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https://www.readbyqxmd.com/read/28437792/phase-plate-cryo-em-structure-of-a-class-b-gpcr-g-protein-complex
#1
Yi-Lynn Liang, Maryam Khoshouei, Mazdak Radjainia, Yan Zhang, Alisa Glukhova, Jeffrey Tarrasch, David M Thal, Sebastian G B Furness, George Christopoulos, Thomas Coudrat, Radostin Danev, Wolfgang Baumeister, Laurence J Miller, Arthur Christopoulos, Brian K Kobilka, Denise Wootten, Georgios Skiniotis, Patrick M Sexton
Class B G-protein-coupled receptors are major targets for the treatment of chronic diseases, such as osteoporosis, diabetes and obesity. Here we report the structure of a full-length class B receptor, the calcitonin receptor, in complex with peptide ligand and heterotrimeric Gαsβγ protein determined by Volta phase-plate single-particle cryo-electron microscopy. The peptide agonist engages the receptor by binding to an extended hydrophobic pocket facilitated by the large outward movement of the extracellular ends of transmembrane helices 6 and 7...
April 24, 2017: Nature
https://www.readbyqxmd.com/read/28437685/rapid-label-free-identification-of-klebsiella-pneumoniae-antibiotic-resistant-strains-by-the-drop-coating-deposition-surface-enhanced-raman-scattering-method
#2
Youjin Cheong, Young Jin Kim, Heeyoon Kang, Samjin Choi, Hee Joo Lee
Although many methodologies have been developed to identify unknown bacteria, bacterial identification in clinical microbiology remains a complex and time-consuming procedure. To address this problem, we developed a label-free method for rapidly identifying clinically relevant multilocus sequencing typing-verified quinolone-resistant Klebsiella pneumoniae strains. We also applied the method to identify three strains from colony samples, ATCC70063 (control), ST11 and ST15; these are the prevalent quinolone-resistant K...
April 20, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28437337/axial-plane-deformity-of-the-shoulder-in-adolescent-idiopathic-scoliosis
#3
Venugopal K Menon, Naveen Tahasildar, Haroon M Pillay, Anbuselvam M
STUDY DESIGN: Prospective observational study. OBJECTIVE: To study axial plane deformation of the shoulder in adolescent idiopathic scoliosis (AIS) and try to correlate it with curve type and surgical correction. SUMMARY OF BACKGROUND DATA: It is established that AIS is a 3-dimensional deformity. The rib hump is the most common manifestation of axial plane deformations; the least common manifestation seems to be upper trunk and shoulder rotation, which has been hitherto undescribed...
May 2017: Clinical Spine Surgery
https://www.readbyqxmd.com/read/28437228/first-case-of-ndm-1-producing-klebsiella-pneumoniae-in-annaba-university-hospital-algeria
#4
Amel Abderrahim, Nassima Djahmi, Charlotte Pujol, Sabina Nedjai, Mohamed Cherif Bentakouk, Djamila Kirane-Gacemi, Mazouz Dekhil, Albert Sotto, Jean-Philippe Lavigne, Alix Pantel
AIM: The aim of this study was to characterize two carbapenem-resistant Klebsiella pneumoniae isolates recovered from urine samples in a patient hospitalized at Annaba University hospital (Algeria) in 2014. RESULTS: Two K. pneumoniae isolates were studied because they proved resistant to almost all antibiotics tested with a high level resistance to ertapenem (minimum inhibitory concentration = 32 mg/L). The results of modified Hodge test and combined disk test (ROSCO Diagnostica, Taastrup, Denmark) were positive...
February 22, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28436984/genomic-analyses-identify-hundreds-of-variants-associated-with-age-at-menarche-and-support-a-role-for-puberty-timing-in-cancer-risk
#5
Felix R Day, Deborah J Thompson, Hannes Helgason, Daniel I Chasman, Hilary Finucane, Patrick Sulem, Katherine S Ruth, Sean Whalen, Abhishek K Sarkar, Eva Albrecht, Elisabeth Altmaier, Marzyeh Amini, Caterina M Barbieri, Thibaud Boutin, Archie Campbell, Ellen Demerath, Ayush Giri, Chunyan He, Jouke J Hottenga, Robert Karlsson, Ivana Kolcic, Po-Ru Loh, Kathryn L Lunetta, Massimo Mangino, Brumat Marco, George McMahon, Sarah E Medland, Ilja M Nolte, Raymond Noordam, Teresa Nutile, Lavinia Paternoster, Natalia Perjakova, Eleonora Porcu, Lynda M Rose, Katharina E Schraut, Ayellet V Segrè, Albert V Smith, Lisette Stolk, Alexander Teumer, Irene L Andrulis, Stefania Bandinelli, Matthias W Beckmann, Javier Benitez, Sven Bergmann, Murielle Bochud, Eric Boerwinkle, Stig E Bojesen, Manjeet K Bolla, Judith S Brand, Hiltrud Brauch, Hermann Brenner, Linda Broer, Thomas Brüning, Julie E Buring, Harry Campbell, Eulalia Catamo, Stephen Chanock, Georgia Chenevix-Trench, Tanguy Corre, Fergus J Couch, Diana L Cousminer, Angela Cox, Laura Crisponi, Kamila Czene, George Davey Smith, Eco J C N de Geus, Renée de Mutsert, Immaculata De Vivo, Joe Dennis, Peter Devilee, Isabel Dos-Santos-Silva, Alison M Dunning, Johan G Eriksson, Peter A Fasching, Lindsay Fernández-Rhodes, Luigi Ferrucci, Dieter Flesch-Janys, Lude Franke, Marike Gabrielson, Ilaria Gandin, Graham G Giles, Harald Grallert, Daniel F Gudbjartsson, Pascal Guénel, Per Hall, Emily Hallberg, Ute Hamann, Tamara B Harris, Catharina A Hartman, Gerardo Heiss, Maartje J Hooning, John L Hopper, Frank Hu, David J Hunter, M Arfan Ikram, Hae Kyung Im, Marjo-Riitta Järvelin, Peter K Joshi, David Karasik, Manolis Kellis, Zoltan Kutalik, Genevieve LaChance, Diether Lambrechts, Claudia Langenberg, Lenore J Launer, Joop S E Laven, Stefania Lenarduzzi, Jingmei Li, Penelope A Lind, Sara Lindstrom, YongMei Liu, Jian'an Luan, Reedik Mägi, Arto Mannermaa, Hamdi Mbarek, Mark I McCarthy, Christa Meisinger, Thomas Meitinger, Cristina Menni, Andres Metspalu, Kyriaki Michailidou, Lili Milani, Roger L Milne, Grant W Montgomery, Anna M Mulligan, Mike A Nalls, Pau Navarro, Heli Nevanlinna, Dale R Nyholt, Albertine J Oldehinkel, Tracy A O'Mara, Sandosh Padmanabhan, Aarno Palotie, Nancy Pedersen, Annette Peters, Julian Peto, Paul D P Pharoah, Anneli Pouta, Paolo Radice, Iffat Rahman, Susan M Ring, Antonietta Robino, Frits R Rosendaal, Igor Rudan, Rico Rueedi, Daniela Ruggiero, Cinzia F Sala, Marjanka K Schmidt, Robert A Scott, Mitul Shah, Rossella Sorice, Melissa C Southey, Ulla Sovio, Meir Stampfer, Maristella Steri, Konstantin Strauch, Toshiko Tanaka, Emmi Tikkanen, Nicholas J Timpson, Michela Traglia, Thérèse Truong, Jonathan P Tyrer, André G Uitterlinden, Digna R Velez Edwards, Veronique Vitart, Uwe Völker, Peter Vollenweider, Qin Wang, Elisabeth Widen, Ko Willems van Dijk, Gonneke Willemsen, Robert Winqvist, Bruce H R Wolffenbuttel, Jing Hua Zhao, Magdalena Zoledziewska, Marek Zygmunt, Behrooz Z Alizadeh, Dorret I Boomsma, Marina Ciullo, Francesco Cucca, Tõnu Esko, Nora Franceschini, Christian Gieger, Vilmundur Gudnason, Caroline Hayward, Peter Kraft, Debbie A Lawlor, Patrik K E Magnusson, Nicholas G Martin, Dennis O Mook-Kanamori, Ellen A Nohr, Ozren Polasek, David Porteous, Alkes L Price, Paul M Ridker, Harold Snieder, Tim D Spector, Doris Stöckl, Daniela Toniolo, Sheila Ulivi, Jenny A Visser, Henry Völzke, Nicholas J Wareham, James F Wilson, Amanda B Spurdle, Unnur Thorsteindottir, Katherine S Pollard, Douglas F Easton, Joyce Y Tung, Jenny Chang-Claude, David Hinds, Anna Murray, Joanne M Murabito, Kari Stefansson, Ken K Ong, John R B Perry
The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P < 5 × 10(-8)) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues...
April 24, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28436950/mre11-stability-is-regulated-by-ck2-dependent-interaction-with-r2tp-complex
#6
P von Morgen, K Burdova, T G Flower, N J O'Reilly, S J Boulton, S J Smerdon, L Macurek, Z Hořejší
The MRN (MRE11-RAD50-NBS1) complex is essential for repair of DNA double-strand breaks and stalled replication forks. Mutations of the MRN complex subunit MRE11 cause the hereditary cancer-susceptibility disease ataxia-telangiectasia-like disorder (ATLD). Here we show that MRE11 directly interacts with PIH1D1, a subunit of heat-shock protein 90 cochaperone R2TP complex, which is required for the assembly of large protein complexes, such as RNA polymerase II, small nucleolar ribonucleoproteins and mammalian target of rapamycin complex 1...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28436620/arginine-rich-peptide-based-mrna-nanocomplexes-efficiently-instigate-cytotoxic-t-cell-immunity-dependent-on-the-amphipathic-organization-of-the-peptide
#7
Vimal K Udhayakumar, Ans De Beuckelaer, Joanne McCaffrey, Cian M McCrudden, Jonathan L Kirschman, Daryll Vanover, Lien Van Hoecke, Kenny Roose, Kim Deswarte, Bruno G De Geest, Stefan Lienenklaus, Philip J Santangelo, Johan Grooten, Helen O McCarthy, Stefaan De Koker
To date, the mRNA delivery field has been heavily dominated by lipid-based systems. Reports on the use of nonlipid carriers for mRNA delivery in contrast are rare in the context of mRNA vaccination. This paper describes the potential of a cell-penetrating peptide containing the amphipathic RALA motif to deliver antigen-encoding mRNA to the immune system. RALA condenses mRNA into nanocomplexes that display acidic pH-dependent membrane disruptive properties. RALA mRNA nanocomplexes enable mRNA escape from endosomes and thereby allow expression of mRNA inside the dendritic cell cytosol...
April 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28436537/error-prone-replication-bypass-of-the-imidazole-ring-opened-formamidopyrimidine-deoxyguanosine-adduct
#8
Yan Sha, Irina G Minko, Chanchal K Malik, Carmelo J Rizzo, R Stephen Lloyd
Addition of hydroxyl radicals to the C8 position of 2'-deoxyguanosine generates an 8-hydroxyguanyl radical that can be converted into either 8-oxo-7,8-dihydro-2'-deoxyguanosine or N-(2-deoxy-d-pentofuranosyl)-N-(2,6-diamino-4-hydroxy-5-formamidopyrimidine) (Fapy-dG). The Fapy-dG adduct can adopt different conformations and in particular, can exist in an unnatural α anomeric configuration in addition to canonical β configuration. Previous studies reported that in 5'-TGN-3' sequences, Fapy-dG predominantly induced G → T transversions in both mammalian cells and Escherichia coli, suggesting that mutations could be formed either via insertion of a dA opposite the 5' dT due to primer/template misalignment or as result of direct miscoding...
April 24, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28436497/metal-ion-binding-by-laterally-non-symmetric-macrobicyclic-oxa-aza-cryptands
#9
Parimal K Bharadwaj
Macrobicyclic cryptands incorporating amine groups along with oxygen donors that are laterally non-symmetric constitute an important class of organic compounds. These molecules can form inclusion complexes with different transition and main group metal ions. It is also possible to modify the binding characteristics of these compounds through attachment of different groups. Some of these metal complexes can be useful homogeneous catalysts in different organic transformations. If there are chiral centers present in the cryptands, they can be useful in asymmetric syntheses...
April 24, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28436482/pathospotter-k-a-computational-tool-for-the-automatic-identification-of-glomerular-lesions-in-histological-images-of-kidneys
#10
George O Barros, Brenda Navarro, Angelo Duarte, Washington L C Dos-Santos
PathoSpotter is a computational system designed to assist pathologists in teaching about and researching kidney diseases. PathoSpotter-K is the version that was developed to detect nephrological lesions in digital images of kidneys. Here, we present the results obtained using the first version of PathoSpotter-K, which uses classical image processing and pattern recognition methods to detect proliferative glomerular lesions with an accuracy of 88.3 ± 3.6%. Such performance is only achieved by similar systems if they use images of cell in contexts that are much less complex than the glomerular structure...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436453/functional-thermodynamics-structural-and-biological-studies-of-in-silico-identified-inhibitors-of-mycobacterium-tuberculosis-enoyl-acp-coa-reductase-enzyme
#11
Leonardo K B Martinelli, Mariane Rotta, Anne D Villela, Valnês S Rodrigues-Junior, Bruno L Abbadi, Rogério V Trindade, Guilherme O Petersen, Giuliano M Danesi, Laura R Nery, Ivani Pauli, Maria M Campos, Carla D Bonan, Osmar Norberto de Souza, Luiz A Basso, Diogenes S Santos
Novel chemotherapeutics agents are needed to kill Mycobacterium tuberculosis, the main causative agent of tuberculosis (TB). The M. tuberculosis 2-trans-enoyl-ACP(CoA) reductase enzyme (MtInhA) is the druggable bona fide target of isoniazid. New chemotypes were previously identified by two in silico approaches as potential ligands to MtInhA. The inhibition mode was determined by steady-state kinetics for seven compounds that inhibited MtInhA activity. Dissociation constant values at different temperatures were determined by protein fluorescence spectroscopy...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436451/empirical-modeling-of-physiochemical-immune-response-of-multilayer-zinc-oxide-nanomaterials-under-uv-exposure-to-melanoma-and-foreskin-fibroblasts
#12
Muhammad Fakhar-E-Alam, M Waseem Akram, Seemab Iqbal, K S Alimgeer, M Atif, K Sultana, M Willander, Zhiming M Wang
Carcinogenesis is a complex molecular process starting with genetic and epigenetic alterations, mutation stimulation, and DNA modification, which leads to proteomic adaptation ending with an uncontrolled proliferation mechanism. The current research focused on the empirical modelling of the physiological response of human melanoma cells (FM55P) and human foreskin fibroblasts cells (AG01518) to the multilayer zinc oxide (ZnO) nanomaterials under UV-A exposure. To validate this experimental scheme, multilayer ZnO nanomaterials were grown on a femtotip silver capillary and conjugated with protoporphyrin IX (PpIX)...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436375/evaluation-of-treatment-of-low-energy-distal-radial-fractures-in-postmenopausal-women
#13
Mariusz Tomaszuk, Jan Kiryluk, Andrzej Tomaszuk, Janusz Popko
BACKGROUND: Distal radial fractures are one of the most common injuries seen in traumatology. Most are treated conservatively with closed reduction and immobilisation in a plaster cast. However, this method does not always allow for achieving and maintaining normal fracture reduction in unstable fractures. The aim of this study was assess clinical and radiographic outcomes of treatment of distal radial fractures depending on the method used. MATERIAL AND METHODS: A total of 77 postmenopausal female subjects were divided into three subgroups, depending on the treatment methods: 1...
January 26, 2017: Ortopedia, Traumatologia, Rehabilitacja
https://www.readbyqxmd.com/read/28436082/tricellulin-is-a-target-of-the-ubiquitin-ligase-itch
#14
Susanne Jennek, Sonnhild Mittag, Juliane Reiche, Julie K Westphal, Stefanie Seelk, Max J Dörfel, Thorsten Pfirrmann, Karlheinz Friedrich, Anja Schütz, Udo Heinemann, Otmar Huber
Tricellulin, a member of the tight junction-associated MAGUK protein family, preferentially localizes to tricellular junctions in confluent polarized epithelial cell layers and is downregulated during the epithelial-mesenchymal transition. Posttranslational modifications are assumed to play critical roles in the process of downregulation of tricellulin at the protein level. Here, we report that the E3 ubiquitin ligase Itch forms a complex with tricellulin and thereby enhances its ubiquitination. Pull-down assays confirmed a direct interaction between tricellulin and Itch, which is mediated by the Itch WW domain and the N-terminus of tricellulin...
April 24, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28436054/low-cost-manufacturing-of-bioresorbable-conductors-by-evaporation-condensation-mediated-laser-printing-and-sintering-of-zn-nanoparticles
#15
Wan Shou, Bikram K Mahajan, Brandon Ludwig, Xiaowei Yu, Joshua Staggs, Xian Huang, Heng Pan
Currently, bioresorbable electronic devices are predominantly fabricated by complex and expensive vacuum-based integrated circuit (IC) processes. Here, a low-cost manufacturing approach for bioresorbable conductors on bioresorbable polymer substrates by evaporation-condensation-mediated laser printing and sintering of Zn nanoparticle is reported. Laser sintering of Zn nanoparticles has been technically difficult due to the surface oxide on nanoparticles. To circumvent the surface oxide, a novel approach is discovered to print and sinter Zn nanoparticle facilitated by evaporation-condensation in confined domains...
April 24, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28435957/an-asymmetric-vinylogous-mukaiyama-michael-reaction-of-%C3%AE-%C3%AE-unsaturated-2-acyl-imidazoles-catalyzed-by-chiral-sc-iii-or-er-iii-pybox-complexes
#16
Subhrajit Rout, Arko Das, Vinod K Singh
A highly diastereo- and enantioselective vinylogous Mukaiyama-Michael reaction of silyloxyfurans with α,β-unsaturated 2-acyl imidazoles catalyzed by either chiral Sc(iii) or Er(iii) complexes of a pybox ligand has been reported. The enantioenriched γ-butenolides formed in the reaction were further transformed into highly functionalized γ-lactones found as important structural frameworks in a wide range of biologically active natural products.
April 24, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28435954/electrostatically-stabilized-hybrids-of-carbon-and-maghemite-nanoparticles-electrochemical-study-and-application
#17
D Baratella, M Magro, P Jakubec, E Bonaiuto, J de Almeida Roger, E Gerotto, G Zoppellaro, J Tucek, K C Safarova, R Zbořil, A Cecconello, I Willner, S Santagata, P Sambo, F Vianello
Binary hybrids have been investigated for the past few decades due to the emerging properties of nanoparticle composites. Electrostatically stabilized core-shell nanostructures composed of surface active magnetic nanoparticles (SAMNs) and differently charged carbon nanomaterials display specific electrochemical properties. In this work, a set of binary hybrids that include a new class of magnetic nanoparticles is presented and the electrochemical features of the hybrids are reported. Gallic acid derived carbon dots (GA-CDs), PEG derived graphene dots (PEG-GDs), and quaternized carbon dots (Q-CDs) characterized by different charged groups were used for the preparation of different complexes with SAMNs...
April 24, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28435738/crystal-structure-of-2-2-2-azanidyl-benzyl-idene-amino-benzyl-idene-amino-4-chloro-phenol-ato-nickel-ii
#18
Fumiya Kobayashi, Atsushi Koga, Ryo Ohtani, Shinya Hayami, Masaaki Nakamura
The title complex, [Ni(C20H14ClN3O)], with an asymmetrically chloride-appended Schiff base ligand has been synthesized and structurally characterized at 100 K. In the compound, the central nickel(II) ion has a square-planar coordination geometry with N3O donors of the π-conjugated tetra-dentate Schiff base ligand. In the crystal, the complexes are connected into an inversion dimer via an Ni⋯Ni inter-action [3.1753 (5) Å] and a pair of π-π inter-actions [centroid-centroid distance = 3.8416 (16) Å]...
April 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28435584/intra-articular-entrapment-of-medial-epicondyle-fracture-fragment-in-elbow-joint-dislocation-causing-ulnar-neuropraxia-a-case-report
#19
J Syed, A R Zamri, S Jamaluddin, J K Ruben, M Gopindran
Traumatic elbow dislocations in children are rare but most of them are complex dislocations, and in such dislocations, medial humerus epicondyle fractureis the most common associated injury. Fracture incarceration in the elbow joint occurs in 5-18% of medial humerus epicondyle fractures but ulnar neuropraxia is very rare. Open reduction internal fixation is indicated in medial humerus epicondyle fracture with fracture incarceration, ulnar neuropraxia, marked instability or open fracture. Operative treatment options include fragment excision and sutures, closed or open reduction and Kirschner wire fixation, open reduction and suture fixation, open reduction and smooth pin fixation, and open reduction and screw fixation...
March 2017: Malaysian Orthopaedic Journal
https://www.readbyqxmd.com/read/28435528/discovery-of-highly-selective-inhibitors-of-the-immunoproteasome-low-molecular-mass-polypeptide-2-lmp2-subunit
#20
Henry W B Johnson, Janet L Anderl, Erin K Bradley, John Bui, Jeffrey Jones, Shirin Arastu-Kapur, Lisa M Kelly, Eric Lowe, David C Moebius, Tony Muchamuel, Christopher Kirk, Zhengping Wang, Dustin McMinn
Building upon the success of bortezomib (VELCADE) and carfilzomib (KYPROLIS), the design of a next generation of inhibitors targeting specific subunits within the immunoproteasome is of interest for the treatment of autoimmune disease. There are three catalytic subunits within the immunoproteasome (low molecular mass polypeptide-7, -2, and multicatalytic endopeptidase complex subunit-1; LMP7, LMP2, and MECL-1), and a campaign was undertaken to design a potent and selective LMP2 inhibitor with sufficient properties to allow for sustained inhibition in vivo...
April 13, 2017: ACS Medicinal Chemistry Letters
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