An additive‐multiplicative mean residual life model for right‐censored data

Many studies have focused on determining the effect of the body mass index (BMI) on the mortality in different cohorts. In this article, we propose an additive‐multiplicative mean residual life (MRL) model to assess the effects of BMI and other risk factors on the MRL function of survival time in a cohort of Chinese type 2 diabetic patients. The proposed model can simultaneously manage additive and multiplicative risk factors and provide a comprehensible interpretation of their effects on the MRL function of interest. We develop an estimation procedure through pseudo partial score equations to obtain parameter estimates. We establish the asymptotic properties of the proposed estimators and conduct simulations to demonstrate the performance of the proposed method. The application of the procedure to a study on the life expectancy of type 2 diabetic patients reveals new insights into the extension of the life expectancy of such patients.     

Feature screening with latent responses

A novel feature screening method is proposed to examine the correlation between latent responses and potential predictors in ultrahigh-dimensional data analysis. First, a confirmatory factor analysis (CFA) model is used to characterize latent responses through multiple observed variables. The expectation-maximization algorithm is employed to estimate the parameters in the CFA model. Second, R-Vector (RV) correlation is used to measure the dependence between the multivariate latent responses and covariates of interest. Third, a feature screening procedure is proposed on the basis of an unbiased estimator of the RV coefficient. The sure screening property of the proposed screening procedure is established under certain mild conditions. Monte Carlo simulations are conducted to assess the finite-sample performance of the feature screening procedure. The proposed method is applied to an investigation of the relationship between psychological well-being and the human genome.     

Impact of MtrA on phosphate metabolism genes and the response to altered phosphate conditions in Streptomyces

Phosphate metabolism is known to be regulated by the PhoPR regulatory system in Streptomyces and some other bacteria. In this study, we report that MtrA also regulates phosphate metabolism in Streptomyces. Our data showed that, in Streptomyces coelicolor, MtrA regulates not only phosphate metabolism genes such as phoA but also phoP under different phosphate conditions, including growth on rich complex media without added inorganic phosphate and on defined media with low or high concentrations of inorganic phosphate. Cross-regulation was also observed among mtrA, phoP and glnR under these conditions. We demonstrated both in vitro and in vivo binding of MtrA to the promoter regions of genes associated with phosphate metabolism and to the intergenic region between phoR and phoU, indicating that these phosphate metabolism genes are targets of MtrA. We further showed that MtrA in S. lividans and S. venezuelae has detectable regulatory effects on expression of phosphate metabolism genes. Additionally, the MtrA homologue from Corynebacterium glutamicum bound predicted MtrA sites of multiple phosphate metabolism genes, implying its potential for regulating phosphate metabolism in this species. Overall, our findings support MtrA as a major regulator for phosphate metabolism in Streptomyces and also potentially in other actinobacteria.     

不同沙化阶段高寒草甸植物群落与表土环境因子的关系

沙漠化是玛曲高寒草甸最为严重的生态问题之一，明晰区域内不同沙化阶段植物群落与表土环境因子的关系，有助于为玛曲高寒草甸沙漠化的监测与防治提供科学参考。鉴于此，研究应用方差分析与典范对应分析，厘清了潜在、轻度、中度、重度和极重度沙化阶段植物的组成格局与变化规律，并对其与表土环境因子的关系进行了分析。结果表明：（1）伴随沙漠化的发展，表土水分与电导率呈逐步降低的趋势，下降幅度显著（P<0.05）；温度呈先降低后增加的变化规律，其中轻度沙化阶段最低，为24.32℃，极重度阶段最高，达30.79℃；（2）伴随沙漠化的发展，植物的盖度、多度依次降低，下降幅度显著（P<0.05）；物种丰富度、Shannon-Wiener指数、Simpson指数与Pielou指数的变化趋势相近，呈潜在至轻度阶段上升，之后逐步下降的规律；（3）典范对应分析（CCA）表明，表土水分和电导率对群落组成的影响程度达到极显著水平（P<0.01）。潜在与轻度沙化阶段，CCA前两轴的方差解释率分别是71.91%和55.25%，表土环境因子能够较好的描述植物群落特征与多样性水平的变化规律；中度、重度和极重度沙化阶段，CCA前两轴的方差解释率不足40%，表土环境因子难以有效表征植物群落特征，预示放牧等人类活动在这些演替阶段的影响更为突出。     

Expression of CAMK1 and its association with clinicopathologic characteristics in pancreatic cancer

Calcium/calmodulin-dependent protein kinase (CAMKs) can control a wide range of cancer-related functions in multiple tumour types. Herein, we explore the expressions and clinical significances of calcium/calmodulin-dependent protein kinase 1 (CAMK1) in pancreatic cancer (PC). The expression of CAMK1 in PC was analysed by Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) database and the Oncomine database. For further validation, the protein level of CAMK1 in PC tissues was also detected in the Human Protein Atlas (HPA) database and the tissue microarray (TMA)-based immunohistochemistry (IHC). GEPIA 2 and Kaplan-Meier Plotter (KM Plotter) databases were used to explore the prognostic significances of CAMK1 in overall survival (OS) and disease-free survival (DFS) of PC at mRNA level. The relationship between CAMK1 expression and the clinicopathological characteristics of PC was further explored. Additionally, the Search Tool for the Retrieval of Interacting Genes (STRING) database was used to analyse protein-protein interactions (PPI). We found CAMK1 was highly expressed in PC both in bioinformatics analyses and TMA-IHC results. The prognostic analyses from the public databases also showed consistent results with follow-up data. The PPI network suggested that CALM1, CALM3, CREB1, CALM2, SYN1, NOS3, ATF1, GAPDH, PPM1F and FBXL12 were important significant genes associated with CAMK1. Our finding revealed CAMK1 has prognostic value in PC patients, suggesting that CAMK1 may has a distinct role in PC patients and can be used as a candidate marker for investigating clinical prognosis of PC.     

Schistosoma japonicum: A comparison of the development of the parasite and associated pathological changes in mice and jirds (Meriones unguiculatus)

In this paper an attempt is made to compare the development of Schistosoma japonicum in Meriones unguiculatus and in mice, as well as the associated pathological changes. Total worm recovery was lower and worm development more rapid in jirds than in mice but there was no obvious difference in the copulation rate of worms in the two hosts. Differences observed in the pathological lesions indicate that those which develop in jirds bear a stronger resemblance to those seen in man than do the corresponding changes in mice, and that the immune reactions elicited against egg antigens is stronger in jirds. It is concluded that M. unguiculatus may serve as a useful experimental model for studies on the immunopathology of Schistosomiasis japonicum.     

Growth pattern of Picea rubens prior to canopy recruitment

A majority (72%) of Picea rubens Sarg. (red spruce) trees in an old-growth spruce-fir forest in the Great Smoky Mountains underwent episodes of radial growth suppression and release before they reached the forest canopy. Prior to canopy recruitment, trees experienced an average of 1.43 and a maximum of 7 suppression periods with an average ring width of 0.257 mm. Duration of suppression periods ranged from 4 to 79 years with an average of 19.05 years, which was significantly shorter than the average duration of release periods (29.00 years). Mean ring width in a suppression period was negatively correlated with duration of the suppression period. The opposite was true for release periods. The severity of suppression had no significant effect on mean ring width in subsequent release periods. Greater suppression was observed in the recent growth pattern of current non-canopy trees than in the historical growth pattern reconstructed from current canopy trees. Growth releases prior to canopy recruitment, triggered by small gaps or neighboring gaps, displayed a continuous pattern over the last two centuries and had consistent frequency in recent decades. By contrast, canopy recruitment resulting from large-gap disturbances was discontinuous over the last two centuries, and less frequent after 1850.     

KIF2C: a novel link between Wnt/β-catenin and mTORC1 signaling in the pathogenesis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide. HCC is refractory to many standard cancer treatments and the prognosis is often poor, highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments. Kinesin family member 2C (KIF2C) is reported to be highly expressed in several human tumors. Nevertheless, the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated. In this study, we found that KIF2C expression was significantly upregulated in HCC, and that KIF2C up-regulation was associated with a poor prognosis. Utilizing both gain and loss of function assays, we showed that KIF2C promoted HCC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Additionally, we found that KIF2C is a direct target of the Wnt/β-catenin pathway, and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORC1 signaling. Thus, the results of our study establish a link between Wnt/β-catenin and mTORC1 signaling, which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.Electronic supplementary materialThe online version of this article (10.1007/s13238-020-00766-y) contains supplementary material, which is available to authorized users.