Visualizing spatiotemporal dynamics of apoptosis after G1 arrest by human T cell leukemia virus type 1 Tax and insights into gene expression changes using microarray-based gene expression analysis

BACKGROUND: Human T cell leukemia virus type 1 (HTLV-1) Tax is a potent activator of viral and cellular gene expression that interacts with a number of cellular proteins. Many reports show that Tax is capable of regulating cell cycle progression and apoptosis both positively and negatively. However, it still remains to understand why the Tax oncoprotein induces cell cycle arrest and apoptosis, or whether Tax-induced apoptosis is dependent upon its ability to induce G1 arrest. The present study used time-lapse imaging to explore the spatiotemporal patterns of cell cycle dynamics in Tax-expressing HeLa cells containing the fluorescent ubiquitination-based cell cycle indicator, Fucci2. A large-scale host cell gene profiling approach was also used to identify the genes involved in Tax-mediated cell signaling events related to cellular proliferation and apoptosis. RESULTS: Tax-expressing apoptotic cells showed a rounded morphology and detached from the culture dish after cell cycle arrest at the G1 phase. Thus, it appears that Tax induces apoptosis through pathways identical to those involved in G1 arrest. To elucidate the mechanism(s) by which Tax induces cell cycle arrest and apoptosis, regulation of host cellular genes by Tax was analyzed using a microarray containing approximately 18,400 human mRNA transcripts. Seventeen genes related to cell cycle regulation were identified as being up or downregulated \u3e 2.0-fold in Tax-expressing cells. Several genes, including SMAD3, JUN, GADD45B, DUSP1 and IL8, were involved in cellular proliferation, responses to cellular stress and DNA damage, or inflammation and immune responses. Additionally, 23 pro- and anti-apoptotic genes were deregulated by Tax, including TNFAIP3, TNFRS9, BIRC3 and IL6. Furthermore, the kinetics of IL8, SMAD3, CDKN1A, GADD45A, GADD45B and IL6 expression were altered following the induction of Tax, and correlated closely with the morphological changes observed by time-lapse imaging. CONCLUSIONS: Taken together, the results of this study permit a greater understanding of the biological events affected by HTLV-1 Tax, particularly the regulation of cellular proliferation and apoptosis. Importantly, this study is the first to demonstrate the dynamics of morphological changes during Tax-induced apoptosis after cell cycle arrest at the G1 phase

Visualizing spatiotemporal dynamics of apoptosis after G1 arrest by human T cell leukemia virus type 1 Tax and insights into gene expression changes using microarray-based gene expression analysis.

BACKGROUND: Human T cell leukemia virus type 1 (HTLV-1) Tax is a potent activator of viral and cellular gene expression that interacts with a number of cellular proteins. Many reports show that Tax is capable of regulating cell cycle progression and apoptosis both positively and negatively. However, it still remains to understand why the Tax oncoprotein induces cell cycle arrest and apoptosis, or whether Tax-induced apoptosis is dependent upon its ability to induce G1 arrest. The present study used time-lapse imaging to explore the spatiotemporal patterns of cell cycle dynamics in Tax-expressing HeLa cells containing the fluorescent ubiquitination-based cell cycle indicator, Fucci2. A large-scale host cell gene profiling approach was also used to identify the genes involved in Tax-mediated cell signaling events related to cellular proliferation and apoptosis. RESULTS: Tax-expressing apoptotic cells showed a rounded morphology and detached from the culture dish after cell cycle arrest at the G1 phase. Thus, it appears that Tax induces apoptosis through pathways identical to those involved in G1 arrest. To elucidate the mechanism(s) by which Tax induces cell cycle arrest and apoptosis, regulation of host cellular genes by Tax was analyzed using a microarray containing approximately 18,400 human mRNA transcripts. Seventeen genes related to cell cycle regulation were identified as being up or downregulated \u3e 2.0-fold in Tax-expressing cells. Several genes, including SMAD3, JUN, GADD45B, DUSP1 and IL8, were involved in cellular proliferation, responses to cellular stress and DNA damage, or inflammation and immune responses. Additionally, 23 pro- and anti-apoptotic genes were deregulated by Tax, including TNFAIP3, TNFRS9, BIRC3 and IL6. Furthermore, the kinetics of IL8, SMAD3, CDKN1A, GADD45A, GADD45B and IL6 expression were altered following the induction of Tax, and correlated closely with the morphological changes observed by time-lapse imaging. CONCLUSIONS: Taken together, the results of this study permit a greater understanding of the biological events affected by HTLV-1 Tax, particularly the regulation of cellular proliferation and apoptosis. Importantly, this study is the first to demonstrate the dynamics of morphological changes during Tax-induced apoptosis after cell cycle arrest at the G1 phase

Zerumbone Exhibits Anti-Inflammatory Functions via HSF1

Zerumbone is a sesquiterpene present in Zinger zerumbet. Many studies have demonstrated its marked anti-inflammatory and anti-carcinogenesis activities. Recently, we showed that zerumbone binds to numerous proteins with scant selectivity and induces the expression of heat shock proteins (HSPs) in hepatocytes. To dampen proteo-toxic stress, organisms have a stress-responsive molecular machinery, known as heat shock response. Heat shock factor 1 (HSF1) plays a key role in this protein quality control system by promoting activation of HSPs. In this study, we investigated whether zerumbone-induced HSF1 activation contributes to its anti-inflammatory functions in stimulated macrophages. Our findings showed that zerumbone increased cellular protein aggregates and promoted nuclear translocation of HSF1 for HSP expression. Interestingly, HSF1 down-regulation attenuated the suppressive effects of zerumbone on mRNA and protein expressions of pro-inflammatory genes, including inducible nitric oxide synthase and interlukin-1β. These results suggest that proteo-stress induced by zerumbone activates HSF1 for exhibiting its anti-inflammatory functions

Widely Extended [OIII] 88 um Line Emission around the 30 Doradus Region Revealed with AKARI FIS-FTS

We present the distribution map of the far-infrared [OIII] 88um line emission around the 30 Doradus (30 Dor) region in the Large Magellanic Cloud obtained with the Fourier Transform Spectrometer of the Far-Infrared Surveyor onboard AKARI. The map reveals that the [OIII] emission is widely distributed by more than 10' around the super star cluster R136, implying that the 30 Dor region is affluent with interstellar radiation field hard enough to ionize O^{2+}. The observed [OIII] line intensities are as high as (1-2) x 10^{-6} W m^{-2} sr^{-1} on the peripheral regions 4'-5' away from the center of 30 Dor, which requires gas densities of 60-100 cm^{-3}. However the observed size of the distribution of the [OIII] emission is too large to be explained by massive stars in the 30 Dor region enshrouded by clouds with the constant gas density of 10^2 cm^{-3}. Therefore the surrounding structure is likely to be highly clumpy. We also find a global correlation between the [OIII] and the far-infrared continuum emission, suggesting that the gas and dust are well mixed in the highly-ionized region where the dust survives in clumpy dense clouds shielded from the energetic photons.Comment: 17 pages, 9 figures, accepted for publication in Publications of the Astronomical Society of Japan (PASJ

The meaning of life for an elderly man living alone : a narrative approach

Aim: To improve nursing care for the elderly in order to allow them to live independently. This study has used the narrative of an elderly man to learn about what has given his life meaning.Method: Fifteen key concepts were extracted from interviews using the narrative approach.Results and Conclusions: Mr. A, now near the end of his life, has found meaning in living his life, not only for himself, but also for those around him. The elderly support their own physical and mental health,and adjust to day-to-day life. Nursing care for the elderly should watch for and support these self-supporting efforts

Views of Students Undergoing Home Economics Teacher Training : Reconstructing the Human Life Sciences Curriculum of Hiroshima University

We reconsidered the core subject of the human life sciences education curriculum at Hiroshima University to examine the views of students undergoing home economics teacher training. Although it is possible to understand the task of living conceptually and abstractly, an issue that students were taught in the previous year, our study revealed that students did not understand their role as prosumers. In addition, we found that understanding of Home Economics as a background science did not help. We confirmed the effect of Problem Based Learning (PBL) in advance, by testing students who took the same subjects in a previous year. Moreover, we examined product and performance issues including cooking practice, and proposed a learning process to address the issue proactively and cooperatively. This proposed process involves the recognition of conscious living by deeply examining important issues, to enhance students’ awareness of their role as prosumers, and highlighting the significance of Home Economics as a background science

出来事の残響 : 〈原爆文学〉と〈戦後沖縄文学〉

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 小森 陽一, 東京大学教授 エリス 俊子, 東京大学准教授 田尻 芳樹, 東京大学准教授 武田 将明, 琉球大学教授 新城 郁夫University of Tokyo(東京大学

Clinical Relevance of Parafoveal Intercapillary Spaces and Foveal Avascular Zone in Diabetic Retinopathy Without Macular Edema

Purpose: To investigate the clinical significance of intercapillary spaces on swept source optical coherence tomography angiography images in diabetic retinopathy. Methods: We retrospectively reviewed 110 eyes of 110 patients suffering from diabetic retinopathy without macular edema for whom 3 × 3 mm swept source optical coherence tomography angiography images centered on the fovea were obtained. Automatic image processing of the superficial slab images allowed us to define the areas encircled by retinal vessels as intercapillary spaces within the central 2-mm circle. We evaluated how the quantitative parameters of intercapillary spaces are associated with logMAR and feasible to diagnose diabetic macular ischemia. Results: Total counts (ρ = −0.419; P < 0.001) rather than morphologic parameters of the intercapillary spaces showed a significant correlation with logMAR. There were individual levels of correlations between logMAR and counts of intercapillary spaces in individual sectors. In particular, the summed numbers of the spaces in three highly significant sectors were more significantly associated with logMAR (ρ = −0.515; P < 0.001). Multivariate analyses confirmed that the number of the intercapillary spaces (β = −0.266; P = 0.016) and foveal avascular zone area (β = 0.227; P = 0.042) were related to logMAR. The clustering using the foveal avascular zone area and the number of intercapillary spaces revealed two major clusters; one had fewer intercapillary spaces (P < 0.001) and poorer logMAR (P < 0.001) than the other, with a wide range of the foveal avascular zone area. Conclusions: Decreased intercapillary spaces contribute to visual impairment in diabetic retinopathy and suggest one possible criterion of objective diagnosis of diabetic macular ischemia