Leptin Is an Endogenous Protective Protein against the Toxicity Exerted by Tumor Necrosis Factor

Tumor necrosis factor (TNF) is a central mediator of a number of important pathologies such as the systemic inflammatory response syndrome. Administration of high TNF doses induces acute anorexia, metabolic derangement, inflammation, and eventually shock and death. The in vivo effects of TNF are largely mediated by a complex network of TNF-induced cytokines and hormones acting together or antagonistically. Since TNF also induces leptin, a hormone secreted by adipocytes that modulates food intake and metabolism, we questioned the role of leptin in TNF-induced pathology. To address this question, we tested mouse strains that were defective either in leptin gene (ob/ob) or in functional leptin receptor gene (db/db), and made use of a receptor antagonist of leptin. Ob/ob and db/db mice, as well as normal mice treated with antagonist, exhibited increased sensitivity to the lethal effect of TNF. Exogenous leptin afforded protection to TNF in ob/ob mice, but failed to enhance the protective effect of endogenous leptin in normal mice. We conclude that leptin is involved in the protective mechanisms that allow an organism to cope with the potentially autoaggressive effects of its immune system

Magnetic properties of epitaxial Fe3_3O4_4 films with various crystal orientations and TMR effect in room temperature

Fe$_3$O$_4$ is a ferrimagnetic spinel ferrite that exhibits electric conductivity at room temperature (RT). Although the material has been predicted to be a half metal according to ab-initio calculations, magnetic tunnel junctions (MTJs) with Fe$_3$O$_4$ electrodes have demonstrated a small tunnel magnetoresistance effect. Not even the sign of the TMR ratio has been experimentally established. Here, we report on the magnetic properties of epitaxial Fe$_3$O$_4$ films with various crystal orientations. The films exhibited apparent crystal orientation dependence on hysteresis curves. In particular, Fe$_3$O$_4$(110) films exhibited in-plane uniaxial magnetic anisotropy. With respect to the squareness of hysteresis, Fe$_3$O$_4$ (111) demonstrated the largest squareness. Furthermore, we fabricated MTJs with Fe$_3$O$_4$(110) electrodes, and obtained an TMR effect of -12\% at RT. The negative TMR ratio corresponded to the negative spin polarization of Fe$_3$O$_4$ predicted from band calculations

A feasibility study of the measurement of Higgs pair creation at a Photon Linear Collider

We studied the feasibility of the measurement of Higgs pair creation at a Photon Linear Collider (PLC). From the sensitivity to the anomalous self-coupling of the Higgs boson, the optimum $\gamma \gamma$ collision energy was found to be around 270 GeV for a Higgs mass of 120 GeV/$c^2$. We found that large backgrounds such as $\gamma \gamma \rightarrow W^+W^-, ZZ,$ and $b\bar{b}b\bar{b}$, can be suppressed if correct assignment of tracks to parent partons is achieved and Higgs pair events can be observed with a statistical significance of $\sim 5 \sigma$ by operating the PLC for 5 years.Comment: 7 pages, 8 figures, 5 table

Long-term changes in the relationship between the seasonal precipitation and El Niño–Southern Oscillation over the Asian summer monsoon region

Interdecadal changes in the relationship between the Asian summer monsoon precipitation and El Niño-Southern Oscillation (ENSO) for the period 1950 onwards were investigated. During the third quarter of the 20th century, the summer seasonal precipitation over the whole India was negatively correlated to sea surface temperature anomaly (SSTA) over the Niño 3.4 region (5°S-5°N, 120°-170°W) associated with ENSO, which is a well-known inverse relationship between Indian summer monsoon precipitation and ENSO. However, during the final quarter of the 20th century, this negative correlation appeared only in the southern and northern parts of India. The negative correlation in northeast India has weakened and changed to a weak positive correlation. Concurrent with this long-term change, the relationship between summer seasonal precipitation over the Indochina Peninsula and the SSTA over the Niño 3.4 region also changed from a weak negative to a weak positive correlation during the second half of the 20th century. The interannual dipole structure between the summer seasonal precipitation over peninsular and northeast India strengthened from the 1970s, consistent with the weakening of the inverse relationship between the summer seasonal precipitation over the whole India and ENSO. The SSTA pattern of ENSO was related to the summer seasonal precipitation over peninsular India throughout the analyzed period, whereas the relationship between the SSTA pattern of ENSO and the summer seasonal precipitation over northeast India and the Indochina Peninsula became unclear from the third quarter of the 20th century to the final quarter. These long-term changes in the relationship between the precipitation and SSTA were consistent with the changes in the relationship between the precipitation and the large-scale atmospheric circulations

卵巣の病態における小胞体ストレス応答の意義の解明

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 南學 正臣, 東京大学准教授 永松 健, 東京大学講師 坊垣 昌彦, 東京大学講師 平田 陽一郎, 東京大学講師 山下 裕玄University of Tokyo(東京大学

Depletion of RIPK3 or MLKL blocks TNF-driven necroptosis and switches towards a delayed RIPK1 kinase-dependent apoptosis

In human cells, the RIPK1-RIPK3-MLKL-PGAM5-Drp1 axis drives tumor necrosis factor (TNF)-induced necroptosis through mitochondrial fission, but whether this pathway is conserved among mammals is not known. To answer this question, we analyzed the presence and functionality of the reported necroptotic axis in mice. As in humans, knockdown of receptorinteracting kinase-3 (RIPK3) or mixed lineage kinase domain like (MLKL) blocks TNF-induced necroptosis in L929 fibrosarcoma cells. However, repression of either of these proteins did not protect the cells from death, but instead induced a switch from TNF-induced necroptosis to receptor-interacting kinase-1 (RIPK1) kinase-dependent apoptosis. In addition, although mitochondrial fission also occurs during TNF-induced necroptosis in L929 cells, we found that knockdown of phosphoglycerate mutase 5 (PGAM5) and dynamin 1 like protein (Drp1) did not markedly protect the cells from TNF-induced necroptosis. Depletion of Pink1, a reported interactor of both PGAM5 and Drp1, did not affect TNF-induced necroptosis. These results indicate that in these murine cells mitochondrial fission and Pink1 dependent processes, including Pink-Parkin dependent mitophagy, apparently do not promote necroptosis. Our data demonstrate that the core components of the necrosome (RIPK1, RIPK3 and MLKL) are crucial to induce TNF-dependent necroptosis both in human and in mouse cells, but the associated mechanisms may differ between the two species or cell types

A unique stroke case with contralateral sulcal hyperintensity on fluid-attenuated inversion recovery image changed to linear serpiginous structures

An 83-year-old man developed acute ischemic stroke. Brain magnetic resonance imaging (MRI) showed ischemic stroke in the left parietal lobe gyri, but fluid-attenuated inversion recovery (FLAIR) showed hyperintensity in the contralateral right temporal-occipital lobe sulci. Follow-up FLAIR image showed the gradual disappearance of the sulcal hyperintensity in the sulci and changed to linear serpiginous structures. This is a unique stroke case showing transitioned FLAIR findings suggesting that the sulcal hyperintensity findings are more severe and an earlier ischemic condition than the linear serpiginous structures

<論文>学位に付記する専攻分野の名称の多様性の構造 : 平成27年度調査からみる現状と変動

The 1991 revision of educational codes has brought about a diversification of nomenclatures of academic degrees in Japanese higher education. A series of surveys on the nomenclature of academic degrees awarded by universities has been conducted by the National Institution for Academic Degrees and Quality Enhancement of Higher Education（NIAD-QE）. More than a decade has passed since the results of this longitudinal study were reported for the last time. So, it is time to determine how the revision of the code may or may not have changed state of, and trend in, the nomenclature of academic degrees in Japan

Viral dosing of influenza A infection reveals involvement of RIPK3 and FADD, but not MLKL

RIPK3 was reported to play an important role in the protection against influenza A virus (IAV) in vivo. Here we show that the requirement of RIPK3 for protection against IAV infection in vivo is only apparent within a limited dose range of IAV challenge. We found that this protective outcome is independent from RIPK3 kinase activity and from MLKL. This shows that platform function of RIPK3 rather than its kinase activity is required for protection, suggesting that a RIPK3 function independent of necroptosis is implicated. In line with this finding, we show that FADD-dependent apoptosis has a crucial additional effect in protection against IAV infection. Altogether, we show that RIPK3 contributes to protection against IAV in a narrow challenge dose range by a mechanism that is independent of its kinase activity and its capacity to induce necroptosis