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Artificial transcriptional factor

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https://www.readbyqxmd.com/read/27908936/genome-editing-technologies-principles-and-applications
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
November 8, 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
#7
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
#8
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
#9
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 (VEGF) promoter-targeted artificial transcriptional repressor zinc-finger protein and GNR-mediated mild hyperthermia to improve antitumor effect...
November 2, 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
#10
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 non-sumoylatable form of Gcn4 showed increased chromatin occupancy, but only if Cdk8 was present...
October 21, 2016: Genetics
https://www.readbyqxmd.com/read/27741243/amplification-of-tlo-mediator-subunit-genes-facilitate-filamentous-growth-in-candida-spp
#11
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
https://www.readbyqxmd.com/read/27729511/life-without-division-physiology-of-escherichia-coli-ftsz-deprived-filaments
#12
Alicia Sánchez-Gorostiaga, Pilar Palacios, Rocío Martínez-Arteaga, Manuel Sánchez, Mercedes Casanova, Miguel Vicente
: When deprived of FtsZ, Escherichia coli cells (VIP205) grown in liquid form long nonseptated filaments due to their inability to assemble an FtsZ ring and their failure to recruit subsequent divisome components. These filaments fail to produce colonies on solid medium, in which synthesis of FtsZ is induced, upon being diluted by a factor greater than 4. However, once the initial FtsZ levels are recovered in liquid culture, they resume division, and their plating efficiency returns to normal...
October 11, 2016: MBio
https://www.readbyqxmd.com/read/27720752/in-vivo-induction-of-human-chorionic-gonadotropin-by-osmotic-pump-advances-sexual-maturation-during-pre-spawning-phase-in-adult-catfish
#13
Raju Murugananthkumar, Yarikipati Prathibha, Balasubramanian Senthilkumaran, Anbazhagan Rajakumar, Hirohiko Kagawa
Gonadal maturation is a critical event wherein gonads, under the influence of several hormones and factors, undergo cyclic morphological and physiological changes to produce functional gametes during the spawning phase. However, artificial induction can be effectively used to advance the maturation of gonad vis-à-vis spawning like behavior in seasonal breeders during the off-breeding season. In the present study, osmotic pumps loaded with 5000IU of human chorionic gonadotropin (hCG) or saline as control were implanted intraperitoneally for 21days during the pre-spawning phase (May-June) in catfish Clarias batrachus and C...
October 5, 2016: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/27709373/novel-snps-and-indels-discovered-in-two-promoter-regions-of-porcine-pregnancy-associated-glycoprotein-2-like-subfamily-ppag2-ls-in-crossbreed-pigs
#14
Martyna Bieniek-Kobuszewska, Grzegorz Panasiewicz, Aleksandra Lipka, Marta Majewska, Bozena Szafranska
This is a pioneer study of single nucleotide polymorphisms (SNPs) within the entire promoter region (1204 bp) of the dominant pPAG2-L subfamily in the pig. The pPAG2-L subfamily was sequenced/examined using genomic deoxyribonucleic acid (gDNA) templates of crossbreed pigs (Landrace x Large White), and compared to two bacterial artificial chromosome (BAC) clones containing gDNA of the Duroc breed (as the positive controls). Our analysis of the pPAG2-L promoter identified 31 SNPs and one InDel mutation in crossbreed pigs...
October 5, 2016: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/27698081/small-rna-gcvb-promotes-mutagenic-break-repair-by-opposing-the-membrane-stress-response
#15
Brittany Barreto, Elizabeth Rogers, Jun Xia, Ryan L Frisch, Megan Richters, Devon M Fitzgerald, Susan M Rosenberg
: Microbes and human cells possess mechanisms of mutagenesis activated by stress responses. Stress-inducible mutagenesis mechanisms may provide important models for mutagenesis that drives host-pathogen interactions, antibiotic resistance, and possibly much of evolution generally. In Escherichia coli, repair of DNA double-strand breaks is switched to a mutagenic mode, using error-prone DNA polymerases, via the SOS DNA-damage and the general (σ(S)) stress responses. We investigated small RNA (sRNA) clients of Hfq, an RNA chaperone that promotes mutagenic break repair (MBR), and found that GcvB promotes MBR by allowing a robust σ(S) response, achieved via opposing the membrane stress (σ(E)) response...
October 3, 2016: Journal of Bacteriology
https://www.readbyqxmd.com/read/27687740/opposite-effects-of-acute-and-chronic-amphetamine-on-nurr1-and-nf-%C3%AE%C2%BAb-p65-in-the-rat-ventral-tegmental-area
#16
Cristian Arredondo, Marcela González, María Estela Andrés, Katia Gysling
Dopamine neurons are overstimulated by drugs of abuse and suffer molecular alterations that lead to addiction behavior. Nurr1 is a transcription factor crucial for dopamine neurons survival and dopamine production, activating the transcription of key genes like tyrosine hydroxylase (TH). Interestingly, nuclear factor-kappa B (NF-κB) has emerged as a new Nurr1 partner in response to inflammatory stimulus. In this study we evaluated the effects of single and repeated amphetamine administration in the expression of Nurr1 and the NF-κB p65 subunit in the rat ventral tegmental area (VTA)...
September 26, 2016: Brain Research
https://www.readbyqxmd.com/read/27683001/molecular-stripping-targets-and-decoys-as-modulators-of-oscillations-in-the-nf-%C3%AE%C2%BAb-i%C3%AE%C2%BAb%C3%AE-dna-genetic-network
#17
Zhipeng Wang, Davit A Potoyan, Peter G Wolynes
Eukaryotic transcription factors in the NF-κB family are central components of an extensive genetic network that activates cellular responses to inflammation and to a host of other external stressors. This network consists of feedback loops that involve the inhibitor IκBα, numerous downstream functional targets, and still more numerous binding sites that do not appear to be directly functional. Under steady stimulation, the regulatory network of NF-κB becomes oscillatory, and temporal patterns of NF-κB pulses appear to govern the patterns of downstream gene expression needed for immune response...
September 2016: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/27671072/a-novel-genome-editing-platform-for-drug-resistant-acinetobacter-baumannii-revealed-an-ader-unrelated-tigecycline-resistance-mechanism
#18
Vincent Trebosc, Sarah Gartenmann, Kevin Royet, Pablo Manfredi, Marcus Tötzl, Birgit Schellhorn, Michel Pieren, Marcel Tigges, Sergio Lociuro, Peter C Sennhenn, Marc Gitzinger, Dirk Bumann, Christian Kemmer
Infections with the Gram-negative coccobacillus Acinetobacter baumannii are a major threat in hospital settings. The progressing emergence of multidrug resistant clinical strains significantly reduces the treatment options for clinicians to fight A. baumannii infections. The current lack of robust methods to genetically manipulate drug resistant A. baumannii isolates impedes research on resistance and virulence mechanisms in clinically relevant strains. In this study we developed a highly efficient and versatile genome editing platform enabling the markerless modification of the genome of A...
September 26, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27668608/-inhibition-of-the-expression-of-proteasomal-genes-saccharomyces-cerevisiae-by-artificial-transcriptional-repressor
#19
B M Kirilenko, E N Grineva, D S Karpov, V L Karpov
26S proteasome is an ATP-dependent protease complex that takes part in cell homeostasis maintenance by the selective degradation of regulatory and damaged proteins. The proteasomal genes expression in Saccharomyces cerevisiae yeast is coordinately regulated by the system, which consists of the Rpn4 transcription factor and its binding site, called PACE. The ability to modulate proteasomal activity by changing the expression of its genes is an essential tool that can be used in fundamental studies devoted to the mechanisms of proteasome dependent cell processes, as well as in applied research for developing strategies to correct proteasome activity in some pathological processes...
July 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27667693/computational-repacking-of-hif-2%C3%AE-cavity-replaces-water-based-stabilized-core
#20
Fernando Corrêa, Jason Key, Brian Kuhlman, Kevin H Gardner
Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors central to hypoxia response and cancer development. Within the HIF-2 complex, one domain (HIF-2α PAS-B) contains a large (290 Å(3)) buried cavity filled with water molecules within its hydrophobic core. Such cavities are uncommon except in the case of ligand-binding proteins, leading to the hypothesis that HIF-2α can be regulated by small molecules. The development of artificial HIF-2α inhibitors validates this hypothesis but raises questions about the impact of this cavity on HIF-2α PAS-B structure and function...
September 20, 2016: Structure
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