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1004 Publications visible to you, out of a total of 1004
The value of noncoronary atherosclerosis for identifying coronary artery disease: results of the Leipzig LIFE Heart Study.
Genetical Statistics and Systems Biology, LIFE Heart

Abstract (Expand)

BACKGROUND: Despite the widespread use of noninvasive testing prior to invasive coronary diagnostic the diagnostic yield of elective coronary angiography has been reported low in subjects with suspected … obstructive CAD. OBJECTIVE: To determine the predictive value of noncoronary atherosclerosis (NCA) in subjects with suspected stable coronary artery disease (CAD) intended to invasive coronary angiography. METHODS: Ultrasound-based assessment of carotid artery plaque (CAP), carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) was performed in 2216 subjects with suspected CAD prior to coronary angiography. Logistic regression and c-statistics were used to analyze the diagnostic value of NCA for the presence of obstructive CAD and the intention to revascularization. RESULTS: Percentage of positive results of elective coronary angiography was low but comparable to other studies (41% obstructive CAD). We identified 1323 subjects (60%) with NCA, most of them were characterized by CAP (93%). CAP independently predicted obstructive CAD in addition to traditional risk factors and clinical factors while CIMT and ABI failed to improve the prediction. The presence of NCA and typical angina were the strongest predictors for obstructive CAD (OR 4.0 and 2.4, respectively). A large subgroup of patients (n = 703, 32%) with atypical clinical presentation and lack of NCA revealed a low indication for revascularization <15% indicating a large proportion of subjects with non-obstructive CAD in this subgroup. CONCLUSION: The evaluation of noncoronary atherosclerosis has the potential to impact clinical decision making and to direct subsequent diagnostic procedures in subjects with suspected coronary artery disease. CLINICAL TRIAL REGISTRATION: NCT00497887.

Authors: A. Weissgerber, M. Scholz, A. Teren, M. Sandri, D. Teupser, S. Gielen, J. Thiery, G. Schuler, F. Beutner

Date Published: 13th Sep 2015

Publication Type: Not specified

Human Diseases: coronary artery disease, atherosclerosis

Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States.
MMML-MYC-SYS

Abstract (Expand)

Mature B-cell lymphoma is a clinically and biologically highly diverse disease. Its diagnosis and prognosis is a challenge due to its molecular heterogeneity and diverse regimes of biological dysfunctions, … which are partly driven by epigenetic mechanisms. We here present an integrative analysis of DNA methylation and gene expression data of several lymphoma subtypes. Our study confirms previous results about the role of stemness genes during development and maturation of B-cells and their dysfunction in lymphoma locking in more proliferative or immune-reactive states referring to B-cell functionalities in the dark and light zone of the germinal center and also in plasma cells. These dysfunctions are governed by widespread epigenetic effects altering the promoter methylation of the involved genes, their activity status as moderated by histone modifications and also by chromatin remodeling. We identified four groups of genes showing characteristic expression and methylation signatures among Burkitt's lymphoma, diffuse large B cell lymphoma, follicular lymphoma and multiple myeloma. These signatures are associated with epigenetic effects such as remodeling from transcriptionally inactive into active chromatin states, differential promoter methylation and the enrichment of targets of transcription factors such as EZH2 and SUZ12.

Authors: L. Hopp, H. Loffler-Wirth, H. Binder

Date Published: 7th Sep 2015

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma, B-cell lymphoma

Serum Neuron-Specific Enolase Is Related to Cerebellar Connectivity: A Resting-State Functional Magnetic Resonance Imaging Pilot Study.
LIFE Adult

Abstract (Expand)

Neuron-specific enolase (NSE) has been suggested as a prognostic biomarker for neuronal alterations resulting from conditions such as traumatic brain injury (TBI), neurodegenerative disease, or cardiac … arrest. To validate serum NSE (sNSE) as a brain-specific biomarker, we related it to functional brain imaging data in 38 healthy adults to create a physiological framework for future studies in neuropsychiatric diseases. sNSE was measured by monoclonal two-site immunoluminometric assays, and functional connectivity was investigated with resting-state functional magnetic resonance imaging (rfMRI). To identify neural hubs most essentially related to sNSE, we applied graph theory approaches, namely, the new data-driven and parameter-free approach, eigenvector centrality mapping. sNSE and eigenvector centrality were negatively correlated in the female cerebellum, without any effects in male subjects. In cerebellar cortex, NSE expression was significantly higher than whole-brain expression as investigated in the whole brain and whole genome-wide atlas of the Allen Institute for Brain Sciences (Seattle, WA). Our study shows a specific linkage between the neuronal marker protein, sNSE, and cerebellar connectivity as measured with rfMRI in the female human brain, although this finding shall be proven in future studies including more subjects. Results suggest that the inclusion of sNSE in the analysis of imaging data is a useful approach to obtain more-specific information on the neuronal mechanisms that underlie functional connectivity at rest. Establishing such a baseline resting-state pattern that is tied to a neuronal serum marker opens new perspectives in the characterization of neuropsychiatric disorders as disconnective syndromes or nexopathies, in particular, resulting from TBI, neurodegenerative disease, or cardiac arrest, in the future.

Authors: M. L. Schroeter, K. Mueller, K. Arelin, J. Sacher, S. Holiga, J. Kratzsch, T. Luck, S. Riedel-Heller, A. Villringer

Date Published: 1st Sep 2015

Publication Type: Not specified

Impact of chronic smoking on P3 components in a three-stimulus oddball paradigm
LIFE Adult

Abstract (Expand)

Background: The P3 is related to cognitive functions, psychopathology and effects of cognition-improving and -impairing drugs. Studies assessing the chronic effects of smoking on P3 mostly reported a … reduction of P3 amplitude for chronic and former smokers. To date, only a few studies have analyzed this impact by using a three-stimulus oddball paradigm. This study tries to replicate previous smoking associations applying an eyes-closed active three-stimulus oddball paradigm in a well-diagnosed population based sample of healthy elderly subjects who were allowed to smoke ad libitum. The study also tries to estimate whether smoking is a relevant confounder in P3 assessment within the analyzed sample. Methods: From the Leipzig Health Care Study (LIFE) current, former and non-smokers without mental or neurological disorders were matched by age, sex and qualification. Risky alcohol consumption was further exclusion criterion given the strong association between alcoholism and P3 amplitude reduction. Results: Smoking status was not associated with any P3 parameter, with exception of prolonged P3a latency at Fz in former smokers compared to never smokers. Also, there were no significant effects of smoking status on any of the behavioral measures or a correlation with smoking-related data. Discussion: This study indicates that smoking does not seem to relevantly impact the P3 components in non-abstaining healthy elderly subjects when confounders are controlled for.

Authors: N. Mauche, C. Sander, P. Jawinski, C. Enzenbach, S. Olbrich, P. Schonknecht, U. Hegerl, T. Hensch

Date Published: 1st Sep 2015

Publication Type: Not specified

Dissociation of amyloid biomarkers in PET and CSF in Alzheimer's disease: a case report.
LIFE Adult

Abstract (Expand)

BACKGROUND: Recently, biomarkers have been suggested to be incorporated into diagnostic criteria for Alzheimer's disease (AD). Regarding disease-specific brain amyloid-beta deposition these comprise … low amyloid-beta 1-42 in cerebrospinal fluid (CSF) and positive positron emission tomography (PET) amyloid imaging, while neuronal degeneration is evidenced by high total and phosphorylated tau levels in CSF (t-/p-tau), regional hypometabolism ([(18)F]fluorodeoxyglucose PET, FDG-PET) and characteristic atrophy-patterns (magnetic resonance imaging, MRI). CASE PRESENTATION: Here we present a case of clinically and biomarker supported AD (CSF t-/p-tau, MRI, FDG-PET) in a 59-year-old Caucasian man in whom indicators of amyloid-beta deposition dissociated between CSF parameters and the respective PET imaging. CONCLUSIONS: Such cases highlight the necessity to better understand potential dissociations between PET and CSF data for amyloid-beta biomarkers, because they are currently considered interchangeably valid with regard to in-vivo evidence for AD pathology. This is more important since amyloid deposition markers can be considered a very first prognostic indicator of imminent AD, prior to neurodegenerative biomarkers and cognitive symptoms. The case illustrates the need for further longitudinal data on potential dissociations of AD biomarkers to devise recommendations for their better prognostic and diagnostic interpretation in the future.

Authors: M. L. Schroeter, S. Tiepolt, A. Marschhauser, A. Thone-Otto, K. T. Hoffmann, H. Barthel, H. Obrig, O. Sabri

Date Published: 26th Aug 2015

Publication Type: Not specified

Human Diseases: Alzheimer's disease

Cortical differences in preliterate children at familiar risk of dyslexia are similar to those observed in dyslexic readers
Genetical Statistics and Systems Biology

Abstract

Not specified

Authors: Indra Kraft, Riccardo Cafiero, Gesa Schaadt, Jens Brauer, Nicole E. Neef, Bent Müller, Holger Kirsten, Arndt Wilcke, Johannes Boltze, Angela D. Friederici, Michael A. Skeide

Date Published: 24th Aug 2015

Publication Type: Journal article

Dissecting the genetics of the human transcriptome identifies novel trait-related trans-eQTLs and corroborates the regulatory relevance of non-protein coding locidagger.
Genetical Statistics and Systems Biology, LIFE Heart

Abstract (Expand)

Genetics of gene expression (eQTLs or expression QTLs) has proved an indispensable tool for understanding biological pathways and pathomechanisms of trait-associated SNPs. However, power of most … genome-wide eQTL studies is still limited. We performed a large eQTL study in peripheral blood mononuclear cells of 2112 individuals increasing the power to detect trans-effects genome-wide. Going beyond univariate SNP-transcript associations, we analyse relations of eQTLs to biological pathways, polygenetic effects of expression regulation, trans-clusters and enrichment of co-localized functional elements. We found eQTLs for about 85% of analysed genes, and 18% of genes were trans-regulated. Local eSNPs were enriched up to a distance of 5 Mb to the transcript challenging typically implemented ranges of cis-regulations. Pathway enrichment within regulated genes of GWAS-related eSNPs supported functional relevance of identified eQTLs. We demonstrate that nearest genes of GWAS-SNPs might frequently be misleading functional candidates. We identified novel trans-clusters of potential functional relevance for GWAS-SNPs of several phenotypes including obesity-related traits, HDL-cholesterol levels and haematological phenotypes. We used chromatin immunoprecipitation data for demonstrating biological effects. Yet, we show for strongly heritable transcripts that still little trans-chromosomal heritability is explained by all identified trans-eSNPs; however, our data suggest that most cis-heritability of these transcripts seems explained. Dissection of co-localized functional elements indicated a prominent role of SNPs in loci of pseudogenes and non-coding RNAs for the regulation of coding genes. In summary, our study substantially increases the catalogue of human eQTLs and improves our understanding of the complex genetic regulation of gene expression, pathways and disease-related processes.

Authors: H. Kirsten, H. Al-Hasani, L. Holdt, A. Gross, F. Beutner, K. Krohn, K. Horn, P. Ahnert, R. Burkhardt, K. Reiche, J. Hackermuller, M. Loffler, D. Teupser, J. Thiery, M. Scholz

Date Published: 15th Aug 2015

Publication Type: Journal article

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