Hermanussen M.,Aschauhof |
Stec K.,University of Potsdam |
Assmann C.,University of Bamberg |
Meigen C.,Deutsches Zentrum fur Neurodegenerative Erkrankungen |
Van Buuren S.,TNO
American Journal of Human Biology | Year: 2016
Objectives: To reanalyze the between-population variance in height, weight, and body mass index (BMI), and to provide a globally applicable technique for generating synthetic growth reference charts. Methods: Using a baseline set of 196 female and 197 male growth studies published since 1831, common factors of height, weight, and BMI are extracted via Principal Components separately for height, weight, and BMI. Combining information from single growth studies and the common factors using in principle a Bayesian rationale allows for provision of completed reference charts. Results: The suggested approach can be used for generating synthetic growth reference charts with LMS values for height, weight, and BMI, from birth to maturity, from any limited set of height and weight measurements of a given population. Conclusion: Generating synthetic growth reference charts by incorporating information from a large set of reference growth studies seems suitable for populations with no autochthonous references at hand yet. © 2015 Wiley Periodicals, Inc.
PubMed | University of Bamberg, Deutsches Zentrum fur Neurodegenerative Erkrankungen, TNO, Aschauhof and University of Potsdam
Type: Journal Article | Journal: American journal of human biology : the official journal of the Human Biology Council | Year: 2016
To reanalyze the between-population variance in height, weight, and body mass index (BMI), and to provide a globally applicable technique for generating synthetic growth reference charts.Using a baseline set of 196 female and 197 male growth studies published since 1831, common factors of height, weight, and BMI are extracted via Principal Components separately for height, weight, and BMI. Combining information from single growth studies and the common factors using in principle a Bayesian rationale allows for provision of completed reference charts.The suggested approach can be used for generating synthetic growth reference charts with LMS values for height, weight, and BMI, from birth to maturity, from any limited set of height and weight measurements of a given population.Generating synthetic growth reference charts by incorporating information from a large set of reference growth studies seems suitable for populations with no autochthonous references at hand yet.
Bartesaghi S.,University College London |
Graziano V.,University College London |
Graziano V.,University of Chieti Pescara |
Galavotti S.,University College London |
And 11 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015
Alterations of mitochondrial metabolism and genomic instability have been implicated in tumorigenesis in multiple tissues. High-grade glioma (HGG), one of the most lethal human neoplasms, displays genetic modifications of Krebs cycle components as well as electron transport chain (ETC) alterations. Furthermore, the p53 tumor suppressor, which has emerged as a key regulator of mitochondrial respiration at the expense of glycolysis, is genetically inactivated in a large proportion of HGG cases. Therefore, it is becoming evident that genetic modifications can affect cell metabolism in HGG; however, it is currently unclear whether mitochondrial metabolism alterations could vice versa promote genomic instability as a mechanism for neoplastic transformation. Here, we show that, in neural progenitor/stem cells (NPCs), which can act as HGG cell of origin, inhibition of mitochondrial metabolism leads to p53 genetic inactivation. Impairment of respiration via inhibition of complex I or decreased mitochondrial DNA copy number leads to p53 genetic loss and a glycolytic switch. p53 genetic inactivation in ETC-impaired neural stem cells is caused by increased reactive oxygen species and associated oxidative DNA damage. ETC-impaired cells display a marked growth advantage in the presence or absence of oncogenic RAS, and form undifferentiated tumors when transplanted into the mouse brain. Finally, p53 mutations correlated with alterations in ETC subunit composition and activity in primary glioma-initiating neural stem cells. Together, these findings provide previously unidentified insights into the relationship between mitochondria, genomic stability, and tumor suppressive control, with implications for our understanding of brain cancer pathogenesis.
PubMed | Max Planck Institute for Biology of Ageing, University of Cologne, Deutsches Zentrum fur Neurodegenerative Erkrankungen, Max Planck Institute for Developmental Biology and 11 more.
Type: Journal Article | Journal: Microscopy research and technique | Year: 2016
Core Facilities (CF) for advanced light microscopy (ALM) have become indispensable support units for research in the life sciences. Their organizational structure and technical characteristics are quite diverse, although the tasks they pursue and the services they offer are similar. Therefore, throughout Europe, scientists from ALM-CFs are forming networks to promote interactions and discuss best practice models. Here, we present recommendations for ALM-CF operations elaborated by the workgroups of the German network of ALM-CFs, German Bio-Imaging (GerBI). We address technical aspects of CF planning and instrument maintainance, give advice on the organization and management of an ALM-CF, propose a scheme for the training of CF users, and provide an overview of current resources for image processing and analysis. Further, we elaborate on the new challenges and opportunities for professional development and careers created by CFs. While some information specifically refers to the German academic system, most of the content of this article is of general interest for CFs in the life sciences. Microsc. Res. Tech. 79:463-479, 2016. 2016 THE AUTHORS MICROSCOPY RESEARCH AND TECHNIQUE PUBLISHED BY WILEY PERIODICALS, INC.
PubMed | Deutsches Zentrum fur Neurodegenerative Erkrankungen and Witten/Herdecke University
Type: Journal Article | Journal: Zeitschrift fur Gerontologie und Geriatrie | Year: 2016
Criteria for the handover between healthcare settings were identified based on a review and on results of empirical data.This study was carried out to select the most relevant criteria for defining the quality of continuity of care of people with dementia (PwD) in the context of the handover between care at home and respite care facilities.A modified classical two-step Delphi design was used in combination with a group Delphi design.A total of 28 core criteria with a consensus strength of >60% are presented. Safety-relevant information, especially the personal habits of PwD and the role of informal caregivers in the handover between care settings are important. Furthermore, the following general principles to ensure the quality of continuity of the care of PwD were deduced: completeness, verification, multipath communication, timeliness and topicality, accessibility and defined responsibilities, roles and standardization.A successful transition of PwD to respite care facilities relies on the provision of relevant information, considering personal habits, before the day of transition. Furthermore, a timely preparation for discharge is important. The individual needs of the informal caregivers with regard to their support should be considered. Professionals who are responsible in handover processes should have solid communication competence in order to collect relevant information from informal caregivers, who have a strong individual care experience with the PwD.
Hochgrafe K.,Deutsches Zentrum fur Neurodegenerative Erkrankungen |
Hochgrafe K.,Max Planck Institute for Neurological Research |
Sydow A.,Deutsches Zentrum fur Neurodegenerative Erkrankungen |
Sydow A.,Max Planck Institute for Neurological Research |
And 3 more authors.
FEBS Journal | Year: 2013
Accumulation of amyloidogenic proteins such as Tau is a hallmark of neurodegenerative diseases including Alzheimer disease and fronto-temporal dementias. To link Tau pathology to cognitive impairments and defects in synaptic plasticity, we created four inducible Tau transgenic mouse models with expression of pro- and anti-aggregant variants of either full-length human Tau (hTau40/ΔK280 and hTau40/ΔK280/PP) or the truncated Tau repeat domain (TauRD/ΔK280 and TauRD/ΔK280/PP). Here we review the histopathological features caused by pro-aggregant Tau, and correlate them with behavioral deficits and impairments in synaptic transmission. Both pro-aggregant Tau variants cause Alzheimer-like features, including synapse loss, mis-localization of Tau into the somatodendritic compartment, conformational changes and hyperphosphorylation. However, there is a clear difference in the extent of Tau aggregation and neurotoxicity. While pro-aggregant full-length hTau40/ΔK280 leads to a 'pre-tangle' pathology, the repeat domain TauRD/ΔK280 causes massive formation of neurofibrillary tangles and neuronal loss in the hippocampus. However, both Tau variants cause co-aggregation of human and mouse Tau and similar functional impairments. Thus, earlier Tau pathological stages and not necessarily neurofibrillary tangles are critical for the development of cognitive malfunctions. Most importantly, memory and synapses recover after switching off expression of pro-aggregant Tau. The rescue of functional impairments correlates with the rescue of most Tau pathological changes and most strikingly the recovery of synapses. This implies that tauopathies as such are reversible, provided that amyloidogenic Tau is removed. Therefore, our Tau transgenic mice may serve as model systems for in vivo validation of therapeutic strategies and drug candidates with regard to cognition and synaptic function. The review deals with the onset, reversibility and spreading of Tau pathology observed in Tau transgenic mouse models. We summarize histopathological features caused by inducible expression of pro-aggregant Tau and correlate them to behavioral deficits and impairments in synaptic transmission, which recover after removal of amyloidogenic Tau. Furthermore we discuss mechanisms of Tau spreading and transmission throughout mouse brain regions. © 2013 The Authors Journal compilation © 2013 FEBS.
Bano D.,Deutsches Zentrum Fur Neurodegenerative Erkrankungen |
Zanetti F.,Deutsches Zentrum Fur Neurodegenerative Erkrankungen |
Mende Y.,Deutsches Zentrum Fur Neurodegenerative Erkrankungen |
Nicotera P.,Deutsches Zentrum Fur Neurodegenerative Erkrankungen
Cell Death and Disease | Year: 2011
Huntington's disease (HD) is a complex and severe disorder characterized by the gradual and the progressive loss of neurons, predominantly in the striatum, which leads to the typical motor and cognitive impairments associated with this pathology. HD is caused by a highly polymorphic CAG trinucleotide repeat expansion in the exon-1 of the gene encoding for huntingtin protein. Since the first discovery of the huntingtin gene, investigations with a consistent number of in-vitro and in-vivo models have provided insights into the toxic events related to the expression of the mutant protein. In this review, we will summarize the progress made in characterizing the signaling pathways that contribute to neuronal degeneration in HD. We will highlight the age-dependent loss of proteostasis that is primarily responsible for the formation of aggregates observed in HD patients. The most promising molecular targets for the development of pharmacological interventions will also be discussed. © 2011 Macmillan Publishers Limited All rights reserved.
Kadavath H.,Max Planck Institute for Biophysical Chemistry |
Hofele R.V.,Max Planck Institute for Biophysical Chemistry |
Biernat J.,Deutsches Zentrum fur Neurodegenerative Erkrankungen |
Kumar S.,Deutsches Zentrum fur Neurodegenerative Erkrankungen |
And 4 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015
The structure, dynamic behavior, and spatial organization of microtubules are regulated by microtubule-associated proteins. An important microtubule-associated protein is the protein Tau, because its microtubule interaction is impaired in the course of Alzheimer's disease and several other neurodegenerative diseases. Here, we show that Tau binds to microtubules by using small groups of evolutionary conserved residues. The binding sites are formed by residues that are essential for the pathological aggregation of Tau, suggesting competition between physiological interaction and pathogenic misfolding. Tau residues in between the microtubule-binding sites remain flexible when Tau is bound to microtubules in agreement with a highly dynamic nature of the Tau-microtubule interaction. By binding at the interface between tubulin heterodimers, Tau uses a conserved mechanism of microtubule polymerization and, thus, regulation of axonal stability and cell morphology.
Forstl H.,TU Munich |
Haass C.,Deutsches Zentrum fur Neurodegenerative Erkrankungen |
Hemmer B.,TU Munich |
Meyer B.,TU Munich |
Halle M.,TU Munich
Deutsches Arzteblatt | Year: 2010
Background: Boxing has received increased public attention and acceptance in recent years. However, this development has not been accompanied by a critical discussion of the early and late health complications. Methods: We selectively review recent studies on the acute, subacute, and chronic neuropsychiatric consequences of boxing. Results: Cerebral concussions ("knock-outs") are the most relevant acute consequence of boxing. The number of reported cases of death in the ring seems to have mildly decreased. Subacute neuropsychological deficits appear to last longer than subjective symptoms. The associated molecular changes demonstrate neuronal and glial injury correlated with the number and severity of blows to the head (altered total tau, beta-amyloid, neurofilament light protein, glial fibrillary acidic protein, and neuron-specific enolase). The risk of a punch-drunk syndrome (boxer's dementia, dementia pugilistica) as a late effect of chronic traumatic brain injury is associated with the duration of a boxer's career and with his earlier stamina. There are similarities (e.g. increased risk with ApoE4-polymorphism, beta-amyloid pathology) and differences (more tau pathology in boxers) compared with Alzheimer's disease. Conclusion: Protective gear has led to a remarkable reduction of risks in amateur boxing. Similar measures can also be used in professional boxing, but may decrease the thrill, which does appeal to many supporters.
Kaut O.,University of Bonn |
Ramirez A.,University of Bonn |
Pieper H.,University of Bonn |
Schmitt I.,Deutsches Zentrum fur Neurodegenerative Erkrankungen |
And 2 more authors.
Dementia and Geriatric Cognitive Disorders | Year: 2014
Background: The cytokine tumor necrosis factor-alpha (TNF-α) is elevated in the blood of Alzheimer's disease (AD) patients. Epigenetic DNA modifications of the TNF-α promoter may account for the observed upregulation. Methods: We analyzed blood samples of 50 AD patients and 55 controls plus 4 AD and 4 control cortex samples using bisulfite sequencing PCR. Results: A significant hypomethylation of the TNF-α promoter was found in AD patients' brains but not in their blood. Cortical TNF-α promoter DNA was higher methylated than blood-derived DNA, both in AD patients and controls. Conclusion: In AD patients, epigenetic mechanisms of TNF-α gene regulation, like aberrant DNA methylation, are not relevant in blood. © 2014 S. Karger AG, Basel.