透析企业经营管理中的帕累托现象

从人力资源管理、企业环境分析和营销管理三个方面阐述帕累托定律在企业经营决策中的体现,具体包括权责分配、决策、绩效考核、激励和市场分析等经营活动,通过透析企业经营管理中的帕累托现象,可以得出:帕累托定律在企业经营管理过程中是不能被忽视的。     

TBX1, a DiGeorge syndrome candidate gene, is inhibited by retinoic acid

Both retinoic acid (RA) and Tbx1 are definitively indispensable for the development of the pharyngeal arches. The defects produced by a loss of Tbx1 highly resemble those induced by hyper- and hypo-RA. Based on these similarities, the effects of RA on Tbx1 expression pattern were explored during pharyngeal arch development in zebrafish. Whole-mount in situ hybridization and real-time quantitative PCR were used. Zebrafish embryos were treated with 5 x 10(-8)mol/L and 10(-7)mol/L RA at 12.5 hours post fertilization for 1.5 hours, respectively. Whole-mount in situ hybridization showed that Tbx1 was expressed in the cardiac region, pharyngeal arch and otic vesicle between 24 hpf and 72 hpf in zebrafish. Tbx1 expression was obviously reduced, even lost, in the pharyngeal arch and outflow tract in RA treated groups. Real-time quantitative PCR analysis showed that Tbx1 expression rose to a peak level at 36 hpf in wild type group. Repression of Tbx1 expression was most evident at 36 hpf, 24 hours after RA treatment. 10(-7 )mol/L RA caused a more severe effect on the Tbx1 expression level than 5 x 10(-8)mol/L RA.The results suggested that RA could produce an altered Tbx1 expression pattern in zebrafish. In addition, RA could repress Tbx1 expression in a dose-dependent manner.     

Transmembrane protein 97 exhibits oncogenic properties via enhancing LRP6-mediated Wnt signaling in breast cancer

Upregulation of transmembrane protein 97 (TMEM97) has been associated with progression and poor outcome in multiple human cancers, including breast cancer. Recent studies suggest that TMEM97 may be involved in the activation of the Wnt/β-catenin pathway. However, the molecular mechanism of TMEM97 action on Wnt/β-catenin signaling is completely unclear. In the current study, TMEM97 was identified as an LRP6-interacting protein. TMEM97 could interact with LRP6 intracellular domain and enhance LRP6-mediated Wnt signaling in a CK1δ/ε-dependent manner. The binding of TMEM97 to LRP6 facilitated the recruitment of CK1δ/ε to LRP6 complex, resulting in LRP6 phosphorylation at Ser 1490 and the stabilization of β-catenin. In breast cancer cells, knockout of TMEM97 attenuated the Wnt/β-catenin signaling cascade via regulating LRP6 phosphorylation, leading to a decrease in the expression of Wnt target genes AXIN2, LEF1, and survivin. TMEM97 deficiency also suppressed cell viability, proliferation, colony formation, migration, invasion, and stemness properties in breast cancer cells. Importantly, TMEM97 knockout suppressed tumor growth through downregulating the Wnt/β-catenin signaling pathway in a breast cancer xenograft model. Taken together, our results revealed that TMEM97 is a positive modulator of canonical Wnt signaling. TMEM97-mediated Wnt signaling is implicated in the tumorigenesis of breast cancer, and its targeted inhibition may be a promising therapeutic strategy for breast cancer.Subject terms: Protein-protein interaction networks, Breast cancer     

A screening of inhibitors targeting the receptor kinase FERONIA reveals small molecules that enhance plant root immunity

Receptor-like kinases (RLKs) constitute the largest receptor family involved in the regulation of plant immunity and growth, but small-molecule inhibitors that target RLKs to improve agronomic traits remain unexplored. The RLK member FERONIA (FER) negatively regulates plant resistance to certain soil-borne diseases that are difficult to control and cause huge losses in crop yields and economy. Here, we identified 33 highly effective FER kinase inhibitors from 1494 small molecules by monitoring FER autophosphorylation in vitro. Four representative inhibitors (reversine, cenisertib, staurosporine and lavendustin A) inhibited the kinase activity of FER and its homologues in several crops by targeting the conserved ATP pocket in the kinase structure. FER contributes to the physiological impact of representative inhibitors in plants. The treatment of roots with reversine, staurosporine and lavendustin A enhanced innate immunity in plant roots and thus alleviated soil-borne diseases in tobacco, tomato and rice without growth penalties. Consistently, RNA sequencing assays showed that lavendustin A and reversine exert profound impacts on immunity-related gene expression. Our results will set a new milestone in the development of the plant RLK kinase regulation theory and provide a novel strategy for the prevention and control of plant soil-borne diseases without growth penalties.     

Sirt1 deacetylates and stabilizes p62 to promote hepato-carcinogenesis

p62/SQSTM1 is frequently up-regulated in many cancers including hepatocellular carcinoma. Highly expressed p62 promotes hepato-carcinogenesis by activating many signaling pathways including Nrf2, mTORC1, and NFκB signaling. However, the underlying mechanism for p62 up-regulation in hepatocellular carcinoma remains largely unclear. Herein, we confirmed that p62 was up-regulated in hepatocellular carcinoma and its higher expression was associated with shorter overall survival in patients. The knockdown of p62 in hepatocellular carcinoma cells decreased cell growth in vitro and in vivo. Intriguingly, p62 protein stability could be reduced by its acetylation at lysine 295, which was regulated by deacetylase Sirt1 and acetyltransferase GCN5. Acetylated p62 increased its association with the E3 ligase Keap1, which facilitated its poly-ubiquitination-dependent proteasomal degradation. Moreover, Sirt1 was up-regulated to deacetylate and stabilize p62 in hepatocellular carcinoma. Additionally, Hepatocyte Sirt1 conditional knockout mice developed much fewer liver tumors after Diethynitrosamine treatment, which could be reversed by the re-introduction of exogenous p62. Taken together, Sirt1 deacetylates p62 at lysine 295 to disturb Keap1-mediated p62 poly-ubiquitination, thus up-regulating p62 expression to promote hepato-carcinogenesis. Therefore, targeting Sirt1 or p62 is a reasonable strategy for the treatment of hepatocellular carcinoma.Subject terms: Cancer, Post-translational modifications     

Changes in the Length of the Neuraminidase Stalk Region Impact H7N9 Virulence in Mice

The neuraminidase stalk of the newly emerged H7N9 influenza virus possesses a 5-amino-acid deletion. This study focuses on characterizing the biological functions of H7N9 with varied neuraminidase stalk lengths. Results indicate that the 5-amino-acid deletion had no impact on virus infectivity or replication in vitro or in vivo compared to that of a virus with a full-length stalk, but enhanced virulence in mice was observed for H7N9 encoding a 19- to 20-amino-acid deletion, suggesting that N9 stalk length impacts virulence in mammals, as N1 stalk length does.     

Endocrine pheromones couple fat rationing to dauer diapause through HNF4α nuclear receptors

Science China Life Sciences - Developmental diapause is a widespread strategy for animals to survive seasonal starvation and environmental harshness. Diapaused animals often ration body fat to...     

Circular RNA circ_103820 suppresses lung cancer tumorigenesis by sponging miR-200b-3p to release LATS2 and SOCS6

A growing number of circular RNAs (circRNAs) have been identified and verified in several cancers. However, highly efficient therapeutic methods based on circRNAs in lung cancer remain largely unexplored. In the present study, we identified a novel circular RNA, hsa_circ_103820, based on Gene Expression Omnibus (GEO) data. Functionally, overexpression of hsa_circ_103820 showed significant inhibitory effects on the proliferation, migration and invasion of lung cancer cells, and knockdown of hsa_circ_103820 played promoting roles. Regarding the mechanism, we revealed that miR-200b-3p was a direct target of hsa_circ_103820 and that LATS2 and SOCS6 were the downstream target genes of miR-200b-3p. Therefore, we identified a novel potential tumor suppressive function of hsa_circ_103820 in lung cancer.Subject terms: RNA, Non-small-cell lung cancer     

Rapid evolutionary trade-offs between resistance to herbivory and tolerance to abiotic stress in an invasive plant

Release from enemies can lead to rapid evolution in invasive plants, including reduced metabolic investment in defence. Conversely, reassociation with enemies leads to renewed evolution of defence, but the potential costs of this evolution are poorly documented. We report increased resistance of the invader Ambrosia artemisiifolia after reassociation with a coevolved specialist herbivore, and that this increase corresponds with reduced abiotic stress tolerance. Herbivore resistance was higher, but drought tolerance was lower in plants from populations with a longer reassociation history, and this corresponded with changes in phenylpropanoids involved in insect resistance and abiotic stress tolerance. These changes were corroborated by shifts in the expression of underlying biosynthetic genes and plant anti-oxidants. Together, our findings suggest rapid evolution of plant traits after reassociation with coevolved enemies, resulting in genetically based shifts in investment between abiotic and biotic stress responses, providing insights into co-evolution, plant invasion and biological control.