Residues forming a hydrophobic pocket in ARF3 are determinants of GDP dissociation and effector interactions

Three residues of human ADP-ribosylation factor 3 (ARF3) (F51, W66 and Y81) cluster into a hydrophobic pocket in the inactive, GDP-bound protein. Disruption of the hydrophobic pocket with mutations at these residues increased the rate of GDP dissociation and association, but not always that of GTPgammaS. Several of the same mutants were found to be defective, often selectively, in binding different ARF effectors in two-hybrid assays. These results highlight three features of these hydrophobic residues in regulating (1) the rate of GDP dissociation, (2) the conformational changes that promote GTP binding and (3) their role in binding target proteins.     

Mechanisms and relevant genes of drug resistance in gastric cancer

Gastric cancer (GC) is one of the most common malignancies in China, and chemotherapy is an important treatment for GC. However, drug resistance remains the main barrier to successful chemotherapy. Drug resistance is a complex phenomenon resulting from a combination of factors and mechanisms. The number of known relevant genes implicated in this phenomenon is growing rapidly. This review focuses on the mechanisms involved in the occurrence of drug resistance and explores the functions of several relevant genes in GC chemotherapy resistance.     

Predictive value of plasma copeptin level for the risk and mortality of heart failure: a meta‐analysis

Epidemiologic studies are inconsistent regarding the association between plasma copeptin level and heart failure (HF). The aim of this study was to perform a meta‐analysis to determine whether high level of copeptin is correlated with incidence of HF and mortality in patients with HF. We searched PUBMED and EMBASE databases for studies conducted from 1966 through May 2016 to identify studies reporting hazard ratio (HR) estimates with 95% confidence intervals (CIs) for the association between plasma copeptin level and HF. A random‐effects model was used to combine study‐specific risk estimates. A total of 13 studies were included in the meta‐analysis, with five studies on the incidence of HF and eight studies on the mortality of patients with HF. For incidence of HF, the summary HR indicated a borderline positive association of high plasma copeptin level with HF risk (HR, 1.60; 95% CI, 0.90–2.85). Furthermore, an increase of 1 standard deviation in log copeptin level was associated with a 17% increase in the risk of incident HF (HR, 1.17; 95% CI, 1.02–1.33). For all‐cause mortality of patients with HF, we also found a significant association between elevated plasma copeptin level and increased mortality of HF (HR, 1.76; 95% CI, 1.33–2.33). Our dose–response analysis indicated that an increment in copeptin level of 1 pmol/l was associated with a 3% increase in all‐cause mortality (HR, 1.03; 95% CI, 1.01–1.05). In conclusion, our results suggest that elevated plasma copeptin level is associated with an increased risk of HF and all‐cause mortality in patients with HF.     

Trop-2 targeted CAR-T cells inflict enhanced killing of ovarian cancer cells

T cell modified by chimeric antigen receptor (CAR) is considered one of the most promising tumor therapies for its almost magic effect in the treatment of hematologic malignancies. Encouraged by breakthroughs in this area, we produced Trop-2-redirected chimeric antigen receptor-modified T (Trop-2 CAR-T) cells and tested their function on ovarian cancer cells in vitro molecular cloning. Gene recombination technology was introduced to construct the Trop-2 CAR vector. The expression of Trop-2 CAR on 293T cells was tested by western blot. The effect of Trop-2 CAR-T cells on the proliferation of ovarian cancer cells was evaluated by CCK-8 assay. We found that Trop-2 CAR-T cells prominently inhibited the growth of ovarian cancer cells with Trop-2 antigen expression (P<0.05), moreover, high levels of IFN-γ and IL-2 were detected in supernatant by ELISA (P<0.01). These results suggest that Trop-2 CAR-T cells have the potential to be a clinical treatment for patients with Trop-2 positive ovarian cancer.     

Pre-S Deletion and Complex Mutations of Hepatitis B Virus Related to Young Age Hepatocellular Carcinoma in Qidong,China

Background/Aim

To investigate the roles of biomedical factors, hepatitis B virus (HBV) DNA levels, genotypes, and specific viral mutation patterns on the progression of hepatocellular carcinoma (HCC) patients below 40 years of age in Qidong, China.

Methods

We conducted a case-control study within a cohort of 2387 male HBV carriers who were recruited from August, 1996. The HBV DNA sequence was determined in 49 HCC and 90 chronic hepatitis (CH) patients below 40 years of age. Mutation exchanges during follow-up in 32 cases were compared with 65 controls with paired serum samples. In addition, a consecutive series of samples from 14 HCC cases were employed to compare the sequences before and after the occurrence of HCC.

Results

After adjustment for age, history of cigarette smoking and alcohol consumption, HBeAg positive, HBV DNA levels ≥4.00 log₁₀ copies/mL, pre-S deletion, T1762/A1764 double mutations, and T1766 and/or A1768 mutations were associated with risk of young age HCC. Moreover, the presence of an increasing number of HCC-related mutations (pre-S deletion, T1762/A1764, and T1766 and/or A1768 mutations) was associated with an increased risk of young age HCC. Paired samples analysis indicated that the increased HCC risk for at-risk sequence mutations were attributable to the persistence of these mutations, but not a single time point mutation. The longitudinal observation demonstrated a gradual combination of pre-S deletion, T1762/A1764 double mutations, and T1766 and/or A1768 mutations during the development of HCC.

Conclusion

High HBV DNA levels and pre-S deletion were independent risk factors of young age HCC. Combination of pre-S deletion and core promoter mutations increased the risk and persistence of at-risk sequence mutations is critical for HCC development.     

Drought Stress in Brassica napus: Effects,Tolerance Mechanisms,and Management Strategies

Journal of Plant Growth Regulation - Drought poses serious threats to global crop production and its intensity is continuously soaring due to global warming. Brassica napus L. is an essential...     

Correction to: MKK4/MKK5‑MPK1/MPK2 cascade mediates SA‑activated leaf senescence via phosphorylation of NPR1 in Arabidopsis

Plant Molecular Biology - Due to an unfortunate turn of events, the second co-corresponding author, Dr. Benke Kuai, was omitted from the original publication. The corrected authors’ list and...     

设施黄瓜连作土壤对黄瓜枯萎病菌致病力的影响

为系统研究设施蔬菜连作障碍的发生机制,探讨连作年限对蔬菜土传病害病原菌致病力的影响。本文以山东省德州市王杲铺镇看水庄村不同连作年限的设施黄瓜大棚中采集的土壤样品为研究对象,通过测定其土壤理化性质分析土壤次生盐渍化的程度,并用不同连作年限土壤进行盆栽实验,分析黄瓜植株的生长情况、发病情况及黄瓜枯萎病菌在黄瓜植株内和根际土壤中的定殖情况,研究不同连作年限土壤对黄瓜枯萎病菌致病力的影响。结果表明,所有土壤样品的pH均在8.0以上,呈碱性;土壤样品的全磷含量与pH变化趋势一致;连作8年土壤中黄瓜枯萎病菌在黄瓜植株茎部的定殖数量最多,黄瓜植株的病情指数和发病率最高,说明黄瓜枯萎病菌在黄瓜植株茎部定殖数量多少与黄瓜植株的病情指数和发病率高低的变化趋势一致。综上所述,本研究为设施蔬菜土壤土传病害的防控提供了理论依据。