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https://www.readbyqxmd.com/read/28640881/t3ss-effector-vopl-inhibits-the-host-ros-response-promoting-the-intracellular-survival-of-vibrio-parahaemolyticus
#1
Marcela de Souza Santos, Dor Salomon, Kim Orth
The production of antimicrobial reactive oxygen species by the nicotinamide dinucleotide phosphate (NADPH) oxidase complex is an important mechanism for control of invading pathogens. Herein, we show that the gastrointestinal pathogen Vibrio parahaemolyticus counteracts reactive oxygen species (ROS) production using the Type III Secretion System 2 (T3SS2) effector VopL. In the absence of VopL, intracellular V. parahaemolyticus undergoes ROS-dependent filamentation, with concurrent limited growth. During infection, VopL assembles actin into non-functional filaments resulting in a dysfunctional actin cytoskeleton that can no longer mediate the assembly of the NADPH oxidase at the cell membrane, thereby limiting ROS production...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28634231/hyperactivity-of-the-arabidopsis-cryptochrome-cry1-l407f-mutant-is-caused-by-a-structural-alteration-close-to-the-cry1-atp-binding-sit
#2
Christian Orth, Nils Niemann, Lars Hennig, Lars-Oliver Essen, Alfred Batschauer
Plant cryptochromes (cry) act as UV-A/blue light receptors. The prototype, Arabidopsis thaliana cry1, regulates several light responses during the life cycle, including de-etiolation, and is also involved in regulating flowering time. The cry1 photocycle is initiated by light absorption by its FAD chromophore, which is most likely fully oxidized (FADox) in the dark state and photoreduced to the neutral flavin semiquinone (FADH(o)) in its lit state. Cryptochromes lack the DNA-repair activity of the closely related DNA photolyases, but retain the ability to bind nucleotides such as ATP...
June 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28630066/porphyromonas-gulae-activates-unprimed-and-ifn%C3%AE-primed-macrophages-via-the-pattern-recognition-receptors-tlr-2-tlr-4-and-nod2
#3
James A Holden, Neil M O'Brien-Simpson, Jason C Lenzo, Rebecca K H Orth, Ashley Mansell, Eric C Reynolds
Porphyromonas gulae is an anaerobic, Gram-negative coccobacillus that has been associated with periodontal disease in companion animals. The aims of this study were to analyse the ligation of pattern recognition receptors by P. gulae and the subsequent activation of macrophages. Exposure of HEK cells transfected with Toll-like receptors or NOD-like receptors to P. gulae resulted in the ligation of TLR2, TLR4 and NOD2. The effect of this engagement of receptors was investigated by measuring the synthesis of nitric oxide, CD86 expression and inflammatory cytokine production using wild type, TLR2-/- and TLR4-/- macrophages...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28607559/bone-marrow-aspirate-concentrate-enhanced-marrow-stimulation-of-chondral-defects
#4
REVIEW
Henning Madry, Liang Gao, Hermann Eichler, Patrick Orth, Magali Cucchiarini
Mesenchymal stem cells (MSCs) from bone marrow play a critical role in osteochondral repair. A bone marrow clot forms within the cartilage defect either as a result of marrow stimulation or during the course of the spontaneous repair of osteochondral defects. Mobilized pluripotent MSCs from the subchondral bone migrate into the defect filled with the clot, differentiate into chondrocytes and osteoblasts, and form a repair tissue over time. The additional application of a bone marrow aspirate (BMA) to the procedure of marrow stimulation is thought to enhance cartilage repair as it may provide both an additional cell population capable of chondrogenesis and a source of growth factors stimulating cartilage repair...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28604476/pet-mr-in-the-assessment-of-pediatric-histiocytoses-a-comparison-to-pet-ct
#5
Andrew C Sher, Robert Orth, Kenneth McClain, Carl Allen, Shireen Hayatghaibi, Victor Seghers
PURPOSE: The aim of this study was to analyze the feasibility and diagnostic performance of F-FDG PET/MR compared with F-FDG PET/CT in a cohort of pediatric histiocytosis patients with regard to image quality, lesion detection, and FDG quantification. METHODS: Children with a diagnosis of Langerhans cell histiocytosis or Rosai-Dorfman disease were prospectively recruited. Seventeen PET/CT and PET/MR examinations were performed on 9 patients (mean age, 6.2 years) following a single-injection dual-imaging protocol...
June 9, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28597054/-benign-tumours-of-the-musculoskeletal-system
#6
EDITORIAL
P Orth, D Kohn
No abstract text is available yet for this article.
June 2017: Der Orthopäde
https://www.readbyqxmd.com/read/28589731/next-steps-in-ewing-sarcoma-epi-genomics
#7
Giuseppina Sannino, Martin F Orth, Thomas Gp Grünewald
No abstract text is available yet for this article.
June 7, 2017: Future Oncology
https://www.readbyqxmd.com/read/28587659/glutaminyl-cyclase-activity-correlates-with-levels-of-a%C3%AE-peptides-and-mediators-of-angiogenesis-in-cerebrospinal-fluid-of-alzheimer-s-disease-patients
#8
Claire Bridel, Torsten Hoffmann, Antje Meyer, Sisi Durieux, Marleen A Koel-Simmelink, Matthias Orth, Philip Scheltens, Inge Lues, Charlotte E Teunissen
BACKGROUND: Pyroglutamylation of truncated Aβ peptides, which is catalysed by enzyme glutaminyl cyclase (QC), generates pE-Aβ species with enhanced aggregation propensities and resistance to most amino-peptidases and endo-peptidases. pE-Aβ species have been identified as major constituents of Aβ plaques and reduction of pE-Aβ species is associated with improvement of cognitive tasks in animal models of Alzheimer's disease (AD). Pharmacological inhibition of QC has thus emerged as a promising therapeutic approach for AD...
June 6, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28558971/fused-bi-heteroaryl-substituted-hydantoin-compounds-as-tace-inhibitors
#9
Ling Tong, Seong Heon Kim, Kristin Rosner, Wensheng Yu, Bandarpalle B Shankar, Lei Chen, Dansu Li, Chaoyang Dai, Vinay Girijavallabhan, Janeta Popovici-Muller, Liping Yang, Guowei Zhou, Aneta Kosinski, M Arshad Siddiqui, Neng-Yang Shih, Zhuyan Guo, Peter Orth, Shiying Chen, Daniel Lundell, Xiaoda Niu, Shelby Umland, Joseph A Kozlowski
We have identified a series of hydantoin-derived TNF-a converting enzyme (TACE) inhibitors containing a pendant fused bi-heteroaryl group, which demonstrate sub-nanomolar potency (Ki), excellent activity in human whole blood assay, and improved DMPK profiles over prior series.
May 22, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28542590/the-mth1-inhibitor-th588-demonstrates-anti-tumoral-effects-alone-and-in-combination-with-everolimus-5-fu-and-gamma-irradiation-in-neuroendocrine-tumor-cells
#10
Elke Tatjana Aristizabal Prada, Michael Orth, Svenja Nölting, Gerald Spöttl, Julian Maurer, Christoph Auernhammer
Modulation of the redox system in cancer cells has been considered a promising target for anti-cancer therapy. The novel MTH1 inhibitor TH588 proved tremendous potential in terms of cancer cell eradication, yet its specificity has been questioned by recent reports, indicating that TH588 may also induce cancer cell death by alternative mechanisms than MTH1 inhibition. Here we used a panel of heterogeneous neuroendocrine tumor cells in order to assess cellular mechanisms and molecular signaling pathways implicated in the effects of TH588 alone as well as dual-targeting approaches combining TH588 with everolimus, cytotoxic 5-fluorouracil or γ-irradiation...
2017: PloS One
https://www.readbyqxmd.com/read/28533562/accelerating-tropicalization-and-the-transformation-of-temperate-seagrass-meadows
#11
Glenn A Hyndes, Kenneth L Heck, Adriana Vergés, Euan S Harvey, Gary A Kendrick, Paul S Lavery, Kathryn McMahon, Robert J Orth, Alan Pearce, Mathew Vanderklift, Thomas Wernberg, Scott Whiting, Shaun Wilson
Climate-driven changes are altering production and functioning of biotic assemblages in terrestrial and aquatic environments. In temperate coastal waters, rising sea temperatures, warm water anomalies and poleward shifts in the distribution of tropical herbivores have had a detrimental effect on algal forests. We develop generalized scenarios of this form of tropicalization and its potential effects on the structure and functioning of globally significant and threatened seagrass ecosystems, through poleward shifts in tropical seagrasses and herbivores...
November 1, 2016: Bioscience
https://www.readbyqxmd.com/read/28526202/capnocytophaga-canimorsus-an-underestimated-cause-of-periprosthetic-joint-infection
#12
Marcel Orth, Patrick Orth, Konstantinos Anagnostakos
BACKGROUND: Periprosthetic joint infection (PJI) is a major clinical problem in orthopedic surgery. Capnocytophaga canimorsus (C. canimorsus) is an unusual and hardly detectable bacterium. A review of the literature indicates that C. canimorsus affects mainly immunocompromised patients. It has not been reported to cause periprosthetic joint infections in immunocompetent patients so far. This case report aims to raise awareness of C. canimorsus in orthopedic surgery with special regard to joint arthroplasty...
May 16, 2017: Knee
https://www.readbyqxmd.com/read/28516419/abstracts-of-the-52nd-workshop-for-pediatric-research-frankfurt-germany-27-28-october-2016
#13
Rhea van den Bruck, Patrick P Weil, Thomas Ziegenhals, Philipp Schreiner, Stefan Juranek, Daniel Gödde, Silvia Vogel, Frauke Schuster, Valerie Orth, Johannes Dörner, Daniel Pembaur, Meike Röper, Stefan Störkel, Hubert Zirngibl, Stefan Wirth, Andreas C W Jenke, Jan Postberg, Nikolas Boy, Jana Heringer, Gisela Haege, Esther M Glahn, Georg F Hoffmann, Sven F Garbade, Peter Burgard, Stefan Kölker, Cho-Ming Chao, Faady Yahya, Alena Moiseenko, Amit Shrestha, Negah Ahmadvand, Jennifer Quantius, Jochen Wilhelm, Elie El-Agha, Klaus-Peter Zimmer, Saverio Bellusci, Christian Staufner, Stefan Kölker, Holger Prokisch, Georg F Hoffmann, Stephan Seeliger, Matthias Müller, Andreas Hippe, Henrik Steinkraus, Roland Wauer, Burkhard Lachmann, Sigrun R Hofmann, Christian M Hedrich, Jakob Zierk, Farhad Arzideh, Rainer Haeckel, Wolfgang Rascher, Manfred Rauh, Markus Metzler, Sebastian Thieme, Joanna Bandoła, Cornelia Richter, Martin Ryser, Arshad Jamal, Michelle P Ashton, Malte von Bonin, Matthias Kuhn, Christian M Hedrich, Ezio Bonifacio, Reinhard Berner, Sebastian Brenner, Johanna Hammersen, Cristina Has, Nora Naumann-Bartsch, Daniel Stachel, Dimitra Kiritsi, Stephan Söder, Mathilde Tardieu, Markus Metzler, Leena Bruckner-Tuderman, Holm Schneider, F Bohne, D Langer, R Cencic, T Eggermann, U Zechner, J Pelletier, F Zepp, T Enklaar, D Prawitt, Martin Pech, Markus Weckmann, Femke-Anouska Heinsen, Andre Franke, Christine Happle, Anna-Maria Dittrich, Gesine Hansen, Oliver Fuchs, Erika von Mutius, Brian G Oliver, Matthias V Kopp, Claudia Paret, Alexandra Russo, Johanna Theruvath, Bettina Keller, Khalifa El Malki, Nadine Lehmann, Arthur Wingerter, Marie A Neu, Gerhold-Ay Aslihan, Wolfgang Wagner, Clemens Sommer, Torsten Pietsch, Larissa Seidmann, Jörg Faber, Felix Schreiner, Merle Ackermann, Michael Michalik, Eva Rother, Andras Bilkei-Gorzo, Ildiko Racz, Laura Bindila, Beat Lutz, Jörg Dötsch, Andreas Zimmer, Joachim Woelfle, Hendrik S Fischer, Tim L Ullrich, Christoph Bührer, Christoph Czernik, Gerd Schmalisch, Robert Stein, Sigrun R Hofmann, Judith Hagenbuchner, Ursula Kiechl-Kohlendorfer, Petra Obexer, Michael J Ausserlechner, Niki T Loges, Adrien Tobias Frommer, Julia Wallmeier, Heymut Omran, Soner Öner-Sieben, Martina Gimpfl, Jan Rozman, Martin Irmler, Johannes Beckers, Martin Hrabe De Angelis, Adelbert Roscher, Eckhard Wolf, Regina Ensenauer, Karolina Nemes, Michael Frühwald, Martin Hasselblatt, Reiner Siebert, Uwe Kordes, Marcel Kool, Haicui Wang, Holly Hardy, Osama Refai, Katy E S Barwick, Holly H Zimmerman, Joachim Weis, Emma L Baple, Andrew H Crosby, Sebahattin Cirak, C Hellmuth, O Uhl, M Standl, J Heinrich, E Thiering, B Koletzko, Lena Blümel, Kornelius Kerl, Daniel Picard, Michael C Frühwald, Max C Liebau, Guido Reifenberger, Arndt Borkhardt, Martin Hasselblatt, Marc Remke, D Tews, M Wabitsch, P Fischer-Posovszky, Mike-Andrew Westhoff, Lisa Nonnenmacher, Julia Langhans, Lukas Schneele, Nancy Trenkler, Klaus-Michael Debatin
No abstract text is available yet for this article.
May 2017: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/28515982/current-concepts-on-the-genetic-factors-in-rotator-cuff-pathology-and-future-implications-for-sports-physical-therapists
#14
Travis Orth, Jessica Paré, John E Froehlich
CONTEXT: Recent advances within the field of genetics are currently changing many of the methodologies in which medicine is practiced. These advances are also beginning to influence the manner in which physical therapy services are rendered. Rotator cuff pathology is one of the most common diagnoses treated by the sports physical therapist. The purpose of this commentary is to educate sports physical therapists on the recent advances regarding how genetics influences rotator cuff pathology, including rotator cuff tears, and provide a perspective on how this information will likely influence post-operative shoulder rehabilitation in the near future...
April 2017: International Journal of Sports Physical Therapy
https://www.readbyqxmd.com/read/28512146/science-signaling-podcast-for-16-may-2017-vibrio-rewires-host-cells
#15
Nicole J De Nisco, Kim Orth, Annalisa M VanHook
This Podcast features a conversation with Kim Orth and Nicole De Nisco, authors of a Research Resource that appears in the 16 May 2017 issue of Science Signaling, about how the marine bacterium Vibrio parahaemolyticus rewires host cell signaling networks. V. parahaemolyticus thrives in warm brackish waters and infects both shellfish and finfish. This bacterium causes gastroenteritis when humans consume contaminated seafood that is raw or undercooked. V. parahaemolyticus delivers virulence factors into host cells through two different type 3 secretion systems (T3SSes)...
May 16, 2017: Science Signaling
https://www.readbyqxmd.com/read/28512145/the-cytotoxic-type-3-secretion-system-1-of-vibrio-rewires-host-gene-expression-to-subvert-cell-death-and-activate-cell-survival-pathways
#16
Nicole J De Nisco, Mohammed Kanchwala, Peng Li, Jessie Fernandez, Chao Xing, Kim Orth
Bacterial effectors potently manipulate host signaling pathways. The marine bacterium Vibrio parahaemolyticus (V. para) delivers effectors into host cells through two type 3 secretion systems (T3SSs). T3SS1 is vital for V. para survival in the environment, whereas T3SS2 causes acute gastroenteritis in human hosts. Although the natural host is undefined, T3SS1 effectors attack highly conserved cellular processes and pathways to orchestrate nonapoptotic cell death. To understand how the concerted action of T3SS1 effectors globally affects host cell signaling, we compared gene expression changes over time in primary fibroblasts infected with V...
May 16, 2017: Science Signaling
https://www.readbyqxmd.com/read/28492237/proline-metabolism-supports-metastasis-formation-and-could-be-inhibited-to-selectively-target-metastasizing-cancer-cells
#17
Ilaria Elia, Dorien Broekaert, Stefan Christen, Ruben Boon, Enrico Radaelli, Martin F Orth, Catherine Verfaillie, Thomas G P Grünewald, Sarah-Maria Fendt
Metastases are the leading cause of mortality in patients with cancer. Metastasis formation requires cancer cells to adapt their cellular phenotype. However, how metabolism supports this adaptation of cancer cells is poorly defined. We use 2D versus 3D cultivation to induce a shift in the cellular phenotype of breast cancer cells. We discover that proline catabolism via proline dehydrogenase (Prodh) supports growth of breast cancer cells in 3D culture. Subsequently, we link proline catabolism to in vivo metastasis formation...
May 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28467801/inhibition-of-exportin-1-function-results-in-rapid-cell-cycle-associated-dna-damage-in-cancer-cells
#18
Russell T Burke, Joshua M Marcus, James D Orth
Selective inhibitors of nuclear export (SINE) are small molecules in development as anti-cancer agents. The first-in-class SINE, selinexor, is in clinical trials for blood and solid cancers. Selinexor forms a covalent bond with exportin-1 at cysteine-528, and blocks its ability to export cargos. Previous work has shown strong cell cycle effects and drug-induced cell death across many different cancer-derived cell lines. Here, we report strong cell cycle-associated DNA double-stranded break formation upon the treatment of cancer cells with SINE...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28467017/peripheral-blood-aspirates-overexpressing-igf-i-via-raav-gene-transfer-undergo-enhanced-chondrogenic-differentiation-processes
#19
Janina Frisch, Patrick Orth, Ana Rey-Rico, Jagadeesh Kumar Venkatesan, Gertrud Schmitt, Henning Madry, Dieter Kohn, Magali Cucchiarini
Implantation of peripheral blood aspirates induced towards chondrogenic differentiation upon genetic modification in sites of articular cartilage injury may represent a powerful strategy to enhance cartilage repair. Such a single-step approach may be less invasive than procedures based on the use of isolated or concentrated MSCs, simplifying translational protocols in patients. In this study, we provide evidence showing the feasibility of overexpressing the mitogenic and pro-anabolic insulin-like growth factor I (IGF-I) in human peripheral blood aspirates via rAAV-mediated gene transfer, leading to enhanced proliferative and chondrogenic differentiation (proteoglycans, type-II collagen, SOX9) activities in the samples relative to control (reporter rAAV-lacZ) treatment over extended periods of time (at least 21 days, the longest time-point evaluated)...
May 3, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28447331/understanding-action-and-adventure-sports-participation-an-ecological-dynamics-perspective
#20
Tuomas Immonen, Eric Brymer, Dominic Orth, Keith Davids, Francesco Feletti, Jarmo Liukkonen, Timo Jaakkola
Previous research has considered action and adventure sports using a variety of associated terms and definitions which has led to confusing discourse and contradictory research findings. Traditional narratives have typically considered participation exclusively as the pastime of young people with abnormal characteristics or personalities having unhealthy and pathological tendencies to take risks because of the need for thrill, excitement or an adrenaline 'rush'. Conversely, recent research has linked even the most extreme forms of action and adventure sports to positive physical and psychological health and well-being outcomes...
December 2017: Sports Medicine—Open
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