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Synthetic transcriptional factor

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https://www.readbyqxmd.com/read/28720517/transient-receptor-potential-trpm3-channels-pharmacology-signaling-and-biological-functions
#1
REVIEW
Gerald Thiel, Sandra Rubil, Andrea Lesch, Lisbeth A Guethlein, Oliver G Rössler
The transient receptor potential melastatin-3 (TRPM3) channel belongs to the family of transient receptor potential (TRP) cation channels that are expressed in a variety of tissues and cell types, including dorsal root ganglia, cardiomyocytes and pancreatic beta-cells. Although its natural ligands are currently unknown, TRPM3 channels can be activated by the neurosteroid pregnenolone sulfate, the synthetic ligand CIM0216, and by noxious heat. TRPM3 channels are regulated by phosphoinositides, and perhaps by calmodulin...
July 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28720427/the-challenges-and-promise-of-targeting-the-liver-x-receptors-for-treatment-of-inflammatory-disease
#2
REVIEW
Michael B Fessler
The Liver X Receptors (LXRs) are oxysterol-activated transcription factors that upregulate a suite of genes that together promote coordinated mobilization of excess cholesterol from cells and from the body. The LXRs, like other nuclear receptors, are anti-inflammatory, inhibiting signal-dependent induction of pro-inflammatory genes by nuclear factor-κB, activating protein-1, and other transcription factors. Synthetic LXR agonists have been shown to ameliorate atherosclerosis and a wide range of inflammatory disorders in preclinical animal models...
July 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28717003/surface-toll-like-receptor-3-expression-in-metastatic-intestinal-epithelial-cells-induces-inflammatory-cytokine-production-and-promotes-invasiveness
#3
Marit Bugge, Bjarte Bergstrom, Oda Kamilla Eide, Helene Solli, Ingrid F Kjønstad, Jørgen Stenvik, Terje Espevik, Nadra J Nilsen
Toll-like receptors (TLR)s are innate immune receptors for sensing microbial molecules and damage-associated molecular patterns released from host cells. Double-stranded RNA and the synthetic analog polyinosinic:polycytidylic acid (Poly(I:C)) bind and activate TLR3. This stimulation leads to recruitment of the adaptor molecule TRIF and activation of the transcription factors nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF-3), classically inducing IFNβ production. Here, we report that unlike non-metastatic intestinal epithelial cells (IECs), metastatic IECs express TLR3, and that TLR3 promotes invasiveness of these cells...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28706437/comparison-of-two-neurotrophic-serpins-reveals-a-small-fragment-with-cell-survival-activity
#4
Paige N Winokur, Preeti Subramanian, Jeanee L Bullock, Veronique Arocas, S Patricia Becerra
PURPOSE: Protease nexin-1 (PN-1), a serpin encoded by the SERPINE2 gene, has serine protease inhibitory activity and neurotrophic properties in the brain. PN-1 inhibits retinal angiogenesis; however, PN-1's neurotrophic capacities in the retina have not yet been evaluated. Pigment epithelium-derived factor (PEDF) is a serpin that exhibits neurotrophic and antiangiogenic activities but lacks protease inhibitory properties. The aim of this study is to compare PN-1 and PEDF. METHODS: Sequence comparisons were performed using computer bioinformatics programs...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28706417/indole-phytoalexin-derivatives-induce-mitochondrial-mediated-apoptosis-in-human-colorectal-carcinoma-cells
#5
Viera Tischlerova, Martin Kello, Mariana Budovska, Jan Mojzis
AIM: To investigate the mechanism of the antiproliferative effect of synthetic indole phytoalexin derivatives on human colorectal cancer cell lines. METHODS: Changes in cell proliferation and the cytotoxic effect of the tested compounds on human colorectal cancer cell lines and human fibroblasts were evaluated using MTS and BrdU assay, allowing us to choose the most potent substance. Cell cycle alterations were analyzed using flow cytometric analysis. The apoptosis-inducing effect of compound K-453 on the HCT116 cell line was examined with annexin V/PI double staining using flow cytometry, as well as acridine orange/propidium iodide (AO/PI) staining...
June 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28705346/efficient-generation-of-dopamine-neurons-by-synthetic-transcription-factor-mrnas
#6
Sang-Mi Kim, Mi-Sun Lim, Eun-Hye Lee, Sung Jun Jung, Hee Yong Chung, Chun-Hyung Kim, Chang-Hwan Park
Generation of functional dopamine (DA) neurons is an essential step for the development of effective cell therapy for Parkinson's disease (PD). The generation of DA neurons can be accomplished by overexpression of DA-inducible genes using virus- or DNA-based gene delivery methods. However, these gene delivery methods often cause chromosomal anomalies. In contrast, mRNA-based gene delivery avoids this problem and therefore is considered safe to use in the development of cell-based therapy. Thus, we used mRNA-based gene delivery method to generate safe DA neurons...
July 11, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28702937/genetic-engineering-strategies-for-biotic-and-abiotic-stress-tolerance-and-quality-enhancement-in-horticultural-crops-a-comprehensive-review
#7
REVIEW
Nehanjali Parmar, Kunwar Harendra Singh, Deepika Sharma, Lal Singh, Pankaj Kumar, J Nanjundan, Yasin Jeshima Khan, Devendra Kumar Chauhan, Ajay Kumar Thakur
Genetic engineering technique offers myriads of applications in improvement of horticultural crops for biotic and abiotic stress tolerance, and produce quality enhancement. During last two decades, a large number of transgenic horticultural crops has been developed and more are underway. A number of genes including natural and synthetic Cry genes, protease inhibitors, trypsin inhibitors and cystatin genes have been used to incorporate insect and nematode resistance. For providing protection against fungal and bacterial diseases, various genes like chitinase, glucanase, osmotin, defensin and pathogenesis-related genes are being transferred to many horticultural crops world over...
August 2017: 3 Biotech
https://www.readbyqxmd.com/read/28701475/hif-activation-causes-synthetic-lethality-between-the-vhl-tumor-suppressor-and-the-ezh1-histone-methyltransferase
#8
Abhishek A Chakraborty, Eijiro Nakamura, Jun Qi, Amanda Creech, Jacob D Jaffe, Joshiawa Paulk, Jesse S Novak, Kshithija Nagulapalli, Samuel K McBrayer, Glenn S Cowley, Javier Pineda, Jiaxi Song, Yaoyu E Wang, Steven A Carr, David E Root, Sabina Signoretti, James E Bradner, William G Kaelin
Inactivation of the von Hippel-Lindau tumor suppressor protein (pVHL) is the signature lesion in the most common form of kidney cancer, clear cell renal cell carcinoma (ccRCC). pVHL loss causes the transcriptional activation of hypoxia-inducible factor (HIF) target genes, including many genes that encode histone lysine demethylases. Moreover, chromatin regulators are frequently mutated in this disease. We found that ccRCC displays increased H3K27 acetylation and a shift toward mono- or unmethylated H3K27 caused by an HIF-dependent increase in H3K27 demethylase activity...
July 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28701322/functional-and-neurochemical-characterization-of-angiotensin-type-1a-receptor-expressing-neurons-in-the-nucleus-of-the-solitary-tract-of-the-mouse
#9
David A Carter, Yan-Ting Choong, Angela A Connelly, Jaspreet K Bassi, Nicole O Hunter, Nattaya Thongsepee, Ida J Llewellyn-Smith, Angelina Y Fong, Stuart James McDougall, Andrew Mark Allen
Angiotensin II acts via two main receptors within the CNS, with the type 1A receptor (AT1AR) most widely expressed in adult neurons. Activation of the AT1R in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the AT1R occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the AT1AR-expressing NTS neurons are not known...
July 12, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28686585/constructing-cellular-niche-properties-by-localized-presentation-of-wnt-proteins-on-synthetic-surfaces
#10
Molly Lowndes, Sergi Junyent, Shukry J Habib
Wnt signaling is crucial during embryonic development and for the maintenance of adult tissues. Depending on the tissue type, the Wnt pathway can promote stem cell self-renewal and/or direct lineage commitment. Wnt proteins are subject to lipid modification, often restricting them to act in a localized manner on responsive cells. Most methods for inducing Wnt signaling in stem cell cultures do not control the spatial presentation of the protein. To recreate the local presentation of Wnt proteins often seen in vivo, we previously developed a method to immobilize the protein onto synthetic surfaces...
July 2017: Nature Protocols
https://www.readbyqxmd.com/read/28650102/endocrine-influence-on-neuroinflammation-the-use-of-reporter-systems
#11
REVIEW
Nicoletta Rizzi, Alessandro Villa, Valeria Benedusi, Electra Brunialti, Nicoletta Cesari, Paolo Ciana, Adriana Maggi
Most of the ageing-associated pathologies are coupled with a strong inflammatory component that accelerates the progress of the physio-pathological functional decline related to ageing. The currently available pharmacological tools for the control of neuroinflammation present several side effects which restrict their application, particularly in chronic disorders. The discovery of the potential anti-inflammatory action exerted by endogenous estrogens and that activation of ERα results in a significant decrease of inflammation at the cellular level and in models of inflammatory diseases, prompted us to embark in a series of studies aimed at the generation of reporter systems allowing to i...
June 26, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28650069/transcriptional-engineering-of-the-glyceraldehyde-3-phosphate-dehydrogenase-promoter-for-improved-heterologous-protein-production-in-pichia-pastoris
#12
Özge Ata, Roland Prielhofer, Brigitte Gasser, Diethard Mattanovich, Pınar Çalık
The constitutive glyceraldehyde-3-phosphate dehydrogenase promoter (PGAP ), which is one of the benchmark promoters of Pichia pastoris, was analyzed in terms of putative transcription factor binding sites. We constructed a synthetic library with distinct regulatory properties through deletion and duplication of these putative transcription factor binding sites and selected transcription factor (TF) genes were overexpressed or deleted to understand their roles on heterologous protein production. Using enhanced green fluorescent protein, an expression strength in a range between 0...
June 26, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28649419/identification-of-transcription-factors-that-promote-the-differentiation-of-human-pluripotent-stem-cells-into-lacrimal-gland-epithelium-like-cells
#13
Masatoshi Hirayama, Shigeru B H Ko, Tetsuya Kawakita, Tomohiko Akiyama, Sravan K Goparaju, Atsumi Soma, Yuhki Nakatake, Miki Sakota, Nana Chikazawa-Nohtomi, Shigeto Shimmura, Kazuo Tsubota, Minoru S H Ko
Dry eye disease is the most prevalent pathological condition in aging eyes. One potential therapeutic strategy is the transplantation of lacrimal glands, generated in vitro from pluripotent stem cells such as human embryonic stem cells, into patients. One of the preceding requirements is a method to differentiate human embryonic stem cells into lacrimal gland epithelium cells. As the first step for this approach, this study aims to identify a set of transcription factors whose overexpression can promote the differentiation of human embryonic stem cells into lacrimal gland epithelium-like cells...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28637236/the-ribosome-assembly-gene-network-is-controlled-by-the-feedback-regulation-of-transcription-elongation
#14
Fernando Gómez-Herreros, Thanasis Margaritis, Olga Rodríguez-Galán, Vicent Pelechano, Victoria Begley, Gonzalo Millán-Zambrano, Macarena Morillo-Huesca, Mari Cruz Muñoz-Centeno, José E Pérez-Ortín, Jesús de la Cruz, Frank C P Holstege, Sebastián Chávez
Ribosome assembly requires the concerted expression of hundreds of genes, which are transcribed by all three nuclear RNA polymerases. Transcription elongation involves dynamic interactions between RNA polymerases and chromatin. We performed a synthetic lethal screening in Saccharomyces cerevisiae with a conditional allele of SPT6, which encodes one of the factors that facilitates this process. Some of these synthetic mutants corresponded to factors that facilitate pre-rRNA processing and ribosome biogenesis...
June 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28630007/rna-localization-making-its-way-to-the-center-stage
#15
REVIEW
Ashley Chin, Eric Lécuyer
Cells are highly organized entities that rely on intricate addressing mechanisms to sort their constituent molecules to precise subcellular locations. These processes are crucial for cells to maintain their proper organization and carry out specialized functions in the body, consequently genetic perturbations that clog up these addressing systems can contribute to disease aetiology. The trafficking of RNA molecules represents an important layer in the control of cellular organization, a process that is both highly prevalent and for which features of the regulatory machineries have been deeply conserved evolutionarily...
June 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28624538/analysis-of-mrna-deadenylation-by-multi-protein-complexes
#16
Michael W Webster, James A W Stowell, Terence T L Tang, Lori A Passmore
Poly(A) tails are found at the 3' end of almost every eukaryotic mRNA and are important for the stability of mRNAs and their translation into proteins. Thus, removal of the poly(A) tail, a process called deadenylation, is critical for regulation of gene expression. Most deadenylation enzymes are components of large multi-protein complexes. Here, we describe an in vitro deadenylation assay developed to study the exonucleolytic activities of the multi-protein Ccr4-Not and Pan2-Pan3 complexes. We discuss how this assay can be used with short synthetic RNAs, as well as longer RNA substrates generated using in vitro transcription...
June 13, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28624210/low-dose-gene-therapy-for-murine-pku-using-episomal-naked-dna-vectors-expressing-pah-from-its-endogenous-liver-promoter
#17
Hiu Man Grisch-Chan, Andrea Schlegel, Tanja Scherer, Gabriella Allegri, Raphael Heidelberger, Panagiota Tsikrika, Marco Schmeer, Martin Schleef, Cary O Harding, Johannes Häberle, Beat Thöny
Limited duration of transgene expression, insertional mutagenesis, and size limitations for transgene cassettes pose challenges and risk factors for many gene therapy vectors. Here, we report on physiological expression of liver phenylalanine hydroxylase (PAH) by delivery of naked DNA/minicircle (MC)-based vectors for correction of homozygous enu2 mice, a model of human phenylketonuria (PKU). Because MC vectors lack a defined size limit, we constructed a MC vector expressing a codon-optimized murine Pah cDNA that includes a truncated intron and is under the transcriptional control of a 3...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623587/generation-of-dtales-and-libraries-of-synthetic-tale-activated-promoters-for-engineering-of-gene-regulatory-networks-in-plants
#18
Tom Schreiber, Alain Tissier
Transcription factors with programmable DNA-binding specificity constitute valuable tools for the design of orthogonal gene regulatory networks for synthetic biology. Transcription activator-like effectors (TALEs), as natural transcription regulators, were used to design, build, and test libraries of synthetic TALE-activated promoters (STAPs) that show a broad range of expression levels in plants. In this chapter, we present protocols for the construction of artificial TALEs and corresponding STAPs.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28621681/overexpression-of-emt-inducing-transcription-factors-as-a-potential-poor-prognostic-factor-for-hepatocellular-carcinoma-in-asian-populations-a-meta-analysis
#19
Tao Wan, Tianwei Zhang, Xiaoying Si, Yanming Zhou
BACKGROUND AND OBJECTIVES: The clinical relevance of epithelial to mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) progression has been highlighted during the last decade. The zinc finger E-box binding homeobox (ZEB) family, the zinc-finger transcriptional repressor (SNAI) family, and the basic helix-loop-helix transcription factor (Twist) family, known as the prominent EMT-inducing transcription factors (EMT-TFs), played a crucial role in the process of EMT. Here, this meta-analysis aimed to evaluate the prognostic value of EMT-TFs high expression in patients with HCC after hepatectomy...
June 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28621262/a-peptide-antagonist-of-prep1-p160-interaction-improves-ceramide-induced-insulin-resistance-in-skeletal-muscle-cells
#20
Ilaria Cimmino, Virginia Lorenzo, Francesca Fiory, Nunzianna Doti, Serena Ricci, Serena Cabaro, Antonietta Liotti, Luigi Vitagliano, Michele Longo, Claudia Miele, Pietro Formisano, Francesco Beguinot, Menotti Ruvo, Francesco Oriente
Prep1 is a homeodomain transcription factor belonging to the TALE protein family. Its overexpression affects glucose metabolism in several tissues. In particular, in skeletal muscle tissue the interaction of Prep1 with its cofactor p160 impairs GLUT4 expression and glucose uptake.In this study, we show that ceramides (C2cer), a class of lipids antagonizing insulin signalling, increase the levels of Prep1 and p160 in a dose and time-dependent fashion in L6 cells and induce their association by 80%. We find that C2cer exposure inhibits insulin receptor, IRS1 and Akt phosphorylation and reduces insulin-stimulated glycogen content and glucose uptake by 1...
May 30, 2017: Oncotarget
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