References of "Antony, Paul 50000431"
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See detailIntegrating Pathways of Parkinson's Disease in a Molecular Interaction Map
Fujita, Kazuhiro A.; Ostaszewski, Marek UL; Matsuoka, Yukiko et al

in Molecular Neurobiology (2014)

Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a complex interplay of genetic and environmental factors. Information on various aspects of PD pathogenesis is ... [more ▼]

Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a complex interplay of genetic and environmental factors. Information on various aspects of PD pathogenesis is rapidly increasing and needs to be efficiently organized, so that the resulting data is available for exploration and analysis. Here we introduce a computationally tractable, comprehensive molecular interaction map of PD. This map integrates pathways implicated in PD pathogenesis such as synaptic and mitochondrial dysfunction, impaired protein degradation, alpha-synuclein pathobiology and neuroinflammation. We also present bioinformatics tools for the analysis, enrichment and annotation of the map, allowing the research community to open new avenues in PD research. The PD map is accessible at http://minerva.uni.lu/pd_map . [less ▲]

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See detailAutomated nuclei clump splitting by combining local concavity orientation and graph partitioning
Samsi, Siddharth UL; Trefois, Christophe UL; Antony, Paul UL et al

in International Conference on Biomedical and Health Informatics (2014)

Automated clump decomposition is essential for single cell based analysis of fluorescent microscopy images. This paper presents a new method for automatically splitting clumps of cell nuclei in ... [more ▼]

Automated clump decomposition is essential for single cell based analysis of fluorescent microscopy images. This paper presents a new method for automatically splitting clumps of cell nuclei in fluorescence microscopy images. Nuclei are first segmented using histogram concavity analysis. Clumps of nuclei are detected by fitting an ellipse to the segmented objects and examining objects where the fitted ellipse does not overlap accurately with the segmented object. These clumps are then further processed to find concave points on the object boundaries. The orientation of the detected concavities is subsequently calculated based on the local shape of the object border. Finally, a graph segmentation based approach is used to pair concavities that represent best candidates for splitting touching nuclei based on properties derived from the local concavity properties. This approach was validated by manual inspection and has shown promising results in the high throughput analysis of HeLa cell images. [less ▲]

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See detailThe hallmarks of Parkinson's disease.
Antony, Paul UL; Diederich, Nico UL; Krüger, Rejko UL et al

in FEBS Journal (2013)

Since the discovery of dopamine as a neurotransmitter in the 1950s, Parkinson's disease (PD) research has generated a rich and complex body of knowledge, revealing PD to be an age-related multifactorial ... [more ▼]

Since the discovery of dopamine as a neurotransmitter in the 1950s, Parkinson's disease (PD) research has generated a rich and complex body of knowledge, revealing PD to be an age-related multifactorial disease, influenced by both genetic and environmental factors. The tremendous complexity of the disease is increased by a non-linear progression of the pathogenesis between molecular, cellular, and organic systems. In this mini-review, we explore the complexity of PD and propose a systems-based approach, organizing the available information around cellular disease hallmarks. We encourage our peers to adopt this cell-based view with the aim of improving communication in interdisciplinary research endeavors targeting the molecular events, modulatory cell-to-cell signaling pathways, and emerging clinical phenotypes related to PD. This article is protected by copyright. All rights reserved. [less ▲]

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See detailLight microscopy applications in systems biology: opportunities and challenges.
Antony, Paul UL; Trefois, Christophe UL; Stojanovic, Aleksandar UL et al

in Cell Communication and Signaling (2013), 11(1), 1-19

Biological systems present multiple scales of complexity, ranging from molecules to entire populations. Light microscopy is one of the least invasive techniques used to access information from various ... [more ▼]

Biological systems present multiple scales of complexity, ranging from molecules to entire populations. Light microscopy is one of the least invasive techniques used to access information from various biological scales in living cells. The combination of molecular biology and imaging provides a bottom-up tool for direct insight into how molecular processes work on a cellular scale. However, imaging can also be used as a top-down approach to study the behavior of a system without detailed prior knowledge about its underlying molecular mechanisms. In this review, we highlight the recent developments on microscopy-based systems analyses and discuss the complementary opportunities and different challenges with high-content screening and high-throughput imaging. Furthermore, we provide a comprehensive overview of the available platforms that can be used for image analysis, which enable community-driven efforts in the development of image-based systems biology. [less ▲]

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See detailThe Parkinson's Disease Map: A Framework for Integration, Curation and Exploration of Disease-related Pathways
Ostaszewski, Marek UL; Fujita, Kazuhiro; Matsuoka, Yukiko et al

Poster (2013, March 09)

Objectives: The pathogenesis of Parkinson's Disease (PD) is multi-factorial and age-related, implicating various genetic and environmental factors. It becomes increasingly important to develop new ... [more ▼]

Objectives: The pathogenesis of Parkinson's Disease (PD) is multi-factorial and age-related, implicating various genetic and environmental factors. It becomes increasingly important to develop new approaches to organize and explore the exploding knowledge of this field. Methods: The published knowledge on pathways implicated in PD, such as synaptic and mitochondrial dysfunction, alpha-synuclein pathobiology, failure of protein degradation systems and neuroinflammation has been organized and represented using CellDesigner. This repository has been linked to a framework of bioinformatics tools including text mining, database annotation, large-scale data integration and network analysis. The interface for online curation of the repository has been established using Payao tool. Results: We present the PD map, a computer-based knowledge repository, which includes molecular mechanisms of PD in a visually structured and standardized way. A bioinformatics framework that facilitates in-depth knowledge exploration, extraction and curation supports the map. We discuss the insights gained from PD map-driven text mining of a corpus of over 50 thousands full text PD-related papers, integration and visualization of gene expression in post mortem brain tissue of PD patients with the map, as well as results of network analysis. Conclusions: The knowledge repository of disease-related mechanisms provides a global insight into relationships between different pathways and allows considering a given pathology in a broad context. Enrichment with available text and bioinformatics databases as well as integration of experimental data supports better understanding of complex mechanisms of PD and formulation of novel research hypotheses. [less ▲]

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See detailDifferentiated SH-SY5Y Cells as PD Model for Mitochondrial Dysfunction: From Whole Genome Sequencing to an Educated Design of High-Throughput Experiments
Antony, Paul UL; Krishna, Abhimanyu UL; May, Patrick UL et al

Poster (2013)

Objectives: Mitochondrial dysfunction is a cellular hallmark of Parkinson's disease (PD) and energetic stress of dopaminergic neurons appears to be a physiological risk factor for mitochondrial ... [more ▼]

Objectives: Mitochondrial dysfunction is a cellular hallmark of Parkinson's disease (PD) and energetic stress of dopaminergic neurons appears to be a physiological risk factor for mitochondrial dysfunction. It is however challenging to assess the high variety of factors regulating mitochondrial physiology in living neurons in a high throughput manner. To overcome this bottleneck, we established an analysis platform, using the neuroblastoma cell line SH-SY5Y. For the first time ever we have characterized the SH-SY5Y cell line in an integrated whole genome, transcriptome, and proteome approach. In addition, we show that neuronal differentiation improves the physiological properties of this experimental model for studying mitochondrial dysfunction in PD. Methods: Whole genome sequencing, RNA-Seq, qRT-PCR, MS, FRET using Voltage sensing proteins, Immunofluorescence, cytometry, and live cell imaging. Results: The integrated molecular characterization of SH-SY5Y uncovers the level of molecular network integrity and hence the relevance of this cell line for targeted studies in selected molecular processes. Furthermore, we dissect changes in mitochondrial and energetic stress factors during the process of neuronal differentiation. Conclusions: In terms of both morphology and energetic stress response, differentiated SH-SY5Y cells are more similar to dopaminergic neurons than their undifferentiated precursors. Thanks to dividing progenitors and the short duration of differentiation, combined with the use of specific endpoints analysed with high-content microscopy, our platform paves the route for high throughput experiments on a neuronal cell culture model for PD. Our genomic characterization and expression profiling of SH-SY5Y cells furthermore helps guiding the experimental design and interpretation of such studies. [less ▲]

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See detailFrom Systems Biology to Systems Biomedicine
Antony, Paul UL; Balling, Rudi UL; Vlassis, Nikos UL

in Current Opinion in Biotechnology (2012), 23(4), 604-8

Systems Biology is about combining theory, technology, and targeted experiments in a way that drives not only data accumulation but knowledge as well. The challenge in Systems Biomedicine is to ... [more ▼]

Systems Biology is about combining theory, technology, and targeted experiments in a way that drives not only data accumulation but knowledge as well. The challenge in Systems Biomedicine is to furthermore translate mechanistic insights in biological systems to clinical application, with the central aim of improving patients’ quality of life. The challenge is to find theoretically well-chosen models for the contextually correct and intelligible representation of multiscale biological systems. In this review, we discuss the current state of Systems Biology, highlight the emergence of Systems Biomedicine, and highlight some of the topics and views that we think are important for the efficient application of Systems Theory in Biomedicine. [less ▲]

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See detailAnalysis of critical transitions in Parkinson's disease
Trefois, Christophe UL; Antony, Paul UL; Baumuratov, Aidos UL et al

Poster (2011, December 12)

Background Parkinson’s disease is the most common neurodegenerative movement disorder and is clinically characterized by resting tremor, bradykinesia and cogwheel rigidity. The disease affects 1-2% of the ... [more ▼]

Background Parkinson’s disease is the most common neurodegenerative movement disorder and is clinically characterized by resting tremor, bradykinesia and cogwheel rigidity. The disease affects 1-2% of the global population with prevalence in the people above 65 years of age. The main pathological hallmark of Parkinson’s disease is a progressive loss of dopaminergic neurons in the substantia nigra. Therefore, one important challenge is to improve the understanding of regime shifts between health and disease states. Improving predictions of critical transitions triggering the onset of parkinsonian phenotypes could contribute to the improvement of preventive treatments. Methods Based on cellular models, we will use the mathematical concept of critical transitions to create a toolbox for potentially predicting tipping points towards cellular Parkinson’s disease phenotypes, e.g. mitochondrial dysfunction. Experimentally, we will induce and analyze potential critical transitions in the SH-SY5Y cell line. To do this, we will apply Parkinson’s disease relevant chemical and genetic perturbations and analyze multiple scales of the resulting temporal system behavior. We will combine high content imaging with genetic and biochemical data. A significant informatics challenge arises from the aim to perform the analysis of high time-resolved 3D imaging data. We are therefore developing an automated image analysis pipeline that relies on latest technologies and techniques, such as 3D deconvolution and 3D particle tracking. This pipeline will be applied to study parameters, such as mitochondrial dynamics, which include for instance velocity, morphology, and spatial organization. [less ▲]

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See detailParkinson’s disease mouse models in translational research
Antony, Paul UL; Diederich, Nico UL; Balling, Rudi UL

in Mammalian Genome : Official Journal of the International Mammalian Genome Society (2011), 22(7-8), 401-19

Animal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson's disease (PD), the higher is the predictive value for clinical ... [more ▼]

Animal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson's disease (PD), the higher is the predictive value for clinical trials. An ideal PD model should present behavioral signs and pathology that resemble the human disease. The increasing understanding of PD stratification and etiology, however, complicates the choice of adequate animal models for preclinical studies. An ultimate mouse model, relevant to address all PD-related questions, is yet to be developed. However, many of the existing models are useful in answering specific questions. An appropriate model should be chosen after considering both the context of the research and the model properties. This review addresses the validity, strengths, and limitations of current PD mouse models for translational research. [less ▲]

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See detailIdentification and functional dissection of localization signals within ataxin-3.
Antony, Paul UL; Mäntele, Simone; Mollenkopf, Phillip et al

in Neurobiology of Disease (2009), 36(2), 280-92

Spinocerebellar ataxia type 3 (SCA3) or Machado-Joseph disease (MJD) belongs to a group of autosomal dominant neurodegenerative diseases, which are caused by the expansion of a polyglutamine repeat in the ... [more ▼]

Spinocerebellar ataxia type 3 (SCA3) or Machado-Joseph disease (MJD) belongs to a group of autosomal dominant neurodegenerative diseases, which are caused by the expansion of a polyglutamine repeat in the affected protein, in this case ataxin-3. Ataxin-3 is mainly localized in the cytoplasm; however, one hallmark of SCA3 is the formation of ataxin-3-containing protein aggregates in the nucleus of neurons. Currently, it is not known how mutant ataxin-3 translocates into the nucleus. We performed localization assays of recently proposed and novel potential signals, functionally confirmed the activity of a nuclear localization signal, identified two novel nuclear export signals (NES 77 and NES 141), and determined crucial amino acids. In addition, we demonstrate the relevance of the identified signals for the intracellular localization of the N- and C-terminus of ataxin-3. Our findings stress the importance of investigating the mechanisms, which influence the intracellular distribution of ataxin-3 during the pathogenesis of SCA3. [less ▲]

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See detailLocalization signals within ataxin-3 influence the formation of intranuclear aggregates in spinocerebellar ataxia type 3
Antony, Paul UL; Boy, J; Henderson, B et al

in Aktuelle Neurologie (2007)

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