驱动蛋白定向运动的动力学分析

将布朗粒子的定向运动,看作是系统受到外部非平衡涨落作用的结果,并建立相应的扩散模型。通过蒙特卡罗模拟方法,得到布郎粒子定向梯跳运动曲线。结果表明：非对称锯齿势,外部含时闪烁力及加性色噪声协调与联合作用,可使布朗粒子做梯跳或锯齿运动。作为一种可能的解释,将驱动蛋白Ｋｉｎｅｓｉｎｓ沿微管定向梯跳运动看作是上述协调作用的结果。     

Interactive effect between dietary valine and isoleucine on growth performance,blood parameters and resistance against low salinity stress of Japanese flounder Paralichthys olivaceus

The interaction between dietary valine (Val) and isoleucine (Ile) on growth, blood parameters, and tolerance against low salinity stress of Japanese flounder Paralichthys olivaceus was studied in a 60-day feeding trial. Fish (initial body weight: 3.57 ± 0.05 g) were fed six experimental diets containing different proportions of Ile and Val, two levels of Ile 0% (LI) and 2% diet (HI), combine with three levels of Val 0% (LV), 0.83% (MV), and 2.27% diet (HV), respectively. The results revealed that significant interactive effect of Ile and Val was found on body weight gain and feed conversion ratio, also stimulative effect was found in high Ile groups. Meanwhile, interactive effect of these two amino acids was also observed on high-density lipoprotein (HDL), the maximum of Ile with maximum of Val group has the highest concentration of HDL, which was significantly higher than other groups (p < .05). Moreover, no interaction was found on whole body proximate composition, muscle Ile and Val concentration, and tolerance ability against low salinity stress (reflected by LT₅₀). But high level of Ile combined with high level of Val diet altered tolerance ability against low salinity stress of Japanese flounder. It would be indicated that dietary Ile and Val interacted in the diet of Japanese flounder, and the flounders fed the diet supplemented with 2% Ile and 2.27% Val was superior to the other groups on growth and blood parameters, and tolerance against low salinity stress.     

Harnessing Genetic Diversity in Saccharomyces cerevisiae for Fermentation of Xylose in Hydrolysates of Alkaline Hydrogen Peroxide-Pretreated Biomass

The fermentation of lignocellulose-derived sugars, particularly xylose, into ethanol by the yeast Saccharomyces cerevisiae is known to be inhibited by compounds produced during feedstock pretreatment. We devised a strategy that combined chemical profiling of pretreated feedstocks, high-throughput phenotyping of genetically diverse S. cerevisiae strains isolated from a range of ecological niches, and directed engineering and evolution against identified inhibitors to produce strains with improved fermentation properties. We identified and quantified for the first time the major inhibitory compounds in alkaline hydrogen peroxide (AHP)-pretreated lignocellulosic hydrolysates, including Na⁺, acetate, and p-coumaric (pCA) and ferulic (FA) acids. By phenotyping these yeast strains for their abilities to grow in the presence of these AHP inhibitors, one heterozygous diploid strain tolerant to all four inhibitors was selected, engineered for xylose metabolism, and then allowed to evolve on xylose with increasing amounts of pCA and FA. After only 149 generations, one evolved isolate, GLBRCY87, exhibited faster xylose uptake rates in both laboratory media and AHP switchgrass hydrolysate than its ancestral GLBRCY73 strain and completely converted 115 g/liter of total sugars in undetoxified AHP hydrolysate into more than 40 g/liter ethanol. Strikingly, genome sequencing revealed that during the evolution from GLBRCY73, the GLBRCY87 strain acquired the conversion of heterozygous to homozygous alleles in chromosome VII and amplification of chromosome XIV. Our approach highlights that simultaneous selection on xylose and pCA or FA with a wild S. cerevisiae strain containing inherent tolerance to AHP pretreatment inhibitors has potential for rapid evolution of robust properties in lignocellulosic biofuel production.     

Combination of mTOR and EGFR Kinase Inhibitors Blocks mTORC1 and mTORC2 Kinase Activity and Suppresses the Progression of Colorectal Carcinoma

Mammalian target of rapamycin complex 1 and 2 (mTORC1/2) are overactive in colorectal carcinomas; however, the first generation of mTOR inhibitors such as rapamycin have failed to show clinical benefits in treating colorectal carcinoma in part due to their effects only on mTORC1. The second generation of mTOR inhibitors such as PP242 targets mTOR kinase; thus, they are capable of inhibiting both mTORC1 and mTORC2. To examine the therapeutic potential of the mTOR kinase inhibitors, we treated a panel of colorectal carcinoma cell lines with PP242. Western blotting showed that the PP242 inhibition of mTORC2-mediated AKT phosphorylation at Ser 473 (AKT^S473) was transient only in the first few hours of the PP242 treatment. Receptor tyrosine kinase arrays further revealed that PP242 treatment increased the phosphorylated epidermal growth factor receptor (EGFR) at Tyr 1068 (EGFR^T1068). The parallel increase of AKT^S473 and EGFR^T1068 in the cells following PP242 treatment raised the possibility that EGFR phosphorylation might contribute to the PP242 incomplete inhibition of mTORC2. To test this notion, we showed that the combination of PP242 with erlotinib, an EGFR small molecule inhibitor, blocked both mTORC1 and mTORC2 kinase activity. In addition, we showed that the combination treatment inhibited colony formation, blocked cell growth and induced apoptotic cell death. A systemic administration of PP242 and erlotinib resulted in the progression suppression of colorectal carcinoma xenografts in mice. This study suggests that the combination of mTOR kinase and EGFR inhibitors may provide an effective treatment of colorectal carcinoma.     

Permeation mechanism of a two-state potassium channel

A two-state hopping model was proposed to study the permeation of ion channel.The Nemst equation in equilibrium and the Michaelis-Menten relation in steady state were derived from the two-state kinetic model.The currentvoltage relationship obtained in the symmetrical solutions case was linear when the applied potential was less than 100 mV,which met Ohm's law.The conductance-concentration relationship exhibited the saturation property.Moreover,the characteristic time reaching the steady state of the KcsA channel was also discussed.     

Short- and long-distance signaling in plant defense

When encountering microbial pathogens, plant cells can recognize danger signals derived from pathogens, activate plant immune responses and generate cell-autonomous as well as non-cell-autonomous defense signaling molecules, which promotes defense responses at the infection site and in the neighboring cells. Meanwhile, local damages can result in the release of immunogenic signals including damage-associated molecule patterns and phytocytokines, which also serve as danger signals to potentiate immune responses in cells surrounding the infection site. Activation of local defense responses further induces the production of long-distance defense signals, which can move to distal tissue to activate systemic acquired resistance. In this review, we summarize current knowledge on various signaling molecules involved in short- and long-distance defense signaling, and emphasize the roles of regulatory proteins involved in the processes.     

Novel chitosan/collagen scaffold containing transforming growth factor-beta1 DNA for periodontal tissue engineering

The current rapid progression in tissue engineering and local gene delivery system has enhanced our applications to periodontal tissue engineering. In this study, porous chitosan/collagen scaffolds were prepared through a freeze-drying process, and loaded with plasmid and adenoviral vector encoding human transforming growth factor-beta1 (TGF-beta1). These scaffolds were evaluated in vitro by analysis of microscopic structure, porosity, and cytocompatibility. Human periodontal ligament cells (HPLCs) were seeded in this scaffold, and gene transfection could be traced by green fluorescent protein (GFP). The expression of type I and type III collagen was detected with RT-PCR, and then these scaffolds were implanted subcutaneously into athymic mice. Results indicated that the pore diameter of the gene-combined scaffolds was lower than that of pure chitosan/collagen scaffold. The scaffold containing Ad-TGF-beta1 exhibited the highest proliferation rate, and the expression of type I and type III collagen up-regulated in Ad-TGF-beta1 scaffold. After implanted in vivo, EGFP-transfected HPLCs not only proliferated but also recruited surrounding tissue to grow in the scaffold. This study demonstrated the potential of chitosan/collagen scaffold combined Ad-TGF-beta1 as a good substrate candidate in periodontal tissue engineering.