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           Search results for: miRNASelect™ pEP_hsa_mir_766 Expression Vector   

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Leishmania proteophosphoglycans regurgitated from infected sand flies accelerate dermal wound repair and exacerbate leishmaniasis via insulin-like growth factor 1-dependent signalling.

Leishmania parasites are transmitted to vertebrate hosts by female phlebotomine sand flies as they bloodfeed by lacerating the upper capillaries of the dermis with their barbed mouthparts. In the sand fly midgut secreted proteophosphoglycans from Leishmania form a biological plug known as the promastigote secretory gel (PSG), which blocks the gut and facilitates the regurgitation of infective parasites. The interaction between the wound created by the sand fly bite and PSG is not known. Here we nanoinjected a sand fly egested dose of PSG into BALB/c mouse skin that lead to the differential expression of 7,907 transcripts. These transcripts were transiently up-regulated during the first 6 hours post-wound and enriched for pathways involved in inflammation, cell proliferation, fibrosis, epithelial cell differentiation and wound remodelling. We found that PSG significantly accelerated wound healing in vitro and in mice; which was associated with an early up-regulation of transcripts involved in inflammation (IL-1β, IL-6, IL-10, TNFα) and inflammatory cell recruitment (CCL2, CCL3, CCL4, CXCL2), followed 6 days later by enhanced expression of transcripts associated with epithelial cell proliferation, fibroplasia and fibrosis (FGFR2, EGF, EGFR, IGF1). Dermal expression of IGF1 was enhanced following an infected sand fly bite and was acutely responsive to the deposition of PSG but not the inoculation of parasites or sand fly saliva. Antibody blockade of IGF1 ablated the gel's ability to promote wound closure in mouse ears and significantly reduced the virulence of Leishmania mexicana infection delivered by an individual sand fly bite. Dermal macrophages recruited to air-pouches on the backs of mice revealed that IGF1 was pivotal to the PSG's ability to promote macrophage alternative activation and Leishmania infection. Our data demonstrate that through the regurgitation of PSG Leishmania exploit the wound healing response of the host to the vector bite by promoting the action of IGF1 to drive the alternative activation of macrophages.

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Human Insulin-like Growth Human Insulin-like Growth Mouse Insulin-like Growth Rat Insulin-like Growth F IGF-1R Signaling Phospho- IGF1, Insulin-like growth Mouse Anti-Insulin-Like G Human Insulin-like Growth Mouse Insulin-like Growth Rat monoclonal anti mouse Rat monoclonal anti mouse Rat monoclonal anti mouse

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AV2 protein of tomato leaf curl Palampur virus promotes systemic necrosis in Nicotiana benthamiana and interacts with host Catalase2.

Tomato leaf curl Palampur virus (ToLCPalV) is a whitefly-transmitted, bipartite begomovirus. Here, we demonstrated that ectopic expression of AV2 from a Potato virus X (PVX)-based vector accelerated systemic necrosis and reactive oxygen species (ROS) accumulation in Nicotiana benthamiana. Furthermore, 10 amino acids from N-terminal region of AV2 were found to be associated with the systemic necrosis symptom/phenotype. Mutational studies of ToLCPalV infectious clones lacking the AV2 revealed that AV2 is essential for the systemic movement of DNA-A, symptom severity and viral DNA accumulation. In a yeast two-hybrid assay, Catalase2 (Cat2) was found to associate with AV2 protein. Further, silencing of Cat2 resulted in appearance of necrotic lesions on N. benthamiana and these plants were highly susceptible to ToLCPalV infection in comparison to control plants. Infection ToLCPalV on Solanum lycopersicum resulted in downregulation of Cat2 transcripts, followed by accumulation of ROS and stress marker transcripts. The AV2 protein also suppressed virus-induced gene silencing (VIGS) of the Phytoene desaturase (PDS) gene. Our results show that AV2 is essential for the pathogenicity, systemic movement and suppression of gene silencing in the host. Altogether, our findings suggest that interactions between AV2 and Cat2 might play a crucial role in the establishment of ToLCPalV infection.

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Anti-Infectious Pancreati Anti-Infectious Pancreati Anti-Infectious Pancreati Anti-Infectious Pancreati Mouse AntiInfluenza B Nuc Rabbit AntiFNIP1 Target A Goat Anti-Influenza A Vir Mouse Anti-Influenza A Vi FIV Core Ag, recombinant Polyclonal Antibody Recep Interleukin-34 IL34 (N-t Interleukin-34 IL34 anti

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Compositional Bias in Naïve and Chemically-modified Phage-Displayed Libraries uncovered by Paired-end Deep Sequencing.

Understanding the composition of a genetically-encoded (GE) library is instrumental to the success of ligand discovery. In this manuscript, we investigate the bias in GE-libraries of linear, macrocyclic and chemically post-translationally modified (cPTM) tetrapeptides displayed on the M13KE platform, which are produced via trinucleotide cassette synthesis (19 codons) and NNK-randomized codon. Differential enrichment of synthetic DNA {S}, ligated vector {L} (extension and ligation of synthetic DNA into the vector), naïve libraries {N} (transformation of the ligated vector into the bacteria followed by expression of the library for 4.5 hours to yield a "naïve" library), and libraries chemically modified by aldehyde ligation and cysteine macrocyclization {M} characterized by paired-end deep sequencing, detected a significant drop in diversity in {L} → {N}, but only a minor compositional difference in {S} → {L} and {N} → {M}. Libraries expressed at the N-terminus of phage protein pIII censored positively charged amino acids Arg and Lys; libraries expressed between pIII domains N1 and N2 overcame Arg/Lys-censorship but introduced new bias towards Gly and Ser. Interrogation of biases arising from cPTM by aldehyde ligation and cysteine macrocyclization unveiled censorship of sequences with Ser/Phe. Analogous analysis can be used to explore library diversity in new display platforms and optimize cPTM of these libraries.

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Goat Anti-Human Endotheli GLP 1 ELISA Kit, Rat Gluc Anti 3 DG imidazolone Mon Cultrex In Vitro Angiogen BYL-719 Mechanisms: PI3K- Human Small Intestine Mic Human Large Intestine Mic Human Internal Mammary Ar GFP Expressing Human Inte Endometrium cancer and no Endocrine cancer tissue a Endocrine system benign,

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Peroxisome Proliferator-Activated Receptor γ and Retinoic Acid Receptor Synergistically Up-Regulate the Tumor Suppressor PTEN in Human Promyeloid Leukemia Cells.

Peroxisome proliferator-activated receptor γ (PPARγ) and retinoic acid receptors (RARs) have been a focus in chemotherapy for human cancers. The tumor suppressor PTEN plays a pivotal role in the growth of human cancer cells. We investigated whether costimulation of PPARγ and RAR could synergistically up-regulate PTEN in human leukemia cells and consequently potentiate the inhibition of growth and cell cycle progression of these cells. We found that overexpression of PTEN with the adenoviral vector Ad/PTEN caused growth arrest at the G1 phase of the cell cycle of HL-60 cells. HL-60 cells treated with either a PPARγ ligand (ciglitazone) or a RAR ligand(all-trans retinoic acid [ATRA]) up-regulated PTEN in HL-60 cells. The 2 compounds in combination showed synergistic effects on PTEN expression at the protein and messenger RNA levels. Moreover, the combination of ciglitazone and ATRA synergistically reduced cell growth rates and cell cycle arrest at the G1 phase. Our results suggest that, PPARγ and RAR play an important role in controlling the growth of leukemia cells via the up-regulation of PTEN.

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anti Transferrin receptor Human Tumor Necrosis Fact Interferon-a Receptor Typ Mouse Anti-Human Interleu Rabbit Anti-Human Androge Rabbit Anti-Human Androge RANK Ligand Soluble, Huma interleukin 17 receptor C interferon-alpha receptor Human integrin aVb3, affi Human soluble interleukin Rabbit Anti-Human Androge

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Visceral Hypersensitivity Induced by Optogenetic Activation of the Amygdala in Conscious Rats.

In vivo optogenetics identifies brain circuits controlling behaviors in conscious animals by using light to alter neuronal function and offers a novel tool to study the brain-gut axis. Using adenoviral-mediated expression, we aimed to investigate whether photoactivation with channelrhodopsin (ChR2) or photoinhibition with halorhodopsin (HR3.0) of fibers originating from the central nucleus of the amygdala (CeA) at the bed nucleus of the stria terminalis (BNST) had any effect on colonic sensitivity. We also investigated whether that there was any deleterious effect of the adenovirus on the neuronal population or the neuronal phenotype within the CeA-BNST circuitry activated during the optogenetic stimulation. In male rats, the CeA was infected with vectors expressing ChR2 or HR3.0 and fiber optic cannulae were implanted on the BNST. After 8-10 weeks, the response to graded, isobaric colonic distension was measured with and without laser stimulation of CeA fibers at the BNST. Immunohistochemistry and histology were used to evaluate vector expression, neuronal integrity, and neurochemical phenotype. Photoactivation of CeA fibers at the BNST with ChR2 induced colonic hypersensitivity, whereas photoinhibition of CeA fibers at the BNST with HR3.0 had no effect on colonic sensitivity. Control groups treated with virus expressing reporter proteins showed no abnormalities in neuronal morphology, neuronal number, or neurochemical phenotype following laser stimulation. Our experimental findings reveal that optogenetic activation of discrete brain nuclei can be used to advance our understanding of complex visceral nociceptive circuitry in a freely moving rat model.

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Anti-AICDA(Activation-ind Anti AICDA(Activation ind Anti AGO2 Human, Monoclon Anti AGO2 Mouse, Monoclon Anti AGO2 Human, Monoclon Anti AGO2 Mouse, Monoclon Human Epstein-Barr Virus Jurkat Cell Extract (Indu Jurkat Cell Extract (Indu Jurkat Cell Extract (Indu Jurkat Cell Extract (Indu Stat3 Activation Inhibito

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Doxycycline modulates VEGF-A expression: Failure of doxycycline-inducible lentivirus shRNA vector to knockdown VEGF-A expression in transgenic mice.

Vascular endothelial growth factor-A (VEGF-A) is the master regulator of angiogenesis, vascular permeability and growth. However, its role in mature blood vessels is still not well understood. To better understand the role of VEGF-A in the adult vasculature, we generated a VEGF-A knockdown mouse model carrying a doxycycline (dox)-regulatable short hairpin RNA (shRNA) transgene, which silences VEGF-A. The aim was to find the critical level of VEGF-A reduction for vascular well-being in vivo. In vitro, the dox-inducible lentiviral shRNA vector decreased VEGF-A expression efficiently and dose-dependently in mouse endothelial cells and cardiomyocytes. In the generated transgenic mice plasma VEGF-A levels decreased shortly after the dox treatment but returned back to normal after two weeks. VEGF-A expression decreased shortly after the dox treatment only in some tissues. Surprisingly, increasing the dox exposure time and dose led to elevated VEGF-A expression in some tissues of both wildtype and knockdown mice, suggesting that dox itself has an effect on VEGF-A expression. When the effect of dox on VEGF-A levels was further tested in naïve/non-transduced cells, the dox administration led to a decreased VEGF-A expression in endothelial cells but to an increased expression in cardiomyocytes. In conclusion, the VEGF-A knockdown was achieved in a dox-regulatable fashion with a VEGF-A shRNA vector in vitro, but not in the knockdown mouse model in vivo. Dox itself was found to regulate VEGF-A expression explaining the unexpected results in mice. The effect of dox on VEGF-A levels might at least partly explain its previously reported beneficial effects on myocardial and brain ischemia. Also, this effect on VEGF-A should be taken into account in all studies using dox-regulated vectors.

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pCAMBIA0105.1R Vector, (G DNA (cytosine 5) methyltr pCMVLuxA Mammalian LuxA E pCdgCAT Mammalian CAT Exp pCAMBIA2300 Vector (No Re AKT1 (dn) Inducible Expression Media Products Expression Media Products Expression Media Products Anti Human, mab VEGF A ( Anti Human, mab VEGF A ( Anti Human, mab VEGF A (

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TCR modifications that enhance chain pairing in gene-modified T cells can augment cross-reactivity and alleviate CD8 dependence.

T cell receptor (TCR) gene-modified T cells are a promising immunotherapy but require refinement to improve clinical responses and limit off-target toxicities. A variety of TCR and gene-delivery vector modifications have been developed to enhance introduced TCR expression and limit introduced/endogenous TCR chain mispairing, improving target antigen recognition and minimizing mispairing-induced cross-reactivity. Using our well-characterized HCV1406 TCR, we previously compared the impact of various chain pairing enhancing modifications on TCR expression and cognate antigen recognition. HCV1406 TCR is also natively cross-reactive against naturally occurring altered peptide ligands (APLs), which was shown to be dependent on high TCR surface density. In this report, we observed in a Jurkat model that absent TCR chain pairing competition alleviated CD8-dependent APL recognition and induced novel cross-reactivity of HCV1406 TCR. We then compared chain pairing enhancing modifications' effects on TCR cross-reactivity in Jurkat and T cells, showing C-terminal leucine zippers and constant region murinization alleviated CD8 dependence and induced novel APL recognition. While modifications enhancing TCR chain pairing intend to avoid cross-reactivity by limiting mispairing with the endogenous TCR, these data suggest they may also enhance natural cross-reactivity and reduce dependence on CD8. These observations have significant implications on the design/implementation of TCR gene-modified T cells.

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Interferon-a Receptor Typ Rat TGF-beta-inducible ea Rat TGF-beta-inducible ea Glucagon ELISA KIT, Rat G Leptin ELISA Kit, Rat Lep Top five cancer tissue ar Multiple organ cancer tis Lung cancer tissue array, Lung cancer tissue array Colon cancer and normal t Colon cancer and normal t Colon cancer, metastasize

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AAV-9 mediated phosphatase-1 inhibitor-1 overexpression improves cardiac contractility in unchallenged mice but is deleterious in pressure-overload.

The downregulation of β-adrenergic receptors (β-AR) and decreased cAMP-dependent protein kinase activity in failing hearts results in decreased phosphorylation and inactivation of phosphatase-inhibitor-1 (I-1), a distal amplifier element of β-adrenergic signaling, leading to increased protein phosphatase 1 activity and dephosphorylation of key phosphoproteins, including phospholamban. Downregulated and hypophosphorylated I-1 likely contributes to β-AR desensitization; therefore its modulation is a promising approach in heart failure treatment. Aim of our study was to assess the effects of adeno-associated virus serotype 9 (AAV9) - mediated cardiac-specific expression of constitutively active inhibitor-1 (I-1c) and to investigate whether I-1c is able to attenuate the development of heart failure in mice subjected to transverse aortic constriction (TAC). 6-8 week-old C57BL/6N wild-type mice were subjected to banding of the transverse aorta (TAC). Two days later 2.8 × 1012 AAV-9 vector particles harbouring I-1c cDNA under transcriptional control of a human troponin T-promoter (AAV9/I-1c) were intravenously injected into the tail vein of these mice (n=12). AAV9 containing a Renilla luciferase reporter (AAV9/hRluc) was used as a control vector (n=12). Echocardiographic analyses were performed weekly to evaluate cardiac morphology and function. 4 weeks after TAC pressure- volume measurements were performed and animals were sacrificed for histological and molecular analyses. Both groups exhibited progressive contractile dysfunction and myocardial remodeling. Surprisingly, echocardiographic assessment and histological analyses showed significantly increased left ventricular hypertrophy in AAV9/I-1c treated mice compared to AAV9/hRluc treated controls as well as reduced contractility. Pressure-volume loops revealed significantly impaired contractility after AAV9/I-1c treatment. At the molecular level, hearts of AAV9/I-1c treated TAC mice showed a hyperphosphorylation of the SR Ca2+-ATPase inhibitor phospholamban. In contrast, expression of AAV9/I-1c in unchallenged animals resulted in selective enhancement of phospholamban phosphorylation and augmented cardiac contractility. Our data suggest that AAV9-mediated cardiac-specific overexpression of I-1c, previously associated with enhanced calcium cycling, improves cardiac contractile function in unchallenged animals but failed to protect against cardiac remodeling induced by hemodynamic stress questioning the use of I-1c as a potential strategy to treat heart failure in conditions with increased afterload.Gene Therapy accepted article preview online, 19 January 2018. doi:10.1038/gt.2017.97.

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OSI-906 Mechanisms: IGF-1 Rabbit Anti-G protein alp Rabbit Anti-G protein alp Rabbit Anti-G protein alp Rabbit Anti-G protein alp Rabbit Anti-G protein alp Rabbit Anti-G protein alp Rabbit Anti-G protein alp Rabbit Anti-G protein alp Rabbit Anti-G protein alp Rabbit Anti-G protein alp Rabbit Anti-G protein alp

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Safety and Efficacy of AAV Retrograde Pancreatic Ductal Gene Delivery in Normal and Pancreatic Cancer Mice.

Recombinant adeno-associated virus (rAAV)-mediated gene delivery shows promise to transduce the pancreas, but safety/efficacy in a neoplastic context is not well established. To identify an ideal AAV serotype, route, and vector dose and assess safety, we have investigated the use of three AAV serotypes (6, 8, and 9) expressing GFP in a self-complementary (sc) AAV vector under an EF1α promoter (scAAV.GFP) following systemic or retrograde pancreatic intraductal delivery. Systemic delivery of scAAV9.GFP transduced the pancreas with high efficiency, but gene expression did not exceed >45% with the highest dose, 5 × 1012 viral genomes (vg). Intraductal delivery of 1 × 1011 vg scAAV6.GFP transduced acini, ductal cells, and islet cells with >50%, ∼48%, and >80% efficiency, respectively, and >80% pancreatic transduction was achieved with 5 × 1011 vg. In a KrasG12D-driven pancreatic cancer mouse model, intraductal delivery of scAAV6.GFP targeted acini, epithelial, and stromal cells and exhibited persistent gene expression 5 months post-delivery. In normal mice, intraductal delivery induced a transient increase in serum amylase/lipase that resolved within a day of infusion with no sustained pancreatic inflammation or fibrosis. Similarly, in PDAC mice, intraductal delivery did not increase pancreatic intraepithelial neoplasia progression/fibrosis. Our study demonstrates that scAAV6 targets the pancreas/neoplasm efficiently and safely via retrograde pancreatic intraductal delivery.

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High density pancreatic c Multiple pancreatic cance Pancreatic cancer and nor Pancreatic cancer tissue Pancreatic cancer and nor Pancreatic cancer tissue Pancreatic cancer test ti Pancreatic cancer test ti Pancreatic cancer test ti High density (188 cases 2 High density (188 cases 2 Multiple pancreatic cance

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The potential mechanism of extracellular high mobility group box-1 protein mediated p53 expression in immune dysfunction of T lymphocytes.

In the present study, we examined the activity of p53 protein in Jurkat cells treated with high mobility group box-1 protein (HMGB1), thereafter we investigated the mechanism of extracellular HMGB1 mediated p53 expression in immune dysfunction of T lymphocytes. mRNA expression of p53, mdm2, and p21 was determined by Real-time reverse transcription-polymerase chain reaction(RT-PCR). The apoptotic rate of Jurkat cells was analyzed by flow cytometry. Expressions of bcl-2, bax, caspase-3, phosphorylated (p) extracellular signal-regulated kinase (ERK)1/2, ERK1/2, p-p38 mitogen-activated protein kinase (MAPK), p38 MAPK, and p-c-jun amino-terminal kinase (JNK)1/2 and JNK1/2 were simultaneously determined by Western blotting. After treatment with HMGB1 (100 ng/ml or 1000 ng/ml), the proliferative activity of Jurkat cells was significantly decreased, and a low and medium concentration of HMGB1 induced an up-regulation of p53 mRNA, p-p53 and p53 protein expression. Meanwhile, levels of mdm2 and p21 were elevated by incubated with HMGB1 (100 ng/ml) for 24 or 48 hours. Moreover, the proliferation of Jurkat cells in response to HMGB1 (100 ng/ml) in the vector group was significantly depressed. The bax and caspase-3 levels in p53 shRNA-expressed cells treated with HMGB1 (100 ng/ml) was markedly decreased, whereas expression of bcl-2 was obviously enhanced. Among ERK1/2, p38 MAPK and JNK1/2 signaling, only p38 MAPK pathway could be significantly activated by treatment with HMGB1, and the specific inhibitor of p38 MAPK was used, p53 and p-p53 expression induced by HMGB1 were significantly down-regulated. Taken together, our data strongly indicated that HMGB1 might enhance p53 expression, which was associated with both the proliferative activity as well as apoptosis of T cells.

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Signal transduction antib Chromatin Transcription P p53 Signaling Phospho-Spe TGF-Beta Signaling Phosph Human High Mobility Group HMG2 (High mobility group Recombinant Sheep Interfe Native Influenza HA (A Ta Native Influenza HA (A Ta Recombinant Human PKC the Recombinant Human PKC the Native Influenza HA (A To

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