Biology subjects

Engel, E.

Publications and source records attributed to Engel, E..

8 recordsLinked to original sources

bioRxiv2024

L-lactic acid induces short- and long-term cardioprotective effects through MCT1 transport, induction of metabolic reprogramming, and gene expression modulation.

Lactic acid is recognized as an alternative fuel source for various tissues and is acknowledged for its protective effects in the brain. However, its potential as a cardioprotective agent remains controversial. Here, we aimed to (1) evaluate the impact of acute L-lactic acid administration, given at the onset of reperfusion, on myocardial infarct size in isolated mouse hearts submitted to transient global ischemia, (2) assess the effects of chronic L-lactic acid exposure in living myocardial slices (LMS) from human hearts, and (3) elucidate the underlying mechanisms. Isolated mouse hearts were submitted to global ischaemia (35 min) followed by reperfusion (60 min), with L-lactic acid being or not administered during the first 15 min of reperfusion. L-lactic acid reduced infarct size by 23% at 20 mmol/L. An acidic Krebs induced less protection, and monocarboxylate transporter 1 (MCT1) inhibition with AR-C 141990 attenuated L-lactic acids protection to the level of acidic Krebs. 1H NMR spectroscopy revealed significant metabolic changes in L-lactic acid-treated hearts, with pathway enrichment analysis showing a nearly a 3-fold enrichment in pyruvate metabolism, fatty acid biosynthesis, and gluconeogenesis, suggesting a metabolic shift. Moreover, electrically stimulated human LMS treated with L-lactic acid for 48 h exhibited improved contractility and upregulation of structural and functional cardiomyocyte components, stemness-related markers, and pro-angiogenic proteins. These findings support a cardioprotective role for L-lactic acid in both short- and long-term contexts, mediated in part by its uptake through the MCT1 transporter, induction of metabolic reprogramming, and gene expression modulation.

cell biology↗

bioRxiv2024

Impact of Obesity on the CCR6-CCL20 Axis in Epidermal γδ T Cells and IL-17A Production in Murine Wound Healing and Psoriasis

Obesity is associated with comorbidities including type 2 diabetes, chronic nonhealing wounds and psoriasis. Normally skin homeostasis and repair is regulated through the production of cytokines and growth factors derived from skin-resident cells including epidermal {gamma}{delta} T cells. However epidermal {gamma}{delta} T cells exhibit reduced proliferation and defective growth factor and cytokine production during obesity and type 2 diabetes. One of the genes modulated in epidermal {gamma}{delta} T cells during obesity and type 2 diabetes is CCR6, which is the receptor for CCL20. CCL20 is elevated in the skin during obesity and type 2 diabetes. Here we identify a subset of murine epidermal {gamma}{delta} T cells that expresses CCR6 in response to activation in vitro and post-wounding or psoriasis induction with imiquimod in vivo. We show that CCL20 stimulates epidermal {gamma}{delta} T cells to produce IL-17 suggesting CCR6 regulates the IL-17 axis as in dermal {gamma}{delta} T cells. Further, epidermal {gamma}{delta} T cells upregulate CCR6 and produce IL-17 during murine models of wound repair and psoriasis. Obesity increases CCR6 and IL-17 expression by epidermal {gamma}{delta} T cells during wound repair but has less of an effect during psoriasis. These findings have novel implications for the regulation of a specific population of IL-17-producing epidermal {gamma}{delta} T cells during skin damage and inflammation.

immunology↗

bioRxiv2023

Heterogeneity analysis of acute exacerbations of chronic obstructive pulmonary disease and a deep learning framework with weak supervision and privacy protection

11.1 BackgroundChronic obstructive pulmonary disease (COPD) affects 5-10% of the adult US population and is a major cause of mortality. Acute exacerbations of COPD (AECOPDs) are a major driver of COPD morbidity and mortality, but there are no cost-effective methods to identify early AECOPDs when treatment is most likely to reduce the severity and duration of AECOPDs. 1.2 MethodsWe conducted the first long-term (> 12 months), real-time monitoring studies of AECOPD with wearable sensors and self-reporting. We applied a deep learning-based autoencoder for feature extractions, then applied K-means clustering to detect heterogeneity. Accordingly, we proposed a weakly supervised active learning framework to develop anomaly detection models for robust identification of early AECOPD, and a clustered federated learning approach to personalize the anomaly detection models for early detection of heterogeneous subtypes of AECOPD. We evaluated this model by comparing it with other unsupervised learning models and federated learning models. 1.3 FindingsWe identified two clusters based on the Silhouette score and SHAP analysis.One cluster shows high heart rate, low calories, and low steps; and the other has opposite characteristics. We also found out that a single subject could have exacerbation events from both clusters, indicating that there is not only subject-level heterogeneity but also event-level heterogeneity. Our weakly supervised framework outperformed unsupervised methods by 0.06 in average precision with 25 human annotation labels per subject. Our federated learning framework outperformed standard federated learning methods by 0.14 in F1 score and 0.17 in average precision. 1.4 InterpretationWe showed subject-level and event-level heterogeneity in AECOPD using mobile and wearable device data and developed a practical AECOPD detection framework with limited human annotated labels and keeping data private in each device.

bioinformatics↗

bioRxiv2023

Highly pathogenic avian influenza causes mass mortality in Sandwich tern (Thalasseus sandvicensis) breeding colonies across northwestern Europe

AO_SCPLOWBSTRACTC_SCPLOWIn 2022, highly pathogenic avian influenza (HPAI) A(H5N1) virus clade 2.3.4.4b became enzootic and caused mass mortality in Sandwich terns and other seabird species across northwestern Europe. We present data on characteristics of the spread of the virus between breeding colonies and the number of dead adult Sandwich terns recorded at breeding sites throughout northwestern Europe. Within two months after the first mortalities were reported, in total 20,531 adult Sandwich terns were found dead, which is >17% of the total northwestern European breeding population. Losses are likely higher, as we expect that many victims were not found (mortality rate might be up to 74% of the breeding population). Inside the colonies almost all chicks died. After the peak of the outbreak, in a colony established by late breeders, 25.7% of adults showed immunity against HPAI subtype H5. Removal of carcasses helped in reducing the spread of the disease and consequently total mortality. More research on the sources and modes of transmission, incubation times, effective containment and immunity is urgently needed to combat this major threat for colonial seabirds.

ecology↗

bioRxiv2023

Quantification of extracellular matrix components in immunolabeled tissue samples

In recent years, the interaction between cells and the extracellular matrix (ECM) has become a new focus in understanding tissue morphogenesis, regeneration, and disease. However, the lack of specific techniques to study the ECM composition in preserved tissue structures remains a major obstacle to explaining ECM changes in response to extrinsic stimuli. To overcome this, we propose a novel strategy that uses multidimensional fluorescence microscopy and computational tools to quantify ECM composition in immunolabeled tissues and/or cell-derived matrices (CDM). This approach includes a detailed protocol for densitometric fluorescence calibration and procedures for image acquisition, processing, and automated quantification. Using this method, we present new data comparing collagen types I, III, and IV, and fibronectin contents in various tissues. These results emphasize the importance of studying ECM composition in situ under both normal homeostatic and disease conditions. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/535641v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1203e08org.highwire.dtl.DTLVardef@1c88c1borg.highwire.dtl.DTLVardef@1664ac2org.highwire.dtl.DTLVardef@b63154_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2020

Lactate promotes cardiomyocyte dedifferentiation through metabolic reprogramming

Cardiomyocytes undergo different metabolic changes during development and differentiation crucial for their maturation and adult function, such as contraction, growth and survival. Alterations of cardiac metabolism have been associated with multiple disease states and pathological hypertrophy. The shift in substrate preference can impair the stress response, but it may also have a role in cell growth and survival. Here, we evaluated the response of cardiomyocytes to the presence of exogenous lactate, an important metabolite for the fetal heart and cardiogenesis. Lactate-exposed mouse primary cardiomyocytes and human iPSC-derived cardiomyocytes quickly acquired a characteristic dedifferentiated phenotype, with enhanced proliferative capacity as determined by an increased expression of cell cycle (Ki67) and cytokinesis (Aurora-B) effectors. This effect was specific to cardiomyocytes and did not affect other heart cell populations (e.g. cardiac fibroblasts). Nevertheless, cardiac fibroblasts exposed to lactate promoted a pro-regenerative environment through the modulation of the release of cytokines (such as Fas, IL-13 or SDF1a). We characterized lactate-induced cardiomyocyte dedifferentiation through RNA-sequencing and gene expression analysis and identified increased expression of BMP10 (a TGF{beta} family protein involved in embryonic cardiomyocyte proliferation and stemness) and proteins associated to cell fate regulation (LIN28, TCIM) together with downregulation of cardiac maturation genes (GRIK1, DGKK). Bottom-up analysis suggested the phenotype promoted by lactate could be related to the activation of hypoxia signaling pathways. This finding indicated that, indeed, lactate may be a key player of hypoxic regenerative responses in the heart, as it usually accumulates as a result of glycolysis. In addition, ex vivo neonatal heart culture showed prolonged beating function and cardiac tissue integrity when culture media was supplemented with lactate. Thus, we conclude that lactate enhances cardiac proliferation by reprogramming cardiomyocytes towards a dedifferentiated stem cell-like state, supporting the notion that modulation of the metabolic microenvironment might be a powerful novel approach for promoting cardiac regeneration and tissue engineering applications.

bioengineering↗

bioRxiv2019

Andropogon bicornis L. (Poales: Poaceae): a stink bug shelter in the soybean and corn off-season in southern Brazil

Associated host plants promote the survival of various species of pest insects during unfavorable periods. The objective of this study was to evaluate the diversity, abundance and structure of the pentatomid bugs community during the soybean and corn off-season in Andropogon bicornis L. (Poales, Poaceae) plants. The experiment was carried out in the municipality of Cruz Alta, RS, Brazil. During the soybean and corn off-season from 2014 to 2018, clumps of 10 to 50 centimeters in diameter were observed around the growing area. Data on the number of species and abundance of individuals were used for statistical analysis (ANOVA, linear regression and Pearson correlation) and faunistic (diversity and abundance distribution). At the end of the experiment 4050 adults belonging to the species Euschistus heros (F.), Dichelops furcatus (F.), Dichelops melacanthus (Dallas), Edessa meditabunda (F.), Edessa ruformaginata (De Geer) and Piezodorus guildini. Among the species, we found greater abundance for E. meditabunda, E. heros and D. furcatus (96.07%) of the individuals sampled. Higher interspecific correlation was observed between the same species, we also observed a direct effect of the clump diameter on the population density. Among the six species observed, at least five are economically important for soybean and corn crops, so further studies are needed in order to verify the effects of this hibernation site on the population present in the crop and its damages.

ecology↗

bioRxiv2019

Chloris distichophylla Lag. (Poaceae) as stink bug (Pentatomidae) shelter in soybean and corn off-season in southern Brazil

The objective of this study was to evaluate the composition and abundance of dormant bedbugs in Chloris distichophylla Lag (Poales: Poaceae) over the soybean and corn off-season. The work was carried out in the municipality of Cruz Alta, over the soybean and corn off-season between 2014 and 2018. Plants of C. distichophylla with different clump diameter were sampled, and the bugs contained in them were counted and submitted to data analysis for the evaluation of the composition, structure, and diversity of occurring species. At the end of the experiment, 3543 hibernating adults were counted and divided into six species: Euschistus heros (F.), Dichelops furcatus (F.), Dichelops melacanthus Dallas, Edessa meditabunda (F.), Edessa ruformaginata (De Geer) (Hemiptera: Pentatomidae). The species E. heros was the most abundant, followed by D. furcatus. The diameter of the clumps directly affects the population density of the stink bugs. Finally, C. distichophylla is shown as a hibernate favorable to the maintenance of the stink bug populations over the soybean and corn off-season.

ecology↗