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Jason Yolitz, Catherine Schwing, Julia Chang, Donald Van Ryk, Fatima Nawaz, Danlan Wei, Claudia Cicala, James Arthos, Anthony S Fauci
The HIV-1 envelope protein (Env) of early-replicating viruses encodes several distinct transmission signatures. One such signature involves a reduced number of potential N-linked glycosylation sites (PNGs). This transmission signature underscores the importance of posttranslational modifications in the fitness of early-replicating isolates. An additional signature in Env involves the overrepresentation of basic amino acid residues at a specific position in the Env signal peptide (SP). In this report, we investigated the potential impact of this SP signature on gp120 glycosylation and antigenicity...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
(no author information available yet)
Vet Ryk Botes is a branch partner at Medivet. He has a special interest in orthopaedics and enjoys refining new techniques, most recently in elbow replacement surgery.
February 3, 2018: Veterinary Record
H Halawi, P Vijayvargiya, I Busciglio, I Oduyebo, D Khemani, M Ryks, D Rhoten, D Burton, L A Szarka, A Acosta, M Camilleri
BACKGROUND: Nausea, vomiting, and constipation (OIC) are common adverse effects of acute or chronic opioid use. Naloxegol (25 mg) is an approved peripherally active mu-opiate opioid receptor antagonist. AIM: To compare the effects on pan-gut transit of treatment with codeine, naloxegol, or combination in healthy volunteers. METHODS: We conducted a randomized, double-blind, placebo-controlled, single-center, parallel-group study in 72 healthy opioid-naïve adults, randomized to: codeine (30 mg q...
February 6, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Wen-Hsuan Chang, Si Ho Choi, Byoung-San Moon, Mingyang Cai, Jungmook Lyu, Jinlun Bai, Fan Gao, Ibrahim Hajjali, Zhongfang Zhao, Daniel B Campbell, Leslie P Weiner, Wange Lu
The receptor-like tyrosine kinase (Ryk), a Wnt receptor, is important for cell fate determination during corticogenesis. During neuronal differentiation, the Ryk intracellular domain (ICD) is cleaved. Cleavage of Ryk and nuclear translocation of Ryk-ICD are required for neuronal differentiation. However, the mechanism of translocation and how it regulates neuronal differentiation remain unclear. Here, we identified Smek1 and Smek2 as Ryk-ICD partners that regulate its nuclear localization and function together with Ryk-ICD in the nucleus through chromatin recruitment and gene transcription regulation...
December 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
Martin Rykær, Birte Svensson, Michael J Davies, Per Hägglund
Oxidation generates multiple diverse post-translational modifications resulting in changes in protein structure and function associated with a wide range of diseases. Of these modifications, carbonylations have often been used as hallmarks of oxidative damage. However, accumulating evidence supports the hypothesis that other oxidation products may be quantitatively more important under physiological conditions. To address this issue, we have developed a holistic mass spectrometry-based approach for the simultaneous identification, localization, and quantification of a broad range of oxidative modifications based on so-called "dependent peptides"...
September 29, 2017: Journal of Proteome Research
Deepti Jacob, Irene Busciglio, Duane Burton, Houssam Halawi, Ibironke Oduyebo, Deborah Rhoten, Michael Ryks, W Scott Harmsen, Michael Camilleri
Aprepitant, an NK1 receptor antagonist, is approved for the treatment of chemotherapy-induced or postoperative emesis by blocking NK1 receptors in the brain stem vomiting center. The effects of NK1 receptors on gastric functions and postprandial symptoms in humans are unclear; a single, crossover study did not show a significant effect of aprepitant on gastrointestinal transit. Our aim was to compare, in a randomized, double-blind, placebo-controlled, parallel-group study (12 healthy volunteers per group), the effects of aprepitant vs...
November 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
Vanessa Lanoue, Michael Langford, Amanda White, Kai Sempert, Lily Fogg, Helen M Cooper
The unique dendritic architecture of a given neuronal subtype determines its synaptic connectivity and ability to integrate into functional neuronal networks. It is now clear that abnormal dendritic structure is associated with neuropsychiatric and neurodegenerative disorders. Currently, however, the nature of the extrinsic factors that limit dendritic growth and branching within predetermined boundaries in the mammalian brain is poorly understood. Here we identify the Wnt receptor Ryk as a novel negative regulator of dendritic arborisation...
July 20, 2017: Scientific Reports
Tom Skaria, Gabriele Schoedon
Wnt5A is a chemokine secreted by inflammatory-activated human macrophages that sustains their inflammatory response in an autocrine manner. High levels of Wnt5A are found in sera of patients with sepsis and septic shock. Here, we comment on recently reported Wnt5A signalling pathways in human vascular endothelial cells (VEC). In human VEC, Wnt5A regulates cytoskeleton remodelling and barrier function through Ryk receptor and Rho-associated protein serine/threonine kinase, targeting LIMK2 and CFL1 involved in actin polymerisation...
2017: Journal of Inflammation
Xin Duan, Yarong Gao, Yaobo Liu
It was previously reported a role for Ryk in mediating Wnt5a repulsion of the corticospinal tract (CST) in mice. Recent evidence has shown that Ryk regulates planar cell polarity (PCP) signaling through interacting with Vangl2. Here, in vivo, in vitro and biochemical analyses were applied to investigate the molecular cross-talk between the Ryk and PCP signaling pathways, revealing that PCP pathway components play important roles in CST anterior-posterior guidance. Ryk-Vangl2 interactions are crucial for PCP signaling to mediate Wnt5a repulsion of CST axons...
2017: Cell Discovery
Stephen Leadbeatter, Ryk James
BACKGROUND: Despite public inquiries, and some changes to legislation following high-profile multiple homicides that were not detected by autopsy, coroners continue to rely largely on the autopsy. Regardless of the extent of quality failings and excess deaths at some hospitals, not detected through the coroner system, the autopsy is scarcely used by hospitals to monitor standards and educate. OBJECTIVE: To explore when a compulsory medicolegal autopsy should, and should not, be used...
June 23, 2017: Journal of Clinical Pathology
Qing Ou Yang, Wen-Jing Yang, Jian Li, Fang-Ting Liu, Hongbin Yuan, Yue-Ping Ou Yang
Background Neuropathic pain is a major pathology of the central nervous system associated with neuroinflammation. Ryk (receptor-like tyrosine kinase) receptors act as repulsive axon-guidance molecules during development of central nervous system and neural injury. Increasing evidence suggests the potential involvement of Wnt/Ryk (wingless and Int) signaling in the pathogenesis of neuropathic pain. However, its underlying mechanism remains unknown. Results The expression and location of Ryk receptor as well as its ligand Wnt1 were detected by qPCR, Western blot, and immunohistochemistry...
January 2017: Molecular Pain
Tom Skaria, Esther Bachli, Gabriele Schoedon
BACKGROUND: Wnt5A is released by activated macrophages and elevated levels have been detected in sepsis patients with severe systemic inflammation. However, the signalling and functional effects of Wnt5A in the vascular endothelial cells (VEC) remained unclear. Recently, we showed that Wnt5A affects barrier function in human VEC through Ryk interaction. Wnt5A/Ryk signalling activates LIMK to inactivate the actin depolymerisation factor CFL by phosphorylation, promotes actin polymerisation and disrupts endothelial adherens junctions...
2017: Journal of Inflammation
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
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