Cell cycle regulation and novel structural features of thymidine kinase, an essential enzyme in Trypanosoma brucei

Thymidine kinase (TK) is a key enzyme in the pyrimidine salvage pathway which catalyzes the transfer of the γ-phosphate of ATP to 2′-deoxythymidine (dThd) forming thymidine monophosphate (dTMP). Unlike other type II TKs, the Trypanosoma brucei enzyme (TbTK) is a tandem protein with two TK homolog domains of which only the C-terminal one is active. In this study, we establish that TbTK is essential for parasite viability and cell cycle progression, independently of extracellular pyrimidine concentrations. We show that expression of TbTK is cell cycle regulated and that depletion of TbTK leads to strongly diminished dTTP pools and DNA damage indicating intracellular dThd to be an essential intermediate metabolite for the synthesis of thymine-derived nucleotides. In addition, we report the X-ray structure of the catalytically active domain of TbTK in complex with dThd and dTMP at resolutions up to 2.2 Å. In spite of the high conservation of the active site residues, the structures reveal a widened active site cavity near the nucleobase moiety compared to the human enzyme. Our findings strongly support TbTK as a crucial enzyme in dTTP homeostasis and identify structural differences within the active site that could be exploited in the process of rational drug design

Studies on Explosion II On the Measurement of the Dynamic Pressure Caused by Explosion of Powders

Smokeless powders such as nitrocellulose containing nitroglycerine have been used for common propellants. Recently, these powders have also been used as the propellant of rivet steels. The efficiency of a rivet ejector is mainly influenced by the exploding properties of powders. In this respect, we especially measured the dynamic pressure caused by the explosion of powders, and discussed the relation between the dynamic pressure and the several properties of these powders such as particle size, particle from, and surface conditions of particles. We further discussed the initiating methods of these powders. From the results of these expariments, we recognized the following facts : (1) The wave form of the dynamic pressure caused by the explosion of powders is scarcely influenced by the components and particle form of these powders, if an explosion is caused in a closed chamber with the loading density of powders of 0.3g/cc or more. (2) Reacting period of powders in a closed chamber is not effected by the initiating methods. (3) Wave form of the dynamic pressure is influenced by the state of the closed chamber. The details of the measuring methnds for the dynamic pressure and the overall results of the experiments are shown in this paper

加齢黄斑変性に対するアフリベルセプト治療後の脈絡膜新生血管病変活動性の再発

京都大学0048新制・課程博士博士(医学)甲第20975号医博第4321号新制||医||1026(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 川上 浩司, 教授 鈴木 茂彦, 教授 開 祐司学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

大発破に関する研究(I) ―発破計画および爆薬について―

In order to discuss about the method and the explosives for the coyote blasting and also themethod for verifying whether whole charges have been detonated or not, a specially designedcoyote blasting was carried out at Maeshima, Ushimadocho Okayama prefecture, on 18th April1962.Rocks around test site is a kind of granite. In this blasting, 11 chambers were formedwithin rocks and these were filled up with proper explosives. Total weight of explosives filledup in these chambers were about 6, 500 kg, and these explosives were fired by some delay de-tonators. The time from the instant of detonation of the initial chamber to that of the last wasabout 4, 000 ins.Some high speed moving camera and some pick-up which were used for observing the vi-bration of rocks caused by these explosions were used for verifying the detonation of each ex-plosive.It was recognized on this coyote blasting that the breakage of rocks by the delay blastingwas better than that by the instantaneous blasting, therefore, the delay blasting was useful inthe coyote blasting as same as the general blasting which was performed by the explosives load-ed in some drill holes, and also the verification of detonation was more easily on the delayblasting, therefore, adopting the delay blasting method to the coyote blasting was available onthe stand point of safety in operations.In order to discuss about the method and the explosives for the coyote blasting and also themethod for verifying whether whole charges have been detonated or not, a specially designedcoyote blasting was carried out at Maeshima, Ushimadocho Okayama prefecture, on 18th April1962.Rocks around test site is a kind of granite. In this blasting, 11 chambers were formedwithin rocks and these were filled up with proper explosives. Total weight of explosives filledup in these chambers were about 6,500 kg, and these explosives were fired by some delay de-tonators. The time from the instant of detonation of the initial chamber to that of the last wasabout 4,000 ins.Some high speed moving camera and some pick-up which were used for observing the vi-bration of rocks caused by these explosions were used for verifying the detonation of each ex-plosive.It was recognized on this coyote blasting that the breakage of rocks by the delay blastingwas better than that by the instantaneous blasting, therefore, the delay blasting was useful inthe coyote blasting as same as the general blasting which was performed by the explosives load-ed in some drill holes, and also the verification of detonation was more easily on the delayblasting, therefore, adopting the delay blasting method to the coyote blasting was available onthe stand point of safety in operations

大発破に関する研究(II) ―爆破点近傍の振動測定―

The ground motions near shot point are measured at various places, that is, in the quarryand on the ground surface of each different geological structure. The weights of charge are inthe range of 0.1-1 tons and the distances from shot point and measure points are 20--~--120 in.It is confirmed that the displacement, particle velocity and acceleration of the ground motioncaused by explosion are largely related to the blasting conditions, geological structure of themeasure point and the path through which the waves passes. Especially, the tainping of thecharge and the shape of the free surface before the blast are mainly concerned with the emis-sion of elastic waves from the shot point. The size of rock fragments after the blast is foundto be a function of C which is expressed by C=a/W'/'d'. (a: amplitude, W: weight of charge, d: distance between shot point and measure point.)The ground motions near shot point are measured at various places, that is, in the quarryand on the ground surface of each different geological structure. The weights of charge are inthe range of 0.1-1 tons and the distances from shot point and measure points are 20--~--120 in.It is confirmed that the displacement, particle velocity and acceleration of the ground motioncaused by explosion are largely related to the blasting conditions, geological structure of themeasure point and the path through which the waves passes. Especially, the tainping of thecharge and the shape of the free surface before the blast are mainly concerned with the emis-sion of elastic waves from the shot point. The size of rock fragments after the blast is foundto be a function of C which is expressed by C=a/W'/'d'. (a: amplitude, W: weight of charge,d: distance between shot point and measure point.