RNAi-directed downregulation of betaine aldehyde dehydrogenase 1 (OsBADH1) results in decreased stress tolerance and increased oxidative markers without affecting glycine betaine biosynthesis in rice (Oryza sativa)

Chemically inducible gene switches can provide precise control over gene expression, enabling more specific analyses of gene function and expanding the plant biotechnology toolkit beyond traditional constitutive expression systems. The alc gene expression system is one of the most promising chemically inducible gene switches in plants because of its potential in both fundamental research and commercial biotechnology applications. However, there are no published reports demonstrating that this versatile gene switch is functional in transgenic monocotyledonous plants, which include some of the most important agricultural crops. We found that the original alc gene switch was ineffective in the monocotyledonous plant sugar cane, and describe a modified alc system that is functional in this globally significant crop. A promoter consisting of tandem copies of the ethanol receptor inverted repeat binding site, in combination with a minimal promoter sequence, was sufficient to give enhanced sensitivity and significantly higher levels of ethanol inducible gene expression. A longer CaMV 35S minimal promoter than was used in the original alc gene switch also substantially improved ethanol inducibility. Treating the roots with ethanol effectively induced the modified alc system in sugar cane leaves and stem, while an aerial spray was relatively ineffective. The extension of this chemically inducible gene expression system to sugar cane opens the door to new opportunities for basic research and crop biotechnology.     

The overexpression of MCPH1 inhibits cell growth through regulating cell cycle-related proteins and activating cytochrome c-caspase 3 signaling in cervical cancer

MCPH1, initially identified as an hTERT repressor, has recently been implicated in mediating DNA damage response and maintaining chromosome integrity. This study is to investigate its potential role in the onset of cervical cancer. In the study, decreased expression of MCPH1 was observed in 19 of 31 cases (61.3 %) at mRNA level and 44 of 63 cases (69.8 %) at protein level of cervical tumor tissues compared with the paired nontumor tissues. Reduced MCPH1 protein expression was significantly associated with high-tumor grade (1 vs. 3 P = 0.013; 2 vs. 3 P = 0.047). In addition to inhibit SiHa cell migration and invasion, the overexpression of MCPH1 inhibited cervical cancer cells growth through inducing S phase arrest and mitochondrial apoptosis. Further analysis demonstrated cyclinA2/CDK2, CDC25C-cyclinB/CDC2, and p53/p21 pathways were involved in the MCPH1 overexpression-induced S phase arrest. Moreover, the overexpression of MCPH1 activated mitochondrial apoptosis through regulating several apoptosis-related proteins such as p53, Bcl-2, Bax, cytochrome c, caspase-3, and PARP-1. Our findings indicate that downregulated MCPH1 correlates with tumor progression in cervical cancer, and MCPH1 has an important role in regulating cell growth through regulating the cell cycle and apoptosis. Thus, it may be a crucial tumor suppressor gene and a novel candidate therapeutic target for cervical cancer.     

On generalized Simes critical constants

We consider the problem treated by Simes of testing the overall null hypothesis formed by the intersection of a set of elementary null hypotheses based on ordered p‐values of the associated test statistics. The Simes test uses critical constants that do not need tabulation. Cai and Sarkar gave a method to compute generalized Simes critical constants which improve upon the power of the Simes test when more than a few hypotheses are false. The Simes constants can be viewed as the first order (requiring solution of a linear equation) and the Cai‐Sarkar constants as the second order (requiring solution of a quadratic equation) constants. We extend the method to third order (requiring solution of a cubic equation) constants, and also offer an extension to an arbitrary kth order. We show by simulation that the third order constants are more powerful than the second order constants for testing the overall null hypothesis in most cases. However, there are some drawbacks associated with these higher order constants especially for , which limits their practical usefulness.     

Tailoring lignin biosynthesis for efficient and sustainable biofuel production

Increased global interest in a bio‐based economy has reinvigorated the research on the cell wall structure and composition in plants. In particular, the study of plant lignification has become a central focus, with respect to its intractability and negative impact on the utilization of the cell wall biomass for producing biofuels and bio‐based chemicals. Striking progress has been achieved in the last few years both on our fundamental understanding of lignin biosynthesis, deposition and assembly, and on the interplay of lignin synthesis with the plant growth and development. With the knowledge gleaned from basic studies, researchers are now able to invent and develop elegant biotechnological strategies to sophisticatedly manipulate the quantity and structure of lignin and thus to create economically viable bioenergy feedstocks. These concerted efforts open an avenue for the commercial production of cost‐competitive biofuel to meet our energy needs.     

Comparison of GLP-1 Analogues versus Sitagliptin in the Management of Type 2 Diabetes: Systematic Review and Meta-Analysis of Head-to-Head Studies

Background

Incretin–based therapies which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are recommended by several practice guidelines as second-line agents for add-on therapy to metformin in patients with type 2 diabetes (T2DM) who do not achieve glycemic control with metformin plus lifestyle interventions alone. The purpose of this study is to perform a systematic review with meta-analysis of existing head to head studies to compare the efficacy and safety of GLP-1 analogues with DPP-4 inhibitors.

Methods

We performed a systematic review and meta-analysis of head-to-head studies to compare GLP-1 analogues with DPP-4 inhibitors in the management of type 2 diabetes. A random effects model was selected to perform the meta-analyses, results were expressed as weighted mean differences for continuous outcomes and relative risks for dichotomous outcomes, both with 95% confidence intervals, and with I² values and P values as markers of heterogeneity.

Results

Four head-to-head randomized controlled studies with 1755 patients were included. Compared to sitagliptin, GLP-1 analogues are more effective in reducing HbA1C (weight mean difference −0.41%, 95% CI −0.51 to −0.31) and body weight (weight mean difference −1.55 kg, 95% CI −1.98 to −1.12). Conversely, GLP-1 analogues are associated with a higher incidence of gastrointestinal adverse events compared to sitagliptin: nausea (relative risk 3.14, 95% CI 2.15 to 4.59), vomiting (relative risk 2.60, 95% CI 1.48 to 4.56), diarrhea (relative risk 1.82, 95% CI 1.24 to 2.69), and constipation (relative risk 2.50, 95% CI 1.33 to 4.70).

Conclusions

The result of this meta-analysis demonstrates that compared to sitagliptin, GLP-1 analogues are more effective for glycemic control and weight loss, but have similar efficacy in reducing blood pressure and lipid parameters, however, GLP-1 analogues are associated with a higher incidence of gastrointestinal adverse events and a similar incidence of hypoglycemia compared to sitagliptin.     

基于鸟类特有种亚种分化的保护优先性

我们以中国鸟类特有种为代表,基于鸟类物种分化程度来探讨多样性保护优先区。本文参照105种中国特有鸟种的分化等级来制作物种地理分布图。依据生物种的概念,给单型种赋值“1”,对具有n各亚种分化的物种赋值“n”。利用GIS叠加与制图功能对物种的分布做图以反映不同区域的物种分化等级。结果发现分布中心赋值很高并以同心圆形式向周边递减,反映了物种在中国西南部横断山区至秦岭高度分化的地理格局,并由此向外递减。作为全球25个生物多样性热点之一的横断山区,可能不仅是物种种级而且是种下级多样性的热点。因此,该地区的多样性保护优先性,不仅要考虑目前物种多样性分布的格局而且要考虑其未来发展     

低频脉冲电场对PC12细胞酪氨酸羟化酶和多巴胺合成的影响

运用Western印迹和HPLC分别测定不同时间电场刺激和刺激后不同培养时间条件下,PC12细胞内酪氨酸羟化酶(TH)和细胞培养液中多巴胺(DA)含量的变化。结果显示,受到短时间(5、10min)脉冲电场刺激的PC12细胞,经较短时间(2天)的培养后,细胞内TH的含量和培养液中DA的含量均比对照组有所提高,但随着培养时间的延长(3~5天),TH和DA的含量均明显下降。然而,长时间(15、20、30min)脉冲电场刺激组则先表现为TH和DA的合成受到抑制,但随着培养时间的延长,其合成则被逐渐激活。采用蛋白激酶A(PKA)特异性抑制剂H-89和有丝分裂原活化蛋白激酶的激酶(MEK1/2)特异性抑制剂U0126,研究脉冲电场刺激所激活的与TH和DA合成相关的信号通路。结果表明,在没有神经生长因子(NGF)存在的情况下,PC12细胞主要通过PKA通路来激活TH的合成,低频脉冲电场刺激也主要激活PKA通路,因为抑制这条信号通路能显著抑制电场刺激所诱导的TH合成。     

Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts

The receptor tyrosine kinase Tie2, and its activating ligand Angiopoietin-1 (Ang1), are required for vascular remodelling and vessel integrity, whereas Ang2 may counteract these functions. However, it is not known how Tie2 transduces these different signals. Here, we show that Ang1 induces unique Tie2 complexes in mobile and confluent endothelial cells. Matrix-bound Ang1 induced cell adhesion, motility and Tie2 activation in cell-matrix contacts that became translocated to the trailing edge in migrating endothelial cells. In contrast, in contacting cells Ang1 induced Tie2 translocation to cell-cell contacts and the formation of homotypic Tie2-Tie2 trans-associated complexes that included the vascular endothelial phosphotyrosine phosphatase, leading to inhibition of paracellular permeability. Distinct signalling proteins were preferentially activated by Tie2 in the cell-matrix and cell-cell contacts, where Ang2 inhibited Ang1-induced Tie2 activation. This novel type of cellular microenvironment-dependent receptor tyrosine kinase activation may explain some of the effects of angiopoietins in angiogenesis and vessel stabilization.