0000000000991574
AUTHOR
Steffen Rapp
Environmental stressors and cardiovascular risk: Impact of environmental noise exposure on vascular oxidative stress and damage
Epidemiological studies have demonstrated that traffic noise exposure is associated with cardiovascular diseases such as arterial hypertension, myocardial infarction and stroke. Persistent chronic noise exposure increases the risk of cardiovascular and metabolic diseases such as arterial hypertension, coronary artery disease, diabetes and stroke. Large epidemiological studies (reviewed in Munzel et al. Eur. Heart J. 2017, 38 (8):550–556) point towards a link between the incidence of ischemic heart diseases and exposure to noise, supporting its role as an independent cardiovascular risk factor. Recently, the underlying molecular mechanisms leading to noise-dependent adverse effects on the va…
A prospective cohort study to identify and evaluate endotypes of venous thromboembolism: Rationale and design of the Genotyping and Molecular Phenotyping in Venous ThromboEmbolism project (GMP-VTE)
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 …
Additional file 9 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
Additional file 9: Web Table 1B. Differentially expressed genes 4 h after exposure to low dose ionizing radiation (0.05 Gray).
Isolated Pulmonary Embolism Is Associated With a High Risk of Arterial Thrombotic Disease
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…
High efficacy of face masks explained by characteristic regimes of airborne SARS-CoV-2 virus abundance
Abstract Airborne transmission is an important transmission pathway for viruses, including SARS-CoV-2. Regions with a higher proportion of people wearing masks show better control of COVID-19, but the effectiveness of masks is still under debate due to their limited and variable efficiencies in removing respiratory particles. Here, we analyze experimental data and perform model calculations to show that this contrast can be explained by the different regimes of abundance of particles and viruses. Because of the large number of particles exhaled during human respiration and vocalization, indoor environments are usually in a particle-rich regime which means that masks cannot prevent the inhal…
Germline loss-of-function variants in the BARD1 gene are associated with early-onset familial breast cancer but not ovarian cancer
Background The role of the BARD1 gene in breast cancer (BC) and ovarian cancer (OC) predisposition remains elusive, as published case-control investigations have revealed controversial results. We aimed to assess the role of deleterious BARD1 germline variants in BC/OC predisposition in a sample of 4920 BRCA1/2-negative female BC/OC index patients of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). Methods A total of 4469 female index patients with BC, 451 index patients with OC, and 2767 geographically matched female control individuals were screened for loss-of-function (LoF) mutations and potentially damaging rare missense variants in BARD1. All patients met the …
Additional file 10 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
Additional file 10: Web Table 1C. Differentially expressed genes 2 h after exposure to high dose ionizing radiation (2 Gray).
Additional file 8 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
Additional file 8: Web Table 1A. Differentially expressed genes 2 h after exposure to low dose ionizing radiation (0.05 Gray).
Face masks effectively limit the probability of SARS-CoV-2 transmission.
Masking out air sharing The effectiveness of masks in preventing the transmission of severe acute respiratory syndrome coronavirus 2 has been debated since the beginning of the COVID-19 pandemic. One important question is whether masks are effective despite the forceful expulsion of respiratory matter during coughing and sneezing. Cheng et al. convincingly show that most people live in conditions in which the airborne virus load is low. The probability of infection changes nonlinearly with the amount of respiratory matter to which a person is exposed. If most people in the wider community wear even simple surgical masks, then the probability of an encounter with a virus particle is even fur…
Additional file 2 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
Additional file 2: Web Figure 7. Shared pathways from low and high dose ionizing radiation experiments. Gy = Gray. Web Figure 8. Pathways only affected in high dose ionizing radiation experiments. Gy = Gray.
Additional file 3 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
Additional file 3: Web Figure 9. Predicted downsteam diseases and functions. Web Figure 10. Predicted upstream regulators. LDIR = Low dose of ionizing radiation (0.05 Gray), HDIR = High dose of ionizing radiation (2 Gray).
Additional file 1 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
Additional file 1: Web Figure 1. Representative measurements of the cell cycle distribution of HOECHST33258-stained fibroblasts by flow cytometry during (A) log-phase growth or (B) after G0/1 synchronization over 14 days for radiation experiments. Web Figure 2. Total number of differentially expressed genes in human fibroblasts from cancer free-controls at 0.25 h, 2 h and 24 h after exposure to low (0.05 Gray (Gy)) or high dose (2Gy) of X-rays compared to unirradiated fibroblasts (N = 3). Web Figure 3. Correlation of RNA quality metrics (RIN, Qbit RNA-concentration), expression variation (PC1–3) and number of aligned reads (aligned reads, aligned reads normalized) for all experiments. The c…
Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
Abstract Background Exposure to ionizing radiation induces complex stress responses in cells, which can lead to adverse health effects such as cancer. Although a variety of studies investigated gene expression and affected pathways in human fibroblasts after exposure to ionizing radiation, the understanding of underlying mechanisms and biological effects is still incomplete due to different experimental settings and small sample sizes. Therefore, this study aims to identify the time point with the highest number of differentially expressed genes and corresponding pathways in primary human fibroblasts after irradiation at two preselected time points. Methods Fibroblasts from skin biopsies of…
Crucial role for Nox2 and sleep deprivation in aircraft noise-induced vascular and cerebral oxidative stress, inflammation, and gene regulation
Abstract Aims Aircraft noise causes endothelial dysfunction, oxidative stress, and inflammation. Transportation noise increases the incidence of coronary artery disease, hypertension, and stroke. The underlying mechanisms are not well understood. Herein, we investigated effects of phagocyte-type NADPH oxidase (Nox2) knockout and different noise protocols (around-the-clock, sleep/awake phase noise) on vascular and cerebral complications in mice. Methods and results C57BL/6j and Nox2 −/− (gp91phox −/−) mice were exposed to aircraft noise (maximum sound level of 85 dB(A), average sound pressure level of 72 dB(A)) around-the-clock or during sleep/awake phases for 1, 2, and 4 days. Adverse effec…
Additional file 1: of Germline loss-of-function variants in the BARD1 gene are associated with early-onset familial breast cancer but not ovarian cancer
Table S1. Inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) for BRCA1 and BRCA2 germline testing. Table S2. Genotype, phenotype and cancer family history of familial BC index patients carrying heterozygous germline loss-of-function (LoF) variants in the BARD1 gene (transcript NM_000465.3). Table S3. Prevalence of heterozygous germline LoF variants identified in the BARD1 gene (transcript NM_000465.3). Table S4. Potentially damaging rare missense variants identified in the BARD1 gene (transcript NM_000465.3). (DOCX 76 kb)
Additional file 5 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
Additional file 5: Web Figure 12. Comparison of predicted downstream diseases and functions in different data sets.
Additional file 6 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
Additional file 6: Web Figure 13. Comparison of predicted upstream regulators in different data sets.
Missing value imputation in proximity extension assay-based targeted proteomics data
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…
Relative Telomere Length and Cardiovascular Risk Factors
(1) Background: Telomeres are repetitive DNA sequences located at the extremities of chromosomes that maintain genetic stability. Telomere biology is relevant to several human disorders and diseases, specifically cardiovascular disease. To better understand the link between cardiovascular disease and telomere length, we studied the effect of relative telomere length (RTL) on cardiovascular risk factors in a large population-based sample. (2) Methods: RTL was measured by a real-time quantitative polymerase chain reaction in subjects of the population-based Gutenberg Health Study (n = 4944). We then performed an association study of RTL with known cardiovascular risk factors of smoking status…
Additional file 7 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
Additional file 7: Gene expression in the "Not a Number" pathways (blue = downregulation, red = upregulation). Web Figure 14. Base excision repair (BER) system. Web Fig. 15. Molecular mechanisms of cancer. Web Fig. 16. Assembly of RNA polymerase III complex. Web Fig. 17. DNA double-strand break repair by homologous recombination. Web Fig. 18. Interleukin 4 (IL-4) signaling. Web Fig. 19. Interleukin 17 (IL-17) signaling. Web Fig. 20. Interleukin 17A (IL-17A) signaling in fibroblasts. Web Fig. 21. Mitochondrial dysfunction. Web Fig. 22. Myc mediated apoptosis signaling. Web Fig. 23.Nucleotide excision repair. Web Fig. 24. Protein ubiquitination. Web Fig. 25. Retinoic acid receptor (RAR) activ…
Additional file 4 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
Additional file 4: Web Figure 11. Comparison of affected pathways in different data sets.
A targeted proteomics investigation of the obesity paradox in venous thromboembolism
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
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…
Additional file 11 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
Additional file 11: Web Table 1D. Differentially expressed genes 4 h after exposure to high dose ionizing radiation (2 Gray).
Additional file 12 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
Additional file 12: Web Table 2. Differential expression activity in cellular pathways and involved molecules
Effects of noise on vascular function, oxidative stress, and inflammation: mechanistic insight from studies in mice
Aims Epidemiological studies indicate that traffic noise increases the incidence of coronary artery disease, hypertension and stroke. The underlying mechanisms remain largely unknown. Field studies with nighttime noise exposure demonstrate that aircraft noise leads to vascular dysfunction, which is markedly improved by vitamin C, suggesting a key role of oxidative stress in causing this phenomenon. Methods and results We developed a novel animal model to study the vascular consequences of aircraft noise exposure. Peak sound levels of 85 and mean sound level of 72 dBA applied by loudspeakers for 4 days caused an increase in systolic blood pressure, plasma noradrenaline and angiotensin II lev…
Additional file 13 of Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
Additional file 13: Supplement file 1. Settings for comparison analyses in IPA.