Time-course transcriptome analysis of human cellular reprogramming from multiple cell types reveals the drastic change occurs between the mid phase and the late phase

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Detecting a Taxi from a Video for Visually Handicapped People

This paper proposes a method of detecting a specific moving object, a taxi in particular, on a road from a video provided from a camera attached to a user. In order to raise the quality of life of visually handicapped people, a computer vision system which works in place of their eyes and a brain may be useful. As one of such systems, this study focuses its attention on finding a taxi on a road which is a convenient vehicle to such people as a means of transfer outdoors. The novel idea of this study is that a camera and a PC system for finding a taxi is carried by a user, a visually handicapped person, for example. The proposed method employs the HOG features to represent a vehicle, and finds a taxi by Real AdaBoost and color information with the detected vehicle. The performance of the proposed method is shown experimentally.The 34th Chinese Control Conference and SICE Annual Conference 2015, July 28-30, 2015, Hangzhou, Chin

Salubrinal acts as a Dusp2 inhibitor and suppresses inflammation in anti-collagen antibody-induced arthritis

Dual-specificity phosphatase 2 (Dusp2; also called phosphatase of activated cells 1, PAC1) is highly expressed in activated immune cells. We examined whether a potential inhibitor of Dusp2, salubrinal, prevents inflammatory cytokine expression in immune cells and arthritic responses in a mouse model of anti-collagen antibody-induced arthritis (CAIA). Salubrinal is a synthetic chemical that inhibits de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). In this study, we examined the effects of salubrinal on expression of inflammation linked genes as well as a family of DUSP genes using genome-wide microarrays, qPCR, and RNA interference. We also evaluated the effects of salubrinal on arthritic responses in CAIA mice using clinical and histological scores. The results revealed that salubrinal decreased inflammatory gene expression in macrophages, T lymphocytes, and mast cells. Dusp2 was suppressed by salubrinal in LPS-activated macrophages as well as PMA/ionomycin-activated T lymphocytes and mast cells. Furthermore, a partial silencing of Dusp2 downregulated IL1β and Cox2, and the inflammatory signs of CAIA mice were significantly suppressed by salubrinal. Collectively, this study presents a novel therapeutic possibility of salubrinal for inflammatory arthritis such as RA through inhibition of Dusp2

Predicting and validating the pathway of Wnt3a-driven suppression of osteoclastogenesis

Wnt signaling plays a major role in bone homeostasis and mechanotransduction, but its role and regulatory mechanism in osteoclast development are not fully understood. Through genome-wide in silico analysis, we examined Wnt3a-driven regulation of osteoclast development. Mouse bone marrow-derived cells were incubated with RANKL in the presence and absence of Wnt3a. Using microarray mRNA expression data, we conducted principal component analysis and predicted transcription factor binding sites (TFBSs) that were potentially involved in the responses to RANKL and Wnt3a. The principal component analysis predicted potential Wnt3a responsive regulators that would reverse osteoclast development, and a TFBS prediction algorithm indicated that the AP1 binding site would be linked to Wnt3a-driven suppression. Since c-Fos was upregulated by RANKL and downregulated by Wnt3a in a dose-dependent manner, we examined its role using RNA interference. The partial silencing of c-Fos suppressed RANKL-driven osteoclastogenesis by downregulating NFATc1, a master transcription factor of osteoclast development. Although the involvement of c-Myc was predicted and partially silencing c-Myc slightly reduced the level of TRAP, c-Myc silencing did not alter the expression of NFATc1. Collectively, the presented systems-biology approach demonstrates that Wnt3a attenuates RANKL-driven osteoclastogenesis by blocking c-Fos expression and suggests that mechanotransduction of bone alters the development of not only osteoblasts but also osteoclasts through Wnt signaling

送粉生態、宿主種および集団遺伝構造から迫る小笠原諸島固有寄生植物シマウツボ(ハマウツボ科）の進化

京都大学新制・課程博士博士(理学)甲第25144号理博第5051号京都大学大学院理学研究科生物科学専攻(主査)准教授 高山 浩司, 教授 田村 実, 教授 石田 厚学位規則第4条第1項該当Doctor of ScienceKyoto UniversityDGA

Time-course transcriptome analysis of human cellular reprogramming from multiple cell types reveals the drastic change occurs between the mid phase and the late phase

BackgroundHuman induced pluripotent stem cells (hiPSCs) have been attempted for clinical application with diverse iPSCs sources derived from various cell types. This proposes that there would be a shared reprogramming route regardless of different starting cell types. However, the insights of reprogramming process are mostly restricted to only fibroblasts of both human and mouse. To understand molecular mechanisms of cellular reprogramming, the investigation of the conserved reprogramming routes from various cell types is needed. Particularly, the maturation, belonging to the mid phase of reprogramming, was reported as the main roadblock of reprogramming from human dermal fibroblasts to hiPSCs. Therefore, we investigated first whether the shared reprogramming routes exists across various human cell types and second whether the maturation is also a major blockage of reprogramming in various cell types.ResultsWe selected 3615 genes with dynamic expressions during reprogramming from five human starting cell types by using time-course microarray dataset. Then, we analyzed transcriptomic variances, which were clustered into 3 distinct transcriptomic phases (early, mid and late phase); and greatest difference lied in the late phase. Moreover, functional annotation of gene clusters classified by gene expression patterns showed the mesenchymal-epithelial transition from day 0 to 3, transient upregulation of epidermis related genes from day 7 to 15, and upregulation of pluripotent genes from day 20, which were partially similar to the reprogramming process of mouse embryonic fibroblasts. We lastly illustrated variations of transcription factor activity at each time point of the reprogramming process and a major differential transition of transcriptome in between day 15 to 20 regardless of cell types. Therefore, the results implied that the maturation would be a major roadblock across multiple cell types in the human reprogramming process.ConclusionsHuman cellular reprogramming process could be traced into three different phases across various cell types. As the late phase exhibited the greatest dissimilarity, the maturation step could be suggested as the common major roadblock during human cellular reprogramming. To understand further molecular mechanisms of the maturation would enhance reprogramming efficiency by overcoming the roadblock during hiPSCs generation

On the Characteristic Difference of Neoclassical Bootstrap Current and Its Effects on MHD Equilibria between CHS Heliotron/Torsatron and CHS-qa Quasi-Axisymmetric Stellarator

The characteristic difference of neoclassical bootstrap current and its effects on MHD equilibria are described for the CHS heliotron/torsatron and the CHS-qa quasi-axisymmetric stellarator. The direction of bootstrap current strongly depends on collisionality in CHS, whereas it does not in CHS-qa because of quasi-axisymmetry. In the CHS configuration, it appears that enhanced bumpy (Bs1) and sideband components of helical ripple (By1) play an important role in reducing the magnetic geometrical factor, which is a key factor in evaluating the value of bootstrap cuffent, and determining its polarity. The bootstrap current in CHS-qa is theoretically predicted to be larger than that in CHS and produces significant effects on the resulting rotational transform and magnetic shear. In the finite B plasmas, the magnetic well becomes deeper in both CHS and CHS-qa and its region is expanded in CHS. The existence of co-flowing bootstrap current makes the magnetic well shallow in comparison with that in currentless equilibrium

Guanabenz Downregulates Inflammatory Responses via eIF2α Dependent and Independent Signaling

Integrated stress responses (ISR) may lead to cell death and tissue degeneration via eukaryotic translation initiation factor 2 α (eIF2α)-mediated signaling. Alleviating ISR by modulating eIF2α phosphorylation can reduce the symptoms associated with various diseases. Guanabenz is known to elevate the phosphorylation level of eIF2α and reduce pro-inflammatory responses. However, the mechanism of its action is not well understood. In this study, we investigated the signaling pathway through which guanabenz induces anti-inflammatory effects in immune cells, in particular macrophages. Genome-wide mRNA profiling followed by principal component analysis predicted that colony stimulating factor 2 (Csf2, or GM-CSF as granulocyte macrophage colony stimulating factor) is involved in the responses to guanabenz. A partial silencing of Csf2 or eIF2α by RNA interference revealed that Interleukin-6 (IL6), Csf2, and Cyclooxygenase-2 (Cox2) are downregulated by guanabenz-driven phosphorylation of eIF2α. Although expression of IL1β and Tumor Necrosis Factor-α (TNFα) was suppressed by guanabenz, their downregulation was not directly mediated by eIF2α signaling. Collectively, the result herein indicates that anti-inflammatory effects by guanabenz are mediated by not only eIF2α-dependent but also eIF2α-independent signaling

Orbit Topology and Confinement of Energetic Ions in the CHS-qa Quasi-Axisymmetric Stellarator

The orbit topology and confinement of neutral beam-injected energetic ions are investigated for the current target configuration of the CHS-qa quasi-axisymmetric stellarator. It was shown that tangentially co-injected neutral beam (NB) heating is efficient even at a low magnetic field strength Bt of 0.5 T, whereas the heating efficiency of the counter-injected NB becomes significantly lower as Bt decreases because of the increase of first orbit loss. The energy loss rate increases as the beam injection angle becomes perpendicular, suggesting that the residual non-axisymmetric ripple in the peripheral domain plays a role in enhancing the transport of trapped ions. An interesting observation involves the appearance of the island structure in both the gyro motion following orbit and the guiding center collisionless orbit of counter-moving transit beam ions. It appears under a particular, narrow range of parameters, i.e., energy, pitch angle v///v, normalized minor radius r/a at the launching point and Bt

Effects of Current Profile on Global Ideal MHD Stability in a Compact Quasi-Axisymmetric Stellarator

The global ideal magnetohydrodynamic (MHD) stability for a proposed compact quasi-axisymmetric stellarator CHS-qa has been investigated taking the effect of bootstrap current into account. Assuming experimentally achievable density and temperature profiles, the stability properties of global low-n modes have been studied by using threedimensionalnumerical codes based on fixed boundary MHD equilibria including self-consistent bootstrap current for the CHS-qa reference configuration. Consequently it has been shown that values of edge rotational transform play a crucial role in triggering external kink instability. Concerning a lot of other possibilities in experimental practice to change the total parallel current, we have also studied equilibria with increased or decreased parallel current, but fixed profile. The onset of external kink modes depends on rotational transform or current profile, and we found a stable equilibrium in spite of the edge rotational transform above 0.5. The results imply the possibility of stabilizing external kink modes through current and/or pressure profile control in high beta equilibria