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Search Results: 1 - 10 of 2369 matches for " Bernhard Radlwimmer "
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Co-localization of CENP-C and CENP-H to discontinuous domains of CENP-A chromatin at human neocentromeres
Alicia Alonso, Bj?rn Fritz, Dan Hasson, Gy?rgy Abrusan, Fanny Cheung, Kinya Yoda, Bernhard Radlwimmer, Andreas G Ladurner, Peter E Warburton
Genome Biology , 2007, DOI: 10.1186/gb-2007-8-7-r148
Abstract: We have examined the distribution of CENP-A, as well as two additional centromeric chromatin-associated proteins (CENP-C and CENP-H), across neocentromeric DNA using chromatin immunoprecipitation (ChIP) on CHIP assays on custom genomic microarrays at three different resolutions. Analysis of two neocentromeres using a contiguous bacterial artificial chromosome (BAC) microarray spanning bands 13q31.3 to 13q33.1 shows that both CENP-C and CENP-H co-localize to the CENP-A chromatin domain. Using a higher resolution polymerase chain reaction (PCR)-amplicon microarray spanning the neocentromere, we find that the CENP-A chromatin is discontinuous, consisting of a major domain of about 87.8 kilobases (kb) and a minor domain of about 13.2 kb, separated by an approximately 158 kb region devoid of CENPs. Both CENP-A domains exhibit co-localization of CENP-C and CENP-H, defining a distinct inner kinetochore chromatin structure that is consistent with higher order chromatin looping models at centromeres. The PCR microarray data suggested varying density of CENP-A nucleosomes across the major domain, which was confirmed using a higher resolution oligo-based microarray.Centromeric chromatin consists of several CENP-A subdomains with highly discontinuous CENP-A chromatin at both the level of individual nucleosomes and at higher order chromatin levels, raising questions regarding the overall structure of centromeric chromatin.The centromere, which is the chromosome component that is responsible for the proper segregation of sister chromatids to daughter cells during cell division, is a specialized chromatin structure [1,2]. Centromeric chromatin has a distinctive nucleosome structure that contains the histone H3 variant centromere protein (CENP)-A [3-8]. CENP-A containing chromatin associates with a large number of proteins, which are assembled in a hierarchical manner [9-12]. Essential among the proximal proteins are several associated with the centromere throughout the cell cycle,
Matrix-comparative genomic hybridization from multicenter formalin-fixed paraffin-embedded colorectal cancer tissue blocks
Heiko Fensterer, Bernhard Radlwimmer, J?rn Str?ter, Malte Buchholz, Daniela E Aust, Catherine Julié, Fran?ois Radvanyi, Bernard Nordlinger, Claudio Belluco, Eric Van Cutsem, Claus-Henning K?hne, Hans A Kestler, Carsten Schwaenen, Michelle Nessling, Manfred P Lutz, Peter Lichter, Thomas M Gress, the EORTC Gastrointestinal (GI) Group
BMC Cancer , 2007, DOI: 10.1186/1471-2407-7-58
Abstract: To verify if this material is technically suitable to perform matrix-CGH, we performed a pilot study using macrodissected 29 formalin-fixed, paraffin-embedded tissue samples collected within the framework of the EORTC-GI/PETACC-2 trial for colorectal cancer. The scientific aim was to identify prognostic genomic signatures differentiating locally restricted (UICC stages II-III) from systemically advanced (UICC stage IV) colorectal tumours.The majority of archived tissue samples collected in the different centers was suitable to perform matrix-CGH. 5/7 advanced tumours displayed 13q-gain and 18q-loss. In locally restricted tumours, only 6/12 tumours showed a gain on 13q and 7/12 tumours showed a loss on 18q. Interphase-FISH and high-resolution array-mapping of the gain on 13q confirmed the validity of the array-data and narrowed the chromosomal interval containing potential oncogenes.Archival, paraffin-embedded tissue samples collected in multicentric clinical trials are suitable for matrix-CGH analyses and allow the identification of prognostic signatures and aberrations harbouring potential new oncogenes.Genomic copy number changes are frequently found in different types of cancer and are believed to contribute to their development and progression through inactivation of tumour suppressor genes, activation of oncogenes, or more subtle through gene dosage changes. Comparative genomic hybridization (CGH) [1] was developed to allow genome-wide screening for such copy number changes. Conventional CGH has a limited resolution and can detect losses of 10 Mb or greater [2]. High-level amplifications achieve a maximum resolution of 3 Mb [3]. The resolution of CGH has been improved by replacing the metaphase chromosomes, which have traditionally served as hybridization targets, with mapped and sequenced genomic DNA clones (bacterial artificial chromosomes, P1-derived artificial chromosome or cosmids) arrayed onto glass slides which was named "matrix-CGH" [4] or "array-CGH" [
Epigenetic Upregulation of lncRNAs at 13q14.3 in Leukemia Is Linked to the In Cis Downregulation of a Gene Cluster That Targets NF-kB
Angela Garding equal contributor,Nupur Bhattacharya equal contributor,Rainer Claus,Melanie Ruppel,Cordula Tschuch,Katharina Filarsky,Irina Idler,Manuela Zucknick,Ma?wen Caudron-Herger,Christopher Oakes,Verena Fleig,Ioanna Keklikoglou,Danilo Allegra,Leticia Serra,Sudhir Thakurela,Vijay Tiwari,Dieter Weichenhan,Axel Benner,Bernhard Radlwimmer,Hanswalter Zentgraf,Stefan Wiemann,Karsten Rippe,Christoph Plass,Hartmut D?hner,Peter Lichter,Stephan Stilgenbauer,Daniel Mertens
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003373
Abstract: Non-coding RNAs are much more common than previously thought. However, for the vast majority of non-coding RNAs, the cellular function remains enigmatic. The two long non-coding RNA (lncRNA) genes DLEU1 and DLEU2 map to a critical region at chromosomal band 13q14.3 that is recurrently deleted in solid tumors and hematopoietic malignancies like chronic lymphocytic leukemia (CLL). While no point mutations have been found in the protein coding candidate genes at 13q14.3, they are deregulated in malignant cells, suggesting an epigenetic tumor suppressor mechanism. We therefore characterized the epigenetic makeup of 13q14.3 in CLL cells and found histone modifications by chromatin-immunoprecipitation (ChIP) that are associated with activated transcription and significant DNA-demethylation at the transcriptional start sites of DLEU1 and DLEU2 using 5 different semi-quantitative and quantitative methods (aPRIMES, BioCOBRA, MCIp, MassARRAY, and bisulfite sequencing). These epigenetic aberrations were correlated with transcriptional deregulation of the neighboring candidate tumor suppressor genes, suggesting a coregulation in cis of this gene cluster. We found that the 13q14.3 genes in addition to their previously known functions regulate NF-kB activity, which we could show after overexpression, siRNA–mediated knockdown, and dominant-negative mutant genes by using Western blots with previously undescribed antibodies, by a customized ELISA as well as by reporter assays. In addition, we performed an unbiased screen of 810 human miRNAs and identified the miR-15/16 family of genes at 13q14.3 as the strongest inducers of NF-kB activity. In summary, the tumor suppressor mechanism at 13q14.3 is a cluster of genes controlled by two lncRNA genes that are regulated by DNA-methylation and histone modifications and whose members all regulate NF-kB. Therefore, the tumor suppressor mechanism in 13q14.3 underlines the role both of epigenetic aberrations and of lncRNA genes in human tumorigenesis and is an example of colocalization of a functionally related gene cluster.
Method and Apparatus for Creating Problem-Solving Complexes from Individual Elements  [PDF]
Bernhard Mitterauer
Advances in Bioscience and Biotechnology (ABB) , 2014, DOI: 10.4236/abb.2014.54038

Based on the biological key-lock-principle common in various biological systems such as the human brain, this paper relates to a method and device for creating problem-solving complexes from individual elements that can be coupled with one another and that have different properties to solve problems. The problem solution can be carried out either serially with a large computer, or with several independent, hierarchically joined computers. In this system, an independent control unit that assumes a multitude of tasks and also acts as an interface with access to all participating computers, is assigned to each problem or object class according to the amount of potential problem-oriented solutions. Such a unit prepares the partial solutions found in its computer for the totality of the solutions computed in the associated computers, finally leading to a total problem solution.

Computer system for simulation of human perception. Some implications for the pathophysiology of the schizophrenic syndrome  [PDF]
Bernhard J. Mitterauer
Journal of Biomedical Science and Engineering (JBiSE) , 2010, DOI: 10.4236/jbise.2010.310127
Abstract: After the description of a brain model based on glial-neuronal interactions, a computer system for simulation of human perception, called clocked perception system, is proposed. The computer system includes a receptor field with sensors, each of which receives data with specific characteristics. These data are passed to processors, whereby only those connections between sensors and processors are released that are suited for an evaluation of the data according to a combination of specific data dictated by a phase program circuit. The computer system also includes a selector circuit that discards those dictated program commands that lead to a “senseless” computation result. A motor program circuit for the control of effectors may be connected to the computer system which at least contributes to the movement of the receptor field in order to bring the receptor field closer to suitable data with specific characteristics for better execution of the program. From disorders of the computer system implications are deduced for the pathophysiology of the schizophrenic syndrome. Finally, a novel treatment approach to this syndrome is proposed.
Significance of the astrocyte domain organization for qualitative information structuring in the brain  [PDF]
Bernhard J. Mitterauer
Advances in Bioscience and Biotechnology (ABB) , 2010, DOI: 10.4236/abb.2010.15052
Abstract: Astrocytes, the dominant glial cell type, modulate synaptic information transmission. Each astrocyte is organized in non-overlapping domains. Here, a formally based model of the possible significance of astrocyte domain organization is proposed. It is hypothesized that each astrocyte contacting n neurons with m synapses via its processes generates dynamic domains of synaptic interactions based on qualitative criteria so that it exerts a structuring of neuronal information processing. The formalism (morpho-grammatics) describes the combinatorics of the various astrocytic receptor types for occupancy with cognate neurotransmitters. Astrocytic processes are able both to contact synapses and retract from them. Rhythmic oscillations of the astrocyte may program the domain organization, where clock genes may play a role in rhythm generation. For the interpretation of a domain organization a player of a string instrument is used as a paradigm. Since astrocytes form networks (syncytia), the interactions between astrocyte domains may be comparable to the improvisations in a jazz ensemble. Given the fact of a high combinational complexity of an astrocyte domain organization, which is formally demonstrable, and an uncomputable complexity of a network of astrocyte domains, the model proposed may not be testable in biological brains, but robotics could be a real alternative.
Pathophysiology of Schizophrenia Based on Impaired Glial-Neuronal Interactions  [PDF]
Bernhard J. Mitterauer
Open Journal of Medical Psychology (OJMP) , 2014, DOI: 10.4236/ojmp.2014.32016
Abstract: The model of impaired glial-neuronal interactions in schizophrenia is based on the core hypothesis that non-functional astrocyte receptors may cause an unconstrained synaptic information flux such that glia lose their modulatory function in tripartite synapses. This may lead to a generalization of information processing in the neuronal networks responsible for delusions and hallucinations on the behavioral level. In this acute paranoid stage of schizophrenia, non-functional astrocytic receptors or their loss decompose the astrocyte domain organization with the effect that a gap between the neuronal and the glial networks arises. If the illness progresses the permanent synaptic neurotransmitter flux may additionally impair the oligodendrocyte-axonic interactions, accompanied by a “creeping” decay of oligodendroglia, axons and glial gap junctions responsible for severe cognitive impairment. Here we may deal with after-effects caused by the basic fault of information processing in tripartite synapses. The gaps between the neuronal and glial networks prohibit the neuronal reality testing of intentional programs presumably generated in the glial networks, called schizophrenic dysintentionality. In non-schizophrenic delusions glia may not be disturbed, but exhausted extrasynaptic information processing may cause an unconstrained synaptic flux responsible for delusions.
Interactive Graphics for Presentation and Exploration of Student Performance Profiles in IGLU/TIMSS 2011 Educational Surveys  [PDF]
Ali ünlü, Bernhard Gschrey
Open Journal of Social Sciences (JSS) , 2015, DOI: 10.4236/jss.2015.39018
Abstract: This paper advocates the application of interactive graphics as a qualitative research method for comparative large-scale assessments, known to supplement and extend analytical techniques. Graphics can be easily generated for effective display of information. Interaction is essential for exploring data in a flexible and controlled manner. The national results of the common sample of the large-scale educational assessment studies Internationale Grundschul-Lese-Untersuchung (IGLU)/ Trends in International Mathematics and Science Study (TIMSS) 2011 demonstrated the effectiveness of interactive graphics. The performance profiles of elementary school students in terms of the competency domains of reading, mathematics, and science are analyzed. Furthermore, spineplots are used to investigate the background characteristics of students of different performance types in order to identify possible educational disadvantage. The study aims to simplify data exploration before reporting, and to more effectively present the findings obtained from comparison studies on school achievement.
Self-Structuring of Motile Astrocytic Processes within the Network of a Single Astrocyte  [PDF]
Bernhard J. Mitterauer
Advances in Bioscience and Biotechnology (ABB) , 2015, DOI: 10.4236/abb.2015.612074
Abstract: Dynamic structuring and functions of perisynaptic astrocytic processes and of the gap junction network within a single astrocyte are outlined. Motile perisynaptic astrocytic processes are generating microdomains. By contacting and retracting of their endfeet an appropriate receptor pattern is selected that modulates the astrocytic receptor sheath for its activation by neurotransmitter substances, ions, transporters, etc. This synaptic information processing occurs in three distinct time scales of milliseconds to seconds, seconds to minutes, hours or longer. Simultaneously, the interconnecting gap junctions are activated by building a network within the astrocyte. Frequently activated gap junction cycles become embodied in gap junction plaques. The gap junction network formation and gap junction plaques are governed and controlled in the same time scales as synaptic information processing. Biomimetic computer systems may represent an alternative to limitations of brainphysiological research. The model proposed allows the interpretation of affective psychoses and schizophrenia as time disorders basically determined by a shortened, prolonged or lacking time scale of synaptic information processing.
Towards a Comprehensive Psychobiological Model of Major Depressive Disorder  [PDF]
Bernhard J. Mitterauer
Open Journal of Depression (OJD) , 2018, DOI: 10.4236/ojd.2018.72003
Abstract: A psychobiological model of the etiopathology of major depression is proposed. It is hypothesized that a hyperintentional personality structure, if faced with non-feasible intentional programs in the environment, suffers from inner and outer stress. This stress situation leads to an excess of astrocytic receptors in glial-neuronal synaptic units, called tripartite synapses, and an overexpression of gap junctions in astroglial networks. The imbalance of synaptic information processing caused by the excess of astrocytic receptors leads to a protracted information processing which affects the behavior generating systems in the reticular formation in the brainstem. Since the activation of these systems is delayed, they cannot decide in real time which mode of behavior (e.g. eating, working, communicating, etc.) is appropriate to a specific sensory information from the environment. The modes of behavior comprise all psychobiological action patterns occurring in circadian time periods. A delay of synaptic activation of the systems in the brainstem reticular formation may lead to a displacement of the modes of behavior in the sense of a persistence of some modes (“must do”) and the inability to produce others (”cannot do”). Such a severe behavioral disorder also affects the self-understanding of the patient resulting in a depressive mood. The mechanism of the displacement of the modes of behavior is shown in a computer simulation. Preliminary clinical data may support the model proposed and is briefly discussed.
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