Transmembrane proteins of tight junctions

AbstractTight junctions contribute to the paracellular barrier, the fence dividing plasma membranes, and signal transduction, acting as a multifunctional complex in vertebrate epithelial and endothelial cells. The identification and characterization of the transmembrane proteins of tight junctions, claudins, junctional adhesion molecules (JAMs), occludin and tricellulin, have led to insights into the molecular nature of tight junctions. We provide an overview of recent progress in studies on these proteins and highlight their roles and regulation, as well as their functional significance in human diseases

Experimental effect of retinoic acids on apoptosis during the development of diabetic retinopathy

Nami Nishikiori1,2, Makoto Osanai2, Hideki Chiba2, Takashi Kojima2, Shuichiro Inatomi1,2, Hiroshi Ohguro1, Norimasa Sawada2Departments of 1Ophthalmology and 2Pathology, Sapporo Medical University School of MedicinePurpose: This study was conducted to investigate whether retinoic acids (RAs) had any effect on apoptosis during the development of diabetic retinopathy.Methods: To investigate whether RAs had any effect on apoptosis during the development of diabetic retinopathy, we housed 32 C57BL/6 male mice and induced diabetes in 24 by intra peritoneal injections of streptozotocin (STZ; Sigma, St Louis, MO) and treated 16 of the diabetic mice with the RAs, all-trans-retinoic acid (ATRA) (seven mice) and 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido] benzoic acid (Am580) (nine mice). The other eight mice were used as diabetic controls. We then measured apoptosis in the retina by TdT-dUTP terminal nick-end labeling assay.Results: RAs inhibited the apoptosis of retinal cells in diabetic retinopathy. Many apoptotic cells were observed in retinas of the eight diabetic control mice (mean value and SD: 37.8 ± 6.9), whereas when diabetic mice were treated with RAs, the number of apoptotic cells significantly decreased (mean value and SD: 9.9 ± 6.4 for the seven ATRA-treated diabetic mice and 9.8 ± 5.9 for the nine Am580-treated diabetic mice) (p < 0.05).Conclusion: Treatment with RAs decreases apoptosis during the development of diabetic retinopathy.Keywords: retinoic acids, apoptosis, diabetic retinopathy, glial cell line-derived neurotrophic facto

マイクロコントローラを組み込んだ歯科インプラント動揺測定装置の開発

The aim of this study was to develop a portable device (IM checker) for measuring dental implant mobility using a microcontroller. A constant amplitude and frequency vibration was applied to a dental implant model and the acceleration signal was detected using measuring probe. Then the IM score was obtained using the criteria developed in this study. We made several implant models of different implant lengths, diameters and material of Rigolac® or Molteno®. There was a linear relationship between mechanical mobility at 400 Hz of the models and the IM scores (R(2) = 0.92). The IM checker could discriminate the mobility of dental implant models in twelve measurements with P < 0.01. There was no significant difference in the means of the IM score measured by four operators with P < 0.01. The results indicated that the IM checker had sufficient reliability and could be available in dental clinics.本研究の目的は歯科インプラントの動揺を簡易に測定できる装置の開発である｡本装置では測定プローブで一定振幅の周波数を歯科インプラントに与え､その加速度信号を検出する｡そして本研究で考察した評価基準に基づいてIM値を表示する｡さらにRigolac®やMolteno®を用い､インプラント体の長さおよび直径を変えたインプラントモデルを作製した｡400Hzにおけるモデルの機械モビリティとIM値との間には､よい相関が見られた(R(2)=0.92)｡IMチェッカーを用い､一人の測定者が行った12回の測定において､インプラントの動揺を判別することが可能であった(P<0.01)｡また4人の測定者による測定では,その平均値に対し測定者間の有意差は見られなかった(P<0.01)｡従ってIMチェッカーは十分な信頼性を有し､歯科臨床に有効であると考える

Dual induction of caspase 3- and transglutaminase-dependent apoptosis by acyclic retinoid in hepatocellular carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma has a high mortality rate due to its rate of recurrence. Acyclic retinoid prevents recurrence of hepatocellular carcinoma in patients after surgical removal of their primary tumors by inducing apoptosis in hepatocellular carcinoma cells, although the molecular mechanisms of action are not understood.</p> <p>Methods</p> <p>Human hepatocellular carcinoma cells in culture, as well as nude mice transplanted with hepatocellular carcinoma cells and rats given with <it>N</it>-diethylnitrosamine were treated with acyclic retinoid. Changes in activated caspase 3 and transglutaminase 2 (TG2) levels, Sp1 cross-linking and its activities, expression of epidermal growth factor receptor, and apoptotic levels were measured.</p> <p>Results</p> <p>Acyclic retinoid simultaneously stimulated the activation of caspase 3, and the expression, nuclear localization and crosslinking activity of TG2, resulting in crosslinking and inactivation of the transcription factor, Sp1, thereby reducing expression of epidermal growth factor receptor and cell death in three hepatocellular carcinoma cell lines. These effects were partially restored by a caspase inhibitor, transfection of antisense TG2, restoration of functional Sp1, or an excess of epidermal growth factor. Nuclear expression of TG2 and crosslinked Sp1, as also activated caspase 3 were found in both hepatocellular carcinoma cells transplanted into nude mice and cancerous regions within the liver in <it>N</it>-diethylnitrosamine-induced hepatocarcinogenesis model in rats, following treatment of animals with acyclic retinoid.</p> <p>Conclusions</p> <p>Treatment with acyclic retinoid produces a dual activation of caspase 3 and TG2 induced apoptosis of hepatocellular carcinoma cells via modification and inactivation of Sp1, resulting in reduced expression of epidermal growth factor receptor.</p

The nuclear receptor hepatocyte nuclear factor 4α acts as a morphogen to induce the formation of microvilli

Microvilli are actin-based organelles found on apical plasma membranes that are involved in nutrient uptake and signal transduction. Numerous components, including ezrin/radixin/moesin (ERM) proteins, have been identified that link filamentous actins to transmembrane proteins, but the signals driving microvillus biogenesis are not known. In this study, we show that the conditional and/or ectopic expression of a nuclear receptor, hepatocyte nuclear factor 4α (HNF4α), triggers microvillus morphogenesis. We also demonstrate that HNF4α expression induces ERM-binding phosphoprotein 50 (EBP50) expression and that attenuation of EBP50 using RNA interference inhibits microvillus development. We conclude that HNF4α acts as a morphogen to trigger microvillus formation

An accurate prediction of high-frequency circuit behaviour, Journal of Telecommunications and Information Technology, 2005, nr 1

An accurate way to predict the behaviour of an RF analogue circuit is presented. A lot of effort is required to eliminate the inaccuracies that may generate the deviation between simulation and measurement. Efficient use of computer-aided design and incorporation of as many physical effects as possible overcomes this problem. Improvement of transistor modelling is essential, but there are many other un-solved problems affecting the accuracy of RF analogue circuit modelling. In this paper, the way of selection of accurate transistor model and the extraction of parasitic elements from the physical layout, as well as implementation to the circuit simulation will be presented using two CMOS circuit examples: an amplifier and a voltage controlled oscillator (VCO). New simulation technique, electro-magnetic (EM)-co-simulation is introduced

Evaluation of Kidney Histological Images Using Unsupervised Deep Learning

[Introduction] Evaluating histopathology via machine learning has gained research and clinical interest, and the performance of supervised learning tasks has been described in various areas of medicine. Unsupervised learning of histological images has the advantage of reproducibility for labeling; however, the relationship between unsupervised evaluation and clinical information remains unclear in nephrology. [Methods] We propose an unsupervised approach combining convolutional neural networks (CNNs) and a visualization algorithm to cluster the histological images and calculate the score for patients. We applied the approach to the entire images or patched images of the glomerulus of kidney biopsy samples stained with hematoxylin and eosin obtained from 68 patients with immunoglobulin A nephropathy. We assessed the relationship between the obtained scores and clinical variables of urinary occult blood, urinary protein, serum creatinine (SCr), systolic blood pressure, and age. [Results] The glomeruli of the patients were classified into 12 distinct classes and 10 patches. The output of the fine-tuned CNN, which we defined as the histological scores, had significant relationships with assessed clinical variables. In addition, the clustering and visualization results suggested that the defined clusters captured important findings when evaluating renal histopathology. For the score of the patch-based cluster containing crescentic glomeruli, SCr (coefficient = 0.09, P = 0.019) had a significant relationship. [Conclusion] The proposed approach could successfully extract features that were related to the clinical variables from the kidney biopsy images along with the visualization for interpretability. The approach could aid in the quantified evaluation of renal histopathology