Ralf Mrowka

Universitätsklinikum Jena

AI-based methods to generate images have seen unprecedented advances in recent years challenging both image forensic and human perceptual capabilities. Accordingly, these methods are expected to play an increasingly important role in the fraudulent fabrication of data. This includes images with complicated intrinsic structures such as histological...

P2X receptors are ATP-activated, non-specific cation channels involved in sensory signalling, inflammation, and certain forms of pain. Investigations of agonist binding and activation are essential for comprehending the fundamental mechanisms of receptor function. This encompasses the ligand recognition by the receptor, conformational changes follo...

AI-based methods to generate images have seen unprecedented advances in recent years challenging both image forensic and human perceptual capabilities. Accordingly, they are expected to play an increasingly important role in the fraudulent fabrication of data. This includes images with complicated intrinsic structures like histological tissue sampl...

The identification of small molecules capable of replacing transcription factors has been a longstanding challenge in the generation of human chemically induced pluripotent stem cells (iPSCs). Recent studies have shown that ectopic expression of OCT4, one of the master pluripotency regulators, compromised the developmental potential of resulting iP...

Kidneys are complex organs, and reproducing their function and physiology in a laboratory setting remains difficult. During drug development, potential compounds may exhibit unexpected nephrotoxic effects, which imposes a significant financial burden on pharmaceutical companies. As a result, there is an ongoing need for more accurate model systems....

The human neurotensin receptor 1 (NTSR1) is a G protein-coupled receptor. The receptor is activated by a small peptide ligand neurotensin. NTSR1 can be expressed in HEK cells by stable transfection. Previously we used the fluorescent protein markers mRuby3 or mNeonGreen fused to NTSR1 for EMCCD-based structured illumination microscopy (SIM) in livi...

Non-resolving inflammation plays a critical role during the transition from renal injury towards end-stage renal disease. The glucocorticoid-inducible protein annexin A1 has been shown to function as key regulator in the resolution phase of inflammation, but its role in immune-mediated crescentic glomerulonephritis has not been studied so far. Meth...

Epithelia compartmentalize multicellular organisms and provide interfacing between the inside and outside. Apart from regulating the exchange of solutes, uptake of nutrients, and excretion of waste products, their major function is to prevent uncontrolled access of foreign material to immune‐competent compartments. Progress in understanding this ba...

Microfluidic tissue culture and organ-on-a-chip models provide efficient tools for drug testing in vivo and are considered to become the basis of in vitro test systems to analyze drug response, drug interactions and toxicity to complement and reduce animal testing. A major limitation is the efficient recording of drug action. Here we present an eff...

Microbial pathogens carry specific structural patterns which were termed pathogenassociated molecular patterns (PAMPs). Toll-like receptors (TLRs) as key elements for the recognition of microbial pathogens are necessary for the activation of innate immune pathways. TLRs are activated by binding PAMPs of bacteria, viruses and fungi and initiate a si...

Preselection digests are a common strategy to reduce the background in the ligation step of molecular cloning. However, choosing fitting restriction enzymes by hand is not trivial and may lead to errors, potentially costing a lot of time and work. We therefore created preselector.uni-jena.de (https://preselector.uni-jena.de/), a free online tool to...

A number of recent contributions to Acta Physiologica relate to blood pressure research and closely related fields. Interestingly, the research objects in that context addressed by the authors in Acta Physiologica are of different geometric sizes. The smallest research object, namely the small molecule nitric oxide, has a diameter of about 100 pm,...

Fungal infections caused by the ancient lineage Mucorales are emerging and increasingly reported in humans. Comprehensive surveys on promising attributes from a multitude of possible virulence factors are limited and so far, focused on Mucor andRhizopus. This study addresses a systematic approach to monitor phagocytosis after physical and enzymatic...

While females are less affected by non-diabetic kidney diseases compared to males, available data on sex differences in diabetic nephropathy (DN) are controversial. Although there is evidence for an imbalance of sex hormones in diabetes and hormone-dependent mechanisms in transforming growth factor β1 (TGF-β1) signaling, causes and consequences are...

Betge, Stefan, Stefan Drinda, Thomas Neumann, Laura Bäz, Alexander Pfeil, Christian Schulze, Ralf Mrowka, Christian Jung, and Marcus Franz. Influence of macitentan on the vascular tone and recruitment of finger capillaries under hypobaric hypoxia in high altitude. High Alt Med Biol. 00:000-000, 2020. Introduction: Acute normobaric (NH) and hypobar...

Background Understanding complex mechanisms of human transcriptional regulation remains a major challenge. Classical reporter studies already enabled the discovery of cis-regulatory elements within the non-coding DNA; however, the influence of genomic context and potential interactions are still largely unknown. Using a modified Cas9 activation com...

The new coronavirus SARS‐COV‐2 is currently impacting life around the globe 1. The rapid spread of this viral disease might be highly challenging for health care systems. This was seen in Northern Italy and in New York City for example2. Governments reacted with different measures such as shutdown of all schools, universities and up to a general cu...

According to the World health organization (WHO) elevated blood pressure, known as arterial Hypertension, is a condition in which the arterial blood vessels have persistently raised pressure, putting them under increased stress. The higher the blood pressure, the higher the risk of damage to the heart and blood vessels in major organs such as the b...

Raised blood pressure affects 1.13 billion people worldwide according to Global Health Observatory (GHO) data. Interestingly, according to WHO statistics, the prevalence of elevated blood pressure depends on World Bank income group. The change over the last 40 years might be due to better awareness and better treatment options in regions with highe...

Inflammation is a natural protective response to microbial infections and tissue injury. It functions to eliminate harmful stimuli and to repair damaged tissue. The inflammatory response is initiated by different inducers of exogenous and endogenous origin. Exogenous inducers can be microbial (pathogen‐associated molecular patterns (PAMPs) and viru...

Calcineurin inhibitors (CnI) such as Cyclosporin A (CsA) are instrumental for immunosuppression after organ transplantation but may cause serious neurologic side effects, including seizures. Neuronal excitability depends on intact Cl ⁻ homeostasis. Generation of hyperpolarizing synaptic responses to GABA and glycine requires a Cl ⁻ gradient across...

Cancer is a wide‐ranging term for diseases which are characterized by the rapid appearance of abnormal cells that grow beyond their usual boundaries. Thereby spreading of tumor cells to other organs and parts of the body can occur and cause metastasizing. With 9.6 million deaths in 2018 cancer is the second leading cause of death worldwide and ther...

G protein-coupled receptors (GPCRs) are a large superfamily of membrane proteins that are activated by extracellular small molecules or photons. Neurotensin receptor 1 (NTSR1) is a GPCR that is activated by neurotensin, i.e. a 13 amino acid peptide. Binding of neurotensin induces conformational changes in the receptor that trigger the intracellular...

Pioneering human induced pluripotent stem cell (iPSC)-based pre-clinical studies have raised safety concerns and pinpointed the need for safer and more efficient approaches to generate and maintain patient-specific iPSCs. One approach is searching for compounds that influence pluripotent stem cell reprogramming using functional screens of known dru...

The human neurotensin receptor 1 (NTSR1) is a G protein-coupled receptor that can be expressed in HEK293T cells by stable transfection. Its ligand is a 13-amino-acid peptide that binds with nanomolar affinity from the extracellular side to NTSR1. Ligand binding induces conformational changes that trigger the intracellular signaling processes. Recen...

Since the 1980s there has been an alarming increase in obesity all over the world. A sedentary life style and the uptake of energy‐dense foods are drivers of this trend, exacerbated by changes in food systems and environments. In 2015 about 107 million children and 603 million adults were obese with an overall prevalence of 5% among children and 12...

The study of drug toxicity in human organs is complicated by their complex inter-relations and by the obvious difficulty to testing drug effects on biologically relevant material. Animal models and human cell cultures offer alternatives for systematic and large-scale profiling of drug effects on gene expression level, as typically found in the so-c...

Compound-specific AUC (ROC) performance across model systems. Each plot represents a single compound, depicting ROC curves for (compound-specific) model system-specific gene rankings (each color represents one model system), with literature-derived genes used as positive examples. Curves are not smoothed, and the straight line fragments of the curv...

Functional enrichment analysis of the top-100 RL ranked genes. Text file with the output of a functional term enrichment analysis using the g:Profiler web tool for the top-100 RL ranked genes. (TXT)

Functional enrichment analysis for genes dys-regulated in rat hepatocytes but not in human hepatocytes. Text file with the output of a functional term enrichment analysis using the g:Profiler web tool for the top-100 ranked genes according to the difference between the RH and the HH ranking. (TXT)

Dose-dependent summary of differential expression analysis. The distributions of the number of differentially expressed genes are depicted with violin-plots by model systems, with each dot representing the number of genes modulated by a single compound. Each row corresponds to one dose level. The median and interquartile range of each distribution...

Compound-specific distribution of differentially expressed gene set sizes. Each plot corresponds to one compound (only high dose treatments results), with each dot corresponding to the number of differentially expressed genes (all) obtained in a single model system including the subset of genes having a rat otholog (othologs) and the subset found i...

Literature-derived genes. Excel file with full lists of literature-derived organ-specific toxicity-related genes, including the output of the co-occurrence analysis as well as the disease enrichment of the organ-specific lists. (XLSX)

Functional enrichment analysis of the top-100 RK ranked genes. Text file with the output of a functional term enrichment analysis using the g:Profiler web tool for the top-100 RK ranked genes. (TXT)

Functional enrichment analysis for genes dys-regulated in the four model systems. Text file with the output of a functional term enrichment analysis using the g:Profiler web tool for the top-100 ranked genes according to the sum of the four rankings: HH, RH, RL, RK. (TXT)

Functional enrichment analysis for genes dys-regulated in human hepatocytes but not in rat hepatocytes. Text file with the output of a functional term enrichment analysis using the g:Profiler web tool for the top-100 ranked genes according to the difference between the HH and the RH ranking. (TXT)

Functional enrichment analysis of the top-100 RH ranked genes. Text file with the output of a functional term enrichment analysis using the g:Profiler web tool for the top-100 RH ranked genes. (TXT)

Functional enrichment analysis for genes dys-regulated in rat hepatocytes but not in rat liver. Text file with the output of a functional term enrichment analysis using the g:Profiler web tool for the top-100 ranked genes according to the difference between the RH and the RL ranking. (TXT)

Compounds and data samples summary. Excel file with description of the 33 compounds profiled across all model systems in Open TG-GATEs database. The file includes full and abbreviated names, and if available the toxicity labels, compound IDs in on-line compound databases (PubChem and DrugBank), chemical structure description (by SMILES), mechanism,...

Gene rankings. Excel file with all gene rankings (obtained by the different ranking methods) for each model system in a separate data sheet. All data sheets are ranked according to the finally chosen AR-ranking. The gene Entrez IDs and gene symbols correspond to the human annotation space. Note that this file uses compound abbreviations introduced...

Aggregation of AR ranks. Excel file with full gene list ranked according to the sum of all model system-specific AR ranks. The gene Entrez IDs and gene symbols correspond to the human annotation space. Extra columns include combinations of the AR rankings needed for comparison between the modeled systems. (XLS)

Functional enrichment analysis of the top-100 HH ranked genes. Text file with the output of a functional term enrichment analysis using the g:Profiler web tool for the top-100 HH ranked genes. (TXT)

Functional enrichment analysis for genes dys-regulated in rat liver but not in rat hepatocytes. Text file with the output of a functional term enrichment analysis using the g:Profiler web tool for the top-100 ranked genes according to the difference between the RL and the RH ranking. (TXT)

Regulation of blood pressure and the understanding of its mechanisms have been one focus of current publications in Acta Physiologica. Among those are many publications that investigate mechanistic aspects of blood pressure regulation. A number of papers in Acta Physiologica deal with modifiers of blood pressure that received attention only recentl...

Hormones: They control the human circadian rhythm, cause happiness after physical exercise, cause butterflies in one′s stomach and contribute to the chemistry of love, turn a pregnant woman′s life upside down and influence the growth of the fetus, in short, they are essential in the human individual development and homeostasis of organs. Hormones a...

Nephropathy denotes a loss of kidney function due to renal disease or kidney damage. In general this can be caused by inflammation or non‐inflammatory causes. Non‐inflammatory processes leading to nephropathy are for example a decreased glomerular flow rate (GFR), exposure to renal toxins (e. g. drugs) and renal trauma. Acute kidney injuries (AKI)...

The causes for the development of chronic diseases like diabetes, cardiovascular disease or cancer are multifactorial and often influence each other. With increasing age the risk for developing type 2 diabetes increases and the risk to suffer from cardiovascular and chronic kidney disease is increased once a patient is diabetic. Besides pharmacolog...

Knock out technologies and the application of siRNA made it possible to turn off genes or to diminish their activity. The opposite application was much harder so far. Directed switching on of endogenous genes has been virtually impossible. One option of overexpression of a gene of interest is to bring the complete genetic information of that gene i...

The metabolic activity of hepatocytes is a central prerequisite for drug activity and a key element in drug–drug interaction. This central role in metabolism largely depends on the activity of the cytochrome P450 (CYP450) enzyme family, which is not only dependent on liver cell maturation but is also controlled in response to drug and chemical expo...

Background: The use of fetal bovine serum (FBS) as growth supplement for human cell and tissue culture is widely spread in basic research as well as in clinical approaches, although several limitations must be considered, such as unstable composition and availability, biosafety and ethical aspects. Regarding interspecies differences, xenogeneic gr...

Advances in organ-on-chip technologies for the application in in-vitro drug development provide an attractive alternative approach to replace ethically controversial animal testing and to establish a basis for accelerated drug development. In recent years, various chip-based tissue culture systems have been developed, which are mostly optimized for...

Origins and progresses of nephropathies are manifold and include inflammatory or non-inflammatory causes. The incidence of nephropathies increases all over the world, supported by the growing elderly population. Nowadays there are about two million fatalities per year due to acute kidney injury (AKI) 1. Clinical outcomes of AKI have not improved ov...

Toxicity affecting humans is studied by observing the effects of chemical substances in animal organisms (in vivo) or in animal and human cultivated cell lines (in vitro). Toxicogenomics studies collect gene expression profiles and histopathology assessment data for hundreds of drugs and pollutants in standardized experimental designs using differe...

The complement system, a plasma component, was described upon its discovery to augment the opsonisation of bacteria by antibodies, 'complementing' said antibodies' antibacterial activity. In its first and foremost role, the complement cascade helps convert pathogen recognition into an effective host defence. Two recent publications in Acta Physiolo...

Purpose Oct4 was reported to be one of the most important pluripotency transcription factors in the biology of stem cells including cancer stem cells, and progressed malignant cells. Here we report the investigation of gene expression control of Oct4 by selected human microRNAs and the physiological effect of Oct4 silencing in invasive cancer cells...

Anti-Oct4-siRNA downregulates Oct4 expression comparable to microRNA-299-3p. Luciferase reporter assay measuring expression of Oct4 target promoter. Data was taken over 24h. The mean of values of first and last ten minutes were taken to calculate the ratio. Scramble: non-human microRNA sequence (negative control). Error bars indicate SEM. Non-param...

Bioinformatical analysis of microRNA target genes (http://www.targetscan.org). (XLSX)

WebGestalt (http://www.webgestalt.org/) analysis. A: of malignant illness-related genes using KEGG database (Kyoto Encyclopedia of Genes and Genomes) which are putatively regulated by microRNA-299-3p. B: of putatively miR-299-3p influenced pathways using KEGG database (Kyoto Encyclopedia of Genes and Genomes). (DOCX)

Bioinformatical analysis of targets of human microRNA-299-3p in relation to apoptotic processes (http://www.targetscan.org). (XLSX)

WebGestalt (http://www.webgestalt.org/) analysis of microRNA-299-3p target genes using KEGG database (Kyoto Encyclopedia of Genes and Genomes), in process groups (biological, molecular function, cellular component). (TIF)

Human visual perception system is complex and involves a considerable portion of the brain's cortex. Hence, the wish to understand complex neuronal function is obvious, and the idea to model this by means of artificial neuronal networks might have been born at the time when first computational machines were constructed (Alan Turing, Intelligent mac...

Cytochrome C oxidase and FoF1-ATP synthase constitute complex IV and V, respectively, of the five membrane-bound enzymes in mitochondria comprising the respiratory chain. These enzymes are located in the inner mitochondrial membrane (IMM), which exhibits large invaginations called cristae. According to recent cryo-tomography, FoF1-ATP synthases are...

Cytochrome C oxidase and FoF1-ATP synthase constitute complex IV and V, respectively, of the five membrane-bound enzymes in mitochondria comprising the respiratory chain. These enzymes are located in the inner mitochondrial membrane (IMM), which exhibits large invaginations called cristae. According to recent cryo-tomography, FoF1-ATP synthases are...

Blood pressure is an important determinant in the progression of many cardiovascular and renal diseases. The interest of the physiologists in this topic is reflected in the high number of articles that appeared in Acta Physiologica recently. About 20% of the articles in Acta Physiologica contain the keyword blood pressure or hypertension in the yea...

Multicellular tumor spheroids are widely used models in tumor research. Because of their three dimensional organization they can simulate avascular tumor areas comprising proliferative and necrotic cells. Nonetheless, protocols for spheroid generation are still inconsistent. Therefore, in this study the breast cancer cell lines MCF-7, MDA-MB-231 an...

Toxikologische Analysen an plazentarem Gewebe: Der Einfluss von Chemotherapeutika auf Trophoblastzellen

Effects of chemotherapeutics on trophoblast cells in 2D, 3D and placental explant culture

Hearing is a sense that supports us in many aspects of life. Malfunction of hearing limits not only communication. Deafness may contribute to the development of psychotic disorders due to sensory deprivation phenomena, and the interference of hearing loss in attention, perception and communication (Cooper, 1976). Hearing is also important for orien...

Background/aims: We have previously shown that advanced glycation-endproducts (AGEs) induced NFκB activation in differentiated mouse podocytes. This NFκB activation may contribute to the progression of renal disease and mediation of fibrosis by various mechanisms. This study was undertaken to test whether this detrimental response may be reversed...

Cytotoxicity and inhibitory effects of chemotherapy on cervical cancer and trophoblast cells cultured in 2D or 3D

Toxicological testing on placenta-derived cells cultured as monolayer, multicellular spheroids or ex vivo explants

Toxicological testing on placenta-derived cells cultured as monolayer, multicellular spheroids or ex vivo explants

Cytotoxicity and inhibitory effects of chemotherapy on cervical cancer and trophoblast cells cultured in 2D or 3D

Dynamic range, that is the ratio of the largest and smallest values of a quantity, is a crucial characteristic of a sensory system. Our eyes outperform all known biological and technical sensors by orders of magnitude! The dark adapted eye is capable to detect few single photons (Barlow, 1956) whereas vision is also possible in bright sunlight at t...

High blood pressure plays a prominent role in the development of cardiovascular disease such as stroke and myocardial infarction. On the other hand, low blood pressure may also predict cardiovascular disease risk in sub-populations such as in haemodialysis patients (Anker et al., 2016) according to a recent study in almost 5000 patients in an Europ...

Mammals and birds are endothermic animals that control their body temperature very tightly. Keeping the central body temperature within a narrow range allows many essential mechanisms such as kidney function and central nervous activity to operate with high precision. Further this type of thermoregulation allows mammals and birds to be physically a...

The recent discovery that pyrimidines, the fundamental building blocks of all living material, can be created in the laboratory under cosmic conditions (Marlaire, 2015) made the headlines recently. Also, the sophisticated observation technologies used by the NASAs Keppler mission (Batalha, 2014) has made it possible to discover planets that share s...