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Dan Hu, Samuele Notarbartolo, Tom Croonenborghs, Bonny Patel, Ron Cialic, Tun-Hsiang Yang, Dominik Aschenbrenner, Karin M Andersson, Marco Gattorno, Minh Pham, Pia Kivisakk, Isabelle V Pierre, Youjin Lee, Karun Kiani, Maria Bokarewa, Emily Tjon, Nathalie Pochet, Federica Sallusto, Vijay K Kuchroo, Howard L Weiner
We have previously reported the molecular signature of murine pathogenic TH 17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ+ IL-17+ (TH 1/17) and IFN-γ- IL-17+ (TH 17) CD4+ T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to TH 17 cells, TH 1/17 cells have gene signatures with marked similarity to mouse pathogenic TH 17 cells. Assessing 15 representative signature genes in patients with multiple sclerosis, we find that TH 1/17 cells have elevated expression of CXCR3 and reduced expression of IFNG, CCL3, CLL4, GZMB, and IL10 compared to healthy controls...
November 17, 2017: Nature Communications
Susanne Krasemann, Charlotte Madore, Ron Cialic, Caroline Baufeld, Narghes Calcagno, Rachid El Fatimy, Lien Beckers, Elaine O'Loughlin, Yang Xu, Zain Fanek, David J Greco, Scott T Smith, George Tweet, Zachary Humulock, Tobias Zrzavy, Patricia Conde-Sanroman, Mar Gacias, Zhiping Weng, Hao Chen, Emily Tjon, Fargol Mazaheri, Kristin Hartmann, Asaf Madi, Jason D Ulrich, Markus Glatzel, Anna Worthmann, Joerg Heeren, Bogdan Budnik, Cynthia Lemere, Tsuneya Ikezu, Frank L Heppner, Vladimir Litvak, David M Holtzman, Hans Lassmann, Howard L Weiner, Jordi Ochando, Christian Haass, Oleg Butovsky
Microglia play a pivotal role in the maintenance of brain homeostasis but lose homeostatic function during neurodegenerative disorders. We identified a specific apolipoprotein E (APOE)-dependent molecular signature in microglia from models of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Alzheimer's disease (AD) and in microglia surrounding neuritic β-amyloid (Aβ)-plaques in the brains of people with AD. The APOE pathway mediated a switch from a homeostatic to a neurodegenerative microglia phenotype after phagocytosis of apoptotic neurons...
September 19, 2017: Immunity
Ron Cialic, Victor Shvedov, Yaffa Lerman
BACKGROUND/OBJECTIVES: Postoperative urinary retention (POUR) is a common event following surgical procedures. An increase in the number of elderly individuals who undergo hip fracture repair procedures is inevitable due to the aging of population. Postoperative urinary retention is associated with both early (infections, delirium) and late complications (urinary incontinence) of surgery. The objective of the current study is to direct attention to the less studied population of patients admitted to a geriatric rehabilitation ward following hip fracture repair who are at risk of POUR...
March 2017: Geriatric Orthopaedic Surgery & Rehabilitation
Tamara Shiner, Anat Mirelman, Mali Gana Weisz, Anat Bar-Shira, Elissa Ash, Ron Cialic, Naomi Nevler, Tanya Gurevich, Noa Bregman, Avi Orr-Urtreger, Nir Giladi
Importance: Mutations in the glucocerebrosidase (GBA) gene are a risk factor for the development of dementia with Lewy bodies (DLB). These mutations are common among Ashkenazi Jews (AJ) and appear to have an effect on the natural history of the disease. Objectives: To evaluate the clinical and genetic characteristics of an AJ cohort of patients diagnosed with DLB, assess the association of phenotype of DLB with GBA mutations, and explore the effects of these mutations on the clinical course of the disease...
December 1, 2016: JAMA Neurology
Nadiya M Teplyuk, Erik J Uhlmann, Galina Gabriely, Natalia Volfovsky, Yang Wang, Jian Teng, Priya Karmali, Eric Marcusson, Merlene Peter, Athul Mohan, Yevgenya Kraytsberg, Ron Cialic, E Antonio Chiocca, Jakub Godlewski, Bakhos Tannous, Anna M Krichevsky
MicroRNA-10b (miR-10b) is a unique oncogenic miRNA that is highly expressed in all GBM subtypes, while absent in normal neuroglial cells of the brain. miR-10b inhibition strongly impairs proliferation and survival of cultured glioma cells, including glioma-initiating stem-like cells (GSC). Although several miR-10b targets have been identified previously, the common mechanism conferring the miR-10b-sustained viability of GSC is unknown. Here, we demonstrate that in heterogeneous GSC, miR-10b regulates cell cycle and alternative splicing, often through the non-canonical targeting via 5'UTRs of its target genes, including MBNL1-3, SART3, and RSRC1...
March 1, 2016: EMBO Molecular Medicine
Shirong Liu, Andre Pires da Cunha, Rafael M Rezende, Ron Cialic, Zhiyun Wei, Lynn Bry, Laurie E Comstock, Roopali Gandhi, Howard L Weiner
The host gut microbiota varies across species and individuals but is relatively stable over time within an individual. How the host selectively shapes the microbiota is largely unclear. Here, we show that fecal microRNA (miRNA)-mediated inter-species gene regulation facilitates host control of the gut microbiota. miRNAs are abundant in mouse and human fecal samples and present within extracellular vesicles. Cell-specific loss of the miRNA-processing enzyme, Dicer, identified intestinal epithelial cells (IEC) and Hopx-positive cells as predominant fecal miRNA sources...
January 13, 2016: Cell Host & Microbe
Rafael M Rezende, Andre P da Cunha, Chantal Kuhn, Stephen Rubino, Hanane M'Hamdi, Galina Gabriely, Tyler Vandeventer, Shirong Liu, Ron Cialic, Natalia Pinheiro-Rosa, Rafael P Oliveira, Jellert T Gaublomme, Nikolaus Obholzer, James Kozubek, Nathalie Pochet, Ana M C Faria, Howard L Weiner
γδ T cells are a subset of lymphocytes specialized in protecting the host against pathogens and tumours. Here we describe a subset of regulatory γδ T cells that express the latency-associated peptide (LAP), a membrane-bound TGF-β1. Thymic CD27+IFN-γ+CCR9+α4β7+TCRγδ+ cells migrate to the periphery, particularly to Peyer's patches and small intestine lamina propria, where they upregulate LAP, downregulate IFN-γ via ATF-3 expression and acquire a regulatory phenotype. TCRγδ+LAP+ cells express antigen presentation molecules and function as antigen presenting cells that induce CD4+Foxp3+ regulatory T cells, although TCRγδ+LAP+ cells do not themselves express Foxp3...
December 8, 2015: Nature Communications
Oleg Butovsky, Mark P Jedrychowski, Craig S Moore, Ron Cialic, Amanda J Lanser, Galina Gabriely, Thomas Koeglsperger, Ben Dake, Pauline M Wu, Camille E Doykan, Zain Fanek, LiPing Liu, Zhuoxun Chen, Jeffrey D Rothstein, Richard M Ransohoff, Steven P Gygi, Jack P Antel, Howard L Weiner
No abstract text is available yet for this article.
December 2015: International Journal of Developmental Neuroscience
Oleg Butovsky, Mark P Jedrychowski, Ron Cialic, Gopal Murugaiyan, Pauline M Wu, Camille E Doykan, Zain Fanek, David J Greco, Olga Kiner, Robert J Lawson, Matthew P Frosch, Nathalie Pochet, Anna M Krichevsky, Steven P Gygi, James Berry, Merit E Cudkowicz, Howard L Weiner
No abstract text is available yet for this article.
December 2015: International Journal of Developmental Neuroscience
Karin M E Andersson, Nicola Filluelo Cavallini, Dan Hu, Mikael Brisslert, Ron Cialic, Hadi Valadi, Malin C Erlandsson, Sofia Silfverswärd, Rille Pullerits, Vijay K Kuchroo, Howard L Weiner, Maria I Bokarewa
T-helper cells producing interleukin (IL)-17A and IL-17F cytokines (Th17 cells) are considered the source of autoimmunity in rheumatoid arthritis (RA). In this study, we characterized specific pathogenic features of Th17 cells in RA. By using nano-string technology, we analyzed transcription of 419 genes in the peripheral blood CCR6(+)CXCR3(-) CD4(+) cells of 14 RA patients and 6 healthy controls and identified 109 genes discriminating Th17 cells of RA patients from the controls. Th17 cells of RA patients had an aggressive pathogenic profile and in addition to signature cytokines IL-17, IL-23 and IL-21, and transcriptional regulators RAR-related orphan receptor gamma of T cells (RORγt) and Janus kinase 2 (JAK2), they produced high levels of IL-23R, C-C chemokine ligand type 20 (CCL20), granulocyte-monocyte colony-stimulating factor (GM-CSF ) and transcription factor Tbet required for synovial homing...
2015: Molecular Medicine
Oleg Butovsky, Mark P Jedrychowski, Ron Cialic, Susanne Krasemann, Gopal Murugaiyan, Zain Fanek, David J Greco, Pauline M Wu, Camille E Doykan, Olga Kiner, Robert J Lawson, Matthew P Frosch, Nathalie Pochet, Rachid El Fatimy, Anna M Krichevsky, Steven P Gygi, Hans Lassmann, James Berry, Merit E Cudkowicz, Howard L Weiner
OBJECTIVE: To investigate miR-155 in the SOD1 mouse model and human sporadic and familial amyotrophic lateral sclerosis (ALS). METHODS: NanoString microRNA, microglia and immune gene profiles, protein mass spectrometry, and RNA-seq analyses were measured in spinal cord microglia, splenic monocytes, and spinal cord tissue from SOD1 mice and in spinal cord tissue of familial and sporadic ALS. miR-155 was targeted by genetic ablation or by peripheral or centrally administered anti-miR-155 inhibitor in SOD1 mice...
January 2015: Annals of Neurology
Oleg Butovsky, Mark P Jedrychowski, Craig S Moore, Ron Cialic, Amanda J Lanser, Galina Gabriely, Thomas Koeglsperger, Ben Dake, Pauline M Wu, Camille E Doykan, Zain Fanek, LiPing Liu, Zhuoxun Chen, Jeffrey D Rothstein, Richard M Ransohoff, Steven P Gygi, Jack P Antel, Howard L Weiner
No abstract text is available yet for this article.
August 26, 2014: Nature Neuroscience
Ryo Yamasaki, Haiyan Lu, Oleg Butovsky, Nobuhiko Ohno, Anna M Rietsch, Ron Cialic, Pauline M Wu, Camille E Doykan, Jessica Lin, Anne C Cotleur, Grahame Kidd, Musab M Zorlu, Nathan Sun, Weiwei Hu, LiPing Liu, Jar-Chi Lee, Sarah E Taylor, Lindsey Uehlein, Debra Dixon, Jinyu Gu, Crina M Floruta, Min Zhu, Israel F Charo, Howard L Weiner, Richard M Ransohoff
In the human disorder multiple sclerosis (MS) and in the model experimental autoimmune encephalomyelitis (EAE), macrophages predominate in demyelinated areas and their numbers correlate to tissue damage. Macrophages may be derived from infiltrating monocytes or resident microglia, yet are indistinguishable by light microscopy and surface phenotype. It is axiomatic that T cell-mediated macrophage activation is critical for inflammatory demyelination in EAE, yet the precise details by which tissue injury takes place remain poorly understood...
July 28, 2014: Journal of Experimental Medicine
Oleg Butovsky, Mark P Jedrychowski, Craig S Moore, Ron Cialic, Amanda J Lanser, Galina Gabriely, Thomas Koeglsperger, Ben Dake, Pauline M Wu, Camille E Doykan, Zain Fanek, Liping Liu, Zhuoxun Chen, Jeffrey D Rothstein, Richard M Ransohoff, Steven P Gygi, Jack P Antel, Howard L Weiner
Microglia are myeloid cells of the CNS that participate both in normal CNS function and in disease. We investigated the molecular signature of microglia and identified 239 genes and 8 microRNAs that were uniquely or highly expressed in microglia versus myeloid and other immune cells. Of the 239 genes, 106 were enriched in microglia as compared with astrocytes, oligodendrocytes and neurons. This microglia signature was not observed in microglial lines or in monocytes recruited to the CNS, and was also observed in human microglia...
January 2014: Nature Neuroscience
Daniel Azoulay, Jeremy M Jacobs, Ron Cialic, Eliana Ein Mor, Jochanan Stessman
OBJECTIVE: Although pain is common among advanced cancer patients, it can be controlled in a large proportion of patients. Several barriers hinder this, including the concern that opioids hasten death. We examined whether opioids influence survival among advanced cancer patients. DESIGN: Retrospective observational study from September 2006 to October 2007. SETTING: In-patient hospice unit. PARTICIPANTS: Participants were 114 consecutive hospice patients (mean age 71...
February 2011: Journal of the American Medical Directors Association
T Ben-Hur, R Cialic, J Weidenfeld
Experimental models that mimic the clinical syndrome of human viral encephalitis and represent HSV-1 neurotropism were utilized to investigate neuro-pharmacologic changes mediating clinical and behavioral manifestations of encephalitic infection of the central nervous system with HSV-1-induced rapid activation of the hypothalamic--pituitary--adrenocortical (HPA) axis and production of brain derived interleukin-1 (IL-1) and prostaglandin E2 (PG-E2), independently of viral replication. HSV-1 infection induced clinical signs of fever, motor hyperactivity and aggressive behavior...
2003: Acta Microbiologica et Immunologica Hungarica
T Ben-Hur, R Cialic, A Itzik, O Barak, R Yirmiya, J Weidenfeld
Herpes simplex virus type 1 (HSV-1) encephalitis may present with fever and behavioral changes, to the extent of a psychotic state and psychomotor agitation. We developed a clinically relevant experimental model of HSV-1 encephalitis and investigated host brain responses associated with its clinical signs and whether these responses depend on the presence of circulating glucocorticoids. Intracerebral inoculation of HSV-1 in rats induced fever, motor hyperactivity and aggressive behavior. In adrenalectomized rats HSV-1 failed to induce these signs, although mortality rate was identical to sham-operated rats...
2001: Neuroscience
T Ben-Hur, R Cialic, A Itzik, R Yirmiya, J Weidenfeld
UNLABELLED: Herpes simplex virus type 1 (HSV-1) is a common cause of viral encephalitis, manifested by neuroendocrine and behavioral changes. We have previously demonstrated that HSV-1 induces marked hypothalamo-pituitary-adrenocortical (HPA) axis activation. In this study we characterized the acute effects of HSV-1 on the HPA axis occurring before viral replication and appearance of clinical signs of encephalitis. Since in previous studies we used crude virus preparations which may contain immune factors produced by the infected cells, we tested here the effects of purified HSV-1 virions...
September 2001: Neuroendocrinology
S A Vasil'ev, E E Efremov, T A Savenko, G A Ermolin, G V Ignashenkova, L V Zherdeva
The study of circulating complexes fibronectin-fibrin in 21 patients with immunocomplex affections revealed their high levels which occurred in inverse relationships with fibronectin concentrations in the blood, but in direct correlation with indicators of inflammation (fibrinogen, cialic acid). It is suggested that the complexes are involved in the development of fibrosis at the sites of chronic inflammation in immune disorders.
1994: Terapevticheskiĭ Arkhiv
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