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https://www.readbyqxmd.com/read/28549075/age-of-onset-in-huntington-s-disease-is-influenced-by-cag-repeat-variations-in-other-polyglutamine-disease-associated-genes
#1
Geerte Stuitje, Martine J van Belzen, Sarah L Gardiner, Willeke M C van Roon-Mom, Merel W Boogaard, Sarah J Tabrizi, Raymund A C Roos, N A Aziz
No abstract text is available yet for this article.
May 25, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28515281/cxcl4-exposure-potentiates-tlr-driven-polarization-of-human-monocyte-derived-dendritic-cells-and-increases-stimulation-of-t-cells
#2
Sandra C Silva-Cardoso, Alsya J Affandi, Lotte Spel, Marta Cossu, Joel A G van Roon, Marianne Boes, Timothy R D J Radstake
Chemokines have been shown to play immune-modulatory functions unrelated to steering cell migration. CXCL4 is a chemokine abundantly produced by activated platelets and immune cells. Increased levels of circulating CXCL4 are associated with immune-mediated conditions, including systemic sclerosis. Considering the central role of dendritic cells (DCs) in immune activation, in this article we addressed the effect of CXCL4 on the phenotype and function of monocyte-derived DCs (moDCs). To this end, we compared innate and adaptive immune responses of moDCs with those that were differentiated in the presence of CXCL4...
May 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28499347/the-dynamics-of-early-state-transcriptional-changes-and-aggregate-formation-in-a-huntington-s-disease-cell-model
#3
Martijn van Hagen, Diewertje G E Piebes, Wim C de Leeuw, Ilona M Vuist, Willeke M C van Roon-Mom, Perry D Moerland, Pernette J Verschure
BACKGROUND: Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a CAG expansion in the Huntingtin (HTT) gene. Proteolytic cleavage of mutant huntingtin (Htt) protein with an expanded polyglutamine (polyQ) stretch results in production of Htt fragments that aggregate and induce impaired ubiquitin proteasome, mitochondrial functioning and transcriptional dysregulation. To understand the time-resolved relationship between aggregate formation and transcriptional changes at early disease stages, we performed temporal transcriptome profiling and quantification of aggregate formation in living cells in an inducible HD cell model...
May 12, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28463808/no-outcome-disparities-in-patients-with-diffuse-large-b-cell-lymphoma-and-a-low-socioeconomic-status
#4
Karin Boslooper, Mels Hoogendoorn, Eric N van Roon, Robby E Kibbelaar, Huib Storm, Sjoerd Hovenga, Gerhard Woolthuis, Bas P van Rees, Bart Klijs, Nic J G M Veeger, Hanneke C Kluin-Nelemans, Geertruida H de Bock
INTRODUCTION: In patients with diffuse large B-cell lymphoma (DLBCL) socioeconomic status (SES) is associated with outcome in several population-based studies. The aim of this study was to further investigate the existence of disparities in treatment and survival. METHODS: A population-based cohort study was performed including 343 consecutive patients with DLBCL, diagnosed between 2005 and 2012, in the North-west of the Netherlands. SES was based on the socioeconomic position within the Netherlands by use of postal code and categorized as low, intermediate or high...
April 29, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28445782/the-immunohistochemical-distribution-of-the-gabaa-receptor-%C3%AE-1-%C3%AE-2-%C3%AE-3-%C3%AE-2-3-and-%C3%AE-2-subunits-in-the-human-thalamus
#5
H J Waldvogel, M Munkle, W van Roon-Mom, H Mohler, R L M Faull
The GABAA receptor is the most abundant inhibitory receptor in the human brain and is assembled from a variety of different subunit subtypes which determines their pharmacology and physiology. To determine which GABAA receptor subunit proteins are found in the human thalamus we investigated the distribution of five major GABAA receptor subunits α1, α2, α3, β2,3 and γ2 using immunohistochemical techniques. The α1-, β2,3- and γ2- subunits which combine to form a benzodiazepine sensitive GABAA receptor showed the most intense levels of staining and were the most common subunits found throughout the human thalamus especially in the ventral and posterior nuclear groups...
April 23, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28384716/analysis-of-mthfr-cbs-glutathione-taurine-and-hydrogen-sulfide-levels-in-retinas-of-hyperhomocysteinemic-mice
#6
Xuezhi Cui, Soumya Navneet, Jing Wang, Penny Roon, Wei Chen, Ming Xian, Sylvia B Smith
Purpose: Hyperhomocysteinemia (Hhcy) is implicated in certain retinal neurovascular diseases, although whether it is causative remains uncertain. In isolated ganglion cells (GCs), mild Hhcy induces profound death, whereas retinal phenotypes in Hhcy mice caused by mutations in remethylation (methylene tetrahydrofolatereductase [Mthfr+/-]) or transsulfuration pathways (cystathionine β-synthase [Cbs+/-]) demonstrate mild GC loss and mild vasculopathy. The current work investigated compensation in vivo of one pathway for the other, and, because the transsulfuration pathway yields cysteine necessary for formation of glutathione (GSH), taurine, and hydrogen sulfide (H2S), they were analyzed also...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28348170/crystal-structure-of-u2-snrnp-sf3b-components-hsh49p-in-complex-with-cus1p-binding-domain
#7
Anne-Marie A M van Roon, Chris Oubridge, Eiji Obayashi, Benedetta Sposito, Andrew James Newman, Bertrand Seraphin, Kiyoshi Nagai
Spliceosomal proteins Hsh49p and Cus1p are components of SF3b, which together with SF3a, Msl1p/Lea1p, Sm proteins and U2 snRNA, form U2 snRNP, which plays a crucial role in pre-mRNA splicing. Hsh49p, comprising two RRMs, forms a heterodimer with Cus1p. We determined the crystal structures of Saccharomyces cerevisiae full-length Hsh49p as well as its RRM1 in complex with a minimal binding region of Cus1p (residues 290-368). The structures show that the Cus1 fragment binds to the α-helical surface of Hsh49p RRM1, opposite the four-stranded β-sheet, leaving the canonical RNA binding surface available to bind RNA...
March 27, 2017: RNA
https://www.readbyqxmd.com/read/28322270/huntington-s-disease-blood-and-brain-show-a-common-gene-expression-pattern-and-share-an-immune-signature-with-alzheimer-s-disease
#8
Davina J Hensman Moss, Michael D Flower, Kitty K Lo, James R C Miller, Gert-Jan B van Ommen, Peter A C 't Hoen, Timothy C Stone, Amelia Guinee, Douglas R Langbehn, Lesley Jones, Vincent Plagnol, Willeke M C van Roon-Mom, Peter Holmans, Sarah J Tabrizi
There is widespread transcriptional dysregulation in Huntington's disease (HD) brain, but analysis is inevitably limited by advanced disease and postmortem changes. However, mutant HTT is ubiquitously expressed and acts systemically, meaning blood, which is readily available and contains cells that are dysfunctional in HD, could act as a surrogate for brain tissue. We conducted an RNA-Seq transcriptomic analysis using whole blood from two HD cohorts, and performed gene set enrichment analysis using public databases and weighted correlation network analysis modules from HD and control brain datasets...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315277/the-role-of-sigma1r-in-mammalian-retina
#9
Jing Wang, Xuezhi Cui, Penny Roon, Alan Saul, Sylvia B Smith
This review article focuses on studies of Sigma 1 Receptor (Sigma1R) and retina . It provides a brief overview of the earliest pharmacological studies performed in the late 1990s that provided evidence of the presence of Sigma1R in various ocular tissues. It then describes work from a number of labs concerning the location of Sigma1R in several retinal cell types including ganglion, Müller glia , and photoreceptors . The role of Sigma1R ligands in retinal neuroprotection is emphasized. Early studies performed in vitro clearly showed that targeting Sigma1R could attenuate stress-induced retinal cell loss...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28297047/patient-related-factors-influencing-patency-of-autogenous-brachiocephalic-haemodialysis-fistulas
#10
Alexander Lamprou, Cor de Bruin, Arie van Roon, Jan Loonstra, Maarten van der Laan, Ignace Tielliu, Clark Zeebregts
OBJECTIVE: The objective of this study was to analyse the outcome of autogenous brachiocephalic fistula for dialysis purposes and to determine modifiable and non-modifiable patient-related factors of influence on the patency of a newly created fistula. DESIGN OF STUDY: A single-centre retrospective cohort study with the aim of determining patient-related factors of influence on primary failure, primary, primary assisted and secondary patency of autogenous brachiocephalic fistulas...
March 6, 2017: Journal of Vascular Access
https://www.readbyqxmd.com/read/28289078/delivery-is-key-lessons-learnt-from-developing-splice-switching-antisense-therapies
#11
REVIEW
Caroline Godfrey, Lourdes R Desviat, Bård Smedsrød, France Piétri-Rouxel, Michela A Denti, Petra Disterer, Stéphanie Lorain, Gisela Nogales-Gadea, Valentina Sardone, Rayan Anwar, Samir El Andaloussi, Taavi Lehto, Bernard Khoo, Camilla Brolin, Willeke Mc van Roon-Mom, Aurélie Goyenvalle, Annemieke Aartsma-Rus, Virginia Arechavala-Gomeza
The use of splice-switching antisense therapy is highly promising, with a wealth of pre-clinical data and numerous clinical trials ongoing. Nevertheless, its potential to treat a variety of disorders has yet to be realized. The main obstacle impeding the clinical translation of this approach is the relatively poor delivery of antisense oligonucleotides to target tissues after systemic delivery. We are a group of researchers closely involved in the development of these therapies and would like to communicate our discussions concerning the validity of standard methodologies currently used in their pre-clinical development, the gaps in current knowledge and the pertinent challenges facing the field...
May 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28278719/restoration-of-renal-function-in-patients-with-newly-diagnosed-multiple-myeloma-is-not-associated-with-improved-survival-a-population-based-study
#12
Joost C de Vries, Berdien Oortgiesen, Marc H Hemmelder, Eric van Roon, Robby E Kibbelaar, Nic Veeger, Mels Hoogendoorn
Renal impairment (RI) in patients with multiple myeloma (MM) is associated with poor prognosis. In this population-based cohort study, we assessed the effects of renal response, evaluated according to the IMWG-criteria, on overall survival (OS) in patients with newly diagnosed MM with RI at presentation. All included patients were diagnosed between January 2005 and January 2014 with MM and RI in Friesland, a province of the Netherlands. Of the 131 included patients, 61% achieved renal response. Using a time-varying exposure Cox model, no difference in OS between renal response and non-response was observed (HR = 1...
February 14, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28258356/the-role-of-initial-clinical-presentation-comorbidity-and-treatment-in-multiple-myeloma-patients-on-survival-a-detailed-population-based-cohort-study
#13
B E Oortgiesen, E N van Roon, P Joosten, R E Kibbelaar, H Storm, S Hovenga, B van Rees, G Woolthuis, N Veeger, E G de Waal, M Hoogendoorn
PURPOSE: This prospective, observational population-based cohort study was performed to determine overall survival (OS) in multiple myeloma (MM) patients in Friesland, the Netherlands, in the era of novel agents and to analyse the influence of first-line treatment, MM-related end-organ damage and comorbidities at initial presentation on OS. METHODS: Detailed clinical information was obtained from the population-based registry 'HemoBase' during the period January 2005 to January 2013, with a follow-up to January 2014...
March 3, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28244635/effect-of-linagliptin-on-pulse-wave-velocity-in-early-type-2-diabetes-a-randomized-double-blind-controlled-26-week-trial-release
#14
Stefanie A de Boer, Hiddo J L Heerspink, Luis E Juárez Orozco, Arie M van Roon, Pieter W Kamphuisen, Andries J Smit, Riemer H J A Slart, Joop D Lefrandt, Douwe J Mulder
AIMS: To evaluate the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin on aortic pulse wave velocity (PWV) as a surrogate marker of arterial stiffness and early atherosclerosis in people with early type 2 diabetes. METHODS: A total of 45 people with type 2 diabetes (median [interquartile range] age 63 [54-66] years, 61% men, mean ± standard deviation glycated haemoglobin [HbA1c] 6.3% ± 0.4% [45 ± 4.6 mmol/mol]), without cardiovascular disease and naïve to antidiabetic treatment, were randomized (1:1) to treatment with linagliptin 5 mg once daily or placebo for 26 weeks in a double-blind fashion...
February 28, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28112627/high-prevalence-of-tula-hantavirus-in-common-voles-in-the-netherlands
#15
Miriam Maas, Ankje de Vries, Annika van Roon, Katsuhisa Takumi, Joke van der Giessen, Barry Rockx
Tula virus (TULV) is a zoonotic hantavirus. Knowledge about TULV in the Netherlands is very scarce. Therefore in 2014, 49 common voles (Microtus arvalis) from a region in the south of the Netherlands, and in 2015, 241 common voles from regions in the north of the Netherlands were tested with the TULV quantitative RT-PCR. In the southern region, prevalence of TULV was 41% (20/49). In the northern regions, prevalence ranged from 12% (4/34) to 45% (17/38). Phylogenetic analysis of the obtained sequences showed that the regions fall within different clusters...
March 2017: Vector Borne and Zoonotic Diseases
https://www.readbyqxmd.com/read/28076669/medication-discrepancies-at-outpatient-departments-for-mood-and-anxiety-disorders-in-the-netherlands-risks-and-clinical-relevance
#16
Mirjam Simoons, Hans Mulder, Arne J Risselada, Frederik W Wilmink, Robert Schoevers, Henricus G Ruhé, Eric N van Roon
OBJECTIVE: To identify discrepancies between actual drug use by outpatients with mood and anxiety disorders and medication overviews from health care providers as well as to investigate the clinical relevance of those discrepancies. METHODS: A cross-sectional study in adults visiting 1 of 4 participating outpatient departments for mood and anxiety disorders was conducted between March and November 2014. DSM-5 criteria were used to assign the psychiatric diagnosis...
November 2016: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28017939/huntingtin-is-a-scaffolding-protein-in-the-atm-oxidative-dna-damage-response-complex
#17
Tamara Maiuri, Andrew J Mocle, Claudia L Hung, Jianrun Xia, Willeke M C van Roon-Mom, Ray Truant
Huntington's disease (HD) is an age-dependent neurodegenerative disease. DNA repair pathways have recently been implicated as the most predominant modifiers of age of onset in HD patients. We report that endogenous huntingtin protein directly participates in oxidative DNA damage repair. Using novel chromobodies to detect endogenous human huntingtin in live cells, we show that localization of huntingtin to DNA damage sites is dependent on the kinase activity of ataxia telangiectasia mutated (ATM) protein. Super-resolution microscopy and biochemical assays revealed that huntingtin co-localizes with and scaffolds proteins of the DNA damage response pathway in response to oxidative stress...
January 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/27987023/comparative-study-of-episiotomy-angles-achieved-by-cutting-with-straight-mayo-scissors-and-the-episcissors-60-in-a-birth-simulation-model
#18
Yves van Roon, Latha Vinayakarao, Louise Melson, Rebecca Percival, Sangeeta Pathak, Ashish Pradhan
INTRODUCTION AND HYPOTHESIS: We compared the clinician's ability to cut episiotomies at the recommended 60° angle with traditional straight Mayo scissors compared with patented fixed-angle episiotomy scissors EPISCISSORS-60® in a simulated setting using mounted incision pads. The hypothesis was that fixed-angle episiotomies would achieve a more accurate cutting angle of 60°. METHODS: Angles were cut on episiotomy incision pads in a mounted birth model simulating crowning: 110 midwives and doctors cut an 60° episiotomy with Mayo scissors and then EPISCISSORS-60...
December 16, 2016: International Urogynecology Journal
https://www.readbyqxmd.com/read/27981025/long-term-effects-of-a-weight-loss-intervention-with-or-without-exercise-component-in-postmenopausal-women-a-randomized-trial
#19
Martijn de Roon, Willemijn A van Gemert, Petra H Peeters, Albertine J Schuit, Evelyn M Monninkhof
The aim of this study was to determine the long-term effects of a weight loss intervention with or without an exercise component on body weight and physical activity. Women were randomized to diet (n = 97) or exercise (N = 98) for 16 weeks. During the intervention, both groups had achieved the set goal of 5-6 kg weight loss. All women were re-contacted twelve months after study cessation for follow-up where body weight and physical activity were measured (PASE questionnaire and ActiGraph accelerometer)...
March 2017: Preventive Medicine Reports
https://www.readbyqxmd.com/read/27887781/high-psychosis-liability-is-associated-with-altered-autonomic-balance-during-exposure-to-virtual-reality-social-stressors
#20
Jacqueline Counotte, Roos Pot-Kolder, Arie M van Roon, Olivier Hoskam, Mark van der Gaag, Wim Veling
BACKGROUND: Social stressors are associated with an increased risk of psychosis. Stress sensitisation is thought to be an underlying mechanism and may be reflected in an altered autonomic stress response. Using an experimental Virtual Reality design, the autonomic stress response to social stressors was examined in participants with different liability to psychosis. METHOD: Fifty-five patients with recent onset psychotic disorder, 20 patients at ultra-high risk for psychosis, 42 siblings of patients with psychosis and 53 controls were exposed to social stressors (crowdedness, ethnic minority status and hostility) in a Virtual Reality environment...
November 22, 2016: Schizophrenia Research
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