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https://www.readbyqxmd.com/read/28468969/protein-kinase-ck2-controls-the-fate-between-th17-cell-and-regulatory-t-cell-differentiation
#1
Sara A Gibson, Wei Yang, Zhaoqi Yan, Yudong Liu, Amber L Rowse, Amy S Weinmann, Hongwei Qin, Etty N Benveniste
CK2 is a highly conserved and pleiotropic serine/threonine kinase that promotes many prosurvival and proinflammatory signaling pathways, including PI3K/Akt/mTOR and JAK/STAT. These pathways are essential for CD4(+) T cell activation and polarization, but little is known about how CK2 functions in T cells. In this article, we demonstrate that CK2 expression and kinase activity are induced upon CD4(+) T cell activation. Targeting the catalytic activity of CK2 using the next-generation small molecule inhibitor CX-4945 in vitro significantly and specifically inhibited mouse and human Th17 cell differentiation while promoting the generation of Foxp3(+) regulatory T cells (Tregs)...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28422494/genetically-encoded-2-aryl-5-carboxytetrazoles-for-site-selective-protein-photo-cross-linking
#2
Yulin Tian, Marco Paolo Jacinto, Yu Zeng, Zhipeng Yu, Jun Qu, Wenshe R Liu, Qing Lin
The genetically encoded photo-cross-linkers promise to offer a temporally controlled tool to map transient and dynamic protein-protein interaction complexes in living cells. Here we report the synthesis of a panel of 2-aryl-5-carboxytetrazole-lysine analogs (ACTKs) and their site-specific incorporation into proteins via amber codon suppression in Escherichia coli and mammalian cells. Among five ACTKs investigated, N-methylpyrroletetrazole-lysine (mPyTK) was found to give robust and site-selective photo-cross-linking reactivity in E...
May 3, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28410215/cardiac-glycosides-suppress-the-maintenance-of-stemness-and-malignancy-via-inhibiting-hif-1%C3%AE-in-human-glioma-stem-cells
#3
Dae-Hee Lee, Sang Cheul Oh, Amber J Giles, Jinkyu Jung, Mark R Gilbert, Deric M Park
Tissue hypoxia contributes to solid tumor pathogenesis by activating a series of adaptive programs. We previously showed that hypoxia promotes the preferential expansion and maintenance of CD133 positive human glioma stem cells (GSC) in a hypoxia inducible factor 1 alpha (HIF-1α)-dependent mechanism. Here, we examined the activity of digitoxin (DT), a cardiac glycoside and a putative inhibitor of HIF-1α, on human GSC in vitro and in vivo. During hypoxic conditions (1% O2), we observed the effect of DT on the intracellular level of HIF-1α and the extracellular level of vascular endothelial growth factor (VEGF) in human GSC...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410196/the-p38-signaling-pathway-mediates-quiescence-of-glioma-stem-cells-by-regulating-epidermal-growth-factor-receptor-trafficking
#4
Akio Soeda, Justin Lathia, Brian J Williams, Qiulian Wu, Joseph Gallagher, Andreas Androutsellis-Theotokis, Amber J Giles, Chunzhang Yang, Zhengping Zhuang, Mark R Gilbert, Jeremy N Rich, Deric M Park
EGFR pathway is upregulated in malignant gliomas, and its downstream signaling is important for self-renewal of glioma cancer stem-like cells (GSC). p38 mitogen-activated protein kinase (MAPK) signaling, a stress-activated signaling cascade with suppressive and permissive effects on tumorigenesis, can promote internalization and ubiquitin ligase mediated degradation of EGFR. In this study, we investigated the role of p38 MAPK signaling on the self-renewal of GSCs with the hypothesis that inhibition may lead to enhanced self-renewal capacity by retention of EGFR...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28383180/two-tier-screening-platform-for-directed-evolution-of-aminoacyl-trna-synthetases-with-enhanced-stop-codon-suppression-efficiency
#5
Andrew E Owens, Katherine T Grasso, Christine A Ziegler, Rudi Fasan
Genetic code expansion via amber stop suppression provides a powerful tool for introducing non-proteinogenic functionalities into proteins for a broad range of applications. Here, we report the implementation of a versatile platform for the development of engineered aminoacyl-tRNA synthetases with enhanced efficiency in mediating ncAA incorporation via amber stop codon suppression. This system integrates a white/blue colony screen with a plate-based colorimetric assay, thereby combining high-throughput capabilities with reliable and quantitative measurement of AARS-dependent ncAA incorporation efficiency...
April 6, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28320938/effectiveness-of-unaids-targets-and-hiv-vaccination-across-127-countries
#6
Jan Medlock, Abhishek Pandey, Alyssa S Parpia, Amber Tang, Laura A Skrip, Alison P Galvani
The HIV pandemic continues to impose enormous morbidity, mortality, and economic burdens across the globe. Simultaneously, innovations in antiretroviral therapy, diagnostic approaches, and vaccine development are providing novel tools for treatment-as-prevention and prophylaxis. We developed a mathematical model to evaluate the added benefit of an HIV vaccine in the context of goals to increase rates of diagnosis, treatment, and viral suppression in 127 countries. Under status quo interventions, we predict a median of 49 million [first and third quartiles 44M, 58M] incident cases globally from 2015 to 2035...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28288813/a-genomically-modified-escherichia-coli-strain-carrying-an-orthogonal-e-coli-histidyl-trna-synthetase%C3%A2-trna-his-pair
#7
Markus Englert, Oscar Vargas-Rodriguez, Noah M Reynolds, Yane-Shih Wang, Dieter Söll, Takuya Umehara
BACKGROUND: Development of new aminoacyl-tRNA synthetase (aaRS)•tRNA pairs is central for incorporation of novel non-canonical amino acids (ncAAs) into proteins via genetic code expansion (GCE). The Escherichia coli and Caulobacter crescentus histidyl-tRNA synthetases (HisRS) evolved divergent mechanisms of tRNA(His) recognition that prevent their cross-reactivity. Although the E. coli HisRS•tRNA(His) pair is a good candidate for GCE, its use in C. crescentus is limited by the lack of established genetic selection methods and by the low transformation efficiency of C...
March 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28212794/an-efficient-system-for-incorporation-of-unnatural-amino-acids-in-response-to-the-four-base-codon-agga-in-escherichia-coli
#8
Byeong Sung Lee, Suyeon Kim, Byoung Joon Ko, Tae Hyeon Yoo
BACKGROUND: Adding new amino acids to the set of building blocks for protein synthesis expands the scope of protein engineering, and orthogonal pairs of tRNA and aminoacyl-tRNA synthetase have been developed for incorporating unnatural amino acids (UAAs) into proteins. While diverse systems have been developed to incorporate UAAs in response to the amber codon, less research has been focused on four-base codons despites their advantages. In this study, we report an efficient method to incorporate UAA in response to an AGGA codon in Escherichia coli...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28196426/development-of-a-functional-observational-battery-in-the-minipig-for-regulatory-neurotoxicity-assessments
#9
Miao Zhong, Catherine Shoemake, Amber Fuller, David White, Chris Hanks, Derek Brocksmith, Jason Liu, Shayne Gad, Guy Bouchard, Alain Stricker-Krongrad
A functional observational battery (FOB) is recommended as the first-tier neurotoxicity screening in the preclinical safety pharmacology testing guidelines. Minipigs have increasingly been used in regulatory toxicology studies; however, no current FOB protocol is available for neurotoxicity testing in these species. Hence, a minipig FOB instrument was developed. A complete crossover study with Sinclair minipigs was performed to evaluate physiologic, neurologic, and behavioral effects of amphetamine, ketamine, and diazepam...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28165290/improved-fat-suppression-homogeneity-with-mdixon-turbo-spin-echo-tse-in-pediatric-spine-imaging-at-3-0%C3%A2-t
#10
Amber L Pokorney, Jonathan M Chia, Cory M Pfeifer, Jeffrey H Miller, Houchun H Hu
Background Robust fat suppression remains essential in clinical MRI to improve tissue signal contrast, minimize fat-related artifacts, and enhance image quality. Purpose To compare fat suppression between mDIXON turbo spin echo (TSE) and conventional frequency-selective and inversion-recovery methods in pediatric spine MRI. Material and Methods Images from T1-weighted (T1W) and T2-weighted (T2W) TSE sequences coupled with conventional methods and the mDIXON technique were compared in 36 patients (5.8 ± 5...
January 1, 2017: Acta Radiologica
https://www.readbyqxmd.com/read/28131845/safer-topical-treatment-for-inflammation-using-5%C3%AE-tetrahydrocorticosterone-in-mouse-models
#11
Annalisa Gastaldello, Dawn E W Livingstone, Amber J Abernethie, Nicola Tsang, Brian R Walker, Patrick W F Hadoke, Ruth Andrew
Use of topical glucocorticoid for inflammatory skin conditions is limited by systemic and local side-effects. This investigation addressed the hypothesis that topical 5α-tetrahydrocorticosterone (5αTHB, a corticosterone metabolite) inhibits dermal inflammation without affecting processes responsible for skin thinning and impaired wound healing. The topical anti-inflammatory properties of 5αTHB were compared with those of corticosterone in C57Bl/6 male mice with irritant dermatitis induced by croton oil, whereas its effects on angiogenesis, inflammation, and collagen deposition were investigated by subcutaneous sponge implantation...
April 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28106981/controlling-multicycle-replication-of-live-attenuated-hiv-1-using-an-unnatural-genetic-switch
#12
Zhe Yuan, Nanxi Wang, Guobin Kang, Wei Niu, Qingsheng Li, Jiantao Guo
A safe and effective human immunodeficiency virus type 1 (HIV-1) vaccine is urgently needed, but remains elusive. While HIV-1 live-attenuated vaccine can provide potent protection as demonstrated in rhesus macaque-simian immunodeficiency virus model, the potential pathogenic consequences associated with the uncontrolled virus replication preclude such vaccine from clinical applications. We investigated a novel approach to address this problem by controlling live-attenuated HIV-1 replication through an unnatural genetic switch that was based on the amber suppression strategy...
April 21, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28050852/microbial-biomass-in-compost-during-colonization-of-agaricus-bisporus
#13
Aurin M Vos, Amber Heijboer, Henricus T S Boschker, Barbara Bonnet, Luis G Lugones, Han A B Wösten
Agaricus bisporus mushrooms are commercially produced on a microbe rich compost. Here, fungal and bacterial biomass was quantified in compost with and without colonization by A. bisporus. Chitin content, indicative of total fungal biomass, increased during a 26-day period from 576 to 779 nmol N-acetylglucosamine g(-1) compost in the absence of A. bisporus (negative control). A similar increase was found in the presence of this mushroom forming fungus. The fungal phospholipid-derived fatty acid (PLFA) marker C18:2ω6, indicative of the living fraction of the fungal biomass, decreased from 575 to 280 nmol g(-1) compost in the negative control...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28042700/a-versatile-approach-for-site-specific-lysine-acylation-in-proteins
#14
Zhipeng A Wang, Yadagiri Kurra, Xin Wang, Yu Zeng, Yan-Jiun Lee, Vangmayee Sharma, Hening Lin, Susie Y Dai, Wenshe R Liu
Using amber suppression in coordination with a mutant pyrrolysyl-tRNA synthetase-tRNA(Pyl) pair, azidonorleucine is genetically encoded in E. coli. Its genetic incorporation followed by traceless Staudinger ligation with a phosphinothioester allows the convenient synthesis of a protein with a site-specifically installed lysine acylation. By simply changing the phosphinothioester identity, any lysine acylation type could be introduced. Using this approach, we demonstrated that both lysine acetylation and lysine succinylation can be installed selectively in ubiquitin and synthesized histone H3 with succinylation at its K4 position (H3K4su)...
February 1, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/27966891/combining-sense-and-nonsense-codon-reassignment-for-site-selective-protein-modification-with-unnatural-amino-acids
#15
Zhenling Cui, Sergey Mureev, Mark E Polinkovsky, Zakir Tnimov, Zhong Guo, Thomas Durek, Alun Jones, Kirill Alexandrov
Incorporation of unnatural amino acids (uAAs) via codon reassignment is a powerful approach for introducing novel chemical and biological properties to synthesized polypeptides. However, the site-selective incorporation of multiple uAAs into polypeptides is hampered by the limited number of reassignable nonsense codons. This challenge is addressed in the current work by developing Escherichia coli in vitro translation system depleted of specific endogenous tRNAs. The translational activity in this system is dependent on the addition of synthetic tRNAs for the chosen sense codon...
December 30, 2016: ACS Synthetic Biology
https://www.readbyqxmd.com/read/27919800/increasing-the-fidelity-of-noncanonical-amino-acid-incorporation-in-cell-free-protein-synthesis
#16
Qinglei Gan, Chenguang Fan
BACKGROUND: Cell-free protein synthesis provides a robust platform for co-translational incorporation of noncanonical amino acid (ncAA) into proteins to facilitate biological studies and biotechnological applications. Recently, eliminating the activity of release factor 1 has been shown to increase ncAA incorporation in response to amber codons. However, this approach could promote mis-incorporation of canonical amino acids by near cognate suppression. METHODS: We performed a facile protocol to remove near cognate tRNA isoacceptors of the amber codon from total tRNAs, and used the phosphoserine (Sep) incorporation system as validation...
December 2, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27914361/development-of-cxcr4-modulators-by-virtual-hts-of-a-novel-amide-sulfamide-compound-library
#17
Renren Bai, Qi Shi, Zhongxing Liang, Younghyoun Yoon, Yiran Han, Amber Feng, Shuangping Liu, Yoonhyeun Oum, C Chris Yun, Hyunsuk Shim
CXCR4 plays a crucial role in recruitment of inflammatory cells to inflammation sites at the beginning of the disease process. Modulating CXCR4 functions presents a new avenue for anti-inflammatory strategies. However, using CXCR4 antagonists for a long term usage presents potential serious side effect due to their stem cell mobilizing property. We have been developing partial CXCR4 antagonists without such property. A new computer-aided drug design program, the FRESH workflow, was used for anti-CXCR4 lead compound discovery and optimization, which coupled both compound library building and CXCR4 docking screens in one campaign...
January 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27910233/a-genetically-encoded-allysine-for-the-synthesis-of-proteins-with-site-specific-lysine-dimethylation
#18
Zhipeng A Wang, Yu Zeng, Yadagiri Kurra, Xin Wang, Jeffery M Tharp, Erol C Vatansever, Willie W Hsu, Susie Dai, Xinqiang Fang, Wenshe R Liu
Using the amber suppression approach, N(ϵ) -(4-azidobenzoxycarbonyl)-δ,ϵ-dehydrolysine, an allysine precursor is genetically encoded in E. coli. Its genetic incorporation followed by two sequential biocompatible reactions allows convenient synthesis of proteins with site-specific lysine dimethylation. Using this approach, dimethyl-histone H3 and p53 proteins have been synthesized and used to probe functions of epigenetic enzymes including histone demethylase LSD1 and histone acetyltransferase Tip60. We confirmed that LSD1 is catalytically active toward H3K4me2 and H3K9me2 but inert toward H3K36me2, and methylation at p53 K372 directly activates Tip60 for its catalyzed acetylation at p53 K120...
January 2, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/27903651/t-cells-encountering-myeloid-cells-programmed-for-amino-acid-dependent-immunosuppression-use-rictor-mtorc2-protein-for-proliferative-checkpoint-decisions
#19
Lee-Ann Van de Velde, Chitra Subramanian, Amber M Smith, Luke Barron, Joseph E Qualls, Geoffrey Neale, Adolfo Alfonso-Pecchio, Suzanne Jackowski, Charles O Rock, Thomas A Wynn, Peter J Murray
Modulation of T cell proliferation and function by immunoregulatory myeloid cells are an essential means of preventing self-reactivity and restoring tissue homeostasis. Consumption of amino acids such as arginine and tryptophan by immunoregulatory macrophages is one pathway that suppresses local T cell proliferation. Using a reduced complexity in vitro macrophage-T cell co-culture system, we show that macrophage arginase-1 is the only factor required by M2 macrophages to block T cells in G1, and this effect is mediated by l-arginine elimination rather than metabolite generation...
January 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27853654/tumor-necrosis-factor-links-chronic-obstructive-pulmonary-disease-and-k-ras-mutant-lung-cancer-through-induction-of-an-immunosuppressive-pro-tumor-microenvironment
#20
Lei Gong, Mauricio da Silva Caetano, Amber M Cumpian, Soudabeh Daliri, Alejandra Garza Flores, Seon Hee Chang, Cesar E Ochoa, Christopher M Evans, Zhentao Yu, Seyed Javad Moghaddam
Tumor necrosis factor (TNF) is known as an important regulator of tumor microenvironment and inflammation. TNF levels are markedly elevated in the bronchoalveolar lavage fluid (BALF) of patients with chronic obstructive pulmonary disease (COPD), which is an independent risk factor for lung cancer. We have previously shown that COPD-like airway inflammation promotes lung cancer in a K-ras mutant mouse model (CC-LR mouse). This was associated with a significant increase of neutrophils in BALF, accompanied by a marked increase in TNF level, suggesting a link between COPD, TNF, and lung cancer promotion...
2016: Oncoimmunology
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