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https://www.readbyqxmd.com/read/28231433/discovery-of-a-potent-and-selective-sphingosine-kinase-1-inhibitor-through-the-molecular-combination-of-chemotype-distinct-screening-hits
#1
Mark E Schnute, Matthew D McReynolds, Jeffrey Carroll, Jill E Chrencik, Maureen K Highkin, Kaliapan Iyanar, Gina Jerome, John W Rains, Matthew Saabye, Jeffrey A Scholten, Matthew Yates, Marek M Nagiec
Sphingosine kinase (SphK) is the major source of the lipid mediator and GPCR agonist sphingosine-1-phosphate (S1P). S1P promotes cell growth, survival and migration and is a key regulator of lymphocyte trafficking. Inhibition of S1P signaling has been proposed as a strategy for treatment of inflammatory diseases and cancer. Two different formats of an enzyme based high-throughput screen yielded two attractive chemotypes capable of inhibiting S1P formation in cells. The molecular combination of these screening hits led to compound 22a (PF-543) with two orders of magnitude improved potency...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28231366/comparison-of-cidofovir-and-the-measles-mumps-and-rubella-vaccine-in-the-treatment-of-recurrent-respiratory-papillomatosis
#2
Ryan Kent Meacham, Jerome W Thompson
We conducted a retrospective study of the use of cidofovir and the measles, mumps, and rubella (MMR) vaccineas adjunctive treatments to lesion debridement in patients with recurrent respiratory papillomatosis (RRP). Our study population was made up of 15 children-7 boys and 8 girls, aged 1 to 16 years at diagnosis (mean: 6.2)-with pathologically confirmed RRP who had been followed for at least 1 year. In addition to demographic data, we compiled information on disease severity, the type of adjunctive treatment administered to each patient, the frequency of debridements, the length of observation, and remission rates...
February 2017: Ear, Nose, & Throat Journal
https://www.readbyqxmd.com/read/28230464/french-norms-for-the-harvard-group-scale-of-hypnotic-susceptibility-form-a
#3
Hernán Anlló, Jean Becchio, Jérôme Sackur
The authors present French norms for the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A). They administered an adapted translation of Shor and Orne's original text (1962) to a group of 126 paid volunteers. Participants also rated their own responses following our translation of Kihlstrom's Scale of Involuntariness (2006). Item pass rates, score distributions, and reliability were calculated and compared with several other reference samples. Analyses show that the present French norms are congruous with the reference samples...
April 2017: International Journal of Clinical and Experimental Hypnosis
https://www.readbyqxmd.com/read/28230283/low-band-gap-bistetracene-based-organic-semiconductors-exhibiting-air-stability-high-aromaticity-and-mobility
#4
Kamal Sbargoud, Masashi Mamada, Tanguy Jousselin-Oba, Yasunori Takeda, Shizuo Tokito, Abderrahim Yassar, Jérôme Marrot, Michel Frigoli
The benchmark of soluble organic semiconductors based on acenes is the 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-PEN). However TIPS-PEN still suffers from photoinduced oxidation due to its low aromaticity. Increasing the aromaticity while keeping similar optical and electrochemical properties and shape suitable for good transport can be achieved with two-dimensional polycyclic aromatic hydrocarbons (2D-PAHs). Herein, we present an efficient synthesis and characterization of bistetracene derivatives that exhibit a band gap up to 1...
February 23, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28230201/relapsing-remitting-multiple-sclerosis-patients-display-an-altered-lipoprotein-profile-with-dysfunctional-hdl
#5
Winde Jorissen, Elien Wouters, Jeroen F Bogie, Tim Vanmierlo, Jean-Paul Noben, Denis Sviridov, Niels Hellings, Veerle Somers, Roland Valcke, Bart Vanwijmeersch, Piet Stinissen, Monique T Mulder, Alan T Remaley, Jerome J A Hendriks
Lipoproteins modulate innate and adaptive immune responses. In the chronic inflammatory disease multiple sclerosis (MS), reports on lipoprotein level alterations are inconsistent and it is unclear whether lipoprotein function is affected. Using nuclear magnetic resonance (NMR) spectroscopy, we analysed the lipoprotein profile of relapsing-remitting (RR) MS patients, progressive MS patients and healthy controls (HC). We observed smaller LDL in RRMS patients compared to healthy controls and to progressive MS patients...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230188/3d-time-lapse-imaging-and-quantification-of-mitochondrial-dynamics
#6
Miguel Sison, Sabyasachi Chakrabortty, Jérôme Extermann, Amir Nahas, Paul James Marchand, Antonio Lopez, Tanja Weil, Theo Lasser
We present a 3D time-lapse imaging method for monitoring mitochondrial dynamics in living HeLa cells based on photothermal optical coherence microscopy and using novel surface functionalization of gold nanoparticles. The biocompatible protein-based biopolymer coating contains multiple functional groups which impart better cellular uptake and mitochondria targeting efficiency. The high stability of the gold nanoparticles allows continuous imaging over an extended time up to 3000 seconds without significant cell damage...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229811/patient-phenotypes-in-fibromyalgia-comorbid-with-systemic-sclerosis-or-rheumatoid-arthritis-influence-of-diagnostic-and-screening-tests-screening-with-the-first-questionnaire-diagnosis-with-the-acr1990-and-revised-acr-2010-criteria
#7
Serge Perrot, Mariana Peixoto, Philippe Dieudé, Eric Hachulla, Jerome Avouac, Sebastien Ottaviani, Yannick Allanore
OBJECTIVES: Fibromyalgia (FM) may occur with rheumatoid arthritis (RA) and systemic sclerosis (SSc), and debate remains about its diagnosis. We aimed to use three FM tools (a screening tool (FiRST), diagnostic criteria (ACR 1990 and revised 2010), to compare FM prevalence between RA and SSc patients, to describe the phenotypes of patients with comorbid FM, and to analyze links between FM and secondary Sjögren's syndrome (SS). METHODS: Consecutive adult patients with confirmed RA or SSc from four university hospitals were tested with the three FM tools...
February 8, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28228439/loss-of-pollen-specific-phospholipase-not-like-dad-triggers-gynogenesis-in-maize
#8
Laurine M Gilles, Abdelsabour Khaled, Jean-Baptiste Laffaire, Sandrine Chaignon, Ghislaine Gendrot, Jérôme Laplaige, Hélène Bergès, Genséric Beydon, Vincent Bayle, Pierre Barret, Jordi Comadran, Jean-Pierre Martinant, Peter M Rogowsky, Thomas Widiez
Gynogenesis is an asexual mode of reproduction common to animals and plants, in which stimuli from the sperm cell trigger the development of the unfertilized egg cell into a haploid embryo. Fine mapping restricted a major maize QTL (quantitative trait locus) responsible for the aptitude of inducer lines to trigger gynogenesis to a zone containing a single gene NOT LIKE DAD (NLD) coding for a patatin-like phospholipase A. In all surveyed inducer lines, NLD carries a 4-bp insertion leading to a predicted truncated protein...
February 22, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28225571/balancing-selection-maintains-sex-determining-alleles-in-multiple-locus-complementary-sex-determination
#9
Jerome J Weis, Paul J Ode, George E Heimpel
Hymenopteran species in which sex is determined through a haplo-diploid mechanism known as complementary sex determination (CSD) are vulnerable to a unique form of inbreeding depression. Diploids heterozygous at one or more CSD loci develop into females but diploids homozygous at all loci develop into diploid males, which are generally sterile or inviable. Species with multiple polymorphic CSD loci (ml-CSD) may have lower rates of diploid male production than species with a single CSD locus (sl-CSD), but it is not clear if polymorphism is consistently maintained at all loci...
February 22, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28225239/are-environmental-pollutants-in-the-norwegian-diet-harmful-to-children
#10
Bjørn J Bolann, Sandra Huber, Jerome Ruzzin, Jan Brox, Henrik S Huitfeldt, Anne-Lise Bjørke Monsen
No abstract text is available yet for this article.
February 2017: Tidsskrift for Den Norske Lægeforening: Tidsskrift for Praktisk Medicin, Ny Række
https://www.readbyqxmd.com/read/28225161/treatment-of-experimental-status-epilepticus-with-synergistic-drug-combinations
#11
Jerome Niquet, Roger Baldwin, Lucie Suchomelova, Lucille Lumley, Roland Eavey, Claude G Wasterlain
During status epilepticus (SE), synaptic γ-aminobutyric acid A receptors (GABAA Rs) become internalized and inactive, whereas spare N-methyl-d-aspartate receptors (NMDARs) assemble, move to the membrane, and become synaptically active. When treatment of SE is delayed, the number of synaptic GABAA Rs is drastically reduced, and a GABAA agonist cannot fully restore inhibition. We used a combination of low-dose diazepam (to stimulate the remaining GABAA Rs), ketamine (to mitigate the effect of the NMDAR increase), and valproate (to enhance inhibition at a nonbenzodiazepine site) to treat seizures in a model of severe cholinergic SE...
February 22, 2017: Epilepsia
https://www.readbyqxmd.com/read/28224818/adjunctive-low-dose-docosahexaenoic-acid-dha-for-major-depression-an-open-label-pilot-trial
#12
Deidre J Smith, Jerome Sarris, Nathan Dowling, Manjula O'Connor, Chee H Ng
OVERVIEW: Whilst the majority of evidence supports the adjunctive use of eicosapentaenoic acid (EPA) in improving mood, to date no study exists using low-dose docosahexaenoic acid (DHA) alone as an adjunctive treatment in patients with mild to moderate major depressive disorder (MDD). METHODS: A naturalistic 8-week open-label pilot trial of low-dose DHA, (260 mg or 520 mg/day) in 28 patients with MDD who were non-responsive to medication or psychotherapy, with a Hamilton Depression Rating Scale (HAM-D) score of greater than 17, was conducted...
February 22, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28224387/evaluation-of-the-ros-inhibiting-activity-and-mitochondrial-targeting-of-phenolic-compounds-in-fibroblast-cells-model-system-and-enhancement-of-efficiency-by-natural-deep-eutectic-solvent-nades-formulation
#13
Erwann Durand, Jérôme Lecomte, Rashmi Upasani, Béatrice Chabi, Christelle Bayrasy, Bruno Baréa, Elodie Jublanc, Martyn J Clarke, David J Moore, Jonathan Crowther, Chantal Wrutniak-Cabello, Pierre Villeneuve
PURPOSE: Many phenolics have already been tested for their antioxidant activities using in vitro methods. However, such assays do not consider the complexity of real cellular systems, and most of the phenolics characterized with such assays shows disappointing results when evaluated in cells. Accordingly, there is a need to develop effective screening methods. METHODS: Antioxidants were first evaluated by CAT assay and then, evaluated for their ability (i) to reduce the level of ROS using fluorescent probe, (ii) to cross fibroblast cell membranes using confocal microscopy, and (iii) to target mitochondria...
February 21, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28224341/enhanced-transportability-of-zero-valent-iron-nanoparticles-in-aquifer-sediments-surface-modifications-reactivity-and-particle-traveling-distances
#14
Naresh Kumar, Jérôme Labille, Nathan Bossa, Mélanie Auffan, Pierre Doumenq, Jérôme Rose, Jean-Yves Bottero
In this study, we assessed the transportability of zero valent iron nanoparticles (nano-Fe(0)) coated with different organics (carboxy methyl cellulose (CMC), poly acrylic acid (PAA), and xanthan gum) in standard porous sand and in real aquifer sediments. Our results suggest that the organic surface coatings optimized for nano-Fe(0) in porous sand media do not necessarily reflect the same transportability in real field aquifer sediment. Xanthan gum-coated nano-Fe(0) showed highest transportability in standard porous sand, but the performance was much lower in real aquifer sediment, whereas the PAA-coated nano-Fe(0) particle showed better transportability both in aquifer sediment and in porous sand media...
February 22, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28224334/the-trpm4-channel-is-functionally-important-for-the-beneficial-cardiac-remodeling-induced-by-endurance-training
#15
Mélanie Gueffier, Justin Zintz, Karen Lambert, Amanda Finan, Franck Aimond, Nourdine Chakouri, Christophe Hédon, Mathieu Granier, Pierre Launay, Jérôme Thireau, Sylvain Richard, Marie Demion
Cardiac hypertrophy (CH) is an adaptive process that exists in two distinct forms and allows the heart to adequately respond to an organism's needs. The first form of CH is physiological, adaptive and reversible. The second is pathological, irreversible and associated with fibrosis and cardiomyocyte death. CH involves multiple molecular mechanisms that are still not completely defined but it is now accepted that physiological CH is associated more with the PI3-K/Akt pathway while the main signaling cascade activated in pathological CH involves the Calcineurin-NFAT pathway...
February 21, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/28224058/characterization-of-microsatellite-markers-in-two-exploited-african-trees-entandrophragma-candollei-and-e-utile-meliaceae
#16
Franck S Monthe, Jérôme Duminil, Félicien Tosso, Jérémy Migliore, Olivier J Hardy
PREMISE OF THE STUDY: Multiplexes of nuclear microsatellite primers were developed to investigate population genetic structure and diversity in two exploited African rainforest trees: Entandrophragma candollei and E. utile (Meliaceae). METHODS AND RESULTS: Microsatellite isolation was performed simultaneously on two nonenriched genomic libraries after next-generation sequencing. We developed 16 and 22 polymorphic markers for E. candollei and E. utile in three and four multiplexes, respectively...
February 2017: Applications in Plant Sciences
https://www.readbyqxmd.com/read/28223820/flt3-inhibitors-clinical-potential-in-acute-myeloid-leukemia
#17
REVIEW
Marie-Anne Hospital, Alexa S Green, Thiago T Maciel, Ivan C Moura, Anskar Y Leung, Didier Bouscary, Jerome Tamburini
Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy that is cured in as few as 15%-40% of cases. Tremendous improvements in AML prognostication arose from a comprehensive analysis of leukemia cell genomes. Among normal karyotype AML cases, mutations in the FLT3 gene are the ones most commonly detected as having a deleterious prognostic impact. FLT3 is a transmembrane tyrosine kinase receptor, and alterations of the FLT3 gene such as internal tandem duplications (FLT3-ITD) deregulate FLT3 downstream signaling pathways in favor of increased cell proliferation and survival...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28223515/rational-design-of-adjuvants-targeting-the-c-type-lectin-mincle
#18
Alexiane Decout, Sandro Silva-Gomes, Daniel Drocourt, Sophie Barbe, Isabelle André, Francisco J Cueto, Thierry Lioux, David Sancho, Eric Pérouzel, Alain Vercellone, Jacques Prandi, Martine Gilleron, Gérard Tiraby, Jérôme Nigou
The advances in subunit vaccines development have intensified the search for potent adjuvants, particularly adjuvants inducing cell-mediated immune responses. Identification of the C-type lectin Mincle as one of the receptors underlying the remarkable immunogenicity of the mycobacterial cell wall, via recognition of trehalose-6,6'-dimycolate (TDM), has opened avenues for the rational design of such molecules. Using a combination of chemical synthesis, biological evaluation, molecular dynamics simulations, and protein mutagenesis, we gained insight into the molecular bases of glycolipid recognition by Mincle...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223482/a-network-perspective-reveals-decreasing-material-diversity-in-studies-on-nanoparticle-interactions-with-dissolved-organic-matter
#19
Nicole Sani-Kast, Jérôme Labille, Patrick Ollivier, Danielle Slomberg, Konrad Hungerbühler, Martin Scheringer
Dissolved organic matter (DOM) strongly influences the properties and fate of engineered nanoparticles (ENPs) in aquatic environments. There is an extensive body of experiments on interactions between DOM and ENPs and also larger particles. [We denote particles on the nano- and micrometer scale as particulate matter (PM).] However, the experimental results are very heterogeneous, and a general mechanistic understanding of DOM-PM interactions is still missing. In this situation, recent reviews have called to expand the range of DOM and ENPs studied...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28222215/epstein-barr-virus-specific-adoptive-immunotherapy-for-recurrent-metastatic-nasopharyngeal-carcinoma
#20
Julian Huang, Mark Fogg, Lori J Wirth, Heather Daley, Jerome Ritz, Marshall R Posner, Fred C Wang, Jochen H Lorch
BACKGROUND: Early-stage and intermediate stage nasopharyngeal cancer (NPC) generally carry a good prognosis, but for patients with recurrent, metastatic disease, options are limited. In the current study, the authors present a phase 1/2 study to evaluate the efficacy of Epstein-Barr virus (EBV)-stimulated cytotoxic T-lymphocyte (EBV-CTL) immunotherapy in this patient population. METHODS: Screening for patients with active, recurrent, metastatic EBV-associated NPC began in February 2007, and the study was closed to accrual in January 2012...
February 21, 2017: Cancer
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