Alternatively-spliced hypervariable immunoglobulin domainencoding molecules, called Down syndrome cell adhesion molecule (Dscam), have been widely detected as components of the arthropod immune system. Although its ability to specifically bind pathogens and enable phagocytosis of bacteria has been elucidated, the signal transduction mechanisms or effectors that activate post-Dscam-binding pathogens remain poorly characterized. Here, we reveal the alternative splicing exons of Dscam's cytoplasmic tail and its isoforms in the hemocytes of crab (Eriocheir sinensis), showing that the expression of Dscam was acutely induced after an immune challenge, which suggested its functioning for innate immunity. Significantly decreased expression levels of antimicrobial molecular peptides (AMPs) were detected in Dscam-silenced crab hemocytes in vitro, which coincided with their vulnerability to infection by Staphylococcus aureus and higher bacterial concentrations occurring in Dscamsilenced crabs in vivo. Further experimental investigation demonstrated that Dscam-regulated AMP expression via the Src homology (SH)3-binding domain in the first constant exon translated protein of the cytoplasmic tail bound with the SH3 domain of the Dock, an SH3/SH2 adaptor protein required for axon guidance. Dock promoted extracellular signal-regulated kinase (ERK) phosphorylation via indirect binding and then regulated dorsal phosphorylation and translocation from the cytoplasm to the nucleus, subsequently promoting AMP expression for the effective removal of bacteria. To the best of our knowledge, this comprehensive study is the first to highlight the critical role of the alternatively-spliced Dscam cytoplasmic tail in antimicrobial control activity. It also suggests possible crosstalk occurring between Dscam and other pattern recognition receptors.
The rapid development of information and communication technologies has brought the concept of digital economy into the limelight. Data elements have played a more important role in economic production. As an environmentally friendly economic model, the data factor-driven economy, compared to the traditional one, has low energy consumption and less pollution emissions. Hence, the effect of digital economy development on ecological performance is worth exploring. We measured the digital economy index and the ecological performance index for 30 provinces in China. Furthermore, the relationship between the two was analyzed with the help of a dynamic spatial Durbin model. The results showed the following: 1) closely related to the regional economic foundation, the development level of the digital economy showed obvious spatial characteristics that were high in the eastern region and low in the western region in China. 2) Over time, the pattern of ecological performance in China has changed markedly, showing a high level in the south and a low level in the north. 3) The digital economy showed a significant promoting effect on ecological performance, with a strong externality in space that could have a spillover effect on the surrounding areas. 4) The effect of the digital economy on ecological performance had a significant positive effect, although it lagged behind over time. In addition, the effect has regional heterogeneity and was more obvious in developed regions. Based on these findings, we recommend that the role of ICT in economic activity be strengthened in some developed regions. However, in some developing regions, a balance needs to be struck between digitalization and environmental benefits. At the same time, developed regions should be encouraged to realize economic collaboration with developing regions, with the help of data elements in an effort to narrow the regional gap.
ABSTRACT. Variegated plants are highly valuable in the floriculturalmarket, yet the genetic mechanism underlying this attractive phenomenon has not been completely elucidated. In this study, we identified and measured different compounds in pink and white flower petals of peach (Prunus persica) by high-performance liquid chromatography and liquid chromatography/mass spectrometry analyses. No cyanidin-based or pelargonidin-based compounds were detected in white petals, but high levels of these compounds were found in pink petals. Additionally, we sequenced and analyzed the expression of six key structural genes in the anthocyanin biosynthesis pathway (CHI, CHS, DFR, F3'H, ANS, and UFGT) in both white and pink petals. Quantitative real-time polymerase chain reaction revealed all six genes to be expressed at greatly reduced levels in white flower petals, relative to pink. No allelic variations were found in the transcribed sequences. However, alignment of transcribed and genomic sequences of the ANS gene detected alternative splicing, resulting in transcripts (2015) of 1.071 and 942 bp. Only the longer transcript was observed in white flower petals. Since ANS is the key intermediate enzyme catalyzing the colorless leucopelargonidin and leucocyanidin to substrates required for completion of anthocyanin biosynthesis, the ANS gene is implicated in flower color variegation and should be explored in future studies. This article, together with a previous transcriptome study, elucidates the mechanism underlying peach flower color variegation in terms of the key structural genes involved in anthocyanin biosynthesis.
Flaxseed oil is rich in α-linolenic acid (ALA), which is the metabolic precursor of EPA and DHA. The present study investigated the effect of flaxseed oil supplementation on lipopolysaccharide (LPS)-induced muscle atrophy and carbohydrate oxidation impairment in a piglet model. Twenty-four weaned pigs were used in a 2 × 2 factorial experiment including dietary treatment (5 % maize oil v. 5 % flaxseed oil) and LPS challenge (saline v. LPS). On day 21 of treatment, the pigs were injected intraperitoneally with 100 μg/kg body weight LPS or sterile saline. At 4 h after injection, blood, gastrocnemius muscle and longissimus dorsi muscle were collected. Flaxseed oil supplementation increased ALA, EPA, total n-3 PUFA contents, protein:DNA ratio and pyruvate dehydrogenase complex quantity in muscles (P < 0·05). In addition, flaxseed oil reduced mRNA expression of toll-like receptor (TLR) 4 and nucleotide-binding oligomerisation domain protein (NOD) 2 and their downstream signalling molecules in muscles and decreased plasma concentrations of TNF-α, IL-6 and IL-8, and mRNA expression of TNF-α, IL-1β and IL-6 (P < 0·05). Moreover, flaxseed oil inclusion increased the ratios of phosphorylated protein kinase B (Akt) 1:total Akt1 and phosphorylated Forkhead box O (FOXO) 1:total FOXO1 and reduced mRNA expression of FOXO1, muscle RING finger (MuRF) 1 and pyruvate dehydrogenase kinase 4 in muscles (P < 0·05). These results suggest that flaxseed oil might have a positive effect on alleviating muscle protein loss and carbohydrates oxidation impairment induced by LPS challenge through regulation of the TLR4/NOD and Akt/FOXO signalling pathways.
Scope Proliferation and differentiation of intestinal stem cells (ISCs) are crucial for functional restoration after injury, which can be regulated by nutritional molecules. Aspartate is implicated in maintaining intestinal barrier after injury, but underlying mechanisms remain elusive. Here, this study seeks to investigate if aspartate alleviates colonic epithelial damage by regulating ISC function, and to elucidate its mechanisms. Methods and results Eight‐week‐old male C57BL/6 mice supplement with or without 1% L‐aspartate are subjected to drinking water or 2.5% DSS to induce colitis. In this study, aspartate administration alleviates the severity of colitis, as indicated by reduced body weight loss, colon shortening, and inhibited pro‐inflammatory cytokine expression in DSS‐challenged mice. Additionally, aspartate promotes colonic epithelial cell proliferation and differentiation after DSS‐induced damage in mice. Pretreatment with aspartate not only enhances ISC proliferation but also induces ISC differentiation toward enterocytes and goblet cells, which prevent TNF‐α‐induced colonoid damage. Mechanistically, aspartate ameliorates DSS/TNF‐α‐induced perturbation of mitochondrial metabolism and maintains mitochondrial dynamics in colonic epithelium and colonoids. Moreover, aspartate‐mediated ISC proliferation and differentiation are primarily dependent on mitochondrial fusion rather than fission. Conclusions The findings indicate that aspartate promotes ISC proliferation and differentiation to alleviate colonic epithelial damage by regulation of mitochondrial metabolism and dynamics.
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