0000000001113281
AUTHOR
Michael Lenz
showing 24 related works from this author
A prospective cohort study to identify and evaluate endotypes of venous thromboembolism: Rationale and design of the Genotyping and Molecular Phenoty…
2019
Abstract Several clinical, genetic and acquired risk factors for venous thromboembolism (VTE) have been identified. However, the molecular pathophysiology and mechanisms of disease progression remain poorly understood. This is reflected by uncertainties regarding the primary and secondary prevention of VTE and the optimal duration of antithrombotic therapy. A growing body of literature points to clinically relevant differences between VTE phenotypes (e.g. deep vein thrombosis (DVT) versus pulmonary embolism (PE), unprovoked versus provoked VTE). Extensive links to cardiovascular, inflammatory and immune-related morbidities are testament to the complexity of the disease. The GMP-VTE project …
The Impact of Amino Acids on Postprandial Glucose and Insulin Kinetics in Humans
2020
Different amino acids (AAs) may exert distinct effects on postprandial glucose and insulin concentrations. A quantitative comparison of the effects of AAs on glucose and insulin kinetics in humans is currently lacking. PubMed was queried to identify intervention studies reporting glucose and insulin concentrations after acute ingestion and/or intravenous infusion of AAs in healthy adults and those living with obesity and/or type 2 diabetes (T2DM). The systematic literature search identified 55 studies that examined the effects of l-leucine, l-isoleucine, l-alanine, l-glutamine, l-arginine, l-lysine, glycine, l-proline, l-phenylalanine, l-glutamate, branched-chain AAs (i.e., l-leucine, l-iso…
A computational model of postprandial adipose tissue lipid metabolism derived using human arteriovenous stable isotope tracer data
2019
Given the association of disturbances in non-esterified fatty acid (NEFA) metabolism with the development of Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease, computational models of glucose-insulin dynamics have been extended to account for the interplay with NEFA. In this study, we use arteriovenous measurement across the subcutaneous adipose tissue during a mixed meal challenge test to evaluate the performance and underlying assumptions of three existing models of adipose tissue metabolism and construct a new, refined model of adipose tissue metabolism. Our model introduces new terms, explicitly accounting for the conversion of glucose to glyceraldehye-3-phosphate, the postprandial …
Isolated Pulmonary Embolism Is Associated With a High Risk of Arterial Thrombotic Disease
2020
Background Isolated PE is associated with a higher burden of atherosclerotic disease than other manifestations of VTE. Research Question We hypothesized that the presence of isolated PE may signal a chronically elevated risk of arterial thrombotic disease. Study Design and Methods Data from the VTEval Study, a prospective cohort study enrolling individuals with clinical suspicion and imaging-based diagnosis or exclusion of VTE, were analyzed. Patients with PE received whole-leg ultrasonography to assess presence of DVT. Regularized logistic regression identified features that discriminate between isolated PE and other VTE phenotypes at clinical presentation. Survival analyses were performed…
Use of deep learning methods to translate drug-induced gene expression changes from rat to human primary hepatocytes
2020
In clinical trials, animal and cell line models are often used to evaluate the potential toxic effects of a novel compound or candidate drug before progressing to human trials. However, relating the results of animal and in vitro model exposures to relevant clinical outcomes in the human in vivo system still proves challenging, relying on often putative orthologs. In recent years, multiple studies have demonstrated that the repeated dose rodent bioassay, the current gold standard in the field, lacks sufficient sensitivity and specificity in predicting toxic effects of pharmaceuticals in humans. In this study, we evaluate the potential of deep learning techniques to translate the pattern of …
The fine structure of colleterial glands in two cockroaches and three termites, including a detailed study of Cryptocercus punctulatus (Blattaria, Cr…
2007
1873-5495 (Electronic) Journal Article Research Support, U.S. Gov't, Non-P.H.S.; The colleterial glands of insects are organs associated with the female genital apparatus. In cockroaches, these glands produce secretions that cover two parallel rows of eggs during oviposition, and in oviparous species, these secretions become the tanned, sculpted, rigid outer casing of the ootheca. The goal of this study was to compare the gross anatomy of the colleterial glands and the ultrastructure of their component tubules in the phylogenetically significant genera Cryptocercus (Blattaria) and Mastotermes (Isoptera). Recent studies indicate that cockroaches in the genus Cryptocercus are the sister group…
Assessing the Contribution of Relative Macrophage Frequencies to Subcutaneous Adipose Tissue
2021
Background: Macrophages play an important role in regulating adipose tissue function, while their frequencies in adipose tissue vary between individuals. Adipose tissue infiltration by high frequencies of macrophages has been linked to changes in adipokine levels and low-grade inflammation, frequently associated with the progression of obesity. The objective of this project was to assess the contribution of relative macrophage frequencies to the overall subcutaneous adipose tissue gene expression using publicly available datasets.Methods: Seven publicly available microarray gene expression datasets from human subcutaneous adipose tissue biopsies (n = 519) were used together with TissueDecod…
Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of biopsy samples
2019
Background Psoriasis and atopic dermatitis are two inflammatory skin diseases with a high prevalence and a significant burden on the patients. Underlying molecular mechanisms include chronic inflammation and abnormal proliferation. However, the cell types contributing to these molecular mechanisms are much less understood. Recently, deconvolution methodologies have allowed the digital quantification of cell types in bulk tissue based on mRNA expression data from biopsies. Using these methods to study the cellular composition of the skin enables the rapid enumeration of multiple cell types, providing insight into the numerical changes of cell types associated with chronic inflammatory skin c…
Missing value imputation in proximity extension assay-based targeted proteomics data
2020
Targeted proteomics utilizing antibody-based proximity extension assays provides sensitive and highly specific quantifications of plasma protein levels. Multivariate analysis of this data is hampered by frequent missing values (random or left censored), calling for imputation approaches. While appropriate missing-value imputation methods exist, benchmarks of their performance in targeted proteomics data are lacking. Here, we assessed the performance of two methods for imputation of values missing completely at random, the previously top-benchmarked ‘missForest’ and the recently published ‘GSimp’ method. Evaluation was accomplished by comparing imputed with remeasured relative concentrations…
EFMviz
2020
Elementary Flux Modes (EFMs) are a tool for constraint-based modeling and metabolic network analysis. However, systematic and automated visualization of EFMs, capable of integrating various data types is still a challenge. In this study, we developed an extension for the widely adopted COBRA Toolbox, EFMviz, for analysis and graphical visualization of EFMs as networks of reactions, metabolites and genes. The analysis workflow offers a platform for EFM visualization to improve EFM interpretability by connecting COBRA toolbox with the network analysis and visualization software Cytoscape. The biological applicability of EFMviz is demonstrated in two use cases on medium (Escherichia coli, iAF1…
Trail-following pheromones in basal termites, with special reference to Mastotermes darwiniensis
2007
0098-0331 (Print) Journal Article; In the framework of an evolutionary study, trail pheromones have been studied in the most basal extant termite, Mastotermes darwiniensis (Mastotermitidae), and two other basal termites, the Termopsidae Porotermes adamsoni (Porotermitinae) and Stolotermes victoriensis (Stolotermitinae). Although workers of M. darwiniensis do not walk in single file while exploring a new environment under experimental conditions and are unable to follow artificial trails in 'open field' experiments, they do secrete a trail-following pheromone from their sternal glands. This unique behavior might reflect a primitive function of communication of the sternal gland. The major co…
Identification of multi-component trail pheromones in the most evolutionarily derived termites, the Nasutitermitinae (Termitidae)
2009
In the present study, trail pheromone blends are identified for the first time in termites. In the phylogenetically complex Nasutitermitinae, trail-following pheromones are composed of dodecatrienol and neocembrene, the proportions of which vary according to species, although neocembrene is always more abundant than dodecatrienol (by 25–250-fold). Depending on species, termites were more sensitive to dodecatrienol or to neocembrene but the association of both components always elicited significantly higher trail following, with a clear synergistic effect in most of the studied species. A third component, trinervitatriene, was identified in the sternal gland secretion of several species, but…
A targeted proteomics investigation of the obesity paradox in venous thromboembolism
2021
Abstract The obesity paradox, the controversial finding that obesity promotes disease development but protects against sequelae in patients, has been observed in venous thromboembolism (VTE). The aim of this investigation was to identify a body mass–related proteomic signature in VTE patients and to evaluate whether this signature mediates the obesity paradox in VTE patients. Data from the Genotyping and Molecular Phenotyping in Venous ThromboEmbolism Project, a prospective cohort study of 693 VTE patients, were analyzed. A combined end point of recurrent VTE or all-cause death was used. Relative quantification of 444 proteins was performed using high-throughput targeted proteomics technolo…
Protein expression profiling suggests relevance of noncanonical pathways in isolated pulmonary embolism
2019
Abstract Patients with isolated pulmonary embolism (PE) have a distinct clinical profile from those with deep vein thrombosis (DVT)-associated PE, with more pulmonary conditions and atherosclerosis. These findings suggest a distinct molecular pathophysiology and the potential involvement of alternative pathways in isolated PE. To test this hypothesis, data from 532 individuals from the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism Project, a multicenter prospective cohort study with extensive biobanking, were analyzed. Targeted, high-throughput proteomics, machine learning, and bioinformatic methods were applied to contrast the acute-phase plasma proteomes of isolated PE pa…
Induced Pluripotent Mesenchymal Stromal Cell Clones Retain Donor-derived Differences in DNA Methylation Profiles
2012
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is an epigenetic phenomenon. It has been suggested that iPSC retain some tissue-specific memory whereas little is known about interindividual epigenetic variation. We have reprogrammed mesenchymal stromal cells from human bone marrow (iP-MSC) and compared their DNA methylation profiles with initial MSC and embryonic stem cells (ESCs) using high-density DNA methylation arrays covering more than 450,000 CpG sites. Overall, DNA methylation patterns of iP-MSC and ESC were similar whereas some CpG sites revealed highly significant differences, which were not related to parental MSC. Furthermore, hypermethylation in iP-MSC…
Additional file 8: of Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of …
2019
Figure S5. Changes in cellular composition due to Etanercept treatment before, during, and after treatment. Comparison of the abundance of various cell types in the lesional and non-lesional skin of patients with psoriasis. Expression data from dataset GSE47751 was used for this analysis. The p-values of each comparison are presented above each box in the boxplots. (PDF 701 kb)
Additional file 2: of Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of …
2019
Figure S1. Correlation heatmap of the cellular subsets included in DerM22. (PDF 1013 kb)
Additional file 7: of Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of …
2019
Figure S4. Changes in cellular composition due to UVB phototherapy. Comparison of the abundance of various cell types in the lesional and non-lesional skin of patients with atopic dermatitis before and after narrow-band UVB phototherapy. Expression data from dataset GSE27887 [35] was used for this analysis. The p-value of each comparison is presented above each beanplot. (PDF 863 kb)
Additional file 6: of Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of …
2019
Figure S3. Comparison of the changes in cellular abundance between lesional and non-lesional skin of patients with psoriasis and atopic dermatitis. The p-value (without multiple testing correction) of each comparison is depicted on the top of each bean plot. (PDF 4401 kb)
Additional file 5: of Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of …
2019
Figure S2. Variation in relative abundance of skin related cell types across independent datasets. The relative fraction of 13 different cell types in the skin was derived from nine independent datasets. These datasets comprised samples of healthy skin and skin from patients with atopic dermatitis (AD) and psoriasis (PS). The disease samples accounted for lesional (L) and non-lesional skin (NL). The standard deviation is derived for each data point in the panels of this figure. (PDF 461 kb)
Additional file 4: of Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of …
2019
Table S1. Table of flow cytometry data used in this study. (DOCX 21 kb)
Additional file 9: of Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of …
2019
Figure S6. Changes in cellular composition due to Etanercept treatment at baseline and treatment weeks 1 and 12. Comparison of the abundance of various cell types in the lesional and non-lesional skin of patients with psoriasis. Expression data from dataset GSE17239 was used for this analysis. The p-values of each comparison are presented above each box in the boxplots. (PDF 2240 kb)
Additional file 1: of Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of …
2019
Table S2. Signature matrix DerM22. (XLSX 654 kb)
Additional file 3: of Characterization of disease-specific cellular abundance profiles of chronic inflammatory skin conditions from deconvolution of …
2019
Table S3. Reference dataset for DerM22. (XLSX 17 kb)