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https://www.readbyqxmd.com/read/28088077/rhoa-knockdown-by-cationic-amphiphilic-copolymer-sirhoa-polyplexes-enhances-axonal-regeneration-in-rat-spinal-cord-injury-model
#1
So-Jung Gwak, Christian Macks, Da Un Jeong, Mark Kindy, Michael Lynn, Ken Webb, Jeoung Soo Lee
Spinal cord injury (SCI) results in permanent loss of motor and sensory function due to developmentally-related and injured-induced changes in the extrinsic microenvironment and intrinsic neuronal biochemistry that limit plasticity and axonal regeneration. Our long term goal is to develop cationic, amphiphilic copolymers (poly (lactide-co-glycolide)-g-polyethylenimine, PgP) for combinatorial delivery of therapeutic nucleic acids (TNAs) and drugs targeting these different barriers. In this study, we evaluated the ability of PgP to deliver siRNA targeting RhoA, a critical signaling pathway activated by multiple extracellular inhibitors of axonal regeneration...
January 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28087981/humanized-chondroitinase-abc-sensitizes-glioblastoma-cells-to-temozolomide
#2
Alena Cristina Jaime-Ramirez, Nina Dmitrieva, Ji Young Yoo, Yeshavanth Banasavadi-Siddegowda, Jianying Zhang, Theresa Relation, Chelsea Bolyard-Blessing, Jeffrey Wojton, Balveen Kaur
INTRODUCTION: Malignant gliomas (GBMs) are extremely aggressive and have a median survival of approximately 15 months. Current treatment modalities, which include surgical resection, radiation and chemotherapy, have done little to prolong the lives of GBM patients. Chondroitin sulfate proteoglycans (CSPG) are critical for cell-cell and cell-extra cellular matrix (ECM) interactions and are implicated in glioma growth and invasion. Chondroitinase (Chase) ABC is a bacterial enzyme that cleaves chondroitin sulfate disaccharide chains from CSPGs in the tumor ECM...
January 14, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28087918/-research-progress-on-the-role-of-tank-binding-kinase-1-in-anti-virus-innate-immune-response
#3
Xue Wang, Yuchuan Zhang, Wei Chen
The innate immune response against viral infection is mainly relies on type I interferon, the production of which is mediated by TANK-binding kinase 1 (TBK1). It is revealed that the downstream TBK1 is activated by viral nucleic acid sensors RIG-I, cGAS and TLR3. The activity of TBK1 is complexly and precisely regulated by different type of protein modifications, including phosphorylation, ubiquitination and Sumolylation. This article focuses on the role of TBK1 in anti-viral innate immunity and the regulatory mechanism for the TBK1 activation...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28087801/occurrence-of-similar-mycoviruses-in-pathogenic-saprotrophic-and-mycorrhizal-fungi-inhabiting-the-same-forest-stand
#4
Eeva J Vainio, Taina Pennanen, Tiina Rajala, Jarkko Hantula
Fungal viruses (mycoviruses) are considered to be highly host specific, but phylogenetic analysis supports the occasional occurrence of horizontal transmission between species. We used an extensive sampling strategy to investigate whether similar viruses occur in more than one fungal species of the same forest habitat. Mycelial samples were collected from in-growth mesh bags (N = 259), fruiting bodies (N = 173) and cultured isolates (N = 68) at a forest site where the spatial distribution of viral infections in clonal individuals of the wood decay fungus H...
January 12, 2017: FEMS Microbiology Ecology
https://www.readbyqxmd.com/read/28087772/possible-roles-of-new-mutations-shared-by-asian-and-american-zika-viruses
#5
Shozo Yokoyama, William T Starmer
Originating in Africa, the Zika virus (ZIKV) has spread to Asia, Pacific Islands and now to the Americas and beyond. Since the first isolation in 1947, ZIKV strains have been sampled at various times in the last 69 years, but this history has not been reflected in studying the patterns of mutation accumulation in their genomes. Implementing the viral history, we show that the ZIKV ancestor appeared sometime in 1930-1945 and, at that point, its mutation rate was probably less than 0.2 x 10(-3)/nucleotide site/year and subsequently increased significantly in most of its descendants...
January 12, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28087699/activation-of-c-abl-kinase-potentiates-the-anti-myeloma-drug-lenalidomide-by-promoting-dda1-recruitment-to-the-crl4-ubiquitin-ligase
#6
Shaobing Gao, Chenlu Geng, Tianyu Song, Xuanru Lin, Jiye Liu, Zhen Cai, Yong Cang
Cullin Ring Ligase 4 (CRL4), a complex of Cul4 and DDB1, regulates cell cycle, DNA damage repair, and chromatin replication by targeting a variety of substrates for ubiquitination. CRL4 is also hijacked by viral proteins or thalidomide-derived compounds to degrade host restriction factors. Here we report that the c-Abl non-receptor kinase phosphorylates DDB1 at residue Y316 to recruit a small regulatory protein DDA1, leading to increased substrate ubiquitination. Pharmacological inhibition or genetic ablation of the Abl-DDB1-DDA1 axis decreases the ubiquitination of CRL4 substrates, including IKZF1 and IKZF3 in lenalidomide-treated multiple myeloma cells...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087685/bst-2-restricts-iav-release-and-is-countered-by-the-viral-m2-protein
#7
Siqi Hu, Lijuan Yin, Shan Mei, Jian Li, Fengwen Xu, Hong Sun, Xiaoman Liu, Shan Cen, Chen Liang, Ailing Li, Fei Guo
BST-2 (tetherin, CD317, HM1.24) is induced by interferon and restricts virus release by tethering the enveloped viruses to the cell surface. The effect of BST-2 on influenza A virus (IAV) infection has been inconclusive. In this study, we report that BST-2 diminishes the production of IAV virus-like particles, that are generated by viral NA and HA proteins, to a much greater degree than inhibits the production of wild type IAV particles. This relatively weaker inhibition of IAV is associated with reduction of BST-2 levels, which is caused by the M2 protein that interacts with BST-2 and leads to downregulation of cell surface BST-2 via the proteasomal pathway...
January 13, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28087593/norovirus-mediated-modification-of-the-translational-landscape-via-virus-and-host-induced-cleavage-of-translation-initiation-factors
#8
Edward Emmott, Frederic Sorgeloos, Sarah L Caddy, Surender Vashist, Stanislav Sosnovtsev, Richard Lloyd, Kate Heesom, Nicolas Locker, Ian Goodfellow
Noroviruses produce viral RNAs lacking a 5' cap structure and instead use a virus-encoded VPg protein covalently linked to viral RNA to interact with translation initiation factors and drive viral protein synthesis. Norovirus infection results in the induction of the innate response leading to interferon stimulated gene (ISG) transcription. However the translation of the induced ISG mRNAs is suppressed. A SILAC-based mass spectrometry approach was employed to analyse changes to protein abundance in both whole cell and m7GTP-enriched samples to demonstrate that diminished host mRNA translation correlates with changes to the composition of the eukaryotic initiation factor complex...
January 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28087494/porcine-kobuvirus-1-in-healthy-and-diarrheic-pigs-genetic-detection-and-characterization-of-virus-and-co-infection-with-rotavirus-a
#9
Anna Jackova, Ivan Sliz, Rene Mandelik, Slavomira Salamunova, Jaroslav Novotny, Mariana Kolesarova, Michaela Vlasakova, Stefan Vilcek
The porcine kobuvirus 1 (PKV-1) is believed to be an enteric virus. To investigate the prevalence of PKV-1 in pigs, virus was detected by RT-PCR in rectal swabs originating from 414 healthy and diarrheic pigs of different age categories on farms in Slovakia. Among all ages of animals, PKV-1 was detected equally in diarrheic (63.8%) and clinically healthy (62.9%) pigs. PKV-1 was more often detected in diarrheic (74.6%) than in healthy (64.4%) suckling piglets (<28days) but data was not statistically significant...
January 10, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28087399/advances-with-using-crispr-cas-mediated-gene-editing-to-treat-infections-with-hepatitis-b-virus-and-hepatitis-c-virus
#10
REVIEW
Buhle Moyo, Kristie Bloom, Tristan Scott, Abdullah Ely, Patrick Arbuthnot
Chronic infections with hepatitis B and hepatitis C viruses (HBV and HCV) account for the majority of cases of cirrhosis and hepatocellular carcinoma. Current therapies for the infections have limitations and improved efficacy is necessary to prevent complications in carriers of the viruses. In the case of HBV persistence, the replication intermediate comprising covalently closed circular DNA (cccDNA) is particularly problematic. Licensed therapies have little effect on cccDNA and HBV replication relapses following treatment withdrawal...
January 10, 2017: Virus Research
https://www.readbyqxmd.com/read/28087379/pegylated-liposomes-for-topical-vaginal-therapy-improve-delivery-of-interferon-alpha
#11
May Wenche Jøraholmen, Purusotam Basnet, Ganesh Acharya, Nataša Škalko-Basnet
Recent studies regarding mucosal drug delivery indicate that nanosystems with surface-available polyethylene glycol (PEG) are able to penetrate mucus barrier, assure closer contact with the epithelium, and improve drug delivery to vagina. In the present work, we developed the mucus-penetrating PEGylated liposomes containing interferon alpha-2b (IFN α-2b), destined to provide localized therapy for human papilloma virus (HPV) vaginal infections. The PEGylated liposomes were of a mean size of 181 ± 8 nm, bearing a negative zeta potential of - 13 mV and an entrapment efficiency of 81 ± 10 %...
January 10, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28087327/ige-cross-linking-impairs-monocyte-antiviral-responses-and-inhibits-influenza-driven-th1-differentiation
#12
Regina K Rowe, David M Pyle, Andrew R Tomlinson, Tinghong Lv, Zheng Hu, Michelle A Gill
IgE-mediated allergic activation impairs the virus-induced Th1 lymphocyte priming capacity of human monocytes in response to influenza exposure. These findings represent one potential mechanism contributing to the link between viral infections and allergic disease.
January 10, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28087313/an-m2-v27a-channel-blocker-demonstrates-potent-in-vitro-and-in-vivo-antiviral-activities-against-amantadine-sensitive-and-resistant-influenza-a-viruses
#13
Yanmei Hu, Rami Musharrafieh, Chunlong Ma, Jiantao Zhang, Donald F Smee, William F DeGrado, Jun Wang
Adamantanes such as amantadine (1) and rimantadine (2) are FDA-approved anti-influenza drugs that act by inhibiting the wild-type M2 proton channel from influenza A viruses, thereby inhibiting the uncoating of the virus. Although adamantanes have been successfully used for more than four decades, their efficacy was curtailed by emerging drug resistance. Among the limited number of M2 mutants that confer amantadine resistance, the M2-V27A mutant was found to be the predominant mutant under drug selection pressure, thereby representing a high profile antiviral drug target...
January 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28087292/loss-of-cd28-within-cd4-t-cell-subsets-from-cervical-cancer-patients-is-accompanied-by-the-acquisition-of-intracellular-perforin-and-is-further-enhanced-by-nkg2d-expression
#14
Marta Escarra-Senmarti, Miriam Ruth Bueno-Topete, Luis Felipe Jave-Suarez, Eduardo Gomez-Bañuelos, Jorge Gutierrez-Franco, Natali Vega-Magaña, Adriana Aguilar-Lemarroy, Ana Laura Pereira-Suarez, Jesse Haramati, Susana Del Toro-Arreola
CD28 is well characterized as an essential co-stimulatory receptor critical for activation, proliferation and survival processes in CD4(+) T cells. Populations of CD4(+)CD28(null) T cells, with apparently contradictory physiological roles, have recently been reported, along with the co-expression of the NK activating receptor NKG2D, in autoimmune diseases and chronic viral inflammation. Paradoxically, studies in cancer suggest that an expanded CD4(+)NKG2D(+) population may be armed with immunosuppressive properties...
January 10, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28087227/a-novel-kindred-with-inherited-stat2-deficiency-and-severe-viral-illness
#15
Leen Moens, Lien Van Eyck, Dirk Jochmans, Tania Mitera, Glynis Frans, Xavier Bossuyt, Patrick Matthys, Johan Neyts, Michael Ciancanelli, Shen-Ying Zhang, Rik Gijsbers, Jean-Laurent Casanova, Stephanie Boisson-Dupuis, Isabelle Meyts, Adrian Liston
No abstract text is available yet for this article.
January 5, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28087147/immune-responses-to-in-ovo-vaccine-formulations-containing-inactivated-fowl-adenovirus-8b-with-poly-di-sodium-carboxylatoethylphenoxy-phosphazene-pcep-and-avian-beta-defensin-as-adjuvants-in-chickens
#16
Mishal Sarfraz, Muhammed Suleman, Suresh K Tikoo, Colette Wheler, Andrew A Potter, Volker Gerdts, Arshud Dar
Inclusion body hepatitis (IBH) is one of the major viral infections causing substantial economic loss to the global poultry industry. The disease is characterized by a sudden onset of mortality (2-30%) and high morbidity (60-70%). IBH is caused by a number of serotypes of fowl adenovirus with substantially low levels of serotype cross protection. Thus far, there is no effective and safe vaccine commercially available in the North America for the control of IBH in chickens. Poly[di(sodium carboxylatoethylphenoxy)]phosphazene (PCEP) is a high molecular weight, biodegradable water soluble polymer that has been well characterized as a safe and effective adjuvant for a number of experimental veterinary vaccines...
January 10, 2017: Vaccine
https://www.readbyqxmd.com/read/28087069/safety-tolerability-and-antiviral-effect-of-rg-101-in-patients-with-chronic-hepatitis-c-a-phase-1b-double-blind-randomised-controlled-trial
#17
Meike H van der Ree, J Marleen de Vree, Femke Stelma, Sophie Willemse, Marc van der Valk, Svend Rietdijk, Richard Molenkamp, Janke Schinkel, Ad C van Nuenen, Ulrich Beuers, Salah Hadi, Marten Harbers, Eva van der Veer, Kai Liu, John Grundy, Amy K Patick, Adam Pavlicek, Jacqueline Blem, Michael Huang, Paul Grint, Steven Neben, Neil W Gibson, Neeltje A Kootstra, Hendrik W Reesink
BACKGROUND: miR-122 is an important host factor for hepatitis C virus (HCV) replication. The aim of this study was to assess the safety and tolerability, pharmacokinetics, and antiviral effect of a single dose of RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated oligonucleotide that antagonises miR-122, in patients with chronic HCV infection with various genotypes. METHODS: In this randomised, double-blind, placebo-controlled, multicentre, phase 1B study, patients were randomly assigned to RG-101 or placebo (7:1)...
January 10, 2017: Lancet
https://www.readbyqxmd.com/read/28086981/does-antiretroviral-treatment-change-hiv-1-codon-usage-patterns-in-its-genes-a-preliminary-bioinformatics-study
#18
Navaneethan Palanisamy, Nathan Osman, Frédéric Ohnona, Hong-Tao Xu, Bluma Brenner, Thibault Mesplède, Mark A Wainberg
BACKGROUND: Codon usage bias has been described for various organisms and is thought to contribute to the regulation of numerous biological processes including viral infections. HIV-1 codon usage has been previously shown to be different from that of other viruses and man. It is evident that the antiretroviral drugs used to restrict HIV-1 replication also select for resistance variants. We wanted to test whether codon frequencies in HIV-1 sequences from treatment-experienced patients differ from those of treatment-naive individuals due to drug pressure affecting codon usage bias...
January 7, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28086964/anti-%C3%AE-synuclein-immunotherapy-reduces-%C3%AE-synuclein-propagation-in-the-axon-and-degeneration-in-a-combined-viral-vector-and-transgenic-model-of-synucleinopathy
#19
Brian Spencer, Elvira Valera, Edward Rockenstein, Cassia Overk, Michael Mante, Anthony Adame, Wagner Zago, Peter Seubert, Robin Barbour, Dale Schenk, Dora Games, Robert A Rissman, Eliezer Masliah
Neurodegenerative disorders such as Parkinson's Disease (PD), PD dementia (PDD) and Dementia with Lewy bodies (DLB) are characterized by progressive accumulation of α-synuclein (α-syn) in neurons. Recent studies have proposed that neuron-to-neuron propagation of α-syn plays a role in the pathogenesis of these disorders. We have previously shown that antibodies against the C-terminus of α-syn reduce the intra-neuronal accumulation of α-syn and related deficits in transgenic models of synucleinopathy, probably by abrogating the axonal transport and accumulation of α-syn in in vivo models...
January 13, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28086957/regulatory-t-cells-and-il10-suppress-pulmonary-host-defense-during-early-life-exposure-to-radical-containing-combustion-derived-ultrafine-particulate-matter
#20
Sridhar Jaligama, Jordy Saravia, Dahui You, Nikki Yadav, Greg I Lee, Bishwas Shrestha, Stephania A Cormier
BACKGROUND: Exposure to elevated levels of particulate matter (PM) is associated with increased risk of morbidity and mortality due to respiratory tract viral infections in infants. Recent identification of environmentally persistent free radicals (EPFRs) in the PM from a variety of combustion sources suggests its role in the enhancement of disease severity of lower respiratory tract infections (LRTI). Our previous studies demonstrated that acute exposure to EPFRs induces pulmonary immunosuppression allowing for enhanced influenza disease severity...
January 13, 2017: Respiratory Research
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