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https://www.readbyqxmd.com/read/27933336/shp-1-activation-inhibits-vascular-smooth-muscle-cell-proliferation-and-intimal-hyperplasia-in-a-rodent-model-of-insulin-resistance-and-diabetes
#1
Weier Qi, Qian Li, Chong Wee Liew, Christian Rask-Madsen, Samuel M Lockhart, Lars Melholt Rasmussen, Yu Xia, Xuanchun Wang, Mogher Khamaisi, Kevin Croce, George L King
AIMS/HYPOTHESIS: Accelerated migration and proliferation of vascular smooth muscle cells (VSMCs) enhances arterial restenosis after angioplasty in insulin resistance and diabetes. Elevation of Src homology 2-containing protein tyrosine phosphatase 1 (SHP-1) induces apoptosis in the microvasculature. However, the role of SHP-1 in intimal hyperplasia and restenosis has not been clarified in insulin resistance and diabetes. METHODS: We used a femoral artery wire injury mouse model, rodent models with insulin resistance and diabetes, and patients with type 2 diabetes...
December 9, 2016: Diabetologia
https://www.readbyqxmd.com/read/27933310/dynamics-of-antigen-presentation-to-transgene-product-specific-cd4-t-cells-and-of-treg-induction-upon-hepatic-aav-gene-transfer
#2
George Q Perrin, Irene Zolotukhin, Alexandra Sherman, Moanaro Biswas, Ype P de Jong, Cox Terhorst, Andrew M Davidoff, Roland W Herzog
The tolerogenic hepatic microenvironment impedes clearance of viral infections but is an advantage in viral vector gene transfer, which often results in immune tolerance induction to transgene products. Although the underlying tolerance mechanism has been extensively studied, our understanding of antigen presentation to transgene product-specific CD4(+) T cells remains limited. To address this, we administered hepatotropic adeno-associated virus (AAV8) vector expressing cytoplasmic ovalbumin (OVA) into wt mice followed by adoptive transfer of transgenic OVA-specific T cells...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933309/impact-of-age-and-vector-construct-on-striatal-and-nigral-transgene-expression
#3
Nicole K Polinski, Fredric P Manfredsson, Matthew J Benskey, D Luke Fischer, Christopher J Kemp, Kathy Steece-Collier, Ivette M Sandoval, Katrina L Paumier, Caryl E Sortwell
Therapeutic protein delivery using viral vectors has shown promise in preclinical models of Parkinson's disease (PD) but clinical trial success remains elusive. This may partially be due to a failure to include advanced age as a covariate despite aging being the primary risk factor for PD. We investigated transgene expression following intracerebral injections of recombinant adeno-associated virus pseudotypes 2/2 (rAAV2/2), 2/5 (rAAV2/5), 2/9 (rAAV2/9), and lentivirus (LV) expressing green fluorescent protein (GFP) in aged versus young adult rats...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933308/tailored-transgene-expression-to-specific-cell-types-in-the-central-nervous-system-after-peripheral-injection-with-aav9
#4
Jonathan Dashkoff, Eli P Lerner, Nhi Truong, Jacob A Klickstein, Zhanyun Fan, Dakai Mu, Casey A Maguire, Bradley T Hyman, Eloise Hudry
The capacity of certain adeno-associated virus (AAV) vectors to cross the blood-brain barrier after intravenous delivery offers a unique opportunity for noninvasive brain delivery. However, without a well-tailored system, the use of a peripheral route injection may lead to undesirable transgene expression in nontarget cells or organs. To refine this approach, the present study characterizes the transduction profiles of new self-complementary AAV9 (scAAV9) expressing the green fluorescent protein (GFP) either under an astrocyte (glial fibrillary acidic (GFA) protein) or neuronal (Synapsin (Syn)) promoter, after intravenous injection of adult mice (2 × 10(13) vg/kg)...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933307/impact-of-intravenous-infusion-time-on-aav8-vector-pharmacokinetics-safety-and-liver-transduction-in-cynomolgus-macaques
#5
Jenny A Greig, Jayme Ml Nordin, Erin Bote, Leah Makaron, Mason E Garnett, Lisa M Kattenhorn, Peter Bell, Tamara Goode, James M Wilson
Systemically delivered adeno-associated viral (AAV) vectors are now in early-phase clinical trials for a variety of diseases. While there is a general consensus on inclusion and exclusion criteria for each of these trials, the conditions under which vectors are infused vary significantly. In this study, we evaluated the impact of intravenous infusion rate of AAV8 vector in cynomolgus macaques on transgene expression, vector clearance from the circulation, and potential activation of the innate immune system...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933306/significant-changes-in-endogenous-retinal-gene-expression-assessed-1-year-after-a-single-intraocular-injection-of-aav-cntf-or-aav-bdnf
#6
Chrisna J LeVaillant, Anil Sharma, Jill Muhling, Lachlan Pg Wheeler, Greg S Cozens, Mats Hellström, Jennifer Rodger, Alan R Harvey
Use of viral vectors to deliver therapeutic genes to the central nervous system holds promise for the treatment of neurodegenerative diseases and neurotrauma. Adeno-associated viral (AAV) vectors encoding brain-derived neurotrophic factor (BDNF) or ciliary derived neurotrophic factor (CNTF) promote the viability and regeneration of injured adult rat retinal ganglion cells. However, these growth-inducing transgenes are driven by a constitutively active promoter, thus we examined whether long-term AAV-mediated secretion of BDNF or CNTF affected endogenous retinal gene expression...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933305/robust-generation-of-transgenic-mice-by-simple-hypotonic-solution-mediated-delivery-of-transgene-in-testicular-germ-cells
#7
Abul Usmani, Nirmalya Ganguli, Subodh K Jain, Nilanjana Ganguli, Rajesh Kumar Sarkar, Mayank Choubey, Mansi Shukla, Hironmoy Sarkar, Subeer S Majumdar
Our ability to decipher gene sequences has increased enormously with the advent of modern sequencing tools, but the ability to divulge functions of new genes have not increased correspondingly. This has caused a remarkable delay in functional interpretation of several newly found genes in tissue and age specific manner, limiting the pace of biological research. This is mainly due to lack of advancements in methodological tools for transgenesis. Predominantly practiced method of transgenesis by pronuclear DNA-microinjection is time consuming, tedious, and requires highly skilled persons for embryo-manipulation...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933303/purification-of-baculovirus-vectors-using-heparin-affinity-chromatography
#8
Md Nasimuzzaman, Danielle Lynn, Johannes Cm van der Loo, Punam Malik
Baculoviruses are commonly used for recombinant protein and vaccine production. Baculoviruses are nonpathogenic to vertebrates, have a large packaging capacity, display broad host and cell type tropism, infect both dividing and nondividing cells, and do not elicit strong immune or allergic responses in vivo. Hence, their use as gene delivery vehicles has become increasingly popular in recent years. Moreover, baculovirus vectors carrying mammalian regulatory elements can efficiently transduce and express transgenes in mammalian cells...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933291/endocytosis-and-physiology-insights-from-disabled-2-deficient-mice
#9
REVIEW
Wensi Tao, Robert Moore, Elizabeth R Smith, Xiang-Xi Xu
Disabled-2 (Dab2) is a clathrin and cargo binding endocytic adaptor protein, and cell biology studies revealed that Dab2 plays a role in cellular trafficking of a number of transmembrane receptors and signaling proteins. A PTB/PID domain located in the N-terminus of Dab2 binds the NPXY motif(s) present at the cytoplasmic tails of certain transmembrane proteins/receptors. The membrane receptors reported to bind directly to Dab2 include LDL receptor and its family members LRP1 and LRP2 (megalin), growth factor receptors EGFR and FGFR, and the cell adhesion receptor beta1 integrin...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27933212/spontaneous-destructive-periodontitis-and-skeletal-bone-damage-in-transgenic-mice-carrying-a-human-shared-epitope-coding-hla-drb1-allele
#10
Prashasnika Gehlot, Sarah L Volk, Hector F Rios, Karl J Jepsen, Joseph Holoshitz
OBJECTIVE: Shared epitope (SE)-coding DRB1 alleles are associated with bone erosion in several diseases, including rheumatoid arthritis (RA) and periodontal disease (PD), but the underlying mechanism is unknown. We have recently identified the SE as an osteoclast-activating ligand. To better understand the biological effects of the SE in vivo, here we sought to determine whether it can facilitate spontaneous bone damage in naïve mice. METHODS: 3-month old naïve transgenic mice that carry the human SE-coding allele DRB1*04:01, or a SE-negative allele DRB1*04:02 were studied...
2016: RMD Open
https://www.readbyqxmd.com/read/27933142/salidroside-reduces-tau-hyperphosphorylation-via-up-regulating-gsk-3%C3%AE-phosphorylation-in-a-tau-transgenic-drosophila-model-of-alzheimer-s-disease
#11
Bei Zhang, Qiongqiong Li, Xingkun Chu, Suya Sun, Shengdi Chen
BACKGROUND: Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disease that causes substantial public health care burdens. Intensive efforts have been made to find effective and safe treatment against AD. Salidroside (Sal) is the main effective component of Rhodiola rosea L., which has several pharmacological activities. The objective of this study was to investigate the efficacy of Sal in the treatment of AD transgenic Drosophila and the associated mechanisms...
2016: Translational Neurodegeneration
https://www.readbyqxmd.com/read/27933081/the-density-and-length-of-root-hairs-are-enhanced-in-response-to-cadmium-and-arsenic-by-modulating-gene-expressions-involved-in-fate-determination-and-morphogenesis-of-root-hairs-in-arabidopsis
#12
Ramin Bahmani, Dong G Kim, Jin A Kim, Seongbin Hwang
Root hairs are tubular outgrowths that originate from epidermal cells. Exposure of Arabidopsis to cadmium (Cd) and arsenic [arsenite, As(III)] increases root hair density and length. To examine the underlying mechanism, we measured the expression of genes involved in fate determination and morphogenesis of root hairs. Cd and As(III) downregulated TTG1 and GL2 (negative regulators of fate determination) and upregulated GEM (positive regulator), suggesting that root hair fate determination is stimulated by Cd and As(III)...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27933076/overexpression-of-tanac2d-displays-opposite-responses-to-abiotic-stresses-between-seedling-and-mature-stage-of-transgenic-arabidopsis
#13
Quanjun Huang, Yan Wang
Environmental stresses frequently affect plant growth and development, and many genes have been found to be induced by unfavorable environmental conditions. Here, we reported the biological functions of TaNAC2D, a stress-related NAC (NAM, ATAF, and CUC) gene from wheat. TaNAC2D showed transcriptional activator activity in yeast. TaNAC2D-GFP fusion protein was localized in the nucleus of wheat mesophyll protoplasts. TaNAC2D transcript abundance was significantly induced by NaCl, PEG6000, and abscisic acid (ABA) at seedling stage, and repressed by NaCl and PEG6000 at mature plant stage...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27933075/a-non-specific-setaria-italica-lipid-transfer-protein-gene-plays-a-critical-role-under-abiotic-stress
#14
Yanlin Pan, Jianrui Li, Licong Jiao, Cong Li, Dengyun Zhu, Jingjuan Yu
Lipid transfer proteins (LTPs) are a class of cysteine-rich soluble proteins having small molecular weights. LTPs participate in flower and seed development, cuticular wax deposition, also play important roles in pathogen and abiotic stress responses. A non-specific LTP gene (SiLTP) was isolated from a foxtail millet (Setaria italica) suppression subtractive hybridization library enriched for differentially expressed genes after abiotic stress treatments. A semi-quantitative reverse transcriptase PCR analysis showed that SiLTP was expressed in all foxtail millet tissues...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27932977/human-neural-stem-cell-transplantation-rescues-cognitive-defects-in-app-ps1-model-of-alzheimer-s-disease-by-enhancing-neuronal-connectivity-and-metabolic-activity
#15
Xueyuan Li, Hua Zhu, Xicai Sun, Fuxing Zuo, Jianfeng Lei, Zhanjing Wang, Xinjie Bao, Renzhi Wang
Alzheimer's disease (AD), the most frequent type of dementia, is featured by Aβ pathology, neural degeneration and cognitive decline. To date, there is no cure for this disease. Neural stem cell (NSC) transplantation provides new promise for treating AD. Many studies report that intra-hippocampal transplantation of murine NSCs improved cognition in rodents with AD by alleviating neurodegeneration via neuronal complement or replacement. However, few reports examined the potential of human NSC transplantation for AD...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27932790/motor-neurons-derived-from-als-related-mouse-ips-cells-recapitulate-pathological-features-of-als
#16
Ju-Hwang Park, Hang-Soo Park, Sunghoi Hong, Seongman Kang
Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease characterized by the loss of motor neurons in the spinal cord and brain. Mutations in Cu/Zn superoxide dismutase 1 (SOD1) are known to induce ALS. Although many research models have been developed, the exact pathological mechanism of ALS remains unknown. The recently developed induced pluripotent stem (iPS) cell technology is expected to illuminate the pathological mechanisms and new means of treatment for neurodegenerative diseases...
December 9, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27932454/inducible-colonic-m-cells-are-dependent-on-tnfr2-but-not-lt%C3%AE-r-identifying-distinct-signaling-requirements-for-constitutive-versus-inducible-m-cells
#17
Erinn A Parnell, Erin M Walch, David D Lo
BACKGROUND AND AIMS: M cells associated with organized lymphoid tissues such as intestinal Peyer's patches provide surveillance of the intestinal lumen. Inflammation or infection in the colon can induce an M cell population associated with lymphoid infiltrates; paradoxically, induction is dependent on the inflammatory cytokine Tumor Necrosis Factor (TNF)-α. Anti-TNFα blockade is an important therapeutic in Inflammatory Bowel Disease, so understanding the effects of TNFα signaling is important in refining therapeutics...
December 7, 2016: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/27932267/human-pre-pik3c2b-an-intronic-cis-element-with-dual-function-of-activation-and-repression
#18
Jayant Maini, Mohsen Ghasemi, Deepti Yandhuri, Suman S Thakur, Vani Brahmachari
The Polycomb/Trithorax Responsive Elements (PRE/TREs) are the cis-regulatory sequences that interact with both repressive (PcG) as well as activating (TrxG) complexes. However, most of the mammalian PREs are demonstrated to interact with the repressive polycomb (PcG) complexes only. We have carried out an unbiased search for proteins interacting with human PRE-PIK3C2B (hPRE-PIK3C2B) based on DNA affinity purification followed by mass spectrometry and identified MLL, MLL4 and WDR87 among other proteins in three biological replicates in HEK, U87 and HeLa cell lines...
December 5, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27931938/improving-the-secretory-capacity-of-chinese-hamster-ovary-cells-by-ectopic-expression-of-effector-genes-lessons-learned-and-future-directions
#19
REVIEW
Henning Gram Hansen, Nuša Pristovšek, Helene Faustrup Kildegaard, Gyun Min Lee
Chinese hamster ovary (CHO) cells are the preferred cell factory for the production of therapeutic glycoproteins. Although efforts primarily within bioprocess optimization have led to increased product titers of recombinant proteins (r-proteins) expressed in CHO cells, post-transcriptional bottlenecks in the biosynthetic pathway of r-proteins remain to be solved. To this end, the ectopic expression of transgenes (effector genes) offers great engineering potential. However, studies on effector genes have in some cases led to inconsistent results...
December 5, 2016: Biotechnology Advances
https://www.readbyqxmd.com/read/27931819/results-of-rat-pig-a-pigret-assay-with-a-single-dose-regimen-of-1-3-propane-sultone-and-2-acetyl-aminofluorene
#20
Miyuki Shigano, Nana Ishii, Rie Takashima, Hideki Harada, Hironao Takasawa, Shuichi Hamada
The Pig-a assay is a useful in vivo mutation detecting test and is easier to perform than the in vivo transgenic mutation assay. This assay is now recognized to be able to detect a number of mutagenic chemicals administered to rats in sub-acute or sub-chronic dose studies. The present investigation was conducted to evaluate the usefulness of peripheral blood Pig-a assays with total red blood cells (RBC Pig-a assay) and with reticulocytes (PIGRET assay) using two genotoxic rodent carcinogens, 1,3-propane sultone (1,3-PS) and 2-acetylaminofluorene (2-AAF)...
November 15, 2016: Mutation Research
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