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Trachtenberg A.J.,Massachusetts | Susa M.,Tohoku UniversitySendai | Bahammam L.,King Abdulaziz University
Anatomical Record | Year: 2016

Apical periodontitis (periapical lesions) is an infection-induced chronic inflammation in the jaw, ultimately resulting in the destruction of apical periodontal tissue. Toll-like receptors (TLRs) are prominent in the initial recognition of pathogens. Our previous study showed that TLR4 signaling is proinflammatory in periapical lesions induced by a polymicrobial endodontic infection. In contrast, the functional role of TLR2 in regulation of periapical tissue destruction is still not fully understood. Using TLR2 deficient (KO), TLR2/TLR4 double deficient (dKO), and wild-type (WT) mice, we demonstrate that TLR2 KO mice are highly responsive to polymicrobial infection-induced periapical lesion caused by over activation of TLR4 signal transduction pathway that resulted in elevation of NF-kB (nuclear factor kappa B) and proinflammatory cytokine production. The altered TLR4 signaling is caused by TLR2 deficiency-dependent elevation of CD14 (cluster of differentiation 14), which is a co-receptor of TLR4. Indeed, neutralization of CD14 strikingly suppresses TLR2 deficiency-dependent inflammation and tissue destruction in vitro and in vivo. Our findings suggest that a network of TLR2, TLR4, and CD14 is a key factor in regulation of polymicrobial dentoalveolar infection and subsequent tissue destruction. © 2016 Wiley Periodicals, Inc.


Guo Y.,Tohoku UniversitySendai | Miyamoto K.-I.,Tohoku UniversitySendai | Wagner T.,FH Aachen | Schoning M.J.,FH Aachen | And 2 more authors.
Physica Status Solidi (A) Applications and Materials Science | Year: 2014

The light-addressable potentiometric sensor (LAPS) is a semiconductor-based potentiometric sensor using a light probe with an ability of detecting the concentration of biochemical species in a spatially resolved manner. As an important biomedical sensor, research has been conducted to improve its performance, for instance, to realize high-speed measurement. In this work, the idea of facilitating the device-level simulation, instead of using an equivalent-circuit model, is presented for detailed analysis and optimization of the performance of the LAPS. Both carrier distribution and photocurrent response have been simulated to provide new insight into both amplitude-mode and phase-mode operations of the LAPS. Various device parameters can be examined to effectively design and optimize the LAPS structures and setups for enhanced performance. Distribution of minority carriers inside a Si-based LAPS structure under illumination with different wavelengths. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Previous reports have described that simple cognitive training using reading aloud and solving simple arithmetic calculations, so-called learning therapy, can improve executive functions and processing speed in the older adults. Nevertheless, it is not well-known whether learning therapy improve a wide range of cognitive functions or not. We investigated the beneficial effects of learning therapy on various cognitive functions in healthy older adults.We used a single-blinded intervention with two groups (learning therapy group: LT and waiting list control group: WL). Sixty-four elderly were randomly assigned to LT or WL. In LT, participants performed reading Japanese aloud and solving simple calculations training tasks for 6 months. WL did not participate in the intervention. We measured several cognitive functions before and after 6 months intervention periods.Compared to WL, results revealed that LT improved inhibition performance in executive functions (Stroop: LT (Mean = 3.88) vs. WL (Mean = 1.22), adjusted p = 0.013 and reverse Stroop LT (Mean = 3.22) vs. WL (Mean = 1.59), adjusted p = 0.015), verbal episodic memory (Logical Memory (LM): LT (Mean = 4.59) vs. WL (Mean = 2.47), adjusted p = 0.015), focus attention (D-CAT: LT (Mean = 2.09) vs. WL (Mean = -0.59), adjusted p = 0.010) and processing speed compared to the WL control group (digit symbol coding: LT (Mean = 5.00) vs. WL (Mean = 1.13), adjusted p = 0.015 and Symbol Search (SS): LT (Mean = 3.47) vs. WL (Mean = 1.81), adjusted p = 0.014).This randomized controlled trial (RCT) can be showed the benefit of LT on inhibition of executive functions, verbal episodic memory, focus attention and processing speed in healthy elderly people. Our results were discussed under overlapping hypothesis.


PubMed | Tohoku University, Tohoku UniversitySendai, Fukushima Medical University and Tohoku Pharmaceutical University
Type: | Journal: Frontiers in psychology | Year: 2016

Plasma oxytocin (OT) and arginine vasopressin (AVP) are associated with individual differences in emotional responses and behaviors. The amygdala is considered to be an important brain region for regulating emotion-based behavior, with OT and AVP modulating activity in the amygdala during the processing of negative emotions. In particular, increased OT levels may diminish amygdala activation (anxiolytic effects) and enhanced AVP levels may augment amygdala activation (anxiogenic effects) when negative emotions are processed. A growing body of research has shown that the effects of OT and AVP are modulated by sex: the aforementioned anxiolytic effects of OT and the anxiogenic effects of AVP occur in men, but not in women. However, we have little knowledge regarding the biological mechanisms underlying OT and AVP plasma levels or their respective anxiogenic and anxiolytic effects; similarly, little is known about the causes and nature of sex differences related to these neuropeptides and their effects on emotional processing. In the current study, we focused on the neural functions associated with the biological mechanisms underlying such effects. We hypothesized that amygdala activation would correlate with trait plasma OT (anxiolytic effects) and AVP (anxiogenic effects) levels because the amygdala is thought to affect the coordinated release of these neuropeptides following affective experiences. We further hypothesized that the effects would be modulated by sex. We assessed 51 participants (male and female) using a paradigm involving negative emotion in conjunction with functional magnetic resonance imaging and measurements of plasma OT and AVP levels. We determined that increased plasma AVP levels were positively associated with amygdala activation (anxiogenic effects) in men, but not in women. These findings highlight the potential underlying neural mechanisms of plasma AVP levels in men.


PubMed | Tohoku University, University of Human Arts and Sciences, ADVANTAGE Risk Management Co., Japan National Institute of Health Sciences and 3 more.
Type: | Journal: Frontiers in psychology | Year: 2016

Poor sleep quality negatively affects memory performance, and working memory in particular. We investigated sleep habits related to sleep quality including sleep duration, daytime nap duration, nap frequency, and dream content recall frequency (DCRF). Declarative working memory can be subdivided into verbal working memory (VWM) and visuospatial working memory (VSWM). We hypothesized that sleep habits would have different effects on VWM and VSWM. To our knowledge, our study is the first to investigate differences between VWM and VSWM related to daytime nap duration, nap frequency, and DCRF. Furthermore, we tested the hypothesis that the effects of duration and frequency of daytime naps and DCRF on VWM and VSWM differed according to sex. We assessed 779 healthy right-handed individuals (434 males and 345 females; mean age: 20.7 1.8 years) using a digit span forward and backward VWM task, a forward and backward VSWM task, and sleep habits scales. A correlation analysis was used to test the relationships between VWM capacity (VWMC) and VSWM capacity (VSWMC) scores and sleep duration, nap duration, nap frequency, and DCRF. Furthermore, multiple regression analyses were conducted to identify factors associated with VWMC and VSWMC scores and to identify sex-related differences. We found significant positive correlations between VSWMC and nap duration and DCRF, and between VWMC and sleep duration in all subjects. Furthermore, we found that working memory capacity (WMC) was positively correlated with nap duration in males and with sleep duration in females, and DCRF was positively correlated with VSWMC in females. Our finding of sex-related differences in the effects of sleep habits on WMC has not been reported previously. The associations between WMC and sleep habits differed according to sex because of differences in the underlying neural correlates of VWM and VSWM, and effectiveness of the sleep habits in males and females.


Kanehira M.,Miyagi University | Fujiwara T.,Miyagi University | Nakajima S.,Red Cross | Okitsu Y.,Miyagi University | And 5 more authors.
Stem Cells | Year: 2016

Mesenchymal stromal cells (MSCs) are multipotent progenitor cells and there is much interest in how MSCs contribute to the regulation of the tumor microenvironment. Whether MSCs exert a supportive or suppressive effect on tumor progression is still controversial, but is likely dependent on a variety of factors that are tumor-type dependent. Multiple myeloma (MM) is characterized by growth of malignant plasma cells in the bone marrow. It has been shown that the progression of MM is governed by MSCs, which act as a stroma of the myeloma cells. Although stroma is created via mutual communication between myeloma cells and MSCs, the mechanism is poorly understood. Here we explored the role of lysophosphatidic acid (LPA) signaling in cellular events where MSCs were converted into either MM-supportive or MM-suppressive stroma. We found that myeloma cells stimulate MSCs to produce autotaxin, an indispensable enzyme for the biosynthesis of LPA, and LPA receptor 1 (LPA1) and 3 (LPA3) transduce opposite signals to MSCs to determine the fate of MSCs. LPA3-silenced MSCs (siLPA3-MSCs) exhibited cellular senescence-related phenotypes in vitro, and significantly promoted progression of MM and tumor-related angiogenesis in vivo. In contrast, siLPA1-MSCs showed resistance to cellular senescence in vitro, and efficiently delayed progression of MM and tumor-related angiogenesis in vivo. Consistently, anti-MM effects obtained by LPA1-silencing in MSCs were completely reproduced by systemic administration of Ki6425, an LPA1 antagonist. Collectively, our results indicate that LPA signaling determines the fate of MSCs and has potential as a therapeutic target in MM. © 2016 AlphaMed Press.


Movila A.,The Forsyth Institute | Ishii T.,The Forsyth Institute | Ishii T.,Tokyo Dental College | Albassam A.,The Forsyth Institute | And 15 more authors.
Journal of Bone and Mineral Research | Year: 2016

By binding to its chemokine receptor CXCR4 on osteoclast precursor cells (OCPs), it is well known that stromal cell-derived factor-1 (SDF-1) promotes the chemotactic recruitment of circulating OCPs to the homeostatic bone remodeling site. However, the engagement of circulating OCPs in pathogenic bone resorption remains to be elucidated. The present study investigated a possible chemoattractant role of macrophage migration inhibitory factor (MIF), another ligand for C-X-C chemokine receptor type 4 (CXCR4), in the recruitment of circulating OCPs to the bone lytic lesion. To accomplish this, we used Csf1r-eGFP-knock-in (KI) mice to establish an animal model of polymethylmethacrylate (PMMA) particle-induced calvarial osteolysis. In the circulating Csf1r-eGFP+ cells of healthy Csf1r-eGFP-KI mice, Csf1r+/CD11b+ cells showed a greater degree of RANKL-induced osteoclastogenesis compared to a subset of Csf1r+/RANK+ cells in vitro. Therefore, Csf1r-eGFP+/CD11b+ cells were targeted as functionally relevant OCPs in the present study. Although expression of the two cognate receptors for MIF, CXCR2 and CXCR4, was elevated on Csf1r+/CD11b+ cells, transmigration of OCPs toward recombinant MIF in vitro was facilitated by ligation with CXCR4, but not CXCR2. Meanwhile, the level of PMMA-induced bone resorption in calvaria was markedly greater in wild-type (WT) mice compared to that detected in MIF-knockout (KO) mice. Interestingly, in contrast to the elevated MIF, diminished SDF-1 was detected in a particle-induced bone lytic lesion of WT mice in conjunction with an increased number of infiltrating CXCR4+ OCPs. However, such diminished SDF-1 was not found in the PMMA-injected calvaria of MIF-KO mice. Furthermore, stimulation of osteoblasts with MIF in vitro suppressed their production of SDF-1, suggesting that MIF can downmodulate SDF-1 production in bone tissue. Systemically administered anti-MIF neutralizing monoclonal antibody (mAb) inhibited the homing of CXCR4+ OCPs, as well as bone resorption, in the PMMA-injected calvaria, while increasing locally produced SDF-1. Collectively, these data suggest that locally produced MIF in the inflammatory bone lytic site is engaged in the chemoattraction of circulating CXCR4+ OCPs. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research


Williams M.C.,Tohoku UniversitySendai | Winkler W.,Tohoku UniversitySendai | Winkler W.,University of Hamburg | Suzuki A.,Tohoku UniversitySendai | Miyamoto A.,Tohoku UniversitySendai
EFC 2011 - Proceedings of the 4th European Fuel Cell Piero Lunghi Conference and Exhibition | Year: 2011

There are five useful concepts in understanding fuel cell performance. Thermal and exergetic efficiencies, power, area specific resistance (ASR), and degradation. The later two must be developed for different fuel cell operating modes. The concepts of exergetic efficiency and entropy production are related to ASR and degradation. It is shown that exergetic efficiency is a time-dependent function useful in describing the thermal efficiency of a fuel cell and the change in thermal efficiency of a degrading fuel cell.


Kadota I.,Okayama University | Sato Y.,Tohoku UniversitySendai | Fujita N.,Okayama University | Takamura H.,Okayama University | Yamamoto Y.,Tohoku UniversitySendai
Tetrahedron | Year: 2015

Abstract Convergent synthesis of the EFGH ring segment of ciguatoxin CTX3C was investigated by using the intramolecular allylation of an α-chloroacetoxy ether and/or O,S-acetal, and subsequent ring-closing metathesis. A new method for the preparation of γ-alkoxyallylstannane is also described. © 2015 Elsevier Ltd.

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