Synapsin I bundles F-actin in a phosphorylation-dependent manner

Synapsin I is a neuron-specific phosphoprotein localized to the cytoplasmic surface of synaptic vesicles. This phosphoprotein is a major substrate for cyclic AMP-dependent and calcium/calmodulin-dependent protein kinases. Its state of phosphorylation can be altered both in vivo and in vitro by a variety of physiological and pharmacological manipulations known to affect synaptic function. Recent direct evidence suggests that it may be involved in the regulation of neurotransmitter release from the nerve terminal. In the nerve terminal, synaptic vesicles are embedded in a cytoskeletal network, consisting in part of actin. We report here the ability of the dephospho-form of synapsin I to bundle F-actin. This bundling activity is reduced when synapsin I is phosphorylated by cAMP-dependent protein kinase and virtually abolished when it is phosphorylated by calcium/calmodulin-dependent protein kinase II or by both kinases. These results, demonstrating an interaction of synapsin I with actin in vitro, support the possibility that synapsin I is involved in clustering of synaptic vesicles at the presynaptic terminal and that the phosphorylation of synapsin I may be involved in regulating the translocation of synaptic vesicles to their sites of release.     

RNAi-mediated gene silencing in non-human primates

The opportunity to harness the RNA interference (RNAi) pathway to silence disease-causing genes holds great promise for the development of therapeutics directed against targets that are otherwise not addressable with current medicines. Although there are numerous examples of in vivo silencing of target genes after local delivery of small interfering RNAs (siRNAs), there remain only a few reports of RNAi-mediated silencing in response to systemic delivery of siRNA, and there are no reports of systemic efficacy in non-rodent species. Here we show that siRNAs, when delivered systemically in a liposomal formulation, can silence the disease target apolipoprotein B (ApoB) in non-human primates. APOB-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP) and administered by intravenous injection to cynomolgus monkeys at doses of 1 or 2.5 mg kg(-1). A single siRNA injection resulted in dose-dependent silencing of APOB messenger RNA expression in the liver 48 h after administration, with maximal silencing of >90%. This silencing effect occurred as a result of APOB mRNA cleavage at precisely the site predicted for the RNAi mechanism. Significant reductions in ApoB protein, serum cholesterol and low-density lipoprotein levels were observed as early as 24 h after treatment and lasted for 11 days at the highest siRNA dose, thus demonstrating an immediate, potent and lasting biological effect of siRNA treatment. Our findings show clinically relevant RNAi-mediated gene silencing in non-human primates, supporting RNAi therapeutics as a potential new class of drugs.     

Enhancements of energetic particles near the heliospheric termination shock

The spacecraft Voyager 1 is at a distance greater than 85 au from the Sun, in the vicinity of the termination shock that marks the abrupt slowing of the supersonic solar wind and the beginning of the extended and unexplored distant heliosphere. This shock is expected to accelerate 'anomalous cosmic rays', as well as to re-accelerate Galactic cosmic rays and low-energy particles from the inner Solar System. Here we report a significant increase in the numbers of energetic ions and electrons that persisted for seven months beginning in mid-2002. This increase differs from any previously observed in that there was a simultaneous increase in Galactic cosmic ray ions and electrons, anomalous cosmic rays and low-energy ions. The low-intensity level and spectral energy distribution of the anomalous cosmic rays, however, indicates that Voyager 1 still has not reached the termination shock. Rather, the observed increase is an expected precursor event. We argue that the radial anisotropy of the cosmic rays is expected to be small in the foreshock region, as is observed.     

A general model for ontogenetic growth.

Several equations have been proposed to describe ontogenetic growth trajectories for organisms justified primarily on the goodness of fit rather than on any biological mechanism. Here, we derive a general quantitative model based on fundamental principles for the allocation of metabolic energy between maintenance of existing tissue and the production of new biomass. We thus predict the parameters governing growth curves from basic cellular properties and derive a single parameterless universal curve that describes the growth of many diverse species. The model provides the basis for deriving allometric relationships for growth rates and the timing of life history events.     

Analysis of the formation conditions and characteristics of interphase and random vanadium precipitation in a low-carbon steel during isothermal heat treatment

The characteristics of nanosized precipitates in steels depend on the heat-treatment parameters. The effects of characteristics of vanadium precipitates formed during isothermal heat treatment on the hardness of the ferrite matrix in low-carbon vanadium-alloyed steel were investigated through analysis of transmission electron microscopy images and microhardness measurements. The results show that, during isothermal holding in the temperature range from 675 to 750℃, only interphase precipitation occurs, whereas only random precipitation occurs in the ferrite matrix during holding at 600℃. Furthermore, during isothermal heat treatment between 600 and 675℃, both random and interphase precipitates occurred in the ferrite. Nanoscale vanadium carbides with different atomic ratios of vanadium (V) and carbon (C) were the dominant precipitates in the random and interphase precipitates. The sizes of random precipitation carbides were smaller than those of interphase ones. Also, the sample isothermally heat treated at 650℃ for 900 s exhibited a higher hardness with a narrower hardness distribution.     

斜置旋耕比功耗模型的建立与参数优选

采用试验建模的方法 ,建立了斜置旋耕比功耗模型并应用最优化理论确定了斜置旋耕最佳斜置角。     

脾气虚证动物模型规范化的初步研究——部分免疫功能方面

目的　在脾气虚证动物模型规范化的初步研究中 ,探讨其部分免疫功能改变。方法　首先改进、完善脾气虚证模型的诊断标准和造模方法 ,然后观察其部分细胞免疫、非特异性免疫、红细胞免疫功能改变 ;同时与 5种目前有代表性的脾气 (阳 )虚证模型进行比较。动物采用WistarⅡ级大鼠 ,雄性 ,分为对照组、初步规范组、大黄组、耗气破气组、限量营养组、劳倦过度组和利血平组。初步规范组采用体质、苦寒泻下加耗气破气降气法造模 ,其他模型组采用相应常规方法造模。取样检测指标前进行游泳或寒冷负荷。结果　从胸腺湿重和指数 ,胸腺皮质厚度 ,脾脏中央动脉周围淋巴鞘直径 ,脾脏T淋巴细胞增殖功能 ,脾脏NK细胞对YAC 1肿瘤细胞杀伤率 ,脾脏巨噬细胞中性红吞噬活性等指标的改变看 ,初步规范组的造模结果与脾气虚证模型诊断标准有较高的符合率 ,包括自然恢复较慢 ,且与诊断标准的符合率明显优于目前 5种有代表性的脾气 (阳 )虚证模型。结论　本实验达到了初步优化、规范脾气虚证模型的目的。     

Soil fertility limits carbon sequestration by forest ecosystems in a CO2-enriched atmosphere

Northern mid-latitude forests are a large terrestrial carbon sink. Ignoring nutrient limitations, large increases in carbon sequestration from carbon dioxide (CO2) fertilization are expected in these forests. Yet, forests are usually relegated to sites of moderate to poor fertility, where tree growth is often limited by nutrient supply, in particular nitrogen. Here we present evidence that estimates of increases in carbon sequestration of forests, which is expected to partially compensate for increasing CO2 in the atmosphere, are unduly optimistic. In two forest experiments on maturing pines exposed to elevated atmospheric CO2, the CO2-induced biomass carbon increment without added nutrients was undetectable at a nutritionally poor site, and the stimulation at a nutritionally moderate site was transient, stabilizing at a marginal gain after three years. However, a large synergistic gain from higher CO2 and nutrients was detected with nutrients added. This gain was even larger at the poor site (threefold higher than the expected additive effect) than at the moderate site (twofold higher). Thus, fertility can restrain the response of wood carbon sequestration to increased atmospheric CO2. Assessment of future carbon sequestration should consider the limitations imposed by soil fertility, as well as interactions with nitrogen deposition.     

Sub-laser-cycle electron pulses for probing molecular dynamics

Experience shows that the ability to make measurements in any new time regime opens new areas of science. Currently, experimental probes for the attosecond time regime (10(-18) 10(-15) s) are being established. The leading approach is the generation of attosecond optical pulses by ionizing atoms with intense laser pulses. This nonlinear process leads to the production of high harmonics during collisions between electrons and the ionized atoms. The underlying mechanism implies control of energetic electrons with attosecond precision. We propose that the electrons themselves can be exploited for ultrafast measurements. We use a 'molecular clock', based on a vibrational wave packet in H(2)(+) to show that distinct bunches of electrons appear during electron ion collisions with high current densities, and durations of about 1 femtosecond (10(-15) s). Furthermore, we use the molecular clock to study the dynamics of non-sequential double ionization.