings in experimental models suggest that CD8+ T cells drive disease pathogenesis. However, ... Read more >>

J Clin Invest (The Journal of clinical investigation)
[2020, 130(3):1128-1138]

Cited: 12 times

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ATIM-32. PREDICTORS OF IMPROVED SURVIVAL FOLLOWING ONCOLYTIC VIRUS TREATMENT IN PATIENTS WITH RECURRENT GLIOBLASTOMA: GENE EXPRESSION ANALYSIS FROM THE PHASE IB G207 CLINICAL TRIAL

Kevin Cassady, Katherine Miller, Nripesh Prasad, Dragan Maric, Josh Bernstock, Justin Roth, Naomi Barker, Jennifer Coleman, Kathleen Schieffer, Kristen Leraas, Anthony Miller, Jianmei Leavenworth, Gary Cutter, Richard Whitley, Bernard Roizman, G Yancey Gillespie, Elaine Mardis, James Markert,

Abstract Our Phase I trials of experimental virotherapy for recurrent glioblastoma (GBM) have shown that inoculation with a conditionally replication-competent early generation oncolytic herpes simplex virus (oHSV), G207, is safe. However, while 17 of 37 subjects experienced objective clinical responses, the highly attenuated oHSV did not uniformly improve survival. We ... Read more >>

Neuro Oncol (Neuro-oncology)
[2019, 21(Suppl 6):vi8-vi8]

Cited: 0 times

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