To see the other types of publications on this topic, follow the link: Shona novels.

Dissertations / Theses on the topic 'Shona novels'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 19 dissertations / theses for your research on the topic 'Shona novels.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.

1

Mitchell, Andrea Michelle. "Ngozi : a novel." Thesis, University of Canterbury. School of Humanities, 2009. http://hdl.handle.net/10092/4450.

Full text
Abstract:
Living as a white Zimbabwean in the 1990s meant a near-perfect life: your clothes were always clean and ironed, there was always tea in the silver teapot, gins and tonics were served on the verandah, and, in theory at least, black and white lived in harmony. As Mugabe’s presidency turned sour, however, this idyllic and privileged world began to crumble into anarchy. My family and I left to escape the political violence in 2002, and moved to New Zealand. My novel Ngozi draws on these experiences to tell the story of one troubled white family who struggle to stay afloat in the collapsing economy and escalating horror of Mugabe’s Zimbabwe. The story is told through the eyes of a young white girl, who is partly based on myself. When the farm invasions begin, the violence threatens to destroy the family’s way of life forever. They eventually leave Zimbabwe, but escaping the vengeful ghosts (‘ngozi’) of their past still seems impossible.
APA, Harvard, Vancouver, ISO, and other styles
2

Brightwell, Sara. "Identifying novel regulators of reprogramming using RNA interference." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/16156.

Full text
Abstract:
Since Yamanaka and Takahashi first described the isolation of induced pluripotent stem cells (iPSCs) in 2006, researchers have invested a vast amount of time and resources into trying to understand the process of reprogramming. However, the exact mechanisms underlying the induction of somatic cells to pluripotency is still incompletely understood. With this in mind, a screening approach was undertaken to identify shRNA that enhance the reprogramming process. A retrovirus based system was used to knock down candidate genes during reprogramming of mouse embryonic fibroblasts (MEF) containing doxycycline-inducible reprogramming factors and a Nanog-GFP reporter, which is activated when cells become iPSCs. The initial round of screening with over 150 shRNA vectors successfully identified several shRNAs that enhance reprogramming. One of these shRNA vectors exhibited both faster reprogramming kinetics as determined by activation of the Nanog-GFP reporter 2 to 3 days earlier and increased reprogramming efficiency giving rise to >5 fold more GFP+ colonies when compared with a control. Cell surface marker analysis with flow cytometry demonstrated that changes in CD44 and ICAM1 expression, which occur preceding Nanog-GFP expression, were also accelerated. Validation of this shRNA determined that the enhanced reprogramming phenotype is the result of an unknown off-target effect. Microarray and RNA-sequencing analysis was carried out to identify the off target gene with a view to investigate the functional importance of this knock down and its role in establishing the pluripotency transcriptional network during reprogramming.
APA, Harvard, Vancouver, ISO, and other styles
3

Evans, Matthew C. "Quantitative Analysis of Novel Chemical and shRNA Based Methods to Increase Survival of Motor Neuron Protein Levels." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/566.

Full text
Abstract:
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder that is the leading genetic cause of infantile death. SMA is caused by homozygous deletion or mutation of the survival of motor neuron 1 gene (SMN1). The SMN2 gene is nearly identical to SMN1, however is alternatively spliced. The close relationship to SMN1 results in SMN2 being a very power genetic modifier of SMA disease severity and a target for therapies. In this study we attempt to characterize novel chemical compounds identified as potential activators of the SMN2 gene. Additionally, we sought to determine the regulatory role individual HDAC proteins use to control expression of full length protein from the SMN2 gene. We used quantitative PCR to determine the effects of novel compounds and shRNA silencing of individual HDACs on the steady state levels of a SMN2-luciferase reporter transcripts. We determined that the compounds identified in multiple reporter high throughput screens increased SMN protein levels via transcriptional activation of the SMN2 gene. Other compounds identified in the same screen functioned post-transcriptionally, possibly stabilizing the SMN protein itself by decreasing degradation. Furthermore, we determined that reduction of individual HDAC proteins was sufficient to increase SMN protein levels in a transgenic reporter system. Knockdown of class I HDAC proteins preferentially activated the reporter by increased promoter transcription. Silencing of class II HDAC proteins maintained transcriptional activity; however silencing of HDAC 5 and 6 also appeared to enhance inclusion of an alternatively spliced exon. This collective work defines a quantitative RNA based protocol to determine mechanism of SMN reporter increase in response to any chosen treatment method. Additionally, this work highlights HDAC proteins 2 and 6 as excellent investigative targets. These data are important to the basic understanding of SMN expression regulation and the refinements of current therapeutic compounds as well as the development of novel SMA therapeutics.
APA, Harvard, Vancouver, ISO, and other styles
4

Kim, Yun Cheol. "Novel strategies for studying gene and protein function random shRNA library synthesis and trasnposon directed base-exchange mutagenesis /." Diss., Restricted to subscribing institutions, 2008. http://proquest.umi.com/pqdweb?did=1693038461&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.

Full text
APA, Harvard, Vancouver, ISO, and other styles
5

Miller, Tyler Eugene. "Identifying Novel In Vivo Epigenetic Dependencies in Glioblastoma." Case Western Reserve University School of Graduate Studies / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1464856610.

Full text
APA, Harvard, Vancouver, ISO, and other styles
6

Zigara, Herbert. "Gender bias in selected Shona novels." Diss., 2016. http://hdl.handle.net/10500/22168.

Full text
Abstract:
This study sought to uncover gender bias in selected Shona novels and examine the manner in which authors present the subject. The major objectives were to identify the effects of hostile gender relations and assess Shona novel authors’ commitments to promote healthy gender relations which are pre-requisites for national development. The study adopted the dual approach by fusing feminism with Afrocentricity as the literary tool of analysis. These theories served as lenses for exploring gender biases in selected Shona novels. The liberal feminism was the most relevant feminist theory to this study because it advocates more about inclusion and unrestricted participation of women in all spheres of social life. The research was anchored on the qualitative design. The methodology used to gather data for analysis involved interviewing three out of four authors of this research’s selected Shona novels, eight Shona literature lecturers from teachers’ colleges and universities in Zimbabwe as well as five accomplished scholars who have also written their own Shona novels. Questionnaires were administered to thirty two students, twenty from teachers’ colleges and twelve from universities in Zimbabwe. The total number of all participants in this study was forty-eight and purposive sampling was used to come up with the sample. Data was analysed in descriptive form. This study has established that most Shona novelists are not gender neutral. While some authors are championing the emancipation of women others are perpetuating their marginalisation. Basing on the findings of this study, the researcher recommends that Shona authors should be sensitised through workshops, seminars or conferences on the need to pen gender balanced novels if national development is to be realised. This would help the societies who are the consumers of such novels to be gender neutral through emulating the positive portrayal attributed to characters. The Zimbabwe Schools Examinations Council (ZIMSEC), teachers’ colleges and universities should approve gender neutral Shona novels so that students can have appropriate role models to emulate. It is envisaged that this research will be of great benefit to all those who will have the privilege to access it. Gained knowledge will help to extricate women from marginalisation and also promote healthy gender relations.
African Languages
M.A. (African Languages)
APA, Harvard, Vancouver, ISO, and other styles
7

Nenduva, Aphios. "Investigating moral perversion in post-Independence Shona detective novels." Thesis, 2018. http://uir.unisa.ac.za/handle/10500/25689.

Full text
Abstract:
Text in English
The study unravels moral perversion in selected post-independence detective Shona novels. Moral perversion is a multi-faceted concept and the study focuses on corruption, sexual harassment, abuse of office, stealing, poaching and illegal manufacturing of intoxicating products as the key definers of moral perversion. Afrocentricity merged with Kawaida philosophy are the lenses used to pass critical judgements on the extent the selected literary practitioners portrayed literature rooted in the African ontological existence on moral perversion. Fictional works used as primary sources are Sajeni Chimedza (1984), Mutikitivha Dumbuzenene (1991), Munzwa mundove (1999) and Dandemutande, (1998). All the novels are set in the post-independence era in Zimbabwe when moral perversion is rife. The study is qualitative in nature and data was gathered using questionnaires and interviews from literary critics, publishers and novelists. Particular attention is paid on the causes of moral perversion, images of people in leadership positions and the implications of character assassination of leaders in relation to the development of purposeful literature. The study contends that moral insanity is an acknowledged problem in the post-independence era and novelists are portraying leaders as the chief culprits manning factionalism and unorthodox ways of acquiring resources at the expense of the majority of citizenry. Guided and informed by Afrocentricity, the study argues that novelists are raising pertinent issues although their views are myopic, simplistic and self-defeating because they are failing to see that the leaders are also victims who are victimizing other victims. Blaming the leadership on moral perversion ignoring the impact of colonialism, and neo-colonialism in shaping African personality creates more harm than good as this exonerates the imperialistic system of exploitation which impinges on African culture and personality. Therefore, the study argues that novelists erroneously blame individuals for the sins of a system. There is need to interrogate both external and internal factors to establish sustainable home-grown problem solving solutions to improve human condition and the development of functional literature in Africa.
African Languages
D. Litt. et Phil. (African Languages)
APA, Harvard, Vancouver, ISO, and other styles
8

Mapara, Jacob. "The Bible and literature: a case of biblical influence in some Shona novels." Diss., 2003. http://hdl.handle.net/10500/1235.

Full text
Abstract:
A lot has been written on the development of the Shona novel and the influence of orature on it. This research while acknowledging the importance of such an observation makes yet another one. This other view is that there is also another element that has had a significant impact on the development and growth of the Shona novel. This research has endeavoured to highlight that the Shona novel is a product of the society where it is found which is influenced by The Bible. The novelists Chakaipa, Chidzero, Makari, Musengezi, Tsodzo, Zvarevashe and Ngugi wa Thiong'o's A Grain of Wheat which has been translated into Shona as Tsanga Yembeu have used The Bible as the backbone of their novels. Although these novelists have all used The Bible they have not used it in the same way and for the same purpose. They have used The Bible to justify the themes embedded in their works. This research at the end shows that it is difficult to label a literary product as either a success or a failure.
African Languages
M.A. (African Languages)
APA, Harvard, Vancouver, ISO, and other styles
9

Wasosa, Wellington. "Deviance and moralisiation as portrayed in selected post-independence Shona novels and short stories." Thesis, 2014. http://hdl.handle.net/10500/19842.

Full text
Abstract:
This thesis is an exegesis of the portrayal of deviance in selected post-independence Shona fictional works. The analysis is done within the context of moralisation in Shona literature. The forms of deviant behaviour discussed include prostitution, homosexuality, crime and violence and negligence of duty within families. The fictional works are Mapenzi (1999), Totanga Patsva (2003), Ndozviudza Aniko? (2006), Ndafa Here? (2008), and Makaitei? (2008). All the fictional works are set during the period of the Zimbabwe Crisis and this becomes the context of the criticism of the manner in which deviance is handled by the writers. Particular attention is paid on the causes and solutions to deviance, images of deviants and the implications of such images in attempting to understand the realities of deviant behaviour. The research adopts an eclectic approach through a combination of literary and sociological theories to unpack issues concerning the litigious subject of deviance. The research fully acknowledges that deviance is a fluid and controversial concept as it varies with cultural frameworks and historical periods of certain societies. Thus the research has endeavoured to locate deviance with the ambit of Shona existential philosophy and the period of the Zimbabwe crisis. The research advances the argument that no human being is inherently deviant but there are certain circumstances and eventualities that are responsible for the development of such a personality. Therefore deviance herein is viewed as a response to the situation and in the case of this research it is the crisis which then is responsible for nurturing the people into deviance. In most of the situations, deviance is shown to be essentially a survival strategy by those who engage in it. Prostitution, homosexuality and crime have been shown to be largely economic necessities as the collapsing economy during the period of the crisis came with amorphous challenges and people resorted to anti-social behaviour in an attempt to live contenting lives. With regards to prostitution, homosexuality and crime, the writers have to a larger extent been able to contextualise deviance in terms of the crisis although Mabasa has been shown to display some ambivalence in his treatment of prostitutes in Mapenzi and Ndafa Here? There are instances he castigates prostitutes as social renegades which somehow weakens his vision. Apart from this, it has also been argued that deviant behaviour can be a result of the frustrations people face as they battle the vagaries of life. Violence and negligence of duty within families is argued to be a consequence of the frustrations from the poverty brought by the crisis and the movement into the diaspora as this has its own challenges that disempower people to carry out their duties as sanctioned by culture. Also, the research advances the argument that oral literature continues to impact on written literature and one such area is that of moralisation which continues to be a major priority of the writers. Except for the authors of the short stories in Totanga Patsva, moralisation on issues to do with deviance has been done in an enlightening way as the writers unearth the underlying causes of deviant behaviour and these are found in society and not individuals. The writers of the short stories have shown to be largely influenced by feminism and erroneously blame male deviants for the problems faced by women instead of explaining men`s behaviour in the context colonialism and neo-colonialism which brought various challenges related to gender relations in Africa not experienced hitherto. The direction in terms of qualitative development which Shona literature is taking in post-independence era is positive as the writers are shown to be tackling sensitive political, social and economic issues and their impact on the human condition.
African Languages
D. Litt. et Phil.
APA, Harvard, Vancouver, ISO, and other styles
10

Viriri, Eunitah. "The promotion of unhu in Zimbabwean secondary schools through the teaching of Shona literature : Masvingo urban district, a case study." Thesis, 2017. http://hdl.handle.net/10500/23737.

Full text
Abstract:
This study examines the extent to which the teaching of Shona novels can be used to promote unhu (humanness) in Zimbabwean secondary schools where there has been a call for the teaching of cultural values. The school syllabi for Shona make this position abundantly clear. For that reason, anchoring the discussion on the role of literature in Africa as expounded by African scholars such as Ngugi wa Thiong’o (1981), p’Bitek (1986) and Achebe (1989) among others, the study observes that literature plays an important role in moulding character through advancing unhu. For instance, as Achebe (1989) argues that the novelist is a teacher, the study therefore locates literature as a life-affirming and life-extending affair. The discussion of the role of literature as a potential conduit for expressing unhu takes place within the theoretical confines of Afrocentricity, an African-centred theory that places the interests of Africa at the centre of any analysis involving African people. The selected novels namely Pfumo Reropa (1961), Kunyarara Hakusi Kutaura? (1983) and Ndafa Here? (2007) are therefore interrogated from an Afrocentric point of view. The three novels are representative of different historical epochs in Zimbabwe’s cultural trajectory. In addition, they have featured quite prominently on the school syllabi for Shona. Through a combination of interviews and critical analysis of the novels, the study crucially observes that the proper teaching of literature can effectively transform the thinking of learners thereby locating them in their own cultural platforms. However, for this to happen, teachers must be properly trained in order that they develop an appreciation of the value of literature in imparting unhu among learners. As a result, the study thus proposes sufficient conscientisation of teachers and learners on the concept and practice of unhu be systematically carried out. At the same, there is need for greater planning in constructing a more informing syllabus, as well as the deliberate inclusion of texts that canonise unhu.
African Languages
D. Litt. et Phil. (African Languages)
APA, Harvard, Vancouver, ISO, and other styles
11

Nyaungwa, Oscar. "Folktale influence on the Shona novel." Thesis, 2008. http://hdl.handle.net/10500/2710.

Full text
Abstract:
This dissertation investigates the extent and type of influence the Shona folktale has had on the writing of the Shona novel. Of particular interest is how much influence the folktale has had on the early writers of Shona novels as compared to the modern writers. The study investigates folktale influence on the development of plot, setting and characterisation in targeted novels. With regard to the development of plot, the study focuses on folktale influence on the following aspects; the exposition, complication, climax and resolution. Looking at setting, the study investigates folktale influence on setting as place, time or social circumstances in which the stories happen. The study also investigates the type of characters the novelists portray and seek to detect any folktale influence on characterisation.
African Languages and Literature
Thesis (M.A.)
APA, Harvard, Vancouver, ISO, and other styles
12

Mazuruse, Mickson. "The theme of protest in the post-independence Shona novel." Diss., 2010. http://hdl.handle.net/10500/3949.

Full text
Abstract:
The study discusses selected Shona novels‟ depiction of the theme of protest in the post-independence era in Zimbabwe. The ideas that these novels generate on protest are examined in the context of socio-political and socio-cultural issues in post-independent Zimbabwe. The study is an investigation of the extent to which protest literature is indispensable in the struggle of African people to liberate themselves from imperialist servitude. Novels on socio-political protest show how the government has failed to deliver on most of its promises because of neocolonialism and corruption. Novels on socio-cultural protest show how cultural innovations in post-independence Zimbabwe brought problems .The study comes to the conclusion that for literature to be reliable and useful to society it is not enough to highlight weaknesses in criticizing, but it should go beyond that and offer constructive and corrective criticism. This shows that protest literature is a vital tool for social transformation in Zimbabwe.
African languages
M.A. (African languages)
APA, Harvard, Vancouver, ISO, and other styles
13

Mapara, Jacob. "An analysis of the reliability and validity of the Shona novel as a historical document." Thesis, 2007. http://hdl.handle.net/10500/1341.

Full text
Abstract:
A lot of research on the Shona novel has focussed on the influence of orature and the Bible. It has also focused on the influence that the Southern Rhodesia Literature Bureau had on its development. This research has endeavoured to highlight the reliability and validity of the Shona novel as a historical document. The dependability of the novel as an alternative site from which history can be deciphered is corroborated by historical documents. The history that comes out in the Shona novels that have been studied covers the pre-colonial period right up to the post-independence period. Among the issues that come up in the research that relate to history are the Rozvi state under Chirisamhuru, the economic activities in pre-colonial Shona society that include raids for cattle and women as well as hunting and external trade. The Shona novel has also proved historically reliable in as far as it relates to the navigability of the Save River. It has highlighted the living conditions and the wages that Blacks got in colonial Rhodesia and exposed the land imbalances that came into existence because of the Land Apportionment Act of 1930, which left Blacks living on the periphery and in overcrowded, hot and dry reserves that were hardly fertile. The Rhodesian authorities, as the novels have exposed, denied most Blacks access to education. When schools were provided, they were poorly staffed and those on farms functioned more as labour pools than schools. The novel has also proved its dependability when it highlights the early days of the nationalist movement and the unilateral declaration of independence of 1965. It has also brought to the fore the birth of the armed struggle and the Rhodesian responses to it. The Rhodesians responded politically and militarily. Politically, it was through the Internal Settlement Agreement of March 1978. Militarily they moved people into 'protected villages' in an effort to deny guerrillas access to food and clothing. The novel also highlights the post-independence period especially political intolerance.
African Languages
D.Litt. et Phil. (African Languages)
APA, Harvard, Vancouver, ISO, and other styles
14

Yen, Meng-Chi, and 顏孟畿. "The novel approach for cancer therapy:by skin delivery of IDO shRNA." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/49566124315074026533.

Full text
Abstract:
博士
國立成功大學
基礎醫學研究所
97
Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme of tryptophan degradating pathway and a negative immunoregulatory molecule of dendritic cells. IDO-expressing dendritic cells suppress proliferation and activation of effector T cells and induce proliferation of regulatory T cells. We hypothesized that knockdown the IDO expression of dendritic cells could elicit the antitumor response. Besides the IDO specific inhibitor, short hairpin RNA (shRNA) is another approach to silence the IDO expression of dendritic cells. Thus, the IDO specific short hairpin RNA (shRNA) was constructed and evaluated the silencing efficiency on the mRNA and protein expression in vitro and in vivo. We observed the slower tumor growth rate and better survival rate on mouse bladder tumor cell MBT-2 and mouse colon cancer cell CT-26 bearing mice after IDO shRNA vaccinated. Adoptive transfer of CD11c+ cells which were isolated from IDO shRNA vaccinated mice was shown delayed tumor progression. The data indicated that IDO low-expressing CD11c+ cells played a critical role in antitumor response. Depletion the CD8+ and CD4+T cells abolished the IDO shRNA induced antitumor responses. Mice vaccinated with IDO shRNA targeting to different sequence induced similar therapeutic efficacy. IDO shRNA-resistant IDO expression vector delivered into dendritic cells abolished the therapeutic effect. It was suggesting that the therapeutic effect is not due to off-target and is dependent on IDO. In addition, the therapeutic effect was dependent on the vaccinated dose of IDO shRNA plasmid. IDO shRNA fused with Her2/neu DNA vaccine further enhanced the therapeutic effect on the bladder cancer model. On the other hand, IDO2 was an IDO-like protein. IDO2 shRNA induced similar antitumor immune responses with IDO siRNA, but the interaction between IDO and IDO2 was still unknown in this study. In conclusion, we provide a novel and simple approach to induce the antitumor immune response through skin delivery of IDO shRNA. Her2/neu DNA vaccine fused with IDO shRNA further enhanced the therapeutic efficacy. Moreover, the IDO2 might involve in immune regulation of dendritic cells.
APA, Harvard, Vancouver, ISO, and other styles
15

Ntabeni, Sally-Susan. "Theme and character : some reflections on the historical context of the Ndebele novel." Diss., 1999. http://hdl.handle.net/10500/15668.

Full text
Abstract:
According to Chiwome, ' ... a writer's social vislon is a soclo-spiritual and historical product. A response to a complex process of Indoctrination' (1996: 16).The response can be a reaction depending on whose interests the issue is considered. The Ndebele novelist finds himself caught in the crossfire between two great traditions. He tries to be true to his background while still having to do justice to his newly acquired skill of graphically presenting his thoughts, feelings, and experiences He is a Victim of socio-political systems bent on giving education which moulds the mind to built-in- choices. Both poilitical eras use the printed word to further their ideologies . The Ndebele novelist finds himself having to remould his artistic genius if he is to fit in. In the process the goals of novelistic practice are missed. The novel will not communicate effectively since it has to answer to particular external forces. These forces derive,' ... from the urge of power to protect itself, to perpetuate itself, to prevail' (Chiwome 1996 :22). On the threshold of the two eras, the novel becomes a political statement. It Is this political aspect of the novel which continues to create what Chiwome (1996) has called creative timidity and mediocrity.
African Languages
M.A. (African Languages)
APA, Harvard, Vancouver, ISO, and other styles
16

Muwati, Itai. "Interface of history and fiction : the Zimbabwean liberation war novel." Thesis, 2009. http://hdl.handle.net/10500/18686.

Full text
Abstract:
The research examines the interface of history and fiction. It predominantly focuses on historical fiction on the Zimbabwean liberation war written in Shona, Ndebele and English and published after the attainment of political independence in 1980. Historical fiction on the liberation war is both biographical and autobiographical. Consequently, the study comes to the conclusion that historical fiction is a veritable stakeholder in the history issue in Zimbabwe. It becomes another type or source of history that cannot be papered over when dealing with the nation’s history. In a nation where liberation war history is not only taken seriously, but is also a vigorously contested terrain, historical fiction becomes part of those discursive contestations, particularly on nation and nationalism. It is in this regard that the study problematises the interface of history and fiction by reasoning that historical fiction published in the early 1980s largely advances a state-centered perspective which views history, nation and nationalism in positive terms. This discourse uses history in order to argue for a single nation that derives its identity from the heroic and symbolic guerrilla characters. Nationalism is exclusively presented as humanising and as being the sole legitimate political brand capable of leading the nation. On the other hand, historical fiction written in English and published in the late 1980s onwards represents alternative historical truths that contest nationalism and debunk official definitions of nation. This discourse leads to the pluralisation of perspectives on nation and nationalism. The focus on historical fiction published in three languages used in Zimbabwe is a conscious attempt to transcend ethnicity in critical scholarship. Discussing novels in Shona, Ndebele and English, which are the three main languages in Zimbabwe, makes it possible for the study to draw reasoned conclusions on the bearing of time, language, region and background among others on historical representation. This undertaking brings to the fore how literature responding to similar historical processes appears moderately conjunctive and principally disjunctive. Correspondingly, it also shows various trends in the development of liberation war fiction in Zimbabwe.
African Languages
D. Litt. et Phil. (African Languages)
APA, Harvard, Vancouver, ISO, and other styles
17

Tsai, Yi-Hsuan, and 蔡依璇. "Using a novel lipoplex LPPC-Cetuximab with the shRNA-expressed transgenes for therapy of mutant EGFR-expressed lung carcinoma." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/01810063323022983123.

Full text
Abstract:
碩士
國立交通大學
分子醫學與生物工程研究所
101
Recent studies have revealed that EGFR inhibitors were no longer effective in the treatment of EGFR-activating lung cancer due to the development of resistance. Although the irreversible second-generation EGFR TKIs were clinically developed to overcome the resistances, there was still the emergence of other resistant mechanisms. Therefore, our strategy was to search for the potent therapeutic genes which were commonly over-expressed in EGFR-activating lung cancer and directly silenced the genes for tumor inhibition. With powerful analysis tools of bioinformatics and rich online published microarray datasets from Gene Expression Omnibus (GEO), we developed a screening system and to search for the best therapeutic targets of lung tumors. The total gene profiles of 55 lung cancer cell lines and 279 clinical lung cancer samples were obtained from online GEO datasets. Following the process of screening filters, we got the 22 candidate genes which were commonly over-expressed and all associated with cell cycle regulation. After ranking the importance and experimental verification, we finally chose the potent therapeutic gene for further lung cancer gene therapy. By using the well-established LPPC/cetuximab delivery system, we delivered the shRNA-expressed transgene into EGFR-mutant NCI-H1650 and verified its anti-cancer effects.
APA, Harvard, Vancouver, ISO, and other styles
18

Chen, Yu-tsung Shane. "Structural Dynamics and Novel Biological Function of Topoisomerase 2." Diss., 2015. http://hdl.handle.net/10161/9919.

Full text
Abstract:

Eukaryotic Topoisomerase 2 is an essential enzyme that solves DNA topological problems such as DNA knotting, catenation, and supercoiling. It alters the DNA topology by introducing transient double strand break in one DNA duplex as a gate for the passage of another DNA duplex. Two different aspects of studies about eukaryotic Topoisomerase 2 will be covered in this thesis. In the first half of the thesis, we investigated conformational changes of human Topoisomerase 2 (hsTop2) in the presence of cofactors and inhibitors. In the second half, we focused on an unknown regulatory function in the C-terminal domain (CTD) of Drosophila Topoisomerase 2 (Top2).

In the project of studying enzyme conformational changes, we adapted a previously developed methodology, Pulse-Alkylation Mass Spectrometry, with monobromobimane to study the protein dynamics of hsTop2. Using this method, we captured the evidence of conformational changes in the presence of ATP and Mg2+ or the Top2 inhibitor, ICRF-193 which were not previously observed. Last, by using CTD truncated hsTop2, the increasing reactivity of Cys427 suggested the CTD domain might be tethered adjacent to the core enzyme.

Following the study of enzyme conformational changes, we switched gear to examine an interaction between Drosophila Top2 and Mus101, homolog of human TopBP1. We first found that Mus101 interacts with CTD of Top2 in a phosphorylation-dependent manner. Next, in the co-immunoprecipitation and pull-down experiments using truncated or mutant Top2 with various Ser to Ala substitutions, we mapped the binding motif to the last amino acids of Top2 and identified that phosphorylation of Ser1428 and Ser1443 is important for Top2 to interact with the N-terminus of Mus101, which contains BRCT1/2 domains (BRCT, BRCA1 C-terminus). The binding affinity of the N-terminal Mus101 with a synthetic phosphorylated peptide covering the last 25 amino acids of Top2 (with pS1428 and pS1443) was determined by surface plasmon resonance with a Kd of 0.57 μM. In an in vitro decatenation assay, Mus101 can specifically reduce the decatenation activity of Top2, and dephosphorylation of Top2 attenuates this response to Mus101. Next, we endeavored to establish a cellular system for testing the biological function of Top2-Mus101 interaction. Top2-silenced S2 cells rescued by Top220, truncation of 20 amino acids from the C-terminus of Top2, developed abnormally high chromosome numbers, which implies an infidelity in chromosome segregation during mitosis. Lastly, Top2-null flies rescued by Top2 with S1428A and S1443A were found to be viable but sterile. After investigating spermatogenesis, telophase of meiosis I was delayed, indicating Top2-Mus101 interaction is also important in segregating DNA in meiosis.


Dissertation
APA, Harvard, Vancouver, ISO, and other styles
19

Mund, Julie Ann. "A Synthetic Lethal shRNA Screen and Genetic Proof of Concept Identifies RAC1 as a Novel Target to Disrupt Plexiform Neurofibroma Formation." Diss., 2019. http://hdl.handle.net/1805/21933.

Full text
Abstract:
Indiana University-Purdue University Indianapolis (IUPUI)
Neurofibromatosis Type 1 (NF1) is a highly penetrant autosomal dominant genetic disorder where mutations in the tumor suppressor gene NF1 leads to decreased neurofibromin. The most debilitating manifestation is the presence of complex multilineage Schwann cell-derived plexiform neurofibromas (PN). Historically, little clinical success has been achieved targeting PN through surgery or chemotherapies. I performed an shRNA library screen of patient-derived Schwann cell lines to identify novel therapeutic targets to disrupt PN formation and progression. An shRNA library screen of human kinases and Rho-GTPases was performed in NF1-/- and paired NF1 competent immortalized Schwann cell lines. Following sequencing, candidates were identified. We previously developed a novel mouse model of NF1 wherein a neural crest specific Postncre targeted loxp-flanked Nf1 that replicated the PN found in patients. Additional cohorts of mice were generated with biallelic deletion of Rac1 (Nf1f/fRac1f/f Postn-Cre+; DKO ). Mice were aged for 9 months and peripheral nerves were harvested and fixed in formalin. Peripheral nerve size was measured and tumors were identified through blinded analysis of hematoxylin and eosin and Masson’s Trichrome (collagen) stained slides. Rho family members, including RAC1, were identified as candidates through an shRNA library screen. Genetic disruption of Rac1 in the Schwann cell lineage resulted in the prevention of tumor formation in DKO mice, as observed by peripheral nerve size and histological analysis. I observed an average of 14.8 +/- 2.65 tumors per mouse in the Nf1f/f Postnviii Cre+ cohort compared to 0 tumors in the DKO (p<0.0001). Following an shRNA library screen, RAC1 was identified as a candidate to modulate PN formation. Biallelic deletion of Rac1 in vivo prevented PN formation. I demonstrate that a candidate identified in an shRNA library screen can translate to an biological effect in a mouse model of PN.
APA, Harvard, Vancouver, ISO, and other styles
We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!

To the bibliography