マウス歯発生時におけるインシュリン様成長因子ファミリーの遺伝子発現(Gene expression of insulin-like growth factor family during tooth development of the mouse)

マウス臼歯発生時におけるインシュリン様成長因子(IGF)とIGF結合蛋白質(IGFBP)の発現の時間的・空間的パターンを調べた。IGFとIGFBP発現はin situハイブリダイゼーションにて決定した。E14マウス胚の帽状期、E15胚の帽状期後期、E17-P0の鐘状期、P0-P13のクラウン形成期、P5-P13のルート形成期につき、IGF-I、IGF-II、IGFBP-2、-3、-4、-5、IGF-I受容体(IGF-IR)の発現部位と時期を網羅した。IGFおよびその作用調節因子は歯の成長分化の局所仲介因子となり、歯胚の上皮と間充織で局所的に発現するIGFBP-2、-3、-4、-5は歯の成長分化に役割を果たす可能性が示唆された。マウス臼歯発生時におけるインシュリン様成長因子(IGF)とIGF結合蛋白質(IGFBP)の発現の時間的・空間的パターンを調べた。IGFとIGFBP発現はin situハイブリダイゼーションにて決定した。E14マウス胚の帽状期、E15胚の帽状期後期、E17-P0の鐘状期、P0-P13のクラウン形成期、P5-P13のルート形成期につき、IGF-I、IGF-II、IGFBP-2、-3、-4、-5、IGF-I受容体(IGF-IR)の発現部位と時期を網羅した。IGFおよびその作用調節因子は歯の成長分化の局所仲介因子となり、歯胚の上皮と間充織で局所的に発現するIGFBP-2、-3、-4、-5は歯の成長分化に役割を果たす可能性が示唆された

Transnational Images Of Hiroshima And Nagasaki: Knowledge Production And The Politics Of Representation

This dissertation explores how knowledge on the atomic bombings has been produced in relation to postwar reconstruction, the formation of national discourses, and memories of war and colonialism. By examining cinematic representations of Hiroshima and Nagasaki in Japanese, European, and American films, such as the canonical Hiroshima, Mon Amour and the Japanese documentaries used within it, the dissertation argues that while engaging in an open dialogue with each other in the form of refutation, divergence, and affirmation, these films respond to historical changes in the idea of a human being and the postwar world order resulting from the collapse of Japanese and European colonialisms and the emergence of the US as an atomic superpower in the Cold War. It also contends that the ostensible disjunction between Japanese and Euroamerican discursive spheres precisely constitutes a structure of interdependence substantiated by the complicity of nationalisms. This is a process of an active creation rather than a direct suppression and preclusion of knowledge. Chapter One examines the discrepancies in knowledge about films on the atomic bombing by tracing a variety of ways in which they are consumed, questioned, neglected and censored, while participating in the on-going debates about the disciplinary limitations of Japanese film studies. Chapter Two discusses how the creation of the epic world and the narrative of martyrdom that appear in Japanese films on Hiroshima and Nagasaki have contributed to the isolation of atomic victimization as a "Japanese" tragedy by locating them within a genealogy of these films made in the 1950's and the prewar and postwar histories of these cities. Chapter Three analyzes cinematic strategies to approach the atomic bomb victims, especially the performative aspect of victimization, the automaton-like human beings found in the ruins, and post-bombing victimization, in conjunction with a discussion of the plausibility of film narratives. Chapter Four reconsiders Hiroshima, Mon Amour by redefining the signification of Hiroshima in this film. It posits that what this film has portrayed is not a Hiroshima haunted by the memory of the bombing, but rather a Hiroshima obsessed with the memory of occupation, the on-going reconstruction, and prewar colonial legacies

発生中および除神経された味蕾におけるβ-カテニンの発現と活性化(Expression and activation of β-catenin in developing and denervated taste buds)

出生後発育期間または神経除去後期間の味蕾における活性化β-カテニンの発現の発現機構を明らかにすることを目的として、マウス味蕾におけるβ-カテニン、Wnt10b、Wnt5aおよびWntのレセプターであるFrizzled(Fzd)の発現パターンを調べた。これらパターンはin situハイブリダイゼーションおよび免疫組織化学法を用いて測定した。活性化β-カテニンの細胞質内の蓄積および核内への移行をソニックヘッジホッグ(Shh)免疫反応性基底細胞および味蕾内細胞において観察し、WntおよびそのレセプターであるFzd-1および-3の細胞内挙動を追跡した。これらの結果から、発生および再生の初期段階におけるβ-カテニン転写増大が基底細胞および未熟細胞の味蕾細胞への分化を促進すること、およびマウス味蕾細胞におけるWnt10bおよびFzd-1および-3はWnt/β-カテニン経路を構成し、その経路がβ-カテニンを活性化して、発生および再生の初期段階におけるβ-カテニン遺伝子の発現を上方調節する役割を持つことが示唆された。出生後発育期間または神経除去後期間の味蕾における活性化β-カテニンの発現の発現機構を明らかにすることを目的として、マウス味蕾におけるβ-カテニン、Wnt10b、Wnt5aおよびWntのレセプターであるFrizzled(Fzd)の発現パターンを調べた。これらパターンはin situハイブリダイゼーションおよび免疫組織化学法を用いて測定した。活性化β-カテニンの細胞質内の蓄積および核内への移行をソニックヘッジホッグ(Shh)免疫反応性基底細胞および味蕾内細胞において観察し、WntおよびそのレセプターであるFzd-1および-3の細胞内挙動を追跡した。これらの結果から、発生および再生の初期段階におけるβ-カテニン転写増大が基底細胞および未熟細胞の味蕾細胞への分化を促進すること、およびマウス味蕾細胞におけるWnt10bおよびFzd-1および-3はWnt/β-カテニン経路を構成し、その経路がβ-カテニンを活性化して、発生および再生の初期段階におけるβ-カテニン遺伝子の発現を上方調節する役割を持つことが示唆された

The endogenous soluble VEGF receptor-2 isoform suppresses lymph node metastasis in a mouse immunocompetent mammary cancer model

BACKGROUND: Cancer metastasis contributes significantly to cancer mortality and is facilitated by lymphangiogenesis and angiogenesis. A new splicing variant, endogenous soluble vascular endothelial growth factor receptor-2 (esVEGFR-2) that we recently identified is an endogenous selective inhibitor of lymphangiogenesis. To evaluate the antimetastatic potential of esVEGFR-2, gene therapy with vector expressing esVEGFR-2 (pesVEGFR-2) or endostatin (pEndo) as a positive control was conducted on murine metastatic mammary cancer. METHODS: Syngeneic inoculated metastatic mammary cancers received direct intratumoral injection of pesVEGFR-2, pEndo or pVec as control, once a week for six weeks. In vivo gene electrotransfer was performed on the tumors after each injection. RESULTS: Deaths from metastasis were much lower in the pesVEGFR-2 and pEndo groups than in those of the pVec. Tumor volume was significantly lower in the pesVEGFR-2 and the pEndo groups throughout the study. Multiplicity of lymph node and lung metastatic nodules was significantly suppressed in the pesVEGFR-2 and pEndo groups. Moreover, the total number of overall metastasis including the other organs was also decreased in these groups. However, pesVEGFR-2 was not able to decrease the number of lungs, ovaries, kidneys and adrenals with metastasis as counted by unilateral or bilateral metastasis. The number of CD34+/Lyve-1⁻ blood microvessels was significantly decreased in the pEndo group, while the number of CD34⁻/Lyve-1+ lymphatic vessels was significantly decreased in the pesVEGFR-2 and pEndo groups. In addition, a significant reduction in the number of dilated lymphatic vessels containing intraluminal cancer cells was observed in the pesVEGFR-2 and pEndo groups. Levels of apoptosis were significantly increased in the pEndo group, whereas the rates of cell proliferation were significantly decreased in the pesVEGFR-2 and pEndo groups. CONCLUSIONS: Our data demonstrate that esVEGFR-2 can inhibit mainly lymph node metastasis. The antimetastatic activity of esVEGFR-2 may be of high clinical significance in the treatment of metastatic breast cancer because lymph node involvement is a most important prognostic factor in cancer patients

Predicting Wearing-Off of Parkinson’s Disease Patients Using a Wrist-Worn Fitness Tracker and a Smartphone: A Case Study

Parkinson’s disease (PD) patients experience varying symptoms related to their illness. Therefore, each patient needs a tailored treatment program from their doctors. One approach is the use of anti-PD medicines. However, a “wearing-off” phenomenon occurs when these medicines lose their effect. As a result, patients start to experience the symptoms again until their next medicine intake. In the long term, the duration of “wearing-off” begins to shorten. Thus, patients and doctors have to work together to manage PD symptoms effectively. This study aims to develop a prediction model that can determine the “wearing-off” of anti-PD medicine. We used fitness tracker data and self-reported symptoms from a smartphone application in a real-world environment. Two participants wore the fitness tracker for a month while reporting any symptoms using the Wearing-Off Questionnaire (WoQ-9) on a smartphone application. Then, we processed and combined the datasets for each participant’s models. Our analysis produced prediction models for each participant. The average balanced accuracy with the best hyperparameters was at 70.0–71.7% for participant 1 and 76.1–76.9% for participant 2, suggesting that our approach would be helpful to manage the “wearing-off” of anti-PD medicine, motor fluctuations of PD patients, and customized treatment for PD patients

L-BSE prions after propagation in a non-human primate model

Classical- (C-) and atypical L-type bovine spongiform encephalopathy (BSE) prions cause different pathological phenotypes in cattle brains, and the disease-associated forms of each prion protein (PrPSc) has a dissimilar biochemical signature. Bovine C-BSE prions are the causative agent of variant Creutzfeldt-Jakob disease. To date, human infection with L-BSE prions has not been reported, but they can be transmitted experimentally from cows to cynomolgus monkeys (Macaca fascicularis), a non-human primate model. When transmitted to monkeys, C- and L-BSE prions induce different pathological phenotypes in the brain. However, when isolated from infected brains, the two prion proteins (PrPSc) have similar biochemical signatures (i.e., electrophoretic mobility, glycoforms, and resistance to proteinase K). Such similarities suggest the possibility that L-BSE prions alter their virulence to that of C-BSE prions during propagation in monkeys. To clarify this possibility, we conducted bioassays using inbred mice. C-BSE prions with or without propagation in monkeys were pathogenic to mice, and exhibited comparable incubation periods in secondary passage in mice. By contrast, L-BSE prions, either with or without propagation in monkeys, did not cause the disease in mice, indicating that the pathogenicity of L-BSE prions does not converge towards a C-BSE prion type in this primate model. These results suggest that, although C- and L-BSE prions propagated in cynomolgus monkeys exhibit similar biochemical PrPSc signatures and consist of the monkey amino acid sequence, the two prions maintain strain-specific conformations of PrPSc in which they encipher and retain unique pathogenic traits

Targeting of MAPK-associated molecules identifies SON as a prime target to attenuate the proliferation and tumorigenicity of pancreatic cancer cells

Abstract Background Pancreatic cancer is characterized by constitutive activation of mitogen-activated protein kinase (MAPK). Activation of MAPK is associated with the upregulation of genes implicated in the proliferation and survival of pancreatic cancer cells. We hypothesized that knockdown of these MAPK-associated molecules could produce notable anticancer phenotypes. Methods A RNA interference-mediated knockdown screening of 78 MAPK-associated molecules previously identified was performed to find molecules specifically associated with proliferation of pancreatic cancer cells in vitro. Expression of an identified molecule in pancreatic cancer tissues was examined by immunohistochemistry. In vivo tumorigenicity of cancer cells with stable knockdown of the molecule was assayed by using xenograft models. Flow cytometry and live cell imaging were employed to assess an association of the molecule with cell cycle. Results The knockdown screening revealed that knockdown of SON, the gene encoding SON, which is a large serine/arginine-rich protein involved in RNA processing, substantially suppressed pancreatic cancer cell proliferation and survival in vitro and tumorigenicity in vivo. SON expression was higher in ductal adenocarcinomas than in cells of normal ducts and precursor lesions in pancreatic cancer tissues. Knockdown of SON induced G2/M arrest and apoptosis in cultured cancer cells. The suppressive effect of SON knockdown on proliferation was less pronounced in cultured normal duct epithelial cells. SON formed nuclear speckles in the interphase of the cell cycle and dispersed in the cytoplasm during mitosis. Live cell imaging showed that SON diffusely dispersed in the early mitotic phase, accumulated in some foci in the cytoplasm in the late mitotic phase, and gradually reassembled into speckles after mitosis. Conclusion These results indicate that SON plays a critical role in the proliferation, survival, and tumorigenicity of pancreatic cancer cells, suggesting that SON is a novel therapeutic molecular target for pancreatic cancer.</p