Complex Interplay between the RUNX Transcription Factors and Wnt/β-Catenin Pathway in Cancer: A Tango in the Night

Sweeney, Kerri,Cameron, Ewan R.,Blyth, Karen Korean Society for Molecular and Cellular Biology 2020 Molecules and cells Vol.43 No.2

Cells are designed to be sensitive to a myriad of external cues so they can fulfil their individual destiny as part of the greater whole. A number of well-characterised signalling pathways dictate the cell's response to the external environment and incoming messages. In healthy, well-ordered homeostatic systems these signals are tightly controlled and kept in balance. However, given their powerful control over cell fate, these pathways, and the transcriptional machinery they orchestrate, are frequently hijacked during the development of neoplastic disease. A prime example is the Wnt signalling pathway that can be modulated by a variety of ligands and inhibitors, ultimately exerting its effects through the β-catenin transcription factor and its downstream target genes. Here we focus on the interplay between the three-member family of RUNX transcription factors with the Wnt pathway and how together they can influence cell behaviour and contribute to cancer development. In a recurring theme with other signalling systems, the RUNX genes and the Wnt pathway appear to operate within a series of feedback loops. RUNX genes are capable of directly and indirectly regulating different elements of the Wnt pathway to either strengthen or inhibit the signal. Equally, β-catenin and its transcriptional co-factors can control RUNX gene expression and together they can collaborate to regulate a large number of third party co-target genes.

Quotas and Quality in an International Duopoly

Sweeney, George,Thompson, Henry,Randolph Beard, T. 세종대학교 국제경제연구소 1997 Journal of Economic Integration Vol.12 No.2

This paper examines possible adjustments to a change in a binding quota in the context of an international duopoly. Consumers directly value embodied quality of goods, which is chosen simultaneously with quantity, and before quantity in a sequential model. Possible responses to a small change in a binding quota are derived. The same three types of equilibria occur in the simultaneous and sequential models. Foreign quality downgrading can occur if domestic quality falls, and is more likely starting with a low quantity of high quality imports. Domestic quality and quantity respond in opposite directions. Welfare effects are discussed.

Targeted Repair of CYBB in X-CGD iPSCs Requires Retention of Intronic Sequences for Expression and Functional Correction

Sweeney, Colin L.,Zou, Jizhong,Choi, Uimook,Merling, Randall K.,Liu, Alexander,Bodansky, Aaron,Burkett, Sandra,Kim, Jung-Woong,De Ravin, Suk See,Malech, Harry L. Elsevier 2017 Molecular therapy Vol.25 No.2

<P>X-linked chronic granulomatous disease (X-CGD) is an immune deficiency resulting from defective production of microbicidal reactive oxygen species (ROS) by phagocytes. Causative mutations occur throughout the CYBB gene, resulting in absent or defective gp91(phox) protein expression. To correct CYBB exon 5 mutations while retaining normal gene regulation, we utilized TALEN or Cas9 for exon 5 replacement in induced pluripotent stem cells (iPSCs) from patients, which restored gp91phox expression and ROS production in iPSC derived granulocytes. Alternate approaches for correcting the majority of X-CGD mutations were assessed, involving TALEN- or Cas9-mediated insertion of CYBB minigenes at exon 1 or 2 of the CYBB locus. Targeted insertion of an exon 1-13 minigene into CYBB exon 1 resulted in no detectable gp91phox expression or ROS activity in iPSC-derived granulocytes. In contrast, targeted insertion of an exon 2-13 minigene into exon 2 restored both gp91phox and ROS activity. This demonstrates the efficacy of two correction strategies: seamless repair of specific CYBB mutations by exon replacement or targeted insertion of an exon 2-13 minigene to CYBB exon 2 while retaining exon/intron 1. Furthermore, it highlights a key issue for targeted insertion strategies for expression from an endogenous promoter: retention of intronic elements can be necessary for expression.</P>

Early Mentions of Korea in British Parliamentary Debates

Loughlin Sweeney 한국학술연구원 2017 Korea Observer Vol.48 No.4

In the late nineteenth century, Korea was at the nexus of Great Power contestation in East Asia. Having existed within the sphere of China for centuries, it found itself the subject of expansionary ambitions by the Russian and Japanese empires, and also drawn, in a limited way, into the sphere of Britain’s informal empire. This paper discusses the extent to which a Korean dimension was incorporated into British parliamentary discourse in this period. It analyzes the Korean issues that captured the attention of British MPs, and examines the extent of their knowledge of Korean affairs in the late nineteenth century. It also considers the relevance of concepts of ‘informal empire’ and the ‘official mind’ to the discussion of East Asian imperial and geopolitical history in the late nineteenth century.

The association between PGC-1a and Alzheimer’s disease

Gary Sweeney,Juhyun Song 대한해부학회 2016 Anatomy & Cell Biology Vol.49 No.1

Alzheimer’s disease (AD) is a neurodegenerative disorder and its reported pathophysiological features in the brain include the deposition of amyloid beta peptide, chronic inflammation, and cognitive impairment. The incidence of AD is increasing worldwide and researchers have studied various aspects of AD pathophysiology in order to improve our understanding of the disease. Thus far, the onset mechanisms and means of preventing AD are completely unknown. Peroxisome proliferator-activated receptor-g coactivator (PGC-1a) is a protein related to various cellular mechanisms that lead to the alteration of downstream gene regulation. It has been reported that PGC-1a could protect cells against oxidative stress and reduce mitochondrial dysfunction. Moreover, it has been demonstrated to have a regulatory role in inflammatory signaling and insulin sensitivity related to cognitive function. Here, we present further evidence of the involvement of PGC-1a in AD pathogenesis. Clarifying the relationship between PGC-1a and AD pathology might highlight PGC-1a as a possible target for therapeutic intervention in AD.

Orientalism or Pragmatism? Irishness and Colonial Encounter in the British Military Sphere

Loughlin Joseph Sweeney 단국대학교 동양학연구원 2017 東洋學 Vol.69 No.-

Edward Said’s concept of ‘Orientalism’ has been instrumental in refocusing colonial history towards the attitudes of colonizers at the metropolis and periphery, and the cultural preconceptions that mediated colonial encounter. Historians have taken Said’s work in many innovative directions: a greater emphasis on indigenous agency and the practicalities of direct and indirect colonial rule; the role of the ‘subaltern’ in mediating encounter between colonizers and the colonized; and, crucially, the extent to which orientalist preconceptions were eroded by the pragmatic, ‘transactional’ nature of colonial relations at an imperial frontier that was contested and ambiguous. Metropolitan attitudes toward empire have been given further complexity with the recognition of the differences between the ‘four nations’ constituting the Union. This paper reviews these new methodological frameworks and examines their relevance to the study of ‘imperial Irishmen’ in multiple Asian localities, all of whom were inculcated in the colonial military sphere, as officers, correspondents, and administrators. It cites new indicative examples of Irish attitudes to empire derived from correspondence and memoirs, and proposes new avenues of research into the complexities of colonial rule which marry the lens of orientalism with historical approaches emphasizing transaction and indigenous agency.

Unfinished Tasks in the Book of lsaiah

Marvin A. Sweeney 한국구약학회 2012 구약논단 Vol.18 No.1

오리엔탈리즘인가 프래그머티즘인가? 영국군의 장에서 아일랜드다움 그리고 식민 대립

러글린스위니 ( Loughlin Sweeney ) 단국대학교 동양학연구원(구 단국대학교 동양학연구소) 2017 東洋學 Vol.69 No.-

에드워드 사이드(Edward Said)의 ‘오리엔탈리즘(Orientalism)’의 분석은 식민 셰계의 지배자로서 제국(empire)에 대한 연구의 시선을 대도시(metropolis)와 주변부(periphery)의 이항 대립적 담론, 식민 지배자들이 가졌던 태도와, 그리고 그들이 식민지의 토착문화의 해석에 사용된 문화적 편견으로 옮겨놓음으로서 식민지 역사 연구에 있어 근본적인 변화를 남겼다. 그 이후로, 사이드의 연구를 새로운 방향으로 이끈 다수의 해석이 식민지 역사 연구에서 제기되었다. 예를 들어, 식민지의 행위성(agency)과 직간접적인 식민지 규율의 현실 적합성에 대한 강조라든가, 식민 지배자와 피지배자사이의 대면을 중재함에 있어서의 ‘하위주체’(subaltern)의 역할에 대한 연구들이 있었다. 또 한 가지 결정적인 연구는, 논란의 여지가 있고 모호했던 제국주의의 첨병에서 실제로는 실용적이고 ‘상호적인’ 특성을 가졌던 식민 관계가 오히려 오리엔탈리스트(orientalist)적인 선입견을 얼마나 무녀뜨렸었는가에 대한 연구이다. 이와 더불어 ‘4민족’적 - 민족과 제국의 개념에 대한 잉글랜드, 아일랜드, 스코틀랜드, 웨일즈 4개국의 차이를 인식하는 - 접근법으로 인하여 영국 제국주의에 대한 대도시 식민지배자(metropolitan)들의 태도에 대한 연구는 더 큰 복잡성을 띠게 되었다. 따라서, 본 연구는 상기된 새로운 방법론적 틀들을 검토하고, 이 방법론들이 아시아 내 여러 지역에 식민시대 군대의 장(sphere) 장교, 특파원, 행정직으로 투입되었던 아일랜드인의 예시에 타당하게 적용될 수 있는지 고찰하고자 한다. 또한, 서신과 회고록에서 찾을 수 있는 아일랜드인들의 제국에 대한 태도를 인용하고 오리엔탈리즘의 시각을 상호성과 토착 행위성을 강조하는 역사적 접근법을 결합함으로써, 식민지 규율의 복잡성에 대한 새로운 연구 영역을 제시한다. Edward Said’s concept of ‘Orientalism’ has been instrumental in refocusing colonial history towards the attitudes of colonizers at the metropolis and periphery, and the cultural preconceptions that mediated colonial encounter. Historians have taken Said’s work in many innovative directions: a greater emphasis on indigenous agency and the practicalities of direct and indirect colonial rule; the role of the ‘subaltern’ in mediating encounter between colonizers and the colonized; and, crucially, the extent to which orientalist preconceptions were eroded by the pragmatic, ‘transactional’ nature of colonial relations at an imperial frontier that was contested and ambiguous. Metropolitan attitudes toward empire have been given further complexity with the recognition of the differences between the ‘four nations’ constituting the Union. This paper reviews these new methodological frameworks and examines their relevance to the study of ‘imperial Irishmen’ in multiple Asian localities, all of whom were inculcated in the colonial military sphere, as officers, correspondents, and administrators. It cites new indicative examples of Irish attitudes to empire derived from correspondence and memoirs, and proposes new avenues of research into the complexities of colonial rule which marry the lens of orientalism with historical approaches emphasizing transaction and indigenous agency.

Seventh Century Judean Historiography: The Pentateuch

Marvin A. Sweeney 한국신학정보연구원 2019 Canon&Culture Vol.13 No.1

Discussion of seventh century historiography normally focuses on the so-called Deuteronomistic History, better known as the Former Prophets of the Hebrew Bible, including the books of Joshua, Judges, Samuel, and Kings. The Former Prophets or DtrH presents an account of Israel’s history from the conquest under Joshua through the sixth century B.C.E. destruction of Jerusalem and the Temple and the Babylonian Exile. American biblical scholarship, led by Frank Moore Cross, Jr., generally argues that an earlier seventh century “Josianic” edition of the Deuteronomistic History that concluded with Josiah’s reign underlies the current form of the Former Prophets. The proposed Josianic edition of the DtrH was designed to support the reform program of King Josiah of Judah (r. 640-609 B.C.E.) to purify the Jerusalem Temple and to reestablish independent Davidic rule over both Judah and the former northern kingdom of Israel. Although debate continues on the DtrH, I do not plan to focus on this issue in this paper. Instead, I wish to address a related issue, the role of the Pentateuch in seventh century Judean historiography. Deuteronomy has long been viewed correctly as the foundation for all models of the DtrH, but changes in Pentateuchal criticism, particularly the dating of the J stratum of the Pentateuch to the late-monarchic or even to the early exilic period, raises fundamental questions concerning the relationship between the Pentateuch and the DtrH. I will focus on the development of the Pentateuch. My discussion will first treat narratives that appear to derive from the northern kingdom of Israel, i.e., the Jacob narratives in Genesis 25—35, the Joseph narratives in Genesis 37—50, and the Exodus narratives in Exodus 1-15. I will then turn to narratives that appear to be shaped by the J stratum of the Pentateuch and that in turn bracket and contextualize the earlier northern narratives, including the Abraham-Sarah narratives in Genesis 11—25 and elements of the Wilderness narratives in Exodus 17—40 and Numbers 11—25. Overall, I will argue for a seventh century edition of the Pentateuch in Genesis, Exodus, and Numbers, that was designed to serve as the prelude to the so-called Josianic edition of the Deuteronomistic History in Deuteronomy, Joshua, Judges, Samuel, and Kings.

Learned Societies, Cultural Encounter, and Social Distinction : The Royal Asiatic Society and Pre-War Western Relations with Korea, Japan, and China

Loughlin J. Sweeney 이화여자대학교 국제통상협력연구소 2019 Asian International Studies Review Vol.20 No.2

The Royal Asiatic Society (RAS), a British learned society for the antiquarian study of Asian civilizations, established a number of branches in East Asia between 1865 and 1900 and quickly became a central location for the socialization of elite westerners within these states. This paper examines the social function of three RAS branches by analyzing their membership characteristics between 1865 and 1934, and draws out the role of Western associational culture in pre-war interactions between Western states and Northeast Asia. The activities of the RAS presented an opportunity for prominent personalities to demonstrate social distinction and reinforce their status as leading members of their communities, and to make claims to local expertise through the study and discussion of East Asian societies. RAS branches attracted a diverse mixture of diplomats, customs officials, military officers, missionaries, educators, merchants and medical professionals. Through a comparative analysis of the membership characteristics of RAS branches in Seoul, Tokyo, and Shanghai (the branches covering Korea, Japan, and North China respectively), the different social structures of the Western communities in these three states can be discerned. These reflect particular aspects of international relations between Northeast Asia and the West before the Second World War.