膵癌，胆管癌および大腸癌細胞株におけるMHC class Iの発現と、抗原提示機能関連分子との関係についての検討

博士（医学）神戸大

Rho-associated protein kinase and cyclophilin a are involved in inorganic phosphate-induced calcification signaling in vascular smooth muscle cells

Arterial calcification, a risk factor of cardiovascular events, develops with differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. Cyclophilin A (CypA) is a peptidyl-prolyl isomerase involved in cardiovascular diseases such as atherosclerosis and aortic aneurysms, and rho-associated protein kinase (ROCK) is involved in the pathogenesis of vascular calcification. CypA is secreted in a ROCK activity-dependent manner and works as a mitogen via autocrine or paracrine mechanisms in VSMCs. We examined the involvement of the ROCK-CypA axis in VSMC calcification induced by inorganic phosphate (Pi), a potent cell mineralization initiator. We found that Pi stimulated ROCK activity, CypA secretion, extracellular signal-regulated protein kinase (ERK) 1/2 phosphorylation, and runt-related transcription factor 2 expression, resulting in calcium accumulation in rat aortic smooth muscle cells (RASMCs). The ROCK inhibitor Y-27632 significantly suppressed Pi-induced CypA secretion, ERK1/2 phosphorylation, and calcium accumulation. Recombinant CypA was found to be associated with increased calcium accumulation in RASMCs. Based on these results, we suggest that autocrine CypA is mediated by ROCK activity and is involved in Pi-induced ERK1/2 phosphorylation following calcification signaling in RASMCs

Ultrasonic shears assistance can shorten the console time in robotic gastrectomy for early gastric cancer

markdownabstract__Abstract__ Why do legal arrangements for the institutions of government (legislative, executive, judicial branches) in Western liberal democracies develop faster, or in a different way, in one jurisdiction in comparison to another? In this article, it is argued that constitutional theory can help us understand the development of these legal institutional arrangements, for example in light of of the changing role of national highest courts in the the globalised legal context. For this purpose, the concept of constitutional (in-)flexibility is introduced, which can explain how national constitutional frameworks enable or constrain the integration of normative changes in national legal systems. Four elements encompassed by this concept are identified: the detail of constitutional norms, the modalities for revising the national Constitution, the approach to legal argumentation taken by interpreters of the Constitution, and the influence attributed to international law within the national legal system. This analytical framework is applied to the illustrative case of judicial globalisation - concerning, inter alia, the judicial use of non-binding foreign law - to explain similarities and differences concerning the way in which changes affecting the functioning of national highest courts are integrated within different legal systems. This analysis, in turn, yields some insight into the further development of constitutional theory in the era of globalisation

Positive and negative cooperativity of modularly assembled zinc fingers.

One simple and widespread method to create engineered zinc fingers targeting the desired DNA sequences is to modularly assemble multiple finger modules pre-selected to recognize each DNA triplet. However, it has become known that a sufficient DNA binding affinity is not always obtained. In order to create successful zinc finger proteins, it is important to understand the context-dependent contribution of each finger module to the DNA binding ability of the assembled zinc finger proteins. Here, we have created finger-deletion mutants of zinc finger proteins and examined the DNA bindings of these zinc fingers to clarify the contributions of each finger module. Our results indicate that not only a positive cooperativity but also a context-dependent reduction in the DNA binding activity can be induced by assembling zinc finger modules

Phase Noise of Multiphase CMOS LC Oscillators Coupled by Mutual Inductors

There have beem many studies on the analysis and design of low-noise oscillators. Recently, much attention has been paid to the noise reduction technique using coupled oscillators. When oscillators are coupled, the coupling method is very important and affects various factors, for example, the level of noise. In this study, we analyze the phase noise of multiphase CMOS LC oscillators coupled by mutual inductors by using the impulse sensitivity function. From the simulation results, using mutual inductors as coupling elements can reduce the phase noise. Also, for oscillators coupled by mutual inductors, we show that setting a coupling coefficient of around 0.2 can realize the lowest phase noise near the oscillation frequency

Artificial Nine Zinc-Finger Peptide with 30-Base Pair Binding Sites (BIOORGANIC CHEMISTRY-Bioactive Chemistry)

Newly designed zinc-finger peptide Sp1ZF9 containing nine Cys2-His2 type motifs has been manipulated. The DNA binding property of Sp1ZF9 was compared with those of native three zinc-finger Sp1(530-623) and artificial six zinc-finger Sp1ZF6 peptides. Although the equilibrium time was less than 0.5 hr for Sp1(530-623)-DNA complex, Sp1ZF6 and Sp1ZF9 required approximately 48 and 72 hrs respectively for full complex formation. Evidently, the footprinting analysis demonstrated that Sp1ZF9 and Sp1ZF6 bind at least 27 and 18 contiguous base pairs of DNA sequence, respectively. Sp1ZF9 showed two step bindings to DNA, namely first the recognition of GC (5'-GGG-GCG-GGGCC-3' ) sequence by the N-terminal Sp1 domain and next the recognition of the corresponding target sequences by the middle and C-terminal Sp1 domains. In contrast with unimolecular binding of Sp1ZF9 and Sp1ZF6, two Sp1(530-623) molecules bind to one GCIII (5'-GGG-GCG-GGG-GGG-GCG-GGG-GGG-GCG-GGGCC-3') site region. Of special interest is the fact that new nine zinc-finger peptide Sp1ZF9 can bind to DNA sequence of approximately 30-base pairs. Such multi zinc-finger peptides may be useful as genome-specific transcriptional switches in future