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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of both the immunodeficiency viruses, human (HIV) and simian (SIV); however, virus rebounds soon after ART is withdrawn.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normal CD4(+) T cell counts in plasma and gastrointestinal tissues for more than 9 months, even after all treatment was withdrawn...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...
June 9, 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...
2016: Journal of Health, Population, and Nutrition
Tom Skaria, Esther Bachli, Gabriele Schoedon
Objective- 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. Approach and Results-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...
May 9, 2016: 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
Marike M van Beuge, Evert-Jan P M Ten Dam, Paul M N Werker, Ruud A Bank
A role of Wnt signaling in Dupuytren disease, a fibroproliferative disease of the hand and fingers, has not been fully elucidated. We examined a large set of Wnt pathway components and signaling targets and found significant dysregulation of 41 Wnt-related genes in tissue from the Dupuytren nodules compared with patient-matched control tissue. A large proportion of genes coding for Wnt proteins themselves was downregulated. However, both canonical Wnt targets and components of the noncanonical signaling pathway were upregulated...
December 2015: Translational Research: the Journal of Laboratory and Clinical Medicine
Su Liu, Yue-Peng Liu, Zhi-Jiang Huang, Yan-Kai Zhang, Angela A Song, Ping-Chuan Ma, Xue-Jun Song
Treating neuropathic pain continues to be a major clinical challenge and underlying mechanisms of neuropathic pain remain elusive. We have recently demonstrated that Wnt signaling, which is important in developmental processes of the nervous systems, plays critical roles in the development of neuropathic pain through the β-catenin-dependent pathway in the spinal cord and the β-catenin-independent pathway in primary sensory neurons after nerve injury. Here, we report that Wnt signaling may contribute to neuropathic pain through the atypical Wnt/Ryk signaling pathway in rats...
December 2015: Pain
Gerhard Hamilton, Barbara Rath, Lukas Klameth, Maximilian Hochmair
Small cell lung cancer (SCLC) has a poor prognosis and is found disseminated at first presentation in the majority of cases. The cell biological mechanisms underlying metastasis and drug resistance are not clear. SCLC is characterized by high numbers of circulating tumor cells (CTCs) and we were able to expand several CTC lines ex vivo and to relate chitinase-3-like-1/YKL-40 (CHI3L1) as marker. Availability of expanded SCLC CTC cells allowed for a screening of receptor tyrosine kinases (RTKs) expressed. The metastatic CHI3L1-negative SCLC cell line SCLC26A, established from a pleural effusion was used for comparison...
2015: Oncoscience
Kei-ichiro Yasunaga, Akane Tezuka, Natsuko Ishikawa, Yusuke Dairyo, Kazuya Togashi, Hiroyuki Koizumi, Kazuo Emoto
Sensory neurons with common functions are often nonrandomly arranged and form dendritic territories in stereotypic spatial patterns throughout the nervous system, yet molecular mechanisms of how neurons specify dendritic territories remain largely unknown. In Drosophila larvae, dendrites of class IV sensory (C4da) neurons completely but nonredundantly cover the whole epidermis, and the boundaries of these tiled dendritic fields are specified through repulsive interactions between homotypic dendrites. Here we report that, unlike the larval C4da neurons, adult C4da neurons rely on both dendritic repulsive interactions and external positional cues to delimit the boundaries of their dendritic fields...
August 15, 2015: Genes & Development
Charlotta Ryk, Lotta Renström Koskela, Tomas Thiel, N Peter Wiklund, Gunnar Steineck, Martin C Schumacher, Petra J de Verdier
PURPOSE: Bacillus Calmette-Guérin (BCG)-treatment is an established treatment for bladder cancer, but its mechanisms of action are not fully understood. High-risk non-muscle invasive bladder-cancer (NMIBC)-patients failing to respond to BCG-treatment have worse prognosis than those undergoing immediate radical cystectomy and identification of patients at risk for BCG-failure is of high priority. Several studies indicate a role for nitric oxide (NO) in the cytotoxic effect that BCG exerts on bladder cancer cells...
December 2015: Redox Biology
Ambrose R Kidd, Vanessa Muñiz-Medina, Channing J Der, Adrienne D Cox, David J Reiner
Wnt signaling controls various aspects of developmental and cell biology, as well as contributing to certain cancers. Expression of the human Rho family small GTPase Wrch/RhoU is regulated by Wnt signaling, and Wrch and its paralog Chp/RhoV are both implicated in oncogenic transformation and regulation of cytoskeletal dynamics. We performed developmental genetic analysis of the single Caenorhabditis elegans ortholog of Chp and Wrch, CHW-1. Using a transgenic assay of the distal tip cell migration, we found that wild-type CHW-1 is likely to be partially constitutively active and that we can alter ectopic CHW-1-dependent migration phenotypes with mutations predicted to increase or decrease intrinsic GTP hydrolysis rate...
2015: PloS One
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