21 results on '"Welzenbach J"'
Search Results
2. MiRNA-149 as a Candidate for Facial Clefting and Neural Crest Cell Migration.
- Author
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Stüssel, L.G., Hollstein, R., Laugsch, M., Hochfeld, L.M., Welzenbach, J., Schröder, J., Thieme, F., Ishorst, N., Romero, R. Olmos, Weinhold, L., Hess, T., Gehlen, J., Mostowska, A., Heilmann-Heimbach, S., Mangold, E., Rada-Iglesias, A., Knapp, M., Schaaf, C.P., and Ludwig, K.U.
- Subjects
CLEFT lip ,MICRORNA ,CELL migration ,PLURIPOTENT stem cells ,GENE expression - Abstract
Nonsyndromic cleft lip with or without palate (nsCL/P) ranks among the most common human birth defects and has a multifactorial etiology. Human neural crest cells (hNCC) make a substantial contribution to the formation of facial bone and cartilage and are a key cell type in terms of nsCL/P etiology. Based on increasing evidence for the role of noncoding regulatory mechanisms in nsCL/P, we investigated the role of hNCC-expressed microRNAs (miRNA) in cleft development. First, we conducted a systematic analysis of miRNAs expressed in human-induced pluripotent stem cell–derived hNCC using Affymetrix microarrays on cell lines established from 4 unaffected donors. These analyses identified 152 candidate miRNAs. Based on the hypothesis that candidate miRNA loci harbor genetic variation associated with nsCL/P risk, the genomic locations of these candidates were cross-referenced with data from a previous genome-wide association study of nsCL/P. Associated variants were reanalyzed in independent nsCL/P study populations. Jointly, the results suggest that miR-149 is implicated in nsCL/P etiology. Second, functional follow-up included in vitro overexpression and inhibition of miR-149 in hNCC and subsequent analyses at the molecular and phenotypic level. Using 3′RNA-Seq, we identified 604 differentially expressed (DE) genes in hNCC overexpressing miR-149 compared with untreated cells. These included TLR4 and JUNB, which are established targets of miR-149, and NOG, BMP4, and PAX6, which are reported nsCL/P candidate genes. Pathway analyses revealed that DE genes were enriched in pathways including regulation of cartilage development and NCC differentiation. At the cellular level, distinct hNCC migration patterns were observed in response to miR-149 overexpression. Our data suggest that miR-149 is involved in the etiology of nsCL/P via its role in hNCC migration. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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3. P5012 Integrative analysis of metabolomic, proteomic and genomic data to reveal functional pathways and candidate genes for drip loss in pigs
- Author
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Welzenbach, J., primary, Grosse-Brinkhaus, C., additional, Neuhoff, C., additional, Looft, C., additional, Schellander, K., additional, and Tholen, E., additional
- Published
- 2016
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4. P2007 Sulforaphane enhances proliferation of porcine satellite cells through suppression of TGF-β signaling pathway
- Author
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Zhang, R., primary, Neuhoff, C., additional, Fan, H., additional, Welzenbach, J., additional, Yang, Q., additional, Uddin, M. J., additional, Cinar, M. U., additional, Tesfaye, D., additional, Tholen, E., additional, Looft, C., additional, and Schellander, K., additional
- Published
- 2016
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5. Automatic full field analysis of perfusion images gained by scanning laser Doppler flowmetry
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Michelson, G., primary, Welzenbach, J., additional, Pal, I., additional, and Harazny, J., additional
- Published
- 1998
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6. New software analyses increase the reliability of measurements of retinal arterioles morphology by scanning laser Doppler flowmetry in humans.
- Author
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Harazny JM, Raff U, Welzenbach J, Ott C, Ritt M, Lehmann M, Michelson G, and Schmieder RE
- Published
- 2011
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7. Importance of Metal-Support Interactions for CO 2 Hydrogenation: An Operando Near-Ambient Pressure X-ray Photoelectron Spectroscopy Study on Gold-Loaded In 2 O 3 and CeO 2 Catalysts.
- Author
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Ziemba M, Weyel J, Zeller P, Welzenbach J, Efimenko A, Hävecker M, and Hess C
- Abstract
Metal-support interactions, which are essential for the design of supported metal catalysts, used, e.g., for CO
2 activation, are still only partially understood. In this study of gold-loaded In2 O3 and CeO2 catalysts during CO2 hydrogenation using near-ambient pressure X-ray photoelectron spectroscopy, supported by near edge X-ray absorption fine structure, we demonstrate that the role of the noble metal strongly depends upon the choice of the support material. Temperature-dependent analyses of X-ray photoelectron spectra under reaction conditions reveal that gold is reduced on CeO2 , enabling direct H2 activation, but oxidized on In2 O3 , leading to decreased activity of Au/In2 O3 compared to bare In2 O3 . At elevated temperatures, the catalytic activity of the In2 O3 catalysts strongly increases as a result of facilitated CO2 and (In2 O3 -based) H2 activation, while the catalytic activity of Au/CeO2 is limited by reoxidation by CO2 . Our results underline the importance of operando studies for understanding metal-support interactions to enable a rational support selection in the future.- Published
- 2024
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8. Unraveling surface and bulk dynamics of iron(III) molybdate during oxidative dehydrogenation using operando and transient spectroscopies.
- Author
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Schumacher L, Radtke M, Welzenbach J, and Hess C
- Abstract
Iron(III) molybdate (Fe
2 (MoO4 )3 ) is a commercial catalyst for the oxidative dehydrogenation (ODH) of methanol, but it has recently been shown to be relevant for other substrates as well. Despite its commercial use, a detailed mechanistic understanding of Fe2 (MoO4 )3 catalysts at the surface and in the bulk has been lacking, largely hampered by the lack of suitable spectroscopic methods, directly applicable under reaction conditions. Using propane ODH as an example, we highlight the potential of operando Raman and impedance spectroscopy combined with transient IR spectroscopy, to identify surface active sites and monitor the hydrogen transfer and oxygen dynamics. By comparison with the behavior of reference compounds (MoO3 , MoOx /Fe2 O3 ) a mechanistic model is proposed. The presence of iron greatly influences the reactivity behavior via oxygen diffusion but is moderated in its oxidative capacity by surface MoOx . Our approach directly elucidates fundamental properties of Fe2 (MoO4 )3 of general importance to selective oxidation catalysis., (© 2023. The Author(s).)- Published
- 2023
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9. Identification of de novo variants in nonsyndromic cleft lip with/without cleft palate patients with low polygenic risk scores.
- Author
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Ishorst N, Henschel L, Thieme F, Drichel D, Sivalingam S, Mehrem SL, Fechtner AC, Fazaal J, Welzenbach J, Heimbach A, Maj C, Borisov O, Hausen J, Raff R, Hoischen A, Dixon M, Rada-Iglesias A, Bartusel M, Rojas-Martinez A, Aldhorae K, Braumann B, Kruse T, Kirschneck C, Spanier G, Reutter H, Nowak S, Gölz L, Knapp M, Buness A, Krawitz P, Nöthen MM, Nothnagel M, Becker T, Ludwig KU, and Mangold E
- Subjects
- Humans, Genome-Wide Association Study, DNA-Binding Proteins genetics, Risk Factors, Cleft Palate genetics, Cleft Lip genetics
- Abstract
Background: Nonsyndromic cleft lip with/without cleft palate (nsCL/P) is a congenital malformation of multifactorial etiology. Research has identified >40 genome-wide significant risk loci, which explain less than 40% of nsCL/P heritability. Studies show that some of the hidden heritability is explained by rare penetrant variants., Methods: To identify new candidate genes, we searched for highly penetrant de novo variants (DNVs) in 50 nsCL/P patient/parent-trios with a low polygenic risk for the phenotype (discovery). We prioritized DNV-carrying candidate genes from the discovery for resequencing in independent cohorts of 1010 nsCL/P patients of diverse ethnicities and 1574 population-matched controls (replication). Segregation analyses and rare variant association in the replication cohort, in combination with additional data (genome-wide association data, expression, protein-protein-interactions), were used for final prioritization., Conclusion: In the discovery step, 60 DNVs were identified in 60 genes, including a variant in the established nsCL/P risk gene CDH1. Re-sequencing of 32 prioritized genes led to the identification of 373 rare, likely pathogenic variants. Finally, MDN1 and PAXIP1 were prioritized as top candidates. Our findings demonstrate that DNV detection, including polygenic risk score analysis, is a powerful tool for identifying nsCL/P candidate genes, which can also be applied to other multifactorial congenital malformations., (© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
- Published
- 2023
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10. Prioritization of non-coding elements involved in non-syndromic cleft lip with/without cleft palate through genome-wide analysis of de novo mutations.
- Author
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Zieger HK, Weinhold L, Schmidt A, Holtgrewe M, Juranek SA, Siewert A, Scheer AB, Thieme F, Mangold E, Ishorst N, Brand FU, Welzenbach J, Beule D, Paeschke K, Krawitz PM, and Ludwig KU
- Subjects
- Humans, Genome-Wide Association Study, Alleles, Mutation genetics, Cleft Palate genetics, Cleft Lip genetics
- Abstract
Non-syndromic cleft lip with/without cleft palate (nsCL/P) is a highly heritable facial disorder. To date, systematic investigations of the contribution of rare variants in non-coding regions to nsCL/P etiology are sparse. Here, we re-analyzed available whole-genome sequence (WGS) data from 211 European case-parent trios with nsCL/P and identified 13,522 de novo mutations (DNMs) in nsCL/P cases, 13,055 of which mapped to non-coding regions. We integrated these data with DNMs from a reference cohort, with results of previous genome-wide association studies (GWASs), and functional and epigenetic datasets of relevance to embryonic facial development. A significant enrichment of nsCL/P DNMs was observed at two GWAS risk loci (4q28.1 (p = 8 × 10
-4 ) and 2p21 (p = 0.02)), suggesting a convergence of both common and rare variants at these loci. We also mapped the DNMs to 810 position weight matrices indicative of transcription factor (TF) binding, and quantified the effect of the allelic changes in silico . This revealed a nominally significant overrepresentation of DNMs (p = 0.037), and a stronger effect on binding strength, for DNMs located in the sequence of the core binding region of the TF Musculin (MSC). Notably, MSC is involved in facial muscle development, together with a set of nsCL/P genes located at GWAS loci. Supported by additional results from single-cell transcriptomic data and molecular binding assays, this suggests that variation in MSC binding sites contributes to nsCL/P etiology. Our study describes a set of approaches that can be applied to increase the added value of WGS data., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)- Published
- 2022
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11. Allele-specific transcription factor binding in a cellular model of orofacial clefting.
- Author
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Ruff KLM, Hollstein R, Fazaal J, Thieme F, Gehlen J, Mangold E, Knapp M, Welzenbach J, and Ludwig KU
- Subjects
- Alleles, Binding Sites, Cell Line, Chromatin Immunoprecipitation Sequencing, Cleft Lip metabolism, Cleft Palate metabolism, Gene Expression Regulation, Developmental, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Protein Binding, RNA-Seq, Transcription Factor AP-2 metabolism, Transcriptome, Cleft Lip genetics, Cleft Palate genetics, Human Embryonic Stem Cells metabolism, Mesenchymal Stem Cells metabolism, Transcription Factor AP-2 genetics
- Abstract
Non-syndromic cleft lip with/without cleft palate (nsCL/P) is a frequent congenital malformation with multifactorial etiology. While recent genome-wide association studies (GWAS) have identified several nsCL/P risk loci, the functional effects of the associated non-coding variants are largely unknown. Furthermore, additional risk loci remain undetected due to lack of power. As genetic variants might alter binding of transcription factors (TF), we here hypothesized that the integration of data from TF binding sites, expression analyses and nsCL/P GWAS might help to (i) identify functionally relevant variants at GWAS loci, and (ii) highlight novel risk variants that have been previously undetected. Analysing the craniofacial TF TFAP2A in human embryonic palatal mesenchyme (HEPM) cells, we identified 2845 TFAP2A ChIP-seq peaks, several of which were located near nsCL/P candidate genes (e.g. MSX1 and SPRY2). Comparison with independent data suggest that 802 of them might be specific to craniofacial development, and genes near these peaks are enriched in processes relevant to nsCL/P. Integration with nsCL/P GWAS data, however, did not show robust evidence for co-localization of common nsCL/P risk variants with TFAP2A ChIP-seq peaks. This data set represents a new resource for the analyses of craniofacial processes, and similar approaches with additional cell lines and TFs could be applied to generate further insights into nsCL/P etiology., (© 2022. The Author(s).)
- Published
- 2022
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12. Integrative approaches generate insights into the architecture of non-syndromic cleft lip with or without cleft palate.
- Author
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Welzenbach J, Hammond NL, Nikolić M, Thieme F, Ishorst N, Leslie EJ, Weinberg SM, Beaty TH, Marazita ML, Mangold E, Knapp M, Cotney J, Rada-Iglesias A, Dixon MJ, and Ludwig KU
- Abstract
Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common congenital facial malformation with a multifactorial etiology. Genome-wide association studies (GWASs) have identified multiple genetic risk loci. However, functional interpretation of these loci is hampered by the underrepresentation in public resources of systematic functional maps representative of human embryonic facial development. To generate novel insights into the etiology of nsCL/P, we leveraged published GWAS data on nsCL/P as well as available chromatin modification and expression data on mid-facial development. Our analyses identified five novel risk loci, prioritized candidate target genes within associated regions, and highlighted distinct pathways. Furthermore, the results suggest the presence of distinct regulatory effects of nsCL/P risk variants throughout mid-facial development and shed light on its regulatory architecture. Our integrated data provide a platform to advance hypothesis-driven molecular investigations of nsCL/P and other human facial defects., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)
- Published
- 2021
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13. Synergistic activity of IDH1 inhibitor BAY1436032 with azacitidine in IDH1 mutant acute myeloid leukemia.
- Author
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Chaturvedi A, Gupta C, Gabdoulline R, Borchert NM, Goparaju R, Kaulfuss S, Görlich K, Schottmann R, Othman B, Welzenbach J, Panknin O, Wagner M, Geffers R, Ganser A, Thol F, Jeffers M, Haegebarth A, and Heuser M
- Subjects
- Aged, Aniline Compounds, Animals, Benzimidazoles, Humans, Isocitrate Dehydrogenase genetics, Mice, Azacitidine, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics
- Abstract
Mutant IDH1 (mIDH1) inhibitors have shown single-agent activity in relapsed/refractory AML, though most patients eventually relapse. We evaluated the efficacy and molecular mechanism of the combination treatment with azacitidine, which is currently the standard of care in older AML patients, and mIDH1 inhibitor BAY1436032. Both compounds were evaluated in vivo as single agents and in combination with sequential (azacitidine, followed by BAY1436032) or simultaneous application in two human IDH1 mutated AML xenograft models. Combination treatment significantly prolonged survival compared to single agent or control treatment (P<.005). The sequential combination treatment depleted leukemia stem cells (LSC) by 470-fold. Interestingly, the simultaneous combination treatment depleted LSCs by 33,150-fold compared to control mice. This strong synergy is mediated through inhibition of MAPK/ERK and RB/E2F signaling. Our data strongly argues for the concurrent application of mIDH1 inhibitors and azacitidine and predicts improved outcome of this regimen in IDH1 mutated AML patients.
- Published
- 2021
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14. Non-Syndromic Cleft Lip with or without Cleft Palate: Genome-Wide Association Study in Europeans Identifies a Suggestive Risk Locus at 16p12.1 and Supports SH3PXD2A as a Clefting Susceptibility Gene.
- Author
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van Rooij IA, Ludwig KU, Welzenbach J, Ishorst N, Thonissen M, Galesloot TE, Ongkosuwito E, Bergé SJ, Aldhorae K, Rojas-Martinez A, Kiemeney LA, Vermeesch JR, Brunner H, Roeleveld N, Devriendt K, Dormaar T, Hens G, Knapp M, Carels C, and Mangold E
- Subjects
- Animals, Belgium, Chromosomes, Human, Pair 10 genetics, Female, Genome-Wide Association Study, Humans, Male, Mice, Mice, Knockout, Netherlands, Risk Factors, Zebrafish, Adaptor Proteins, Vesicular Transport genetics, Chromosomes, Human, Pair 16 genetics, Cleft Lip genetics, Cleft Palate genetics
- Abstract
Non-syndromic cleft lip with or without cleft palate (nsCL/P) ranks among the most common human congenital malformations, and has a multifactorial background in which both exogenous and genetic risk factors act in concert. The present report describes a genome-wide association study (GWAS) involving a total of 285 nsCL/P patients and 1212 controls from the Netherlands and Belgium. Twenty of the 40 previously reported nsC/LP susceptibility loci were replicated, which underlined the validity of this sample. SNV-based analysis of the data identified an as yet unreported suggestive locus at chromosome 16p12.1 ( p -value of the lead SNV: 4.17 × 10
-7 ). This association was replicated in two of three patient/control replication series (Central European and Yemeni). Gene analysis of the GWAS data prioritized SH3PXD2A at chromosome 10q24.33 as a candidate gene for nsCL/P. To date, support for this gene as a cleft gene has been restricted to data from zebrafish and a knockout mouse model. The present GWAS was the first to implicate SH3PXD2A in non-syndromic cleft formation in humans. In summary, although performed in a relatively small sample, the present GWAS generated novel insights into nsCL/P etiology.- Published
- 2019
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15. p63 establishes epithelial enhancers at critical craniofacial development genes.
- Author
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Lin-Shiao E, Lan Y, Welzenbach J, Alexander KA, Zhang Z, Knapp M, Mangold E, Sammons M, Ludwig KU, and Berger SL
- Subjects
- Brain abnormalities, Cleft Lip genetics, Cleft Palate genetics, Fibroblasts metabolism, Foreskin cytology, Genome-Wide Association Study, HEK293 Cells, Humans, Kruppel-Like Factor 4, Kruppel-Like Transcription Factors metabolism, Male, Point Mutation, Polymorphism, Single Nucleotide, Transcription Factors metabolism, Transcription, Genetic, Transfection, Tumor Suppressor Proteins metabolism, Up-Regulation genetics, Enhancer Elements, Genetic genetics, Epithelial Cells metabolism, Facial Bones growth & development, Skull growth & development, Transcription Factors genetics, Tumor Suppressor Proteins genetics
- Abstract
The transcription factor p63 is a key mediator of epidermal development. Point mutations in p63 in patients lead to developmental defects, including orofacial clefting. To date, knowledge on how pivotal the role of p63 is in human craniofacial development is limited. Using an inducible transdifferentiation model, combined with epigenomic sequencing and multicohort meta-analysis of genome-wide association studies data, we show that p63 establishes enhancers at craniofacial development genes to modulate their transcription. Disease-specific substitution mutation in the DNA binding domain or sterile alpha motif protein interaction domain of p63, respectively, eliminates or reduces establishment of these enhancers. We show that enhancers established by p63 are highly enriched for single-nucleotide polymorphisms associated with nonsyndromic cleft lip ± cleft palate (CL/P). These orthogonal approaches indicate a strong molecular link between p63 enhancer function and CL/P, illuminating molecular mechanisms underlying this developmental defect and revealing vital regulatory elements and new candidate causative genes.
- Published
- 2019
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16. Integrative Analysis of Metabolomic, Proteomic and Genomic Data to Reveal Functional Pathways and Candidate Genes for Drip Loss in Pigs.
- Author
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Welzenbach J, Neuhoff C, Heidt H, Cinar MU, Looft C, Schellander K, Tholen E, and Große-Brinkhaus C
- Subjects
- Animals, Chromosomes genetics, Genome-Wide Association Study, Phenotype, Polymorphism, Single Nucleotide, Proteome genetics, Swine metabolism, Metabolic Networks and Pathways, Metabolome, Proteome metabolism, Quantitative Trait Loci, Red Meat standards, Swine genetics
- Abstract
The aim of this study was to integrate multi omics data to characterize underlying functional pathways and candidate genes for drip loss in pigs. The consideration of different omics levels allows elucidating the black box of phenotype expression. Metabolite and protein profiling was applied in Musculus longissimus dorsi samples of 97 Duroc × Pietrain pigs. In total, 126 and 35 annotated metabolites and proteins were quantified, respectively. In addition, all animals were genotyped with the porcine 60 k Illumina beadchip. An enrichment analysis resulted in 10 pathways, amongst others, sphingolipid metabolism and glycolysis/gluconeogenesis, with significant influence on drip loss. Drip loss and 22 metabolic components were analyzed as intermediate phenotypes within a genome-wide association study (GWAS). We detected significantly associated genetic markers and candidate genes for drip loss and for most of the metabolic components. On chromosome 18, a region with promising candidate genes was identified based on SNPs associated with drip loss, the protein "phosphoglycerate mutase 2" and the metabolite glycine. We hypothesize that association studies based on intermediate phenotypes are able to provide comprehensive insights in the genetic variation of genes directly involved in the metabolism of performance traits. In this way, the analyses contribute to identify reliable candidate genes., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.
- Published
- 2016
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17. Different Statistical Approaches to Investigate Porcine Muscle Metabolome Profiles to Highlight New Biomarkers for Pork Quality Assessment.
- Author
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Welzenbach J, Neuhoff C, Looft C, Schellander K, Tholen E, and Große-Brinkhaus C
- Subjects
- Animals, Biomarkers metabolism, Phenotype, Swine, Energy Metabolism physiology, Metabolome, Muscle, Skeletal metabolism, Red Meat standards
- Abstract
The aim of this study was to elucidate the underlying biochemical processes to identify potential key molecules of meat quality traits drip loss, pH of meat 1 h post-mortem (pH1), pH in meat 24 h post-mortem (pH24) and meat color. An untargeted metabolomics approach detected the profiles of 393 annotated and 1,600 unknown metabolites in 97 Duroc × Pietrain pigs. Despite obvious differences regarding the statistical approaches, the four applied methods, namely correlation analysis, principal component analysis, weighted network analysis (WNA) and random forest regression (RFR), revealed mainly concordant results. Our findings lead to the conclusion that meat quality traits pH1, pH24 and color are strongly influenced by processes of post-mortem energy metabolism like glycolysis and pentose phosphate pathway, whereas drip loss is significantly associated with metabolites of lipid metabolism. In case of drip loss, RFR was the most suitable method to identify reliable biomarkers and to predict the phenotype based on metabolites. On the other hand, WNA provides the best parameters to investigate the metabolite interactions and to clarify the complex molecular background of meat quality traits. In summary, it was possible to attain findings on the interaction of meat quality traits and their underlying biochemical processes. The detected key metabolites might be better indicators of meat quality especially of drip loss than the measured phenotype itself and potentially might be used as bio indicators.
- Published
- 2016
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18. First experience in analysing pulsatile retinal capillary flow and arteriolar structural parameters measured noninvasively in hypertensive patients.
- Author
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Harazny JM, Ott C, Raff U, Welzenbach J, Kwella N, Michelson G, and Schmieder RE
- Subjects
- Adult, Capillaries physiopathology, Diastole, Female, Humans, Laser-Doppler Flowmetry methods, Male, Middle Aged, Pulsatile Flow, Reproducibility of Results, Retina physiopathology, Systole, Arterioles physiopathology, Hypertension physiopathology, Retinal Vessels physiopathology
- Abstract
Objective: Increased pulsatile pressure induces as well as aggravates microvascular damage. Scanning laser Doppler flowmetry allows the noninvasive assessment of both retinal capillary flow (RCF) and arteriolar structural parameters of the retinal circulation. Moreover, pulsatile characteristics of the retinal arterioles can be assessed., Methods: In study 1, reliability of pulsatile RCF and structural parameters were examined in randomly selected patients. In study 2, pulsatile RCF as well as the structural parameters of retinal arterioles were assessed in hypertension grade 1-2 (HT1-2; n = 20) and treatment-resistant hypertension (TRH; n = 19)., Results: In study 1, test-retest, interobserver and intraobserver reliability of all parameters showed coefficients of variation of less than 10%. In study 2, it was shown that patients with TRH had higher pulse pressure (P = 0.003) and pulsed RCF values (P < 0.001) as patients with HT1-2. Patients with HT1-2 had no change in the vessel diameter, but a significant difference in lumen diameter, resulting in an altered wall thickness (P = 0.001) between systole and diastole. In contrast, patients with TRH showed differences in vessel diameter (P = 0.005) as well as lumen diameter (P = 0.001), resulting in an unaltered wall thickness between systole and diastole. Hence, wall thickness change as a result of pulsed flow regulation observed in HT1-2 was missing in TRH., Conclusion: We suggest a new reliable tool for evaluating the pulsatility in the retinal circulation in humans, and found significant differences in pulsatile RCF and structural parameters between patients with HT1-2 and those with TRH.
- Published
- 2014
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19. Local application of tropicamide 0.5% reduces retinal capillary blood flow.
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Harazny JM, Schmieder RE, Welzenbach J, and Michelson G
- Subjects
- Administration, Topical, Adult, Blood Flow Velocity drug effects, Capillaries drug effects, Female, Hemodynamics, Humans, Male, Microcirculation drug effects, Muscarinic Antagonists administration & dosage, Mydriatics administration & dosage, Ophthalmic Solutions, Retinal Vessels physiology, Eye blood supply, Retinal Vessels drug effects, Tropicamide administration & dosage
- Abstract
Introduction: Scanning laser Doppler flowmetry (SLDF) plays an important role in the study of arterial hypertension, diabetes and stroke. The technology enables non-invasive measurement of the retinal capillary perfusion (RCF), retinal haemodynamics and arteriolar morphology in human. The values can be measured in mydriasis or in non-mydriatic eyes. It is not clear whether the using of vasoactive mydriatica for pupil dilation affects the measured parameters in retina. Acetylcholine, a vasoactive neurotransmitter in human retina, affects the contractility of pericytes using muscarinic receptors and stimulates endothelial synthesis of nitric oxide (NO). We examined whether blockade of the retinal cholinergic receptors by tropicamide affects the RCF., Methods: We measured RCF in both eyes of 13 healthy subjects before and 30 min after the local application of one drop of 0.5% tropicamide to the right eye. The mean age of the group was 44 ± 14 years. The left eye was used as control. RCF was measured by Heidelberg retina flowmetry., Results: Thirty minutes after local application of one drop of 0.5% tropicamide to the right eye RCF decreased significantly (p = 0.001) by 31.9 ± 13% but did not change in the control eye. The maximal decrease was observed 20 min after application of the tropicamide., Conclusion: Locally administered tropicamide profoundly affects the RCF. Thus pupil dilatation impairs any assessment of retinal microcirculation.
- Published
- 2013
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20. Morphometric age-related evaluation of small retinal vessels by scanning laser Doppler flowmetry: determination of a vessel wall index.
- Author
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Michelson G, Wärntges S, Baleanu D, Welzenbach J, Ohno-Jinno A, Pogorelov P, and Harazny J
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Arterioles anatomy & histology, Blood Flow Velocity, Child, Female, Humans, Male, Middle Aged, Regional Blood Flow, Reproducibility of Results, Venules anatomy & histology, Aging physiology, Laser-Doppler Flowmetry, Retinal Artery anatomy & histology, Retinal Vein anatomy & histology
- Abstract
Background: Measurement of the retinal vessel wall thickness may contribute to the diagnosis of microvascular diseases. We present a methodical approach to calculate these alterations and to determine age-related differences., Methods: One hundred fifty-three subjects without eye or internal diseases (mean age +/- SD, 47.6 +/- 14.9 years) underwent measurement of the retinal temporal superior artery and vein by scanning laser Doppler flowmetry (Heidelberg retina flowmeter). We calculated the difference between the diameter of reflectivity and the Doppler signal (Delta[VD-FD]/2) and determined a "vessel wall index" (VWI) by normalization of Delta(VD-FD)/2 for age and vessel diameter., Results: Delta(VD-FD)/2 correlated with vessel diameter (artery, r = +0.60, P < 0.001; vein, r = +0.49, P<0.001) and age (artery, r = +0.19, P = 0.02; vein, r = +0.27, P = 0.001) but not with sex, if controlled for the other variables each. The venous, but not the arterial, vessel diameter correlated with age (r = +0.18, P = 0.02), if controlled for sex. The relative statistical weight of these empirical contributions to the variation observed in Delta(VD-FD)/2 was 36.5% (P < 0.001, artery) and 21.7% (P< 0.001, vein), and that of age was 3.6% (P = 0.02, artery) and 7.3% (P = 0.001, vein). The limit value of VWI to pathologic changes (80th percentile) was 1.25 microm/y (artery) and 1.31 microm/y (vein). Delta(VD-FD)/2 normalized for vessel diameter correlated with the 10-year categories of age (artery, r = +0.196, P = 0.017; vein, r = +0.250, P = 0.002)., Conclusion: In a group of subjects aged 21 years to 70 years, we detected an increase of Delta(VD-FD)/2 in the retinal temporal superior artery and vein with age.
- Published
- 2007
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21. Functional imaging of the retinal microvasculature by scanning laser Doppler flowmetry.
- Author
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Michelson G, Welzenbach J, Pal I, and Harazny J
- Subjects
- Adult, Blood Flow Velocity, Humans, Microcirculation, Observer Variation, Reproducibility of Results, Laser-Doppler Flowmetry methods, Retinal Vessels physiology
- Abstract
Purpose: to image functionally perfused retinal vessels and to assess quantitatively the intercapillary space of the retinal microvasculature., Method: The base of functional imaging and the quantitative assessment of the retinal vasculature is the two-dimensional map of the retina encoded by the laser Doppler frequency shift. By Scanning Laser Doppler Flowmetry (HRF. Heidelberg Engineering) the laser Doppler frequency shift of 16.384 retinal sites (256 pixels x 64 lines, spatial resolution 10 mum) of a retinal area of 2.7 x 0.7 mm was gained. The image processing was performed by a recently described algorithm (AFFPIA). Using the data of the laser Doppler frequency shift of every retinal site, a color-coded retinal image was established showing perfused vessels and capillaries. By automatic pattern analysis of this image vessels and capillaries were identified and segmented. Based on this image the distances in [microm] of every retinal site to the next vessel or capillary were calculated ("distance to next capillary"). The functional imaging of the retinal perfusion was demonstrated in (1) normal retina, (2) retinal arterial occlusion, and (3) proliferative retinopathy. Intraobserver reliability of the quantitative assessment of the parameter "distance to next capillary" was estimated by measuring 10 eyes of 10 subjects at 5 different days by one observer. Interobserver reliability of the quantitative assessment was evaluated by analysing 10 perfusion maps by 5 different operators. In 93 eyes of 71 normal subjects (mean age 40.4 mu 15 years) the juxtapapillary retina was quantitatively evaluated., Results: QUALITATIVE EVALUATION: The functional images of the retinal perfusion of eyes with normal retina, with retinal arterial occlusion, and with proliferative retinopathy corresponded well with the fluorescein angiography. Perfused vessels and capillaries became visible in a high local resolution. QUANTITITATIVE ASSESSMENT: The coefficient of reliability of the introobserver and interobserver reproducibility of the parameter 'mean distance to next capillary" was 0.74, and 0.95, respectively. The quantitative assessment of the perfusion showed that the major part of the retinal sites (>700%) had distances to the next capillary lower than 30 microm 46% of the retinal area had distances to the next capillary from 0-20 microm 26% of the retina had distances from 20-30 microm, 12% of the retina had distances from 30-40 microm 7% of the retina had distances from 40-50 microm, 4% of the retina had distances from 50-60 microm, and 4% of the retinal sites showed distances to the next capillary greater than 60 mum. The mean distance to the next capillary or vessel was calculated with 21 +/- 6.5 microm., Conclusion: By non-invasive Scanning Laser Doppler Flowmetry in combination with adequate software it is possible to perform a functional imaging of the retinal vasculature and to measure all index for the functional density of retinal capillaries and vessels.
- Published
- 2001
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