Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 4 of 4

Full-Text Articles in Medicine and Health Sciences

Cryo-Em Structures Of Eastern Equine Encephalitis Virus Reveal Mechanisms Of Virus Disassembly And Antibody Neutralization, Saif Hasan, Chengqun Sun, Arthur S. Kim, Yasunori Watanabe, Chun-Liang Chen, Thomas Klose, Geeta Buda, Max Crispin, Michael S. Diamond, William B. Klimstra, Michael G. Rossmann Dec 2018

Cryo-Em Structures Of Eastern Equine Encephalitis Virus Reveal Mechanisms Of Virus Disassembly And Antibody Neutralization, Saif Hasan, Chengqun Sun, Arthur S. Kim, Yasunori Watanabe, Chun-Liang Chen, Thomas Klose, Geeta Buda, Max Crispin, Michael S. Diamond, William B. Klimstra, Michael G. Rossmann

Department of Biological Sciences Faculty Publications

Alphaviruses are enveloped pathogens that cause arthritis and encephalitis. Here, we report a 4.4-Å cryoelectron microscopy (cryo-EM) structure of eastern equine encephalitis virus (EEEV), an alphavirus that causes fatal encephalitis in humans. Our analysis provides insights into viral entry into host cells. The envelope protein E2 showed a binding site for the cellular attachment factor heparan sulfate. The presence of a cryptic E2 glycan suggests how EEEV escapes surveillance by lectin-expressing myeloid lineage cells, which are sentinels of the immune system. A mechanism for nucleocapsid core release and disassembly upon viral entry was inferred based on pH changes and capsid …


De Novo Sequence And Copy Number Variants Are Strongly Associated With Tourette Disorder And Implicate Cell Polarity In Pathogenesis, Sheng Wang, Jeffrey D. Mandell, Yogesh Kumar, Nawei Sun, Montana T. Morris, Juan Arbelaez, Cara Nasello, Shan Dong, Clif Duhn, Xin Zhao, Zhiyu Yang, Shanmukha S. Padmanabhuni, Dongmei Yu, Robert A. King, Andrea Dietrich, Najah Khalifa, Niklas Dahl, Alden Y. Huang, Benjamin M. Neale, Giovanni Coppola, Carol A. Mathews, Jeremiah M. Scharf, Tourette International Collaborative Genetics Study (Tic Genetics), Tourette Syndrome Genetics Southern And Eastern Europe Initiative (Tsgenesee), Tourette Association Of America International Consortium For Genetics (Taaicg), Thomas V. Fernandez, Joseph D. Buxbaum, Silvia De Rubeus, Dorothy E. Grice, Jinchuan Xing, Gary A. Heiman, Jay A. Tischfield, Peristera Paschou, A Jeremy Wilsey, Matthew W. State Sep 2018

De Novo Sequence And Copy Number Variants Are Strongly Associated With Tourette Disorder And Implicate Cell Polarity In Pathogenesis, Sheng Wang, Jeffrey D. Mandell, Yogesh Kumar, Nawei Sun, Montana T. Morris, Juan Arbelaez, Cara Nasello, Shan Dong, Clif Duhn, Xin Zhao, Zhiyu Yang, Shanmukha S. Padmanabhuni, Dongmei Yu, Robert A. King, Andrea Dietrich, Najah Khalifa, Niklas Dahl, Alden Y. Huang, Benjamin M. Neale, Giovanni Coppola, Carol A. Mathews, Jeremiah M. Scharf, Tourette International Collaborative Genetics Study (Tic Genetics), Tourette Syndrome Genetics Southern And Eastern Europe Initiative (Tsgenesee), Tourette Association Of America International Consortium For Genetics (Taaicg), Thomas V. Fernandez, Joseph D. Buxbaum, Silvia De Rubeus, Dorothy E. Grice, Jinchuan Xing, Gary A. Heiman, Jay A. Tischfield, Peristera Paschou, A Jeremy Wilsey, Matthew W. State

Department of Biological Sciences Faculty Publications

We previously established the contribution of de novo damaging sequence variants to Tourette disorder (TD) through whole-exome sequencing of 511 trios. Here, we sequence an additional 291 TD trios and analyze the combined set of 802 trios. We observe an overrepresentation of de novo damaging variants in simplex, but not multiplex, families; we identify a high-confidence TD risk gene, CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3); we find that the genes mutated in TD patients are enriched for those related to cell polarity, suggesting a common pathway underlying pathobiology; and we confirm a statistically significant excess of de novo …


Zika Virus Can Strongly Infect And Disrupt Secondary Organizers In The Ventricular Zone Of The Embryonic Chicken Brain, Ankita Thawani, Devika Sirohi, Richard J. Kuhn, Donna Fekete Apr 2018

Zika Virus Can Strongly Infect And Disrupt Secondary Organizers In The Ventricular Zone Of The Embryonic Chicken Brain, Ankita Thawani, Devika Sirohi, Richard J. Kuhn, Donna Fekete

Department of Biological Sciences Faculty Publications

Zika virus (ZIKV) is associated with severe neurodeve- lopmental impairments in human fetuses, including microencephaly. Previous reports examining neural progenitor tropism of ZIKV in organoid and animal models did not address whether the virus infects all neural progenitors uniformly. To explore this, ZIKV was injected into the neural tube of 2-day-old chicken embryos, resulting in nonuniform periventricular infec- tion 3 days later. Recurrent foci of intense infection were present at specific signaling centers that influ- ence neuroepithelial patterning at a distance through secretion of morphogens. ZIKV infection reduced transcript levels for 3 morphogens, SHH, BMP7, and FGF8 expressed at the …


Microrna-223 Suppresses The Canonical Nf-Kb Pathway In Basal Keratinocytes To Dampen Neutrophilic Inflammation, Wenqing Zhou, Arpita S. Pal, Alan Yi-Hui Hsu, Theodore Gurol, Xiaoguang Zhu, Sara E. Wirbisk-Hershberger, Jennifer L. Freeman, Andrea L. Kasinski, Qing Deng Feb 2018

Microrna-223 Suppresses The Canonical Nf-Kb Pathway In Basal Keratinocytes To Dampen Neutrophilic Inflammation, Wenqing Zhou, Arpita S. Pal, Alan Yi-Hui Hsu, Theodore Gurol, Xiaoguang Zhu, Sara E. Wirbisk-Hershberger, Jennifer L. Freeman, Andrea L. Kasinski, Qing Deng

Department of Biological Sciences Faculty Publications

MicroRNA-223 is known as a myeloid-enriched anti-inflammatory microRNA that is dysregulated in numerous inflammatory conditions. Here, we report that neutrophilic inflammation (wound response) is augmented in miR-223-deficient zebrafish, due pri- marily to elevated activation of the canonical nuclear factor kB (NF-kB) pathway. NF-kB over-activation is restricted to the basal layer of the surface epithelium, although miR-223 is detected throughout the epithe- lium and in phagocytes. Not only phagocytes but also epithelial cells are involved in miR-223-medi- ated regulation of neutrophils’ wound response and NF-kB activation. Cul1a/b, Traf6, and Tab1 are iden- tified as direct targets of miR-223, and their levels …