Biology subjects

Krieg, T.

Publications and source records attributed to Krieg, T..

6 recordsLinked to original sources

bioRxiv2025

Infarctsize-AI: an efficient infarct size image analysis tool for small rodent myocardial infarction studies

BackgroundMyocardial infarct size (IS) is the gold standard end-point in shorth-term studies on cardioprotection. However, IS quantification in rodent models with standard Evans Blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining is time-consuming and prone to inter-observer variance. Therefore, we aimed to develop an artificial intelligence (AI)-based application to reduce time and inter-observer variability of IS analysis in rodent acute myocardial infarction (MI) models. MethodsWe used TTC/Evans blue-stained heart slice images of independent laboratories from previously published projects. Rat (n = 325 and 248 slices) and mouse (n = 77 slices) datasets were used to train deep learning segmentation models with three different neural network architectures, which were combined into a single AI analysis. AI analysis was compared with manual analysis on rat data from a training laboratory (internal data, n = 496 slices, n = 41 whole-hearts) and data from independent laboratories (external data, n = 60 and 62 slices). Additionally, two independent evaluators performed manual and AI-assisted analysis, consisting of AI-analysis and its manual correction, on internal (n = 36 slices) and external data (n = 37 slices). ResultsLins concordance correlation coefficient (CCC) between IS/AAR values from manual and AI analysis was 0.844 with 95% CI of [0.814; 0.869] for images of internal data heart slices. On external data heart slices, AI accurately annotated slice area and AAR but failed to annotate infarcted area. On internal whole-heart data, CCC between AI and AI-assisted IS/AAR was 0.894 with 95% CI of [0.812; 0.942]. AI-assisted analysis reduced evaluation time on both internal and external datasets and increased region overlap for AAR between the two independent evaluators on dependent data. ConclusionsAI-assisted analysis significantly reduced analysis time and inter-observer variability. For optimal performance, lab-specific AI training is recommended. Infarctsize-AI is available at https://infarctsize.com. Translational perspectiveMyocardial infarct size (IS) is the gold-standard end-point in shorth-term studies to assess potential cardioprotective therapies against acute myocardial infarction (AMI). However, IS quantification in rodent AMI models is time-consuming and prone to inter-observer variance. Therefore, we developed an AI-based software that can reduce analysis time and inter-observer variability and facilitate documentation, which facilitates the clinical translation of potential cardioprotective therapies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=34 SRC="FIGDIR/small/688527v1_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@187c938org.highwire.dtl.DTLVardef@1ab8bb4org.highwire.dtl.DTLVardef@160dc68org.highwire.dtl.DTLVardef@264617_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2025

Optical Brain Pulse Monitoring for Detection of Large Vessel Occlusion Stroke in a Sheep Model

Early stroke detection and treatment are critical for improving patient outcomes. Optical brain pulse monitoring (OBPM) uses red and infrared light to capture brain pulse waveforms reflecting arteriole-to-venous pressure levels driving microvascular blood flow. This study assessed OBPMs potential to detect middle cerebral artery occlusion (MCAo) and reperfusion in a clinically relevant sheep model. Stroke was induced in 11 Merino wethers via 4-hour occlusion of the right MCA, followed by 6 hours of reperfusion. OBPM recordings were taken at baseline, MCAo, early and late reperfusion. The OBPM brain pulse waveform classes were classified based on the presence of arterial or central venous circulation wave features. Magnetic resonance imaging assessed infarct volume at 2 hours post-reperfusion. Invasive brain tissue oxygen and intracranial pressures were also monitored. The OBPM brain pulse waveform classes changed during MCAo and reperfusion (p <0.0001). MCAo was associated brain pulses with venous circulation features (p = 0.0007). Reperfusion was associated with the return of arterial circulation features (p = 0.001). Early reperfusion was also associated with an increase in the brain pulse amplitude (p < 0.05) and the respiratory wave amplitude (p < 0.05). OBPM may aid in early stroke detection and reperfusion assessment following intervention.

physiology↗

bioRxiv2024

Spatially informed phenotyping by cyclic-in-situ-hybridization identifies novel fibroblast populations and their pathogenic niches in systemic sclerosis

Spatially non-resolved transcriptomic data identified functionally distinct populations of fibroblasts in health and disease. However, in-depth transcriptional profiling in situ at single-cell resolution has not been possible so far. Here, we studied fibroblast populations in the skin of SSc patients and healthy individuals using cyclic in situ hybridization (cISH) as a novel approach for spatially-resolved transcriptional phenotyping with subcellular resolution. cISH deconvoluted the heterogeneity of 20,979 cells including 3,764 fibroblasts (FB). BANKSY-based spatially-informed clustering identified nine FB subpopulations, with SFRP2+ RetD FB and CCL19+ nonPV FB as novel subpopulations that reside in specific cellular niches and display unique gene expression profiles. SFRP2+ RetD FB and CCL19+ nonPV FB as well as COL8A1+ FB, display altered frequencies in SSc skin and play specific, disease-promoting roles for extracellular matrix release and leukocyte recruitment as revealed by their transcriptional profile, their cellular interactions and ligand-receptor analyses. The frequencies of COL8A1+ FB and their interactions with monocytic cells and B cells are associated with progression of skin fibrosis in SSc. In summary, our spatially-resolved transcriptomic approach identified novel fibroblast subpopulations deregulated in SSc skin with specific pathogenic roles, some of which may potentially serve as biomarkers for progression of skin fibrosis.

immunology↗

bioRxiv2023

A transient modified mRNA encoding Myc and Cyclin T1 induces cardiac regeneration and improves cardiac function after myocardial injury

Cardiac injury, such as myocardial infarction (MI), results in permanent loss of cardiomyocytes and in many cases heart failure. Transgenic expression of the pro-proliferative transcription factor Myc and Cyclin T1 can drive substantial adult cardiomyocyte proliferation to replace lost cardiomyocytes. Herein, we show that Myc and Cyclin T1 induced cardiomyocyte proliferation leads to myocardial repair and functional (long-term) recovery post-MI in mice. To provide a more translational approach, we developed modified mRNA (modRNA) encoding Myc-Ccnt1 as a transient and non-integrating strategy for regeneration. One dose of Myc-Ccnt1 modRNA is sufficient to transiently drives cardiomyocyte proliferation in human pluripotent stem cell-derived cardiomyocytes and a mouse MI model, where it leads to better heart function. Using single nuclei sequencing and proteomics, we show this was functionally mediated by transcriptional activation of cell-cycle regulating genes, which ultimately results in mitosis and cytokinesis of cardiomyocytes. Collectively, these findings indicate that Myc-Ccnt1 modRNA has the potential to be an effective regenerative therapeutic.

molecular biology↗

bioRxiv2020

Variable environments select for short lifespan

The role of environmental variation in the evolution of lifespan is contested. Classic theory predicts that variable environments favour the evolution of long life, but recent theoretical work suggests that environmental variation can instead select for shorter lifespan when the changes are rapid relative to generation time. Here, we used experimental evolution to study how lifespan evolves in response to temperature variation. Genetically diverse populations of the outcrossing nematode Caenorhabditis remanei, were exposed to a novel, stressful temperature for 30 generations, under stable, gradually warming or fluctuating thermal regimes. We found the evolution of shorter lifespan in populations exposed to environments that fluctuated within the individuals lifetime, compared to populations evolving in stable warm temperature. While climate warming is predicted to increase environmental stochasticity, our results show that fast temperature cycles can rapidly select for short lifespan.

evolutionary biology↗

bioRxiv2019

Environmental variation mediates the evolution of anticipatory parental effects

Theory maintains that when future environment is predictable, parents should adjust the phenotype of their offspring to match the anticipated environment. The plausibility of positive anticipatory parental effects is hotly debated and the experimental evidence for the evolution of such effects is currently lacking. We experimentally investigated the evolution of anticipatory maternal effects in a range of environments that differ drastically in how predictable they are. Populations of the nematode Caenorhabditis remanei, adapted to 20{degrees}C, were exposed to a novel temperature (25{degrees}C) for 30 generations with either positive or zero correlation between parent and offspring environment. We found that populations evolving in novel environments that were predictable across generations evolved a positive anticipatory maternal effect, since they required maternal exposure to 25{degrees}C to achieve maximum reproduction in that temperature. In contrast, populations evolving under zero environmental correlation had lost this anticipatory maternal effect. Similar but weaker patterns were found if instead rate-sensitive population growth was used as a fitness measure. These findings demonstrate that anticipatory parental effects evolve in response to environmental change so that ill-fitting parental effects can be rapidly lost. Evolution of positive anticipatory parental effects can aid population viability in rapidly changing but predictable environments. Impact summaryParents can help their offspring by adjusting offsprings phenotype to match their environment. Such anticipatory parental effects would be beneficial, but only if parents can accurately predict the environment in which their offspring will develop and live. The plausibility of such anticipatory parental effects is hotly debated. The theory is clear that the predictability of the environment should play a defining role. We used an "experimental evolution" approach in a fast reproducing nematode worm Caenorhabditis remanei to tackle this question and follow the evolution of parental effects in different environments in real-time. We found that populations evolving in a novel but predictable environment indeed had anticipatory parental effects that increased fitness of their offspring in that environment. In contrast, when evolving in an unpredictable environment where such parental effects would be disadvantageous, the parental effect was rapidly lost in evolution. Our novel experimental environments were constructed by exposing worms to increased temperature. Anticipatory parental effects play an important role in adaptation to novel environments and will affect the viability of populations under climate heating.

evolutionary biology↗