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Artificial transcriptional factor

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https://www.readbyqxmd.com/read/28095489/transgenic-expression-of-the-anti-parasitic-factor-tep1-in-the-malaria-mosquito-anopheles-gambiae
#1
Gloria Volohonsky, Ann-Katrin Hopp, Mélanie Saenger, Julien Soichot, Heidi Scholze, Jens Boch, Stéphanie A Blandin, Eric Marois
Mosquitoes genetically engineered to be resistant to Plasmodium parasites represent a promising novel approach in the fight against malaria. The insect immune system itself is a source of anti-parasitic genes potentially exploitable for transgenic designs. The Anopheles gambiae thioester containing protein 1 (TEP1) is a potent anti-parasitic protein. TEP1 is secreted and circulates in the mosquito hemolymph, where its activated cleaved form binds and eliminates malaria parasites. Here we investigated whether TEP1 can be used to create malaria resistant mosquitoes...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28088729/new-insights-into-aox2-transcriptional-regulation-in-chlamydomonas-reinhardtii
#2
Mariya Ostroukhova, Zhanneta Zalutskaya, Elena Ermilova
A feature of the mitochondrial electron transport chain in plants, some protists and many fungi is the presence of two terminal oxidases, the energy-conserving cytochrome oxidase and another termed alternative oxidase (AOX). AOX branches from the main respiratory chain, directly coupling the oxidation of ubiquinol with reduction of oxygen to water. The AOX genes can be divided into two discrete subfamilies, AOX1 and AOX2. Although AOX has been proposed to play essential roles in stress tolerance of organisms, the role of subfamily AOX2 is largely unknown...
December 13, 2016: European Journal of Protistology
https://www.readbyqxmd.com/read/28065574/a-blueprint-for-a-synthetic-genetic-feedback-controller-to-reprogram-cell-fate
#3
Domitilla Del Vecchio, Hussein Abdallah, Yili Qian, James J Collins
To artificially reprogram cell fate, experimentalists manipulate the gene regulatory networks (GRNs) that maintain a cell's phenotype. In practice, reprogramming is often performed by constant overexpression of specific transcription factors (TFs). This process can be unreliable and inefficient. Here, we address this problem by introducing a new approach to reprogramming based on mathematical analysis. We demonstrate that reprogramming GRNs using constant overexpression may not succeed in general. Instead, we propose an alternative reprogramming strategy: a synthetic genetic feedback controller that dynamically steers the concentration of a GRN's key TFs to any desired value...
January 3, 2017: Cell Systems
https://www.readbyqxmd.com/read/28054069/challenge-and-perspective-the-relevance-of-ultraviolet-uv-radiation-and-the-vitamin-d-endocrine-system-vdes-for-psoriasis-and-other-inflammatory-skin-diseases
#4
Jörg Reichrath, Roman Saternus, Thomas Vogt
During evolution, the ability of many organisms to synthesize vitamin D photochemically represented, and still represents, a major driving factor for the development of life on earth. In humans because not more than 10-20% of the requirement of vitamin D can be satisfied by the diet (under most living conditions in the US and Europe), the remaining 80-90% need to be photochemically synthesized in the skin through the action of solar or artificial ultraviolet-B (UV-B) radiation. The skin is a key organ of the human body's vitamin D endocrine system (VDES), representing both the site of vitamin D synthesis and a target tissue for biologically active vitamin D metabolites...
January 5, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/28052257/a-fully-synthetic-transcriptional-platform-for-a-multicellular-eukaryote
#5
Justin Crocker, Albert Tsai, David L Stern
Regions of genomic DNA called enhancers encode binding sites for transcription factor proteins. Binding of activators and repressors increase and reduce transcription, respectively, but it is not understood how combinations of activators and repressors generate precise patterns of transcription during development. Here, we explore this problem using a fully synthetic transcriptional platform in Drosophila consisting of engineered transcription factor gradients and artificial enhancers. We found that binding sites for a transcription factor that makes DNA accessible are required together with binding sites for transcriptional activators to produce a functional enhancer...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/27987116/roles-of-pkr-in-differentiation-and-apoptosis-of-bone-related-cells
#6
REVIEW
Tatsuji Haneji
Double-stranded RNA-dependent protein kinase (PKR) is a serine/threonine protein kinase which is activated by double-stranded RNAs and related to several signal transduction pathways. To examine the effects of PKR on bone metabolism, we established PKR-K/R mutant cells in which amino acid lysine at 296 is substituted with arginine. PKR regulated apoptosis in osteoblastic cells via nuclear factor kappa-B (NF-κB) cascade. MC3T3-E1 cells cultured with osteoblast differentiation medium differentiated into osteoblasts, while the mutant cells did not differentiate into osteoblasts...
December 16, 2016: Anatomical Science International
https://www.readbyqxmd.com/read/27982027/engineering-orthogonal-dual-transcription-factors-for-multi-input-synthetic-promoters
#7
Andreas K Brödel, Alfonso Jaramillo, Mark Isalan
Synthetic biology has seen an explosive growth in the capability of engineering artificial gene circuits from transcription factors (TFs), particularly in bacteria. However, most artificial networks still employ the same core set of TFs (for example LacI, TetR and cI). The TFs mostly function via repression and it is difficult to integrate multiple inputs in promoter logic. Here we present to our knowledge the first set of dual activator-repressor switches for orthogonal logic gates, based on bacteriophage λ cI variants and multi-input promoter architectures...
December 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27940549/repression-of-telomerase-gene-promoter-requires-human-specific-genomic-context-and-is-mediated-by-multiple-hdac1-containing-corepressor-complexes
#8
De Cheng, Yuanjun Zhao, Shuwen Wang, Fan Zhang, Mariano Russo, Steven B McMahon, Jiyue Zhu
The human telomerase reverse transcriptase (hTERT) gene is repressed in most somatic cells, whereas the expression of the mouse mTert gene is widely detected. To understand the mechanisms of this human-specific repression, we constructed bacterial artificial chromosome (BAC) reporters using human and mouse genomic DNAs encompassing the TERT genes and neighboring loci. Upon chromosomal integration, the hTERT, but not the mTert, reporter was stringently repressed in telomerase-negative human cells in a histone deacetylase (HDAC)-dependent manner, replicating the expression of their respective endogenous genes...
December 9, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27930301/reprogramming-cell-fate-with-a-genome-scale-library-of-artificial-transcription-factors
#9
Asuka Eguchi, Matthew J Wleklinski, Mackenzie C Spurgat, Evan A Heiderscheit, Anna S Kropornicka, Catherine K Vu, Devesh Bhimsaria, Scott A Swanson, Ron Stewart, Parameswaran Ramanathan, Timothy J Kamp, Igor Slukvin, James A Thomson, James R Dutton, Aseem Z Ansari
Artificial transcription factors (ATFs) are precision-tailored molecules designed to bind DNA and regulate transcription in a preprogrammed manner. Libraries of ATFs enable the high-throughput screening of gene networks that trigger cell fate decisions or phenotypic changes. We developed a genome-scale library of ATFs that display an engineered interaction domain (ID) to enable cooperative assembly and synergistic gene expression at targeted sites. We used this ATF library to screen for key regulators of the pluripotency network and discovered three combinations of ATFs capable of inducing pluripotency without exogenous expression of Oct4 (POU domain, class 5, TF 1)...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27908936/genome-editing-technologies-principles-and-applications
#10
REVIEW
Thomas Gaj, Shannon J Sirk, Sai-Lan Shui, Jia Liu
Targeted nucleases have provided researchers with the ability to manipulate virtually any genomic sequence, enabling the facile creation of isogenic cell lines and animal models for the study of human disease, and promoting exciting new possibilities for human gene therapy. Here we review three foundational technologies-clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), and zinc-finger nucleases (ZFNs)...
December 1, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27905661/artificial-cartilage-bio-matrix-formed-of-hyaluronic-acid-and-mg2-polyphosphate
#11
X Wang, M Ackermann, E Tolba, M Neufurth, F Wurm, Q Feng, S Wang, H C Schröder, W E Müller
Here we show that inorganic polyphosphate (polyP), a polyanionic metabolic regulator consisting of multiple phosphate residues linked by energy-rich phosphoanhydride bonds, is present in the synovial fluid. In a biomimetic approach, to enhance cartilage synthesis and regeneration, we prepared amorphous polyP microparticles with Mg2+ as counterions. The particles were characterised by X-ray diffraction (XRD), energy-dispersive X-ray (EDX) and Fourier transformed infrared spectroscopic (FTIR) analyses. Similar particles were obtained after addition of Mg2+ ions to a solution containing hyaluronic acid, as a major component of the synovial fluid, and soluble Na-polyP...
November 29, 2016: European Cells & Materials
https://www.readbyqxmd.com/read/27899062/scleraxis-is-essential-for-tendon-differentiation-by-equine-embryonic-stem-cells-and-in-equine-fetal-tenocytes
#12
Emma Bavin, Francesca Atkinson, Tom Barsby, Debbie Guest
The transcription factor scleraxis is required for tendon development and is upregulated during embryonic stem cell (ESC) differentiation into tenocytes. However, its role beyond early embryonic development is not defined. We utilised a short hairpin RNA to knockdown scleraxis expression in ESCs, adult and fetal tenocytes. No effect on growth or morphology was observed in 2D cultures. However, scleraxis knockdown in fetal tenocytes significantly reduced COL1A1, COMP and SOX9 gene expression. Scleraxis knockdown in adult tenocytes had no effect on the expression of these genes...
November 29, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27882145/microrna-22-attenuates-myocardial-ischemia-reperfusion-injury-via-an-anti-inflammatory-mechanism-in-rats
#13
Jian Yang, Zhixing Fan, Jun Yang, Jiawang Ding, Chaojun Yang, Lihua Chen
Previous studies have reported that microRNA-22 (miR-22) may be implicated in ischemia-reperfusion (I/R)-induced myocardial injury. Our previously published data also demonstrated that miR-22 may protect against myocardial I/R injury via anti-apoptosis in rats by targeting cAMP response element-binding protein binding protein (CBP). However, the specific function of miR-22 in myocardial I/R injury is far from fully elucidated. The present study was designed to investigate another cardioprotective signaling mechanism of miR-22 in myocardial I/R injury...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27869129/reprogramming-mouse-fibroblasts-into-engraftable-myeloerythroid-and-lymphoid-progenitors
#14
Hui Cheng, Heather Yin-Kuan Ang, Chadi A El Farran, Pin Li, Hai Tong Fang, Tong Ming Liu, Say Li Kong, Michael Lingzi Chin, Wei Yin Ling, Edwin Kok Hao Lim, Hu Li, Tara Huber, Kyle M Loh, Yuin-Han Loh, Bing Lim
Recent efforts have attempted to convert non-blood cells into hematopoietic stem cells (HSCs) with the goal of generating blood lineages de novo. Here we show that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally distant lineage (fibroblasts) into 'induced hematopoietic progenitors' (iHPs). Functionally, iHPs generate acetylcholinesterase(+) megakaryocytes and phagocytic myeloid cells in vitro and can also engraft immunodeficient mice, generating myeloerythoid and B-lymphoid cells for up to 4 months in vivo...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27860204/angelman-syndrome-current-and-emerging-therapies-in-2016
#15
REVIEW
Wen-Hann Tan, Lynne M Bird
Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by a loss of the maternally-inherited UBE3A; the paternal UBE3A is silenced in neurons by a mechanism involving an antisense transcript (UBE3A-AS) at the unmethylated paternal locus. We reviewed all published information on the clinical trials that have been completed as well as the publicly available information on ongoing trials of therapies in AS. To date, all clinical trials that strove to improve neurodevelopment in AS have been unsuccessful...
December 2016: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/27842598/exploratory-analysis-of-real-personal-emergency-response-call-conversations-considerations-for-personal-emergency-response-spoken-dialogue-systems
#16
Victoria Young, Elizabeth Rochon, Alex Mihailidis
BACKGROUND: The purpose of this study was to derive data from real, recorded, personal emergency response call conversations to help improve the artificial intelligence and decision making capability of a spoken dialogue system in a smart personal emergency response system. The main study objectives were to: develop a model of personal emergency response; determine categories for the model's features; identify and calculate measures from call conversations (verbal ability, conversational structure, timing); and examine conversational patterns and relationships between measures and model features applicable for improving the system's ability to automatically identify call model categories and predict a target response...
November 14, 2016: Journal of Neuroengineering and Rehabilitation
https://www.readbyqxmd.com/read/27822460/the-transcriptome-of-exophiala-dermatitidis-during-ex-vivo-skin-model-infection
#17
Caroline Poyntner, Barbara Blasi, Elsa Arcalis, Ursula Mirastschijski, Katja Sterflinger, Hakim Tafer
The black yeast Exophiala dermatitidis is a widespread polyextremophile and human pathogen, that is found in extreme natural habitats and man-made environments such as dishwashers. It can cause various diseases ranging from phaeohyphomycosis and systemic infections, with fatality rates reaching 40%. While the number of cases in immunocompromised patients are increasing, knowledge of the infections, virulence factors and host response is still scarce. In this study, for the first time, an artificial infection of an ex-vivo skin model with Exophiala dermatitidis was monitored microscopically and transcriptomically...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27805805/mild-hyperthermia-induced-by-gold-nanorod-mediated-plasmonic-photothermal-therapy-enhances-transduction-and-replication-of-oncolytic-adenoviral-gene-delivery
#18
Bo-Kyeong Jung, Yeon Kyung Lee, JinWoo Hong, Hamidreza Ghandehari, Chae-Ok Yun
Oncolytic adenovirus (Ad) is a promising candidate for cancer gene therapy. However, as a monotherapy, it has shown insufficient therapeutic efficacy in clinical trials. In this work, we demonstrate that gold nanorod (GNR)-mediated mild hyperthermia enhances the cellular uptake and consequent gene expression of oncolytic Ad to head and neck tumor cells. We examined the combination of oncolytic Ad expressing vascular endothelial growth factor promoter-targeted artificial transcriptional repressor zinc-finger protein and GNR-mediated mild hyperthermia to improve antitumor effects...
November 22, 2016: ACS Nano
https://www.readbyqxmd.com/read/27770033/chromatin-association-of-gcn4-is-limited-by-post-translational-modifications-triggered-by-its-dna-binding-in-saccharomyces-cerevisiae
#19
Akhi Akhter, Emanuel Rosonina
The Saccharomyces cerevisiae transcription factor Gcn4 is expressed during amino acid starvation, and its abundance is controlled by ubiquitin-mediated proteolysis. Cdk8, a kinase component of the RNA polymerase II Mediator complex, phosphorylates Gcn4, which triggers its ubiquitination/proteolysis, and is thought to link Gcn4 degradation with transcription of target genes. In addition to phosphorylation and ubiquitination, we previously showed that Gcn4 becomes sumoylated in a DNA-binding dependent manner, while a nonsumoylatable form of Gcn4 showed increased chromatin occupancy, but only if Cdk8 was present...
December 2016: Genetics
https://www.readbyqxmd.com/read/27741243/amplification-of-tlo-mediator-subunit-genes-facilitate-filamentous-growth-in-candida-spp
#20
Zhongle Liu, Gary P Moran, Derek J Sullivan, Donna M MacCallum, Lawrence C Myers
Filamentous growth is a hallmark of C. albicans pathogenicity compared to less-virulent ascomycetes. A multitude of transcription factors regulate filamentous growth in response to specific environmental cues. Our work, however, suggests the evolutionary history of C. albicans that resulted in its filamentous growth plasticity may be tied to a change in the general transcription machinery rather than transcription factors and their specific targets. A key genomic difference between C. albicans and its less-virulent relatives, including its closest relative C...
October 2016: PLoS Genetics
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