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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/28078104/discovery-of-flavivirus-derived-endogenous-viral-elements-in-anopheles-mosquito-genomes-supports-the-existence-of-anopheles-associated-insect-specific-flaviviruses
#3
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/28077261/ventral-medullary-control-of-rapid-eye-movement-sleep-and-atonia
#4
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/28074350/a-comparative-study-of-the-bone-regenerative-effect-of-chemically-modified-rna-encoding-bmp-2-or-bmp-9
#5
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
#6
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/28072887/dengue-fever-in-travellers-and-risk-of-local-spreading-case-reports-from-southern-italy-and-literature-update
#7
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/28068367/cell-surface-integrins-and-car-are-both-essential-for-adenovirus-type-5-transduction-of-canine-cells-of-lymphocytic-origin
#8
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/28067229/tubules-of-plant-reoviruses-exploit-tropomodulin-to-regulate-actin-based-tubule-motility-in-insect-vector
#9
Qian Chen, Linghua Zhang, Yanshuang Zhang, Qianzhuo Mao, Taiyun Wei
Plant reoviruses are known to exploit virion-packaging tubules formed by virus-encoding non-structural proteins for viral spread in insect vectors. Tubules are propelled by actin-based tubule motility (ABTM) to overcome membrane or tissue barriers in insect vectors. To further understand which insect factors mediate ABTM, we utilized yeast two-hybrid and bimolecular fluorescence complementation assays to test interactions between tubule protein Pns10 of rice dwarf virus (RDV), a plant reovirus, and proteins of its insect vector, the leafhopper Nephotettix cincticeps...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28060823/the-antiviral-rnai-response-in-vector-and-non-vector-cells-against-orthobunyaviruses
#10
Isabelle Dietrich, Xiaohong Shi, Melanie McFarlane, Mick Watson, Anne-Lie Blomström, Jessica K Skelton, Alain Kohl, Richard M Elliott, Esther Schnettler
BACKGROUND: Vector arthropods control arbovirus replication and spread through antiviral innate immune responses including RNA interference (RNAi) pathways. Arbovirus infections have been shown to induce the exogenous small interfering RNA (siRNA) and Piwi-interacting RNA (piRNA) pathways, but direct antiviral activity by these host responses in mosquito cells has only been demonstrated against a limited number of positive-strand RNA arboviruses. For bunyaviruses in general, the relative contribution of small RNA pathways in antiviral defences is unknown...
January 6, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28059103/radioiodinated-capsids-facilitate-in-vivo-non-invasive-tracking-of-adeno-associated-gene-transfer-vectors
#11
P Kothari, B P De, B He, A Chen, M J Chiuchiolo, D Kim, A Nikolopoulou, A Amor-Coarasa, J P Dyke, H U Voss, S M Kaminsky, C P Foley, S Vallabhajosula, B Hu, S G DiMagno, D Sondhi, R G Crystal, J W Babich, D Ballon
Viral vector mediated gene therapy has become commonplace in clinical trials for a wide range of inherited disorders. Successful gene transfer depends on a number of factors, of which tissue tropism is among the most important. To date, definitive mapping of the spatial and temporal distribution of viral vectors in vivo has generally required postmortem examination of tissue. Here we present two methods for radiolabeling adeno-associated virus (AAV), one of the most commonly used viral vectors for gene therapy trials, and demonstrate their potential usefulness in the development of surrogate markers for vector delivery during the first week after administration...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28054985/novel-pei-poly-%C3%AE-gutamic-acid-nanoparticles-for-high-efficient-sirna-and-plasmid-dna-co-delivery
#12
Shu-Fen Peng, Hung-Kun Hsu, Chun-Cheng Lin, Ya-Ming Cheng, Kuang-Hsing Hsu
The efficient delivery of sufficient amounts of nucleic acids into target cells is critical for successful gene therapy and gene knockdown. The DNA/siRNA co-delivery system has been considered a promising approach for cancer therapy to simultaneously express and inhibit tumor suppressor genes and overexpressed oncogenes, respectively, triggering synergistic anti-cancer effects. Polyethylenimine (PEI) has been identified as an efficient non-viral vector for transgene expression. In this study, we created a very high efficient DNA/siRNA co-delivery system by incorporating a negatively-charged poly-γ-glutamic acid (γ-PGA) into PEI/nucleic acid complexes...
January 4, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28051192/global-warming-and-its-health-impact
#13
Antonella Rossati
Since the mid-19th century, human activities have increased greenhouse gases such as carbon dioxide, methane, and nitrous oxide in the Earth's atmosphere that resulted in increased average temperature. The effects of rising temperature include soil degradation, loss of productivity of agricultural land, desertification, loss of biodiversity, degradation of ecosystems, reduced fresh-water resources, acidification of the oceans, and the disruption and depletion of stratospheric ozone. All these have an impact on human health, causing non-communicable diseases such as injuries during natural disasters, malnutrition during famine, and increased mortality during heat waves due to complications in chronically ill patients...
January 2017: International Journal of Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/28042945/minicircle-orip-mir-31-as-a-novel-ebna1-specific-mirna-therapy-approach-for-nasopharyngeal-carcinoma
#14
Jiang-Xue Wu, Xin Tan, Jiaxin Lin, Luping Yuan, Jiemin Chen, Lin Qiu, Wen-Lin Huang
MicroRNAs (miRNAs) are important post-transcriptional regulators that control cancer development and progression. However, the application of miRNA therapy in cancer has been hampered by a lack of an efficient and targeted delivery system. In our previous studies, an oriP promoter-based minicircle system successfully mediated targeted foreign gene expression in EBNA1-positive nasopharyngeal carcinoma (NPC). However, it remains to be evaluated whether this system can be applied for tumor miRNA therapy. miR-31-5p, a tumor suppressive miRNA involved in the tumorigenesis of EBV-positive NPC, was selected as the therapeutic miRNA to be transferred...
January 2, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28042541/rational-development-of-a-polycistronic-plasmid-with-a-cpg-free-bacterial-backbone-as-a-potential-tool-for-direct-reprogramming
#15
Kianoush Dormiani, Hamid Mir Mohammad Sadeghi, Hojjat Sadeghi-Aliabadi, Mahboobeh Forouzanfar, Hossein Baharvand, Kamran Ghaedi, Mohammad Hossein Nasr-Esfahani
OBJECTIVE: Induced pluripotent stem cells are generated from somatic cells by direct reprogramming. These reprogrammed pluripotent cells have different applications in biomedical fields such as regenerative medicine. Although viral vectors are widely used for efficient reprogramming, they have limited applications in the clinic due to the risk for immunogenicity and insertional mutagenesis. Accordingly, we designed and developed a small, non-integrating plasmid named pLENSO/Zeo as a 2A-mediated polycistronic expression vector...
2017: Cell Journal
https://www.readbyqxmd.com/read/28035105/the-epidemiology-of-dengue-infection-harnessing-past-experience-and-current-knowledge-to-support-implementation-of-future-control-strategies
#16
REVIEW
Narayan Gyawali, Richard S Bradbury, Andrew W Taylor-Robinson
Dengue is the most important mosquito-borne viral infection of humans. Although outbreaks of disease which are now recognized as clinically consistent with dengue have been reported for centuries, it was not until half a century ago that laboratory identification of dengue viruses as the etiological agent of febrile illness was achieved. This debilitating and sometimes fatal disease is widely distributed in >125 countries in tropical and subtropical zones of the world. Asia, South America and the Pacific Islands are hyper-epidemic regions while currently there is less prevalence in Europe, North America and Australia...
October 2016: Journal of Vector Borne Diseases
https://www.readbyqxmd.com/read/28017770/efficient-gene-delivery-to-primary-human-retinal-pigment-epithelial-cells-the-innate-and-acquired-properties-of-vectors
#17
Nooshin Tasharrofi, Fatemeh Kouhkan, Masoud Soleimani, Zahra-Soheila Soheili, Fatemeh Atyabi, Hamid Akbari Javar, Farid Abedin Dorkoosh
The purpose of this study is designing non-viral gene delivery vectors for transfection of the primary human retinal pigment epithelial cells (RPE). In the design process of gene delivery vectors, considering physicochemical properties of vectors alone does not seem to be enough since they interact with constituents of the surrounding environment and hence gain new characteristics. Moreover, due to these interactions, their cargo can be released untimely or undergo degradation before reaching to the target cells...
December 23, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28012171/mir-15b-mediates-oxaliplatin-induced-chronic-neuropathic-pain-through-bace1-downregulation
#18
Naomi Ito, Atsushi Sakai, Noriko Miyake, Motoyo Maruyama, Hirotoshi Iwasaki, Koichi Miyake, Takashi Okada, Atsuhiro Sakamoto, Hidenori Suzuki
BACKGROUND AND PURPOSE: Although oxaliplatin is an effective anti-cancer platinum compound, it can cause painful chronic neuropathy, and its molecular mechanisms remain poorly understood. MicroRNAs are small non-coding RNAs that negatively regulate gene expression in a sequence-specific manner. Although microRNAs have been increasingly recognised as important modulators in a variety of pain conditions, their involvement in chemotherapy-induced neuropathic pain is unknown. EXPERIMENTAL APPROACH: Oxaliplatin-induced chronic neuropathic pain was induced in rats by intraperitoneal oxaliplatin injections (2 mg kg(-1) ) for 5 consecutive days...
December 23, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28011743/5-ht2c-receptor-knockdown-in-the-amygdala-inhibits-neuropathic-pain-related-plasticity-and-behaviors
#19
Guangchen Ji, Wei Zhang, Lenin Mahimainathan, Madhusudhanan Narasimhan, Takaki Kiritoshi, Xiuzhen Fan, Jigong Wang, Thomas A Green, Volker Neugebauer
: Neuroplasticity in the amygdala drives pain-related behaviors. The central nucleus (CeA) serves major amygdala output functions and can generate emotional-affective behaviors and modulate nocifensive responses. The CeA receives excitatory and inhibitory inputs from the basolateral nucleus (BLA), and serotonin receptor subtype 5-HT2CR in the BLA, but not CeA, has been implicated anxiogenic behaviors and anxiety disorders. Here we tested the hypothesis that 5-HT2CR in the BLA plays a critical role in CeA plasticity and neuropathic pain behaviors in the rat spinal nerve ligation (SNL) model...
December 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28011343/design-and-characterization-of-a-magnetite-pei-multifunctional-nanohybrid-as-non-viral-vector-and-cell-isolation-system
#20
Raúl Megías, Maialen Arco, Jesús Ciriza, Laura Saenz Del Burgo, Gustavo Puras, Margarita López-Viota, Ángel V Delgado, Jon P Dobson, José L Arias, José L Pedraz
It is described the reproducible formulation and complete physicochemical characterization of nanohybrids based on magnetite (Fe3O4) cores embedded within a polyethylenimine (PEI) matrix. Particle size, surface electrical charge, X-ray diffraction and Fourier transform infrared spectroscopy (FTIR) analyses, and magnetic field-responsive behaviour characterizations defined that the 4:3 (Fe3O4:PEI) weight proportion led to the best production performances of magnetically responsive nanocomposites in which the magnetic nuclei are completely covered by the polymeric shell...
December 21, 2016: International Journal of Pharmaceutics
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