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Kuwajima Kunihiro,Inobe Tomonao,Arai Munehito The Polymer Society of Korea 2006 Macromolecular Research Vol.14 No.2
This is a short review article of our recent studies on the ATP-induced, allosteric conformational transition of the chaperonin GroEL complex by solution X-ray scattering. We used synchrotron X-ray scattering with a two-dimensional, charge-coupled, device-based X-ray detector to study (1) the specificity of the chaperonin GroEL for its ligand that induced the allosteric transition, and (2) the identification of the allosteric transition of GroEL in its complicated kinetics induced by ATP. Due to the dramatically increased sensitivity of the X-ray scattering technique based on the use of the two dimensional X-ray detector and synchrotron radiation, different allosteric conformational states of GroEL populated under different conditions were clearly distinguished from each other. It was concluded that solution X-ray scattering is an extremely powerful tool for investigating the equilibrium and kinetics of cooperative conformational transitions of oligomeric protein complex, especially when combined with other spectroscopic techniques such as fluorescence spectroscopy.
Kunihiro Kuwajima,Tomonao Inobe,Munehito Arai 한국고분자학회 2006 Macromolecular Research Vol.14 No.2
This is a short review article of our recent studies on the ATP-induced, allosteric conformational transition of the chaperonin GroEL complex by solution X-ray scattering. We used synchrotron X-ray scattering with a two-dimensional, charge-coupled, device-based X-ray detector to study (1) the specificity of the chaperonin GroEL for its ligand that induced the allosteric transition, and (2) the identification of the allosteric transition of GroEL in its complicated kinetics induced by ATP. Due to the dramatically increased sensitivity of the X-ray scattering technique based on the use of the two dimensional X-ray detector and synchrotron radiation, different allosteric conformational states of GroEL populated under different conditions were clearly distinguished from each other. It was concluded that solution X-ray scattering is an extremely powerful tool for investigating the equilibrium and kinetics of coop erative conformational transitions of oligomeric protein complex, especially when combined with other spectro scopic techniques such as fluorescence spectroscopy.
Iwao Kuwajima, MD 대한고혈압학회 2011 Clinical Hypertension Vol.17 No.1
Although evidence-based medicine (EBM) has changed medical therapy from experience- or experiment-based medicine to the modern science-based medicine, nowadays it seems to be used as a tool of advertizing strategy of industries. Clinical trial is a fundamental component of EBM and it costs very much and are mostly conducted by the financial support of pharmaceutical industries at a tremendous expense. If anticipated results for the sponsor were not shown in the trial, a “spin” has been used to mislead readers as if positive results for test drugs or devices were obtained by emphasizing subgroup analysis, or searching favorable endpoint by post-hoc analysis. Clinical trials on angiotensin receptor blocker (ARB) are continuing succession of defeat all over world except two Japanese clinical trials, JIKEI HEART and KYOTO HEART studies. However, in both trials, subjective soft endpoints, such as angina pectoris or congestive heart failure were used despite of prospective randomized, open labeled, blinded endpoint design. In the era of advertizing-based medicine, It is important to read clinical trial data with critical view points.
Fujikawa, T.,Takatori, N.,Kuwajima, M.,Kim, G.J.,Nishida, H. Academic Press 2011 Developmental biology Vol.355 No.2
Mechanisms that regulate the number of cells constituting the body have remained largely elusive. We approached this issue in the ascidian, Halocynthia roretzi, which develops into a tadpole larva with a small number of cells. The embryonic cells divide 11 times on average from fertilization to hatching. The number of cell division rounds varies among tissue types. For example, notochord cells divide 9 times and give rise to large postmitotic cells in the tadpole. The number of cell division rounds in partial embryos derived from tissue-precursor blastomeres isolated at the 64-cell stage also varied between tissues and coincided with their counterparts in the intact whole embryos to some extent, suggesting tissue-autonomous regulation of cell division. Manipulation of cell fates in notochord, nerve cord, muscle, and mesenchyme lineage cells by inhibition or ectopic activation of the inductive FGF signal changed the number of cell divisions according to the altered fate. Knockdown and missexpression of Brachyury (Bra), an FGF-induced notochord-specific key transcription factor for notochord differentiation, indicated that Bra is also responsible for regulation of the number of cell division rounds, suggesting that Bra activates a putative mechanism to halt cell division at a specific stage. The outcome of precocious expression of Bra suggests that the mechanism involves a putative developmental clock that is likely shared in blastomeres other than those of notochord and functions to terminate cell division at three rounds after the 64-cell stage. Precocious expression of Bra has no effect on progression of the developmental clock itself.