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Synthetic transcriptional factor

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https://www.readbyqxmd.com/read/29215200/mir-424-5p-reduces-ribosomal-rna-and-protein-synthesis-in-muscle-wasting
#1
Martin Connolly, Richard Paul, Roser Farre-Garros, Samantha A Natanek, Susannah Bloch, Jen Lee, Jose P Lorenzo, Harnish Patel, Cyrus Cooper, Avan A Sayer, Stephen J Wort, Mark Griffiths, Michael I Polkey, Paul R Kemp
BACKGROUND: A loss of muscle mass occurs as a consequence of a range of chronic and acute diseases as well as in older age. This wasting results from an imbalance of protein synthesis and degradation with a reduction in synthesis and resistance to anabolic stimulation often reported features. Ribosomes are required for protein synthesis, so changes in the control of ribosome synthesis are potential contributors to muscle wasting. MicroRNAs (miRNAs) are known regulators of muscle phenotype and have been shown to modulate components of the protein synthetic pathway...
December 7, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29212027/melanoma-therapeutic-strategies-that-select-against-resistance-by-exploiting-myc-driven-evolutionary-convergence
#2
Katherine R Singleton, Lorin Crawford, Elizabeth Tsui, Haley E Manchester, Ophelia Maertens, Xiaojing Liu, Maria V Liberti, Anniefer N Magpusao, Elizabeth M Stein, Jennifer P Tingley, Dennie T Frederick, Genevieve M Boland, Keith T Flaherty, Shannon J McCall, Clemens Krepler, Katrin Sproesser, Meenhard Herlyn, Drew J Adams, Jason W Locasale, Karen Cichowski, Sayan Mukherjee, Kris C Wood
Diverse pathways drive resistance to BRAF/MEK inhibitors in BRAF-mutant melanoma, suggesting that durable control of resistance will be a challenge. By combining statistical modeling of genomic data from matched pre-treatment and post-relapse patient tumors with functional interrogation of >20 in vitro and in vivo resistance models, we discovered that major pathways of resistance converge to activate the transcription factor, c-MYC (MYC). MYC expression and pathway gene signatures were suppressed following drug treatment, and then rebounded during progression...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29192133/synthetic-transcription-elongation-factors-license-transcription-across-repressive-chromatin
#3
Graham S Erwin, Matthew P Grieshop, Asfa Ali, Jun Qi, Matthew Lawlor, Deepak Kumar, Istaq Ahmad, Anna McNally, Natalia Teider, Katie Worringer, Rajeev Sivasankaran, Deeba N Syed, Asuka Eguchi, Md Ashraf, Justin Jeffery, Mousheng Xu, Paul M C Park, Hasan Mukhtar, Achal K Srivastava, Mohammed Faruq, James E Bradner, Aseem Z Ansari
Releasing a paused RNA polymerase II into productive elongation is tightly-regulated, especially at genes that impact human development and disease. To exert control over this rate-limiting step, we designed sequence-specific synthetic transcription elongation factors (Syn-TEFs). These molecules are composed of programmable DNA-binding ligands flexibly tethered to a small molecule that engages the transcription elongation machinery. By limiting activity to targeted loci, Syn-TEFs convert constituent modules from broad-spectrum inhibitors of transcription into gene-specific stimulators...
November 30, 2017: Science
https://www.readbyqxmd.com/read/29191759/a-novel-and-versatile-dual-fluorescent-reporter-tool-for-the-study-of-gene-expression-and-regulation-in-multi-and-single-copy-number
#4
Indra Bervoets, Daniel Charlier
To unravel intricate mechanisms of gene regulation it is imperative to work in physiologically relevant conditions and therefore preferentially in single copy constructs, which are not always easy to manipulate. Such in vivo studies are generally based on enzymatic assays, microarrays, RNA-seq, qRT-PCR, or multicopy reporter gene systems, frequently with β-galactosidase, luciferase or a fluorescent protein as reporter. Each method has its advantages and shortcomings and may require validation. Enzyme assays are generally reliable but may be quite complex, time consuming, and require a (expensive) substrate...
November 27, 2017: Gene
https://www.readbyqxmd.com/read/29187214/synthetic-enhancer-design-by-in-silico-compensatory-evolution-reveals-flexibility-and-constraint-in-cis-regulation
#5
Kenneth A Barr, Carlos Martinez, Jennifer R Moran, Ah-Ram Kim, Alexandre F Ramos, John Reinitz
BACKGROUND: Models that incorporate specific chemical mechanisms have been successful in describing the activity of Drosophila developmental enhancers as a function of underlying transcription factor binding motifs. Despite this, the minimum set of mechanisms required to reconstruct an enhancer from its constituent parts is not known. Synthetic biology offers the potential to test the sufficiency of known mechanisms to describe the activity of enhancers, as well as to uncover constraints on the number, order, and spacing of motifs...
November 29, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/29183784/osteocalcin-improves-insulin-resistance-and-inflammation-in-obese-mice-participation-of-white-adipose-tissue-and-bone
#6
REVIEW
J A C Guedes, J V Esteves, M R P T Morais, T M T Zorn, D T Furuya
AIMS/HYPOTHESIS: The discovery of osteocalcin, a protein synthetized by osteoblasts, as a hormone that has positive effects on insulin resistance, contributed to support the concept of bone as an endocrine organ. However, very little is known about the molecular pathways involved in osteocalcin improved-insulin resistance. The present study aimed to investigate the mechanisms of action of osteocalcin on insulin resistance and inflammation in obese mice and 3T3-L1 adipocytes. METHODS AND RESULTS: Lean control, saline-treated obese and uncarboxylated osteocalcin (uOC)-treated obese mice were subjected to insulin tolerance test in vivo...
November 25, 2017: Bone
https://www.readbyqxmd.com/read/29167235/cortisol-limits-selected-actions-of-synthetic-glucocorticoids-in-the-airway-epithelium
#7
Danica Prodanovic, Christine R Keenan, Shenna Langenbach, Meina Li, Qianyu Chen, Michael J Lew, Alastair G Stewart
Cortisol, a physiologic glucocorticoid (GC), is essential for growth and differentiation of the airway epithelium. Epithelial function influences inflammation in chronic respiratory diseases. Synthetic GCs, including inhaled corticosteroids, exert anti-inflammatory effects in airway epithelium by transactivation of genes and by inhibition of proinflammatory cytokine release. We examined the effect of cortisol on the actions of synthetic GCs in the airway epithelium, demonstrating that cortisol acts like a partial agonist at the GC receptor (GR), limiting GC-induced GR-dependent transcription in the BEAS-2B human bronchial epithelial cell line...
November 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29166644/cylindromatosis-cyld-a-deubiquitinase-attenuates-inflammatory-signaling-pathways-by-activating-toll-like-receptor-3-in-human-mesangial-cells
#8
Tadaatsu Imaizumi, Ryo Hayakari, Shojiro Watanabe, Tomomi Aizawa, Tomoh Matsumiya, Hidemi Yoshida, Kazushi Tsuruga, Shogo Kawaguchi, Hiroshi Tanaka
BACKGROUND/AIMS: Cylindromatosis (CYLD), a deubiquitinase, negatively regulates nuclear factor-κB in various cells. However, its potential roles in glomerular inflammation remain unclear. Because the activation of the Toll-like receptor 3 (TLR3)/type I interferon (IFN) pathways plays a pivotal role in chronic kidney diseases (CKD), we examined the role of CYLD in the TLR3 signaling in cultured human mesangial cells (MCs). METHODS: We stimulated CYLD-silenced MCs with polyinosinic-polycytidylic acid (poly IC), a synthetic analogue of dsRNA, and studied representative TLR3/IFN-β pathways (i...
November 22, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29161365/genome-scale-analysis-ofescherichia-coliwith-a-comprehensive-prokaryotic-sequence-based-biophysical-model-of-translation-initiation-and-elongation
#9
Gilad Shaham, Tamir Tuller
Translation initiation in prokaryotes is affected by the mRNA folding and interaction of the ribosome binding site with the ribosomal RNA. The elongation rate is affected, among other factors, by the local biophysical properties of the coding regions, the decoding rates of different codons, and the interactions among ribosomes. Currently, there is no comprehensive biophysical model of translation that enables the prediction of mRNA translation dynamics based only on the transcript sequence and while considering all of these fundamental aspects of translation...
November 17, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/29158022/activation-of-the-nrf2-signaling-pathway-and-neuroprotection-of-nigral-dopaminergic-neurons-by-a-novel-synthetic-compound-kms99220
#10
Ji Ae Lee, Hyo Jin Son, Ji Won Choi, Jinwoo Kim, Se Hee Han, Nari Shin, Ji Hyun Kim, Soo Jeong Kim, Jun Young Heo, Dong Jin Kim, Ki Duk Park, Onyou Hwang
The transcription factor Nrf2 is known to induce gene expression of antioxidant enzymes and proteasome subunits. Because both oxidative stress and protein aggregation have damaging effects on neurons, activation of the Nrf2 signaling should be beneficial against neurodegeneration. In this study, we report a novel synthetic morpholine-containing chalcone KMS99220 that confers neuroprotection. It showed high binding affinity to the Nrf2 inhibitory protein Keap-1 and increased nuclear translocation of Nrf2 and gene expression of the antioxidant enzymes heme oxygenase-1, NAD(P)H:quinone oxidoreductase-1, and the catalytic and modifier subunits of glutamate-cysteine ligase in dopaminergic CATH...
November 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29149221/dietary-protein-sources-differentially-affect-microbiota-mtor-activity-and-transcription-of-mtor-signaling-pathways-in-the-small-intestine
#11
Soumya K Kar, Alfons J M Jansman, Nirupama Benis, Javier Ramiro-Garcia, Dirkjan Schokker, Leo Kruijt, Ellen H Stolte, Johanna J Taverne-Thiele, Mari A Smits, Jerry M Wells
Dietary protein sources can have profound effects on host-microbe interactions in the gut that are critically important for immune resilience. However more knowledge is needed to assess the impact of different protein sources on gut and animal health. Thirty-six wildtype male C57BL/6J mice of 35 d age (n = 6/group; mean ± SEM body weight 21.9 ± 0.25 g) were randomly assigned to groups fed for four weeks with semi synthetic diets prepared with one of the following protein sources containing (300 g/kg as fed basis): soybean meal (SBM), casein, partially delactosed whey powder, spray dried plasma protein, wheat gluten meal and yellow meal worm...
2017: PloS One
https://www.readbyqxmd.com/read/29148103/extracytoplasmic-function-sigma-factor-%C3%AF-d-confers-resistance-to-environmental-stress-by-enhancing-mycolate-synthesis-and-modifying-peptidoglycan-structures-in-corynebacterium-glutamicum
#12
Koichi Toyoda, Inui Masayuki
Mycolates are α-branched, β-hydroxylated, long-chain fatty acid specifically synthesized in bacteria in the suborder Corynebacterineae of the phylum Actinobacteria. They form an outer membrane, which functions as a permeability barrier and confers pathogenic mycobacteria to resistance to antibiotics. Although the mycolate biosynthetic pathway has been intensively studied, knowledge of transcriptional regulation of genes involved in this pathway is limited. Here we report that the extracytoplasmic function sigma factor σ(D) is a key regulator of the mycolate synthetic genes in Corynebacterium glutamicum in the suborder...
November 17, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29143012/%C3%AE-alanine-and-n-terminal-cationic-substituents-affect-polyamide-dna-binding
#13
Beibei Liu, Shuo Wang, Karl Aston, Kevin J Koeller, Shahrzad Fanny Hakami Kermani, Carlos H Castañeda, M José Scuderi, Rensheng Luo, James K Bashkin, W David Wilson
Minor-groove binding hairpin polyamides (PAs) bind specific DNA sequences. Synthetic modifications can improve PA-DNA binding affinity and include flexible modules, such as β-alanine (β) motifs to replace pyrroles (Py), and increasing compound charge using N-terminal cationic substituents. To better understand the variations in kinetics and affinities caused by these modifications on PA-DNA interactions, a comprehensive set of PAs with different numbers and positions of β and different types of N-cationic groups was systematically designed and synthesized to bind their cognate sequence, the λB motif...
November 16, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29137634/profiling-of-saccharomyces-cerevisiae-transcription-factors-for-engineering-the-resistance-of-yeast-to-lignocellulose-derived-inhibitors-in-biomass-conversion
#14
Guochao Wu, Zixiang Xu, Leif J Jönsson
BACKGROUND: Yeast transcription factors (TFs) involved in the regulation of multidrug resistance (MDR) were investigated in experiments with deletion mutants, transformants overexpressing synthetic genes encoding TFs, and toxic concentrations of lignocellulose-derived substances added to cultures as complex mixtures or as specific compounds, viz. coniferyl aldehyde, 5-hydroxymethylfurfural, and furfural. RESULTS: In the presence of complex mixtures of toxic substances from spruce wood, transformants overexpressing YAP1 and STB5, TFs involved in oxidative stress response, exhibited enhanced relative growth rates amounting to 4...
November 14, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/29128625/lxr-activation-increases-the-expression-of-gnrh-and-%C3%AE-msh-in-the-rat-hypothalamus-in-vivo
#15
María Sol Kruse, Lucas Gabriel Suarez, Héctor Coirini
Liver X receptors (LXR) are important transcription factors involved in the regulation of carbohydrate and lipid metabolism. Recently, we described LXR receptors expression in the hypothalamus but their function in this brain area remains unknown. Here, we evaluated the function of LXR on the expression of factors produced in the hypothalamus in vitro and in vivo by Western blotting and immunocytochemistry. More precisely we studied the expression of GnRH and GHRH, αMSH and NPY in male Sprague-Dawley rats...
November 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29122042/peroxisome-proliferator-activated-receptor-gamma-ppar%C3%AE-agonist-fails-to-overcome-trans-10-cis-12-conjugated-linoleic-acid-cla-inhibition-of-milk-fat-in-dairy-sheep
#16
E C Sandri, M Camêra, E M Sandri, K J Harvatine, D E De Oliveira
The trans-10, cis-12 conjugated linoleic acid (CLA) causes milk fat depression by downregulating expression of genes and transcription factors involved in lipogenesis and it has been proposed that peroxisome proliferator-activated receptor gamma (PPARγ) can be inhibited by trans-10, cis-12 CLA. The PPARγ is a nuclear receptor activated by natural or synthetic ligands and promotes expression of lipogenic genes and its effect on mammary lipogenesis and the interaction with trans-10, cis-12 CLA in lactating ewes was evaluated using thiazolidinedione (TZD), a chemical PPARγ agonist...
November 10, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/29119010/epigenetic-impact-of-endocrine-disrupting-chemicals-on-lipid-homeostasis-and-atherosclerosis-a-pregnane-x-receptor-centric-view
#17
Robert N Helsley, Changcheng Zhou
Despite the major advances in developing diagnostic techniques and effective treatments, atherosclerotic cardiovascular disease (CVD) is still the leading cause of mortality and morbidity worldwide. While considerable progress has been achieved to identify gene variations and environmental factors that contribute to CVD, much less is known about the role of "gene-environment interactions" in predisposing individuals to CVD. Our chemical environment has significantly changed in the last few decades, and there are more than 100,000 synthetic chemicals in the market...
October 1, 2017: Environmental Epigenetics
https://www.readbyqxmd.com/read/29115671/fatty-acid-elongase-7-is-regulated-via-sp1-and-is-involved-in-lipid-accumulation-in-bovine-mammary-epithelial-cells
#18
Si Chen, Zhigang Hu, Hua He, Xiaolin Liu
Fatty Acid Elongase 7 (ELOVL7) is the newly discovered protein on human that catalyzes the rate-limiting step towards the synthesis of very long-chain fatty acids and exhibits the highest activity toward C18:3 (n-3) acyl-CoAs, which is the precursor of eicosapentaenoic acid (EPA, 20:5n-3). However, in ruminants, an overall understanding of ELOVLs gene family and the transcriptional regulation of ELOVL7 remain unknown. The purpose of this study is to investigate the transcriptional regulation and the influence of bovine ELOVL7 in bovine mammary epithelial cells (bMECs)...
November 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29114259/identification-of-splicing-quantitative-trait-loci-sqtl-in-drosophila-melanogaster-with-developmental-lead-pb-2-exposure
#19
Wen Qu, Katherine Gurdziel, Roger Pique-Regi, Douglas M Ruden
Lead (Pb) poisoning has been a major public health issue globally and the recent Flint water crisis has drawn nation-wide attention to its effects. To better understand how lead plays a role as a neurotoxin, we utilized the Drosophila melanogaster model to study the genetic effects of lead exposure during development and identified lead-responsive genes. In our previous studies, we have successfully identified hundreds of lead-responsive expression QTLs (eQTLs) by using RNA-seq analysis on heads collected from the Drosophila Synthetic Population Resource...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/29111218/the-notch-pathway-inhibitor-stapled-%C3%AE-helical-peptide-derived-from-mastermind-like-1-sahm1-abrogates-the-hallmarks-of-allergic-asthma
#20
Alex KleinJan, Irma Tindemans, Jeffrey E Montgomery, Melanie Lukkes, Marjolein J W de Bruijn, Menno van Nimwegen, Ingrid Bergen, Raymond E Moellering, Henk C Hoogsteden, Louis Boon, Derk Amsen, R W Hendriks
BACKGROUND: The Notch signaling pathway has been implicated in the pathogenesis of allergic airway inflammation. Targeting the active Notch transactivation complex by using the cell-permeable, hydrocarbon-stapled synthetic peptide stapled α-helical peptide derived from mastermind-like 1 (SAHM1) resulted in genome-wide suppression of Notch-activated genes in leukemic cells and other models. However, the efficacy of SAHM1 in allergic asthma models has remained unexplored. OBJECTIVE: We aimed to investigate the therapeutic efficacy of SAHM1 in a house dust mite (HDM)-driven asthma model...
October 27, 2017: Journal of Allergy and Clinical Immunology
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