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J Willem L Tideman, Margaretha C C Snabel, Milly S Tedja, Gwyneth A van Rijn, King T Wong, Robert W A M Kuijpers, Johannes R Vingerling, Albert Hofman, Gabriëlle H S Buitendijk, Jan E E Keunen, Camiel J F Boon, Annette J M Geerards, Gregorius P M Luyten, Virginie J M Verhoeven, Caroline C W Klaver
Importance: Myopia (ie, nearsightedness) is becoming the most common eye disorder to cause blindness in younger persons in many parts of the world. Visual impairment due to myopia is associated with structural changes of the retina and the globe because of elongation of the eye axis. How axial length-a sum of the anterior chamber depth, lens thickness, and vitreous chamber depth-and myopia relate to the development of visual impairment over time is unknown. Objectives: To evaluate the association between axial length, spherical equivalent, and the risk of visual impairment and to make projections of visual impairment for regions with high prevalence rates...
October 20, 2016: JAMA Ophthalmology
T Huibertus van Essen, Sake I van Pelt, Inge H G Bronkhorst, Mieke Versluis, Fariba Némati, Cécile Laurent, Gregorius P M Luyten, Thorbald van Hall, Peter J van den Elsen, Pieter A van der Velden, Didier Decaudin, Martine J Jager
INTRODUCTION: Uveal melanoma (UM) with an inflammatory phenotype, characterized by infiltrating leukocytes and increased human leukocyte antigen (HLA) expression, carry an increased risk of death due to metastases. These tumors should be ideal for T-cell based therapies, yet it is not clear why prognostically-infaust tumors have a high HLA expression. We set out to determine whether the level of HLA molecules in UM is associated with other genetic factors, HLA transcriptional regulators, or microenvironmental factors...
2016: PloS One
G Kerckhofs, M Durand, R Vangoitsenhoven, C Marin, B Van der Schueren, G Carmeliet, F P Luyten, L Geris, K Vandamme
High resolution microfocus X-ray computed tomography (HR-microCT) was employed to characterize the structural alterations of the cortical and trabecular bone in a mouse model of obesity-driven type 2 diabetes (T2DM). C57Bl/6J mice were randomly assigned for 14 weeks to either a control diet-fed (CTRL) or a high fat diet (HFD)-fed group developing obesity, hyperglycaemia and insulin resistance. The HFD group showed an increased trabecular thickness and a decreased trabecular number compared to CTRL animals. Midshaft tibia intracortical porosity was assessed at two spatial image resolutions...
October 19, 2016: Scientific Reports
Armaghan Mahmoudian, Jaap H van Dieen, Sjoerd M Bruijn, Isabel Ac Baert, Gert S Faber, Frank P Luyten, Sabine Mp Verschueren
BACKGROUND: Varus thrust, defined as an abrupt increase of the knee varus angle during weight-bearing in gait, has been shown to be present in patients with moderate to severe knee osteoarthritis and is considered to be one of the risk factors for progression of symptomatic medial knee osteoarthritis. We evaluated the presence and magnitude of varus thrust and its relation with the Knee Adduction Moment in women with early medial knee osteoarthritis, and compared it to that in a group of controls and in a group of subjects with established medial knee osteoarthritis...
October 8, 2016: Clinical Biomechanics
Marina Marinkovic, Nanda Horeweg, Marta Fiocco, Femke P Peters, Linda W Sommers, Mirjam S Laman, Jaco C Bleeker, Martijn Ketelaars, Gre P M Luyten, Carien L Creutzberg
PURPOSE: To evaluate efficacy and toxicity of two different protocols for eye-conserving treatment of patients with small to intermediate-sized choroidal melanomas; the current ruthenium-106 (Ru106) brachytherapy protocol and the preceding protocol of Ru106-brachytherapy with transpupillary thermotherapy (Ru106/TTT). METHODS AND MATERIALS: Long-term outcomes of 449 consecutive patients, of whom 196 (43.6%) treated using Ru106/TTT and 253 (56.3%) treated using Ru106, were compared in terms of local control, survival, eye preservation and visual outcome...
October 11, 2016: European Journal of Cancer
Antoine Porquier, Guillaume Morgant, Javier Moraga, Bérengère Dalmais, Isabelle Luyten, Adeline Simon, Jean-Marc Pradier, Joëlle Amselem, Isidro González Collado, Muriel Viaud
Botrydial (BOT) is a non-host specific phytotoxin produced by the polyphagous phytopathogenic fungus Botrytis cinerea. The genomic region of the BOT biosynthetic gene cluster was investigated and revealed two additional genes named Bcbot6 and Bcbot7. Analysis revealed that the G+C/A+T-equilibrated regions that contain the Bcbot genes alternate with A+T-rich regions made of relics of transposable elements that have undergone repeat-induced point mutations (RIP). Furthermore, BcBot6, a Zn(II)2Cys6 putative transcription factor was identified as a nuclear protein and the major positive regulator of BOT biosynthesis...
October 6, 2016: Fungal Genetics and Biology: FG & B
Leon H Oosterik, Huruma N Tuntufye, Jessica Tsonos, Tom Luyten, Sam Noppen, Sandra Liekens, Rob Lavigne, Patrick Butaye, Bruno M Goddeeris
Avian pathogenic Escherichia coli (APEC) are responsible for significant economic losses in the poultry industry. In this study, a model for investigating the pathogenesis of APEC infections was established. APEC strain CH2 (O78) was marked with the luciferase operon (luxCDABE) using a Tn7 transposon and tissues of experimentally infected chickens were analysed for a correlation between the bioluminescent signal and the number of bacteria. Transposition of the lux operon into the chromosome of the APEC isolate did not affect sensitivity to lytic bacteriophages and there was no effect on virulence in an intratracheal infection model in 1-day-old chicks, although results with a subcutaneous infection model were inconclusive...
October 2016: Veterinary Journal
Peyman Sardari Nia, Samuel Heuts, Jean Daemen, Peter Luyten, Jindrich Vainer, Jan Hoorntje, Emile Cheriex, Jos Maessen
OBJECTIVES: Mitral valve repair performed by an experienced surgeon is superior to mitral valve replacement for degenerative mitral valve disease; however, many surgeons are still deterred from adapting this procedure because of a steep learning curve. Simulation-based training and planning could improve the surgical performance and reduce the learning curve. The aim of this study was to develop a patient-specific simulation for mitral valve repair and provide a proof of concept of personalized medicine in a patient prospectively planned for mitral valve surgery...
September 27, 2016: Interactive Cardiovascular and Thoracic Surgery
L Luyten, N Schroyens, K Luyck, M S Fanselow, T Beckers
The excessive transfer of fear acquired for one particular context to similar situations has been implicated in the development and maintenance of anxiety disorders, such as post-traumatic stress disorder. Recent evidence suggests that glucose ingestion improves the retention of context conditioning. It has been speculated that glucose might exert that effect by ameliorating hippocampal functioning, and may hold promise as a therapeutic add-on in traumatized patients because improved retention of contextual fear could help to restrict its generalization...
2016: Translational Psychiatry
Anke Vanderstraeten, Sandra Tuyaerts, Tina Everaert, Rieta Van Bree, Godelieve Verbist, Cathérine Luyten, Frederic Amant
BACKGROUND: While immunotherapy moved to the forefront of treatment of various cancers, it remains underexplored for uterine cancer. This might be due to the small patient population with advanced endometrial carcinoma and uterine sarcoma. Data about immunotherapeutic targets are scarce in endometrial carcinoma and lacking in uterine sarcoma. METHODS: Expression of five tumor-associated antigens (TAA) (BORIS, MUC1, hTERT, MAGE-A3 and Sp17) was validated in uterine tumor samples by immunohistochemistry (IHC) and/or quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR)...
September 9, 2016: International Journal of Molecular Sciences
Eddy-Tim Verjans, Sven Zels, Walter Luyten, Bart Landuyt, Liliane Schoofs
The human cathelicidin peptide LL-37 plays a crucial role in the immune system on many levels, from the first line of defense in epithelial cells to restoring the tissue after infection. On host cells, the majority of the LL-37-induced effects are mediated via the direct or indirect activation of several structurally unrelated cell surface receptors or intracellular targets. How LL-37 is able to affect multiple receptors is currently not well understood. So far, the mechanistic details underlying receptor activation are poorly investigated and evidence for a conventional ligand/receptor interaction is scarce...
September 5, 2016: Peptides
Martin Debbané, George Salaminios, Patrick Luyten, Deborah Badoud, Marco Armando, Alessandra Solida Tozzi, Peter Fonagy, Benjamin K Brent
In this review article, we outline the evidence linking attachment adversity to psychosis, from the premorbid stages of the disorder to its clinical forms. To better understand the neurobiological mechanisms through which insecure attachment may contribute to psychosis, we identify at least five neurobiological pathways linking attachment to risk for developing psychosis. Besides its well documented influence on the hypothalamic-pituary-adrenal (HPA) axis, insecure attachment may also contribute to neurodevelopmental risk through the dopaminergic and oxytonergic systems, as well as bear influence on neuroinflammation and oxidative stress responses...
2016: Frontiers in Human Neuroscience
Richard D Morgan, Yvette A Luyten, Samuel A Johnson, Emily M Clough, Tyson A Clark, Richard J Roberts
We identify a new subgroup of Type I Restriction-Modification enzymes that modify cytosine in one DNA strand and adenine in the opposite strand for host protection. Recognition specificity has been determined for ten systems using SMRT sequencing and each recognizes a novel DNA sequence motif. Previously characterized Type I systems use two identical copies of a single methyltransferase (MTase) subunit, with one bound at each half site of the specificity (S) subunit to form the MTase. The new m4C-producing Type I systems we describe have two separate yet highly similar MTase subunits that form a heterodimeric M1M2S MTase...
August 31, 2016: Nucleic Acids Research
Johan Kerkhofs, Jeroen Leijten, Johanna Bolander, Frank P Luyten, Janine N Post, Liesbet Geris
Differentiation of chondrocytes towards hypertrophy is a natural process whose control is essential in endochondral bone formation. It is additionally thought to play a role in several pathophysiological processes, with osteoarthritis being a prominent example. We perform a dynamic analysis of a qualitative mathematical model of the regulatory network that directs this phenotypic switch to investigate the influence of the individual factors holistically. To estimate the stability of a SOX9 positive state (associated with resting/proliferation chondrocytes) versus a RUNX2 positive one (associated with hypertrophy) we employ two measures...
2016: PloS One
Eleonora M de Leede, Mark C Burgmans, Ellen Kapiteijn, Gre P M Luyten, Martine J Jager, Fred G J Tijl, Henk H Hartgrink, Dirk J Grünhagen, Joost Rothbarth, Cornelis J H van de Velde, Cornelis Verhoef, Alexander L Vahrmeijer
Uveal melanoma patients have a poor survival after the diagnosis of metastatic disease. Isolated hepatic perfusion (IHP) was developed to treat patients with unresectable metastases confined to the liver. This retrospective analysis focuses on treatment characteristics, complications, toxicity and survival after IHP. Patients with uveal melanoma metastases confined to the liver treated with IHP in two experienced hepato-pancreatic-biliary surgery centres (Erasmus MC Cancer Institute and Leiden University Medical Center) were included...
August 10, 2016: Melanoma Research
Hristina Ivanova, Abigael Ritane, Larry Wagner, Tomas Luyten, George Shapovalov, Kirsten Welkenhuyzen, Bruno Seitaj, Giovanni Monaco, Humbert De Smedt, Natalia Prevarskaya, David I Yule, Jan B Parys, Geert Bultynck
The anti-apoptotic Bcl-2 protein is emerging as an efficient inhibitor of IP3R function, contributing to its oncogenic properties. Yet, the underlying molecular mechanisms remain not fully understood. Using mutations or pharmacological inhibition to antagonize Bcl-2's hydrophobic cleft, we excluded this functional domain as responsible for Bcl-2-mediated IP3Rs inhibition. In contrast, the deletion of the C-terminus, containing the trans-membrane domain, which is only present in Bcl-2α, but not in Bcl-2β, led to impaired inhibition of IP3R-mediated Ca2+ release and staurosporine-induced apoptosis...
August 2, 2016: Oncotarget
Chongzhi Zang, Annouck Luyten, Justina Chen, X Shirley Liu, Ramesh A Shivdasani
Mutations in mouse and human Nfe2, Fli1 and Runx1 cause thrombocytopenia. We applied genome-wide chromatin dynamics and ChIP-seq to determine these transcription factors' (TFs) activities in terminal megakaryocyte (MK) maturation. Enhancers with H3K4me2-marked nucleosome pairs were most enriched for NF-E2, FLI and RUNX sequence motifs, suggesting that this TF triad controls much of the late MK program. ChIP-seq revealed NF-E2 occupancy near previously implicated target genes, whose expression is compromised in Nfe2-null cells, and many other genes that become active late in MK differentiation...
2016: Scientific Reports
Ekaterina A Ivanova, Mohamed A Elmonem, Inge Bongaerts, Tomas Luyten, Ludwig Missiaen, Lambertus P van den Heuvel, Elena N Levtchenko, Geert Bultynck
Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder caused by loss-of-function mutations in the CTNS gene coding for the lysosomal cystine transporter, cystinosin. Recent studies have demonstrated that, apart from cystine accumulation in the lysosomes, cystinosin-deficient cells, especially renal proximal tubular epithelial cells are characterized by abnormal vesicle trafficking and endocytosis, possible lysosomal dysfunction and perturbed intracellular signalling cascades. It is therefore possible that Ca(2+) signalling is disturbed in cystinosis, as it has been demonstrated for other disorders associated with lysosomal dysfunction, such as Gaucher, Niemann-Pick type C and Alzheimer's diseases...
October 2016: Cell Calcium
Toon Lambrechts, Ioannis Papantoniou, Brent Rice, Jan Schrooten, Frank P Luyten, Jean-Marie Aerts
BACKGROUND AIMS: With the increasing scale in stem cell production, a robust and controlled cell expansion process becomes essential for the clinical application of cell-based therapies. The objective of this work was the assessment of a hollow fiber bioreactor (Quantum Cell Expansion System from Terumo BCT) as a cell production unit for the clinical-scale production of human periosteum derived stem cells (hPDCs). METHODS: We aimed to demonstrate comparability of bioreactor production to standard culture flask production based on a product characterization in line with the International Society of Cell Therapy in vitro benchmarks and supplemented with a compelling quantitative in vivo bone-forming potency assay...
September 2016: Cytotherapy
Peter Fonagy, Patrick Luyten, Alesia Moulton-Perkins, Ya-Wen Lee, Fiona Warren, Susan Howard, Rosanna Ghinai, Pasco Fearon, Benedicte Lowyck
Reflective functioning or mentalizing is the capacity to interpret both the self and others in terms of internal mental states such as feelings, wishes, goals, desires, and attitudes. This paper is part of a series of papers outlining the development and psychometric features of a new self-report measure, the Reflective Functioning Questionnaire (RFQ), designed to provide an easy to administer self-report measure of mentalizing. We describe the development and initial validation of the RFQ in three studies...
2016: PloS One
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