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https://www.readbyqxmd.com/read/29127442/increased-frequencies-of-circulating-cxcl10-cxcl8-and-ccl4-producing-monocytes-and-siglec-3-expressing-myeloid-dendritic-cells-in-systemic-sclerosis-patients
#1
Tiago Carvalheiro, Sara Horta, Joel A G van Roon, Mariana Santiago, Maria J Salvador, Hélder Trindade, Timothy R D J Radstake, José A P da Silva, Artur Paiva
OBJECTIVE: To investigate the ex vivo pro-inflammatory properties of classical and non-classical monocytes as well as myeloid dendritic cells (mDCs) in systemic sclerosis (SSc) patients. METHODS: Spontaneous production of CXCL10, CCL4, CXCL8 and IL-6 was intracellularly evaluated in classical, non-classical monocytes and Siglec-3-expressing mDCs from peripheral blood of SSc patients and healthy controls (HC) through flow cytometry. In addition, production of these cytokines was determined upon toll-like receptor (TLR) 4 plus Interferon-γ (IFN-γ) stimulation...
November 10, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29083044/relapse-in-stage-i-e-diffuse-large-b-cell-lymphoma
#2
Marcel Nijland, Karin Boslooper, Gustaaf van Imhoff, Robbie Kibbelaar, Peter Joosten, Huib Storm, Eric N van Roon, Arjan Diepstra, Hanneke C Kluin-Nelemans, Mels Hoogendoorn
Despite a general favourable outcome in limited stage diffuse large B-cell lymphoma (DLBCL), relapses occur in about 10 to 20% of patients. Prognostic models only partially identify patients at risk for relapse. Moreover, it is not known whether the outcome after such a relapse is similar to the outcome after relapse in advanced stages. From January 2004 through December 2012, all newly diagnosed patients with stage I(E) DLBCL were retrospectively analysed from 2 clinical databases to investigate the relapse pattern and outcome in relation to initial treatment and clinical characteristics...
October 30, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/29021523/high-fidelity-dna-replication-in-mycobacterium-tuberculosis-relies-on-a-trinuclear-zinc-center
#3
Soledad Baños-Mateos, Anne-Marie M van Roon, Ulla F Lang, Sarah L Maslen, J Mark Skehel, Meindert H Lamers
High-fidelity DNA replication depends on a proofreading 3'-5' exonuclease that is associated with the replicative DNA polymerase. The replicative DNA polymerase DnaE1 from the major pathogen Mycobacterium tuberculosis (Mtb) uses its intrinsic PHP-exonuclease that is distinct from the canonical DEDD exonucleases found in the Escherichia coli and eukaryotic replisomes. The mechanism of the PHP-exonuclease is not known. Here, we present the crystal structure of the Mtb DnaE1 polymerase. The PHP-exonuclease has a trinuclear zinc center, coordinated by nine conserved residues...
October 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28992561/bridging-the-gap-between-the-randomised-clinical-trial-world-and-the-real-world-by-combination-of-population-based-registry-and-electronic-health-record-data-a-case-study-in-haemato-oncology
#4
REVIEW
R E Kibbelaar, B E Oortgiesen, A M van der Wal-Oost, K Boslooper, J W Coebergh, N J G M Veeger, P Joosten, H Storm, E N van Roon, M Hoogendoorn
Randomised clinical trials (RCTs) are considered the basis of evidence-based medicine. It is recognised more and more that application of RCT results in daily practice of clinical decision-making is limited because the RCT world does not correspond with the clinical real world. Recent strategies aiming at substitution of RCT databases by improved population-based registries (PBRs) or by improved electronic health record (EHR) systems to provide significant data for clinical science are discussed. A novel approach exemplified by the HemoBase haemato-oncology project is presented...
October 6, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28968826/systemic-and-local-granzyme-b-levels-are-associated-with-disease-activity-kidney-damage-and-interferon-signature-in-systemic-lupus-erythematosus
#5
Helena M Kok, Lucas L van den Hoogen, Joel A G van Roon, Elisabeth J M Adriaansen, Ruth D E Fritsch-Stork, Tri Q Nguyen, Roel Goldschmeding, Timothy R D J Radstake, Niels Bovenschen
Objectives: Granzymes (Grs) are serine proteases that eliminate virally infected or tumour cells by inducing apoptosis. GrB has been shown to be associated to the pathophysiology of SLE, whereas the role of the other Grs in SLE remain unknown. Methods: Gr levels were determined in the serum of SLE patients and controls and linked to SLE activity parameters, including the IFN signature. In addition, GrB expression was investigated in LN biopsies and correlated to kidney function parameters and disease severity...
September 5, 2017: Rheumatology
https://www.readbyqxmd.com/read/28918024/antisense-oligonucleotide-mediated-removal-of-the-polyglutamine-repeat-in-spinocerebellar-ataxia-type-3-mice
#6
Lodewijk J A Toonen, Frank Rigo, Haico van Attikum, Willeke M C van Roon-Mom
Spinocerebellar ataxia type 3 (SCA3) is a currently incurable neurodegenerative disorder caused by a CAG triplet expansion in exon 10 of the ATXN3 gene. The resultant expanded polyglutamine stretch in the mutant ataxin-3 protein causes a gain of toxic function, which eventually leads to neurodegeneration. One important function of ataxin-3 is its involvement in the proteasomal protein degradation pathway, and long-term downregulation of the protein may therefore not be desirable. In the current study, we made use of antisense oligonucleotides to mask predicted exonic splicing signals, resulting in exon 10 skipping from ATXN3 pre-mRNA...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28877319/absence-of-sigma-1-receptor-accelerates-photoreceptor-cell-death-in-a-murine-model-of-retinitis-pigmentosa
#7
Jing Wang, Alan Saul, Xuezhi Cui, Penny Roon, Sylvia B Smith
Purpose: Sigma 1 Receptor (Sig1R) is a novel therapeutic target in neurodegenerative diseases, including retinal disease. Sig1R-/- mice have late-onset retinal degeneration with ganglion cell loss that worsens under stress. Whether Sig1R plays a role in maintaining other retinal neurons is unknown, but was investigated here using rd10 mice, a model of severe photoreceptor degeneration. Methods: Wild-type, rd10, and rd10/Sig1R-/- mice were subjected to ERG and spectral-domain optical coherence tomography (SD-OCT) to assess visual function/structure in situ...
September 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28812075/evidence-for-coherent-mixing-of-excited-and-charge-transfer-states-in-the-major-plant-light-harvesting-antenna-lhcii
#8
Charusheela Ramanan, Marco Ferretti, Henny van Roon, Vladimir I Novoderezhkin, Rienk van Grondelle
LHCII, the major light harvesting antenna from plants, plays a dual role in photosynthesis. In low light it is a light-harvester, while in high light it is a quencher that protects the organism from photodamage. The switching mechanism between these two orthogonal conditions is mediated by protein dynamic disorder and photoprotective energy dissipation. The latter in particular is thought to occur in part via spectroscopically 'dark' states. We searched for such states in LHCII trimers from spinach, at both room temperature and at 77 K...
August 16, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28767105/erratum-genetic-loci-associated-with-heart-rate-variability-and-their-effects-on-cardiac-disease-risk
#9
Ilja M Nolte, M Loretto Munoz, Vinicius Tragante, Azmeraw T Amare, Rick Jansen, Ahmad Vaez, Benedikt von der Heyde, Christy L Avery, Joshua C Bis, Bram Dierckx, Jenny van Dongen, Stephanie M Gogarten, Philippe Goyette, Jussi Hernesniemi, Ville Huikari, Shih-Jen Hwang, Deepali Jaju, Kathleen F Kerr, Alexander Kluttig, Bouwe P Krijthe, Jitender Kumar, Sander W van der Laan, Leo-Pekka Lyytikäinen, Adam X Maihofer, Arpi Minassian, Peter J van der Most, Martina Müller-Nurasyid, Michel Nivard, Erika Salvi, James D Stewart, Julian F Thayer, Niek Verweij, Andrew Wong, Delilah Zabaneh, Mohammad H Zafarmand, Abdel Abdellaoui, Sulayma Albarwani, Christine Albert, Alvaro Alonso, Foram Ashar, Juha Auvinen, Tomas Axelsson, Dewleen G Baker, Paul I W de Bakker, Matteo Barcella, Riad Bayoumi, Rob J Bieringa, Dorret Boomsma, Gabrielle Boucher, Annie R Britton, Ingrid Christophersen, Andrea Dietrich, George B Ehret, Patrick T Ellinor, Markku Eskola, Janine F Felix, John S Floras, Oscar H Franco, Peter Friberg, Maaike G J Gademan, Mark A Geyer, Vilmantas Giedraitis, Catharina A Hartman, Daiane Hemerich, Albert Hofman, Jouke-Jan Hottenga, Heikki Huikuri, Nina Hutri-Kähönen, Xavier Jouven, Juhani Junttila, Markus Juonala, Antti M Kiviniemi, Jan A Kors, Meena Kumari, Tatiana Kuznetsova, Cathy C Laurie, Joop D Lefrandt, Yong Li, Yun Li, Duanping Liao, Marian C Limacher, Henry J Lin, Cecilia M Lindgren, Steven A Lubitz, Anubha Mahajan, Barbara McKnight, Henriette Meyer Zu Schwabedissen, Yuri Milaneschi, Nina Mononen, Andrew P Morris, Mike A Nalls, Gerjan Navis, Melanie Neijts, Kjell Nikus, Kari E North, Daniel T O'Connor, Johan Ormel, Siegfried Perz, Annette Peters, Bruce M Psaty, Olli T Raitakari, Victoria B Risbrough, Moritz F Sinner, David Siscovick, Johannes H Smit, Nicholas L Smith, Elsayed Z Soliman, Nona Sotoodehnia, Jan A Staessen, Phyllis K Stein, Adrienne M Stilp, Katarzyna Stolarz-Skrzypek, Konstantin Strauch, Johan Sundström, Cees A Swenne, Ann-Christine Syvänen, Jean-Claude Tardif, Kent D Taylor, Alexander Teumer, Timothy A Thornton, Lesley E Tinker, André G Uitterlinden, Jessica van Setten, Andreas Voss, Melanie Waldenberger, Kirk C Wilhelmsen, Gonneke Willemsen, Quenna Wong, Zhu-Ming Zhang, Alan B Zonderman, Daniele Cusi, Michele K Evans, Halina K Greiser, Pim van der Harst, Mohammad Hassan, Erik Ingelsson, Marjo-Riitta Järvelin, Stefan Kääb, Mika Kähönen, Mika Kivimaki, Charles Kooperberg, Diana Kuh, Terho Lehtimäki, Lars Lind, Caroline M Nievergelt, Chris J O'Donnell, Albertine J Oldehinkel, Brenda Penninx, Alexander P Reiner, Harriëtte Riese, Arie M van Roon, John D Rioux, Jerome I Rotter, Tamar Sofer, Bruno H Stricker, Henning Tiemeier, Tanja G M Vrijkotte, Folkert W Asselbergs, Bianca J J M Brundel, Susan R Heckbert, Eric A Whitsel, Marcel den Hoed, Harold Snieder, Eco J C de Geus
This corrects the article DOI: 10.1038/ncomms15805.
August 2, 2017: Nature Communications
https://www.readbyqxmd.com/read/28690313/the-hdac-inhibitor-panobinostat-lbh589-exerts-in-vivo-anti-leukaemic-activity-against-mll-rearranged-acute-lymphoblastic-leukaemia-and-involves-the-rnf20-rnf40-wac-h2b-ubiquitination-axis
#10
P G Castro, E H J van Roon, S S M Pinhanços, L Trentin, P Schneider, M Kerstjens, G Te Kronnie, O Heidenreich, R Pieters, R W Stam
MLL-rearranged acute lymphoblastic leukaemia (ALL) represents an aggressive malignancy in infants (<1 year of age), associated with poor outcome. Current treatment intensification is not further possible, and novel therapy strategies are needed. Notably, MLL-rearranged ALL is characterised by a strongly deregulated epigenome and shows sensitivity to epigenetic perturbators. Here, we demonstrate the in vivo efficacy of the histone deacetylase inhibitor Panobinostat (LHB589) using xenograft mouse models of MLL-rearranged ALL...
July 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28622456/increased-ccl25-and-t-helper-cells-expressing-ccr9-in-the-salivary-glands-of-patients-with-primary-sj%C3%A3-gren-s-syndrome-potential-new-axis-in-lymphoid-neogenesis
#11
Sofie L M Blokland, Maarten R Hillen, Aike A Kruize, Stephan Meller, Bernhard Homey, Glennda M Smithson, Timothy R D J Radstake, Joel A G van Roon
OBJECTIVE: Follicular helper T (Tfh) cells play a critical role in germinal center formation and B cell activation, both of which are hallmarks of primary Sjögren's syndrome (SS). CCR9-expressing T helper cells have "Tfh-like" characteristics and their numbers are increased at mucosa-associated sites in several inflammatory conditions. Because the characteristics of these cells are unique and evaluation has been limited, this study was undertaken to investigate the local and systemic CCL25/CCR9 axis in patients with primary SS...
October 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28613276/genetic-loci-associated-with-heart-rate-variability-and-their-effects-on-cardiac-disease-risk
#12
Ilja M Nolte, M Loretto Munoz, Vinicius Tragante, Azmeraw T Amare, Rick Jansen, Ahmad Vaez, Benedikt von der Heyde, Christy L Avery, Joshua C Bis, Bram Dierckx, Jenny van Dongen, Stephanie M Gogarten, Philippe Goyette, Jussi Hernesniemi, Ville Huikari, Shih-Jen Hwang, Deepali Jaju, Kathleen F Kerr, Alexander Kluttig, Bouwe P Krijthe, Jitender Kumar, Sander W van der Laan, Leo-Pekka Lyytikäinen, Adam X Maihofer, Arpi Minassian, Peter J van der Most, Martina Müller-Nurasyid, Michel Nivard, Erika Salvi, James D Stewart, Julian F Thayer, Niek Verweij, Andrew Wong, Delilah Zabaneh, Mohammad H Zafarmand, Abdel Abdellaoui, Sulayma Albarwani, Christine Albert, Alvaro Alonso, Foram Ashar, Juha Auvinen, Tomas Axelsson, Dewleen G Baker, Paul I W de Bakker, Matteo Barcella, Riad Bayoumi, Rob J Bieringa, Dorret Boomsma, Gabrielle Boucher, Annie R Britton, Ingrid Christophersen, Andrea Dietrich, George B Ehret, Patrick T Ellinor, Markku Eskola, Janine F Felix, John S Floras, Oscar H Franco, Peter Friberg, Maaike G J Gademan, Mark A Geyer, Vilmantas Giedraitis, Catharina A Hartman, Daiane Hemerich, Albert Hofman, Jouke-Jan Hottenga, Heikki Huikuri, Nina Hutri-Kähönen, Xavier Jouven, Juhani Junttila, Markus Juonala, Antti M Kiviniemi, Jan A Kors, Meena Kumari, Tatiana Kuznetsova, Cathy C Laurie, Joop D Lefrandt, Yong Li, Yun Li, Duanping Liao, Marian C Limacher, Henry J Lin, Cecilia M Lindgren, Steven A Lubitz, Anubha Mahajan, Barbara McKnight, Henriette Meyer Zu Schwabedissen, Yuri Milaneschi, Nina Mononen, Andrew P Morris, Mike A Nalls, Gerjan Navis, Melanie Neijts, Kjell Nikus, Kari E North, Daniel T O'Connor, Johan Ormel, Siegfried Perz, Annette Peters, Bruce M Psaty, Olli T Raitakari, Victoria B Risbrough, Moritz F Sinner, David Siscovick, Johannes H Smit, Nicholas L Smith, Elsayed Z Soliman, Nona Sotoodehnia, Jan A Staessen, Phyllis K Stein, Adrienne M Stilp, Katarzyna Stolarz-Skrzypek, Konstantin Strauch, Johan Sundström, Cees A Swenne, Ann-Christine Syvänen, Jean-Claude Tardif, Kent D Taylor, Alexander Teumer, Timothy A Thornton, Lesley E Tinker, André G Uitterlinden, Jessica van Setten, Andreas Voss, Melanie Waldenberger, Kirk C Wilhelmsen, Gonneke Willemsen, Quenna Wong, Zhu-Ming Zhang, Alan B Zonderman, Daniele Cusi, Michele K Evans, Halina K Greiser, Pim van der Harst, Mohammad Hassan, Erik Ingelsson, Marjo-Riitta Järvelin, Stefan Kääb, Mika Kähönen, Mika Kivimaki, Charles Kooperberg, Diana Kuh, Terho Lehtimäki, Lars Lind, Caroline M Nievergelt, Chris J O'Donnell, Albertine J Oldehinkel, Brenda Penninx, Alexander P Reiner, Harriëtte Riese, Arie M van Roon, John D Rioux, Jerome I Rotter, Tamar Sofer, Bruno H Stricker, Henning Tiemeier, Tanja G M Vrijkotte, Folkert W Asselbergs, Bianca J J M Brundel, Susan R Heckbert, Eric A Whitsel, Marcel den Hoed, Harold Snieder, Eco J C de Geus
Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4)...
June 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28594282/availability-of-cyp2d6-genotyping-results-in-general-practitioner-and-community-pharmacy-medical-records
#13
Mirjam Simoons, Hans Mulder, Robert A Schoevers, Henricus G Ruhé, Eric N van Roon
AIM: To investigate the availability of CYP450-2D6 (CYP2D6) genotyping results in general practitioner (GP) and/or community pharmacy records, and the influence thereof on psychotropic CYP2D6 substrate dosing. MATERIALS & METHODS: Primary outcome was the percentage of patients genotyped for CYP2D6 with their genotype/phenotype registered in GP and/or pharmacy records. Secondary outcome was the number of defined daily doses of psychotropic CYP2D6 substrates prescribed after genotyping...
June 8, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28585930/large-normal-range-tbp-and-atxn7-cag-repeat-lengths-are-associated-with-increased-lifetime-risk-of-depression
#14
S L Gardiner, M J van Belzen, M W Boogaard, W M C van Roon-Mom, M P Rozing, A M van Hemert, J H Smit, A T F Beekman, G van Grootheest, R A Schoevers, R C Oude Voshaar, H C Comijs, B W J H Penninx, R C van der Mast, R A C Roos, N A Aziz
Depression is one of the most prevalent and debilitating psychiatric disorders worldwide. Recently, we showed that both relatively short and relatively long cytosine-adenine-guanine (CAG) repeats in the huntingtin gene (HTT) are associated with an increased risk of lifetime depression. However, to what extent the variations in CAG repeat length in the other eight polyglutamine disease-associated genes (PDAGs) are associated with depression is still unknown. We determined the CAG repeat sizes of ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, ATN1 and AR in two well-characterized Dutch cohorts-the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons-including 2165 depressed and 1058 non-depressed individuals-aged 18-93 years...
June 6, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28570578/effect-of-post-mortem-delay-on-n-terminal-huntingtin-protein-fragments-in-human-control-and-huntington-disease-brain-lysates
#15
Menno H Schut, Stefano Patassini, Eric H Kim, Jocelyn Bullock, Henry J Waldvogel, Richard L M Faull, Barry A Pepers, Johan T den Dunnen, Gert-Jan B van Ommen, Willeke M C van Roon-Mom
Huntington disease is associated with elongation of a CAG repeat in the HTT gene that results in a mutant huntingtin protein. Several studies have implicated N-terminal huntingtin protein fragments in Huntington disease pathogenesis. Ideally, these fragments are studied in human brain tissue. However, the use of human brain tissue comes with certain unavoidable variables such as post mortem delay, artefacts from freeze-thaw cycles and subject-to-subject variation. Knowledge on how these variables might affect N-terminal huntingtin protein fragments in post mortem human brain is important for a proper interpretation of study results...
2017: PloS One
https://www.readbyqxmd.com/read/28557134/tgf%C3%AE-pathway-deregulation-and-abnormal-phospho-smad2-3-staining-in-hereditary-cerebral-hemorrhage-with-amyloidosis-dutch-type
#16
Laure Grand Moursel, Leon P Munting, Linda M van der Graaf, Sjoerd G van Duinen, Marie-Jose T H Goumans, Uwe Ueberham, Remco Natté, Mark A van Buchem, Willeke M C van Roon-Mom, Louise van der Weerd
Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) is an early onset hereditary form of cerebral amyloid angiopathy (CAA) pathology, caused by the E22Q mutation in the amyloid β (Aβ) peptide. Transforming Growth Factor β1 (TGFβ1) is a key player in vascular fibrosis and in the formation of angiopathic vessels in transgenic mice. Therefore we investigated whether the TGFβ pathway is involved in HCHWA-D pathogenesis in human postmortem brain tissue from frontal and occipital lobes. Components of the TGFβ pathway were analyzed with quantitative RT-PCR...
May 29, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28556560/association-of-microrna-618-expression-with-altered-frequency-and-activation-of-plasmacytoid-dendritic-cells-in-patients-with-systemic-sclerosis
#17
Marzia Rossato, Alsya J Affandi, Soley Thordardottir, Catharina G K Wichers, Marta Cossu, Jasper C A Broen, Frederique M Moret, Lara Bossini-Castillo, Eleni Chouri, Lenny van Bon, Femke Wolters, Wioleta Marut, Maarten van der Kroef, Sandra Silva-Cardoso, Cornelis P J Bekker, Harry Dolstra, Jacob M van Laar, Javier Martin, Joel A G van Roon, Kris A Reedquist, Lorenzo Beretta, Timothy R D J Radstake
OBJECTIVE: Plasmacytoid dendritic cells (PDCs) are a critical source of type I interferons (IFNs) that can contribute to the onset and maintenance of autoimmunity. Molecular mechanisms leading to PDC dysregulation and a persistent type I IFN signature are largely unexplored, especially in patients with systemic sclerosis (SSc), a disease in which PDCs infiltrate fibrotic skin lesions and produce higher levels of IFNα than those in healthy controls. This study was undertaken to investigate potential microRNA (miRNA)-mediated epigenetic mechanisms underlying PDC dysregulation and type I IFN production in SSc...
September 2017: Arthritis & Rheumatology
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
#18
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
#19
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...
July 1, 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
#20
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
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