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Nicklas Skjoldager, Maria Blanner Bang, Martin Rykær, Olof Björnberg, Michael J Davies, Birte Svensson, Pernille Harris, Per Hägglund
The NADPH-dependent homodimeric flavoenzyme thioredoxin reductase (TrxR) provides reducing equivalents to thioredoxin, a key regulator of various cellular redox processes. Crystal structures of photo-inactivated thioredoxin reductase (TrxR) from the Gram-positive bacterium Lactococcus lactis have been determined. These structures reveal novel molecular features that provide further insight into the mechanisms behind the sensitivity of this enzyme toward visible light. We propose that a pocket on the si-face of the isoalloxazine ring accommodates oxygen that reacts with photo-excited FAD generating superoxide and a flavin radical that oxidize the isoalloxazine ring C7α methyl group and a nearby tyrosine residue...
April 11, 2017: Scientific Reports
Kai Kessenbrock, Prestina Smith, Sander Christiaan Steenbeek, Nicholas Pervolarakis, Raj Kumar, Yasuhiro Minami, Andrei Goga, Lindsay Hinck, Zena Werb
The mammary gland consists of an adipose tissue that, in a process called branching morphogenesis, is invaded by a ductal epithelial network comprising basal and luminal epithelial cells. Stem and progenitor cells drive mammary growth, and their proliferation is regulated by multiple extracellular cues. One of the key regulatory pathways for these cells is the β-catenin-dependent, canonical wingless-type MMTV integration site family (WNT) signaling pathway; however, the role of noncanonical WNT signaling within the mammary stem/progenitor system remains elusive...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
Alexandre Girard, Katija Jelicic, Don Van Ryk, Nicolas Rochereau, Claudia Cicala, James Arthos, Blandine Noailly, Christian Genin, Bernard Verrier, Stephanie Laurant, Diane Razanajaoana-Doll, Jean-Jacques Pin, Stéphane Paul
The homing of lymphocytes to the mucosa is mainly controlled by α4β7 integrin, and it is amplified during gut chronic inflammation, as occurs with HIV and/or inflammatory bowel diseases. We designed and applied an improved immunization strategy based on an innovative selection process to isolate new α4β7 lymphocyte-specific monoclonal antibodies that are able to prevent their migration into inflamed gut tissues and/or to counteract HIV infection in vitro. First, 5 monoclonal antibodies (1 IgA, 1 IgM, and 4 IgGs) were selected based on their capacity to recognize α4 or β7 homodimers and α4β7 heterodimers in transfected human cells...
May 1, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
A D Nelson, M Camilleri, A Acosta, A Boldingh, I Busciglio, D Burton, M Ryks, A R Zinsmeister
BACKGROUND: In an open-label study of 26 patients with IBS-C and chronic constipation, treatment with a vibrating (VIBRANT) capsule twice a week for 7.5 weeks resulted in 88.5% responders. Effects on colonic transit are unclear. We aimed to compare effects of VIBRANT and sham capsule treatment on colonic transit in patients with functional constipation. METHODS: Patients with functional constipation (Rome III criteria) were randomized to VIBRANT or sham capsule treatment for 8 weeks and underwent scintigraphic colonic transit measurements during week 8...
February 8, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Andrew M Waa, Amber L Pearson, John L Ryks
Māori (the indigenous peoples of Aotearoa New Zealand) experience of colonisation has negatively affected access to many of the resources (e.g. income, adequate housing) that enable health and well-being. However Māori have actively responded to the challenges they have faced. With the majority of the Māori population now living in urban settings this exploratory study aimed to understand factors contributing to mortality resilience despite exposure to socio-economic adversity with reference to Māori well-being...
November 26, 2016: Health & Place
Farbod Famili, Laura Garcia Perez, Brigitta Ae Naber, Jasprina N Noordermeer, Lee G Fradkin, Frank Jt Staal
The development of blood and immune cells requires strict control by various signaling pathways in order to regulate self-renewal, differentiation and apoptosis in stem and progenitor cells. Recent evidence indicates critical roles for the canonical and non-canonical Wnt pathways in hematopoiesis. The non-canonical Wnt pathway is important for establishment of cell polarity and cell migration and regulates apoptosis in the thymus. We here investigate the role of the non-canonical Wnt receptor Ryk in hematopoiesis and lymphoid development...
November 24, 2016: Cell Death & Disease
Siddappa N Byrareddy, James Arthos, Claudia Cicala, Francois Villinger, Kristina T Ortiz, Dawn Little, Neil Sidell, Maureen A Kane, Jianshi Yu, Jace W Jones, Philip J Santangelo, Chiara Zurla, Lyle R McKinnon, Kelly B Arnold, Caroline E Woody, Lutz Walter, Christian Roos, Angela Noll, Donald Van Ryk, Katija Jelicic, Raffaello Cimbro, Sanjeev Gumber, Michelle D Reid, Volkan Adsay, Praveen K Amancha, Ann E Mayne, Tristram G Parslow, Anthony S Fauci, Aftab A Ansari
Antiretroviral drug therapy (ART) effectively suppresses replication of both the immunodeficiency viruses, human (HIV) and simian (SIV); however, virus rebounds soon after ART is withdrawn. SIV-infected monkeys were treated with a 90-day course of ART initiated at 5 weeks post infection followed at 9 weeks post infection by infusions of a primatized monoclonal antibody against the α4β7 integrin administered every 3 weeks until week 32. These animals subsequently maintained low to undetectable viral loads and normal CD4(+) T cell counts in plasma and gastrointestinal tissues for more than 9 months, even after all treatment was withdrawn...
October 14, 2016: Science
Lone Rykær Hansen, Peter Roslev
Glyphosate (N-(phosphonomethyl)glycine) is the active ingredient in a range of popular broad-spectrum herbicide formulations. Glyphosate is a chelating agent that can form stable complexes with divalent metal ions including Cu(II). Little is known about the bioavailability and ecotoxicity of glyphosate-Cu(II) complexes to aquatic organisms. In this study, we used video tracking and behavior analysis to investigate sublethal effects of binary mixtures of glyphosate and Cu(II) to juvenile D. magna. Behavioral responses were quantified for individual D...
October 2016: Aquatic Toxicology
Raffaello Cimbro, Francis C Peterson, Qingbo Liu, Christina Guzzo, Peng Zhang, Huiyi Miao, Donald Van Ryk, Xavier Ambroggio, Darrell E Hurt, Luca De Gioia, Brian F Volkman, Michael A Dolan, Paolo Lusso
Tyrosine sulfation is a post-translational modification that facilitates protein-protein interaction. Two sulfated tyrosines (Tys173 and Tys177) were recently identified within the second variable (V2) loop of the major HIV-1 envelope glycoprotein, gp120, and shown to contribute to stabilizing the intramolecular interaction between V2 and the third variable (V3) loop. Here, we report that tyrosine-sulfated peptides derived from V2 act as structural and functional mimics of the CCR5 N-terminus and potently block HIV-1 infection...
August 2016: EBioMedicine
A D Nelson, M Camilleri, A Acosta, I Busciglio, S Linker Nord, A Boldingh, D Rhoten, M Ryks, D Burton
BACKGROUND: Synthetic human ghrelin accelerates gastric emptying, reduces gastric accommodation, and results in numerical increases in postprandial symptom scores. The ghrelin receptor agonist, relamorelin, accelerates gastric emptying in patients with diabetic gastroparesis. AIM: To measure pharmacological effects of relamorelin on gastric accommodation, distal antral motility, and satiation in healthy volunteers. METHODS: In a placebo-controlled, double-blind, randomized study of 16 healthy volunteers, we compared effects of 30 μg subcutaneous (s...
November 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Hafiza Fizzah Riaz, Shaheen Mannan, Sajid Malik
BACKGROUND: Rahim Yar Khan (RYK) District is a multi-ethnic assemblage of both ancient and migrated communities in Southern Punjab, Pakistan. There is a paucity of knowledge on the bio-demographic structure of this endogamous population. METHODS: We have carried out a cross-sectional epidemiological study in RYK District and recruited 2174 random Muslim married females. Detailed account of marital union types, level of consanguinity, and subject's fertility, was taken...
May 20, 2016: Journal of Health, Population, and Nutrition
Tom Skaria, Esther Bachli, Gabriele Schoedon
Satisfactory therapeutic strategies for septic shock are still missing. Previously we found elevated levels of Wnt5A in patients with severe sepsis and septic shock. Wnt5A is released by activated macrophages but knowledge of its effects in the vascular system remains scant. Here we investigate the response of human coronary artery endothelial cells (HCAEC) to Wnt5A. We used a genome-wide differential expression approach to define novel targets regulated by Wnt5A. Gene ontology analysis of expression profiles revealed clusters of genes involved in actin cytoskeleton remodeling as the predominant targets of Wnt5A...
January 2, 2017: Cell Adhesion & Migration
Alicja Genc, Małgorzata Ryk, Magdalena Suwała, Tatiana Żurakowska, Wojciech Kosiak
UNLABELLED: Ultrasound, which is a safe and non-invasive diagnostic modality that uses more and more advanced imaging techniques, has become the first-choice examination in various diseases. It is more and more often used in the general practitioner's office to supplement physical examination and interview. AIM: The aim of this paper is to review the Polish medical literature pertaining to the usage of ultrasound imaging in general practice as well as to present advantages, disadvantages and utility associated with conducting ultrasound examinations by general practitioners based on selected publications...
March 2016: Journal of Ultrasonography
Edmund R Hollis, Nao Ishiko, Ting Yu, Chin-Chun Lu, Ariela Haimovich, Kristine Tolentino, Alisha Richman, Anna Tury, Shih-Hsiu Wang, Maysam Pessian, Euna Jo, Alex Kolodkin, Yimin Zou
Limited functional recovery can be achieved through rehabilitation after incomplete spinal cord injury. Eliminating the function of a repulsive Wnt receptor, Ryk, in mice and rats by either conditional knockout in the motor cortex or monoclonal antibody infusion resulted in increased corticospinal axon collateral branches with presynaptic puncta in the spinal cord and enhanced recovery of forelimb reaching and grasping function following a cervical dorsal column lesion. Using optical stimulation, we observed that motor cortical output maps underwent massive changes after injury and that hindlimb cortical areas were recruited to control the forelimb over time...
May 2016: Nature Neuroscience
M Grover, M Camilleri, J Hines, D Burton, M Ryks, A Wadhwa, W Sundt, R Dyer, R J Singh
BACKGROUND: Gastrointestinal (GI) and non-GI disorders are associated with altered intestinal permeability, which can be measured in vivo by urinary excretion after oral lactulose and mannitol ingestion. Inadvertent dietary consumption of (12) Carbon ((12) C, regular) mannitol in food or from other sources may interfere with the test's interpretation. (13) Carbon ((13) C) constitutes 1% of carbon in nature and (13) C mannitol is a stable isotope. Our aim was to determine the performance of (13) C mannitol for measurement of intestinal permeability...
July 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Daniele Conte, Giulia Garaffo, Nadia Lo Iacono, Stefano Mantero, Stefano Piccolo, Michelangelo Cordenonsi, David Perez-Morga, Valeria Orecchia, Valeria Poli, Giorgio R Merlo
The congenital malformation split hand/foot (SHFM) is characterized by missing central fingers and dysmorphology or fusion of the remaining ones. Type-1 SHFM is linked to deletions/rearrangements of the DLX5-DLX6 locus and point mutations in the DLX5 gene. The ectrodactyly phenotype is reproduced in mice by the double knockout (DKO) of Dlx5 and Dlx6. During limb development, the apical ectodermal ridge (AER) is a key-signaling center responsible for early proximal-distal growth and patterning. In Dlx5;6 DKO hindlimbs, the central wedge of the AER loses multilayered organization and shows down-regulation of FGF8 and Dlx2...
February 15, 2016: Human Molecular Genetics
Yuil Kim, Mineui Hong, In-Gu Do, Sang Yun Ha, Dakeun Lee, Yeon-Lim Suh
BACKGROUND: Wnt5a, a non-canonical Wnt ligand, has been shown to play tumor-promoting or tumor-suppressive roles in different neoplasms. Increased Wnt5a expression and Wnt5a-dependent invasive activity that is mediated by one of its receptors, Ryk, have been reported in glioblastomas. METHODS: We investigated the protein expression of Wnt5a, its receptors Ryk and Ror2, and the canonical Wnt pathway marker β-catenin in 186 cases of glioblastoma and its variants...
December 2015: Pathology, Research and Practice
Monserrat Alvarez-Zavala, Alma R Riveros-Magaña, Beatriz García-Castro, Esperanza Barrera-Chairez, Benjamin Rubio-Jurado, Oscar M Garcés-Ruíz, Moisés Ramos-Solano, Adriana Aguilar-Lemarroy, Luis F Jave-Suarez
BACKGROUND: Wnt signaling induces a plethora of intracellular responses that dictate normal or abnormal cellular behavior. Abnormal WNT signaling has been related to the development of leukemogenic processes. In this regard, it is important to know the expression profile of WNT receptors in normal and malignant cells, in order to understand the WNT mechanisms that control the cell behavior. This work aimed to determine the WNT receptors expression profile in normal and leukemia cells...
August 2016: European Journal of Haematology
Dilruba Ahmed, Petra J de Verdier, Charlotta Ryk, Oscar Lunqe, Per Stål, Jenny Flygare
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The multityrosine kinase inhibitor sorafenib is used in the therapy of advanced disease. However, the effects of sorafenib are limited, and combination treatments aiming at improved survival are encouraged. The sphingosine analog FTY720 (Fingolimod), which is approved for treatment of multiple sclerosis, has shown tumor suppressive effects in cell lines and animal models of HCC. In the present study, we combined sorafenib with FTY720 in order to sensitize the HCC cell lines Huh7 and HepG2 to sorafenib treatment...
October 2015: Pharmacology Research & Perspectives
Timmer Robinson, Usman Ali, Adeel Mahmood, Muhammad Jamshed Iqbal Chaudhry, Jun Li, Gan Zhang, Kevin C Jones, Riffat Naseem Malik
The present study was conducted to reveal the concentrations and patterns of organochlorines [i.e., organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs)] in freshwater fish species collected from four ecologically important sites of the Indus River i.e., Taunsa (TAU), Rahim Yar Khan (RYK), Guddu (GUD) and Sukkur (SUK). In the fish muscle tissues, concentrations of 15 OCPs (∑15OCPs) and 29 PCBs (∑29PCBs) varied between 1.93-61.9 and 0.81-44.2 ng/g wet weight (ww), respectively. Overall, the rank order of OCs was DDTs>PCBs>hexachlorocyclohexanes (HCHs)>chlordanes (CHLs)...
January 15, 2016: Science of the Total Environment
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