The ALK gene encodes a transmembrane tyrosine kinase receptor. ALK is physiologically expressed in the nervous system during embryogenesis, but its expression decreases postnatally. ALK first emerged in the field of oncology in 1994 when it was identified to fuse to NPM1 in anaplastic large‐cell lymphoma. Since then, ALK has been associated with other types of cancers, including non‐small‐cell lung cancer (NSCLC). More than 19 different ALK fusion partners have been discovered in NSCLC, including EML4, KIF5B, KLC1, and TPR. Most of these ALK fusions in NSCLC patients respond well to the ALK inhibitor, crizotinib. In this paper, we reviewed fusion partner genes with ALK, detection methods for ALK‐rearrangement (ALK‐R), and the ALK‐tyrosine kinase inhibitor, crizotinib, used in NSCLC patients.
Previous studies based on microarray analysis have found that DELLAs down-regulate several GDSL genes in unopened flowers and/or imbibed seeds. This suggests the role of DELLAs in seed fatty acid (FA) metabolism. In the present study, enhancement of gibberellin (GA) signalling through DELLA mutation or exogenous gibberellin acid A3 (GA3) resulted in the up-regulated expression of transcription factors for embryogenesis and seed development, genes involved in the FA biosynthesis pathway, and five GDSL-type Seed Fatty Acid Reducer (SFAR) genes. SFAR overexpression reduced the total seed FA content and led to a particular pattern of seed FA composition. This 'SFAR footprint' can also be found in plants with enhanced GA3 signalling. By contrast, the loss of SFAR function dramatically increases the seed FA content. The transgenic lines that overexpress SFAR were less sensitive to stressful environments, reflected by a higher germination rate and better seedling establishment compared with the wild type (WT) plants. The GDSL-type hydrolyzer is a family of proteins largely uncharacterized in Arabidopsis. Their biological function remains poorly understood. SFAR reduces seed FA storage and acts downstream of the GA signalling pathway. We provide the first evidence that some GDSL proteins are somehow involved in FA degradation in Arabidopsis seeds.
These authors contributed equally to this work. SUMMARYTRANSPARENT TESTA2 (TT2) regulates the biosynthesis of proanthocyanidins in the seed coat of Arabidopsis. We recently found that TT2 also participates in inhibition of fatty acid (FA) biosynthesis in the seed embryo. However, the mechanism by which TT2 suppresses the accumulation of seed FA remains unclear. In this study, we show that TT2 is expressed in embryos at an early developmental stage. TT2 is directly bound to the regulatory region of FUSCA3 (FUS3), and mediates the expression of numerous genes in the FA biosynthesis pathway. These genes include BCCP2, CAC2, MOD1 and KASII, which encode proteins involved in the initial steps of FA chain formation, FAD2 and FAD3, which are responsible for FA desaturation, and FAE1, which catalyzes very-long-chain FA elongation. Loss of function of TT2 results in reduced expression of GLAB-RA2 but does not cause a significant reduction in the mucilage attached to the seed coats, which competes with FA for photosynthates. TT2 is expressed in both maternal seed coats and embryonic tissues, but proanthocyanidins are only found in wild-type seed coats and not in embryonic tissues. The amount of proanthocyanidins in the seed coat is negatively correlated with the amount of FAs in the embryo.
Fatty acids (FAs) and FA-derived complex lipids play important roles in plant growth and vegetative development and are a class of prominent metabolites stored in mature seeds. The factors and regulatory networks that control FA accumulation in plant seeds remain largely unknown. The role of TRANSPARENT TESTA8 (TT8) in the regulation of flavonoid biosynthesis and the formation of seed coat color is extensively studied; however, its function in affecting seed FA biosynthesis is poorly understood. In this article, we show that Arabidopsis (Arabidopsis thaliana) TT8 acts maternally to affect seed FA biosynthesis and inhibits seed FA accumulation by down-regulating a group of genes either critical to embryonic development or important in the FA biosynthesis pathway. Moreover, the tt8 mutation resulted in reduced deposition of protein in seeds during maturation. Posttranslational activation of a TT8-GLUCOCORTICOID RECEPTOR fusion protein and chromatin immunoprecipitation assays demonstrated that TT8 represses the activities of LEAFY COTYLEDON1, LEAFY COTYLEDON2, and FUSCA3, the critical transcriptional factors important for seed development, as well as CYTIDINEDIPHOSPHATE DIACYLGLYCEROL SYNTHASE2, which mediates glycerolipid biosynthesis. These results help us to understand the entire function of TT8 and increase our knowledge of the complicated networks regulating the formation of FA-derived complex lipids in plant seeds.
Phomopchalasins A (1) and B (2), two novel cytochalasans with unprecedented carbon skeletons, and phomopchalasin C (3), containing a rare hydroperoxyl motif, were obtained from the endophytic fungus Phomopsis sp. shj2, which was first isolated from the Isodon eriocalyx var. laxiflora. Their structures were elucidated by extensive spectroscopic analyses, electronic circular dichroism (ECD) calculation, and X-ray crystallographic analysis. Notably, 1 possessed an unprecedented 5/6/5/8-fused tetracyclic ring system, and 2 featured a novel 5/6/6/7/5-fused pentacyclic skeleton. The cytotoxic, anti-inflammatory, and antimigratory activities of 1-3 were evaluated in vitro.
Background Return to work following acute myocardial infarction (AMI) is an important outcome and is particularly relevant to young patients. Women may be at a greater risk for not returning to work given evidence of their worse recovery after AMI than similarly aged men. However, sex differences in return to work after AMI has not been studied extensively in a young population (≤55 years). Methods and Results We analyzed data from 1680 AMI patients aged 18–55 years (57% women) participating in the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI patients) who were working full time (≥35 hours) prior to the event. Data were obtained by medical record abstraction and patient interviews. We conducted multivariable regression analyses to examine sex differences in return to work at 12 months after AMI, and the association of patient characteristics with return to work. Compared to young men, young women were less likely to return to work (89% vs. 85%, P=0.018); however this sex difference was not significant after adjusting for patient socio-demographic characteristics, psychosocial factors, and health measures. Being married, engaging in a professional or clerical type of work, having more favorable physical health, and having no prior coronary disease or hypertension were significantly associated with a higher likelihood of return to work at 12 months. Conclusion Among a young population, women are less likely to return to work after AMI than men. This disadvantage is explained by differences in demographic, occupational and health characteristics.
Objective. To find a convenient and efficient way to isolate MSCs from human menstrual blood and to investigate their biological characteristics, proliferative capacity, and secretion levels. Methods. MSCs were isolated from menstrual blood of 3 healthy women using adherence. Cell immunological phenotype was examined by flow cytometry; the adipogenic, osteogenic, and chondrogenic differentiation of MSCs was examined by Oil-Red-O staining, ALP staining, and Alcian Blue staining, respectively; and the secretion of cytokines, including vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1), was detected using enzyme-linked immunosorbent assay. Results. MB-MSCs were successfully isolated from human menstrual blood using adherence. They were positive for CD73, CD105, CD29, and CD44, but negative for CD31 and CD45. The differentiated MB-MSCs were positive for ALP staining, Oil-Red-O staining, and Alcian Blue staining. In addition, they could secrete antiapoptotic cytokines, such as VEGF, IGF-1, and HGF. Conclusion. It is feasible to isolate MSCs from human menstrual blood, thus avoiding invasive procedures and ethical controversies. Adherence could be a promising alternative to the density gradient centrifugation for the isolation of MSCs from menstrual blood.
According to the ‘novel weapons hypothesis’, invasive success depends on harmful plant biochemicals, including allelopathic antimicrobial roots exudate that directly inhibit plant growth and soil microbial activity. However, the combination of direct and soil-mediated impacts of invasive plants via allelopathy remains poorly understood. Here, we addressed the allelopathic effects of an invasive plant species (Rhus typhina) on a cultivated plant (Tagetes erecta), soil properties and microbial communities. We grew T. erecta on soil samples at increasing concentrations of R. typhina root extracts and measured both plant growth and soil physiological profile with community-level physiological profiles (CLPP) using Biolog Eco-plates incubation. We found that R. typhina root extracts inhibit both plant growth and soil microbial activity. Plant height, Root length, soil organic carbon (SOC), total nitrogen (TN) and AWCD were significantly decreased with increasing root extract concentration, and plant above-ground biomass (AGB), below-ground biomass (BGB) and total biomass (TB) were significantly decreased at 10 mg·mL-1 of root extracts. In particular, root extracts significantly reduced the carbon source utilization of carbohydrates, carboxylic acids and polymers, but enhanced phenolic acid. Redundancy analysis shows that soil pH, TN, SOC and EC were the major driving factors of soil microbial activity. Our results indicate that strong allelopathic impact of root extracts on plant growth and soil microbial activity by mimicking roots exudate, providing novel insights into the role of plant–soil microbe interactions in mediating invasion success.
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