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Strauch, M.

Publications and source records attributed to Strauch, M..

8 recordsLinked to original sources

GreenSloth: a curated database and executable platform for mechanistic photosynthesis models

Mechanistic models of photosynthesis have expanded substantially over the past decades, covering processes from light reactions to carbon fixation. However, these models remain fragmented across the literature, inconsistently implemented, and difficult to reproduce or reuse, limiting their adoption beyond the research group that developed them. Here, we present GreenSloth, a freely accessible web-based database of 22 published mechanistic photosynthesis models, reimplemented as standardized, executable Python objects within MxlPy, an open-source framework for mechanistic biological modeling. Although the database is primarily designed for dynamic mechanistic models formulated as ordinary differential equations, the current implementation also includes the fields most widely cited steady-state mechanistic model and its variants. GreenSloth provides a structured environment for model discovery, comparison, and reuse, addressing reproducibility challenges in the field and enabling integration into emerging hybrid modeling approaches. It is also interactive: each model runs directly in the browser, with no installation, environment setup, or programming required. The resource is openly accessible and designed for long-term community maintenance, hoping to position itself as foundational infrastructure for the photosynthesis modeling community. Database URLhttps://greensloth.rwth-aachen.de/

systems biology↗

Chronic exposure to low-concentration urban PM2.5 accelerates maladaptive repair after ischemic injury via mitochondrial dysfunction and lysosomal stress.

BackgroundFine particulate matter (PM2.5), airborne particles with an aerodynamic diameter [&le;]2.5 m that can penetrate deep into the lungs and enter the circulation, is increasingly recognized as a risk factor for chronic kidney disease (CKD) with long-term exposure. We previously demonstrated that high-dose PM2.5 exposure prior to ischemia-reperfusion injury (IRI) aggravates acute kidney injury (AKI). Here, we investigated how prolonged, low-concentration urban PM2.5 exposure (<15 {micro}g/m3) affects kidney repair after AKI. MethodsSix-week-old mice underwent bilateral IRI or sham surgery, followed by six months of exposure to either filtered air or ambient PM2.5 exposure in a unique exposome chamber. Kidneys were analyzed using pathomics, electron and super-resolution microscopy, immunohistochemistry, transcriptomics, and LC-MS lipidomics/metabolomics. Complementary in vitro hypoxia-reoxygenation and PM2.5 exposure experiments were performed in proximal tubular epithelial cells. ResultsLong-term PM2.5 exposure had minimal effects in sham-operated mice, including no significant changes in body weight or kidney function. Despite preserved kidney function, IRI+PM2.5 mice exhibited reduced weight gain, a marked expansion of the interstitial area, attributable to enhanced fibrosis and inflammatory responses, microvascular rarefaction, and endothelial-to-mesenchymal transition, consistent with maladaptive repair features. Proximal tubules displayed mitochondrial injury, glycolytic reprogramming, lipid accumulation, and a senescent phenotype. Energy Dispersive X-ray (EDX) microscopy confirmed PM2.5-derived elements within proximal tubules lysosomes, accompanied by lysosomal stress. Transcriptional signature-based drug screening identified nicotinamide as a compound capable of reversing PM2.5-induced metabolic alterations; in vitro validation confirmed restoration of mitochondrial function. ConclusionsTogether, these findings show that chronic post-AKI exposure to PM2.5 at levels currently considered safe by regulatory bodies drives maladaptive repair and accelerates CKD progression through mitochondrial dysfunction, lysosomal stress senescence in proximal tubules, due to local PM2.5 element accumulation. Translational StatementAcute kidney injury frequently progresses to chronic kidney disease due to maladaptive repair, yet environmental drivers of this transition remain underrecognized. Using a controlled exposome chamber, we demonstrate that chronic exposure to low, real-world concentrations of urban PM2.5 during post-ischemic recovery results in the accumulation of PM2.5-derived elements within proximal tubular lysosomes, leading to organelle dysfunction, metabolic reprogramming, lipid accumulation, and a senescence-like phenotype. Importantly, transcriptomics-based drug repurposing identified nicotinamide as a candidate compound capable of reversing metabolic dysfunction in injured proximal tubular cells subjected to hypoxia-reoxygenation and PM2.5 exposure, an effect validated in vitro.

molecular biology↗

Individual dopaminergic neurons induce unique, yet overlapping combinations of behavioural modulations including safety learning, memory retrieval and acute locomotion

Two evolutionary highly conserved functions of dopamine are to carry "teaching" signals during associative learning and to control movement. In mammals and humans, these functions are generally thought to be produced by different populations of neurons. Here, we investigated in the larva of Drosophila melanogaster whether both these functions can be induced by the same individual dopaminergic neurons in the central brain. Focusing on the dopaminergic neurons of the DL1-cluster, we asked whether the optogenetic activation of individual neurons established associative punishment and/or safety memories, controlled the retrieval of the established memories, and acutely modulated locomotion. We found that each neuron had a unique, yet overlapping set of behavioural effects. Several individual neurons both established a memory and modulated acute locomotion by increasing the animals bending and decreasing its velocity. Our results demonstrate that individual dopaminergic neurons can fulfil a surprisingly broad range of functions in different behavioural contexts. Given the highly conserved roles of the dopaminergic system across the animal kingdom, this study raises the question whether a similarly diverse functionality can be found also in other animals, including humans.

neuroscience↗

Neuromuscular dysfunction in patient-derived FUSR244RR-ALS iPSC model via axonal downregulation of neuromuscular junction proteins

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive degeneration of motor neurons, ultimately resulting in death due to respiratory failure. A common feature among ALS cases is the early loss of axons, pointing to defects in axonal transport and translation as initial disease indicators. Here, we established a FUSR244RR-ALS hiPSC-derived model that recapitulates the motor neuron survival and muscle contractility defects characteristic of ALS patients. Analysis of the protein and mRNA expression profiles in axonal and somatodendritic compartments of ALS-afflicted and isogenic control motor neurons revealed a selective downregulation of proteins essential for the neuromuscular junction function in FUS-ALS axons. Furthermore, analysis of FUS CLIP and RIP data showed that FUS binds mRNAs encoding these proteins. This work shed light on the pathogenic mechanisms of ALS and emphasized the importance of axonal gene expression analysis in elucidating the mechanisms of neurodegenerative disorders.

cell biology↗

AFC kinases function as thermosensors that regulate warm temperature-responsive growth in Arabidopsis

Plants respond to elevated temperatures with enhanced elongation growth that depends on rapid transcriptional, post-transcriptional, and post-translational reprogramming. However, it is unclear how temperature information integrates with the splicing machinery to establish warm temperature-dependent splicing patterns. In animals, CDC2-LIKE KINASES (CLKs) function as body temperature sensors that control temperature-dependent splicing via phosphorylation of serine/arginine-rich (SR) proteins. Here we demonstrate that the CLK-homologous ARABIDOPSIS FUS3-COMPLEMENTING (AFC) kinases likewise regulate post-transcriptional RNA processing to control warm temperature-dependent growth in Arabidopsis. The contrasting temperature-activity profiles of the three AFCs depend on specific structural elements, including a conserved activation segment within the kinase domain. Combining protein structure prediction with site-directed mutagenesis, we provide insights into structural features that determine the different temperature-activity profiles of the three AFC paralogs. Analyses of afc mutant plants demonstrate their role in establishing temperature-dependent splicing patterns and thermomorphogenic hypocotyl elongation. Finally, our data indicate SR34 and SR34a as phosphorylation targets mediating temperature-dependent hypocotyl elongation downstream of AFCs. In conclusion, our study provides evidence that temperature-controlled AFC activity is evolutionarily conserved between plants and animals and implicates AFCs in the control of thermomorphogenesis.

plant biology↗

Rewarding capacity of optogenetically activating a giant GABAergic central-brain interneuron in larval Drosophila

Larvae of the fruit fly Drosophila melanogaster are a powerful study case for understanding the neural circuits underlying behavior. Indeed, the numerical simplicity of the larval brain has permitted the reconstruction of its synaptic connectome, and genetic tools for manipulating single, identified neurons allow neural circuit function to be investigated with relative ease and precision. We focus on one of the most complex neurons in the brain of the larva (of either sex), the GABAergic anterior paired lateral neuron (APL). Using behavioral and connectomic analyses, optogenetics, Ca2+ imaging and pharmacology, we study how APL affects associative olfactory memory. We first provide a detailed account of the structure, regional polarity, connectivity, and metamorphic development of APL, and further confirm that optogenetic activation of APL has an inhibiting effect on its main targets, the mushroom body Kenyon cells. All these findings are consistent with the previously identified function of APL in the sparsening of sensory representations. To our surprise, however, we found that optogenetically activating APL can also have a strong rewarding effect. Specifically, APL activation together with odor presentation establishes an odor-specific, appetitive, associative short-term memory, whereas naive olfactory behavior remains unaffected. An acute, systemic inhibition of dopamine synthesis as well as an ablation of the dopaminergic pPAM neurons impair reward learning through APL activation. Our findings provide a study case of complex circuit function in a numerically simple brain, and suggest a previously unrecognized capacity of central-brain GABAergic neurons to engage in dopaminergic reinforcement. Significance statementThe single, identified giant anterior paired lateral (APL) neuron is one of the most complex neurons in the insect brain. It is GABAergic and contributes to the sparsening of neuronal activity in the mushroom body, the memory center of insects. We provide the most detailed account yet of the structure of APL in larval Drosophila as a neurogenetically accessible study case. We further reveal that, contrary to expectations, the experimental activation of APL can exert a rewarding effect, likely via dopaminergic reward pathways. The present study both provides an example of unexpected circuit complexity in a numerically simple brain, and reports an unexpected effect of activity in central-brain GABAergic circuits.

neuroscience↗

Chemical signatures of human odour generate a unique neural code in the brain of Aedes aegypti mosquitoes

A globally invasive form of the mosquito Aedes aegypti specializes in biting humans, making it an efficient vector of dengue, yellow fever, Zika, and chikungunya viruses. Host-seeking females strongly prefer human odour over the odour of non-human animals, but exactly how they distinguish the two is not known. Vertebrate odours are complex blends of volatile chemicals with many shared components, making discrimination an interesting sensory coding challenge. Here we show that human and animal odour blends evoke activity in unique combinations of olfactory glomeruli within the Aedes aegypti antennal lobe. Human blends consistently activate a universal glomerulus, which is equally responsive to diverse animal and nectar-related blends, and a more selective human-sensitive glomerulus. This dual signal robustly distinguishes humans from animals across concentrations, individual humans, and diverse animal species. Remarkably, the human-sensitive glomerulus is narrowly tuned to the long-chain aldehydes decanal and undecanal, which we show are consistently enriched in (though not specific to) human odour and which likely originate from unique human skin lipids. We propose a model of host-odour coding wherein normalization of activity in the human-sensitive glomerulus by that in the broadly-tuned universal glomerulus generates a robust discriminatory signal of the relative concentration of long-chain aldehydes in a host odour blend. Our work demonstrates how animal brains may distil complex odour stimuli of innate biological relevance into simple neural codes and reveals novel targets for the design of next-generation mosquito-control strategies.

neuroscience↗

ATP activation of peritubular cells drives testicular sperm transport

Spermatogenesis, the complex developmental process of male germ cell proliferation, differentiation, and maturation, is the basis of male fertility and reproductive fitness. In the seminiferous tubules of the testes, spermatozoa are constantly generated from spermatogonial stem cells through a stereotyped sequence of mitotic and meiotic divisions. The basic physiological principles, however, that control both maturation and luminal transport of the still immotile spermatozoa within the seminiferous tubules remain poorly, if at all, defined. Here, we show that coordinated contractions of smooth muscle-like testicular peritubular cells provide the propulsive force for luminal sperm transport towards the rete testis and epididymis. Using a mouse model for in vivo imaging, we describe and quantify spontaneous tubular contractions and show a causal relationship between peritubular Ca2+ waves and peristaltic transport. Moreover, we identify P2 receptor-dependent purinergic signaling pathways as physiological triggers of tubular contractions both in vitro and in vivo. When challenged with extracellular ATP, transport of luminal content inside the seminiferous tubules displays stage-dependent directionality. We thus suggest that paracrine purinergic signaling coordinates peristaltic recurrent contractions of the mouse seminiferous tubules to propel immotile spermatozoa to the rete testis. Consequently, our findings could have substantial pharmaceutical implications for both infertility treatment and / or male contraception.

cell biology↗