The protein kinase C family for the regulation of cellular functions

The physiological importance of protein kinase C (PKC) activation is widely appreciated and well documented. It is now clear that there is more than one species of PKC molecule, and several discrete subspecies have been defined. These proteins are derived from both multiple genes and from alternative splicing of a single mRNA transcript, yet possess a primary structure containing conserved structural motifs with a high degree of sequence homology. In mammalian tissues at least seven subspecies can be distinguished, one of which is expressed only in the central nervous tissues. Biochemical and immunocytochemical studies have revealed that these PKC subspecies are differently located in particular cell types, and at limited intracellular locations. The enzyme subspecies purified from tissue show subtle differences in their mode of activation, sensitivity to Ca2+ and catalytic activity. It is worth noting that unsaturated free fatty acids including arachidonic, oleic, and linoleic acids dramatically activate several members of the PKC family in the presence of diacylglycerol at the basal level of Ca2+. It is possible that activation of the enzyme is an integral part of the signal-induced degradation cascade of various membrane phospholipids catalyzed by phospholipases C, A2 and perhaps D as well. Evidence now accumulates that PKC plays pivotal roles in control of a number of membrane functions, such as exocytosis, release reactions, and ion channel conductivity, as well as in cross-talks of various cell-signaling systems. It is also clear that PKC plays roles of crucial importance for regulation of gene expression and cell growth.Biomedical Reviews 1992; 1: 1-6

Functional analysis of human mutations in homeodomain transcription factor PITX3

<p>Abstract</p> <p>Background</p> <p>The homeodomain-containing transcription factor <it>PITX3 </it>was shown to be essential for normal eye development in vertebrates. Human patients with point mutations in <it>PITX3 </it>demonstrate congenital cataracts along with anterior segment defects in some cases when one allele is affected and microphthalmia with brain malformations when both copies are mutated. The functional consequences of these human mutations remain unknown.</p> <p>Results</p> <p>We studied the PITX3 mutant proteins S13N and G219fs to determine the type and severity of functional defects. Our results demonstrate alterations in DNA-binding profiles and/or transactivation activities and suggest a partial loss-of-function in both mutants with the G219fs form being more severely affected. No anomalies in cellular distribution and no dominant-negative effects were discovered for these mutants. Interestingly, the impairment of the G219fs activity varied between different ocular cell lines.</p> <p>Conclusion</p> <p>The G219fs mutation was found in multiple families affected with congenital cataracts along with anterior segment malformations in many members. Our data suggest that the presence/severity of anterior segment defects in families affected with G219fs may be determined by secondary factors that are expressed in the developing anterior segment structures and may modify the effect(s) of this mutation. The S13N mutant showed only minor alteration of transactivation ability and DNA binding pattern and may represent a rare polymorphism in the <it>PITX3 </it>gene. A possible contribution of this mutation to human disease needs to be further investigated.</p

Heart-rate Response to Simulated Anxious Events - Development of kids' friendly wearable device for children's safety

This study aims to know how and when small children between 1 to 6 years, feel anxiety during their daily lives. Pre-school children are our target to be kept them from crimes and accidents while they are taken care in the nurseries or kindergartens or on holidays by any responsible persons. This is basic research for designing a wearable device for children!s safety. We made several simulated anxious situations as movies and facial emotion images to show to kids in a set of room. We found depends on the ages or personal experiences, children!s reactions were different and anxiety was shown up differently

Cyclic phosphatidic acid decreases proliferation and survival of colon cancer cells by inhibiting peroxisome proliferator-activated receptor gamma

Cyclic phosphatidic acid (CPA) a structural analog of lysophosphatidic acid (LPA) is one of the simplest phospholipids found in every cell type cPA is a specific high-affinity antagonist of peroxisome proliferator-activated receptor gamma (PPAR gamma) however the molecular mechanism by which cPA inhibits cellular proliferation remains to be clarified In this study we found that inhibition of PPAR gamma prevents proliferation of human colon cancer HT-29 cells CPA suppressed cell growth and this effect was reversed by the addition of a PPAR gamma agonist These results indicate that the physiological effects of cPA are partly due to PPAR gamma inhibition Our results identify PPAR gamma as a molecular mediator of CPA activity in HT-29 cells and suggest that cPA and the PPAR gamma pathway might be therapeutic targets in the treatment of colon cancerArticlePROSTAGLANDINS & OTHER LIPID MEDIATORS. 93(3-4):126-133 (2010)journal articl

BCG directly induces cell cycle arrest in human transitional carcinoma cell lines as a consequence of integrin cross-linking

BACKGROUND: Current models of the mechanism by which intravesical BCG induces an anti-tumor effect in urothelial carcinoma propose a secondary cellular immune response as principally responsible. Our group has demonstrated that BCG mediated cross-linking of α5 [Image: see text] 1 integrin receptors present on the tumor surface elicits a complex biologic response involving AP1 and NF-κB signaling as well as the transactivation of immediate early genes. This study evaluated the direct biologic effect of cross-linking α5β1 integrin on cell cycle progression and apoptosis in two human urothelial carcinoma cell lines. METHODS: Two independent assays (MTT and Colony forming ability) were employed to measure the effect of α5β1 cross-linking (antibody mediated or BCG) on cellular proliferation. Flow cytometry was employed to measure effect of BCG and α5β1 antibody mediated cross-linking on cell cycle progression. Apoptosis was measured using assays for both DNA laddering and Caspase 3 activation. RESULTS: Results demonstrate that integrin cross-linking by BCG, or antibody mediated crosslinking of α5β1 resulted in a decrease in proliferating cell number. BCG treatment or α5β1 cross-linking increased the percentage of cells in G0/G1, in both 253J and T24 cell lines. Peptide mediated blockade of integrin binding site using RGDS reversed the effect BCG on both proliferation and cell cycle arrest. Apoptosis in response to BCG was not identified by either DNA laddering or Caspase 3 activation. CONCLUSION: These findings show that BCG exerts a direct cytostatic effect on human urothelial carcinoma cell lines. Cell cycle arrest at the G1/S interface is a mechanism by which BCG inhibits cellular proliferation. This effect is duplicated by antibody mediated cross-linking of α5β1 and likely occurs as a consequence of crosslink-initiated signal transduction to cell cycle regulatory genes

高速点火核融合研究の進展: 高速点火実証ターゲット,ペタワットレーザー LFEX

金沢大学先端科学・社会共創推進機構高速点火実証実験で不可欠なターゲットの開発，追加熱に用いるペタワットレーザーLFEX （Laser for First Ignition Experiment）の現状について示した．ターゲットでは新設計，非球対称なコーンつきターゲット内部に中空固体燃料層を形成する技術，低密度フt 一ム材料の現状を示した．LFEX レーザーでは本体が完成し，パルスを短くする回折格子を用いた圧縮器の建設が進められている

Correlation between length of stay in acute stroke wards and the functional prognosis after comprehensive rehabilitation

　脳卒中発症後の機能予後改善には回復期リハビリテーションが有効である．急性期病棟から回復期リハビリテーション病棟に早期に移ることが，機能予後改善につながる可能性がある．本研究では，急性期病棟の在院期間と長期予後改善効果の関連性を検討することを目的とした．2018年１月1日から2018年12月31日までに川崎医科大学附属病院脳卒中科に入院した急性期脳卒中症例のうち，回復期リハビリテーション病棟に転棟・転院した症例を対象とした．脳卒中科退院時に比し，一年後に modified Rankin scale が１以上改善した症例を改善有と定義した．改善有と関連する患者背景因子，入院中の診療データについて検討を行った．関連性はカイ二乗検定を用いて評価し，有意な関連性を示した因子についてはロジスティック回帰分析を用いて解析した．対象期間に入院した急性期脳卒中408例中，回復期リハビリテーション病棟に転棟・転院したのは142例であった（男性90人，中央値76.0歳）．改善有は57例であり，在院期間の第一四分位である17日未満で回復期病棟に移った群で改善有が有意に多かった（P < 0.01）．ロジスティック回帰分析でも急性期病棟の在院期間が短い（17日未満）ことが改善有と独立して関連した．急性期脳卒中患者の急性期病棟在院期間を短縮することが機能予後改善につながることが示唆された．　Neurological symptoms and functional disability of stroke survivors can be improved through comprehensive rehabilitation in the post-acute phase. Early transfer from the stroke unit to the rehabilitation ward possibly leads to an improvement of functional prognosis. The purpose of this study was to investigate the relationship between the length of stay in the stroke unit and the long-term prognosis improvement. The study involved acute stroke patients admitted to the Department of Stroke, Kawasaki Medical School Hospital between January 1, 2018 and December 31, 2018. Specifically, those selected and included in the study were patients eventually transferred to a rehabilitation department or hospital. Improvement of functional prognosis was defined as a 1-point decrease on the modified Rankin scale at 1 year compared with that at the time of discharge from the stroke department. Factors associated with the improvement group were evaluated using the chi-square test and then logistic regression analysis. Of the 408 patients with acute stroke admitted during the study period, 142 were transferred to rehabilitation centers (90 men, median age: 76.0 years). Fifty-seven patients had improvement. The rate of improvement was significantly higher in the group transferred to the rehabilitation ward by day 17, the first quartile of time in the stroke unit (p < 0.01). Logistic regression analysis also showed that a shorter length of stay (< 17 days) in the stroke unit was independently associated with improvement. The results suggest that early initiation of comprehensive rehabilitation in the post-acute phase leads to improved functional outcomes of patients with acute stroke

Hot electron and ion spectra on blow-off plasma free target in GXII-LFEX direct fast ignition experiment

Polystyrene deuteride shell targets with two holes were imploded by the Gekko XII laser and additionally heated by the LFEX laser in a direct fast ignition experiment. In general, when an ultra-intense laser is injected into a blow-off plasma created by the imploding laser, electrons are generated far from the target core and the energies of electrons increase because the electron acceleration distance has been extended. The blow-off plasma moves not only to the vertical direction but to the lateral direction against the target surface. In a shell target with holes, a lower effective electron temperature can be realized by reducing the inflow of the implosion plasma onto the LFEX path, and high coupling efficiency can be expected. The energies of hot electrons and ions absorbed into the target core were calculated from the energy spectra using three electron energy spectrometers and a neutron time-of-flight measurement system, Mandala. The ions have a large contribution of 74% (electron heating of 4.9 J and ion heating of 14.1 J) to target heating in direct fast ignition