@misc{13233, abstract = {{Atranones are secondary metabolites produced by Stachybotrys chartarum, a mold frequently found in water-damaged indoor environments. In contrast to the well-characterized and highly toxic macrocyclic trichothecenes, atranones have received relatively limited scientific attention. Approximately 60% of S. chartarum isolates from indoor environments produce atranones, while 40% form macrocyclic trichothecenes. No strain has been shown to produce both, indicating that the biosynthetic pathways for these two mycotoxin classes are mutually exclusive. Atranones are dolabellane-like diterpenoids synthesized from geranylgeranyl pyrophosphate through multiple enzymatic steps encoded by a specific core gene cluster. While the genetic structure of this cluster has been elucidated, its regulatory mechanisms remain poorly understood. Notably, although atranone-producing S. chartarum strains have been isolated from indoor settings, no study has yet confirmed the actual production of atranones in indoor environments, leaving the question of real-world exposure unresolved. Experimental studies in cell cultures and animal models indicate that atranones possess pro-inflammatory and cytotoxic properties, including the induction of apoptosis and cell cycle arrest. Atranone Q has demonstrated antitumor activity against osteosarcoma cells in vitro, and more recently identified derivatives such as stachatranone and stachybatranone have shown preliminary cardioprotective effects under ischemic conditions. However, these pharmacological effects remain exploratory and require further validation in in vivo models. Major knowledge gaps concern the environmental triggers for atranone biosynthesis, their regulation, actual presence in built environments, and potential health risks. These areas represent key priorities for future research. }}, author = {{Dabisch-Ruthe, Mareike and Pfannebecker, Jens and Straubinger, Reinhard K. and Ebel, Frank and Ulrich, Sebastian}}, booktitle = {{Mycotoxin Research}}, issn = {{1867-1632}}, keywords = {{Atranone, Secondary metabolite, Stachybotrys, Stachatranone, Stachybatranone}}, publisher = {{Springer}}, title = {{{Atranone-an underestimated secondary metabolite?}}}, doi = {{10.1007/s12550-025-00609-x}}, year = {{2025}}, } @misc{12787, abstract = {{Vapor phase hydrogen peroxide (H2O2) can be utilized to inactivate murine norovirus (MNV), a surrogate of human norovirus, on surface areas. However, vapor phase H2O2 inactivation of virus on fruits and vegetables has not been characterized. In this study, MNV was used to determine whether vaporized H2O2 inactivates virus on surfaces of various fruits and vegetables (apples, blueberries, cucumbers, and strawberries). The effect of vapor phase H2O2 decontamination was investigated with two application systems. Plaque assays were performed after virus recovery from untreated and treated fresh produce to compare the quantity of infective MNV. The Mann-Whitney U test was applied to the test results to evaluate the virus titer reductions of treated food samples, with significance set at P <= 0.05. The infective MNV populations were significantly reduced on smooth surfaces by 4.3 log PFU (apples, P < 0.00001) and 4 log PFU or below the detection limit (blueberries, P = 0.0074) by treatment with vapor phase H2O2 (60 min, maximum of 214 ppm of H2O2). Similar treatments of artificially contaminated cucumbers resulted in a virus titer reduction of 1.9 log PFU. Treatment of inoculated strawberries resulted in 0.1and 2.8-log reductions of MNV. However, MNV reduction rates on cucumbers (P = 0.3809) and strawberries (P = 0,7414) were not significant. Triangle tests and color measurements of untreated and treated apples, cucumbers, blueberries, and strawberries revealed no differences in color and consistency after H2O2 treatment. No increase of the H2O2 concentration in treated fruits and vegetables compared with untreated produce was observed. This study reveals for the first time the conditions under which vapor phase H2O2 inactivates MNV on selected fresh fruit and vegetable surfaces.}}, author = {{Becker, Barbara and Dabisch-Ruthe, Mareike and Pfannebecker, Jens}}, booktitle = {{ Journal of food protection }}, issn = {{1944-9097}}, keywords = {{Fruits, Inactivation, Murine norovirus, Vapor phase hydrogen peroxide, Vegetables}}, number = {{1}}, pages = {{45--51}}, publisher = {{IAFP}}, title = {{{Inactivation of Murine Norovirus on Fruit and Vegetable Surfaces by Vapor Phase Hydrogen Peroxide}}}, doi = {{10.4315/0362-028X.JFP-19-238}}, volume = {{83}}, year = {{2020}}, } @misc{12988, abstract = {{BACKGROUND Bacterial contamination of platelet concentrates (PCs) is still a major challenge in transfusion medicine. Different methodologic concepts and screening strategies have been developed and investigated concerning their usability. We evaluated the feasibility of BacT/ALERT automated culture (BacT/A, bioMérieux) with late sampling after 3 days at the earliest. STUDY DESIGN AND METHODS Twenty-four bacterial strains isolated from PCs and six relevant strains from reference stocks were spiked into apheresis-derived PCs (10-60 colony-forming units [CFU]/bag). Sampling was performed after 3 days, and bacterial detection was investigated using the two detection methods (BacT/A and BactiFlow [BF], bioMérieux). The maximum time-to-result of BacT/A was set to less than 12 hours. RESULTS All medium- or high-pathogenic strains are capable of proliferating to high titers, and 100% of contaminated samples were detected by BF and BacT/A (6 to ≤12 h incubation); lower detection rates of BacT/A were obtained within 6 hours of incubation (≤6 h: 76.2-93.4%). The majority of low-pathogenic isolates are also capable of growing in PCs (89.7%), showing a detection rate of 74.3% for BF versus 54.3% for BacT/A (6 to ≤12 h incubation). BacT/A failed to detect bacteria within 6 hours of incubation. Certainly, a small number of strains did not grow under PC storage conditions and were detectable by BacT/A only with increased detection times. CONCLUSIONS Late sampling after 3 days at the earliest, combined with reduced BacT/A incubation following the negative-to-date concept, offer an alternative opportunity to extend the shelf life of PCs from 4 to 5 days in Germany. The sensitivity of BacT/A with late sampling is nearly comparable to BF; the time-to-result is considerably longer. }}, author = {{Vollmer, Tanja and Dabisch-Ruthe, Mareike and Weinstock, Melanie and Knabbe, Cornelius and Dreier, Jens}}, booktitle = {{Transfusion}}, issn = {{1537-2995}}, number = {{7}}, pages = {{1654--1664}}, publisher = {{Wiley-Blackwell}}, title = {{{Late sampling for automated culture to extend the platelet shelf life to 5 days in Germany}}}, doi = {{10.1111/trf.14617}}, volume = {{58}}, year = {{2018}}, } @misc{12989, author = {{Dabisch-Ruthe, Mareike and Weinstock, Melanie and Pfannebecker, Jens and Becker, Barbara}}, booktitle = {{26th International ICFMH Conference - FoodMicro 2018}}, location = {{Berlin}}, pages = {{482}}, title = {{{Usage of cold hydrogen peroxide vapour for inactivation of murine norovirus on fruit and vegetable surfaces.}}}, doi = {{10.13140/RG.2.2.12883.08484}}, year = {{2018}}, } @misc{12990, author = {{Dabisch-Ruthe, Mareike and Weinstock, Melanie and Pfannebecker, Jens and Meyer, Sonja and Schwetka, Mona and Becker, Barbara}}, booktitle = {{70th Annual Conference of the German Society of Hygiene and Microbiology}}, isbn = {{978-3-9816508-6-0}}, location = {{Bochum}}, publisher = {{Conventus Congressmanagement & Marketing GmbH }}, title = {{{Application of cold nebulized hydrogen peroxide for inactivation of murine norovirus, bacteria and bacteria spores on surfaces in food production.}}}, doi = {{10.13140/RG.2.2.22949.41447}}, year = {{2018}}, } @misc{12984, abstract = {{Background Pseudoxanthoma elasticum (PXE) is a rare hereditary disorder characterized by late onset and progressive calcification of elastic fibers in skin, eyes and the cardiovascular system, exemplifying a model for conditions characterized by soft tissue calcification. Objective The aim of our study was to characterize cellular inorganic pyrophosphate (PPi) homeostasis in PXE. Methods Gene expression of PPi metabolizing enzymes was determined by quantitative real-time PCR after incubation up to 21 days with or without addition of Na2HPO4. Extracellular and cytosolic PPi concentrations were measured by enzyme-linked bioluminescence assay. ALP and ENPP1 activity was determined spectrophotometrically. We further established a human cell culture model suitable for investigating PXE and related disorders without addition of artificial calcification triggers. Results Independently of the experimental conditions, PXE fibroblasts revealed a higher degree of matrix calcification. We observed that matrix calcification was associated with altered gene expression of PPi metabolizing enzymes in PXE fibroblasts. In this context, PXE fibroblasts exhibited significantly higher expression of ALP and OPN and reduced mRNA expression and activity of ENPP1. Here, for the first time cytosolic and extracellular PPi levels were shown to be strongly reduced in PXE fibroblasts. We further showed that PPi concentration in bovine and human sera additives had a strong impact on matrix calcification. In a last experimental line, we demonstrated that addition of PPi analogs reduced matrix calcification of PXE fibroblasts most likely by reducing ALP and OPN mRNA expression, restoring ENPP1 activity and subsequently elevating PPi concentrations. Conclusion The results of our study along with recent findings point to the essential role of PPi as the central regulatory metabolites preventing matrix calcification in PXE. But what remains to be determined is the underlying molecular mechanism leading to depletion of PPi in PXE. We further suggest that supplementation of PPi analogs might counteract pathological calcification in PXE and related disorders.}}, author = {{Dabisch-Ruthe, Mareike and Kuzaj, Patricia and Götting, Christian and Knabbe, Cornelius and Hendig, Doris}}, booktitle = {{Journal of Dermatological Science}}, issn = {{1873-569X}}, keywords = {{Pseudoxanthoma elasticum, Calcification, Pyrophosphate, Bisphosphonate, ABCC6, Tissue nonspecific alkaline phosphate, Ectonucleotide pyrophosphatase 1}}, number = {{2}}, pages = {{109--120}}, publisher = {{Elsevier }}, title = {{{Pyrophosphates as a major inhibitor of matrix calcification in Pseudoxanthoma elasticum}}}, doi = {{10.1016/j.jdermsci.2014.04.015}}, volume = {{75}}, year = {{2014}}, } @misc{12985, abstract = {{Objectives Pseudoxanthoma elasticum (PXE) is a rare hereditary disorder characterized by progressive calcification and fragmentation of elastic fibers. Because of the great clinical variability between PXE patients the involvement of modifier genes was recently suggested. Therefore, we investigated the association of single nucleotide variants (SNVs) in selected candidate genes known to regulate cellular pyrophosphate metabolism. Design and methods We used RLFP analyses to evaluate the distribution of SNVs in alkaline phosphatase (ALP), ectonucleotide pyrophosphatase 1 (ENPP1) and ankylosis (ANKH) in DNA samples from 190 German PXE patients and 190 age- and sex-matched healthy controls. Statistical analyses were performed using Fisher exact test and Bonferroni correction. Results The screening revealed three different SNVs in three genes, which were associated with PXE. The SNV c.1190-65C > A (rs1780329, minor allele frequency (MAF) patients: 0.17; controls: 0.11; P = 0.04) in the ALP gene was significantly more frequent in PXE patients. Furthermore, PXE was highly associated with ANKH p.A98A genotype TT (P = 0.0012), although the MAF was not different between patients and controls. After correction for multiple testing according to the Bonferroni method, one SNV in the ENPP1 gene (c.313 + 9G > T, rs7773477) remained significantly associated with PXE with significantly higher MAF values in the patient cohort (MAF: 0.04 vs. 0.00; P = 0.0024) and a high association with PXE susceptibility (OR 27.96). Conclusion Polymorphisms in ALP, ENPP1 and ANKH are important genetic risk factors contributing to PXE.}}, author = {{Dabisch-Ruthe, Mareike and Brock, Alexander and Kuzaj, Patricia and Charbel Issa, Peter and Szliska, Christiane and Knabbe, Cornelius and Hendig, Doris}}, booktitle = {{Clinical Biochemistry}}, issn = {{1873-2933}}, keywords = {{Pseudoxanthoma elasticum, Calcification, Tissue nonspecific alkaline phosphatase, Ectonucleotide pyrophosphatase 1, Ankylosis}}, number = {{15}}, pages = {{60--67}}, publisher = {{Elsevier}}, title = {{{Variants in genes encoding pyrophosphate metabolizing enzymes are associated with Pseudoxanthoma elasticum}}}, doi = {{10.1016/j.clinbiochem.2014.07.003}}, volume = {{47}}, year = {{2014}}, } @misc{12986, abstract = {{Background Dysregulations in cholesterol and lipid metabolism have been linked to human diseases like hypercholesterolemia, atherosclerosis or the metabolic syndrome. Many ABC transporters are involved in trafficking of metabolites derived from these pathways. Pseudoxanthoma elasticum (PXE), an autosomal-recessive disease caused by ABCC6 mutations, is characterized by atherogenesis and soft tissue calcification. Methods In this study we investigated the regulation of cholesterol biosynthesis in human dermal fibroblasts from PXE patients and healthy controls. Results Gene expression analysis of 84 targets indicated dysregulations in cholesterol metabolism in PXE fibroblasts. Transcript levels of ABCC6 were strongly increased in lipoprotein-deficient serum (LPDS) and under serum starvation in healthy controls. For the first time, increased HMG CoA reductase activities were found in PXE fibroblasts. We further observed strongly elevated transcript and protein levels for the proprotein convertase subtilisin/kexin type 9 (PCSK9), as well as a significant reduction in APOE mRNA expression in PXE. Conclusion Increased cholesterol biosynthesis, elevated PCSK9 levels and reduced APOE mRNA expression newly found in PXE fibroblasts could enforce atherogenesis and cardiovascular risk in PXE patients. Moreover, the increase in ABCC6 expression accompanied by the induction of cholesterol biosynthesis supposes a functional role for ABCC6 in human lipoprotein and cholesterol homeostasis.}}, author = {{Kuzaj, Patricia and Kuhn, Joachim and Dabisch-Ruthe, Mareike and Faust, Isabel and Götting, Christian and Knabbe, Cornelius and Hendig, Doris}}, booktitle = {{Lipids in Health and Disease}}, issn = {{1476-511X}}, keywords = {{Pseudoxanthoma elasticum, ABC transporter, ABCC6, Cholesterol biosynthesis, Atherosclerosis, HMG CoA reductase, SREBP2, PCSK9, LDLR, APOE}}, number = {{1}}, publisher = {{Biomed Central }}, title = {{{ABCC6- a new player in cellular cholesterol and lipoprotein metabolism?}}}, doi = {{10.1186/1476-511x-13-118}}, volume = {{13}}, year = {{2014}}, } @misc{12987, abstract = {{Mutations in the ABC transporter ABCC6 were recently identified as cause of Pseudoxanthoma elasticum (PXE), a rare genetic disorder characterized by progressive mineralization of elastic fibers. We used an untargeted metabolic approach to identify biochemical differences between human dermal fibroblasts from healthy controls and PXE patients in an attempt to find a link between ABCC6 deficiency, cellular metabolic alterations and disease pathogenesis. 358 compounds were identified by mass spectrometry covering lipids, amino acids, peptides, carbohydrates, nucleotides, vitamins and cofactors, xenobiotics and energy metabolites. We found substantial differences in glycerophospholipid composition, leucine dipeptides, and polypeptides as well as alterations in pantothenate and guanine metabolism to be significantly associated with PXE pathogenesis. These findings can be linked to extracellular matrix remodeling and increased oxidative stress, which reflect characteristic hallmarks of PXE. Our study could facilitate a better understanding of biochemical pathways involved in soft tissue mineralization.}}, author = {{Kuzaj, Patricia and Kuhn, Joachim and Michalek, Ryan D. and Karoly, Edward D. and Faust, Isabel and Dabisch-Ruthe, Mareike and Knabbe, Cornelius and Hendig, Doris}}, booktitle = {{PLOS ONE / Public Library of Science }}, issn = {{1932-6203}}, number = {{9}}, publisher = {{Public Library of Science (PLoS)}}, title = {{{Large-Scaled Metabolic Profiling of Human Dermal Fibroblasts Derived from Pseudoxanthoma Elasticum Patients and Healthy Controls}}}, doi = {{10.1371/journal.pone.0108336}}, volume = {{9}}, year = {{2014}}, } @misc{12983, abstract = {{Background A broad spectrum of pathogens is causative for respiratory tract infections, but symptoms are mostly similar. Therefore, the identification of the causative viruses and bacteria is only feasible using multiplex PCR or several monoplex PCR tests in parallel. Methods The analytical sensitivity of three multiplex PCR assays, RespiFinder-19, RespiFinder-SMART-22 and xTAG-Respiratory-Virus-Panel-Fast-Assay (RVP), were compared to monoplex real-time PCR with quantified standardized control material. All assays include the most common respiratory pathogens. Results To compare the analytical sensitivity of the multiplex assays, samples were inoculated with 13 different quantified viruses in the range of 101 to 105 copies/ml. Concordant results were received for rhinovirus, whereas the RVP detected influenzavirus, RSV and hMPV more frequently in low concentrations. The RespiFinder-19 and the RespiFinder-SMART-22 showed a higher analytical sensitivity for adenoviruses and coronaviruses, whereas the RVP was incapable to detect adenovirus and coronavirus in concentrations of 104 copies/ml. The RespiFinder-19 and RespiFinder-SMART-22A did not detect influenzaviruses (104 copies/ml) and RSV (103 copies/ml). The detection of all 13 viruses in one sample was only achieved using monoplex PCR. To analyze possible competitive amplification reactions between the different viruses, samples were further inoculated with only 4 different viruses in one sample. Compared to the detection of 13 viruses in parallel, only a few differences were found. The incidence of respiratory viruses was compared in tracheal secretion (TS) samples (n = 100) of mechanically ventilated patients in winter (n = 50) and summer (n = 50). In winter, respiratory viruses were detected in 32 TS samples (64%) by RespiFinder-19, whereas the detection rate with RVP was only 22%. The most frequent viruses were adenovirus (32%) and PIV-2 (20%). Multiple infections were detected in 16 TS samples (32%) by RespiFinder-19. Fewer infections were found in summer (RespiFinder-19: 20%; RVP: 6%). All positive results were verified using monoplex PCR. Conclusions Multiplex PCR tests have a broad spectrum of pathogens to test at a time. Analysis of multiple inoculated samples revealed a different focus of the detected virus types by the three assays. Analysis of clinical samples showed a high concordance of detected viruses by the RespiFinder-19 compared to monoplex tests.}}, author = {{Dabisch-Ruthe, Mareike and Vollmer, Tanja and Adams, Ortwin and Knabbe, Cornelius and Dreier, Jens}}, booktitle = {{BMC Infectious Diseases}}, issn = {{1471-2334}}, keywords = {{Respiratory Virus, Elution Volume, Multiplex Assay, Multiple Infection, Bocavirus}}, number = {{1}}, publisher = {{Springer}}, title = {{{Comparison of three multiplex PCR assays for the detection of respiratory viral infections: evaluation of xTAG respiratory virus panel fast assay, RespiFinder 19 assay and RespiFinder SMART 22 assay}}}, doi = {{10.1186/1471-2334-12-163}}, volume = {{12}}, year = {{2012}}, } @misc{12982, abstract = {{Contaminated food is a significant vehicle for human norovirus transmission. The present study determined the effect of physicochemical treatments on the tenacity of infective human norovirus genogroup II in selected foods. Artificially contaminated produce was subjected to a number of processes used by the food industry for preservation and by the consumer for storage and preparation. Virus recovery was carried out by using ultrafiltration and was monitored by using bacteriophage MS2 as an internal process control. Norovirus was quantified by using monoplex one-step TaqMan real-time reverse transcription (RT)-PCR and an external standard curve based on recombinant RNA standards. An RNase pretreatment step was used to avoid false-positive PCR results caused by accessible RNA, which allowed detection of intact virus particles. Significant reductions in titers were obtained with heat treatments usually applied by consumers for food preparation (baking, cooking, roasting). Generally, processes used for preservation and storage, such as cooling, freezing, acidification (≥pH 4.5), and moderate heat treatments (pasteurization), appear to be insufficient to inactivate norovirus within a food matrix or on the surface of food. Besides data for persistence in processed food, comparable data for individual matrix-specific protective effects, recovery rates, and inhibitory effects on the PCRs were obtained in this study. The established procedure might be used for other noncultivable enteric RNA viruses that are connected to food-borne diseases. The data obtained in this study may also help optimize the process for inactivation of norovirus in food by adjusting food processing technologies and may promote the development of risk assessment systems in order to improve consumer protection.}}, author = {{Mormann, Sascha and Dabisch-Ruthe, Mareike and Becker, Barbara}}, booktitle = {{ Applied and environmental microbiology / American Society for Microbiology}}, issn = {{1098-5336}}, number = {{2}}, pages = {{536--545}}, publisher = {{American Society for Microbiology}}, title = {{{Effects of Technological Processes on the Tenacity and Inactivation of Norovirus Genogroup II in Experimentally Contaminated Foods}}}, doi = {{10.1128/aem.01797-09}}, volume = {{76}}, year = {{2009}}, }