oalib

Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99

Submit

Any time

2020 ( 99 )

2019 ( 776 )

2018 ( 936 )

2017 ( 848 )

Custom range...

Search Results: 1 - 10 of 515816 matches for " Merel A. W. Oortveld "
All listed articles are free for downloading (OA Articles)
Page 1 /515816
Display every page Item
Epigenetic Regulation of Learning and Memory by Drosophila EHMT/G9a
Jamie M. Kramer,Korinna Kochinke,Merel A. W. Oortveld,Hendrik Marks,Daniela Kramer,Eiko K. de Jong,Zoltan Asztalos,J. Timothy Westwood,Hendrik G. Stunnenberg,Marla B. Sokolowski,Krystyna Keleman,Huiqing Zhou,Hans van Bokhoven,Annette Schenck
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1000569
Abstract: The epigenetic modification of chromatin structure and its effect on complex neuronal processes like learning and memory is an emerging field in neuroscience. However, little is known about the “writers” of the neuronal epigenome and how they lay down the basis for proper cognition. Here, we have dissected the neuronal function of the Drosophila euchromatin histone methyltransferase (EHMT), a member of a conserved protein family that methylates histone 3 at lysine 9 (H3K9). EHMT is widely expressed in the nervous system and other tissues, yet EHMT mutant flies are viable. Neurodevelopmental and behavioral analyses identified EHMT as a regulator of peripheral dendrite development, larval locomotor behavior, non-associative learning, and courtship memory. The requirement for EHMT in memory was mapped to 7B-Gal4 positive cells, which are, in adult brains, predominantly mushroom body neurons. Moreover, memory was restored by EHMT re-expression during adulthood, indicating that cognitive defects are reversible in EHMT mutants. To uncover the underlying molecular mechanisms, we generated genome-wide H3K9 dimethylation profiles by ChIP-seq. Loss of H3K9 dimethylation in EHMT mutants occurs at 5% of the euchromatic genome and is enriched at the 5′ and 3′ ends of distinct classes of genes that control neuronal and behavioral processes that are corrupted in EHMT mutants. Our study identifies Drosophila EHMT as a key regulator of cognition that orchestrates an epigenetic program featuring classic learning and memory genes. Our findings are relevant to the pathophysiological mechanisms underlying Kleefstra Syndrome, a severe form of intellectual disability caused by mutations in human EHMT1, and have potential therapeutic implications. Our work thus provides novel insights into the epigenetic control of cognition in health and disease.
Epigenetic Regulation of Learning and Memory by Drosophila EHMT/G9a
Jamie M. Kramer,Korinna Kochinke,Merel A. W. Oortveld,Hendrik Marks,Daniela Kramer,Eiko K. de Jong,Zoltan Asztalos,J. Timothy Westwood,Hendrik G. Stunnenberg,Marla B. Sokolowski,Krystyna Keleman,Huiqing Zhou,Hans van Bokhoven ,Annette Schenck
PLOS Biology , 2011, DOI: 10.1371/journal.pbio.1000569
Abstract: The epigenetic modification of chromatin structure and its effect on complex neuronal processes like learning and memory is an emerging field in neuroscience. However, little is known about the “writers” of the neuronal epigenome and how they lay down the basis for proper cognition. Here, we have dissected the neuronal function of the Drosophila euchromatin histone methyltransferase (EHMT), a member of a conserved protein family that methylates histone 3 at lysine 9 (H3K9). EHMT is widely expressed in the nervous system and other tissues, yet EHMT mutant flies are viable. Neurodevelopmental and behavioral analyses identified EHMT as a regulator of peripheral dendrite development, larval locomotor behavior, non-associative learning, and courtship memory. The requirement for EHMT in memory was mapped to 7B-Gal4 positive cells, which are, in adult brains, predominantly mushroom body neurons. Moreover, memory was restored by EHMT re-expression during adulthood, indicating that cognitive defects are reversible in EHMT mutants. To uncover the underlying molecular mechanisms, we generated genome-wide H3K9 dimethylation profiles by ChIP-seq. Loss of H3K9 dimethylation in EHMT mutants occurs at 5% of the euchromatic genome and is enriched at the 5′ and 3′ ends of distinct classes of genes that control neuronal and behavioral processes that are corrupted in EHMT mutants. Our study identifies Drosophila EHMT as a key regulator of cognition that orchestrates an epigenetic program featuring classic learning and memory genes. Our findings are relevant to the pathophysiological mechanisms underlying Kleefstra Syndrome, a severe form of intellectual disability caused by mutations in human EHMT1, and have potential therapeutic implications. Our work thus provides novel insights into the epigenetic control of cognition in health and disease.
Human Intellectual Disability Genes Form Conserved Functional Modules in Drosophila
Merel A. W. Oortveld,Shivakumar Keerthikumar,Martin Oti,Bonnie Nijhof,Ana Clara Fernandes,Korinna Kochinke,Anna Castells-Nobau,Eva van Engelen,Thijs Ellenkamp,Lilian Eshuis,Anne Galy,Hans van Bokhoven,Bianca Habermann,Han G. Brunner,Christiane Zweier,Patrik Verstreken,Martijn A. Huynen,Annette Schenck
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003911
Abstract: Intellectual Disability (ID) disorders, defined by an IQ below 70, are genetically and phenotypically highly heterogeneous. Identification of common molecular pathways underlying these disorders is crucial for understanding the molecular basis of cognition and for the development of therapeutic intervention strategies. To systematically establish their functional connectivity, we used transgenic RNAi to target 270 ID gene orthologs in the Drosophila eye. Assessment of neuronal function in behavioral and electrophysiological assays and multiparametric morphological analysis identified phenotypes associated with knockdown of 180 ID gene orthologs. Most of these genotype-phenotype associations were novel. For example, we uncovered 16 genes that are required for basal neurotransmission and have not previously been implicated in this process in any system or organism. ID gene orthologs with morphological eye phenotypes, in contrast to genes without phenotypes, are relatively highly expressed in the human nervous system and are enriched for neuronal functions, suggesting that eye phenotyping can distinguish different classes of ID genes. Indeed, grouping genes by Drosophila phenotype uncovered 26 connected functional modules. Novel links between ID genes successfully predicted that MYCN, PIGV and UPF3B regulate synapse development. Drosophila phenotype groups show, in addition to ID, significant phenotypic similarity also in humans, indicating that functional modules are conserved. The combined data indicate that ID disorders, despite their extreme genetic diversity, are caused by disruption of a limited number of highly connected functional modules.
Quantitative Co-Expression of Proteins at the Single Cell Level – Application to a Multimeric FRET Sensor
Joachim Goedhart, Laura van Weeren, Merel J.W. Adjobo-Hermans, Ies Elzenaar, Mark A. Hink, Theodorus W.J. Gadella
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027321
Abstract: Background Co-expression of proteins is generally achieved by introducing two (or more) independent plasmids into cells, each driving the expression of a different protein of interest. However, the relative expression levels may vary strongly between individual cells and cannot be controlled. Ideally, co-expression occurs at a defined ratio, which is constant among cells. This feature is of particular importance for quantitative single cell studies, especially those employing bimolecular F?rster Resonance Energy Transfer (FRET) sensors. Methodology/Principal Findings Four co-expression strategies based on co-transfection, a dual promotor plasmid, an internal ribosome entry site (IRES) and a viral 2A peptide were selected. Co-expression of two spectrally separable fluorescent proteins in single living cells was quantified. It is demonstrated that the 2A peptide strategy can be used for robust equimolar co-expression, while the IRES sequence allows expression of two proteins at a ratio of approximately 3:1. Combined 2A and IRES elements were used for the construction of a single plasmid that drives expression of three individual proteins, which generates a FRET sensor for measuring heterotrimeric G-protein activation. The plasmid drives co-expression of donor and acceptor tagged subunits, with reduced heterogeneity, and can be used to measure G-protein activation in single living cells. Conclusions/Significance Quantitative co-expression of two or more proteins can be achieved with little cell-to-cell variability. This finding enables reliable co-expression of donor and acceptor tagged proteins for FRET studies, which is of particular importance for the development of novel bimolecular sensors that can be expressed from single plasmid.
Predicting Mortality in Patients with Diabetes Starting Dialysis
Merel van Diepen, Marielle A. Schroijen, Olaf M. Dekkers, Joris I. Rotmans, Raymond T. Krediet, Elisabeth W. Boeschoten, Friedo W. Dekker
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089744
Abstract: Background While some prediction models have been developed for diabetic populations, prediction rules for mortality in diabetic dialysis patients are still lacking. Therefore, the objective of this study was to identify predictors for 1-year mortality in diabetic dialysis patients and use these results to develop a prediction model. Methods Data were used from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), a multicenter, prospective cohort study in which incident patients with end stage renal disease (ESRD) were monitored until transplantation or death. For the present analysis, patients with DM at baseline were included. A prediction algorithm for 1-year all-cause mortality was developed through multivariate logistic regression. Candidate predictors were selected based on literature and clinical expertise. The final model was constructed through backward selection. The model's predictive performance, measured by calibration and discrimination, was assessed and internally validated through bootstrapping. Results A total of 394 patients were available for statistical analysis; 82 (21%) patients died within one year after baseline (3 months after starting dialysis therapy). The final prediction model contained seven predictors; age, smoking, history of macrovascular complications, duration of diabetes mellitus, Karnofsky scale, serum albumin and hemoglobin level. Predictive performance was good, as shown by the c-statistic of 0.810. Internal validation showed a slightly lower, but still adequate performance. Sensitivity analyses showed stability of results. Conclusions A prediction model containing seven predictors has been identified in order to predict 1-year mortality for diabetic incident dialysis patients. Predictive performance of the model was good. Before implementing the model in clinical practice, for example for counseling patients regarding their prognosis, external validation is necessary.
Prioritizing Emerging Zoonoses in The Netherlands
Arie H. Havelaar,Floor van Rosse,Catalin Bucura,Milou A. Toetenel,Juanita A. Haagsma,Dorota Kurowicka,J. (Hans) A. P. Heesterbeek,Niko Speybroeck,Merel F. M. Langelaar,Johanna W. B. van der Giessen,Roger M. Cooke,Marieta A. H. Braks
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0013965
Abstract: To support the development of early warning and surveillance systems of emerging zoonoses, we present a general method to prioritize pathogens using a quantitative, stochastic multi-criteria model, parameterized for the Netherlands.
Toxicity and Viral Load in Urine during Valganciclovir Therapy in Premature Infants  [PDF]
Merel Boesveld, Henrica L. M. Van Straaten, Marieke A. C. Hemels
Pharmacology & Pharmacy (PP) , 2017, DOI: 10.4236/pp.2017.88020
Abstract:
Cytomegalovirus (CMV) infection is the most important cause of mental retardation and sensorineural hearing loss. Antiviral treatment with valganciclovir, a relatively new but potential toxic oral drug, is recommended to prevent further hearing deterioration. In this retrospective cohort study we evaluated the relation between the dose of valganciclovir and the reduction of CMV viral load, as well as the toxicity. All neonates with gestational age <32 weeks with CMV infection treated with oral valganciclovir (30 mg/kg/day) were included. Time interval to reach CMV viral load below detection level (<250 copies/ml) was determined. Toxicity was measured by plasma trough levels, thrombocytopenia and leukopenia. Data of 6 infants, median gestational age 252 weeks, were analyzed. Time interval between start of therapy and viral load below detection level was 25 - 54 days. In total, 37 through plasma samples were analyzed. Of these, 28 were in the normal range, 3 above and 6 under the target concentration. Mild transient leukopenia occurred in 1 infant. No thrombocytopenia occurred. Conclusion: Antiviral treatment of CMV infection with oral valganciclovir results in adequate plasma through levels. Also, a progressive reduction of viral load in the urine below detection level was reached within 25 - 54 days, without serious short time side effects.
Contextual control over expression of fear is affected by cortisol
Vanessa A. van Ast,Bram Vervliet,Merel Kindt
Frontiers in Behavioral Neuroscience , 2012, DOI: 10.3389/fnbeh.2012.00067
Abstract: At the core of anxiety disorders is the inability to use contextual information to modulate behavioral responses to potentially threatening events. Models of the pathogenesis of anxiety disorders incorporate stress and concomitant stress hormones as important vulnerability factors, while others emphasize sex as an important factor. However, translational basic research has not yet investigated the effects of stress hormones and sex on the ability to use contextual information to modulate responses to threat. Therefore, the purpose of the present study was threefold: first, we aimed at developing an experimental paradigm specifically capable of capturing contextual modulation of the expression of fear. Second, we tested whether cortisol would alter the contextualization of fear expression. Third, we aimed at assessing whether alterations in contextualization due to cortisol were different for men and women. Healthy participants (n = 42) received placebo or hydrocortisone (20 mg) prior to undergoing a newly developed differential contextual fear-conditioning paradigm. The results indicated that people rapidly acquire differential contextual modulation of the expression of fear, as measured by fear potentiated startle (FPS) and skin conductance responses (SCR). In addition, cortisol impaired the contextualization of fear expression leading to increased fear generalization on FPS data in women. The opposite pattern was found in men. Finally, as assessed by SCR, cortisol impaired differential conditioning in men. The results are in line with models suggesting heightened vulnerability in women for developing anxiety disorders after stressful events.
Bayesian spike inference from calcium imaging data
Eftychios A. Pnevmatikakis,Josh Merel,Ari Pakman,Liam Paninski
Quantitative Biology , 2013,
Abstract: We present efficient Bayesian methods for extracting neuronal spiking information from calcium imaging data. The goal of our methods is to sample from the posterior distribution of spike trains and model parameters (baseline concentration, spike amplitude etc) given noisy calcium imaging data. We present discrete time algorithms where we sample the existence of a spike at each time bin using Gibbs methods, as well as continuous time algorithms where we sample over the number of spikes and their locations at an arbitrary resolution using Metropolis-Hastings methods for point processes. We provide Rao-Blackwellized extensions that (i) marginalize over several model parameters and (ii) provide smooth estimates of the marginal spike posterior distribution in continuous time. Our methods serve as complements to standard point estimates and allow for quantification of uncertainty in estimating the underlying spike train and model parameters.
Working Memory Capacity, Inhibitory Control and the Role of L2 Proficiency in Aging L1 Dutch Speakers of Near-Native L2 English
Merel Keijzer
Brain Sciences , 2013, DOI: 10.3390/brainsci3031261
Abstract: This paper examines the intricate relationship between working memory (WM) capacity and inhibitory control as a function of both L2 proficiency and age. In both its design and research questions, this study closely follows Gass & Lee’s work, where both L1 and L2 Reading Span Tasks (as measures of WM capacity) and L1 and L2 Stroop interference tasks (to measure inhibitory control) were administered. In this study, the test battery is augmented by both an L1 and L2 C-test of overall language proficiency. Participants were 63 L1 Dutch speakers of L2 English, who had been immersed in an L2 environment for a considerable amount of time. Their data were set off against those of 54 monolingual Dutch speakers and 56 monolingual English speakers. At the time of testing, all the bilingual participants had a near-native command of English and their L1 and L2 WM scores were not found to be significantly different. However, discrepancies did occur in Stroop test scores of inhibition, where the bilinguals performed better in their L2 English than L1 Dutch. These main effects often contradicted the results found in Gass & Lee’s study, who examined less proficient L2 learners. An aging effect was furthermore found: older subjects consistently performed more poorly on WM and inhibition tasks than their younger peers. These results can shed light on how individual factors like WM capacity and inhibitory control interact in successful late bilinguals and how these dynamics shift with advanced age.
Page 1 /515816
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.