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Heuer, S.

Publications and source records attributed to Heuer, S..

4 recordsLinked to original sources

Transcriptome Analysis Reveals Organ-Specific Effects of 2-Deoxyglucose Treatment in Healthy Mice

ObjectiveGlycolytic inhibition via 2-deoxy-D-glucose (2DG) has potential therapeutic benefits for a range of diseases, including cancer, epilepsy, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), and COVID-19, but the systemic effects of 2DG on gene function across different tissues are unclear. MethodsThis study analyzed the transcriptional profiles of nine tissues from C57BL/6J mice treated with 2DG to understand how it modulates pathways systemically. Principal component analysis (PCA), weighted gene co-network analysis (WGCNA), analysis of variance, and pathway analysis were all performed to identify modules altered by 2DG treatment. ResultsPCA revealed that samples clustered predominantly by tissue, suggesting that 2DG affects each tissue uniquely. Unsupervised clustering and WGCNA revealed six distinct tissue-specific modules significantly affected by 2DG, each with unique key pathways and genes. 2DG predominantly affected mitochondrial metabolism in the heart, while in the small intestine, it affected immunological pathways. ConclusionsThese findings suggest that 2DG has a systemic impact that varies across organs, potentially affecting multiple pathways and functions. The study provides insights into the potential therapeutic benefits of 2DG across different diseases and highlights the importance of understanding its systemic effects for future research and clinical applications.

systems biology↗

OsPSTOL1 is prevalent in upland rice and its expression in wheat enhances root growth and hastens low phosphate signaling

PHOSPHORUS-STARVATION TOLERANCE 1 (OsPSTOL1) benefits crown root growth and phosphorus (P) sufficiency in rice (Oryza sativa L.). To better understand the importance of this variably present gene, we carried out a biogeographic survey of landraces and cultivars, confirming that functional OsPSTOL1 alleles prevail in low nutrient and drought-prone rainfed ecosystems, whereas loss-of-function alleles and absence haplotypes predominate in control-irrigated paddy varieties of east Asia. To address the evolutionary history of OsPSTOL1 and related genes in cereal crops, phylogenetic and transcript meta-analyses were performed. Finally, to evaluate its potential value in another Gramineae, wheat (Triticum aestivum L.) lines overexpressing OsPSTOL1 were evaluated under field and controlled low P conditions. OsPSTOL1 enhances growth, crown root number, and overall root plasticity under low P in wheat. Survey of root and shoot crown transcriptomes at two developmental stages identifies transcription factors that are differentially regulated in OsPSTOL1 wheat that are similarly controlled by the gene in rice. In wheat, OsPSTOL1 alters the timing and amplitude of regulators of root development in dry soils and hastens induction of the core P-starvation response. Based on these findings, OsPSTOL1 and related genes may aid more sustainable cultivation of cereal crops. Summary statementMight a rice gene that controls root plasticity confer a similar benefit in another grain crop. Here, we evaluate the genetic variation and evolutionary history of OsPSTOL1 and demonstrate its impact in wheat.

plant biology↗

The effects of brief heat during early booting on reproductive, developmental and physiological performance in common wheat (Triticum aestivum L.)

Rising temperatures due to climate change threaten agricultural crop productivity. As a cool-season crop wheat is heat sensitive, but often exposed to high temperatures during cultivation. In the current study, a bread wheat panel of spring wheat genotypes, including putatively heat-tolerant Australian and CIMMYT genotypes, was exposed to a 5-day mild (34{degrees}C/28{degrees}C, day/night) or extreme (37{degrees}C/27{degrees}C) heat stress during the sensitive pollen developmental stage. Worsening effects on anther morphology were observed as heat stress increased from mild to extreme. Even under mild heat a significant decrease in pollen viability and grain number per spike from primary spike was observed compared with the control (21{degrees}C/15{degrees}C), with Sunstar and two CIMMYT breeding lines performing well. A heat-specific positive correlation between the two traits indicates the important role of pollen fertility for grain setting. Interestingly, both mild and extreme heat induced development of new tillers after the heat stress, providing an alternative sink for accumulated photosynthates and significantly contributing to the final yield. Measurements of flag leaf maximum potential quantum efficiency of Photosystem II (Fv/Fm) showed an initial inhibition after the heat treatment, followed by a full recovery within a few days. Despite this, model fitting using chlorophyll SPAD measurements showed an earlier onset or faster senescence rate under heat stress. The data presented here provide interesting entry points for further research into pollen fertility, tillering dynamics and leaf senescence under heat. The identified tolerant wheat genotypes can be used to dissect the underlying mechanisms and breed climate-resilient wheat.

plant biology↗

Analysis of Gene Expression from Systemic Lupus Erythematosus Synovium Reveals a Profile of Activated Immune Cells and Inflammatory Pathways

Arthritis is a common manifestation of systemic lupus erythematosus (SLE) yet understanding of the underlying pathogenic mechanisms remains incomplete. We, therefore, interrogated gene expression profiles of SLE synovium to gain insight into the nature of lupus arthritis (LA), using osteoarthritis (OA) and rheumatoid arthritis (RA) as comparators. Knee synovia from SLE, OA, and RA patients were analyzed for differentially expressed genes (DEGs) and also by Weighted Gene Co-expression Network Analysis (WGCNA) to identify modules of highly co-expressed genes. Genes upregulated and/or co-expressed in LA revealed numerous immune/inflammatory cells dominated by a myeloid phenotype, whereas OA was characteristic of fibroblasts and RA of T- and B-cells. Upstream regulator analysis identified CD40L and inflammatory cytokines as drivers of the LA gene expression profile. Genes governing trafficking of immune cells into the synovium by chemokines were identified, but not in situ generation of germinal centers. GSVA confirmed activation of specific myeloid and lymphoid cell types in LA. Numerous therapies were predicted to target LA, including TNF, NF{kappa}B, MAPK, and CDK inhibitors. Detailed gene expression analysis identified a unique pattern of cellular components and physiologic pathways operative in LA, as well as drugs potentially able to target this common manifestation of SLE.

immunology↗