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Anne C Solga, Joseph A Toonen, Yuan Pan, Patrick J Cimino, Yu Ma, Guillaume A Castillon, Scott M Gianino, Mark H Ellisman, Da Yong Lee, David H Gutmann
Low-grade gliomas are one of the most common brain tumors in children, where they frequently form within the optic pathway (optic pathway gliomas; OPGs). Since many OPGs occur in the context of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome, we have previously employed Nf1 genetically-engineered mouse (GEM) strains to study the pathogenesis of these low-grade glial neoplasms. In the light of the finding that human and mouse low-grade gliomas are composed of Olig2+ cells and that Olig2+ oligodendrocyte precursor cells (OPCs) give rise to murine high-grade gliomas, we sought to determine whether Olig2+ OPCs could be tumor-initiating cells for Nf1 optic glioma...
May 3, 2017: Oncotarget
Gurpreet Kour, Monika Gupta
Silver nanoparticles have been prepared from a chemical reduction approach and supported on modified TEOS (tetraethylorthosilicate) xerogels to be studied as a nanocatalyst in the conversions of benzopyranopyrimidines (with primary as well as secondary amines along with the mechanism by trapping the imine intermediate) and also in the synthesis of gem-bisamides. Different conditions for the performance of the nanocatalyst have been screened and tolerance with respect to variable functionalities has been observed, resulting in excellent yields; and confirmation of products synthesized has been done using studies like (1)H NMR, (13)C NMR and mass analysis...
May 18, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
Tia Jarvis, Carleton G Collins, Janel M Dempsey, Allen G Oliver, Bradley D Smith
Squaraine rotaxanes are mechanically interlocked molecules comprised of a dumbbell shaped squaraine dye inside a tetralactam macrocycle. Previous squaraine rotaxanes have employed planar squaraine dyes with 4-aminophenyl, 2-aminothiophene or N-amino units appended to the central C4O2 core. Here we describe two rotaxanes that encapsulate a 3,3-dimethylindoline squaraine inside a tetralactam with anthracene sidewalls. The rotaxanes were prepared by a templated clipping reaction and an X-ray crystal structure shows that the squaraine gem-dimethyl groups force a relatively wide separation between the macrocycle anthracene sidewalls...
May 18, 2017: Journal of Organic Chemistry
Milan J A van Hoek, Roeland M H Merks
BACKGROUND: The human gut contains approximately 10(14) bacteria, belonging to hundreds of different species. Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e...
May 16, 2017: BMC Systems Biology
Gilberto Fuentes, Bravo A Humberto, Sosa E Rodolfo, Rosas A Sergio, Magaña R Víctor, Caetano D Ernesto, Vázquez C Gustavo
Atmospheric mercury in the environment as a result of the consumption of fossil fuels, such as coal used in electricity generation, has gained increased attention worldwide because of its toxicity, atmospheric persistence, and bioaccumulation. Determining or predicting the concentration of this pollutant in ambient air is essential for determining sensitive areas requiring health protection. This study investigated the spatiotemporal variability of gaseous elemental mercury (GEM) concentrations and its dry deposition surrounding the Presidente Plutarco Elías Calles, (CETEPEC) coal-fired power plant, located on Mexico's Pacific coast...
May 12, 2017: Journal of the Air & Waste Management Association
Juan-Jose Lahuerta, Bruno Paiva, Maria-Belen Vidriales, Lourdes Cordón, Maria-Teresa Cedena, Noemi Puig, Joaquin Martinez-Lopez, Laura Rosiñol, Norma C Gutierrez, María-Luisa Martín-Ramos, Albert Oriol, Ana-Isabel Teruel, María-Asunción Echeveste, Raquel de Paz, Felipe de Arriba, Miguel T Hernandez, Luis Palomera, Rafael Martinez, Alejandro Martin, Adrian Alegre, Javier De la Rubia, Alberto Orfao, María-Victoria Mateos, Joan Blade, Jesus F San-Miguel
Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively)...
May 12, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Karina R Gaisina, Alexander F Khlebnikov, Mikhail S Novikov
The cycloaddition of arenecarbaldehydes and α,α,α-trifluoroacetophenones with gem-difluoro-substituted azomethine ylides, generated from N-benzhydrylideneamines and difluorocarbene, occurs regioselectively to give, after hydrolysis, oxazolidin-4-ones. The primary cycloadducts of trifluoroacetophenones, 4,4-difluoro-5-trifluoromethyloxazolidine derivatives, are sufficiently stable to be isolated in reasonable to excellent yields. The results of correlation analysis and DFT calculations reveal a non-pericyclic step-wise mechanism of the reaction...
May 12, 2017: Organic & Biomolecular Chemistry
Suguru Ito, Kengo Ikeda, Shoma Nakanishi, Yoshitane Imai, Masatoshi Asami
Herein, an unprecedented switching of circularly polarized luminescence (CPL) is described for chiral 4,6-bis(1-(pyren-1-ylamino)propyl)dibenzo[b,d]furan (1). The CPL band of chiral diamine 1, which contains two pyrene rings, can be switched between the monomer and excimer emission regions under concomitant inversion of the handedness, simply by changing the concentration of the fluorophore. In contrast, the maximum photoluminescence (PL) intensity is always observed in the monomer region, regardless of the concentration...
May 12, 2017: Chemical Communications: Chem Comm
Nima Hamzian, Maryam Hashemi, Mahdi Ghorbani, Mohammad Hossein Bahreyni Toosi, Mohammad Ramezani
The aim of this study was to develop a novel multifunctional nanoparticle, which encapsulates SPION and Gemcitabine in PLGA ± PEG to form multifunctional drug delivery system. For this aim, super paramagnetic iron oxide nanoparticles (SPIONs) were simultaneously synthesized and encapsulated with Gemcitabine (Gem) in PLGA ± PEG copolymers via W/O/W double emulsification method. Optimum size and encapsulation efficiency for radiosensitization, hyperthermia and diagnostic applications were considered and the preparation parameters systematically were investigated and physicochemical characteristics of optimized nanoparticle were studied...
2017: Iranian Journal of Pharmaceutical Research: IJPR
Noritoshi Kobayashi, Takeshi Shimamura, Motohiko Tokuhisa, Ayumu Goto, Itaru Endo, Yasushi Ichikawa
BACKGROUND: This study aimed to determine the maximum tolerated dose (MTD), dose-limiting toxicity, and efficacy of second-line chemotherapy with FOLFIRINOX after gemcitabine (GEM)-based chemotherapy failure in metastatic pancreatic cancer (MPC). METHODS: We studied 18 histopathologically proven MPC patients. The schedule was 85 mg/m oxaliplatin, irinotecan, and 400 mg/m leucovorin, followed by 400 mg/m 5-fluorouracil (5-FU) as a bolus on day 1 and 2400 mg/m 5-FU as a 46-hour continuous infusion biweekly...
May 2017: Medicine (Baltimore)
Zong-Feng Zhang, Dong-Xing Zhu, Wen-Wen Chen, Bin Xu, Ming-Hua Xu
An asymmetric dual-metal relay catalysis strategy that combines Rh/chiral sulfur-olefin-catalyzed enantioselective 1,2-addition with a Pd-catalyzed intramolecular C-O coupling has been developed. The method allows rapid and efficient synthesis of quaternary carbon-containing gem-diaryl benzofuran-3(2H)-ones in good yields in a highly enantioselective manner (up to 99% ee) through a simple one-pot cascade reaction.
May 9, 2017: Organic Letters
Chérif Adouama, Robert Keyrouz, Guillaume Pilet, Cyrille Monnereau, David Gueyrard, Timothy Noël, Maurice Médebielle
A variety of unprecedented scaffolds containing a difluoroacyl moiety were obtained in moderate to good yields, with excellent diastereoselectivity, via electrochemical or photochemical activation of difluoroacyl heteroaryles with a series of olefinic substrates.
May 9, 2017: Chemical Communications: Chem Comm
Soo-Jin Kim, Kota Toshimoto, Yoshiaki Yao, Takashi Yoshikado, Yuichi Sugiyama
Quantitative analysis of transporter- and enzyme-mediated complex drug-drug interactions (DDIs) is challenging. Repaglinide (RPG) is transported into the liver by OATP1B1 and then is metabolized by CYP2C8 and CYP3A4. The purpose of this study is to describe the complex DDIs of RPG quantitatively based on unified physiologically-based pharmacokinetic (PBPK) models using in vitro Ki values for OATP1B1, CYP3A4, and/or CYP2C8. Cyclosporin A (CsA) or gemfibrozil (GEM) increased the blood concentrations of RPG. The time profiles of RPG and the inhibitors were analyzed by PBPK models, considering the inhibition of OATP1B1 and CYP3A4 by CsA, or OATP1B1 inhibition by GEM and its glucuronide and the mechanism-based inhibition of CYP2C8 by GEM glucuronide...
May 4, 2017: Journal of Pharmaceutical Sciences
Edward Pym, Nikhil Sasidharan, Katherine L Thompson-Peer, David J Simon, Anthony Anselmo, Ruslan Sadreyev, Qi Hall, Stephen Nurrish, Joshua M Kaplan
Shank is a post-synaptic scaffolding protein that has many binding partners. Shank mutations and copy number variations (CNVs) are linked to several psychiatric disorders, and to synaptic and behavioral defects in mice. It is not known which Shank binding partners are responsible for these defects. Here we show that the C. elegans SHN-1/Shank binds L-type calcium channels and that increased and decreased shn-1 gene dosage alter L-channel current and activity-induced expression of a CRH-1/CREB transcriptional target (gem-4 Copine), which parallels the effects of human Shank copy number variations (CNVs) on Autism spectrum disorders and schizophrenia...
May 6, 2017: ELife
Maria Savva, Katerina Skordi, Adeline D Fournet, Annaliese E Thuijs, George Christou, Spyros P Perlepes, Constantina Papatriantafyllopoulou, Anastasios J Tasiopoulos
The employment of di-2-pyridyl ketone, (py)2CO, in heterometallic Mn/4f and homometallic Mn cluster chemistry has yielded six Mn(III)4Ln2 and two Mn(III)4Mn(II)2 structurally related clusters, namely, [Mn4Ln2O2{(py)2CO2}4(NO3)2(RCO2)2(H2O)6](NO3)2 (Ln = Gd, 1, 5; Dy, 2; Tb, 3; R = Et, 1-3; Me, 5), [Mn4Dy2O2{(py)2CO2}4(NO3)4(EtCO2)2(H2O)3(MeOH)]·0.7MeOH·0.8H2O (4·0.7MeOH·0.8H2O), [Mn4Gd2O2{(py)2CO2}4(NO3)4(C6H4ClCO2)2(MeOH)2(py)2]·2MeOH (6·2MeOH), [Mn6O2{(py)2CO2}4(py)4(H2O)4](ClO4)4·4H2O (7·4H2O), and [Mn6O2{(py)2CO2}4(NO3)4(py)4] (8), where (py)2CO2(2-) is the dianion of the gem-diol derivative of (py)2CO...
May 3, 2017: Inorganic Chemistry
A Tiisanoja, A-M Syrjälä, K Komulainen, S Hartikainen, H Taipale, M Knuuttila, P Ylöstalo
OBJECTIVES: The objective of this study was to determine whether drugs with sedative properties are related to oral health behaviour-such as frequency of toothbrushing, using toothpaste and dental visits-and oral hygiene, measured by the number of teeth with dental plaque, among community-dwelling older people. METHODS: The study population consisted of 159 community-dwelling, dentate, non-smoking, older people from the Oral Health GeMS study (Geriatric Multidisciplinary Strategy for the Good Care of Older People study)...
May 3, 2017: International Journal of Dental Hygiene
Phan T Truong, Eric M Gale, Stephen P Dzul, Timothy L Stemmler, Todd C Harrop
Ni-containing superoxide dismutase (NiSOD) represents an unusual member of the SOD family due to the presence of oxygen-sensitive Ni-SCys bonds at its active site. Reported in this account is the synthesis and properties of the Ni(II) complex of the N3S2 ligand [N3S2(Me2)](3-) ([N3S2(Me2)](3-) = deprotonated form of 2-((2-mercapto-2-methylpropyl)(pyridin-2-ylmethyl)amino)-N-(2-mercaptoethyl)acetamide), namely Na[Ni(N3S2(Me2))] (2), as a NiSOD model that features sterically robust gem-(CH3)2 groups on the thiolate α-C positioned trans to the carboxamide...
May 1, 2017: Inorganic Chemistry
Isaac Schifter, Luis Díaz-Gutiérrez, René Rodríguez-Lara, Carmen González-Macías, Uriel González-Macías
Gasoline-ethanol-methanol fuel blends were formulated with the same stoichiometric air-to-fuel ratio and volumetric energy concentration as any binary ethanol-gasoline blend. When the stoichiometric blends operated in a vehicle, the time period, injector voltage, and pressure for each fuel injection event in the engine corresponded to a given stoichiometric air-to-fuel ratio, and the load was essentially constant. Three low oxygen content iso-stoichiometric ternary gasoline-ethanol-methanol fuel blends were prepared, and the properties were compared with regular-type fuel without added oxygen...
May 2017: Environmental Monitoring and Assessment
Jonathan B Dingwell, Mandy M Salinas, Joseph P Cusumano
Older adults exhibit increased gait variability that is associated with fall history and predicts future falls. It is not known to what extent this increased variability results from increased physiological noise versus a decreased ability to regulate walking movements. To "walk", a person must move a finite distance in finite time, making stride length (Ln) and time (Tn) the fundamental stride variables to define forward walking. Multiple age-related physiological changes increase neuromotor noise, increasing gait variability...
March 31, 2017: Gait & Posture
Yaqing Li, Yinting Chen, Jiajia Li, Zuoquan Zhang, Chumei Huang, Guoda Lian, Kege Yang, Shaojie Chen, Ying Lin, Lingyun Wang, Kaihong Huang, Linjuan Zeng
Tumor metastasis occurs naturally in pancreatic cancer, and the efficacy of chemotherapy is usually poor. Precision medicine, combining down-regulation of target genes with chemotherapy drugs, is expected to improve the therapeutic effects. Therefore, we developed a combined therapy of microRNA-21 antisense oligonucleotides (ASO-miR-21) and Gemcitabine (Gem) using a targeted co-delivery nanoparticle (NP) carrier and investigated the synergistic inhibitory effects on pancreatic cancer cells metastasis and growth...
April 26, 2017: Cancer Science
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