Biology subjects

Manthey, C.

Publications and source records attributed to Manthey, C..

7 recordsLinked to original sources

bioRxiv2025

Contractility governs cardiomyocyte cell cycle activity

The hearts rhythmic contractions keep blood flowing to deliver the oxygen and nutrients that sustain life, but this very strength may also explain why the heart has so little capacity to regenerate. Whereas embryonic and neonatal hearts can repair themselves, this ability is rapidly lost after birth as heart muscle cells (cardiomyocytes) exit the cell cycle. We tested whether the force-generating machinery of the heart acts as a barrier to regeneration. Across human cardiomyocytes, engineered heart tissue, and myocardial slices, we found that active force generation suppresses proliferation, whereas its inhibition, through chemogenetic or pharmacological modulation, enabled cell cycle re-entry. These findings identify contractility as a central regulator of regenerative potential, highlighting new directions for strategies to restore repair in the diseased heart.

cell biology↗

bioRxiv2024

Rapid growth and the evolution of complete metamorphosis in insects

More than 60% of all animal species are insects that undergo complete metamorphosis. The key innovation of these holometabolous insects is a pupal stage between the larva and adult when most structures are completely rebuilt. Why this extreme lifestyle evolved is unclear. Here we test the hypothesis that a trade-off between growth and differentiation explains the evolution of this novelty. Using a comparative approach, we find that holometabolous insects grow much faster than hemimetabolous insects. Using a theoretical model, we then show how holometaboly evolves under a growth-differentiation trade-off and identify conditions under which such temporal decoupling of growth and differentiation is favored. Our work supports the notion that the holometabolous life history evolved to remove developmental constraints on fast growth, primarily under high mortality.

evolutionary biology↗

bioRxiv2022

IMMUNE GENE REGULATION IN THE GUT DURING METAMORPHOSIS IN TWO HOLO- VERSUS A HEMIMETABOLOUS INSECT

During complete metamorphosis, holometabolous insects remodel their entire anatomy, including the gut and must control their microbiota to avoid infectious disease. High activity of antimicrobial peptides and proteins in the gut during metamorphosis has been best described in several Lepidoptera. The immune system of the dipteran Drosophila melanogaster also controls the number of bacteria during metamorphosis. However, little is known about the regulation of immune genes during the larval-adult moult in Hemimetabola which undergo less drastic metamorphic changes. Different patterns of immune effector expression during metamorphosis were shown in a study comparing the lepidopteran Galleria mellonela and the orthopteran Gryllus bimaculatus, where G. mellonella showed a strong up-regulation of antimicrobial peptides in the gut at the larval-pupal moult but not G. bimaculatus. Whether these findings reflect general patterns within holometabolous versus hemimetabolous insects remains unclear. Using RNAseq, we compare the expression of immune effector genes in the gut during metamorphosis in two holometabolous (Calliphora vicina and Tenebrio molitor) and a hemimetabolous insect (Pyrrhocoris apterus). We found high read count abundances of differentially expressed immune effectors in the gut at the larval-pupal moult in C. vicina and T. molitor; no such high abundances were observed at the larval-adult moult in P. apterus. Our findings confirm that only complete metamorphosis elicits a prophylactic immune response as an adaptive response in holometabolous insects, which controls the microbiota during gut replacement.

evolutionary biology↗

bioRxiv2021

Contractile force of transplanted cardiomyocytes contributes to heart function after injury

Transplantation of pluripotent stem cell-derived cardiomyocytes represents an innovative therapeutic strategy for heart failure. Studies in small and large animals have demonstrated functional recovery of left ventricular function after cardiomyocyte transplantation1-4, and first clinical studies are currently underway5. Yet, the mechanism of action underlying graft-induced benefit is unknown6. Here we demonstrate that transplanted cardiomyocytes actively contribute to heart function. We transplanted cardiomyocytes with an optogenetic off-on switch in a guinea pig cardiac injury model. Light-induced inhibition of engrafted cardiomyocyte contractility resulted in a rapid decrease of left ventricular function that was fully reversible with the offset of photostimulation. Hence, our optogenetic approach demonstrated that transplanted cardiomyocytes actively participate in heart function, supporting the hypothesis that the delivery of new force-generating myocardium can serve as a regenerative therapeutic strategy.

pharmacology and toxicology↗

bioRxiv2021

Complete metamorphosis and microbiota turnover in insects

The insects constitute the majority of animal diversity. Most insects are holometabolous: during complete metamorphosis their bodies are radically re-organized. This re-organization poses a significant challenge to the gut microbiota, as the gut is replaced during pupation, a process that does not occur in hemimetabolous insects. In holometabolous hosts, it offers the opportunity to decouple the gut microbiota between the larval and adult life stages resulting in high beta diversity whilst limiting alpha diversity. Here we studied 18 different herbivorous insect species from 5 orders of holometabolous and 3 orders of hemimetabolous insects. Comparing larval and adult specimens, we find a much higher beta-diversity and hence microbiota turnover in holometabolous insects compared to hemimetabolous insects. Alpha diversity did not differ between holo-and hemimetabolous insects nor between developmental stages within these groups. Our results support the idea that pupation offers the opportunity to change the gut microbiota and hence facilitates ecological niche shifts. This effect of niche shift facilitation could explain a selective advantage of the evolution of complete metamorphosis, which is a defining trait of the most speciose insect taxon, the holometabola.

evolutionary biology↗

bioRxiv2021

Comprehensive analysis of chemical and biological problems associated with browning agents used in aquatic studies

Inland waters receive and process large amounts of colored organic matter from the terrestrial surroundings. These inputs dramatically affect the chemical, physical, and biological properties of water bodies, as well as their roles as global carbon sinks and sources. To understand the complex changes associated with allochthonous inputs, experiments are needed. However, manipulative studies, especially at ecosystem scales, require large amounts of dissolved organic matter with optical and chemical properties resembling indigenous organic matter. Here we compared the chemical and biological impacts of two leonardite products (HuminFeed (HF) and SuperHume (SH)) and a freshly derived reverse osmosis concentrate of organic matter (RO) in a set of comprehensive mesocosm- and laboratory-scale experiments and analyses. The chemical properties of RO concentrate and the leonardite products were very different with leonardite products being low and RO being high in carboxylic functional groups. Light had a strong impact on the properties of leonardite products, including loss of color and increased particle formation. Furthermore, HF had drastic impacts on bacteria as light stimulated bacterial production and modified community composition, while dark conditions appeared to inhibit bacterial processes. While none of the browning agents inhibited the growth of the tested phytoplankton, Gonyostomum semen, leonardite products had detrimental effects on zooplankton abundance and Daphnia reproduction. We conclude that the effects of browning agents extracted from leonardite are in sharp contrast to those originating from terrestrially-derived DOM. Hence, they should be used with great caution in experimental studies on the consequences of terrestrial carbon for aquatic systems.

ecology↗

bioRxiv2019

Liver-Chip: Reproducing Human and Cross-Species Toxicities

Nonclinical rodent and non-rodent toxicity models used to support clinical trials of candidate drugs may produce discordant results or fail to predict complications in humans contributing to drug failures in the clinic. Here we applied microengineered Organ-on-Chip (Organ-Chip) technology to design rat, dog, and human Liver-Chips containing species-specific primary hepatocytes interfaced with liver sinusoidal endothelial cells, with or without Kupffer cells and hepatic stellate cells, cultured under physiological fluid flow. The Liver-Chips detected diverse phenotypes of liver toxicity including hepatocellular injury, steatosis, cholestasis, and fibrosis as well as species-specific toxicities when treated with tool compounds. Multi-species Liver-Chips may provide a useful platform for prediction of liver toxicity and inform human relevance of liver toxicities detected in animal studies to better determine safety and human risk.\n\nOne Sentence SummaryMicroengineered Organ-Chip technology has been used to design rat, dog and human Liver-Chips that recapitulate species-specific liver toxicities.

pharmacology and toxicology↗