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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
#1
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/28079203/complexation-of-short-ds-rna-dna-oligonucleotides-with-gemini-micelles-a-time-resolved-saxs-and-computational-study
#2
Sara Falsini, Emanuela Di Cola, Martin In, Maria Giordani, Stefano Borocci, Sandra Ristori
Gene therapy is based on nucleic acid delivery to pathogenic cells in order to modulate their gene expression. The most used non viral vectors are lipid-based nanoaggregates, which are safer than viral carriers and have been shown to assemble easily with both DNA and RNA. However, the transfection efficiency of non viral carriers still needs to be improved before intensive practise in clinical trials can be implemented. For this purpose, the in depth characterization of the complexes formed by nucleic acids and their transporters is of great relevance...
January 12, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28079152/a-novel-toolbox-for-the-in-vitro-assay-of-hepatitis-d-virus-infection
#3
Jing-Hua Zhao, Ya-Li Zhang, Tian-Ying Zhang, Lun-Zhi Yuan, Tong Cheng, Pei-Jer Chen, Quan Yuan, Ning-Shao Xia
Hepatitis D virus (HDV) is a defective RNA virus that requires the presence of hepatitis B virus (HBV) for its life cycle. The in vitro HDV infection system is widely used as a surrogate model to study cellular infection with both viruses owing to its practical feasibility. However, previous methods for running this system were less efficient for high-throughput screening and large-scale studies. Here, we developed a novel method for the production of infectious HDV by adenoviral vector (AdV)-mediated transduction...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28078341/the-role-of-uv-radiation-and-vitamin-d-in-the-seasonality-and-outcomes-of-infectious-disease
#4
Abhimanyu, Anna K Coussens
The seasonality of infectious disease outbreaks suggests that environmental conditions have a significant effect on disease risk. One of the major environmental factors that can affect this is solar radiation, primarily acting through ultraviolet radiation (UVR), and its subsequent control of vitamin D production. Here we show how UVR and vitamin D, which are modified by latitude and season, can affect host and pathogen fitness and relate them to the outcomes of bacterial, viral and vector-borne infections...
January 12, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/28078128/endoscopic-ultrasound-in-pancreatic-cancer-innovative-applications-beyond-the-basics
#5
REVIEW
Joseph Yoo, C Andrew Kistler, Linda Yan, Andrew Dargan, Ali A Siddiqui
Endoscopic ultrasound (EUS) has become a mainstay in assisting in the diagnosis and staging of pancreatic cancer. In addition, EUS provides a modality to treat chronic pain through celiac plexus neurolysis. Currently, there is growing data and utilization of EUS in more diverse and innovative applications aimed at providing more sophisticated diagnostic, prognostic and therapeutic options for patients with pancreatic cancer. EUS delivery of chemotherapy, viral and biological vectors and fiducial markers may eventually revolutionize the way clinicians approach the care of a patient with pancreatic cancer...
December 2016: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28078104/discovery-of-flavivirus-derived-endogenous-viral-elements-in-anopheles-mosquito-genomes-supports-the-existence-of-anopheles-associated-insect-specific-flaviviruses
#6
Sebastian Lequime, Louis Lambrechts
The Flavivirus genus encompasses several arboviruses of public health significance such as dengue, yellow fever, and Zika viruses. It also includes insect-specific flaviviruses (ISFs) that are only capable of infecting insect hosts. The vast majority of mosquito-infecting flaviviruses have been associated with mosquito species of the Aedes and Culex genera in the Culicinae subfamily, which also includes most arbovirus vectors. Mosquitoes of the Anophelinae subfamily are not considered significant arbovirus vectors; however, flaviviruses have occasionally been detected in field-caught Anopheles specimens...
January 2017: Virus Evolution
https://www.readbyqxmd.com/read/28077642/studies-on-the-interaction-of-tumor-derived-hd5-alpha-defensins-with-adenoviruses-and-implications-for-oncolytic-adenovirus-therapy
#7
Charles Vragniau, Jens-Martin Hübner, Peter Beidler, Sucheol Gil, Kamola Saydaminova, Zhuo-Zhuang Lu, Roma Yumul, Hongjie Wang, Maximilian Richter, Pavel Sova, Charles Drescher, Pascal Fender, André Lieber
: Defensins are small anti-microbial peptides capable of neutralizing human adenovirus (HAdV) in vitro by binding capsid proteins and blocking endosomal escape of virus. In humans, the alpha defensin HD5 is produced by specialized epithelial cells of the gastro-intestinal and genito-urinary tracts. Here we demonstrate that HD5 is also expressed as an active, secreted peptide by epithelial ovarian and lung cancer cells in situ, in patient biopsies. This finding triggered us to study the role of HD5 in infection and spread of replication-competent, oncolytic HAdV type 3 virus...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077588/first-in-human-evaluation-of-the-safety-and-immunogenicity-of-an-intranasally-administered-replication-competent-sendai-virus-vectored-hiv-type-1-gag-vaccine-induction-of-potent-t-cell-or-antibody-responses-in-prime-boost-regimens
#8
Julien Nyombayire, Omu Anzala, Brian Gazzard, Etienne Karita, Philip Bergin, Peter Hayes, Jakub Kopycinski, Gloria Omosa-Manyonyi, Akil Jackson, Jean Bizimana, Bashir Farah, Eddy Sayeed, Christopher L Parks, Makoto Inoue, Takashi Hironaka, Hiroto Hara, Tsugumine Shu, Tetsuro Matano, Len Dally, Burc Barin, Harriet Park, Jill Gilmour, Angela Lombardo, Jean-Louis Excler, Patricia Fast, Dagna S Laufer, Josephine H Cox
BACKGROUND:  We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine. METHODS:  Sixty-five HIV-1-uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35-vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (SLA); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (SHA); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (ASH); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH)...
January 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28077443/single-dose-intracardiac-injection-of-pro-regenerative-micrornas-improves-cardiac-function-after-myocardial-infarction
#9
Pierluigi Lesizza, Giulia Prosdocimo, Valentina Martinelli, Gianfranco Sinagra, Serena Zacchigna, Mauro Giacca
RATIONALE: Recent evidence indicates that a few human microRNAs (miRNAs), in particular hsa-miR-199a-3p and hsa-miR-590-3p, stimulate proliferation of cardiomyocytes and, once expressed in the mouse heart using viral vectors, induce cardiac regeneration after myocardial infarction. Viral vectors, however, are not devoid of safety issues and, more notably, drive expression of the encoded miRNAs for indefinite periods of time, which might not be desirable in light of human therapeutic application...
January 11, 2017: Circulation Research
https://www.readbyqxmd.com/read/28077261/ventral-medullary-control-of-rapid-eye-movement-sleep-and-atonia
#10
Michael C Chen, Ramalingam Vetrivelan, Chun-Ni Guo, Catie Chang, Patrick M Fuller, Jun Lu
Discrete populations of neurons at multiple levels of the brainstem control rapid eye movement (REM) sleep and the accompanying loss of postural muscle tone, or atonia. The specific contributions of these brainstem cell populations to REM sleep control remains incompletely understood. Here we show in rats that viral vector-based lesions of the ventromedial medulla at a level rostral to the inferior olive (pSOM) produced violent myoclonic twitches and abnormal electromyographic spikes, but not complete loss of tonic atonia, during REM sleep...
January 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28074644/virus-inspired-self-assembly-nanofibers-with-aggregation-induced-emission-for-highly-efficient-and-visible-gene-delivery
#11
Chunqiu Zhang, Tingbin Zhang, Shubin Jin, Xiangdong Xue, Xiaolong Yang, Ningqiang Gong, Jinchao Zhang, Paul C Wang, Jian-Hua Tian, Jinfeng Xing, Xing-Jie Liang
High-efficiency gene transfer and suitably low cytotoxicity are the main goals of gene transfection systems based on nonviral vectors. In addition, it is desirable to track the gene transfer process in order to observe and explain the mechanism. Herein, inspired by viral structures which are optimized for gene delivery, we designed a small-molecule gene vector (TR4) with aggregation-induced emission properties by capping a peptide containing four arginine residues with tetraphenylethene (TPE) and a lipophilic tail...
January 11, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28074350/a-comparative-study-of-the-bone-regenerative-effect-of-chemically-modified-rna-encoding-bmp-2-or-bmp-9
#12
Behnoush Khorsand, Satheesh Elangovan, Liu Hong, Alexander Dewerth, Michael S D Kormann, Aliasger K Salem
Employing cost-effective biomaterials to deliver chemically modified ribonucleic acid (cmRNA) in a controlled manner addresses the high cost, safety concerns, and lower transfection efficiency that exist with protein and gene therapeutic approaches. By eliminating the need for nuclear entry, cmRNA therapeutics can potentially overcome the lower transfection efficiencies associated with non-viral gene delivery systems. Here, we investigated the osteogenic potential of cmRNA-encoding BMP-9, in comparison to cmRNA-encoding BMP-2...
January 10, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28073086/human-neural-progenitors-derived-from-integration-free-ipscs-for-sci-therapy
#13
Ying Liu, Yiyan Zheng, Shenglan Li, Haipeng Xue, Karl Schmitt, Georgene W Hergenroeder, Jiaqian Wu, Yuanyuan Zhang, Dong H Kim, Qilin Cao
As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs) provide great capability for tissue regeneration, particularly in spinal cord injury (SCI). However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs) to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome...
January 5, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28072927/artificial-induction-of-native-aquaporin-1-expression-in-human-salivary-cells
#14
Z Wang, S Pradhan-Bhatt, M C Farach-Carson, M J Passineau
Gene therapy for dry mouth disorders has transitioned in recent years from theoretical to clinical proof of principle with the publication of a first-in-man phase I/II dose escalation clinical trial in patients with radiation-induced xerostomia. This trial used a prototype adenoviral vector to express aquaporin-1 (AQP1), presumably in the ductal cell layer and/or in surviving acinar cells, to drive transcellular flux of interstitial fluid into the labyrinth of the salivary duct. As the development of this promising gene therapy continues, safety considerations are a high priority, particularly those that remove nonhuman agents (i...
January 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28072887/dengue-fever-in-travellers-and-risk-of-local-spreading-case-reports-from-southern-italy-and-literature-update
#15
Claudia Fabrizio, Luciana Lepore, Maria Chironna, Gioacchino Angarano, Annalisa Saracino
Dengue fever (DF), an arbovirosis caused by Dengue viruses (DV, serotypes 1-4), is responsible for an increasing number of travel-related acute febrile illnesses due to population growth, climate changes, spreading by viremic travellers, and improved laboratory diagnosis. The presence of efficient vectors (mosquito Aedes albopictus) has also been described in temperate regions including Italy which is considered the most heavily infected European country. Normally characterized by non-specific signs and symptoms, DF incidence is probably underestimated, especially in non-endemic countries, but the risk of severe forms is substantial...
January 5, 2017: New Microbiologica
https://www.readbyqxmd.com/read/28072517/arthropod-innate-immune-systems-and-vector-borne-diseases
#16
Richard H G Baxter, Alicia Contet, Kathryn Krueger
Arthropods, especially ticks and mosquitoes, are the vectors for a number of parasitic and viral human diseases including malaria, sleeping sickness, Dengue and Zika. Yet arthropods show tremendous individual variation in their capacity to transmit disease. A key factor in this capacity is genetically encoded immune factors that counteract infection by the pathogen. Arthropod-specific pattern recognition receptors and protease cascades detect and respond to infection. Proteins such as antimicrobial peptides, thioester-containing proteins, and transglutaminases effect responses such as lysis, phagocytosis, melanization and agglutination...
January 10, 2017: Biochemistry
https://www.readbyqxmd.com/read/28069361/dna-mva-protein-vaccination-of-rhesus-macaques-induces-hiv-specific-immunity-in-mucosal-associated-lymph-nodes-and-functional-antibodies
#17
Gerald K Chege, Wendy A Burgers, Tracey L Müller, Clive M Gray, Enid G Shephard, Susan W Barnett, Guido Ferrari, David Montefiori, Carolyn Williamson, Anna-Lise Williamson
Successful future HIV vaccines are expected to generate an effective cellular and humoral response against the virus in both the peripheral blood and mucosal compartments. We previously reported the development of DNA-C and MVA-C vaccines based on HIV-1 subtype C and demonstrated their immunogenicity when given in a DNA prime-MVA boost combination in a nonhuman primate model. In the current study, rhesus macaques previously vaccinated with a DNA-C and MVA-C vaccine regimen were re-vaccinated 3.5years later with MVA-C followed by a protein vaccine based on HIV-1 subtype C envelope formulated with MF59 adjuvant (gp140Env/MF59), and finally a concurrent boost with both vaccines...
January 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28069290/classical-swine-fever-vaccines-state-of-the-art
#18
Sandra Blome, Claudia Moß, Ilona Reimann, Patricia König, Martin Beer
Due to its impact on animal health and pig industry, classical swine fever (CSF) is still one of the most important viral diseases of pigs. To control the disease, safe and highly efficacious live attenuated vaccines exist for decades. These vaccines have usually outstanding efficacy and safety but lack differentiability of infected from vaccinated animals (DIVA or marker strategy). In contrast, the first generation of E2 subunit marker vaccines shows constraints in efficacy, application, and production. To overcome these limitations, new generations of marker vaccines are developed...
January 3, 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28068367/cell-surface-integrins-and-car-are-both-essential-for-adenovirus-type-5-transduction-of-canine-cells-of-lymphocytic-origin
#19
Payal Agarwal, Elizabeth A Gammon, Abdul Mohin Sajib, Maninder Sandey, Bruce F Smith
Adenoviruses are the most widely used vectors in cancer gene therapy. Adenoviruses vectors are well characterized and are easily manipulated. Adenovirus serotype 5 (Ad5) is the most commonly used human serotype. Ad5 internalization into host cells is a combined effect of binding of Ad5 fiber knob with the coxsackie virus and adenovirus receptor (CAR) and binding of RGD motifs in viral penton to cell surface integrins (αvβ3, αvβ5). Ad5's wide range of host-cell transduction and lack of integration into the host genome have made it an excellent choice for cancer therapeutics...
2017: PloS One
https://www.readbyqxmd.com/read/28067416/a-novel-technique-of-delivering-viral-vectors-to-trigeminal-ganglia-in-rats
#20
Hu Long, Lina Liao, Yang Zhou, Di Shan, Meiya Gao, Renhuan Huang, Xin Yang, Wenli Lai
The objective of this study was to develop a viable and reliable technique of delivering viral vectors to rat trigeminal ganglia. Adult Sprague-Dawley rats (200-300 g) were used, and lentiviral vectors containing enhanced green fluorescence protein and calcitonin gene-related peptide short hairpin RNA (shRNA) were generated. Following general anesthesia, viral vectors were delivered to rat trigeminal ganglia using the technique described in this study. Both X-ray and micro-computed tomography (micro-CT) were employed to verify the position of the needles when injecting the vectors...
January 9, 2017: European Journal of Oral Sciences
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