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https://www.readbyqxmd.com/read/28924037/intrinsically-disordered-sequences-enable-modulation-of-protein-phase-separation-through-distributed-tyrosine-motifs
#1
Yuan Lin, Simon L Currie, Michael Keith Rosen
Liquid-liquid phase separation (LLPS) is thought to contribute to establishment of many biomolecular condensates, eukaryotic cell structures that concentrate diverse macromolecules but lack a bounding membrane. RNA granules control RNA metabolism and comprise a large class of condensates that are enriched in RNA-binding proteins and RNA molecules. Many RNA granule proteins are composed of both modular domains and intrinsically disordered regions (IDRs) having low amino acid sequence complexity. Phase separation of these molecules likely plays an important role in the generation and stability of RNA granules...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28917222/validation-of-summer-and-winter-elisa-measurements-of-serum-25-hydroxyvitamin-d-concentrations-in-mongolia
#2
Sabri Bromage, Daria Tselmen, Gary Bradwin, Michael F Holick, Davaasaambuu Ganmaa
BACKGROUND AND OBJECTIVES: Assay cost, quality, and availability pose challenges for vitamin D surveys in limited resource settings. This study aimed to validate an inexpensive vitamin D assay (ELISA) under real-world conditions in Mongolia, the northernmost developing country, to characterize the assay's usefulness and inform the design of epidemiologic studies in similar regions. METHODS AND STUDY DESIGN: We collected paired summer and winter serum samples from 120 men and women (aged 20-57 years) in urban and rural Mongolia, analyzed each sample for 25(OH)D concentration using both Immunodiagnostic Systems ELISA and DiaSorin LIAISON 25(OH)D TOTAL, and compared the assays using multiple statistics...
2017: Asia Pacific Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28916751/understanding-cry2-interactions-for-optical-control-of-intracellular-signaling
#3
Liting Duan, Jen Hope, Qunxiang Ong, Hsin-Ya Lou, Namdoo Kim, Comfrey McCarthy, Victor Acero, Michael Z Lin, Bianxiao Cui
Arabidopsis cryptochrome 2 (CRY2) can simultaneously undergo light-dependent CRY2-CRY2 homo-oligomerization and CRY2-CIB1 hetero-dimerization, both of which have been widely used to optically control intracellular processes. Applications using CRY2-CIB1 interaction desire minimal CRY2 homo-oligomerization to avoid unintended complications, while those utilizing CRY2-CRY2 interaction prefer robust homo-oligomerization. However, selecting the type of CRY2 interaction has not been possible as the molecular mechanisms underlying CRY2 interactions are unknown...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28916725/characterization-of-enhancers-and-the-role-of-the-transcription-factor-klf7-in-regulating-corneal-epithelial-differentiation
#4
Rachel Herndon Klein, William Hu, Ghaidaa Kashgari, Ziguang Lin, Tuyen Nguyen, Michael Doan, Bogi Andersen
During tissue development, transcription factors bind regulatory DNA regions called enhancers, often located at great distances from the genes they regulate, to control gene expression. The enhancer landscape during embryonic stem cell differentiation has been well characterized. By contrast, little is known about the shared and unique enhancer regulatory mechanisms in different ectodermally derived epithelial cells. Here, we use ChIP-seq to identify domains enriched for histone marks H3K4me3, H3K4me1, and H3K27ac, and define for the first time the super enhancers and typical enhancers active in primary human corneal epithelial cells...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916225/stereotactic-radiosurgery-of-early-melanoma-brain-metastases-after-initiation-of-anti-ctl-4-treatment-is-associated-with-improved-intracranial-control
#5
Yi An, Wen Jiang, Betty Y S Kim, Jack M Qian, Chad Tang, Penny Fang, Jennifer Logan, Neil M D'Souza, Lauren E Haydu, Xin A Wang, Kenneth R Hess, Harriet Kluger, Isabella C Glitza, Anita Mahajan, James W Welsh, Steven H Lin, James B Yu, Michael A Davies, Patrick Hwu, Erik P Sulman, Paul D Brown, Veronica L S Chiang, Jing Li
BACKGROUND: Numerous studies suggest that radiation can boost antitumor immune response by stimulating release of tumor-specific antigens. However, the optimal timing between radiotherapy and immune checkpoint blockade to achieve potentially synergistic benefits is unclear. MATERIAL AND METHODS: Multi-institutional retrospective analysis was conducted of ninety-nine metastatic melanoma patients from 2007 to 2014 treated with ipilimumab who later received stereotactic radiosurgery (SRS) for new brain metastases that developed after starting immunotherapy...
September 12, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28913423/opto-thermophoretic-assembly-of-colloidal-matter
#6
Linhan Lin, Jianli Zhang, Xiaolei Peng, Zilong Wu, Anna C H Coughlan, Zhangming Mao, Michael A Bevan, Yuebing Zheng
Colloidal matter exhibits unique collective behaviors beyond what occurs at single-nanoparticle and atomic scales. Treating colloidal particles as building blocks, researchers are exploiting new strategies to rationally organize colloidal particles into complex structures for new functions and devices. Despite tremendous progress in directed assembly and self-assembly, a truly versatile assembly technique without specific functionalization of the colloidal particles remains elusive. We develop a new strategy to assemble colloidal matter under a light-controlled temperature field, which can solve challenges in the existing assembly techniques...
September 2017: Science Advances
https://www.readbyqxmd.com/read/28905451/gene-edited-human-kidney-organoids-reveal-mechanisms-of-disease-in-podocyte-development
#7
Yong Kyun Kim, Ido Refaeli, Craig R Brooks, Peifeng Jing, Ramila E Gulieva, Michael R Hughes, Nelly M Cruz, Yannan Liu, Angela J Churchill, Yuliang Wang, Hongxia Fu, Jeffrey W Pippin, Lih Y Lin, Stuart J Shankland, A Wayne Vogl, Kelly M McNagny, Benjamin S Freedman
A critical event during kidney organogenesis is the differentiation of podocytes, specialized epithelial cells that filter blood plasma to form urine. Podocytes derived from human pluripotent stem cells (hPSC-podocytes) have recently been generated in nephron-like kidney organoids, but the developmental stage of these cells and their capacity to reveal disease mechanisms remains unclear. Here we show that hPSC-podocytes phenocopy mammalian podocytes at the capillary loop stage (CLS), recapitulating key features of ultrastructure, gene expression, and mutant phenotype...
September 14, 2017: Stem Cells
https://www.readbyqxmd.com/read/28904193/mutations-in-the-fusion-protein-of-measles-virus-that-confer-resistance-to-the-membrane-fusion-inhibitors-carbobenzoxy-d-phe-l-phe-gly-and-as-48
#8
Michael N Ha, Sébastien Delpeut, Ryan S Noyce, Gary Sisson, Karen M Black, Liang-Tzung Lin, Darius Bilimoria, Richard K Plemper, Gilbert G Privé, Christopher D Richardson
The inhibitors Z-d-Phe-l-Phe Gly (fusion inhibitor peptide, FIP) and AS-48 have similar efficacy in blocking membrane fusion and syncytia formation mediated by measles virus. Other homologues such as Z-d-Phe are less effective, but may act through the same mechanism. In an attempt to map the site of action of these inhibitors, we generated mutant viruses which were resistant to the inhibitory effects of Z-d-Phe-l-Phe Gly. These 10 mutations were localized to the heptad repeat region (HRB) of the fusion protein and no changes were observed in the viral hemagglutinin, which is the receptor attachment protein...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28902999/self-assembled-2d-free-standing-janus-nanosheets-with-single-layer-thickness
#9
Yiyang Lin, Michael R Thomas, Amy Gelmi, Vincent Leonardo, E Thomas Pashuck, Stephanie A Maynard, Ye Wang, Molly M Stevens
We report the thermodynamically controlled growth of solution-processable and free-standing nanosheets via peptide assembly in two dimensions. By taking advantage of self-sorting between peptide β-strands and hydrocarbon chains, we have demonstrated the formation of Janus 2D structures with single-layer thickness, which enable a predetermined surface heterofunctionalization. A controlled 2D-to-1D morphological transition was achieved by subtly adjusting the intermolecular forces. These nanosheets provide an ideal substrate for the engineering of guest components (e...
September 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28898252/impact-of-common-genetic-determinants-of-hemoglobin-a1c-on-type-2-diabetes-risk-and-diagnosis-in-ancestrally-diverse-populations-a-transethnic-genome-wide-meta-analysis
#10
Eleanor Wheeler, Aaron Leong, Ching-Ti Liu, Marie-France Hivert, Rona J Strawbridge, Clara Podmore, Man Li, Jie Yao, Xueling Sim, Jaeyoung Hong, Audrey Y Chu, Weihua Zhang, Xu Wang, Peng Chen, Nisa M Maruthur, Bianca C Porneala, Stephen J Sharp, Yucheng Jia, Edmond K Kabagambe, Li-Ching Chang, Wei-Min Chen, Cathy E Elks, Daniel S Evans, Qiao Fan, Franco Giulianini, Min Jin Go, Jouke-Jan Hottenga, Yao Hu, Anne U Jackson, Stavroula Kanoni, Young Jin Kim, Marcus E Kleber, Claes Ladenvall, Cecile Lecoeur, Sing-Hui Lim, Yingchang Lu, Anubha Mahajan, Carola Marzi, Mike A Nalls, Pau Navarro, Ilja M Nolte, Lynda M Rose, Denis V Rybin, Serena Sanna, Yuan Shi, Daniel O Stram, Fumihiko Takeuchi, Shu Pei Tan, Peter J van der Most, Jana V Van Vliet-Ostaptchouk, Andrew Wong, Loic Yengo, Wanting Zhao, Anuj Goel, Maria Teresa Martinez Larrad, Dörte Radke, Perttu Salo, Toshiko Tanaka, Erik P A van Iperen, Goncalo Abecasis, Saima Afaq, Behrooz Z Alizadeh, Alain G Bertoni, Amelie Bonnefond, Yvonne Böttcher, Erwin P Bottinger, Harry Campbell, Olga D Carlson, Chien-Hsiun Chen, Yoon Shin Cho, W Timothy Garvey, Christian Gieger, Mark O Goodarzi, Harald Grallert, Anders Hamsten, Catharina A Hartman, Christian Herder, Chao Agnes Hsiung, Jie Huang, Michiya Igase, Masato Isono, Tomohiro Katsuya, Chiea-Chuen Khor, Wieland Kiess, Katsuhiko Kohara, Peter Kovacs, Juyoung Lee, Wen-Jane Lee, Benjamin Lehne, Huaixing Li, Jianjun Liu, Stephane Lobbens, Jian'an Luan, Valeriya Lyssenko, Thomas Meitinger, Tetsuro Miki, Iva Miljkovic, Sanghoon Moon, Antonella Mulas, Gabriele Müller, Martina Müller-Nurasyid, Ramaiah Nagaraja, Matthias Nauck, James S Pankow, Ozren Polasek, Inga Prokopenko, Paula S Ramos, Laura Rasmussen-Torvik, Wolfgang Rathmann, Stephen S Rich, Neil R Robertson, Michael Roden, Ronan Roussel, Igor Rudan, Robert A Scott, William R Scott, Bengt Sennblad, David S Siscovick, Konstantin Strauch, Liang Sun, Morris Swertz, Salman M Tajuddin, Kent D Taylor, Yik-Ying Teo, Yih Chung Tham, Anke Tönjes, Nicholas J Wareham, Gonneke Willemsen, Tom Wilsgaard, Aroon D Hingorani, Josephine Egan, Luigi Ferrucci, G Kees Hovingh, Antti Jula, Mika Kivimaki, Meena Kumari, Inger Njølstad, Colin N A Palmer, Manuel Serrano Ríos, Michael Stumvoll, Hugh Watkins, Tin Aung, Matthias Blüher, Michael Boehnke, Dorret I Boomsma, Stefan R Bornstein, John C Chambers, Daniel I Chasman, Yii-Der Ida Chen, Yduan-Tsong Chen, Ching-Yu Cheng, Francesco Cucca, Eco J C de Geus, Panos Deloukas, Michele K Evans, Myriam Fornage, Yechiel Friedlander, Philippe Froguel, Leif Groop, Myron D Gross, Tamara B Harris, Caroline Hayward, Chew-Kiat Heng, Erik Ingelsson, Norihiro Kato, Bong-Jo Kim, Woon-Puay Koh, Jaspal S Kooner, Antje Körner, Diana Kuh, Johanna Kuusisto, Markku Laakso, Xu Lin, Yongmei Liu, Ruth J F Loos, Patrik K E Magnusson, Winfried März, Mark I McCarthy, Albertine J Oldehinkel, Ken K Ong, Nancy L Pedersen, Mark A Pereira, Annette Peters, Paul M Ridker, Charumathi Sabanayagam, Michele Sale, Danish Saleheen, Juha Saltevo, Peter Eh Schwarz, Wayne H H Sheu, Harold Snieder, Timothy D Spector, Yasuharu Tabara, Jaakko Tuomilehto, Rob M van Dam, James G Wilson, James F Wilson, Bruce H R Wolffenbuttel, Tien Yin Wong, Jer-Yuarn Wu, Jian-Min Yuan, Alan B Zonderman, Nicole Soranzo, Xiuqing Guo, David J Roberts, Jose C Florez, Robert Sladek, Josée Dupuis, Andrew P Morris, E-Shyong Tai, Elizabeth Selvin, Jerome I Rotter, Claudia Langenberg, Inês Barroso, James B Meigs
BACKGROUND: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c...
September 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28893827/atrial-fibrillation-guideline-summary
#11
Jennifer L Frost, Doug Campos-Outcalt, David Hoelting, Michael LeFevre, Kenneth W Lin, William Vaughan, Melanie D Bird
No abstract text is available yet for this article.
September 2017: Annals of Family Medicine
https://www.readbyqxmd.com/read/28893793/chemical-genomic-interaction-profiling-reveals-determinants-of-intrinsic-antibiotic-resistance-in-mycobacterium-tuberculosis
#12
Weizhen Xu, Michael A DeJesus, Nadine Rücker, Curtis A Engelhart, Meredith G Wright, Claire Healy, Kan Lin, Ruojun Wang, Sae Woong Park, Thomas R Ioerger, Dirk Schnappinger, Sabine Ehrt
Chemotherapy for tuberculosis (TB) is lengthy and could benefit from synergistic adjuvant therapeutics that enhance current and novel drug regimens. To identify genetic determinants of intrinsic antibiotic susceptibility in Mycobacterium tuberculosis (Mtb) we applied a chemical genetic interaction (CGI) profiling approach. We screened a saturated transposon mutant library and identified mutants that exhibit altered fitness in the presence of partially-inhibitory concentrations of rifampicin, ethambutol, isoniazid, vancomycin and meropenem, antibiotics of diverse mechanisms-of-action...
September 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28890168/sleep-disturbances-increase-the-risk-of-dementia-a-systematic-review-and-meta-analysis
#13
REVIEW
Le Shi, Si-Jing Chen, Meng-Ying Ma, Yan-Ping Bao, Ying Han, Yu-Mei Wang, Jie Shi, Michael V Vitiello, Lin Lu
Sleep disturbances and dementia are two common and significant health problems in older adults. Investigations suggest that sleep disturbances might increase the risk of dementia. The aim of the present study was to systematically review and meta-analyze the predictive roles of overall sleep disturbances, their subtypes (e.g., insomnia, sleep disordered breathing [SDB]), and other sleep problems (e.g., excessive daytime sleepiness, sleep-related movement disorder, circadian rhythm sleep disorder, and nonspecific sleep problems) in incident all-cause dementia and Alzheimer's disease (AD) and vascular dementia subtypes...
July 6, 2017: Sleep Medicine Reviews
https://www.readbyqxmd.com/read/28889288/gauging-and-visualizing-c-di-gmp-levels-in-pseudomonas-aeruginosa-using-fluorescence-based-biosensors
#14
Morten Rybtke, Song Lin Chua, Joey Kuok Hoong Yam, Michael Givskov, Liang Yang, Tim Tolker-Nielsen
Recent research has shown that the molecule c-di-GMP is an important second messenger regulating various functions in bacteria. In particular, the implication of c-di-GMP as a positive regulator of adhesion and biofilm formation has gained momentum as a highly relevant research topic, as detailed knowledge about the underlying regulatory mechanisms may enable the development of measures to control biofilms in both industrial and medical settings. Accordingly, it is in many cases of interest to measure the c-di-GMP level in bacteria under specific conditions or in specific mutant strains...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28886335/macromolecular-assemblies-of-the-mammalian-circadian-clock
#15
Rajindra P Aryal, Pieter Bas Kwak, Alfred G Tamayo, Michael Gebert, Po-Lin Chiu, Thomas Walz, Charles J Weitz
The mammalian circadian clock is built on a feedback loop in which PER and CRY proteins repress their own transcription. We found that in mouse liver nuclei all three PERs, both CRYs, and Casein Kinase-1δ (CK1δ) are present together in an ∼1.9-MDa repressor assembly that quantitatively incorporates its CLOCK-BMAL1 transcription factor target. Prior to incorporation, CLOCK-BMAL1 exists in an ∼750-kDa complex. Single-particle electron microscopy (EM) revealed nuclear PER complexes purified from mouse liver to be quasi-spherical ∼40-nm structures...
September 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28886243/enantioselective-synthesis-of-1-3-disubstituted-1-3-dihydroisobenzofurans-via-a-cascade-allylboration-oxo-michael-reaction-of-o-formyl-chalcones-catalyzed-by-a-chiral-phosphoric-acid
#16
Xing Yang, Shuai Pang, Feng Cheng, Yue Zhang, Ya-Wei Lin, Quan Yuan, Fang-Lin Zhang, Yi-Yong Huang
The first chiral Brønsted acid-catalyzed asymmetric cascade allylboration/oxo-Michael reaction between o-formyl chalcones and allylboronate has been successfully realized, which afforded chiral 1,3-disubstituted 1,3-dihydroisobenzofurans with yield, diastereoselective ratio (dr) and enantioselective excess (ee) up to 94%, 2.5:1 and 98%, respectively. In addition, 2,3-dienylboronic pinacol ester was also applied into this cascade reaction with good catalytic results.
September 8, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28885247/novel-glaucoma-drug-delivery-devices
#17
Michael M Lin, Joseph B Ciolino, Louis R Pasquale
No abstract text is available yet for this article.
2017: International Ophthalmology Clinics
https://www.readbyqxmd.com/read/28884018/pp2a-b-holoenzyme-substrate-recognition-regulation-and-role-in-cytokinesis
#18
Cheng-Guo Wu, Hui Chen, Feng Guo, Vikash K Yadav, Sean J Mcilwain, Michael Rowse, Alka Choudhary, Ziqing Lin, Yitong Li, Tingjia Gu, Aiping Zheng, Qingge Xu, Woojong Lee, Eduard Resch, Benjamin Johnson, Jenny Day, Ying Ge, Irene M Ong, Mark E Burkard, Ylva Ivarsson, Yongna Xing
Protein phosphatase 2A (PP2A) is a major Ser/Thr phosphatase; it forms diverse heterotrimeric holoenzymes that counteract kinase actions. Using a peptidome that tiles the disordered regions of the human proteome, we identified proteins containing [LMFI]xx[ILV]xEx motifs that serve as interaction sites for B'-family PP2A regulatory subunits and holoenzymes. The B'-binding motifs have important roles in substrate recognition and in competitive inhibition of substrate binding. With more than 100 novel ligands identified, we confirmed that the recently identified LxxIxEx B'α-binding motifs serve as common binding sites for B' subunits with minor variations, and that S/T phosphorylation or D/E residues at positions 2, 7, 8 and 9 of the motifs reinforce interactions...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28883499/a-reminder-before-extinction-strengthens-episodic-memory-via-reconsolidation-but-fails-to-disrupt-generalized-threat-responses
#19
Marijn C W Kroes, Joseph E Dunsmoor, Qi Lin, Michael Evans, Elizabeth A Phelps
A reminder can temporarily renew flexibility of consolidated memories, referred to as reconsolidation. Pavlovian threat-conditioning studies suggest that a reminder can renew flexibility of threat responses but that episodic memories remain stable. In contrast, outside the threat-conditioning domain, studies testing memory for word lists or stories find that a reminder can renew flexibility of episodic memory. This discrepancy in findings leaves it unclear if episodic memories reconsolidate, or only Pavlovian responses...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28882873/abca8-regulates-cholesterol-efflux-and-high-density-lipoprotein-cholesterol-levels
#20
Laia Trigueros-Motos, Julian C van Capelleveen, Federico Torta, David Castaño, Lin-Hua Zhang, Caryn Chai, Martin Kang, Lidiya G Dimova, Alinda W M Schimmel, Ian Tietjen, Chris Radomski, Liang Juin Tan, Thiam Chung Hwee, Pradeep Narayanaswamy, Daniel Wu, Fabian Dorninger, Gopala Krishna Yakala, Amina Barhdadi, Veronique Angeli, Marie-Pierre Dubé, Johannes Berger, Geesje M Dallinga-Thie, Uwe J F Tietge, Markus R Wenk, Michael R Hayden, G Kees Hovingh, Roshni R Singaraja
OBJECTIVE: High-density lipoproteins (HDL) are considered to protect against atherosclerosis in part by facilitating the removal of cholesterol from peripheral tissues. However, factors regulating lipid efflux are incompletely understood. We previously identified a variant in adenosine triphosphate-binding cassette transporter A8 (ABCA8) in an individual with low HDL cholesterol (HDLc). Here, we investigate the role of ABCA8 in cholesterol efflux and in regulating HDLc levels. APPROACH AND RESULTS: We sequenced ABCA8 in individuals with low and high HDLc and identified, exclusively in low HDLc probands, 3 predicted deleterious heterozygous ABCA8 mutations (p...
September 7, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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