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https://www.readbyqxmd.com/read/29434453/faecal-calprotectin-and-magnetic-resonance-imaging-in-detecting-crohn-s-disease-endoscopic-postoperative-recurrence
#1
Pierre Baillet, Guillaume Cadiot, Marion Goutte, Felix Goutorbe, Hedia Brixi, Christine Hoeffel, Christophe Allimant, Maud Reymond, Hélène Obritin-Guilhen, Benoit Magnin, Gilles Bommelaer, Bruno Pereira, Constance Hordonneau, Anthony Buisson
AIM: To assess magnetic resonance imaging (MRI) and faecal calprotectin to detect endoscopic postoperative recurrence in patients with Crohn's disease (CD). METHODS: From two tertiary centers, all patients with CD who underwent ileocolonic resection were consecutively and prospectively included. All the patients underwent MRI and endoscopy within the first year after surgery or after the restoration of intestinal continuity [median = 6 mo (5.0-9.3)]. The stools were collected the day before the colonoscopy to evaluate faecal calprotectin level...
February 7, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29386647/structural-basis-of-the-molecular-ruler-mechanism-of-a-bacterial-glycosyltransferase
#2
Ana S Ramírez, Jérémy Boilevin, Ahmad Reza Mehdipour, Gerhard Hummer, Tamis Darbre, Jean-Louis Reymond, Kaspar P Locher
The membrane-associated, processive and retaining glycosyltransferase PglH from Campylobacter jejuni is part of the biosynthetic pathway of the lipid-linked oligosaccharide (LLO) that serves as the glycan donor in bacterial protein N-glycosylation. Using an unknown counting mechanism, PglH catalyzes the transfer of exactly three α1,4 N-acetylgalactosamine (GalNAc) units to the growing LLO precursor, GalNAc-α1,4-GalNAc-α1,3-Bac-α1-PP-undecaprenyl. Here, we present crystal structures of PglH in three distinct states, including a binary complex with UDP-GalNAc and two ternary complexes containing a chemo-enzymatically generated LLO analog and either UDP or synthetic, nonhydrolyzable UDP-CH2-GalNAc...
January 31, 2018: Nature Communications
https://www.readbyqxmd.com/read/29291349/an-opr3-independent-pathway-uses-4-5-didehydrojasmonate-for-jasmonate-synthesis
#3
Andrea Chini, Isabel Monte, Angel M Zamarreño, Mats Hamberg, Steve Lassueur, Philippe Reymond, Sally Weiss, Annick Stintzi, Andreas Schaller, Andrea Porzel, José M García-Mina, Roberto Solano
Biosynthesis of the phytohormone jasmonoyl-isoleucine (JA-Ile) requires reduction of the JA precursor 12-oxo-phytodienoic acid (OPDA) by OPDA reductase 3 (OPR3). Previous analyses of the opr3-1 Arabidopsis mutant suggested an OPDA signaling role independent of JA-Ile and its receptor COI1; however, this hypothesis has been challenged because opr3-1 is a conditional allele not completely impaired in JA-Ile biosynthesis. To clarify the role of OPR3 and OPDA in JA-independent defenses, we isolated and characterized a loss-of-function opr3-3 allele...
January 1, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29290337/kiaa1109-variants-are-associated-with-a-severe-disorder-of-brain-development-and-arthrogryposis
#4
Lucie Gueneau, Richard J Fish, Hanan E Shamseldin, Norine Voisin, Frédéric Tran Mau-Them, Egle Preiksaitiene, Glen R Monroe, Angeline Lai, Audrey Putoux, Fabienne Allias, Qamariya Ambusaidi, Laima Ambrozaityte, Loreta Cimbalistienė, Julien Delafontaine, Nicolas Guex, Mais Hashem, Wesam Kurdi, Saumya Shekhar Jamuar, Lim J Ying, Carine Bonnard, Tommaso Pippucci, Sylvain Pradervand, Bernd Roechert, Peter M van Hasselt, Michaël Wiederkehr, Caroline F Wright, Ioannis Xenarios, Gijs van Haaften, Charles Shaw-Smith, Erica M Schindewolf, Marguerite Neerman-Arbez, Damien Sanlaville, Gaëtan Lesca, Laurent Guibaud, Bruno Reversade, Jamel Chelly, Vaidutis Kučinskas, Fowzan S Alkuraya, Alexandre Reymond
Whole-exome and targeted sequencing of 13 individuals from 10 unrelated families with overlapping clinical manifestations identified loss-of-function and missense variants in KIAA1109 allowing delineation of an autosomal-recessive multi-system syndrome, which we suggest to name Alkuraya-Kučinskas syndrome (MIM 617822). Shared phenotypic features representing the cardinal characteristics of this syndrome combine brain atrophy with clubfoot and arthrogryposis. Affected individuals present with cerebral parenchymal underdevelopment, ranging from major cerebral parenchymal thinning with lissencephalic aspect to moderate parenchymal rarefaction, severe to mild ventriculomegaly, cerebellar hypoplasia with brainstem dysgenesis, and cardiac and ophthalmologic anomalies, such as microphthalmia and cataract...
December 27, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29237728/slightly-deleterious-genomic-variants-and-transcriptome-perturbations-in-down-syndrome-embryonic-selection
#5
Konstantin Popadin, Stephan Peischl, Marco Garieri, M Reza Sailani, Audrey Letourneau, Federico Santoni, Samuel W Lukowski, Georgii A Bazykin, Sergey Nikolaev, Diogo Meyer, Laurent Excoffier, Alexandre Reymond, Stylianos E Antonarakis
The majority of aneuploid fetuses are spontaneously miscarried. Nevertheless, some aneuploid individuals survive despite the strong genetic insult. Here, we investigate if the survival probability of aneuploid fetuses is affected by the genome-wide burden of slightly deleterious variants. We analyzed two cohorts of live-born Down syndrome individuals (388 genotyped samples and 16 fibroblast transcriptomes) and observed a deficit of slightly deleterious variants on Chromosome 21 and decreased transcriptome-wide variation in the expression level of highly constrained genes...
December 13, 2017: Genome Research
https://www.readbyqxmd.com/read/29209081/low-number-of-fixed-somatic-mutations-in-a-long-lived-oak-tree
#6
Emanuel Schmid-Siegert, Namrata Sarkar, Christian Iseli, Sandra Calderon, Caroline Gouhier-Darimont, Jacqueline Chrast, Pietro Cattaneo, Frédéric Schütz, Laurent Farinelli, Marco Pagni, Michel Schneider, Jérémie Voumard, Michel Jaboyedoff, Christian Fankhauser, Christian S Hardtke, Laurent Keller, John R Pannell, Alexandre Reymond, Marc Robinson-Rechavi, Ioannis Xenarios, Philippe Reymond
Because plants do not possess a defined germline, deleterious somatic mutations can be passed to gametes, and a large number of cell divisions separating zygote from gamete formation may lead to many mutations in long-lived plants. We sequenced the genome of two terminal branches of a 234-year-old oak tree and found several fixed somatic single-nucleotide variants whose sequential appearance in the tree could be traced along nested sectors of younger branches. Our data suggest that stem cells of shoot meristems in trees are robustly protected from the accumulation of mutations...
December 2017: Nature Plants
https://www.readbyqxmd.com/read/29206041/lipidated-peptide-dendrimers-killing-multidrug-resistant-bacteria
#7
Thissa N Siriwardena, Michaela Stach, Runze He, Bee-Ha Gan, Sacha Javor, Marc Heitz, Lan Ma, Xiangjun Cai, Peng Chen, Dengwen Wei, Hongtao Li, Jun Ma, Thilo Koehler, Christian van Delden, Tamis Darbre, Jean-Louis Reymond
New antibiotics are urgently needed to address multidrug resistant (MDR) bacteria. Herein we report that second generation (G2) peptide dendrimers bearing a fatty acid chain at the dendrimer core efficiently kill Gram-negative bacteria including Pseudomonas aeruginosa and Acinetobacter baumannii, two of the most problematic MRD bacteria worldwide. Our most active dendrimer TNS18 is also active against Gram-positive methicillin resistant Staphylococcus aureus (MRSA). Based on circular dichroism and molecular dynamics studies we hypothesize that TNS18 adopts a hydrophobically collapsed conformation in water with the fatty acid chain backfolded onto the peptide dendrimer branches, and that the dendrimer unfolds in contact with the membrane to expose its lipid chain and hydrophobic residues, thereby facilitating membrane disruption leading to rapid bacterial cell death...
December 5, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29195391/micro-view-cell-for-phase-behaviour-and-in-situ-raman-analysis-of-heterogeneously-catalysed-co2-hydrogenation
#8
Helena Reymond, Philipp Rudolf von Rohr
The operando study of CO2 hydrogenation is fundamental for a more rational optimisation of heterogeneous catalyst and reactor designs. To further complement the established efficiency of microreactors in reaction screening and bridge the operating and optical gaps, a micro-view-cell is presented for Raman microscopy at extreme conditions with minimum flow interference for genuine reaction analysis. Based on a flat sapphire window unit sealed in a plug flow-type enclosure holding the sample, the cell features unique 14 mm working distance and 0...
November 2017: Review of Scientific Instruments
https://www.readbyqxmd.com/read/29193635/inactivation-of-ammecr1-is-associated-with-growth-bone-and-heart-alterations
#9
Mariana Moysés-Oliveira, Giuliana Giannuzzi, Richard J Fish, Jill A Rosenfeld, Florence Petit, Maria de Fatima Soares, Leslie Domenici Kulikowski, Adriana Di Battista, Malú Zamariolli, Fan Xia, Thomas Liehr, Nadezda Kosyakova, Gianna Carvalheira, Michael Parker, Eleanor G Seaby, Sarah Ennis, Rodney D Gilbert, R Tanner Hagelstrom, Maria L Cremona, Wenhui L Li, Alka Malhotra, Anjana Chandrasekhar, Denise L Perry, Ryan J Taft, Julie McCarrier, Donald G Basel, Joris Andrieux, Taiza Stumpp, Fernanda Antunes, Gustavo José Pereira, Marguerite Neerman-Arbez, Vera Ayres Meloni, Margaret Drummond-Borg, Maria Isabel Melaragno, Alexandre Reymond
We report five individuals with loss-of-function of the X-linked AMMECR1: a girl with a balanced X-autosome translocation and inactivation of the normal X-chromosome; two boys with maternally-inherited and de novo nonsense variants; and two half-brothers with maternally inherited microdeletion variants. They present with short stature, cardiac and skeletal abnormalities and hearing loss. Variants of unknown significance in AMMECR1 in four male patients from two families with partially overlapping phenotypes were previously reported...
November 28, 2017: Human Mutation
https://www.readbyqxmd.com/read/29186333/fun-a-framework-for-interactive-visualizations-of-large-high-dimensional-datasets-on-the-web
#10
Daniel Probst, Jean-Louis Reymond
Motivation: During the past decade, big data has become a major tool in scientific endeavors. While statistical methods and algorithms are well-suited for analyzing and summarizing enormous amounts of data, the results do not allow for a visual inspection of the entire data. Current scientific software, including R packages and Python libraries such as ggplot2, matplotlib, and plot.ly, do not support interactive visualizations of datasets exceeding 100,000 data points on the web. Other solutions enable the web-based visualization of big data only through data reduction or statistical representations...
November 24, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29163899/design-crystal-structure-and-atomic-force-microscopy-study-of-thioether-ligated-d-l-cyclic-antimicrobial-peptides-against-multidrug-resistant-pseudomonas-aeruginosa
#11
Runze He, Ivan Di Bonaventura, Ricardo Visini, Bee-Ha Gan, Yongchun Fu, Daniel Probst, Alexandre Lüscher, Thilo Köhler, Christian van Delden, Achim Stocker, Wenjing Hong, Tamis Darbre, Jean-Louis Reymond
Here we report a new family of cyclic antimicrobial peptides (CAMPs) targeting MDR strains of Pseudomonas aeruginosa. These CAMPs are cyclized via a xylene double thioether bridge connecting two cysteines placed at the ends of a linear amphiphilic alternating d,l-sequence composed of lysines and tryptophans. Investigations by transmission electron microscopy (TEM), dynamic light scattering and atomic force microscopy (AFM) suggest that these peptide macrocycles interact with the membrane to form lipid-peptide aggregates...
November 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29160609/plant-arthropod-interactions-who-is-the-winner
#12
Elia Stahl, Olivier Hilfiker, Philippe Reymond
Herbivorous arthropods have interacted with plants for millions of years. During feeding they release chemical cues that allow plants to detect the attack and mount an efficient defense response. A signaling cascade triggers the expression of hundreds of genes, which encode defensive proteins and enzymes for synthesis of toxic metabolites. This direct defense is often complemented by emission of volatiles that attract beneficial parasitoids. In return, arthropods have evolved strategies to interfere with plant defenses, either by producing effectors to inhibit detection and downstream signaling steps, or by adapting to their detrimental effect...
November 21, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29154440/mapping-of-the-available-chemical-space-versus-the-chemical-universe-of-lead-like-compounds
#13
Arkadii Lin, Dragos Horvath, Valentina Afonina, Gilles Marcou, Reymond Jean-Louis, Alexandre Varnek
This is, to our knowledge, the to-date most comprehensive analysis based on Generative Topographic Mapping (GTM) of the fragment-like chemical space (40M molecules with no more than 17 heavy atoms, both from the theoretically enumerated GDB-17, and real-world PubChem/ChEMBL). The challenge was to prove that a robust map of fragment-like chemical space can actually be built, in spite of a limited (<105) maximal number of compounds ("frame set") usable for fitting the GTM manifold. An evolutionary map building strategy has been updated with a "coverage check" step, discarding manifolds failing to accommodate compounds outside the frame set...
November 20, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29147502/chemical-space-guided-discovery-of-antimicrobial-bridged-bicyclic-peptides-against-pseudomonas-aeruginosa-and-its-biofilms
#14
Ivan Di Bonaventura, Xian Jin, Ricardo Visini, Daniel Probst, Sacha Javor, Bee-Ha Gan, Gaëlle Michaud, Antonino Natalello, Silvia Maria Doglia, Thilo Köhler, Christian van Delden, Achim Stocker, Tamis Darbre, Jean-Louis Reymond
Herein we report the discovery of antimicrobial bridged bicyclic peptides (AMBPs) active against Pseudomonas aeruginosa, a highly problematic Gram negative bacterium in the hospital environment. Two of these AMBPs show strong biofilm inhibition and dispersal activity and enhance the activity of polymyxin, currently a last resort antibiotic against which resistance is emerging. To discover our AMBPs we used the concept of chemical space, which is well known in the area of small molecule drug discovery, to define a small number of test compounds for synthesis and experimental evaluation...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29130376/the-cuticle-mutant-eca2-modifies-the-plant-defense-responses-to-biotrophic-and-necrotrophic-pathogens-and-herbivory-insects
#15
Catherine Blanc, Fania Coluccia, Floriane L'Haridon, Martha Torres, Marlene Ortiz-Berrocal, Elia Stahl, Philippe Reymond, Lukas Schreiber, Christiane Nawrath, Jean-Pierre Metraux, Mario Serrano
We isolated previously several Arabidopsis thaliana mutants with constitutive expression of the early MAMP-induced gene ATL2, named eca (expresión constitutiva de ATL2). Here we further explored the interaction of eca mutants with pest and pathogens. Of all eca mutants, eca2 was more resistant to a fungal (Botrytis cinerea) and a bacterial (Pseudomonas syringae) pathogen, as well as to a generalist herbivorous insect (Spodoptera littoralis). Permeability of the cuticle is increased in eca2; chemical characterization shows that eca2 has a significant reduction of both cuticular wax and cutin...
November 13, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/29118822/histological-quantification-of-maize-stem-sections-from-fasga-stained-images
#16
David Legland, Fadi El-Hage, Valérie Méchin, Matthieu Reymond
Background: Crop species are of increasing interest both for cattle feeding and for bioethanol production. The degradability of the plant material largely depends on the lignification of the tissues, but it also depends on histological features such as the cellular morphology or the relative amount of each tissue fraction. There is therefore a need for high-throughput phenotyping systems that quantify the histology of plant sections. Results: We developed custom image processing and an analysis procedure for quantifying the histology of maize stem sections coloured with FASGA staining and digitalised with whole microscopy slide scanners...
2017: Plant Methods
https://www.readbyqxmd.com/read/29116786/discovery-of-a-potent-selective-t-type-calcium-channel-blocker-as-a-drug-candidate-for-the-treatment-of-generalized-epilepsies
#17
Olivier Bezençon, Bibia Heidmann, Romain Siegrist, Simon Stamm, Sylvia Richard, Davide Pozzi, Olivier Corminboeuf, Catherine Roch, Melanie Kessler, Eric A Ertel, Isabelle Reymond, Thomas Pfeifer, Ruben de Kanter, Michael Toeroek-Schafroth, Luca G Moccia, Jacques Mawet, Richard Moon, Markus Rey, Bruno Capeleto, Elvire Fournier
We report here the discovery and pharmacological characterization of N-(1-benzyl-1H-pyrazol-3-yl)-2-phenylacetamide derivatives as potent, selective, brain-penetrating T-type calcium channel blockers. Optimization focused mainly on solubility, brain penetration, and search for an aminopyrazole metabolite that would be negative in an Ames test. This resulted in the preparation and complete characterization of compound 66b (ACT-709478), which has been selected as clinical candidate.
November 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29077657/does-portopulmonary-hypertension-impede-liver-transplantation-in-cirrhotic-patients-a-french-multicentric-retrospective-study
#18
Maud Reymond, Louise Barbier, Ephrem Salame, Camille Besh, Jerome Dumortier, Georges-Philippe Pageaux, Christophe Bureau, Sébastien Dharancy, Claire Vanlemmens, Armand Abergel, Marie-Lorraine Woehl Jaegle, Pascal Magro, Frederic Patat, Emeline Laurent, Jean-Marc Perarnau
BACKGROUND: Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension associated with portal hypertension. Its presence is a major stake for cirrhotic patients requiring liver transplantation, with increased postoperative mortality and unpredictable evolution after transplantation. The aim was to study outcomes after liver transplantation in patients with portopulmonary hypertension and to identify factors associated with normalization of pulmonary hypertension...
October 26, 2017: Transplantation
https://www.readbyqxmd.com/read/29070417/milestones-to-the-discovery-of-t-type-calcium-channel-blockers-for-the-treatment-of-generalized-epilepsies
#19
Olivier Bezençon, Romain Siegrist, Bibia Heidmann, Davide Pozzi, Simon Stamm, Luboš Remeň, Sylvia Richard, Lloyd Simons, Rick Gaston, Dennis Downing, Corinna Grisostomi, Catherine Roch, Melanie Kessler, John Gatfield, Richard Moon, Thomas Pfeifer, Johannes Mosbacher, Isabelle Reymond, Eric A Ertel, Ruben de Kanter, Bruno Capeleto, Elvire Fournier, Markus Rey, Luca Moccia, Michael Toeroek-Schafroth, René Roscher, Benno Schindelholz
We describe the discovery and optimization of new, brain-penetrant T-type calcium channel blockers. We present optimized compounds with excellent efficacy in a rodent model of generalized absence-like epilepsy. Along the fine optimization of a chemical series with a pharmacological target located in the CNS (target potency, brain penetration, and solubility), we successfully identified an Ames negative aminopyrazole as putative metabolite of this compound series. Our efforts culminated in the selection of compound 20, which was elected as a preclinical candidate...
October 25, 2017: Chimia
https://www.readbyqxmd.com/read/29070411/chemical-space-big-data-challenge-for-molecular-diversity
#20
Mahendra Awale, Ricardo Visini, Daniel Probst, Josep Arús-Pous, Jean-Louis Reymond
Chemical space describes all possible molecules as well as multi-dimensional conceptual spaces representing the structural diversity of these molecules. Part of this chemical space is available in public databases ranging from thousands to billions of compounds. Exploiting these databases for drug discovery represents a typical big data problem limited by computational power, data storage and data access capacity. Here we review recent developments of our laboratory, including progress in the chemical universe databases (GDB) and the fragment subset FDB-17, tools for ligand-based virtual screening by nearest neighbor searches, such as our multi-fingerprint browser for the ZINC database to select purchasable screening compounds, and their application to discover potent and selective inhibitors for calcium channel TRPV6 and Aurora A kinase, the polypharmacology browser (PPB) for predicting off-target effects, and finally interactive 3D-chemical space visualization using our online tools WebDrugCS and WebMolCS...
October 25, 2017: Chimia
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