Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse

Rab3a is the most abundant Rab (ras-associated binding) protein in the brain and has a regulatory role in synaptic vesicle trafficking. Mice with a targeted loss-of-function mutation in Rab3a have defects in Ca(2+)-dependent synaptic transmission: the number of vesicles released in response to an action potential is greater than in wildtype mice, resulting in greater synaptic depression and the abolishment of CA3 mossy-fiber long term potentiation. The effect of these changes on behavior is unknown. In a screen for mouse mutants with abnormal rest-activity and sleep patterns, we identified a semidominant mutation, called earlybird, that shortens the circadian period of locomotor activity. Sequence analysis of Rab3a identified a point mutation in the conserved amino acid (Asp77Gly) within the GTP-binding domain of this protein in earlybird mutants, resulting in significantly reduced levels of Rab3a protein. Phenotypic assessment of earlybird mice and a null allele of Rab3a revealed anomalies in circadian period and sleep homeostasis, providing evidence that Rab3a-mediated synaptic transmission is involved in these behaviors.     

Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development

To rapidly identify genes required for early vertebrate development, we are carrying out a large-scale, insertional mutagenesis screen in zebrafish, using mouse retroviral vectors as the mutagen. We will obtain mutations in 450 to 500 different genes--roughly 20% of the genes that can be mutated to produce a visible embryonic phenotype in this species--and will clone the majority of the mutated alleles. So far, we have isolated more than 500 insertional mutants. Here we describe the first 75 insertional mutants for which the disrupted genes have been identified. In agreement with chemical mutagenesis screens, approximately one-third of the mutants have developmental defects that affect primarily one or a small number of organs, body shape or swimming behavior; the rest of the mutants show more widespread or pleiotropic abnormalities. Many of the genes we identified have not been previously assigned a biological role in vivo. Roughly 20% of the mutants result from lesions in genes for which the biochemical and cellular function of the proteins they encode cannot be deduced with confidence, if at all, from their predicted amino-acid sequences. All of the genes have either orthologs or clearly related genes in human. These results provide an unbiased view of the genetic construction kit for a vertebrate embryo, reveal the diversity of genes required for vertebrate development and suggest that hundreds of genes of unknown biochemical function essential for vertebrate development have yet to be identified.     

Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration

The neuropathological hallmarks of Alzheimer's disease and other tauopathies include senile plaques and/or neurofibrillary tangles. Although mouse models have been created by overexpressing specific proteins including beta-amyloid precursor protein, presenilin and tau, no model has been generated by gene knockout. Phosphorylation of tau and other proteins on serine or threonine residues preceding proline seems to precede tangle formation and neurodegeneration in Alzheimer's disease. Notably, these phospho(Ser/Thr)-Pro motifs exist in two distinct conformations, whose conversion in some proteins is catalysed by the Pin1 prolyl isomerase. Pin1 activity can directly restore the conformation and function of phosphorylated tau or it can do so indirectly by promoting its dephosphorylation, which suggests that Pin1 is involved in neurodegeneration; however, genetic evidence is lacking. Here we show that Pin1 expression is inversely correlated with predicted neuronal vulnerability and actual neurofibrillary degeneration in Alzheimer's disease. Pin1 knockout in mice causes progressive age-dependent neuropathy characterized by motor and behavioural deficits, tau hyperphosphorylation, tau filament formation and neuronal degeneration. Thus, Pin1 is pivotal in protecting against age-dependent neurodegeneration, providing insight into the pathogenesis and treatment of Alzheimer's disease and other tauopathies.     

黄河沉积物中重金属离子的形态转化及释放研究

以黄河包头段上游清洁河段的沉积物为吸附剂,以Pb^2 、Cu^2 、Zn^2 、Cd^2 等多离子溶液为吸附质,开展了重金属离子被黄河沉积物吸附后的再释放,以及吸附作用对重金属形态转化的影响等实验研究．结果表明,重金属离子被黄河沉积物吸附后,各元素均不转入残渣态,Cu^2 和Zn^2 主要向碳酸盐结合态及铁锰氧化物结合态转化,Pb^2 主要向碳酸盐结合态和可交换态转化;Cd^2 主要转入可交换态和碳酸盐结合态．吸附后的赋存形态决定了Cd^2 的释放量及释放能力远远大于其它3种重金属离子,由Cd^2 排放引起的污染不易消除且影响长久．     

Three-dimensional nonlinear flutter analysis of long-span suspension bridges during erection

In this work, the aerodynamic stability of the Yichang Suspension Bridge over Yangtze River during erection was determined by three-dimensional nonlinear flutter analysis, in which the nonlinearities of structural dynamic characteristics and aeroelastic forces caused by large deformation are fully considered. An interesting result obtained was that the bridge was more stable when the stiffening girders were erected in a non-symmetrical manner as opposed to the traditional symmetrical erection schedule. It was also found that the severe decrease in the aerodynamic stability was due to the nonlinear effects. Therefore, the nonlinear factors should be considered accurately in aerodynamic stability analysis of long-span suspension bridges during erection.     

Signal frequency based self－tuning fuzzy controller for semi－active suspension system

A new kind of fuzzy control scheme, based on the identification of the signal‘ s main frequency and the behavior of the ER damper, is proposed to control the semi-active suspension system. This method ad-justs the fuzzy controller to achieve the best isolation effect by analyzing the main frequency‘ s characters and inspecting the change of system parameters. The input of the fuzzy controller is the main frequency and the op-timal damping ratio is the output. Simulation results indicated that the proposed control method is very effec-tive in isolating the vibration.     

A novel long-chain acyl-derivative of epigallocatechin-3-O-gallate prepared and purified from green tea polyphenols

Lipophilic tea polyphenols (LTP) were prepared by catalytic esterifieation of green tea polyphenols (GRIP) with hexadeeanoyl chloride. A novel long-chain aeyl-derivative of epigalloeateehin-3-o-gallate(EGCG) was first isolated from purification of LTP by high-speed eountereurrent ehromatography (HSCCC)using a solvent system composed of n-hexane-ethyl acetate-methanol-water ( 1 : 1 : 1 : 1, v/v) . The moleeularstructure of the acyl-derivative, Epigallocatechin-3-O-gallate-4‘-O-hexadeeanate , was elucidated by meansof elemental analysis, IR, 1H-NMR and MS spectra.     

随意殴打他人寻衅滋事罪之“随意”的认定

“随意”和“情节恶劣”是我国刑法规定的殴打他人是否构成寻衅滋事罪标准。“随意”是行为人行为时的心理倾向 ,正确把握行为人是否属于“随意”应从行为的对象、时间、原因、动机和地点诸多方面综合考虑