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https://www.readbyqxmd.com/read/28445761/live-cell-super-resolution-reveals-f-actin-and-plasma-membrane-dynamics-at-the-t-cell-synapse
#1
George W Ashdown, Garth L Burn, David J Williamson, Elvis Pandžić, Ruby Peters, Michael Holden, Helge Ewers, Lin Shao, Paul W Wiseman, Dylan M Owen
The cortical actin cytoskeleton has been shown to be critical for the reorganization and heterogeneity of plasma membrane components of many cells, including T cells. Building on previous studies at the T cell immunological synapse, we quantitatively assess the structure and dynamics of this meshwork using live-cell superresolution fluorescence microscopy and spatio-temporal image correlation spectroscopy. We show for the first time, to our knowledge, that not only does the dense actin cortex flow in a retrograde fashion toward the synapse center, but the plasma membrane itself shows similar behavior...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28441076/a-novel-neuroprotective-small-molecule-for-glial-cell-derived-neurotrophic-factor-induction-and-photoreceptor-rescue
#2
Petr Baranov, Hong Lin, Kathryn McCabe, David Gale, Shenshen Cai, Burke Lieppman, Dwight Morrow, Phoebe Lei, Justin Liao, Michael Young
PURPOSE: Degenerative diseases of the retina, such as retinitis pigmentosa and age-related macular degeneration, are characterized by the irreversible loss of photoreceptors. Several growth factors, including glial cell derived neurotrophic factor (GDNF), have been shown to rescue retinal neurons. An alternative strategy to direct GDNF administration is its induction in host retina by small molecules. Here we studied the ability of a novel small molecule GSK812 to induce GDNF in vitro/in vivo and rescue photoreceptors...
April 25, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28441025/structures-interconversions-and-spectroscopy-of-iron-carbonyl-clusters-with-an-interstitial-carbide-localized-metal-center-reduction-by-overall-cluster-oxidation
#3
Subramaniam Kuppuswamy, Joshua D Wofford, Chris Joseph, Zhu-Lin Xie, Azim K Ali, Vincent M Lynch, Paul A Lindahl, Michael J Rose
The syntheses, interconversions, and spectroscopic properties of a set of iron carbonyl clusters containing an interstitial carbide are reported. This includes the low temperature X-ray structures of the six-iron clusters (Y)2[Fe6(μ6-C)(μ2-CO)4(CO)12] (1a-c; where Y = NMe4, NEt4, PPh4); the five-iron cluster [Fe5(μ5-C)(CO)15] (3); and the novel formulation of the five-iron cluster (NMe4)2[Fe5(μ5-C)(μ2-CO)(CO)13] (4). Also included in this set is the novel charge-neutral cluster, [Fe6(μ6-C)(CO)18] (2), for which we were unable to obtain a crystallographic structure...
April 25, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28440318/corrigendum-proteogenomic-integration-reveals-therapeutic-targets-in-breast-cancer-xenografts
#4
Kuan-Lin Huang, Shunqiang Li, Philipp Mertins, Song Cao, Harsha P Gunawardena, Kelly V Ruggles, D R Mani, Karl R Clauser, Maki Tanioka, Jerry Usary, Shyam M Kavuri, Ling Xie, Christopher Yoon, Jana W Qiao, John Wrobel, Matthew A Wyczalkowski, Petra Erdmann-Gilmore, Jacqueline E Snider, Jeremy Hoog, Purba Singh, Beifang Niu, Zhanfang Guo, Sam Qiancheng Sun, Souzan Sanati, Emily Kawaler, Xuya Wang, Adam Scott, Kai Ye, Michael D McLellan, Michael C Wendl, Anna Malovannaya, Jason M Held, Michael A Gillette, David Fenyö, Christopher R Kinsinger, Mehdi Mesri, Henry Rodriguez, Sherri R Davies, Charles M Perou, Cynthia Ma, R Reid Townsend, Xian Chen, Steven A Carr, Matthew J Ellis, Li Ding
No abstract text is available yet for this article.
April 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28437852/a-diagnostic-microdosing-approach-to-investigate-platinum-sensitivity-in-non-small-cell-lung-cancer
#5
Si-Si Wang, Maike Zimmermann, Hongyong Zhang, Tzu-Yin Lin, Michael Malfatti, Kurt Haack, Kenneth W Turteltaub, George D Cimino, Ralph de Vere White, Chong-Xian Pan, Paul T Henderson
The platinum-based drugs cisplatin, carboplatin and oxaliplatin are often used for chemotherapy, but drug resistance is common. The prediction of resistance to these drugs via genomics is a challenging problem since hundreds of genes are involved. A possible alternative is to use mass spectrometry to determine the propensity for cells to form drug-DNA adducts-the pharmacodynamic drug-target complex for this class of drugs. The feasibility of predictive diagnostic microdosing was assessed in non-small cell lung cancer (NSCLC) cell culture and a pilot clinical trial...
April 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28437162/adjuvant-systemic-therapy-and-adjuvant-radiation-therapy-for-stage-i-to-iiia-completely-resected-non-small-cell-lung-cancers-american-society-of-clinical-oncology-cancer-care-ontario-clinical-practice-guideline-update
#6
Mark G Kris, Laurie E Gaspar, Jamie E Chaft, Erin B Kennedy, Christopher G Azzoli, Peter M Ellis, Steven H Lin, Harvey I Pass, Rahul Seth, Frances A Shepherd, David R Spigel, John R Strawn, Yee C Ung, Michael Weyant
Purpose The panel updated the American Society of Clinical Oncology (ASCO) adjuvant therapy guideline for resected non-small-cell lung cancers. Methods ASCO convened an update panel and conducted a systematic review of the literature, investigating adjuvant therapy in resected non-small-cell lung cancers. Results The updated evidence base covered questions related to adjuvant systemic therapy and included a systematic review conducted by Cancer Care Ontario current to January 2016. A recent American Society for Radiation Oncology guideline and systematic review, previously endorsed by ASCO, was used as the basis for recommendations for adjuvant radiation therapy...
April 24, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28437062/molecular-arrangement-and-charge-transfer-in-c60-graphene-heterostructures
#7
Claudia Ojeda-Aristizabal, Elton J G Santos, Seita Onishi, Aiming Yan, Haider Imad Rasool, Salman Kahn, Yinchuan Lv, Drew Latzke, Jairo Velasco, Michael F Crommie, Matthew Sorensen, Kenneth Gotlieb, Chiu-Yun Lin, Kenji Watanabe, Takashi Taniguchi, Alessandra Lanzara, Alex Zettl
Charge transfer at the interface between dissimilar materials is at the heart of electronics and photovoltaics. Here we study the molecular orientation, electronic structure, and local charge transfer at the interface region of C60 deposited on graphene, with and without supporting substrates such as hexagonal boron nitride. We employ ab initio density functional theory with van der Waals (vdW) interactions, and experimentally characterize interface devices using high-resolution transmission electron microscopy and electronic transport...
April 24, 2017: ACS Nano
https://www.readbyqxmd.com/read/28436955/vitamin-a-mediates-conversion-of-monocyte-derived-macrophages-into-tissue-resident-macrophages-during-alternative-activation
#8
Uma Mahesh Gundra, Natasha M Girgis, Michael A Gonzalez, Mei San Tang, Hendrik J P Van Der Zande, Jian-Da Lin, Mireille Ouimet, Lily J Ma, Jordan Poles, Nikollaq Vozhilla, Edward A Fisher, Kathryn J Moore, P'ng Loke
It remains unclear whether activated inflammatory macrophages can adopt features of tissue-resident macrophages, or what mechanisms might mediate such a phenotypic conversion. Here we show that vitamin A is required for the phenotypic conversion of interleukin 4 (IL-4)-activated monocyte-derived F4/80(int)CD206(+)PD-L2(+)MHCII(+) macrophages into macrophages with a tissue-resident F4/80(hi)CD206(-)PD-L2(-)MHCII(-)UCP1(+) phenotype in the peritoneal cavity of mice and during the formation of liver granulomas in mice infected with Schistosoma mansoni...
April 24, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28433078/haplotype-counting-for-sensitive-chimerism-testing-potential-for-early-leukemia-relapse-detection
#9
Marija Debeljak, Evelina Mocci, Max C Morrison, Aparna Pallavajjalla, Katie Beierl, Marie Amiel, Michaël Noë, Laura D Wood, Ming-Tseh Lin, Christopher D Gocke, Alison P Klein, Ephraim J Fuchs, Richard J Jones, James R Eshleman
Fields of forensics, transplantation, and paternity rely on human identity testing. Currently, this is accomplished through amplification of microsatellites followed by capillary electrophoresis. An alternative and theoretically better approach uses multiple single-nucleotide polymorphisms located within a small region of DNA, a method we initially developed using HLA-A and called haplotype counting. Herein, we validated seven additional polymorphic loci, sequenced a total of 45 individuals from three of the 1000 Genomes populations (15 from each), and determined the number of haplotypes, heterozygosity, and polymorphic information content for each locus...
May 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28430197/g-quadruplex-organic-frameworks
#10
Yi-Lin Wu, Noah E Horwitz, Kan-Sheng Chen, Diego A Gomez-Gualdron, Norman S Luu, Lin Ma, Timothy C Wang, Mark C Hersam, Joseph T Hupp, Omar K Farha, Randall Q Snurr, Michael R Wasielewski
Two-dimensional covalent organic frameworks often π stack into crystalline solids that allow precise spatial positioning of molecular building blocks. Inspired by the hydrogen-bonded G-quadruplexes found frequently in guanine-rich DNA, here we show that this structural motif can be exploited to guide the self-assembly of naphthalene diimide and perylene diimide electron acceptors end-capped with two guanine electron donors into crystalline G-quadruplex-based organic frameworks, wherein the electron donors and acceptors form ordered, segregated π-stacked arrays...
May 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28430018/characterization-of-canna-yellow-mottle-virus-in-a-new-host-alpinia-purpurata-in-hawaii
#11
Jingxin Zhang, Kishore K Dey, Birun Lin, Wayne B Borth, Michael J Melzer, Diane Sether, Yanan Wang, I-Chin Wang, Huifang Shen, Xiaoming Pu, Dayuan Sun, John S Hu
Canna yellow mottle virus (CaYMV) is an important badnavirus infecting Canna spp. worldwide. This is the first report of CaYMV in flowering ginger (Alpinia purpurata) in Hawaii, where it is associated with yellow mottling and necrosis of leaves, vein streaking, and stunted plants. We have sequenced CaYMV in A. purpurata (CaYMV-Ap) using a combination of next-generation sequencing and traditional Sanger sequencing techniques. The complete genome of CaYMV-Ap was 7,120 bp with an organization typical of other Badnavirus species...
April 21, 2017: Phytopathology
https://www.readbyqxmd.com/read/28429794/bone-in-culture-array-as-a-platform-to-model-early-stage-bone-metastases-and-discover-anti-metastasis-therapies
#12
Hai Wang, Lin Tian, Amit Goldstein, Jun Liu, Hin-Ching Lo, Kuanwei Sheng, Thomas Welte, Stephen T C Wong, Zbigniew Gugala, Fabio Stossi, Chenghang Zong, Zonghai Li, Michael A Mancini, Xiang H-F Zhang
The majority of breast cancer models for drug discovery are based on orthotopic or subcutaneous tumours. Therapeutic responses of metastases, especially microscopic metastases, are likely to differ from these tumours due to distinct cancer-microenvironment crosstalk in distant organs. Here, to recapitulate such differences, we established an ex vivo bone metastasis model, termed bone-in-culture array or BICA, by fragmenting mouse bones preloaded with breast cancer cells via intra-iliac artery injection. Cancer cells in BICA maintain features of in vivo bone micrometastases regarding the microenvironmental niche, gene expression profile, metastatic growth kinetics and therapeutic responses...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429773/evaluation-of-the-precision-of-contrast-sensitivity-function-assessment-on-a-tablet-device
#13
Michael Dorr, Luis A Lesmes, Tobias Elze, Hui Wang, Zhong-Lin Lu, Peter J Bex
The contrast sensitivity function (CSF) relates the visibility of a spatial pattern to both its size and contrast, and is therefore a more comprehensive assessment of visual function than acuity, which only determines the smallest resolvable pattern size. Because of the additional dimension of contrast, estimating the CSF can be more time-consuming. Here, we compare two methods for rapid assessment of the CSF that were implemented on a tablet device. For a single-trial assessment, we asked 63 myopes and 38 emmetropes to tap the peak of a "sweep grating" on the tablet's touch screen...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427808/rapid-microwave-accelerated-synthesis-and-anti-osteoporosis-activities-evaluation-of-morusin-scaffolds-and-morusignin-l-scaffolds
#14
Bing Lin, Jun-Fei Huang, Xiong-Wei Liu, Xi-Tao Ma, Xiong-Li Liu, Yi Lu, Ying Zhou, Feng-Min Guo, Ting-Ting Feng
Described herein is a facile and efficient methodology toward the synthesis of Morusin scaffolds and Morusignin L scaffolds 4-9 and 12via a novel three-step approach (Michael addition or prenylation, cyclization and cyclization) and use a rapid, microwave-accelerated cyclization as the key step. Furthermore, their biological activities have been preliminarily demonstrated by in vitro evaluation for anti-osteoporosis activity. These Morusin, Morusignin L and newly synthesized compounds 5b, 6a, 8e, 8f greatly exhibited the highest potency, especially at the 10(-5)mol/L (P<0...
April 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28426890/fine-mapping-of-lipid-regions-in-global-populations-discovers-ethnic-specific-signals-and-refines-previously-identified-lipid-loci
#15
Niha Zubair, Mariaelisa Graff, Jose Luis Ambite, William S Bush, Gleb Kichaev, Yingchang Lu, Ani Manichaikul, Wayne H-H Sheu, Devin Absher, Themistocles L Assimes, Suzette J Bielinski, Erwin P Bottinger, Petra Buzkova, Lee-Ming Chuang, Ren-Hua Chung, Barbara Cochran, Logan Dumitrescu, Omri Gottesman, Jeffrey W Haessler, Christopher Haiman, Gerardo Heiss, Chao A Hsiung, Yi-Jen Hung, Chii-Min Hwu, Jyh-Ming J Juang, Loic Le Marchand, I-Te Lee, Wen-Jane Lee, Li-An Lin, Danyu Lin, Shih-Yi Lin, Rachel H Mackey, Lisa W Martin, Bogdan Pasaniuc, Ulrike Peters, Irene Predazzi, Thomas Quertermous, Alex P Reiner, Jennifer Robinson, Jerome I Rotter, Kelli K Ryckman, Pamela J Schreiner, Eli Stahl, Ran Tao, Michael Y Tsai, Lindsay L Waite, Tzung-Dau Wang, Steven Buyske, Yii-Der Ida Chen, Iona Cheng, Dana C Crawford, Ruth J F Loos, Stephen S Rich, Myriam Fornage, Kari E North, Charles Kooperberg, Cara L Carty
Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians...
December 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28425530/interfacial-interactions-between-cotpp-molecules-and-mgo-100-thin-films
#16
Matthias Franke, Daniel Wechsler, Quratulain Tariq, Michael Röckert, Liang Zhang, Pardeep Kumar Thakur, Nataliya Tsud, Sofiia Bercha, Kevin Prince, Tien-Lin Lee, Hans-Peter Steinrück, Ole Lytken
We have investigated the interactions between cobalt(ii)-tetraphenylporphyrin (CoTPP) molecules and MgO(100) thin films on Ag(100) by means of Synchrotron Radiation X-Ray and Ultra-Violet Photoelectron Spectroscopy (SR-XPS and SR-UPS). At room temperature, the CoTPP monolayer consists of two different species. A minority of molecules exhibits a strong electronic interaction with the substrate, whereas for the majority a similar spectroscopic signature as for multilayer molecules is observed. Based on the lateral inhomogeneity of the surface electronic structure, we tentatively suggest that the strongly interacting molecules adsorb with their metal center directly above oxygen ions...
April 20, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28425483/a-genome-wide-association-study-identifies-six-novel-risk-loci-for-primary-biliary-cholangitis
#17
Fang Qiu, Ruqi Tang, Xianbo Zuo, Xingjuan Shi, Yiran Wei, Xiaodong Zheng, Yaping Dai, Yuhua Gong, Lan Wang, Ping Xu, Xiang Zhu, Jian Wu, Chongxu Han, Yueqiu Gao, Kui Zhang, Yuzhang Jiang, Jianbo Zhou, Youlin Shao, Zhigang Hu, Ye Tian, Haiyan Zhang, Na Dai, Lei Liu, Xudong Wu, Weifeng Zhao, Xiaomin Zhang, Zhidong Zang, Jinshan Nie, Weihao Sun, Yi Zhao, Yuan Mao, Po Jiang, Hualiang Ji, Qing Dong, Junming Li, Zhenzhong Li, Xinli Bai, Li Li, Maosong Lin, Ming Dong, Jinxin Li, Ping Zhu, Chan Wang, Yanqiu Zhang, Peng Jiang, Yujue Wang, Rohil Jawed, Jing Xu, Yu Zhang, Qixia Wang, Yue Yang, Fan Yang, Min Lian, Xiang Jiang, Xiao Xiao, Yanmei Li, Jingyuan Fang, Dekai Qiu, Zhen Zhu, Hong Qiu, Jianqiong Zhang, Wenyan Tian, Sufang Chen, Ling Jiang, Bing Ji, Ping Li, Guochang Chen, Tianxue Wu, Yan Sun, Jianjiang Yu, Huijun Tang, Michun He, Min Xia, Hao Pei, Lihua Huang, Zhuye Qing, Jianfang Wu, Qinghai Huang, Junhai Han, Wei Xie, Zhongsheng Sun, Jian Guo, Gengsheng He, M Eric Gershwin, Zhexiong Lian, Xiang Liu, Michael F Seldin, Xiangdong Liu, Weichang Chen, Xiong Ma
Primary biliary cholangitis (PBC) is an autoimmune liver disease with a strong hereditary component. Here, we report a genome-wide association study that included 1,122 PBC cases and 4,036 controls of Han Chinese descent, with subsequent replication in a separate cohort of 907 PBC cases and 2,127 controls. Our results show genome-wide association of 14 PBC risk loci including previously identified 6p21 (HLA-DRA and DPB1), 17q12 (ORMDL3), 3q13.33 (CD80), 2q32.3 (STAT1/STAT4), 3q25.33 (IL12A), 4q24 (NF-κB) and 22q13...
April 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28424965/assessment-of-drug-drug-interaction-potential-between-ceritinib-and-proton-pump-inhibitors-in-healthy-subjects-and-in-patients-with-alk-positive-non-small-cell-lung-cancer
#18
Yvonne Y Lau, Wen Gu, Tiffany Lin, Kalyanee Viraswami-Appanna, Can Cai, Jeffrey W Scott, Michael Shi
PURPOSE: The impact of proton pump inhibitors (PPIs) on the pharmacokinetics (PK) and efficacy of ceritinib was evaluated. METHODS: A healthy subject drug-drug interaction (DDI) study was conducted to assess the effect of esomeprazole on the PK of a single 750 mg dose of ceritinib. To further investigate the impact of PPIs on the PK and efficacy of ceritinib in ALK-positive cancer patients, two subgroup analyses were performed. Analysis 1 evaluated ceritinib steady-state trough concentration (Ctrough,ss) and overall response rate (ORR) by concomitant use of PPIs in patients from the ASCEND-1, -2, and -3 studies; analysis 2 evaluated ceritinib single-dose and steady-state AUC0-24h and C max by concomitant PPI use in patients from ASCEND-1 using a definition of PPI usage similar to that used in the healthy subject study...
April 19, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28424327/rig-i-mavs-and-sting-signaling-promote-gut-integrity-during-irradiation-and-immune-mediated-tissue-injury
#19
Julius C Fischer, Michael Bscheider, Gabriel Eisenkolb, Chia-Ching Lin, Alexander Wintges, Vera Otten, Caroline A Lindemans, Simon Heidegger, Martina Rudelius, Sébastien Monette, Kori A Porosnicu Rodriguez, Marco Calafiore, Sophie Liebermann, Chen Liu, Stefan Lienenklaus, Siegfried Weiss, Ulrich Kalinke, Jürgen Ruland, Christian Peschel, Yusuke Shono, Melissa Docampo, Enrico Velardi, Robert R Jenq, Alan M Hanash, Jarrod A Dudakov, Tobias Haas, Marcel R M van den Brink, Hendrik Poeck
The molecular pathways that regulate the tissue repair function of type I interferon (IFN-I) during acute tissue damage are poorly understood. We describe a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute tissue damage in mice. Mice lacking mitochondrial antiviral-signaling protein (MAVS) were more sensitive to total body irradiation- and chemotherapy-induced intestinal barrier damage. These mice developed worse graft-versus-host disease (GVHD) in a preclinical model of allogeneic hematopoietic stem cell transplantation (allo-HSCT) than did wild-type mice...
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28424162/pembrolizumab-in-patients-with-chronic-lymphocytic-leukemia-with-richter-s-transformation-and-relapsed-cll
#20
Wei Ding, Betsy R LaPlant, Timothy G Call, Sameer A Parikh, Jose F Leis, Rong He, Tait D Shanafelt, Sutapa Sinha, Jennifer Le-Rademacher, Andrew L Feldman, Thomas M Habermann, Thomas E Witzig, Gregory A Wiseman, Yi Lin, Erik Asmus, Grzegorz S Nowakowski, Michael J Conte, Deborah A Bowen, Casey N Aitken, Daniel L Van Dyke, Patricia T Greipp, Xin Liu, Xiaosheng Wu, Henan Zhang, Charla R Secreto, Shulan Tian, Esteban Braggio, Linda E Wellik, Ivana Micallef, David S Viswanatha, Huihuang Yan, Asher A Chanan-Khan, Neil E Kay, Haidong Dong, Stephen M Ansell
CLL patients progressed early on ibrutinib often develop Richter's transformation (RT) with short survival about 4 months. Preclinical studies suggest that programmed death 1 (PD-1) pathway is critical to inhibit immune surveillance in CLL. This phase 2 study MC1485 (NCT02332980) was designed to test the efficacy and safety of pembrolizumab, a humanized PD-1-blocking antibody, at a dose of 200 mg every 3 weeks in relapsed and transformed CLL. Twenty-five patients including 16 relapsed CLL and 9 RT (all proven diffuse large cell lymphoma) patients were enrolled and 60% received prior ibrutinib...
April 19, 2017: Blood
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