Integrated metabolomic and transcriptomic analysis reveals factors underlying differences in fruit quality between Fragaria nilgerrensis and Fragaria pentaphylla.

BACKGROUND: Strawberries have become one of the most popular fruits because of their unique flavor and high nutritional value. Fruit quality and price are the most important criteria that determine consumer acceptability. Fragaria nilgerrensis and Fragaria pentaphylla are two wild Asian diploid strawberry species that differ in fruit color, taste, and aroma. To understand the molecular mechanisms involved in the formation of high-quality strawberry fruit, we integrated transcriptomics and metabolomics research methods to compare the metabolic and biosynthetic mechanisms of the two Fragaria species. RESULTS: F. nilgerrensis fruit has higher amino acid and lipid contents and a higher sugar-to-acid ratio than F. pentaphylla fruit does, underlying their superior nutritional value, aroma, firmness, and taste. Compared with F. nilgerrensis fruit, F. pentaphylla fruit contained more flavonoids, indicating its enhanced color and health benefits. In addition, candidate structural genes that regulate the biosynthesis of flavonoids, amino acids, and glycerophospholipids in the two strawberry fruit were screened. CONCLUSIONS: The differences in aroma, firmness, and taste between F. nilgerrensis fruit and F. pentaphylla fruit are probably due to differences in their amino acid and lipid contents, as well as the difference in their sugar-to-acid ratios. Eight key structural genes that may play important roles in the biosynthesis of amino acids, lipids, and flavonoids were identified. © 2021 Society of Chemical Industry.

GDF15 neutralization restores muscle function and physical performance in a mouse model of cancer cachexia.

Cancer cachexia is a disorder characterized by involuntary weight loss and impaired physical performance. Decline in physical performance of patients with cachexia is associated with poor quality of life, and currently there are no effective pharmacological interventions that restore physical performance. Here we examine the effect of GDF15 neutralization in a mouse model of cancer-induced cachexia (TOV21G) that manifests weight loss and muscle function impairments. With comprehensive assessments, our results demonstrate that cachectic mice treated with the anti-GDF15 antibody mAB2 exhibit body weight gain with near-complete restoration of muscle mass and markedly improved muscle function and physical performance. Mechanistically, the improvements induced by GDF15 neutralization are primarily attributed to increased caloric intake, while altered gene expression in cachectic muscles is restored in caloric-intake-dependent and -independent manners. The findings indicate potential of GDF15 neutralization as an effective therapy to enhance physical performance of patients with cachexia.

Identification of Biological Pathways Contributing to Marbling in Skeletal Muscle to Improve Beef Cattle Breeding.

Red meat is an important dietary source that provides part of the nutritional requirements. Intramuscular fat, known as marbling, is located throughout skeletal muscle. Marbling is a trait of major economic relevance that positively influences sensory quality aspects. The aim of the present study was to identify and better understand biological pathways defining marbling in beef cattle. Pathway analysis was performed in PathVisio with publicly available transcriptomic data from semitendinosus muscle of well-marbled and lean-marbled beef. Moreover, for Bos taurus we created a gene identifier mapping database with bridgeDb and a pathway collection in WikiPathways. The regulation of marbling is possibly the result of the interplay between signaling pathways in muscle, fat, and intramuscular connective tissue. Pathway analysis revealed 17 pathways that were significantly different between well-marbled and lean-marbled beef. The MAPK signaling pathway was enriched, and the signaling pathways that play a role in tissue development were also affected. Interestingly, pathways related to immune response and insulin signaling were enriched.

Increased liver carcinogenesis and enrichment of stem cell properties in livers of Dickkopf 2 (Dkk2) deleted mice.

Dkk2 a antagonist of the Wnt/ß-catenin-signaling pathway was shown to be silenced in diverse cancers. More recent data indicate that Dkk family members may also possess functions independent of Wnt-signaling during carcinogenesis. The detailed biological function of Dkks and its relevance for liver cancer is unknown. We analyzed the effects of a genetic deletion of Dkk2 (Dkk2-/-) in a hepatocarcinogenesis model using DEN/Phenobarbital. Untreated Dkk2-/- animals, showed considerable atypia with variation of hepatocyte size and chromatin density. In livers of Dkk2-/- mice nodule formation was seen at 9 months of age with focal loss of trabecular architecture and atypical hepatocytes and after DEN induction Dkk2-/- mice developed significantly more liver tumors compared to controls. Whole transcriptome analysis of untreated Dkk2-/- liver tissue revealed a Dkk2-dependent genetic network involving Wnt/ß-Catenin but also multiple additional oncogenic factors, such as e.g. Pdgf-b, Gdf-15 and Hnf4a. Dkk2-/- tumor cells showed a significant deregulation of stemness genes associated with enhanced colony forming properties. Integration of the Dkk2-/- signature into human data was strongly associated with patients survival. Dkk2 deletion results in alterations of liver morphology leading to an increased frequency of liver cancer. The associated genetic changes included factors not primarily related to Wnt/ß-Catenin-signaling and correlated with the clinical outcome of HCC-patients.