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Andrew E Teschendorff, Shijie C Zheng, Andy Feber, Zhen Yang, Stephan Beck, Martin Widschwendter
BACKGROUND: Hypermethylation of transcription factor promoters bivalently marked in stem cells is a cancer hallmark. However, the biological significance of this observation for carcinogenesis is unclear given that most of these transcription factors are not expressed in any given normal tissue. METHODS: We analysed the dynamics of gene expression between human embryonic stem cells, fetal and adult normal tissue, as well as six different matching cancer types. In addition, we performed an integrative multi-omic analysis of matched DNA methylation, copy number, mutational and transcriptomic data for these six cancer types...
2016: Genome Medicine
Andrew Feber, Daniel C Worth, Ankur Chakravarthy, Patricia de Winter, Kunal Shah, Manit Arya, Muhammad Saqib, Raj Nigam, Peter R Malone, Wei Shen Tan, Simon Rodney, Alex Freeman, Charles Jameson, Gareth A Wilson, Tom Powles, Stephan Beck, Tim Fenton, Tyson V Sharp, Asif Muneer, John D Kelly
Other than an association with HPV infection, little is known about the genetic alterations determining the development of penile cancer. Although penile cancer is rare in the developed world, it presents a significant burden in developing countries. Here, we report the findings of whole-exome sequencing (WES) to determine the somatic mutational landscape of penile cancer. WES was performed on penile cancer and matched germline DNA from 27 patients undergoing surgical resection. Targeted resequencing of candidate genes was performed in an independent 70 patient cohort...
August 15, 2016: Cancer Research
Kevin C Harris, Geneviève Benoit, Janis Dionne, Janusz Feber, Lyne Cloutier, Kelly B Zarnke, Raj S Padwal, Doreen M Rabi, Anne Fournier
We present the inaugural evidence-based Canadian recommendations for the measurement of blood pressure in children and the diagnosis and evaluation of pediatric hypertension. Rates of pediatric hypertension are increasing concomitant with increased rates of childhood obesity. With this, there is growing awareness of the need to measure blood pressure in children. Consequently, the present recommendations have been developed to address an important gap and improve the clinical care of children. For 2016, a total of 15 recommendations are presented...
May 2016: Canadian Journal of Cardiology
Alexander A Leung, Kara Nerenberg, Stella S Daskalopoulou, Kerry McBrien, Kelly B Zarnke, Kaberi Dasgupta, Lyne Cloutier, Mark Gelfer, Maxime Lamarre-Cliche, Alain Milot, Peter Bolli, Guy Tremblay, Donna McLean, Sheldon W Tobe, Marcel Ruzicka, Kevin D Burns, Michel Vallée, G V Ramesh Prasad, Marcel Lebel, Ross D Feldman, Peter Selby, Andrew Pipe, Ernesto L Schiffrin, Philip A McFarlane, Paul Oh, Robert A Hegele, Milan Khara, Thomas W Wilson, S Brian Penner, Ellen Burgess, Robert J Herman, Simon L Bacon, Simon W Rabkin, Richard E Gilbert, Tavis S Campbell, Steven Grover, George Honos, Patrice Lindsay, Michael D Hill, Shelagh B Coutts, Gord Gubitz, Norman R C Campbell, Gordon W Moe, Jonathan G Howlett, Jean-Martin Boulanger, Ally Prebtani, Pierre Larochelle, Lawrence A Leiter, Charlotte Jones, Richard I Ogilvie, Vincent Woo, Janusz Kaczorowski, Luc Trudeau, Robert J Petrella, Swapnil Hiremath, Denis Drouin, Kim L Lavoie, Pavel Hamet, George Fodor, Jean C Grégoire, Richard Lewanczuk, George K Dresser, Mukul Sharma, Debra Reid, Scott A Lear, Gregory Moullec, Milan Gupta, Laura A Magee, Alexander G Logan, Kevin C Harris, Janis Dionne, Anne Fournier, Geneviève Benoit, Janusz Feber, Luc Poirier, Raj S Padwal, Doreen M Rabi
Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force provides annually updated, evidence-based recommendations to guide the diagnosis, assessment, prevention, and treatment of hypertension. This year, we present 4 new recommendations, as well as revisions to 2 previous recommendations. In the diagnosis and assessment of hypertension, automated office blood pressure, taken without patient-health provider interaction, is now recommended as the preferred method of measuring in-office blood pressure...
May 2016: Canadian Journal of Cardiology
Mieczyslaw Litwin, Janusz Feber, Marcel Ruzicka
Hypertension (HTN) in children is associated with early vascular aging (EVA) and underlying immunologic-metabolic abnormalities and accelerated biological maturation. Morphologic and functional vascular changes underlying EVA and HTN in children resemble those seen in the elderly including but not limited to an increase in intima-media thickness (IMT) and arterial stiffness and endothelial dysfunction. Although progeria syndrome leading to EVA and the development of clinically manifested cardiovascular (CV) disease in the second decade of life is a rare hereditary disorder, primary HTN, which is also associated with EVA, is much more common (reported in up to 10% in adolescents)...
May 2016: Canadian Journal of Cardiology
Christian C Raiss, Theresa S Braun, Irene B M Konings, Heinrich Grabmayr, Gerco C Hassink, Arshdeep Sidhu, Joost le Feber, Andreas R Bausch, Casper Jansen, Vinod Subramaniam, Mireille M A E Claessens
The formation of α-synuclein (α-S) amyloid aggregates, called Lewy bodies (LBs), is a hallmark of Parkinson's disease (PD). The function of LBs in the disease process is however still unclear; they have been associated with both neuroprotection and toxicity. To obtain insight into this contradiction, we induced the formation of α-S inclusions, using three different induction methods in SH-SY5Y cells and rat-derived primary neuronal cells. Using confocal and STED microscopy we observed induction-dependent differences in α-S inclusion morphology, location and function...
2016: Scientific Reports
I V Kabakova, A de Hoogh, R E C van der Wel, M Wulf, B le Feber, L Kuipers
Near-field imaging is a powerful tool to investigate the complex structure of light at the nanoscale. Recent advances in near-field imaging have indicated the possibility for the complete reconstruction of both electric and magnetic components of the evanescent field. Here we study the electro-magnetic field structure of surface plasmon polariton waves propagating along subwavelength gold nanowires by performing phase- and polarization-resolved near-field microscopy in collection mode. By applying the optical reciprocity theorem, we describe the signal collected by the probe as an overlap integral of the nanowire's evanescent field and the probe's response function...
2016: Scientific Reports
Joost le Feber, Stelina Tzafi Pavlidou, Niels Erkamp, Michel J A M van Putten, Jeannette Hofmeijer
Improvement of neuronal recovery in the ischemic penumbra around a brain infarct has a large potential to advance clinical recovery of patients with acute ischemic stroke. However, pathophysiological mechanisms leading to either recovery or secondary damage in the penumbra are not completely understood. We studied neuronal dynamics in a model system of the penumbra consisting of networks of cultured cortical neurons exposed to controlled levels and durations of hypoxia. Short periods of hypoxia (pO2≈20mmHg) reduced spontaneous activity, due to impeded synaptic function...
2016: PloS One
Mattheus T T Oosterwijk, Maaike Le Feber, Enrico Burello
We present a conceptual framework that can be used to assign risk bands to inhaled low aspect ratio nanoparticles starting from exposure bands assigned to a specific exposure situation. The framework mimics a basic physiological scheme that captures the essential mechanisms of fate and toxicity of inhaled nanoparticles and is composed of several models and rules that estimate the result of the following processes: the deposition of particles in the respiratory tract, their (de-)agglomeration, lung burden and clearance, their diffusion through the lung mucus layer, translocation and cellular uptake and local and systemic toxicity...
August 2016: Nanotoxicology
Katarina Prochotska, Laszlo Kovacs, Eva Vitariusova, Janusz Feber
The aim of the article was to evaluate arterial stiffness, an early marker of increased cardiovascular risk, in relation to obesity. The continuous metabolic syndrome (cMetS) score was calculated as sum of Z score of mean arterial pressure, body mass index, serum glucose, triglyceride, and high-density lipoprotein cholesterol in 144 obese patients and 66 nonobese controls. Ambulatory arterial stiffness index (AASI) was calculated as 1 minus regression slope of diastolic on systolic blood pressure from ambulatory blood pressure measurements...
January 2016: Journal of the American Society of Hypertension: JASH
Dirk S Paul, Allison Jones, Rob S Sellar, Neema P Mayor, Andrew Feber, Amy P Webster, Neuza Afonso, Ruhena Sergeant, Richard M Szydlo, Jane F Apperley, Martin Widschwendter, Stephen Mackinnon, Steven G E Marsh, J Alejandro Madrigal, Vardhman K Rakyan, Karl S Peggs, Stephan Beck
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological conditions. Acute graft-versus-host disease (aGVHD) is a prevalent immune-mediated complication following HSCT. Current diagnostic biomarkers that correlate with aGVHD severity, progression, and therapy response in graft recipients are insufficient. Here, we investigated whether epigenetic marks measured in peripheral blood of healthy graft donors stratify aGVHD severity in human leukocyte antigen (HLA)-matched sibling recipients prior to T cell-depleted HSCT...
2015: Genome Medicine
Helena Carén, Stefan H Stricker, Harry Bulstrode, Sladjana Gagrica, Ewan Johnstone, Thomas E Bartlett, Andrew Feber, Gareth Wilson, Andrew E Teschendorff, Paul Bertone, Stephan Beck, Steven M Pollard
Glioblastoma (GBM) is an aggressive brain tumor whose growth is driven by stemcell-like cells. BMP signaling triggers cell-cycle exit and differentiation of GBM stemcells (GSCs) and, therefore, might have therapeutic value. However, the epigenetic mechanisms that accompany differentiation remain poorly defined. It is also unclear whether cell-cycle arrest is terminal. Herewe find only a subset ofGSCcultures exhibit astrocyte differentiation in response to BMP. Although overtly differentiated non-cycling astrocytes are generated, they remain vulnerable to cell-cycle re-entry and fail to appropriately reconfigure DNA methylation patterns...
November 10, 2015: Stem Cell Reports
Joost le Feber, Wybren Postma, Eddy de Weerd, Marcel Weusthof, Wim L C Rutten
Cultured neurons on multi electrode arrays (MEAs) have been widely used to study various aspects of neuronal (network) functioning. A possible drawback of this approach is the lack of structure in these networks. At the single cell level, several solutions have been proposed to enable directed connectivity, and promising results were obtained. At the level of connected sub-populations, a few attempts have been made with promising results. First assessment of the designs' functionality, however, suggested room for further improvement...
2015: Frontiers in Neuroscience
Joost le Feber, Tim Witteveen, Tamar M van Veenendaal, Jelle Dijkstra
During systems consolidation, memories are spontaneously replayed favoring information transfer from hippocampus to neocortex. However, at present no empirically supported mechanism to accomplish a transfer of memory from hippocampal to extra-hippocampal sites has been offered. We used cultured neuronal networks on multielectrode arrays and small-scale computational models to study the effect of memory replay on the formation of memory traces. We show that input-deprived networks develop an activity⇔connectivity balance where dominant activity patterns support current connectivity...
December 2015: Learning & Memory
Irina I Stoyanova, Jeannette Hofmeijer, Michel J A M van Putten, Joost le Feber
Comatose patients after cardiac arrest have a poor prognosis. Approximately half never awakes as a result of severe diffuse postanoxic encephalopathy. Several neuroprotective agents have been tested, however without significant effect. In the present study, we used cultured neuronal networks as a model system to study the general synaptic damage caused by temporary severe hypoxia and the possibility to restrict it by ghrelin treatment. Briefly, we applied hypoxia (pO2 lowered from 150 to 20 mmHg) during 6 h in 55 cultures...
November 6, 2015: Molecular Neurobiology
Mónica Martínez-Fernández, Marta Dueñas, Andrew Feber, Cristina Segovia, Ramón García-Escudero, Carolina Rubio, Fernando F López-Calderón, Claudio Díaz-García, Felipe Villacampa, José Duarte, María J Gómez-Rodriguez, Daniel Castellano, José L Rodriguez-Peralto, Federico de la Rosa, Stephan Beck, Jesús M Paramio
Bladder cancer (BC) is a highly prevalent disease, ranking fifth in the most common cancers worldwide. Various miRNAs have recently emerged as potential prognostic biomarkers in cancer. The miR-200 family, which repressed the epithelial-to-mesenchymal transition (EMT), is repressed in multiple advanced cancers. However, its expression and function in BC is still poorly understood. Here we show that miR-200 family displays increased expression, probably due to the activation of specific oncogenic signaling pathways, and reduced promoter methylation, in BC compared to normal bladder samples...
December 8, 2015: Oncotarget
Mónica Martínez-Fernández, Andrew Feber, Marta Dueñas, Cristina Segovia, Carolina Rubio, Maria Fernandez, Felipe Villacampa, José Duarte, Fernando F López-Calderón, Ma José Gómez-Rodriguez, Daniel Castellano, Jose L Rodriguez-Peralto, Federico de la Rosa, Stephan Beck, Jesús M Paramio
BACKGROUND: Long non-coding RNAs (lncRNAs) have been claimed as key molecular players in gene expression regulation, being involved in diverse epigenetic processes. They are aberrantly expressed in various tumors, but their exact role in bladder cancer is still obscure. We have recently found a major role of the Polycomb repression complex in recurrence of non-muscle-invasive bladder cancer. Here, we report the xpression of Polycomb-related lncRNAs:antisense noncoding RNA in the INK4 locus (ANRIL) and HOX antisense intergenic RNA (HOTAIR) in these tumors...
2015: Clinical Epigenetics
Rosalind F Shaw, Paul J Johnson, David W Macdonald, Ruth E Feber
Drainage ditches, either seasonally flooded or permanent, are commonly found on intensively managed lowland farmland in the UK. They are potentially important for wetland biodiversity but, despite their ubiquity, information on their biodiversity and management in the wider countryside is scarce. We surveyed 175 ditches for their physical and chemical characteristics, spatial connectivity, plant communities and aquatic invertebrates in an area of intensively managed farmland in Oxfordshire, UK and collected information on ditch management from farmer interviews...
2015: PloS One
Ruth E Feber, Paul J Johnson, James R Bell, Dan E Chamberlain, Leslie G Firbank, Robert J Fuller, Will Manley, Fiona Mathews, Lisa R Norton, Martin Townsend, David W Macdonald
Organic farming, a low intensity system, may offer benefits for a range of taxa, but what affects the extent of those benefits is imperfectly understood. We explored the effects of organic farming and landscape on the activity density and species density of spiders and carabid beetles, using a large sample of paired organic and conventional farms in the UK. Spider activity density and species density were influenced by both farming system and surrounding landscape. Hunting spiders, which tend to have lower dispersal capabilities, had higher activity density, and more species were captured, on organic compared to conventional farms...
2015: PloS One
Janusz Feber, Mieczyslaw Litwin
The assessment of blood pressure (BP) can be challenging in children, especially in very young individuals, due to their variable body size and lack of cooperation. In the absence of data relating BP with cardiovascular outcomes in children, there is a need to convert absolute BP values (in mmHg) into age-, gender- and height appropriate BP percentiles or Z-scores in order to compare a patient's BP with the BP of healthy children of the same age, but also of children of different ages. Traditionally, the interpretation of BP has been based mainly on the assessment of the BP level obtained by office, home or 24-h BP monitoring...
July 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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