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https://www.readbyqxmd.com/read/29141216/slc3a2-mediates-branched-chain-amino-acid-dependent-maintenance-of-regulatory-t-cells
#1
Kayo Ikeda, Makoto Kinoshita, Hisako Kayama, Shushi Nagamori, Pornparn Kongpracha, Eiji Umemoto, Ryu Okumura, Takashi Kurakawa, Mari Murakami, Norihisa Mikami, Yasunori Shintani, Satoko Ueno, Ayatoshi Andou, Morihiro Ito, Hideki Tsumura, Koji Yasutomo, Keiichi Ozono, Seiji Takashima, Shimon Sakaguchi, Yoshikatsu Kanai, Kiyoshi Takeda
Foxp3(+) regulatory T (Treg) cells, which suppress immune responses, are highly proliferative in vivo. However, it remains unclear how the active replication of Treg cells is maintained in vivo. Here, we show that branched-chain amino acids (BCAAs), including isoleucine, are required for maintenance of the proliferative state of Treg cells via the amino acid transporter Slc3a2-dependent metabolic reprogramming. Mice fed BCAA-reduced diets showed decreased numbers of Foxp3(+) Treg cells with defective in vivo proliferative capacity...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29141139/the-effect-of-synthetic-high-density-lipoproteins-modification-with-polyethylene-glycol-on-pharmacokinetics-and-pharmacodynamics
#2
Dan Li, Maria V Fawaz, Emily E Morin, Ran Ming, Denis Sviridov, Jie Tang, Rose Ackerman, Karl Olsen, Alan T Remaley, Anna Schwendeman
Synthetic high density lipoprotein nanoparticles (sHDL) capable of mobilizing excess cholesterol from atherosclerotic arteries and delivering it to the liver for elimination have been shown to reduce plaque burden in patients. Unfortunately, sHDLs have a narrow therapeutic index and relative to the endogenous HDL shorter circulation half-life. Surface modification with polyethylene glycol (PEG) was investigated for its potential to extend sHDL circulation in vivo. Various amounts (2.5, 5 and 10%) and different chain lengths (2 and 5 kDa) of PEG-modified lipids were incorporated in sHDL's lipid membrane...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29141134/cellular-analysis-using-microfluidics
#3
Jay Sibbitts, Kathleen A Sellens, Shu Jia, Scott A Klasner, Christopher T Culbertson
Cells are the fundamental building blocks of life. Changes within a cell can propagate throughout much larger, more complex systems. Understanding how these changes arise internally within a cell and how cellular signals are transmitted through larger systems of cells, whether those systems be an organ, organism or a larger environmental assemblage, are critical, for example, to understanding how diseases arise and spread and how cells communicate and coordinate their actions. Microfluidic devices provide unique platforms from which to study many of these intra- and intercellular processes...
November 15, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29141124/the-effects-of-valbenazine-in-participants-with-tardive-dyskinesia-results-of-the-1-year-kinect-3-extension-study
#4
Stewart A Factor, Gary Remington, Cynthia L Comella, Christoph U Correll, Joshua Burke, Roland Jimenez, Grace S Liang, Christopher F O'Brien
BACKGROUND: Valbenazine, a highly selective vesicular monoamine transporter 2 inhibitor, is approved for the treatment of tardive dyskinesia. This is the first report of long-term effects in adults with tardive dyskinesia. METHODS: Participants with a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or a mood disorder who completed the 6-week, double-blind, placebo-controlled period of KINECT 3 were eligible to enter the 42-week valbenazine extension (VE) period and subsequent 4-week washout period...
November 14, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/29141004/lack-of-mitochondrial-muts-homolog-1-in-toxoplasma-gondii-disrupts-maintenance-and-fidelity-of-mitochondrial-dna-and-reveals-metabolic-plasticity
#5
Tamila Garbuz, Gustavo Arrizabalaga
The importance of maintaining the fidelity of the mitochondrial genome is underscored by the presence of various repair pathways within this organelle. Presumably, the repair of mitochondrial DNA would be of particular importance in organisms that possess only a single mitochondrion, like the human pathogens Plasmodium falciparum and Toxoplasma gondii. Understanding the machinery that maintains mitochondrial DNA in these parasites is of particular relevance, as mitochondrial function is a validated and effective target for anti-parasitic drugs...
2017: PloS One
https://www.readbyqxmd.com/read/29140831/relative-efficacies-of-hboc-201-and-polyheme-to-increase-oxygen-transport-compared-to-blood-and-crystalloids-2017-military-supplement
#6
Gregory P Dubé, Arkadiy N Pitman, Colin F Mackenzie
BACKGROUND: Because total hemoglobin in circulation ([THb]) is an established predictor of clinical outcomes in anemic individuals, the relative efficacies of resuscitation fluids to increase [THb] can be used to design better hemoglobin-based oxygen carrier (HBOC) clinical trials. METHODS: Expected efficacies of HBOC-201 (13 g Hb/dL) and packed RBCs (pRBCs, 24 g Hb/dL) to increase [THb] were calculated and interpreted in the context of SAEs in the HEM-0115 phase III clinical trial...
November 14, 2017: Shock
https://www.readbyqxmd.com/read/29140800/glassy-magnetic-ground-state-and-kondo-like-behaviour-in-mn10fege8-alloy
#7
S Pramanick, P Dutta, S Majumdar, S Chatterjee
We report a detailed investigation of the ground-state magnetic properties of newly synthesized [Formula: see text] [Formula: see text] alloy. The sample can be thought of being derived by substituting one Mn atom by Fe of the parent compound [Formula: see text] [Formula: see text]. Fe-substitution leads to a drastic change in the magnetic ground state as well as to the magneto-transport properties of the parent alloy. On cooling below 250 K, [Formula: see text] [Formula: see text] undergoes a transition from paramagnetic phase to a state having significant ferromagnetic correlations...
November 15, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/29140796/temperature-and-impurity-effect-on-parallel-field-magnetoconductance-of-bulk-insulating-topological-insulator-bi1-x-sb-x-2te3
#8
R R Urkude, R Rawat, U A Palikundwar
We have performed a systematic parallel field magnetotransport studies of (Bi1-x Sb x )2Te3 to understand the temperature and impurity effect on the interference of bulk conductance on the surface states of highly insulating topologically insulating compound Bi2Te3. The compound exhibits a weak antilocalization effect (WAL) at low temperature and low magnetic field. WAL weakens and a weak localization effect is observed to be developed in the compound with the increase in temperature due to the creation of topologically trivial 2D electron gas states...
November 15, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/29140789/mechanism-and-dynamics-of-inpp5e-transport-into-and-inside-the-ciliary-compartment
#9
Stefanie Kristine Kösling, Eyad Kalawy Fansa, Stefano Maffini, Alfred Wittinghofer
The inositol polyphosphate 5´-phosphatase E (INPP5E) localizes to cilia. We showed that the carrier protein phosphodiesterase 6 delta subunit (PDE6δ) mediates the sorting of farnesylated INPP5E into cilia due to high affinity binding and release by Arl3 GTP. However, the dynamics of INPP5E transport into and inside the ciliary compartment are not fully understood. Here we first investigate the movement of INPP5E using live cell fluorescence microscopy and fluorescence recovery after photobleaching (FRAP) analysis...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29140748/paramedic-initiated-home-care-referrals-and-use-of-home-care-and-emergency-medical-services
#10
Amol A Verma, John Klich, Adam Thurston, Jordan Scantlebury, Alex Kiss, Gayle Seddon, Samir K Sinha
OBJECTIVE: We examined the association between paramedic-initiated home care referrals and utilization of home care, 9-1-1, and Emergency Department (ED) services. METHODS: This was a retrospective cohort study of individuals who received a paramedic-initiated home care referral after a 9-1-1 call between January 1, 2011 and December 31, 2012 in Toronto, Ontario, Canada. Home care, 9-1-1, and ED utilization were compared in the 6 months before and after home care referral...
November 15, 2017: Prehospital Emergency Care
https://www.readbyqxmd.com/read/29140741/comparative-in-vitro-study-of-11-c-methionine-and-11-c-deuterodeprenyl-uptake-in-three-human-glioma-cell-lines
#11
Elena Vasilskis, Ingrid Kreimerman, Silvia Olivera, Eduardo Savio, Henry Engler
AIM: To compare the uptake of (11)C-deuterodeprenyl ((11)C-DED) and (11)C-methionine ((11)C-MET) in three human glioma cell lines and study the relationship with glial fibrillary acid protein (GFAP) and monoamine oxidase B (MAO B) expression. (11)C-DED is used in positron emission tomography imaging as a marker of astrocytosis in various central nervous system pathologies. It binds irreversibly to MAO B, a glial dimeric enzyme with increased activity in some neurological pathologies. MATERIALS AND METHODS: Binding and internalization studies of (11)C-MET and (11)C-DED were performed in astrocytoma grade III, glioblastoma grade IV, and radio-resistant glioblastoma grade IV cells...
November 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29140712/high-expression-of-ugt1a1-1a6-in-monkey-small-intestine-comparison-of-protein-expression-levels-of-cytochromes-p450-udp-glucuronosyltransferases-and-transporters-in-small-intestine-of-cynomolgus-monkey-and-human
#12
Takanori Akazawa, Yasuo Uchida, Eisuke Miyauchi, Masanori Tachikawa, Sumio Ohtsuki, Tetsuya Terasaki
Cynomolgus monkeys have been widely used for the prediction of drug absorption in humans. The purpose of this study was to clarify the regional protein expression levels of cytochromes P450 (CYPs), UDP-glucuronosyltransferases (UGTs), and transporters in small intestine of cynomolgus monkey using liquid chromatography-tandem mass spectrometry, and to compare them with the corresponding levels in human. UGT1A1 in jejunum and ileum were >4.57- and >3.11-fold, and UGT1A6 in jejunum and ileum were >16...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29140708/role-of-vapor-mass-transfer-in-flow-coating-of-colloidal-dispersions-in-the-evaporative-regime
#13
Charles Loussert, Frédéric Doumenc, Jean-Baptiste Salmon, Vadim S Nikolayev, Beatrice Guerrier
In flow-coating processes at low substrate velocity, solvent evaporation occurs during the film withdrawal and the coating process yields directly a dry deposit. In this regime, often referred to as the evaporative regime, several works performed on blade-coating-like confiurations have reported a deposit thickness hd proportional to the inverse of the substrate velocity V . Such a scaling can be easily derived from simple mass conservation laws, assuming that evaporation occurs on a constant distance, referred to as the evaporation length, noted Lev in the present paper and of the order of the meniscus size...
November 15, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29140707/grapefruit-flavonoid-naringenin-regulates-the-expression-of-lxr%C3%AE-in-thp-1-macrophages-by-modulating-amp-activated-protein-kinase
#14
Javier Saenz, Consuelo Santa-María, Maria Edith Reyes-Quiroz, Isabel Geniz, Juan Jiménez, Francisco Sobrino, Gonzalo Alba
The present work investigates the modulation of grapefruit flavonoid naringenin over Liver X Receptor alpha (LXRα) and its target genes in THP-1 macrophages, focusing on AMP-activated protein kinase (AMPK) implication. Naringenin induced LXRα at mRNA and protein levels besides influencing the expression of LXRα target genes ABCA1, ABCG1 (ATP-binding cassette A1 and G1), and SREBP1c (sterol response element binding protein 1c) in THP-1 macrophages. The increased LXRα mRNA and protein expression was reverted when AMPK was inhibited by its chemical inhibitor, compound C or by transfection with AMPK α1 and α2 siRNA...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29140706/a-galactosylated-pro-drug-of-ursodeoxycholic-acid-design-synthesis-characterization-and-pharmacological-effects-in-a-rat-model-of-estrogen-induced-cholestasis
#15
Francesca Di Guida, Claudio Pirozzi, Salvatore Magliocca, Anna Santoro, Adriano Lama, Roberto Russo, Maria Nieddu, Lucia Burrai, Gianpiero Boatto, Maria Pina Mollica, Federica Sodano, Loretta Lazzarato, Konstantin Chegaev, Rosaria Meli, Giuseppina Mattace Raso, Maria Grazia Rimoli
Ursodeoxycholic acid (UDCA) is considered the first-choice therapy for cholestatic disorders. To enhance solubility and exploit specific transporters in liver, we synthesized a new galactosyl pro-drug of UDCA (UDCAgal). Ethinylestradiol (EE)-induced cholestasis was used to study and compare the effects of UDCAgal with UDCA on bile flow, hepatic canalicular efflux transporter expression, and inflammation. UDCAgal resulted quite stable both at pH 7.4 and 1.2 and regenerated the parent drug after incubation in human plasma...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29140685/heterogeneous-ti3sic2-c-containing-na2ti7o15-architecture-for-high-performance-sodium-storage-at-elevated-temperatures
#16
Guodong Zou, Qingrui Zhang, Carlos Fernandez, Gang Huang, Jianyu Huang, Qiuming Peng
Rational design of heterogeneous electrode materials with hierarchical architecture is a potential approach to significantly improve their energy densities. Herein, we report a tailored microwave-assisted synthetic strategy to create heterogeneous hierarchical Ti3SiC2@ C-containing Na2Ti7O15 (MAX@C-NTO) composites as potential anode materials for high performance sodium storage in a wide temperature range from 25 to 80 oC. This composite delivers first reversible capacities of 230 mAh g-1 at 200 mA g-1 and 149 mAh g-1 at 3000 mA g-1 at 25oC...
November 15, 2017: ACS Nano
https://www.readbyqxmd.com/read/29140675/identification-of-novel-allosteric-modulators-of-glutamate-transporter-eaat2
#17
Sandhya Kortagere, Ole Valente Mortensen, Jingsheng Xia, William Lester, Yuhong Fang, Yellamelli V V Srikanth, Joseph M Salvino, Andreia Cristina Karklin Fontana
Dysfunction of excitatory amino acid transporters (EAATs) has been implicated in the pathogenesis of various neurological disorders, such as stroke, brain trauma, epilepsyand neurodegenerative diseases among others. EAAT2 is the main subtype responsible for glutamate clearance in the brain, having a key role in regulating transmission and preventing excitotoxicity. Therefore, compounds that increase the expression or activity of EAAT2 have therapeutic potential for neuroprotection. Previous studies identified molecular determinants for EAAT2 transport stimulation in a structural domain that lies at the interface of the rigid trimerization domain and the central substrate binding transport domain...
November 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29140639/determining-the-effectiveness-of-mirrors-and-camera-systems-in-monitoring-the-rearward-visibility-of-self-propelled-agricultural-machinery
#18
Shawn G Ehlers, William E Field
This study concerned the ability of operators of tractors and other self-propelled agricultural machinery to visually recognize objects and/or hazards within close proximity to the rear of those machines and/or any implements in tow, especially when backing up. It was hypothesized that the data collected would identify the factors affecting rearward visibility and help determine the effectiveness of two backup-assisting devices (i.e., mirrors and camera systems) in enhancing the operator's ability to observe objects or hazards...
July 31, 2017: Journal of Agricultural Safety and Health
https://www.readbyqxmd.com/read/29140620/how-agricultural-media-cover-safety-compared-with-periodicals-in-two-other-hazardous-industries
#19
Amanda Marolf, Scott Heiberger, James Evans, Lura Joseph
This analysis featured a uniquely broad look at challenges and potentials for engaging agricultural and other industrial media more effectively in covering safety. It involved a content analysis of selected industry periodicals serving agriculture, mining, and transportation, which are three of the nation's most hazardous industries, in terms of human safety. Use of the social amplification of risk framework (SARF) provided insight on safety coverage. In particular, it tested previous research indicating that media coverage tends to amplify (increase) more than attenuate (decrease) a sense of risk...
January 26, 2017: Journal of Agricultural Safety and Health
https://www.readbyqxmd.com/read/29140549/improving-pancreas-graft-utilization-through-importation
#20
Julia Torabi, Juan P Rocca, Krystina Choinski, Katherine Lorenzen, Camille Yongue, Michelle L Lubetzsky, Melvon E Herbert, Attasit Chokechanachaisakul, Maria Ajaimy, Layla Kamal, Enver Akalin, Milan Kinkhabwala, Jay A Graham
BACKGROUND: We analyze our outcomes utilizing imported allografts as a strategy to shorten wait list time for pancreas transplantation. METHODS: This is an observational retrospective cohort of 26 recipients who received either a locally procured (n=16) or an imported pancreas graft (n=10) at our center between January 2014 and May 2017. Wait list times of this cohort were compared to UNOS Region 9 (New York State and Western Vermont). Hospital financial data was also reviewed to analyze the cost effectiveness of this strategy...
November 15, 2017: Clinical Transplantation
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