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https://www.readbyqxmd.com/read/27935476/assessing-the-mechanism-and-therapeutic-potential-of-modulators-of-the-human-mediator-complex-associated-protein-kinases
#1
Paul Andrew Clarke, Maria-Jesus Ortiz-Ruiz, Robert TePoele, Olajumoke Adeniji-Popoola, Gary Box, Will Court, Stefanie Czasch, Samer El Bawab, Christina Esdar, Ken Ewan, Sharon Gowan, Alexis De Haven Brandon, Phllip Hewitt, Stephen M Hobbs, Wolfgang Kaufmann, Aurélie Mallinger, Florence Raynaud, Toby Roe, Felix Rohdich, Kai Schiemann, Stephanie Simon, Richard Schneider, Melanie Valenti, Stefan Weigt, Julian Blagg, Andree Blaukat, Trevor C Dale, Suzanne A Eccles, Stefan Hecht, Klaus Urbahns, Paul Workman, Dirk Wienke
Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis. Their inhibition is predicted to have pleiotropic effects, but it is unclear whether this will impact on the clinical utility of CDK8/19 inhibitors. We discovered two series of potent chemical probes with high selectivity for CDK8/19. Despite pharmacodynamic evidence for robust on-target activity, the compounds exhibited modest, though significant, efficacy against human tumor lines and patient-derived xenografts...
December 9, 2016: ELife
https://www.readbyqxmd.com/read/27923061/comparative-transcriptomic-and-epigenomic-analyses-reveal-new-regulators-of-murine-brown-adipogenesis
#2
Reinhard Brunmeir, Jingyi Wu, Xu Peng, Sun-Yee Kim, Sofi G Julien, Qiongyi Zhang, Wei Xie, Feng Xu
Increasing energy expenditure through brown adipocyte recruitment is a promising approach to combat obesity. We report here the comprehensive profiling of the epigenome and transcriptome throughout the lineage commitment and differentiation of C3H10T1/2 mesenchymal stem cell line into brown adipocytes. Through direct comparison to datasets from differentiating white adipocytes, we systematically identify stage- and lineage-specific coding genes, lncRNAs and microRNAs. Utilizing chromatin state maps, we also define stage- and lineage-specific enhancers, including super-enhancers, and their associated transcription factor binding motifs and genes...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27909248/regulation-of-chemokine-receptor-ccr2-recycling-by-filamin-a-phosphorylation
#3
Mònica Pons, Ismael Izquierdo, Mireia Andreu-Carbó, Georgina Garrido, Jesús Planagumà, Olivia Muriel, M Isabel Geli, Anna M Aragay
Proper endosomal trafficking of ligand-activated G protein-coupled receptors (GPCRs) is essential to spatiotemporally tune their physiological responses. For the monocyte chemoattractant receptor 2 (CCR2B), endocytic recycling is important to sustain monocyte migration; while filamin A (FLNa) is essential for CCL2-induced monocyte migration. Here, we analyze the role of FLNa in the trafficking of CCR2B along the endocytic pathway. In FLNa knockdown cells, activated CCR2B accumulated in enlarged EEA-1-positive endosomes, which exhibited slow movement and fast fluorescence recovery, suggesting an imbalance between receptor entry and exit rates...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27897135/improved-dielectric-constant-and-breakdown-strength-of-%C3%AE-phase-dominant-super-toughened-polyvinylidene-fluoride-tio2-nanocomposite-film-an-excellent-material-for-energy-storage-applications-and-piezoelectric-throughput
#4
Md Mehebub Alam, Sujoy Kumar Ghosh, Debabrata Sarkar, Shrabanee Sen, Dipankar Mandal
Titanium dioxide (TiO2) nanoparticles (NPs) embedded γ-phase containing polyvinylidene fluoride (PVDF) nanocomposite (PNC) film turns to an excellent material for energy storage application due to an increased dielectric constant (32 at 1 kHz), enhanced electric breakdown strength (400 MV m(-1)). It also exhibits a high energy density of 4 J cm(-3) which is 25 times higher than that of virgin PVDF. 98% of the electroactive γ-phase has been acheived by the incorporation of TiO2 NPs and the resulting PNC behaves like a super-toughened material due to a dramatic improvement (more than 80%) in the tensile strength...
January 6, 2017: Nanotechnology
https://www.readbyqxmd.com/read/27893388/sparse-representation-based-multiple-frame-video-super-resolution
#5
Qiqin Dai, Seunghwan Yoo, Armin Kappeler, Aggelos K Katsaggelos
In this paper, we propose two multiple-frame superresolution (SR) algorithms based on dictionary learning and motion estimation. First, we adopt the use of video bilevel dictionary learning which has been used for single-frame SR. It is extended to multiple frames by using motion estimation with subpixel accuracy. We propose a batch and a temporally recursive multi-frame SR algorithm, which improve over single frame SR. Finally, we propose a novel dictionary learning algorithm utilizing consecutive video frames, rather than still images or individual video frames, which further improves the performance of the video SR algorithms...
November 22, 2016: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
https://www.readbyqxmd.com/read/27883055/gapmer-cellular-internalization-by-macropinocytosis-induces-sequence-specific-gene-silencing-in-human-primary-t-cells
#6
Mobashar Hussain Urf Turabe Fazil, Seow Theng Ong, Madhavi Latha Somaraju Chalasani, Jian Hui Low, Atish Kizhakeyil, Akshay Mamidi, Carey Fang Hui Lim, Graham D Wright, Rajamani Lakshminarayanan, Dermot Kelleher, Navin Kumar Verma
Post-transcriptional gene silencing holds great promise in discovery research for addressing intricate biological questions and as therapeutics. While various gene silencing approaches, such as siRNA and CRISPR-Cas9 techniques, are available, these cannot be effectively applied to "hard-to-transfect" primary T-lymphocytes. The locked nucleic acid-conjugated chimeric antisense oligonucleotide, called "GapmeR", is an emerging new class of gene silencing molecule. Here, we show that GapmeR internalizes into human primary T-cells through macropinocytosis...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27875882/on-the-feasibility-of-designing-hyperalkali-cations-using-superalkali-clusters-as-ligands
#7
Wei-Ming Sun, Xiang-Hui Li, Ying Li, Jia-Yuan Liu, Di Wu, Chun-Yan Li, Bi-Lian Ni, Zhi-Ru Li
The possibility of using superalkali clusters instead of alkali atoms as ligands to design a class of cationic compounds, referred to as hyperalkali cations, has been examined by using gradient-corrected density functional theory. By taking typical superalkalis (FLi2, OLi3, and NLi4) as examples, a series of hyperalkali cations ML2(+) [M = (super)halogen; L = superalkali] have been constructed and investigated. Calculational results show that all the superalkali moieties preserve their geometric and electronic integrity in these proposed cations...
November 21, 2016: Journal of Chemical Physics
https://www.readbyqxmd.com/read/27827427/establishing-super-resolution-imaging-for-proteins-in-diatom-biosilica
#8
Philip Gröger, Nicole Poulsen, Jennifer Klemm, Nils Kröger, Michael Schlierf
The intricate, genetically controlled biosilica nano- and micropatterns produced by diatoms are a testimony for biology's ability to control mineral formation (biomineralization) at the nanoscale and regarded as paradigm for nanotechnology. Previously, several protein families involved in diatom biosilica formation have been identified, and many of them remain tightly associated with the final biosilica structure. Determining the locations of biosilica-associated proteins with high precision is, therefore expected to provide clues to their roles in biosilica morphogenesis...
November 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27814619/novel-strategies-to-target-cancer-stem-cells-by-nk-cells-studies-in-humanized-mice
#9
Anna K Kozlowska, Kawaljit Kaur, Paytsar Topchyan, Anahid Jewett
We have previously shown that following selection, Natural Killer (NK) cells, differentiate Cancer stem cells (CSCs)/undifferentiated or poorly differentiated tumors via secreted and membrane bound IFN-gamma and TNF-alpha, leading to prevention of tumor growth and remodeling of the tumor microenvironment. Since conventional therapeutic strategies including chemotherapy and radiotherapy remain unsuccessful in treating stem-like tumors, there has been an increasing interest in NK cell based immunotherapy for the treatment of resistant tumors...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27810805/characterisation-of-contrast-agent-microbubbles-for-ultrasound-imaging-and-therapy-research
#10
Helen Mulvana, Richard J Browning, Ying Luan, Nico de Jong, Meng-Xing Tang, Robert J Eckersley, Eleanor Stride
The high efficiency with which gas microbubbles can scatter ultrasound compared to the surrounding blood pool or tissues has led to their widespread employment as contrast agents in ultrasound imaging. In recent years their applications have been extended to include super-resolution imaging and the stimulation of localized bio-effects for therapy. The growing exploitation of contrast agents in ultrasound, and in particular these recent developments, have amplified the need to characterize and fully understand microbubble behavior...
October 26, 2016: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
https://www.readbyqxmd.com/read/27805608/single-molecule-super-resolution-imaging-of-phosphatidylinositol-4-5-bisphosphate-in-the-plasma-membrane-with-novel-fluorescent-probes
#11
Chen Ji, Xuelin Lou
Phosphoinositides in the cell membrane are signaling lipids with multiple cellular functions. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a determinant phosphoinositide of the plasma membrane (PM), and it is required to modulate ion channels, actin dynamics, exocytosis, endocytosis, intracellular signaling, and many other cellular processes. However, the spatial organization of PI(4,5)P2 in the PM is controversial, and its nanoscale distribution is poorly understood due to the technical limitations of research approaches...
October 15, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27798969/the-influence-of-body-mass-index-on-outcomes-in-ureteroscopy-results-from-the-clinical-research-office-of-endourological-society-urs-global-study
#12
Amy Krambeck, Nienke Wijnstok, Peter Olbert, George Mitroi, Simon Bariol, Hemendra N Shah, Ahmed S El-Abd, Bulent Onal, Jean de la Rosette
INTRODUCTION: Although ureteroscopy (URS) has been established as a viable treatment for stones in obese patients, its safety and success has not been fully elucidated. The current study describes the worldwide prevalence of obesity in patients with urolithiasis and examines trends in URS outcomes, safety, and efficacy. METHODS: This study utilized the Clinical Research Office of the Endourological Society (CROES) URS Global Study, which was a prospective, multicenter study including 11,885 patients treated with URS for urinary stones at 1 of 114 urology departments across 32 countries...
November 29, 2016: Journal of Endourology
https://www.readbyqxmd.com/read/27783241/fe-deficiency-induced-changes-in-rice-oryza-sativa-l-thylakoids
#13
Yuwen Wang, Chao Xu, Kang Li, Xiaojie Cai, Min Wu, Guoxiang Chen
Iron deficiency is an important abiotic stress that limits productivity of crops all over the world. We selected a hybrid rice (Oryza sativa L.), LYPJ, which is super high-yield and widely cultured in China, to investigate changes in the components and structure of thylakoid membranes and photosynthetic performance in response to iron deficiency. Our results demonstrated that photosystem I (PSI) is the primary target for iron deficiency, while the changes in photosystem II (PSII) are important for rebuilding a balance in disrupted energy utilization and dissipation caused by differential degradation of photosynthetic components...
October 25, 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/27774452/rna-sequencing-of-formalin-fixed-paraffin-embedded-specimens-for-gene-expression-quantification-and-data-mining
#14
Yan Guo, Jie Wu, Shilin Zhao, Fei Ye, Yinghao Su, Travis Clark, Quanhu Sheng, Brian Lehmann, Xiao-Ou Shu, Qiuyin Cai
Background. Proper rRNA depletion is crucial for the successful utilization of FFPE specimens when studying gene expression. We performed a study to evaluate two major rRNA depletion methods: Ribo-Zero and RNase H. RNAs extracted from 4 samples were treated with the two rRNA depletion methods in duplicate and sequenced (N = 16). We evaluated their reducibility, ability to detect RNA, and ability to molecularly subtype these triple negative breast cancer specimens. Results. Both rRNA depletion methods produced consistent data between the technical replicates...
2016: International Journal of Genomics
https://www.readbyqxmd.com/read/27759378/synthesis-of-plasmon-enhanced-near-infrared-persistent-luminescence-gdalo3-mn-4-ge-4-au-core-shell-nanoprobes-for-in-vivo-tri-modality-bioimaging
#15
Jing-Min Liu, Yao-Yao Liu, Dong-Dong Zhang, Guozhen Fang, Shuo Wang
The rise of multimodal nanoprobes has promoted the development of new methods to explore multiple molecular targets simultaneously, or to combine various bioimaging tools in one assay to more clearly delineate localization and expression of bio-markers. Persistent luminescence nanophosphors (PLNPs) have been qualified as the promising contrast agent for in vivo imaging. The easy surface modification and proper nanostructure design strategy would favor the fabrication of PLNPs based multi-functional nanoprobes for biological application...
October 19, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27753082/costs-and-cost-driving-factors-for-acute-treatment-of-adults-with-status-epilepticus-a-multicenter-cohort-study-from-germany
#16
Lena-Marie Kortland, Anne Alfter, Oliver Bähr, Barbara Carl, Richard Dodel, Thomas M Freiman, Kristina Hubert, Kolja Jahnke, Susanne Knake, Felix von Podewils, Jens-Peter Reese, Uwe Runge, Christian Senft, Helmuth Steinmetz, Felix Rosenow, Adam Strzelczyk
OBJECTIVE: To provide first data on inpatient costs and cost-driving factors due to nonrefractory status epilepticus (NSE), refractory status epilepticus (RSE), and super-refractory status epilepticus (SRSE). METHODS: In 2013 and 2014, all adult patients treated due to status epilepticus (SE) at the university hospitals in Frankfurt, Greifswald, and Marburg were analyzed for healthcare utilization. RESULTS: We evaluated 341 admissions in 316 patients (65...
October 18, 2016: Epilepsia
https://www.readbyqxmd.com/read/27738013/super-dry-reforming-of-methane-intensifies-co2-utilization-via-le-chatelier-s-principle
#17
Lukas C Buelens, Vladimir V Galvita, Hilde Poelman, Christophe Detavernier, Guy B Marin
Efficient CO2 transformation from a waste product to carbon source for chemicals and fuels will require reaction conditions that effect its reduction. We develop a "super-dry" CH4 reforming reaction for enhanced CO production from CH4 and CO2 We used Ni/MgAl2O4 as a CH4 reforming catalyst, Fe2O3/MgAl2O4 as a solid oxygen carrier, and CaO/Al2O3 as a CO2 sorbent. The isothermal coupling of these three different processes resulted in higher CO production compared with conventional dry reforming by avoiding back reactions with water...
October 13, 2016: Science
https://www.readbyqxmd.com/read/27725384/novel-bio-imaging-tools-based-on-the-precise-design-of-functional-fluorescence-probes
#18
Mako Kamiya
 Fluorescence imaging is one of the most powerful techniques currently available for continuous observation of intracellular processes in living cells and tissues, and so it would be useful to have a large toolset of fluorescence probes suitable for visualizing bioactive molecules or biological phenomena. However, design strategies for small molecule-based fluorescence probes have been limited. Therefore, we are interested in establishing novel rational design strategies for developing functional fluorescence probes...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/27723151/water-soluble-thermostable-photomodulated-color-switching-quantum-dots
#19
Sebastián A Díaz, Florencia Gillanders, Kimihiro Susumo, Eunkeu Oh, Igor L Medintz, Thomas M Jovin
Photoswitchable probes are of great utility in fluorescence microscopy, permitting numerous determinations, including molecular localization for super-resolution, based on their modifiable emission intensity and spectra. We have coated a blue (425 nm) emitting quantum dot (QD) with a diheteroarylethene photochrome (PCf), the closed form isomer of which has absorption and emission maxima at 440 and 520-530 nm, respectively, and thus functions as a fluorescent acceptor for the QD donor in Förster resonance energy transfer (FRET)...
October 9, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27720595/drug-therapy-problems-and-medication-discrepancies-during-care-transitions-in-super-utilizers
#20
Satya Surbhi, Kiraat D Munshi, Paula C Bell, James E Bailey
OBJECTIVES: First, to investigate the prevalence and types of drug therapy problems and medication discrepancies among super-utilizers, and associated patient characteristics. Second, to examine the outcomes of pharmacist recommendations and estimated cost avoidance through care transitions support focused on medication management. DESIGN: Retrospective analysis of the pharmacist-led interventions as part of the SafeMed Program. SETTING: A large nonprofit health care system serving the major medically underserved areas in Memphis, Tennessee...
November 2016: Journal of the American Pharmacists Association: JAPhA
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