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Autophagy induced by hypothalamic AMPK increases food intake via inhibiting POMC expression
No full textAMPK, Appetite, Autophagy, Hypothalamus, POMCAMP-activated protein kinase (AMPK) has a major role in the modulation of energy balance. Current evidence has implicated the importance of hypothalamic AMPK regu-lating appetite through the modulation of neuropeptide expression. However, the underlying mechanisMaster of this regulation are largely unknown. Here, I report a nov-el mechanism of AMPK-mediated regulation of neuropeptide expression and feeding behavior.
In hypothalamic cell line expressing anorexigenic neuropeptide POMC, low glucose availability such as glucoprivation or glucose deprivation increased autophagy. Low glucose availability activated AMPK, which regulates ULK1 and mTOR complex 1, fol-lowed by decreased Pomc expression. Inhibition of autophagy by its inhibitors or siRNA diminished the effect of AMPK on Pomc expression in hypothalamic cell line. In accordance with in vitro data, ARC-specific AMPK knockdown suppressed autophagy, leading to a reduction in food intake and body weight in both normal diet- and high fat diet-fed mice. Moreover, hypothalamic AMPK knockdown attenuated Pomc expres-sion, and suppressed hyperphagia, which was induced by intraperitoneal (ip) injec-tion of the 2DG,
Taken together, these results demonstrate a novel role of AMPK-mediated hypotha-lamic autophagy in the regulation of feeding behavior by decreasing Pomc expression in response to low glucose availability. These findings suggest that hypothalamic autophagy may be a potential prognostic marker and therapeutic target in metabolic diseases.|시상하부의 AMPK 효소는 식욕 조절 신경펩티드의 발현을 변화시킴으로써 식욕 조절에 중요한 역할을 하는 것으로 알려져 있지만 아직 자세한 기전은 밝혀져 있지 않다. 본 연구에서는 시상하부 AMPK가 자가 포식 작용을 활성화시켜 식욕 억제 신경펩티드인 POMC의 발현을 억제하는 것을 in vitro, in vivo 모델에서 밝혔다. 마우스 시상하부 세포에서 당 결핍 시, AMPK는 ULK1, mTORC1을 통해 자가 포식 작용은 촉진하여 POMC 발현이 억제됨을 증명했다. 또한 AMPK의 발현을 억제할 경우 자가 포식 작용 감소 및 POMC 발현 증가와 더불어 마우스의 식욕 및 체중 감소를 관찰했다. 본 연구는 활성화된 자가 포식 작용이 식욕 조절 기전 중 하나라는 것을 확인 함으로써, 이러한 연구 결과를 토대로 시상하부 AMPK가 매개된 자가 포식 작용의 역할에 대한 폭넓은 이해로 비만 예방과 치료에 새로운 실마리 제시할 것으로 기대된다.openAbstract i
List of Contents ii
List of Tables iv
List of Figures v
List of Abbreviations vii
Ⅰ. INTRODUCTION
1.1. Hypothalamic circuits regulating appetite and energy homeostasis 1
1.1.1. Regulation of appetite and body metabolism in the hypothalamus
1.1.2. POMC: Anorexigenic neuropeptide
1.2. AMPK in controlling energy balance 10
1.2.1. Structure and regulation of AMPK
1.2.2. Regulation of energy metabolism by hypothalamic AMPK
1.3. Brain autophagy involving appetite and body metabolism 15
1.3.1. Overview of the autophagy process
1.3.2. Role of brain autophagy involved in appetite and body metabolism
Ⅱ. Materials and Methods
2.1 Materials 19
2.1.1. Drugs and Reagents
2.1.2. Antibodies
2.2 Methods 21
2.2.1. Animals
2.2.2. Stereotaxic surgery of lentivirus delivering into the ARC
2.2.3. Administration of 2DG in mice and analysis
2.2.4. Preparation of brain tissue
2.2.5. Immunohistochemistry (IHC)
2.2.6. Cell culture
2.2.7. siRNA and plasmid transfection
2.2.8. Lentivirus production
2.2.9. Generation of stable cell lines by virus infection
2.2.10. mRFP-GFP-LC3 system
2.2.11. Immunocytochemistry (ICC)
2.2.12. Immunoblot analysis
2.2.13. RNA extraction
2.2.14. Quantitative Real-Time PCR
2.2.15. Statistical analysis
Ⅲ. Results
3.1. Glucose deprivation induces autophagy through the AMPK signaling pathway 26
3.2. Hypothalamic AMPK inhibits Pomc expression in response to low glucose availability 37
3.3. Inhibition of autophagy impedes AMPK-dependent downregulation of Pomc expression 40
3.4. Mice with AMPK knockdown in the ARC show decreased autophagy, food intake, and body weight 46
3.5. Knockdown of AMPK in the hypothalamic ARC prevents 2DG-induced hyperphagia 50
Ⅳ. Discussion 55
Ⅴ. References 59
Ⅵ. 국문 요약문 71DoctordCollectio
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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