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https://www.readbyqxmd.com/read/27922009/pet-imaging-guided-chemogenetic-silencing-reveals-a-critical-role-of-primate-rostromedial-caudate-in-reward-evaluation
#1
Yuji Nagai, Erika Kikuchi, Walter Lerchner, Ken-Ichi Inoue, Bin Ji, Mark A G Eldridge, Hiroyuki Kaneko, Yasuyuki Kimura, Arata Oh-Nishi, Yukiko Hori, Yoko Kato, Toshiyuki Hirabayashi, Atsushi Fujimoto, Katsushi Kumata, Ming-Rong Zhang, Ichio Aoki, Tetsuya Suhara, Makoto Higuchi, Masahiko Takada, Barry J Richmond, Takafumi Minamimoto
The rostromedial caudate (rmCD) of primates is thought to contribute to reward value processing, but a causal relationship has not been established. Here we use an inhibitory DREADD (Designer Receptor Exclusively Activated by Designer Drug) to repeatedly and non-invasively inactivate rmCD of macaque monkeys. We inject an adeno-associated viral vector expressing the inhibitory DREADD, hM4Di, into the rmCD bilaterally. To visualize DREADD expression in vivo, we develop a non-invasive imaging method using positron emission tomography (PET)...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27920474/hepatitis-b-virus-upregulates-host-expression-of-%C3%AE-1-2-mannosidases-via-the-ppar%C3%AE-pathway
#2
Song Hu, Li-Bin Jiang, Xiao-Jing Zou, Wei Yi, De-Ying Tian
AIM: To assess the effects of hepatitis B virus (HBV) on the expression of host α-1,2-mannosidases and determine the underlying mechanisms. METHODS: We measured the expression levels of MAN1A1, MAN1A2, MAN1B1, and MAN1C1 in cell lines HepG2.2.15, HepN10, HepAD38 and HepG2 by Western blot. Viral antigens (HBsAg and HBeAg) in the culture medium were measured using the chemiluminescence method. HBV DNA quantification assays were performed using a commercial real-time PCR kit...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27918590/effects-of-circular-dna-length-on-transfection-efficiency-by-electroporation-into-hela-cells
#3
Benjamin D Hornstein, Dany Roman, Lirio M Arévalo-Soliz, Melinda A Engevik, Lynn Zechiedrich
The ability to produce extremely small and circular supercoiled vectors has opened new territory for improving non-viral gene therapy vectors. In this work, we compared transfection of supercoiled DNA vectors ranging from 383 to 4,548 bp, each encoding shRNA against GFP under control of the H1 promoter. We assessed knockdown of GFP by electroporation into HeLa cells. All of our vectors entered cells in comparable numbers when electroporated with equal moles of DNA. Despite similar cell entry, we found length-dependent differences in how efficiently the vectors knocked down GFP...
2016: PloS One
https://www.readbyqxmd.com/read/27905841/cell-delivered-entry-inhibitors-for-hiv-1-ccr5-downregulation-and-blocking-virus-membrane-fusion-in-defending-the-host-cell-population
#4
Geoff Symonds, Jeffrey S Bartlett, Hans-Peter Kiem, Marlene Tsie, Louis Breton
HIV-1 infection requires the presence of the CD4 receptor on the target cell surface and a coreceptor, predominantly CC-chemokine receptor 5 (CCR5). It has been shown that individuals who are homozygous for a defective CCR5 gene are protected from HIV-1 infection. A novel self-inactivating lentiviral vector LVsh5/C46 (Cal-1) has been engineered to block HIV-1 infection with two viral entry inhibitors, conferring resistance to HIV-1 infection from both CCR5 and CXCR4 tropic strains. Cal-1 encodes a short hairpin RNA (sh5) to downregulate CCR5 and C46, an HIV-1 fusion inhibitor...
December 2016: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/27902403/the-non-canonical-tomato-yellow-leaf-curl-virus-recombinant-that-displaced-its-parental-viruses-in-southern-morocco-exhibits-a-high-selective-advantage-in-experimental-conditions
#5
Zineb Belabess, Michel Peterschmitt, Martine Granier, Abdessalem Tahiri, Abdelali Blenzar, Cica Urbino
Recombination events are frequently inferred from the increasing number of sequenced viral genomes, but their impact on natural viral populations has rarely been evidenced. TYLCV-IS76 is a recombinant (Begomovirus, Geminiviridae) between the Israel strain of Tomato yellow leaf curl virus (TYLCV-IL) and the Spanish strain of Tomato yellow leaf curl Sardinia virus (TYLCSV-ES) that was generated most probably in the late 1990s in Southern Morocco (Souss). Its emergence in the 2000s coincided with the increasing use of resistant tomato cultivars bearing the Ty-1 gene, and led eventually to the entire displacement of both parental viruses in the Souss...
October 14, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27893183/toxic-effects-of-human-and-rodent-variants-of-alpha-synuclein-in-vivo
#6
Natalie Landeck, Kerstin Buck, Deniz Kirik
In Parkinson's disease, abnormal alpha-synuclein (asyn) accumulation leads to the formation of soluble oligomeric species thought to be toxic to cells as well as intraneuronal inclusions. To date, the precise mechanisms leading to aggregation of asyn in the brain is not well understood. Previous studies in yeast, drosophila and transgenic mice suggested that a non-A beta component depleted version of human asyn [h-asyn(D70-83)] or human beta-synuclein (h-bsyn), naturally lacking this centrally located hydrophobic region, are less prone to form aggregates in vitro and are expected to be less toxic compared to h-asyn in vivo, although not all experimental studies unequivocally support the latter view...
November 28, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27891076/recombinant-adeno-associated-virus-serotype-6-raav6-potently-and-preferentially-transduces-rat-astrocytes-in-vitro-and-in-vivo
#7
Alexandra L Schober, Dmitriy A Gagarkin, Ying Chen, Guangping Gao, Lauren Jacobson, Alexander A Mongin
Recombinant adeno-associated virus vectors are an increasingly popular tool for gene delivery to the CNS because of their non-pathological nature, low immunogenicity, and ability to stably transduce dividing and non-dividing cells. One of the limitations of rAAVs is their preferential tropism for neuronal cells. Glial cells, specifically astrocytes, appear to be infected at low rates. To overcome this limitation, previous studies utilized rAAVs with astrocyte-specific promoters or assorted rAAV serotypes and pseudotypes with purported selectivity for astrocytes...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27889586/surfactant-effect-on-the-physicochemical-characteristics-of-cationic-solid-lipid-nanoparticles
#8
Chiara Botto, Nicolò Mauro, Erika Amore, Elisabetta Martorana, Gaetano Giammona, Maria Luisa Bondì
Solid lipid nanoparticles (SLNs) may be considered as a new approach for therapeutics for many diseases. In addition to drug delivery, their use as non-viral vectors for gene delivery can be obtained by including cationic lipids, which provide a positive surface potential that favors binding to the nucleic acids as DNA, siRNA, miRNA, etc. In fact, the addition of cationic surfactants is indispensable for obtaining nanoparticles with surface positive charge. In this study, three different cationic lipids (dioctadecyl dimethyl ammonium bromide, cetyltrimethyl ammonium bromide, cetylpyridinium chloride) and Brij 76 as nonionic surfactant were employed to formulate Precirol ATO 5 based cSLN using pEGFP-LUC as model plasmid...
November 23, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27888410/genome-sequence-prevalence-and-quantification-of-the-first-iflavirus-identified-in-a-phytoplasma-insect-vector
#9
Simona Abbà, Luciana Galetto, Marta Vallino, Marika Rossi, Massimo Turina, Anne Sicard, Cristina Marzachì
The leafhopper Euscelidius variegatus is a natural vector of chrysanthemum yellows phytoplasma (CY) and an efficient vector of flavescence dorée phytoplasma (FD) under laboratory conditions. During a transcriptome sequencing (RNA-seq) project aimed at investigating the interactions between the insect and the two phytoplasmas, a 10,616-nucleotide-long contig with high sequence similarity to known picorna-like viruses was identified among the assembled insect transcripts. The discovery came totally unexpected, because insects from the laboratory colony did not show any evident symptom that could be related to the presence of a virus...
November 25, 2016: Archives of Virology
https://www.readbyqxmd.com/read/27881138/bohv-4-based-vector-delivering-ebola-virus-surface-glycoprotein
#10
Alfonso Rosamilia, Sarah Jacca, Giulia Tebaldi, Silvia Tiberti, Valentina Franceschi, Francesca Macchi, Sandro Cavirani, Gary Kobinger, Donald P Knowles, Gaetano Donofrio
BACKGROUND: Ebola virus (EBOV) is a Category A pathogen that is a member of Filoviridae family that causes hemorrhagic fever in humans and non-human primates. Unpredictable and devastating outbreaks of disease have recently occurred in Africa and current immunoprophylaxis and therapies are limited. The main limitation of working with pathogens like EBOV is the need for costly containment. To potentiate further and wider opportunity for EBOV prophylactics and therapies development, innovative approaches are necessary...
November 24, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27874854/graphene-materials-as-2d-non-viral-gene-transfer-vector-platforms
#11
REVIEW
M Vincent, I de Lázaro, K Kostarelos
Advances in genomics and gene therapy could offer solutions to many diseases that remain incurable today, however one of the critical reasons halting clinical progress is due to the difficulty in designing efficient and safe delivery vectors for the appropriate genetic cargo. Safety and large-scale production concerns counter-balance the high gene transfer efficiency achieved with viral vectors, while non-viral strategies have yet to become sufficiently efficient. The extraordinary physicochemical, optical and photothermal properties of graphene-based materials (GBMs) could offer two-dimensional (2D) components for the design of nucleic acid carrier systems...
November 22, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27874090/a-novel-process-of-viral-vector-barcoding-and-library-preparation-enables-high-diversity-library-generation-and-recombination-free-paired-end-sequencing
#12
Marcus Davidsson, Paula Diaz-Fernandez, Oliver D Schwich, Marcos Torroba, Gang Wang, Tomas Björklund
Detailed characterization and mapping of oligonucleotide function in vivo is generally a very time consuming effort that only allows for hypothesis driven subsampling of the full sequence to be analysed. Recent advances in deep sequencing together with highly efficient parallel oligonucleotide synthesis and cloning techniques have, however, opened up for entirely new ways to map genetic function in vivo. Here we present a novel, optimized protocol for the generation of universally applicable, barcode labelled, plasmid libraries...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872706/alkyl-cross-linked-low-molecular-weight-polypropyleneimine-dendrimers-as-efficient-gene-delivery-vectors
#13
Faezeh Moghadam Ariaee, Maryam Hashemi, Sara Amel Farzad, Khalil Abnous, Mohammad Ramezani
OBJECTIVES: In recent years, polypropyleneimine (PPI) dendrimers have attracted great interest as non-viral gene delivery systems because of their attractive features including highly branched architecture with number of reactive end groups. However, without being structurally modified, they are not efficient gene carriers. In the present study, generation 2 and 3 (G2 and G3) of PPI dendrimers were conjugated with alkylcarboxylate groups as linker to enhance the transfection efficiency while maintaining their low cell toxicity...
October 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27871611/toward-a-suitable-structural-analysis-of-gene-delivery-carrier-based-on-polycationic-carbohydrates-by-electron-transfer-dissociation-tandem-mass-spectrometry
#14
Cédric Przybylski, Juan M Benito, Véronique Bonnet, Carmen Ortiz Mellet, José M García Fernández
Polycationic carbohydrates represent an attractive class of biomolecules for several applications and particularly as non viral gene delivery vectors. In this case, the establishment of structure-biological activity relationship requires sensitive and accurate characterization tools to both control and achieve fine structural deciphering. Electrospray-tandem mass spectrometry (ESI-MS/MS) appears as a suitable approach to address these questions. In the study herein, we have investigated the usefulness of electron transfer dissociation (ETD) to get structural data about five polycationic carbohydrates demonstrated as promising gene delivery agents...
December 15, 2016: Analytica Chimica Acta
https://www.readbyqxmd.com/read/27868311/tnf-%C3%AE-induced-il-6-and-mmp-9-expression-in-immortalized-ameloblastoma-cell-line-established-by-htert
#15
K Ohta, T Naruse, Y Ishida, H Shigeishi, T Nakagawa, A Fukui, H Nishi, K Sasaki, I Ogawa, M Takechi
OBJECTIVE: Ameloblastoma (AM) shows locally invasive behaviour. However, biological investigations regarding regulation of gene expression associated with AM pathological features are difficult to perform, because AM cells can be passaged for a few generations due to senescence. We report a newly established immortalized AM cell line, AMB cells, by transfection with human telomerase reverse transcriptase (hTERT). Furthermore, we examined whether TNF-α modulates bone resorption-related genes, IL-6 and MMP-9 in cooperation with TGF-β or IFN-γ...
October 13, 2016: Oral Diseases
https://www.readbyqxmd.com/read/27867077/critical-phases-of-viral-production-processes-monitored-by-capacitance
#16
E Petiot, S Ansorge, Manuel Rosa-Calatrava, A Kamen
Over the last decade industrial manufacturing of viral vaccines and viral vectors for prophylactic and therapeutic applications is experiencing a remarkable growth. Currently, the quality attributes of viral derived products are assessed only at the end-point of the production process, essentially because in-process monitoring tools are not available or not implemented at industrial scale. However, to demonstrate process reproducibility and robustness, manufacturers are strongly advised by regulatory agencies to adopt more on-line process monitoring and control...
November 17, 2016: Journal of Biotechnology
https://www.readbyqxmd.com/read/27866431/microrna-targeted-therapeutics-for-lung-cancer-treatment
#17
Jing Xue, Jiali Yang, Meihui Luo, William C Cho, Xiaoming Liu
Lung cancer is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are endogenous non-coding small RNAs that repress the expression of a broad array of target genes. Many efforts have been made to therapeutically target miRNAs in cancer treatments using miRNA mimics and miRNA antagonists. Areas covered: This article summarizes the recent findings with the role of miRNAs in lung cancer, and discusses the potential and challenges of developing miRNA-targeted therapeutics in this dreadful disease...
November 20, 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27860328/luminescent-ruthenium-ii-polypyridyl-complexes-as-non-viral-carriers-for-dna-delivery
#18
Satish Shantaram Bhat, Vidyanand K Revankar, Ayesha Khan, Rahul V Pinjari, Marek Necas
Two new luminescent ruthenium(II) polypyridyl complexes [Ru(bpy)2(tpt-phen)]Cl2 (1) and [Ru(phen)2(tpt-phen)]Cl2 (2) {bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, tpt-phen = triptycenyl-1,10-phenanthroline} have been developed as potential non-viral vectors for DNA delivery. Photophysical and electrochemical properties of the complexes have been investigated and corroborated with electronic structure calculations. The DNA condensation by these complexes has been investigated by UV-visible and emission spectroscopy, circular dichroism spectroscopy, atomic force microscopy, dynamic light scattering, confocal microscopy and electrophoretic mobility studies...
November 10, 2016: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/27859771/engineering-a-gene-silencing-viral-construct-that-targets-the-cat-hypothalamus-to-induce-permanent-sterility-an-update
#19
G A Dissen, K Adachi, A Lomniczi, T Chatkupt, B L Davidson, H Nakai, S R Ojeda
The intent of this contribution is to provide an update of the progress we have made towards developing a method/treatment to permanently sterilize cats. Our approach employs two complementary methodologies: RNA interference (RNAi) to silence genes involved in the central control of reproduction and a virus-based gene therapy system intended to deliver RNAi selectively to the hypothalamus (where these genes are expressed) via the systemic administration of modified viruses. We selected the hypothalamus because it contains neurons expressing Kiss1 and Tac3, two genes essential for reproduction and fertility...
November 17, 2016: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/27857058/molecular-imaging-and-cancer-gene-therapy
#20
REVIEW
Z Saadatpour, G Bjorklund, S Chirumbolo, M Alimohammadi, H Ehsani, H Ebrahiminejad, H Pourghadamyari, B Baghaei, H R Mirzaei, A Sahebkar, H Mirzaei, M Keshavarzi
Gene therapy is known as one of the most advanced approaches for therapeutic prospects ranging from tackling genetic diseases to combating cancer. In this approach, different viral and nonviral vector systems such as retrovirus, lentivirus, plasmid and transposon have been designed and employed. These vector systems are designed to target different therapeutic genes in various tissues and cells such as tumor cells. Therefore, detection of the vectors containing therapeutic genes and monitoring of response to the treatment are the main issues that are commonly faced by researchers...
November 18, 2016: Cancer Gene Therapy
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