Lesliestevens1610

In response to preharvest priming with exogenous methyl jasmonate (MeJA), tea plants adjust their physiological behavior at the molecular level. The whole-organism reconfiguration of aroma formation from the precursor to storage is poorly understood. In this study, we performed iTRAQ proteomic analysis and identified 337, 246, and 413 differentially expressed proteins in tea leaves primed with MeJA for 12 h, 24 h, and 48 h, respectively. Furthermore, a total of 266 nonvolatile and 100 volatile differential metabolites were identified by utilizing MS-based metabolomics. A novel approach that incorporated the integration of extended self-organizing map-based dimensionality was applied. The vivid time-scale changes tracing physiological responses in MeJA-primed tea leaves are marked in these maps. Jasmonates responded quickly to the activation of the jasmonic acid pathway in tea leaves, while hydroxyl and glycosyl jasmonates were biosynthesized simultaneously on a massive scale to compensate for the exhausted defense. The levels of α-linolenic acid, geranyl diphosphate, farnesyl diphosphate, geranylgeranyl diphosphate, and phenylalanine, which are crucial aroma precursors, were found to be significantly changed in MeJA-primed tea leaves. Green leaf volatiles, volatile terpenoids, and volatile phenylpropanoids/benzenoids were spontaneously biosynthesized from responding precursors and subsequently converted to their corresponding glycosidic forms, which can be stably stored in tea leaves. This study elucidated the physiological response of tea leaves primed with exogenous methyl jasmonate and revealed the molecular basis of source and sink changes on tea aroma biosynthesis and catabolism in response to exogenous stimuli. The results significantly enhance our comprehensive understanding of tea plant responses to exogenous treatment and will lead to the development of promising biotechnologies to improve fresh tea leaf quality.Trees in temperate regions exhibit evident seasonal patterns, which play vital roles in their growth and development. The activity of cambial stem cells is the basis for regulating the quantity and quality of wood, which has received considerable attention. However, the underlying mechanisms of these processes have not been fully elucidated. Here we performed a comprehensive analysis of morphological observations, transcriptome profiles, the DNA methylome, and miRNAs of the cambium in Populus tomentosa during the transition from dormancy to activation. Anatomical analysis showed that the active cambial zone exhibited a significant increase in the width and number of cell layers compared with those of the dormant and reactivating cambium. Furthermore, we found that differentially expressed genes associated with vascular development were mainly involved in plant hormone signal transduction, cell division and expansion, and cell wall biosynthesis. In addition, we identified 235 known miRNAs and 125 novel miRNAs. Differentially expressed miRNAs and target genes showed stronger negative correlations than other miRNA/target pairs. Moreover, global methylation and transcription analysis revealed that CG gene body methylation was positively correlated with gene expression, whereas CHG exhibited the opposite trend in the downstream region. Most importantly, we observed that the number of CHH differentially methylated region (DMR) changes was the greatest during cambium periodicity. Intriguingly, the genes with hypomethylated CHH DMRs in the promoter were involved in plant hormone signal transduction, phenylpropanoid biosynthesis, and plant-pathogen interactions during vascular cambium development. These findings improve our systems-level understanding of the epigenomic diversity that exists in the annual growth cycle of trees.Clubroot disease, a major plant root disease caused by Plasmodiophora brassicae, has become one of the most destructive diseases among cultivated cruciferous vegetables. However, clubroot-resistant Brassica oleracea materials are rare. Selnoflast cell line A few clubroot-resistant cabbage varieties are available on the market, but all are Ogura cytoplasmic male sterile (CMS) types. Therefore, in this study, to reutilize the clubroot-resistant Ogura CMS germplasm of cabbage, a new fertility-restored Ogura CMS material, 16Q2-11, was used as a bridge to transfer the clubroot resistance (CR) gene from the Ogura CMS cytoplasm to the normal cytoplasm by a two-step method (a fertility restoration and cytoplasm replacement method). In the first cross for fertility restoration of Ogura CMS clubroot-resistant cabbage (FRCRC), 16Q2-11 was used as a restorer to cross with Ogura CMS materials containing the CR gene CRb2. Eleven Rfo-positive progenies were generated, of which four contained CRb2 F8-514, F8-620, F8-732 and F8-839. After inoculation with race 4 of P. brassicae, these four CRb2-positive individuals showed resistance. Furthermore, F8-514 and F8-839 were then used as male parents in the second cross of FRCRC to cross with cabbage inbred lines, resulting in the successful introgression of the CRb2 gene into the inbred lines. All offspring produced from this step of cross, which had a normal cytoplasm, showed a high resistance to race 4 of P. brassicae and could be utilized for the breeding of clubroot-resistant cabbage varieties in the future. This is the first time that the Ogura CMS restorer has been used to restore the fertility of Ogura CMS clubroot-resistant cabbages, which could improve germplasm diversity in cabbage and provide a reference method for using CMS germplasm in Brassica crops.Little is known about noncoding tumor suppressor genes. An effective way to identify these genes is by analyzing somatic copy number variation (CNV)-related noncoding genes. By integrated bioinformatics analyses of differentially expressed long noncoding RNAs (lncRNAs) and arm-level CNVs in lung adenocarcinoma (LUAD), we identified a potential antitumor gene, MIR99AHG, encoding lncRNA MIR99AHG as well as a miR-99a/let-7c/miR-125b2 cluster on chromosome 21q. All four of these transcripts were downregulated in LUAD tissues partly due to the copy number deletion of the MIR99AHG gene. Both MIR99AHG and miR-99a expression was positively correlated with the survival of LUAD patients. MIR99AHG suppressed proliferation and metastasis and promoted autophagy both in vitro and in vivo. Mechanistically, the interaction between MIR99AHG and ANXA2 could accelerate the ANXA2-induced ATG16L+ vesicle biogenesis, thus promoting phagophore assembly. Additionally, miR-99a targeted a well-known autophagy suppressor, mammalian target of rapamycin (mTOR), thereby synergistically promoting autophagy and postponing LUAD progression with MIR99AHG. In summary, MIR99AHG emerges as a noncoding tumor suppressor gene in LUAD, providing a new strategy for antitumor therapy.To sustain their malignancy, tumour cells acquire several metabolic adaptations such as increased oxygen, glucose, glutamine, and lipids uptake. Other metabolic processes are also enhanced as part of tumour metabolic reprogramming, for example, increased serine metabolism. Serine is a non-essential amino acid that supports several metabolic processes that are crucial for the growth and survival of proliferating cells, including protein, DNA, and glutathione synthesis. Indeed, increased activity of D-3-phosphoglycerate dehydrogenase (PHGDH), the enzyme rate-limiting de novo serine synthesis, has been extensively reported in several tumours. Therefore, selective inhibition of PHGDH may represent a new therapeutic strategy for over-expressing PHGDH tumours, owing to its downstream inhibition of essential biomass production such as one-carbon units and nucleotides. This perspective article will discuss the current status of research into small molecular inhibitors against PHGDH in colorectal cancer, breast cancer, and Ewing's sarcoma. We will summarise recent studies on the development of PHGDH-inhibitors, highlighting their clinical potential as new therapeutics. It also wants to shed a light on some of the key limitations of the use of PHGDH-inhibitors in cancer treatment which are worth taking into account.Mental health issues, including major depressive disorder, which can lead to suicidal behavior, are considered by the World Health Organization as a major threat to global health. Alterations in neurotransmitter signaling, e.g., serotonin and glutamate, or inflammatory response have been linked to both MDD and suicide. Phosphodiesterase 8A (PDE8A) gene expression is significantly decreased in the temporal cortex of major depressive disorder (MDD) patients. PDE8A specifically hydrolyzes adenosine 3',5'-cyclic monophosphate (cAMP), which is a key second messenger involved in inflammation, cognition, and chronic antidepressant treatment. Moreover, alterations of RNA editing in PDE8A mRNA has been described in the brain of depressed suicide decedents. Here, we investigated PDE8A A-to-I RNA editing-related modifications in whole blood of depressed patients and suicide attempters compared to age-matched and sex-matched healthy controls. We report significant alterations of RNA editing of PDE8A in the blood of depressed patients and suicide attempters with major depression, for which the suicide attempt took place during the last month before sample collection. The reported RNA editing modifications in whole blood were similar to the changes observed in the brain of suicide decedents. Furthermore, analysis and combinations of different edited isoforms allowed us to discriminate between suicide attempters and control groups. Altogether, our results identify PDE8A as an immune response-related marker whose RNA editing modifications translate from brain to blood, suggesting that monitoring RNA editing in PDE8A in blood samples could help to evaluate depressive state and suicide risk.Inflammatory bowel disease (IBD) is driven by multiple genetic and environmental risk factors. Patients with mutations in Bruton's tyrosine kinase (BTK) is known to manifest high prevalence of intestinal disorders including IBD. Although BTK mediates the signaling of various immune receptors, little is known how BTK maintains the homeostasis of the gut immune system. Here, we show that BTK-deficiency promotes IBD progression in a mouse model of colitis. Interestingly, the increased colitis susceptibility of BTK-deficient mice is not caused by gut microbiota changes but rather arises from enhanced pro-inflammatory Th1 response. More importantly, we find the heightened Th1 response in BTK-deficient mice to result from both T cell-extrinsic and -intrinsic mechanisms. BTK-deficient dendritic cells secret elevated levels of the Th1-polarizing cytokine IL-12 and BTK-deficient T cells are inherently more prone to Th1 differentiation. Thus, BTK plays critical roles in maintaining gut immune homeostasis and preventing inflammation via regulating T-cell polarization.The POU Class Homeobox 2 (POU2F2) is a member of POU transcription factors family, which involves in cell immune response by regulating B cell proliferation and differentiation genes. Recent studies have shown that POU2F2 acts as tumor-promoting roles in some cancers, but the underlying mechanism remains little known. Here, we identified that the highly expressed POU2F2 significantly correlated with poor prognosis of glioblastoma (GBM) patients. POU2F2 promoted cell proliferation and regulated glycolytic reprogramming. Mechanistically, the AKT/mTOR signaling pathway played important roles in the regulation of POU2F2-mediated aerobic glycolysis and cell growth. Furthermore, we demonstrated that POU2F2 activated the transcription of PDPK1 by directly binding to its promoter. Reconstituted the expression of PDPK1 in POU2F2-knockdown GBM cells reactivated AKT/mTOR pathway and recovered cell glycolysis and proliferation, whereas this effect was abolished by the PDPK1/AKT interaction inhibitor. In addition, we showed that POU2F2-PDPK1 axis promoted tumorigenesis by regulating glycolysis in vivo.