OBJECTIVE: To assess the diagnostic performance of preoperative application of the Enzian classification (cEnzian) using surgical findings as reference standard. DESIGN: A prospective international non-interventional study. SETTING: Twelve endometriosis centres in four European countries (Austria, Germany, Switzerland and Czech Republic). POPULATION: 1062 women with endometriosis surgery. METHODS: Extent of endometriosis was preoperatively classified using the cEnzian classification based on gynaecological examination and/or transvaginal ultrasound (TVS) and/or magnetic resonance imaging (MRI). After subsequent surgery, the surgeon classified the intraoperative findings using the Enzian classification. MAIN OUTCOME MEASURES: Sensitivity, specificity, PPV, NPV, LR+ , LR- and accuracy were calculated. Conditional frequencies of intraoperative Enzian codings and the corresponding 95% confidence intervals were computed for each preoperative coding and visualised in plots. RESULTS: Although overall consistency of cEnzian and Enzian was poor (35.14%, 95% confidence interval 32.26-38.03), high specificities and negative predictive values (NPVs) of the cEnzian compartments could be demonstrated. Looking at the individual parts of the Enzian classification, the poorest diagnostic performance was detected for compartment B and the highest PPVs were found for category 3 lesions (>3 cm), independent of the compartment. CONCLUSIONS: Using the Enzian classification in a non-invasive setting is a useful tool providing us with an 'at a glance' summary of the diagnostic workup regarding deep endometriosis with high specificities and NPVs. An attempt to merge the two new endometriosis classification systems (#Enzian and AAGL 2021) seems reasonable taking into consideration the respective advantages of each other.

• MeSH
• endometrióza * diagnostické zobrazování   chirurgie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• prospektivní studie MeSH
• senzitivita a specificita MeSH
• ultrasonografie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Rakousko MeSH

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

• Publikační typ
• tisková chyba MeSH

Cardiac fibrosis is a final common pathology in inherited and acquired heart diseases that causes cardiac electrical and pump failure. Here, we use systems genetics to identify a pro-fibrotic gene network in the diseased heart and show that this network is regulated by the E3 ubiquitin ligase WWP2, specifically by the WWP2-N terminal isoform. Importantly, the WWP2-regulated pro-fibrotic gene network is conserved across different cardiac diseases characterized by fibrosis: human and murine dilated cardiomyopathy and repaired tetralogy of Fallot. Transgenic mice lacking the N-terminal region of the WWP2 protein show improved cardiac function and reduced myocardial fibrosis in response to pressure overload or myocardial infarction. In primary cardiac fibroblasts, WWP2 positively regulates the expression of pro-fibrotic markers and extracellular matrix genes. TGFβ1 stimulation promotes nuclear translocation of the WWP2 isoforms containing the N-terminal region and their interaction with SMAD2. WWP2 mediates the TGFβ1-induced nucleocytoplasmic shuttling and transcriptional activity of SMAD2.

• MeSH
• dospělí MeSH
• extracelulární matrix - proteiny metabolismus   MeSH
• fibróza genetika   metabolismus   MeSH
• genetická predispozice k nemoci * genetika   MeSH
• genové regulační sítě * MeSH
• kardiomyopatie genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myši transgenní MeSH
• myši MeSH
• nemoci srdce genetika   metabolismus   MeSH
• protein - isoformy MeSH
• protein Smad2 genetika   metabolismus   MeSH
• regulace genové exprese MeSH
• senioři MeSH
• transformující růstový faktor beta metabolismus   MeSH
• ubikvitinligasy genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• myši MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Coronary flow (CF) measured ex vivo is largely determined by capillary density that reflects angiogenic vessel formation in the heart in vivo. Here we exploit this relationship and show that CF in the rat is influenced by a locus on rat chromosome 2 that is also associated with cardiac capillary density. Mitochondrial tryptophanyl-tRNA synthetase (Wars2), encoding an L53F protein variant within the ATP-binding motif, is prioritized as the candidate at the locus by integrating genomic data sets. WARS2(L53F) has low enzyme activity and inhibition of WARS2 in endothelial cells reduces angiogenesis. In the zebrafish, inhibition of wars2 results in trunk vessel deficiencies, disordered endocardial-myocardial contact and impaired heart function. Inhibition of Wars2 in the rat causes cardiac angiogenesis defects and diminished cardiac capillary density. Our data demonstrate a pro-angiogenic function for Wars2 both within and outside the heart that may have translational relevance given the association of WARS2 with common human diseases.

• MeSH
• dánio pruhované MeSH
• embryo nesavčí MeSH
• endoteliální buňky pupečníkové žíly (lidské) cytologie   enzymologie   MeSH
• fyziologická neovaskularizace genetika   MeSH
• genetické lokusy MeSH
• genom * MeSH
• HEK293 buňky MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• malá interferující RNA genetika   metabolismus   MeSH
• mapování chromozomů MeSH
• mitochondrie genetika   metabolismus   MeSH
• myokard cytologie   enzymologie   MeSH
• savčí chromozomy chemie   MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• sekvenční seřazení MeSH
• signální transdukce MeSH
• tryptofan-tRNA-ligasa antagonisté a inhibitory   genetika   metabolismus   MeSH
• vývojová regulace genové exprese * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

This paper presents a system for correcting motion influences in time-dependent 2D contrast-enhanced ultrasound (CEUS) images to assess tissue perfusion characteristics. The system consists of a semi-automatic frame selection method to find images with out-of-plane motion as well as a method for automatic motion compensation. Translational and non-rigid motion compensation is applied by introducing a temporal continuity assumption. A study consisting of 40 clinical datasets was conducted to compare the perfusion with simulated perfusion using pharmacokinetic modeling. Overall, the proposed approach decreased the mean average difference between the measured perfusion and the pharmacokinetic model estimation. It was non-inferior for three out of four patient cohorts to a manual approach and reduced the analysis time by 41% compared to manual processing.

• MeSH
• břicho ultrasonografie   MeSH
• Crohnova nemoc ultrasonografie   MeSH
• cystická fibróza ultrasonografie   MeSH
• databáze faktografické * MeSH
• interpretace obrazu počítačem metody   MeSH
• kontrastní látky aplikace a dávkování   MeSH
• lidé MeSH
• pohyb těles MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The extent of translational control of gene expression in mammalian tissues remains largely unknown. Here we perform genome-wide RNA sequencing and ribosome profiling in heart and liver tissues to investigate strain-specific translational regulation in the spontaneously hypertensive rat (SHR/Ola). For the most part, transcriptional variation is equally apparent at the translational level and there is limited evidence of translational buffering. Remarkably, we observe hundreds of strain-specific differences in translation, almost doubling the number of differentially expressed genes. The integration of genetic, transcriptional and translational data sets reveals distinct signatures in 3'UTR variation, RNA-binding protein motifs and miRNA expression associated with translational regulation of gene expression. We show that a large number of genes associated with heart and liver traits in human genome-wide association studies are primarily translationally regulated. Capturing interindividual differences in the translated genome will lead to new insights into the genes and regulatory pathways underlying disease phenotypes.

• MeSH
• fenotyp MeSH
• hypertenze metabolismus   MeSH
• játra metabolismus   MeSH
• myokard metabolismus   MeSH
• potkani inbrední BN MeSH
• potkani inbrední SHR MeSH
• proteom MeSH
• regulace genové exprese * MeSH
• ribozomy metabolismus   MeSH
• sekvenční analýza RNA MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: ChIP-seq has become a routine method for interrogating the genome-wide distribution of various histone modifications. An important experimental goal is to compare the ChIP-seq profiles between an experimental sample and a reference sample, and to identify regions that show differential enrichment. However, comparative analysis of samples remains challenging for histone modifications with broad domains, such as heterochromatin-associated H3K27me3, as most ChIP-seq algorithms are designed to detect well defined peak-like features. RESULTS: To address this limitation we introduce histoneHMM, a powerful bivariate Hidden Markov Model for the differential analysis of histone modifications with broad genomic footprints. histoneHMM aggregates short-reads over larger regions and takes the resulting bivariate read counts as inputs for an unsupervised classification procedure, requiring no further tuning parameters. histoneHMM outputs probabilistic classifications of genomic regions as being either modified in both samples, unmodified in both samples or differentially modified between samples. We extensively tested histoneHMM in the context of two broad repressive marks, H3K27me3 and H3K9me3, and evaluated region calls with follow up qPCR as well as RNA-seq data. Our results show that histoneHMM outperforms competing methods in detecting functionally relevant differentially modified regions. CONCLUSION: histoneHMM is a fast algorithm written in C++ and compiled as an R package. It runs in the popular R computing environment and thus seamlessly integrates with the extensive bioinformatic tool sets available through Bioconductor. This makeshistoneHMM an attractive choice for the differential analysis of ChIP-seq data. Software is available from http://histonehmm.molgen.mpg.de .

• MeSH
• algoritmy * MeSH
• chromatinová imunoprecipitace MeSH
• genomika metody   MeSH
• histony chemie   genetika   metabolismus   MeSH
• krysa rodu rattus MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• Markovovy řetězce MeSH
• myši MeSH
• posttranslační úpravy proteinů * MeSH
• software * MeSH
• výpočetní biologie metody   MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Histone modifications are epigenetic marks that play fundamental roles in many biological processes including the control of chromatin-mediated regulation of gene expression. Little is known about interindividual variability of histone modification levels across the genome and to what extent they are influenced by genetic variation. We annotated the rat genome with histone modification maps, identified differences in histone trimethyl-lysine levels among strains, and described their underlying genetic basis at the genome-wide scale using ChIP-seq in heart and liver tissues in a panel of rat recombinant inbred and their progenitor strains. We identified extensive variation of histone methylation levels among individuals and mapped hundreds of underlying cis- and trans-acting loci throughout the genome that regulate histone methylation levels in an allele-specific manner. Interestingly, most histone methylation level variation was trans-linked and the most prominent QTL identified influenced H3K4me3 levels at 899 putative promoters throughout the genome in the heart. Cis- acting variation was enriched in binding sites of distinct transcription factors in heart and liver. The integrated analysis of DNA variation together with histone methylation and gene expression levels showed that histoneQTLs are an important predictor of gene expression and that a joint analysis significantly enhanced the prediction of gene expression traits (eQTLs). Our data suggest that genetic variation has a widespread impact on histone trimethylation marks that may help to uncover novel genotype-phenotype relationships.

• MeSH
• epigeneze genetická * MeSH
• genetická transkripce MeSH
• genetická variace * MeSH
• genom * MeSH
• histony genetika   metabolismus   MeSH
• inbrední kmeny potkanů MeSH
• játra metabolismus   MeSH
• krysa rodu rattus MeSH
• lokus kvantitativního znaku MeSH
• metylace MeSH
• myokard metabolismus   MeSH
• posttranslační úpravy proteinů * MeSH
• promotorové oblasti (genetika) MeSH
• transkripční faktory genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH