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https://www.readbyqxmd.com/read/28646491/sickle-cells-produce-functional-immune-modulators-and-cytotoxics
#1
Chiao-Wang Sun, Li-Chen Wu, Peter L Knopick, David S Bradley, Tim Townes, David S Terman
Sickle erythrocytes' (SSRBCs) unique physical adaptation to hypoxic conditions renders them able to home to hypoxic tumor niches in vivo, shut down tumor blood flow and induce tumoricidal responses. SSRBCs are also useful vehicles for transport of encapsulated drugs and oncolytic virus into hypoxic tumors with enhanced anti-tumor effects. In search of additional modes for arming sickle cells with cytotoxics, we turned to a lentiviral β-globin vector with optimized Locus Control Region/β-globin coding region/promoter/enhancers...
June 24, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28646080/considerations-from-the-iq-induction-working-group-in-response-to-drug-drug-interaction-guidances-from-regulatory-agencies-focus-on-down-regulation-cyp2c-induction-and-cyp2b6-positive-control
#2
Niresh Hariparsad, Diane Ramsden, Jairam Palamanda, Joshua G Dekeyser, Odette A Fahmi, Jane R Kenny, Heidi Einolf, Michael Mohutsky, Magalie Pardon, Amy Y Siu, Liangfu Chen, Michael Sinz, Barry Jones, Robert Walsky, Shannon Dallas, Suresh K Balani, George Zhang, David Buckley, Donald Tweedie
The European Medicines Agency (EMA), the Pharmaceutical and Medical Devices Agency and the Food and Drug Administration have issued guidances for the conduct of drug-drug interaction (DDI) studies. To examine the applicability of these regulatory recommendations specifically for induction, a group of scientists, under the auspices of the Drug Metabolism Leadership Group of the Innovation and Quality (IQ) Consortium, formed the Induction Working Group (WG). A team of 20 scientists, from 16 of the 39 pharmaceutical companies, which are members of the IQ Consortium, and three Contract Research Organizations, reviewed the recommendations, focusing initially on the current EMA guidance...
June 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28645914/bile-salt-homeostasis-in-normal-and-bsep-gene-knock-out-rats-with-single-and-repeated-doses-of-troglitazone
#3
Yaofeng Cheng, Shenjue Chen, Chris Freeden, Weiqi Chen, Yueping Zhang, Pamela Abraham, David Nelson, William G Humphreys, Jinpin Gan, Yurong Lai
The interference of bile acid secretion through bile salt export pump (BSEP) inhibition was one of the mechanisms for troglitazone (TGZ) induced hepatotoxicity. Here we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep KO rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on Day-1 and Day-7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7...
June 23, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28645588/long-term-outcomes-of-mechanical-thrombectomy-for-the-treatment-of-acute-ischemic-stroke
#4
David McCarthy, Christian Theodotou, Samir Sur, Brian Snelling, Stephanie Chen, Eric C Peterson, Robert M Starke
No abstract text is available yet for this article.
June 20, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28645163/variations-in-chloroplast-movement-and-chlorophyll-fluorescence-among-chloroplast-division-mutants-under-light-stress
#5
Siddhartha Dutta, Jeffrey A Cruz, Saif M Imran, Jin Chen, David M Kramer, Katherine W Osteryoung
Chloroplasts divide to maintain consistent size, shape, and number in leaf mesophyll cells. Altered expression of chloroplast division proteins in Arabidopsis results in abnormal chloroplast morphology. To better understand the influence of chloroplast morphology on chloroplast movement and photosynthesis, we compared the chloroplast photorelocation and photosynthetic responses of a series of Arabidopsis chloroplast division mutants with a wide variety of chloroplast phenotypes. Chloroplast movement was monitored by red light reflectance imaging of whole plants under increasing intensities of white light...
June 22, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28644039/parkinson-s-disease-biomarkers-perspective-from-the-ninds-parkinson-s-disease-biomarkers-program
#6
Katrina Gwinn, Karen K David, Christine Swanson-Fischer, Roger Albin, Coryse St Hillaire-Clarke, Beth-Anne Sieber, Codrin Lungu, F DuBois Bowman, Roy N Alcalay, Debra Babcock, Ted M Dawson, Richard B Dewey, Tatiana Foroud, Dwight German, Xuemei Huang, Vlad Petyuk, Judith A Potashkin, Rachel Saunders-Pullman, Margaret Sutherland, David R Walt, Andrew B West, Jing Zhang, Alice Chen-Plotkin, Clemens R Scherzer, David E Vaillancourt, Liana S Rosenthal
Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development...
June 23, 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/28643776/ezrin-enhances-line-tension-along-transcellular-tunnel-edges-via-nmiia-driven-actomyosin-cable-formation
#7
Caroline Stefani, David Gonzalez-Rodriguez, Yosuke Senju, Anne Doye, Nadia Efimova, Sébastien Janel, Justine Lipuma, Meng Chen Tsai, Daniel Hamaoui, Madhavi P Maddugoda, Olivier Cochet-Escartin, Coline Prévost, Frank Lafont, Tatyana Svitkina, Pekka Lappalainen, Patricia Bassereau, Emmanuel Lemichez
Transendothelial cell macroaperture (TEM) tunnels control endothelium barrier function and are triggered by several toxins from pathogenic bacteria that provoke vascular leakage. Cellular dewetting theory predicted that a line tension of uncharacterized origin works at TEM boundaries to limit their widening. Here, by conducting high-resolution microscopy approaches we unveil the presence of an actomyosin cable encircling TEMs. We develop a theoretical cellular dewetting framework to interpret TEM physical parameters that are quantitatively determined by laser ablation experiments...
June 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28642306/-global-strategy-for-the-diagnosis-management-and-prevention-of-chronic-obstructive-lung-disease-2017-report-gold-executive-summary-claus-f-vogelmeier-gerard-j-criner-fernando-j-martinez-antonio-anzueto-peter-j-barnes-jean-bourbeau-bartolome-r-celli-rongchang
#8
https://www.readbyqxmd.com/read/28641124/neural-repair-by-nt3-chitosan-via-enhancement-of-endogenous-neurogenesis-after-adult-focal-aspiration-brain-injury
#9
Peng Hao, Hongmei Duan, Fei Hao, Lan Chen, Min Sun, Kevin S Fan, Yi Eve Sun, David Williams, Zhaoyang Yang, Xiaoguang Li
The latent regenerative potential of endogenous neural stem/progenitor cells (NSCs) in the adult mammalian brain has been postulated as a likely source for neural repair. However, the inflammatory and inhibitory microenvironment after traumatic brain injury (TBI) prohibits NSCs from generating new functional neurons to restore brain function. Here we report a biodegradable material, chitosan, which, when loaded with neurotrophin-3 (NT3) and injected into the lesion site after TBI, effectively engaged endogenous NSCs to proliferate and migrate to the injury area...
April 26, 2017: Biomaterials
https://www.readbyqxmd.com/read/28641109/rare-copy-number-variants-in-nrxn1-and-cntn6-increase-risk-for-tourette-syndrome
#10
Alden Y Huang, Dongmei Yu, Lea K Davis, Jae Hoon Sul, Fotis Tsetsos, Vasily Ramensky, Ivette Zelaya, Eliana Marisa Ramos, Lisa Osiecki, Jason A Chen, Lauren M McGrath, Cornelia Illmann, Paul Sandor, Cathy L Barr, Marco Grados, Harvey S Singer, Markus M Nöthen, Johannes Hebebrand, Robert A King, Yves Dion, Guy Rouleau, Cathy L Budman, Christel Depienne, Yulia Worbe, Andreas Hartmann, Kirsten R Müller-Vahl, Manfred Stuhrmann, Harald Aschauer, Mara Stamenkovic, Monika Schloegelhofer, Anastasios Konstantinidis, Gholson J Lyon, William M McMahon, Csaba Barta, Zsanett Tarnok, Peter Nagy, James R Batterson, Renata Rizzo, Danielle C Cath, Tomasz Wolanczyk, Cheston Berlin, Irene A Malaty, Michael S Okun, Douglas W Woods, Elliott Rees, Carlos N Pato, Michele T Pato, James A Knowles, Danielle Posthuma, David L Pauls, Nancy J Cox, Benjamin M Neale, Nelson B Freimer, Peristera Paschou, Carol A Mathews, Jeremiah M Scharf, Giovanni Coppola
Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (< 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (> 1 Mb), singleton events (OR = 2...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28641074/development-of-novel-antigen-receptors-for-car-t-cell-therapy-directed-toward-solid-malignancies
#11
REVIEW
David Chen, James Yang
Development of chimeric antigen receptor (CAR) T cells have led to remarkable successes in the treatment of B-cell malignancies with anti-CD19 CAR. Here we discuss the development of novel antigen receptors for use in solid malignancies with respect to target antigens, receptor design, and T cell manipulations.
June 1, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28639331/top-down-integration-of-molybdenum-disulfide-transistors-with-wafer-scale-uniformity-and-layer-controllability
#12
Mao-Lin Shi, Lin Chen, Tian-Bao Zhang, Jing Xu, Hao Zhu, Qing-Qing Sun, David Wei Zhang
The lack of stable and efficient techniques to synthesize high-quality large-area thin films is one of the major bottlenecks for the real-world application of the 2D transition metal dichalcogenides. In this work, the growth of molybdenum disulfide (MoS2 ) on sapphire substrates by sulfurizing the MoO3 film deposited by atomic layer deposition (ALD) is reported. The advantages of the ALD method can be well inherited, and the synthesized MoS2 films exhibit excellent layer controllability, wafer-scale uniformity, and homogeneity...
June 22, 2017: Small
https://www.readbyqxmd.com/read/28637830/a-light-harvesting-complex-like-protein-in-maintenance-of-photosynthetic-components-in-chlamydomonas
#13
Lei Zhao, Dongmei Cheng, Xiahe Huang, Mei Chen, Luca Dall'Osto, Jiale Xing, Liyan Gao, Lingyu Li, Yale Wang, Roberto Bassi, Lianwei Peng, Yingchun Wang, Jean-David Rochaix, Fang Huang
Using a genetic approach we have identified and characterized a novel protein, named Msf1 (Maintenance Factor for PSI), which is required for the maintenance of specific components of the photosynthetic apparatus in the green alga Chlamydomonas reinhardtii. Msf1 belongs to the superfamily of light-harvesting complex (LHC) proteins with three trans-membrane domains and consensus chlorophyll binding sites. Loss of Msf1 leads to reduced accumulation of PSI and chlorophyll-binding proteins/complexes. Msf1 is a component of a thylakoid complex containing key enzymes of the tetrapyrrole biosynthetic pathway thus revealing a possible link between Msf1 and chlorophyll biosynthesis...
June 21, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28637315/attenuated-effects-of-bile-acids-on-glucose-metabolism-and-insulin-sensitivity-in-a-male-mouse-model-of-prenatal-undernutrition
#14
Huijuan Ma, Vicencia M Sales, Ashley R Wolf, Sathish Subramanian, Tucker J Matthews, Michael Chen, Aparna Sharma, Walt Gall, Wim Kulik, David E Cohen, Yusuke Adachi, Nicholas W Griffin, Jeffrey I Gordon, Mary-Elizabeth Patti, Elvira Isganaitis
Prenatal undernutrition and low birth weight are associated with risk of type 2 diabetes and obesity. Prenatal caloric restriction results in low birth weight, glucose intolerance, obesity, and reduced plasma bile acids (BA) in offspring mice. Since BAs can regulate systemic metabolism and glucose homeostasis, we hypothesized that BA supplementation could prevent diet-induced obesity and glucose intolerance in this model of developmental programming. Pregnant dams were food restricted by 50% from gestational days 12...
June 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28636870/adherence-to-and-acceptability-of-listerine-%C3%A2-mouthwash-as-a-potential-preventive-intervention-for-pharyngeal-gonorrhoea-among-men-who-have-sex-with-men-in-australia-a-longitudinal-study
#15
Vincent J Cornelisse, Christopher K Fairley, Sandra Walker, Tameka Young, David Lee, Marcus Y Chen, Catriona S Bradshaw, Eric P F Chow
We investigated whether men who have sex with men (MSM) would use mouthwash daily to prevent pharyngeal gonorrhoea. Ten MSM attending the Melbourne Sexual Health Centre were asked to use a Listerine(®) alcohol-containing mouthwash daily for 14 days in August 2015. Mouthwash was used at least once daily for 133 of 140 person-days (95% of days; 95% confidence interval 90-98%). All 10 men were willing to use mouthwash on a daily basis, and nine men were willing to use mouthwash after oral sex. This study showed that daily use of mouthwash is an acceptable intervention to prevent pharyngeal gonorrhoea in MSM...
October 2016: Sexual Health
https://www.readbyqxmd.com/read/28636851/first-line-nivolumab-in-stage-iv-or-recurrent-non-small-cell-lung-cancer
#16
COMMENT
David P Carbone, Martin Reck, Luis Paz-Ares, Benjamin Creelan, Leora Horn, Martin Steins, Enriqueta Felip, Michel M van den Heuvel, Tudor-Eliade Ciuleanu, Firas Badin, Neal Ready, T Jeroen N Hiltermann, Suresh Nair, Rosalyn Juergens, Solange Peters, Elisa Minenza, John M Wrangle, Delvys Rodriguez-Abreu, Hossein Borghaei, George R Blumenschein, Liza C Villaruz, Libor Havel, Jana Krejci, Jesus Corral Jaime, Han Chang, William J Geese, Prabhu Bhagavatheeswaran, Allen C Chen, Mark A Socinski
BACKGROUND: Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. METHODS: We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles)...
June 22, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28636382/development-of-efficient-chemistry-to-generate-site-specific-disulfide-linked-protein-and-peptide-payload-conjugates-application-to-thiomab%C3%A2-antibody-drug-conjugates
#17
Jack David Sadowsky, Thomas H Pillow, Jinhua Chen, Fang Fan, Changrong He, Yanli Wang, Gang Yan, Hui Yao, Zijin Xu, Shanique Martin, Donglu Zhang, Phillip Chu, Josefa Dela Cruz-Chuh, Aimee O'Donohue, Guangmin Li, Geoffrey Del Rosario, Jintang He, Luna Liu, Carl K Ng, Dian Su, Gail D Lewis Phillips, Katherine Ruth Kozak, Shang-Fan Yu, Keyang Xu, Douglas Leipold, John S Wai
Conjugation of small molecule payloads to specific cysteine residues on proteins via a disulfide bond represents an attractive strategy to generate redox-sensitive bioconjugates, which have value as potential diagnostic reagents or therapeutics. Advancement of such "direct-disulfide" bioconjugates to the clinic necessitates chemical methods to form disulfide connections efficiently, without byproducts. The disulfide connection must also be resistant to premature cleavage by thiols prior to arrival at the targeted tissue...
June 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28635955/corrigendum-double-flow-focused-liquid-injector-for-efficient-serial-femtosecond-crystallography
#18
Dominik Oberthuer, Juraj Knoška, Max O Wiedorn, Kenneth R Beyerlein, David A Bushnell, Elena G Kovaleva, Michael Heymann, Lars Gumprecht, Richard A Kirian, Anton Barty, Valerio Mariani, Aleksandra Tolstikova, Luigi Adriano, Salah Awel, Miriam Barthelmess, Katerina Dörner, P Lourdu Xavier, Oleksandr Yefanov, Daniel R James, Garrett Nelson, Dingjie Wang, George Calvey, Yujie Chen, Andrea Schmidt, Michael Szczepek, Stefan Frielingsdorf, Oliver Lenz, Edward Snell, Philip J Robinson, Božidar Šarler, Grega Belšak, Marjan Maček, Fabian Wilde, Andrew Aquila, Sébastien Boutet, Mengning Liang, Mark S Hunter, Patrick Scheerer, John D Lipscomb, Uwe Weierstall, Roger D Kornberg, John C H Spence, Lois Pollack, Henry N Chapman, Saša Bajt
This corrects the article DOI: 10.1038/srep44628.
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634413/topical-fibronectin-improves-wound-healing-of-irradiated-skin
#19
Maxwell B Johnson, Brandon Pang, Daniel J Gardner, Solmaz Niknam-Benia, Vinaya Soundarajan, Athanasios Bramos, David P Perrault, Kian Banks, Gene K Lee, Regina Y Baker, Gene H Kim, Sunju Lee, Yang Chai, Mei Chen, Wei Li, Lawrence Kwong, Young-Kwon Hong, Alex K Wong
Wound healing is significantly delayed in irradiated skin. To better understand global changes in protein expression after radiation, we utilized a reverse phase protein array (RPPA) to identify significant changes in paired samples of normal and irradiated human skin. Of the 210 proteins studied, fibronectin was the most significantly and consistently downregulated in radiation-damaged skin. Using a murine model, we confirmed that radiation leads to decreased fibronectin expression in the skin as well as delayed wound healing...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28632531/a-descriptive-survey-of-anesthesiology-residency-simulation-programs-how-are-programs-preparing-residents-for-the-new-american-board-of-anesthesiology-applied-certification-examination
#20
Robert S Isaak, Fei Chen, Harendra Arora, Susan M Martinelli, David A Zvara, Marjorie P Stiegler
BACKGROUND: Anesthesiology residency programs may need new simulation-based programs to prepare residents for the new Objective Structured Clinical Examination (OSCE) component of the American Board of Anesthesiology (ABA) Primary Certification process. The design of such programs may require significant resources, including faculty time, expertise, and funding, as are currently needed for structured oral examination (SOE) preparation. This survey analyzed the current state of US-based anesthesiology residency programs regarding simulation-based educational programming for SOE and OSCE preparation...
June 19, 2017: Anesthesia and Analgesia
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