Numerous studies have demonstrated that plant species diversity enhances ecosystem functioning in terrestrial ecosystems, including diversity effects on insect arthropods (herbivores, predators and parasitoids) and plants. Yet, the effects of increased plant diversity across trophic levels in different ecosystems and biomes have not yet been explored on a global scale. Through a global meta-analysis of 2914 observations from 351 studies, we found that increased plant species richness reduced herbivore abundance and damage but increased predator and parasitoid abundance, predation, parasitism, and overall plant performance. Moreover, increased predator/parasitoid performance was correlated with reduced herbivore abundance and enhanced plant performance. We

Previous studies show that mortalin, a HSP70 family member, contributes to the development and progression of ovarian cancer. However, details of the transcriptional regulation of mortalin remain unknown. We aimed to determine whether NF‐κB p65 participates in the regulation of mortalin expression in ovarian cancer cells and to elucidate the underlying mechanism. Chromatin immunoprecipitation and luciferase reporter assay were used to identify mortalin gene sequences, to which NF‐κB p65 binds. Results indicated that NF‐κB p65 binds to the mortalin promoter at a site with the sequence ‘CGGGGTTTCA’. Using lentiviral pLVX‐NF‐κB‐puro and Lentivirus‐delivered NF‐κB short hairpin RNA (shRNA), we created ovarian cancer cell lines in which NF‐κB p65 was stably up‐regulated and down‐regulated. Using these cells, we found that downregulation of NF‐κB p65 inhibits the growth and migration of ovarian cancer cells. Further experimental evidence indicated that downregulation of NF‐κB p65 reduced mortalin, and upregulation of mortalin rescued the proliferation and migration of ovarian cancer cells reduced by NF‐κB p65 knockdown. In conclusion, NF‐κB p65 binds to the mortalin promoter and promotes ovarian cancer cells proliferation and migration via regulating mortalin.

A divide and conquer algorithm for exploiting policy function monotonicity is proposed and analyzed. To solve a discrete problem with n states and n choices, the algorithm requires at most nlog2(n)+5n objective function evaluations. In contrast, existing methods for nonconcave problems require n2 evaluations in the worst case. For concave problems, the solution technique can be combined with a method exploiting concavity to reduce evaluations to 14n+2log2(n). A version of the algorithm exploiting monotonicity in two‐state variables allows for even more efficient solutions. The algorithm can also be efficiently employed in a common class of problems that do not have monotone policies, including problems with many state and choice variables. In the sovereign default model of Arellano (2008) and in the real business cycle model, the algorithm reduces run times by an order of magnitude for moderate grid sizes and orders of magnitude for larger ones. Sufficient conditions for monotonicity and code are provided.

Overexpression of Flap endonuclease 1 (FEN1) has been previously implicated in hepatocellular carcinoma (HCC), while its expression features and mechanisms remain unclear. In the current study, differential expression genes (DEGs) were screened in HCC tissues and normal liver tissues in 4 Gene Expression Omnibus (GEO) datasets. FEN1, one of the hub co-overexpressed genes, was further determined overexpressed in HCC tissues in TCGA, local HCC cohorts, and hepatocarcinogenesis model. In addition, high expression of FEN1 indicated poor prognosis of HCC patients. Loss-of-function and gain-of-function assays demonstrated that FEN1 enhanced the proliferation, cell cycle phage transition, migration/ invasion, therapy resistance, xenograft growth, and epithelial-mesenchymal transition (EMT) process of HCC cells. Mechanically, FEN1 could inactivate P53 signaling by preventing the ubiquitination and degradation of mouse double minute 2 (MDM2) via recruiting ubiquitin-specific protease 7 (USP7). Interfering USP7 with P22077 significantly reversed the malignant phenotypes activated by FEN1. In conclusion, this study suggests FEN1 as a robust prognostic biomarker and potential target for HCC.

No abstract

Human E3 ubiquitin protein ligase parkin (Parkin) mediates mitophagy to maintain mitochondrial homeostasis. Parkin mutations are common genetic causes of early onset familial Parkinson's disease. The molecular mechanism of Parkin activation has been widely studied with emerging evidence suggesting an essential role of the phosphorylated (phospho)-ubiquitin interaction. However, the underlying mechanism of the phospho-ubiquitin interaction remains elusive. In the present study, replica exchange molecular dynamics simulations were performed to examine the conformational dynamics of Parkin in monomer and phospho-ubiquitin-bound states. In the Parkin monomer state, high structural flexibilities were observed in the majority of regions of Parkin particularly in the loop domain between the ubiquitin-like (UBL) and really interesting new gene (RING)0 domain. Binding of phospho-ubiquitin stabilizes the RING1/RING in between RING interface but destabilizes the RING1-UBL interface. Furthermore, using steered molecular dynamics simulations of Parkin mutations, it was demonstrated that salt bridge interactions contribute significantly to the interdomain interactions between the RING1 and UBL domain. Taken together, the results of the present study revealed the conformational dynamics of human full-length Parkin in monomer and phospho-ubiquitin-bound states, providing insights into designing potential therapeutics against Parkinson's disease.

The distribution of adrenal chromaffin cells in the control beagle dog was investigated. The presence of chromaffin cells in the adrenal medulla, three zones of the adrenal cortex and capsule was identified by staining with H&E, chromium salts and TH (tyrosine hydroxylase) antibody. With H&E stain, there are morphological differences among the chromaffin cells in the medulla, cortex and capsule. In addition, the number of the capsular chromaffin cells was statistically significantly decreased in the 8-9, 11-12 and 15-16 month age groups compared with the 5-6 month age group. Both medullary and extra-medullary chromaffin cells contained catecholamines, demonstrated via special staining for chromium salts. TH is the first enzyme in catecholamine biosynthesis; it is a useful maker for all cells involved with catecholamine biosynthesis including chromaffin cells. TH antibody confirmed that the extra-medullary cells were chromaffin cells. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay for detecting the apoptotic signalling identified the apoptosis of the chromaffin cells in the capsule.

The aim of this study is to investigate efficacy of a traditional Chinese medicine formula (named Xian-Jia-Tang, XJT) on bladder outlet obstruction (BOO) in rats and explore its mechanisms. Total 80 BOO model rats were established and randomly divided into 4 groups: physiological saline, XJT, Cesium Chloride (CC), and XJT and CC groups. Meanwhile, 12 rats were used as normal control. Bladder weight and urodynamics were measured. Oxidative stress level and mRNA expressions of potassium channels gene were detected in detrusor. The mRNA and protein levels of hypoxia inducible factor-α (HIF-α) in detrusor were detected by RT-PCR and Western blot. BOO model rats showed significantly higher bladder weight and abnormal urodynamics. XJT significantly improved the abnormal urodynamics and inhibited the oxidative stress and changes of mRNA levels of potassium channels genes in detrusor of BOO model rats. Moreover, KATP and SK2/3 mRNA were overexpressed in BOO model rats treated by XJT. Besides, the significantly increased levels of HIF-α mRNA and protein were also inhibited by XJT. However, these inhibition effects of XJT were weakened by CC. XJT could effectively improve the urodynamics and inhibit the oxidative stress caused by hypoxia through suppressing the role of potassium channels in BOO model rats.