Negative regulation of ASK1 by p21Cip1 involves a small domain that includes Serine 98 that is phosphorylated by ASK1 in vivo

The cyclin-dependent kinase inhibitor p21(Cip1) regulates multiple cellular functions and protects cells from genotoxic and other cellular stresses. Activation of apoptosis signal-regulating kinase 1 (ASK1) induced by inhibition of mTOR signaling leads to sustained phospho-c-Jun that is suppressed in cells with functional p53 or by forced expression of p21(Cip1). Here we show that small deletions of p21(Cip1) around S98 abrogate its association with ASK1 but do not affect binding to Cdk1, hence distinguishing between the cell cycle-regulating functions of p21(Cip1) and its ability to suppress activation of the ASK1/Jun N-terminal protein kinase (JNK) pathway. p21(Cip1) is phosphorylated in vitro by both ASK1 and JNK1 at S98. In vivo phosphorylation of p21(Cip1), predominantly carried out by ASK1, is associated with binding to ASK1 and inactivation of ASK1 kinase function. Binding of p21(Cip1) to ASK1 requires ASK1 kinase function and may involve phosphorylation of S98.     

A mesoscopic stochastic mechanism of cytosolic calcium oscillations

Based on a model of intracellular calcium (Ca(2+)) oscillation with self-modulation of inositol 1,4,5-trisphosphate signal, the mesoscopic stochastic differential equations for the intracellular Ca(2+) oscillations are theoretically derived by using the chemical Langevin equation method. The effects of the finite biochemical reaction molecule number on both simple and complex cytosolic Ca(2+) oscillations are numerically studied. In the case of simple intracellular Ca(2+) oscillation, it is found that, with the increase of molecule number, the coherence resonance or autonomous resonance phenomena can occur for some external stimulation parameter values. In the cases of complex cytosolic Ca(2+) oscillations, each extremum of concentration of cytosolic Ca(2+) oscillations corresponds to a peak in the histogram of Ca(2+) concentration, and the most probability appeared during the bursting plateau level for bursting, but at the largest minimum of Ca(2+) concentration for chaos. For quasi-periodicity, however, there are only two peaks in the histogram of Ca(2+) concentration, and the most probability is located at low concentration state.     

High-Oleic Peanut Oils Produced by HpRNA-Mediated Gene Silencing of Oleate Desaturase

The quality of peanut oil largely depends on the quantity of oleic (18:1) and linoleic acids (18:2). These two acids comprise more than 80% of the total fatty acids in peanuts. The oleate desaturase (FAD2) gene is important for maintaining high oleic acid content. A partial conservative sequence of the FAD2 gene from peanut was selected. The sense and antisense 260-bp fragments were amplified and subcloned into pFGC1008 binary expression vectors. A total of 21 transgenic plants were obtained via Agrobacterium-mediated transformation. The resulting down-regulation of the FAD2 gene resulted in a 70% increase in oleic acid content in the seeds of transformed plants compared with a 37.93% increase in untransformed plants. The results demonstrated that the target genes were likely suppressed by hpRNA interference, a pathway capable of achieving phenotypic changes. The silencing of FAD2 enabled the development of peanut oils having novel combinations of oleic acid content that can be used in high-value applications, making this approach a reliable technique for the genetic modification of seed quality and the potential for enhancement of other traits as well.     

Molecular analysis of dispersal in giant pandas

Although dispersal in the giant panda (Ailuropoda melanoleuca) is a demographic mechanism which can potentially counteract the negative effect of habitat fragmentation, little is known about dispersal in this species because of difficulties in observing individuals. Using data from faecal microsatellite genotyping, we compared the spatial distribution of giant pandas in two populations and the proximity of relatives in one key population to infer their dispersal pattern. We conclude that giant pandas exhibit female-biased dispersal because: (i) vAIc (variance of assignment index) for females was significantly larger than for males, suggesting that females comprise both 'local' and 'foreign' genotypes; (ii) the average spatial distance of related female dyads was significantly larger than that of males; (iii) larger r (relatedness), F(ST) (genetic variance among populations) and mAIc (mean of assignment index) values were found in males using the software FSTAT, although the differences were not significant; (iv) males set up territories neighbouring to their birth place; (v) significant population structure using microsatellites with a concomitant lack of mitochondrial structure was found in a previous study, possibly indicating more extensive female dispersal; and (vi) female-biased dispersal was strongly supported by evidence from concomitant ecological studies. Considering previous ecological data and life-history characteristics of the giant panda, female-biased dispersal is most likely to be due to competition for birth dens among females, inbreeding avoidance and enhancing inclusive fitness among related males.     

茶条槭及其次生代谢产物没食子酸的研究进展

综述了茶条槭及其次生代谢产物没食子酸的应用价值和目前的研究概况,探讨了利用细胞培养生产没食子酸的前景。     

超声波对猪胰脂肪酶催化活性影响的机理研究

猪胰脂肪酶(porcine pancreas Lipase,PPL)反应系统经适宜参数的超声波处理,催化活性提高了11.22%～24.42%。PPL经超声波处理后,其动力学参数Km和Vmax都变小,酶分子的紫外吸收光谱不变,荧光发射光谱不变。而酶分子经超声波处理后,其紫外差示光谱出现了明显的正峰或负峰。探讨了超声波影响PPL活性的作用机理。     

How dopamine transporter interacts with dopamine: insights from molecular modeling and simulation

By performing homology modeling, molecular docking, and molecular dynamics simulations, we have developed three-dimensional (3D) structural models of both dopamine transporter and dopamine transporter-dopamine complex in the environment of lipid bilayer and solvent water. According to the simulated structure of dopamine transporter-dopamine complex, dopamine was orientated in a hydrophobic pocket at the midpoint of the membrane. The modeled 3D structures provide some detailed structural and mechanistic insights concerning how dopamine transporter (DAT) interacts with dopamine at atomic level, extending our mechanistic understanding of the dopamine reuptake with the help of Na(+) ions. The general features of the modeled 3D structures are consistent with available experimental data. Based on the modeled structures, our calculated binding free energy (DeltaG(bind) = -6.4 kcal/mol) for dopamine binding with DAT is also reasonably close to the experimentally derived DeltaG(bind) value of -7.4 kcal/mol. Finally, a possible dopamine-entry pathway, which involves formation and breaking of the salt bridge between side chains of Arg(85) and Asp(476), is proposed based on the results obtained from the modeling and molecular dynamics simulation. The new structural and mechanistic insights obtained from this computational study are expected to stimulate future, further biochemical and pharmacological studies on the detailed structures and mechanisms of DAT and other homologous transporters.     

MicroRNAs sequencing of plasma exosomes derived from patients with atrial fibrillation: miR-124-3p promotes cardiac fibroblast activation and proliferation by regulating AXIN1

Journal of Physiology and Biochemistry - MicroRNAs (miRNAs) play an important role in the pathogenesis of atrial fibrillation (AF). Exosomal miRNAs may develop as promising biomarkers for AF. To...     

Comparison of echocardiography and 64-slice spiral computed tomography in the diagnosis of congenital heart disease in children

The diagnosis of congenital heart disease in children has been an issue in the medical community. Timely diagnosis and treatment can provide a greater guarantee for children's healthy growth. In recent years, there have been more and more studies on the diagnosis of congenital heart disease in children. This paper compares the advantages and disadvantages of echocardiography and 64-slice spiral computed tomography (CT) in the diagnosis of congenital heart disease in children. In clinical trials, we also tested 64 patients with spiral computed tomography (SCT) and transthoracic echocardiography (TTE) detection of patients and then confirmed the accuracy of the diagnosis by the surgical methods. The two methods of detection, the rate of missed diagnosis, and the rate of misdiagnosis were counted. Through the test results and pathological diagnosis results, the diagnostic accuracy of the two methods were all above 90%, each with its own advantages and disadvantages. The sensitivity of echocardiographic in detecting intracardiac structure abnormalities was relatively high, but when the diagnosis of extracardiac structural abnormalities less than 64-slice spiral CT method, misdiagnosis of TTE was mainly due to extracardiac vascular malformations. Therefore, it is recommended to combine the two methods to improve the diagnosis of congenital heart disease in children.