Caffeine as a psychomotor stimulant: mechanism of action

The popularity of caffeine as a psychoactive drug is due to its stimulant properties, which depend on its ability to reduce adenosine transmission in the brain. Adenosine A₁ and A_2A receptors are expressed in the basal ganglia, a group of structures involved in various aspects of motor control. Caffeine acts as an antagonist to both types of receptors. Increasing evidence indicates that the psychomotor stimulant effect of caffeine is generated by affecting a particular group of projection neurons located in the striatum, the main receiving area of the basal ganglia. These cells express high levels of adenosine A_2A receptors, which are involved in various intracellular processes, including the expression of immediate early genes and regulation of the dopamine- and cyclic AMP-regulated 32-kDa phosphoprotein DARPP-32. The present review focuses on the effects of caffeine on striatal signal transduction and on their involvement in caffeine-mediated motor stimulation.Received 8 July 2003; received after revision 7 September 2003; accepted 6 October 2003     

Horizontal gene transfer from Eukarya to Bacteria and domain shuffling: the α-amylase model

-Amylases are present in all kingdoms of the living world. Despite strong conservation of the tertiary structure, only a few amino acids are conserved in interkingdom comparisons. Animal -amylases are characterized by several typical motifs and biochemical properties. A few cases of such -amylases have been previously reported in some eubacterial species. We screened the bacterial genomes available in the sequence databases for new occurrences of animal-like -amylases. Three novel cases were found, which belong to unrelated bacterial phyla: Chloroflexus aurantiacus, Microbulbifer degradans, and Thermobifida fusca. All the animal-like -amylases in Bacteria probably result from repeated horizontal gene transfer from animals. The M. degradans genome also contains bacterial-type and plant-type -amylases in addition to the animal-type one. Thus, this species exhibits -amylases of animal, plant, and bacterial origins. Moreover, the similarities in the extra C-terminal domains (different from both the -amylase domain C and the starch-binding domain), when present, also suggest interkingdom as well as intragenomic shuffling.Received 17 October 2003; accepted 6 November 2003     

Apoptotic cell death in the lactating mammary gland is enhanced by a folding variant of α-lactalbumin

Apoptosis is essential to eliminate secretory epithelial cells during the involution of the mammary gland. The environmental regulation of this process is however, poorly understood. This study tested the effect of HAMLET (human -lactalbumin made lethal to tumor cells) on mammary cells. Plastic pellets containing HAMLET were implanted into the fourth inguinal mammary gland of lactating mice for 3 days. Exposure of mammary tissue to HAMLET resulted in morphological changes typical for apoptosis and in a stimulation of caspase-3 activity in alveolar epithelial cells near the HAMLET pellets but not more distant to the pellet or in contralateral glands. The effect was specific for HAMLET and no effects were observed when mammary glands were exposed to native a-lactalbumin or fatty acid alone. HAMLET also induced cell death in vitro in a mouse mammary epithelial cell line. The results suggest that HAMLET can mediate apoptotic cell death in mammary gland tissue.Received 30 January 2004; received after revision 5 March 2004; accepted 16 March 2004     

Role of Cys221 and Asn116 in the zinc-binding sites of the Aeromonas hydrophila metallo-β-lactamase

The CphA metallo--lactamase produced by Aeromonas hydrophila exhibits two zinc-binding sites. Maximum activity is obtained upon binding of one zinc ion, whereas binding of the second zinc ion results in a drastic decrease in the hydrolytic activity. In this study, we analyzed the role of Asn116 and Cys221, two residues of the active site. These residues were replaced by site-directed mutagenesis and the different mutants were characterized. The C221S and C221A mutants were seriously impaired in their ability to bind the first, catalytic zinc ion and were nearly completely inactive, indicating a major role for Cys221 in the binding of the catalytic metal ion. By contrast, the binding of the second zinc ion was only slightly affected, at least for the C221S mutant. Mutation of Asn116 did not lead to a drastic decrease in the hydrolytic activity, indicating that this residue does not play a key role in the catalytic mechanism. However, the substitution of Asn116 by a Cys or His residue resulted in an approximately fivefold increase in the affinity for the second, inhibitory zinc ion. Together, these data suggested that the first zinc ion is located in the binding site involving the Cys221 and that the second zinc ion binds in the binding site involving Asn116 and, presumably, His118 and His196.Received 3 March 2003; received after revision 4 August 2003; accepted 25 August 2003     

关于BR0-代数弱完备性的证明

目的对BR0-代数自身的完备性问题进行研究。方法研究了王国俊教授建立的模糊命题演算的形式演绎系统L*和与之在语义上相匹配的R0-代数,并结合吴洪博教授所定义的BR0-代数,从伴随的角度切入。结果在BR0-代数中定义了BR0-等式和BR0-方程,通过全序BR0-代数证明了BR0-代数自身的弱完备性。结论得到了BR0-代数的完备性定理,为相应形式逻辑系统与模糊推理的研究提供了理论框架。     

掺杂方式对Mg：Ba0．3Sr0．7Zr0．18Ti0．82O3陶瓷微结构及性能的影响

采用溶-凝胶法制备Mg：Ba0．3Sr0．7Zr0．18Ti0．82O3陶瓷粉末,以传统陶瓷制备工艺制备Mg元素掺杂的Mg：Ba0．3Sr0．7Zr0．18Ti0．82O3陶瓷．研究MgO掺杂量为1．6％（质量分数）时,MgO固相掺杂和Mg计湿化学法掺杂两种不同的掺杂方式对Mg掺杂的Mg：Ba0．3Sr0．7Zr0．18Ti0．82O3陶瓷显微结构及电学性能的影响．研究结果表明,当Mg掺杂量相同时,掺杂方式对Mg掺杂的Mg：Ba0．3Sr0．7Zr0．18Ti0．82O3。陶瓷的显微结构和电学特性有显著的影响,相比纯的Mg：Ba0．3Sr0．7Zr0．18Ti0．82O3陶瓷,两种掺杂方式中,Mg2＋湿化学法掺杂相对于MgO固相掺杂,在BSZT陶瓷中的分布更均匀,替位程度更高,所以其对介电常数的影响也相对更大．而MgO固相掺杂相对于Mg2＋湿化学法掺杂明显地促进了陶瓷晶粒的生长,提高了陶瓷的致密性,同时其击穿电场和电阻率也有较大提高．1350℃下烧结的固相MgO掺杂的Mg：Ba0．3Sr0．7Zr0．18Ti0．82O3陶瓷性能较优,介电常数约为590,介电损耗低于0．0005,电阻率为7．78×10^13Ω·mm,击穿场强为6．56kV／mm．     

关于N(2,2,0)代数的稳定化子

进一步研究N(2,2,0)代数的稳定化子,利用稳定化子给出N(2,2,0)代数的一类同余分解,获得自然同态下一类逆像的代数结构和性质.     

用MET分析NdFe_（10）V_2，NdFe_（10）V_2N_（0．5）Nd

用两格点分子场理论分析了ＮｄＦｅ１０Ｖ２，ＮｄＦｅ１０Ｖ２Ｎ０．５，ＮｄＦｅ１０Ｍｏ２，ＮｄＦｅ１０Ｍｏ２Ｎ０．５的饱和磁化强度随温度的变化关系，得到了分子场系数ｎＦＦ，ｎＦＲ和ｎＲＲ，计算结果与实验基本一致，计算结果表明，氮元素增大了交换场ＨＲ．