No description available.

As células Y-1 pertencem a uma linhagem clonal de células funcionais de córtex adrenal de camundongo, que respondem a ACTH. Em células Y-1, ACTH promove a esteroidogênese (função) e tem efeitos regulatórios complexos na transição G0→G1→S do ciclo celular. ACTH promove a transição G0→G1, mas inibe a transição G1→S. É possível que a regulação do ciclo celular por ACTH seja mediada pelo controle da expressão dos proto-oncogenes das famílias fos, jun e myc. Nosso laboratório mostrou, anteriormente, que ACTH induz a expressão dos genes fos e jun, mas inibe c-myc. O objetivo deste trabalho foi identificar pontos de controle na expressão dos genes fos, jun e myc e na atividade dos fatores de transcrição AP-1 (dímeros da proteínas Fos e Jun) por ACTH, derivados de cAMP (ativadores de PKA), PMA (ativador de PKC) e FCS (soro fetal bovino). ACTH, PMA e dcAMP aumentam a atividade de ligação de AP-1 a DNA, independentemente de síntese protéica. Ensaios de elongação de cadeia nascente de RNA (run off transcription) mostram que ACTH, PMA e FCS são fortes indutores de c-fos, c-jun e junB, enquanto dcAMP induz apenas c-fos e junB. Hibridizações Northern permitiram estimar a meia-vida dos mRNAs de c-fos e c-jun em 30 min, independentemente do tratamento com ACTH ou PMA. Diferentemente de c-fos, o mRNA de fosB é superinduzido por ActinomicinaD em células Y-1 tratadas com ACTH e PMA. / The Y-1 cells belong to a clonal lineage of functional mouse adrenocortical cells, which are responsive to ACTH. In Y-1 cells, ACTH promotes esteroidogenesis (function) and has complex effects on the G0→G1→S transition of the Y-1 cell cycle. ACTH induces the G0→G1 transition but inhibits the G1+S transition. Probably, the cell cycle regulation by ACTH is mediated by the expression control of the proto-oncogenes from the fos, jun and myc families. Our laboratory has previously shown that ACTH induces the fos and jun genes expression, but inhibits c-myc expression. The target of this work was to identify control points in the fos, jun and myc genes expression and in the AP-1 transcription factors (Fos and Jun proteins dimers) by ACTH, cAMP derivatives (PKA activators), PMA (PKC activator) and FCS (Fetal Calf Serum). ACTH, PMA and dcAMP raise the AP-1 DNA binding activity, independently of protein synthesis. Run off transcription assays show that ACTH, PMA and FCS are strong c-fos, c-jun and junB inducers, while dcAMP induces only c-fos and junB. Northern hybridisations allowed us to estimate the half life of the fos and jun mRNAs in about 30 min, independently of ACTH or PMA treatment. Differently of c-fos, fosB mRNA is superinduced by ActinomicinD treatment in Y-1 cells treated with ACTH or PMA.

Die Zellen des Hodgkin-Lymphoms sind, neben einer permanenten Aktivierung des NF-kB Signalweges, durch eine konstitutive AP-1 Aktivität gekennzeichnet. Die vorliegende Arbeit beschäftigte sich mit der Analyse der aberranten AP-1 Aktivität in Zellen des Hodgkin-Lymphoms. Von besonderem Interesse ist in diesem Zusammenhang der JUN Promotor, da c-Jun unter anderem die Fähigkeit besitzt seinen eigenen Promotor positiv zu regulieren (Autoregulation). Im Rahmen dieser Arbeit wurden Faktoren, die mit dem JUN Promotor in Zellen des Hodgkin-Lymphoms assoziiert sind, über verschiedene chromatographische Reinigungsschritte angereichert, mittels Massenspektrometrie identifiziert und hinsichtlich ihres Einflusses auf die c-Jun Expression analysiert. Dabei wurden die zwei Faktoren ATF-3, aus der Familie der AP-1 Proteine, und p52, aus der NF-kB Familie, hinsichtlich ihres Einflusses auf die Überexpression von c-Jun in Hodgkinzellen genauer untersucht. Die hier aufgeführten Ergebnisse tragen zu einem besseren Verständnis der Regulation der konstitutiven AP-1 Aktivität in den Hodgkinzellen bei. Im Rahmen dieser Arbeit konnten zwei Faktoren identifiziert werden, die maßgeblich an der Regulation der Expression von c-Jun in Hodgkinzellen beteiligt sind. Eine besondere Rolle kommt dabei dem Transkriptionsfaktor p52 zu, da dieser unter anderem auch die Expression anderer Mitglieder der AP-1 Familie reguliert. Ein weiterer Befund dieser Arbeit, dass p50 und p52 die zentralen Komponenten der konstitutiven NF-kB Aktivität sind, rückt p52 in das Zentrum zukünftiger Forschung. Die Befunde dieser Arbeit belegen, dass die aberrante Aktivierung von AP-1 im Hodgkin-Lymphom nicht auf ein einzelnes Ereignis in der Zelle zurückzuführen ist, sondern das Ergebnis eines komplexen Zusammenspiels vieler Faktoren ist. / The cells of Hodgkin''s lymphoma are characterized by a permanent activation of the NF-kB signaling pathway and a constitutive AP-1 activation. The present study focused on the analysis of aberrant AP-1 activity in cells of Hodgkin''s lymphoma. Of particular interest in this context is the JUN promoter, since c-Jun has the ability to regulate its own promoter (autoregulation). In this work different JUN promoter associated factors were enriched through various chromatographic purification steps, identified by Mass spectrometry and analyzed in terms of its influence on the expression of c-Jun. The focus was on specific factors in cells of Hodgkin''s lymphoma. The two factors ATF-3 and p52, were analyzed in terms of their influence on the overexpression of c-Jun in cells of Hodgkin''s lymphoma. Another interesting finding of this study is, p50 and p52 are central components of the constitutive NF-kB activity. This puts p52 in the center of future research. The results presented here contribute to a better understanding of the regulation of the constitutive AP-1 activity in the Hodgkin cells. In this work two Factors (ATF3 and p52) could be identified, which are are involved in the regulation of the expression of c-Jun in Hodgkin cells. A special role is played by the transcription factor p52, which also regulates the expression of other members of the AP-1 family. The findings of this study also show that the aberrant activation of AP-1 in Hodgkin''s lymphoma is not due to a single event in the cell. It is rather a result of a complex interplay of many factors.

No description available.

Dementia causes an increasing social and economic burden worldwide, demanding action regarding its diagnosis, treatment and everyday management. Recent years have seen many advances in neurodegeneration research, but the search for new truly disease modifying therapies for Alzheimer's disease (AD) and frontotemporal dementia (FTD) has so far not been successful. This is mainly due to a lack of understanding of the precise intracellular events that lead up to neuronal dysfunction in early and in late stages of the disease. This thesis describes the approaches taken to extend the current knowledge about the intracellular effects of neuronal amyloid-beta and the signalling pathways causing neuronal death or disturbed synaptic function in dementia. Endophilin-1(Ep-1), amyloid-binding alcohol dehydrogenase (ABAD), peroxiredoxin-2 (Prx-2) and the EF-hand domain family, member D2 (EFHD2) have been found to be elevated in the human brain with dementia and in mouse models for frontotemporal lobar degeneration (FTLD) or AD. The expression of these proteins as well as the expression of c-Jun N-terminal kinase (JNK), c-Jun and APP were analysed by western blotting and real-time PCR in human brains affected by AD or FTLD as well as in mouse models for AD. This provided a new insight into the regulation of these proteins in relation to each other in the ageing brain and uncovered a new potential link between elevated levels of EFHD2, Prx-2 and APP in FTLD. By studying the effects of the overexpression of Ep-1 in neurons, this research has led to a better understanding of its role in JNK-activation. It furthermore verified a protective role for Prx-2 against neurotoxicity and pointed towards a new function for Prx-2 in the regulation of JNK-signalling. The analysis of the effect of increased levels of EFHD2 uncovered for the first time its involvement in the PI3K-signalling cascade in neuronal cells. The current work has therefore contributed to the knowledge about the cellular processes that are affected by Ep-1, Prx-2 and EFHD2 in different types of dementia and will greatly benefit future research into their actions in the neuronal network.

Expression of sTGFbetaRII-Fc-Jun from recombinant vaccinia virus TGFß has a biphasic role in tumorigenesis. In early phases it acts as tumor sup-pressor. However, in late phases when cells have escaped selectively from the antimito-genic response of TGFß, it may act as a promoter of tumor progression and invasion. One way of control tumor formation and progression is blocking of TGFß signalling pathways in late phases of tumorigenesis. We have constructed recombinant vaccinia virus P13 expressing soluble TGFbeta type II receptor fused with the Fc fragment of IgG1 and with Jun fragment (sTbetaRII-Fc-Jun). This sTbetaRII-Fc-Jun is supposed to increase the effect of antitumor vaccinia virus vaccine expressing SigE7LAMP, which is investigated for the treatment of the HPV-16 associated cervical cancer. Binding of sTbetaRII-Fc-Jun to protein G were tested by SDS-PAGE and by im-munoblotting. We found that Jun fragment and sTbetaRII fragment do not block Fc bind-ing site for protein G. sTbetaRII-Fc-Jun was characterised using SDS-PAGE and immunoblot analysis. We observed that the amount of sTbetaRII-Fc-Jun was higher in cell supernatans of in-fected cells in comparison to cell lysates. In cell lysates we observed higher amount of sTbetaRII than sTbetaRII-Fc-Jun. The expression of sTbetaRII-Fc-Jun was stronger under...

論文(碩士)--香港中文大學, 1967. / Manuscript. / Includes bibliographical references (leaves [95-97]). / Thesis (M.A.)--Xianggang Zhong wen da xue, 1967. / 引言──袁世凱受命練兵之原委 / Chapter 第一章 --- 新建陸軍的建立 / Chapter 第一節 --- 成立年月，營址，組織，兵丁數目及其前身 / Chapter 第二節 --- 營制與餉需 / Chapter 第三節 --- 將弁與兵目的來源 / Chapter 第二章 --- 武衛右軍之擴充及拳亂時之行動 / Chapter 第一節 --- 新建陸軍改編為武衛右軍及武衛右軍先鋒隊之建立 / Chapter 第二節 --- 武衛右軍先鋒隊的組織及營制餉章 / Chapter 第三節 --- 肅清山東拳匪保存實力 / Chapter 第三章 --- 新建陸軍在北洋新軍中之重要性 / Chapter 第一節 --- 為北方各省訓練將目 / Chapter 第二節 --- 附設軍事學校 / Chapter 第四章 --- 袁世凱軍事潛力形成的主因 / Chapter 第一節 --- 結納權貴及輸貢行在 / Chapter 第二節 --- 伸展勢力到新軍 / 結論 / 附：上督辦軍務處原稟營利餉章附歸併東省各營的擬營利餉章

Lee Lai Peng Elizabeth. / "Architecture Department, Chinese University of Hong Kong, Master of Architecture Programme 1996-97, design report." / Includes bibliographical references. / Introduction / Chapter I --- point of departure --- p.1 / Chapter II --- project selection --- p.1 / clients and users / project analysis / Chapter III --- subject analysis / project Portrait --- p.1 / precedents --- p.2 / Chapter IV --- client / user analysis / functional Relationships --- p.1 / schedule of accommodation --- p.2 / Chapter V --- site / context analysis / location --- p.1 / context / access / transportation --- p.2 / future reclamation --- p.3 / restrictions --- p.4 / Chapter VI --- process / archipoint --- p.1 / identify the problem --- p.3 / conceptual --- p.9 / development --- p.15 / master plan --- p.17 / design development --- p.21 / summary --- p.23 / Chapter VII --- final project / major planning strategy --- p.1 / landscape strategy --- p.5 / site planning --- p.7 / volumetrics --- p.8 / functional relationship --- p.9 / circulation --- p.10 / shared use studies --- p.11 / detail studies --- p.13

本論文主要在探討雲林地區「給神明作契子」的現象，主要的研究地區是海豐堡和布嶼西堡二地。本研究針對廟方、契子和其家人三方面作深入的研究，從過渡儀式、傳統觀念中不潔的概念、民俗醫療為理論基礎，分析孩子「給神明作契子」的原因、儀式的進行、影響和社會意義。 本研究主要的發現有以下幾點： 1. 「給神明作契子」儀式的操控者是孩子的父母、家人，而儀式主要治療的對象除了契子以外，還有契子的家人。 2. 從契子家人的觀點出發，在「給神明作契子」的原因方面，可分為四種：「歹育飼」、家中男丁不旺、家族或地方上的傳統習慣、其它的原因。而父母讓孩子「給神明作契子」，主要的心態有二：一是治療性的心態，一是預防性的心態。 3. 在「給神明作契子」的社會意義方面，此儀式主要是處理社會上個人脫序的問題，經過儀式的進行，使個體恢復正常。所以無論在契子或其家人的身上，「給神明作契子」的儀式都展現了過渡儀式的意義。另一方面，從民俗醫療的觀點來看，「給神明作契子」的儀式是一種治療，對於契子來說，它主要是解決社會文化的疾病，同時它也對契子的家人，產生了心理治療的效果。 4. 除此之外，本研究也分析了不同類型的廟宇對於「給神明作契子」的態度。簡單的區分，廟方對於「給神明作契子」事宜的辦理，主要有三種型態：積極推銷型、維持傳統型、消極處理型。 最後，作者整合整個研究的發現，並提出未來研究的方向，認為可更進一步結合村落中的人、神和廟宇，描繪出一個真實生活的圖像。

Chronic hyperglycemia, a hallmark of type 2 diabetes, can decrease β-cell function and mass (β-cell glucotoxicity); however, the mechanisms are incompletely understood. The objective was to examine the mechanisms of β-cell glucotoxicity using in vivo and ex vivo models. The hypothesis is that oxidative stress plays a causal role in high glucose-induced β-cell dysfunction in vivo via pathways that involve endoplasmic reticulum (ER) stress and JNK. The model of β-cell glucotoxicity was achieved by prolonged i.v. glucose infusion (to achieve hyperglycemia). In Study 1, 48h glucose infusion increased total and mitochondrial superoxide levels in islets, and impaired β-cell function in vivo and ex vivo. Co-infusion of the superoxide dismutase mimetic Tempol decreased total and mitochondrial superoxide, and prevented high glucose-induced β-cell dysfunction in vivo and ex vivo. These results suggest that increased superoxide generation plays a role in β-cell glucotoxicity. In Study 2, 48h glucose infusion increased activation of the unfolded protein response (XBP-1 mRNA splicing and phospho-eIF2α levels). This was partially prevented by Tempol. Co-infusion of the chemical chaperone 4-phenylbutyrate with glucose decreased spliced XBP-1 levels, and prevented high glucose-induced β-cell dysfunction in vivo and ex vivo. Co-infusion of 4-phenylbutyrate also decreased total and mitochondrial superoxide induced by high glucose. These results suggest that 1) ER stress plays a causal role in high glucose-induced β-cell dysfunction, and 2) there is a link between oxidative stress and ER stress in high glucose-induced β-cell dysfunction in vivo. In Study 3, JNK inhibition using the inhibitor SP600125 in rats or JNK-1 null mice prevented high glucose-induced β-cell dysfunction ex vivo and in vivo. SP600125 prevented high-glucose-induced β-cell dysfunction without decreasing total and mitochondrial superoxide levels. Both Tempol and 4-phenylbutyrate prevented JNK activation induced by high glucose. These results suggest a role of JNK activation in high glucose-induced β-cell dysfunction downstream of increased superoxide generation and ER stress in vivo. Together, the results suggest that 1) oxidative stress, ER stress and JNK activation are causally involved in β-cell glucotoxicity, and 2) High glucose-induced oxidative stress and ER stress are linked, and both impair β-cell dysfunction via JNK activation in vivo.