Hypoxic regions found in most solid tumors often contain cells which are resistant to various cancer therapies. However, hypoxia also forces cells to rely solely on the catabolism of glucose through glycolysis for ATP production and survival, thereby creating a therapeutic window that can be exploited by glycolytic inhibitors, such as 2-deoxy-D-glucose (2-DG). Previous studies in our lab demonstrated that activation of Hypoxia Inducible Factor (HIF-1) in hypoxic tumor cells confers resistance to glycolytic inhibition by 2-DG. In surveying a number of tumor types for differences in intrinsic levels of HIF-1 alpha under hypoxia, we found that pathways upstream of HIF -- i.e. AKT and mammalian target of rapamycin (mTOR) -- have significantly reduced activity in 2 human non-small lung cancer cell lines (NSCLC) as compared to 4 small cell lung cancer cell (SCLC) lines. This reduced activity of AKT and mTOR correlated with increased sensitivity to 2-DG under hypoxia. Since HIF-1 alpha translation is regulated by the mammalian target of rapamycin (mTOR), we examined the effects of blocking mTOR with an analog of rapamycin (CCI-779) in SCLC cells which express high levels of mTOR activity. Under hypoxia, treatment with CCI-779 resulted in HIF-1 alpha down-regulation. Furthermore, CCI-779 potentiated the cytotoxic effects of 2-DG in hypoxic SCLC cells. Conversely, CCI-779 did not increase 2-DG toxicity in NSCLC lines that do not express HIF, SCLC lines treated with siRNA against HIF-1 alpha, or HIF-deficient mutants. These latter results support the hypothesis that, although mTOR modulates numerous downstream pathways, mTOR inhibition by CCI-779 increases the toxicity of 2-DG in hypoxic cells through down-regulation of HIF-1 alpha. Overall, our findings show that CCI-779 hyper-sensitizes HIF-expressing hypoxic tumor cells to 2-DG. Additionally, our results suggest that the intrinsic expression of AKT, mTOR, and HIF in many tumor types may be important predictors of clinical responsiveness to 2-DG and could be used to guide future treatment decisions on whether to use 2-DG alone or in combination with an mTOR inhibitor.

Depuis le début de leur reconnaissance artistique dans les années 1990, les photographes japonais Homma Takashi (né en 1962), Kawauchi Rinko (née en 1972), Sanai Masafumi (né en 1968) et Yamamoto Masao (né en 1957) ont publié de très nombreux ouvrages. En privilégiant le livre à l’exposition pour la présentation de leurs oeuvres, ils en ont fait un espace de confrontation entre des réflexions occidentales et des modèles nationaux traditionnels déjà existants, notamment esthétiques et littéraires. On observe aussi, chez ces photographes puisant leur inspiration dans leur environnement immédiat, des similitudes dans les thèmes photographiés, les démarches de production, tout comme dans les choix de mise en page des clichés.Au sein d’une étude élargie de l’histoire du livre de photographies au Japon, la démarche exemplaire de ces quatre artistes permettra de développer et d’analyser comment les pratiques de publication de la photographie ont pu nourrir, et nourrissent encore, le renouvellement de la photographie japonaise contemporaine. L’emploi du livre, objet aisément transportable, manipulable et reproductible, impose également de s’interroger sur la diffusion et sur la réception du travail de ces artistes, au Japon comme à l’étranger. En effet, le livre est aussi à envisager comme un médium qui matérialise les échanges entre l’Extrême-Orient et l’Occident. / Since the beginning of their artistic recognition in the 1990s, Japanese photographers Homma Takashi (born in 1962), Kawauchi Rinko (1972-), Sanai Masafumi (1968-) and Yamamoto Masao (1957-) have published numerous photobooks. By favouring the book over the exhibition to display their works, they turned it into a space where Western reflections and traditional Japanese models intersect, especially aesthetic and literary ones. The four photographers all take their inspiration from their own environment, but similarities can also be observed in the photographic subjects, production processes and page settings.In an expanded study of the history of photobooks in Japan, the exemplary approaches of these four artists will enable to develop and to analyse how photography publishing practices have fed – and are still feeding – the renewal of Japanese contemporary photography. Using the book (an object that can be easily carried, handled and mechanically reproduced) makes it necessary to wonder about the circulation and the critical reception of the artists’ work, both in Japan and abroad. Indeed, the book has to be considered as an artistic medium that materialises the relationships between the Far East and the West.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / The Renin-Angiotensin System (RAS) has been associated with various reproductive functions, including the ovulatory cascade. Unlike angiotensin II (AngII), the role of angiotensin-(1-7) [Ang-(1-7)] has not been characterized in the ovary of mono-ovulatory species. The objective of this study was to determine the Ang-(1-7) concentration in follicular fluid and Ang-(1-7)-related enzymes and MAS receptor mRNA expression during the ovulatory process in cattle. Forty cows were synchronized and those with follicular diameter ≥ 12 mm received GnRH analog (i.m.) to induce a LH peak and were ovariectomized at different periods (0, 3, 6, 12 and 24 h). Follicular fluid was stored to measure Ang-(1-7). Theca and granulosa cells were collected to evaluate gene expression by RT-qPCR assay. In a second experiment, the effect of Ang-(1-7) and A-779 (MAS receptor inhibitor) on the epiregulin mRNA expression by granulosa cells was evaluated in vitro. In the third experiment, the hypothesis that Ang-(1-7) is essential for ovulation was tested using an in vivo model by injecting A-779 intrafollicularly. Twenty synchronized cows were intrafollicularly injected with A-779 or saline 0.9% (control group) when the follicles reached a diameter of at least 12 mm and were challenged with an IM application of GnRH analogs. The levels of Ang-(1-7) increased in the follicular fluid at 24 h post-treatment (p < 0.05). Messenger RNA expression of MAS, ECA2, NEP and PEP was detected in theca and granulosa cells at all periods after GnRH injection. In granulosa cells, ACE2, NEP and PEP mRNA expression was regulated in different moments after GnRH treatment (p < 0.05). The addition of Ang-(1-7) or A-779 was not able to change the pattern of Ereg mRNA expression in our granulosa cell culture system. The intrafollicular application of A-779 (10-5M) did not block ovulation when performed before the expected peak of LH (100% of cows ovulated in treated and control groups). Differential expression of ACE2, NEP and PEP in granulosa cells and increased concentrations Ang-(1-7) next ovulation may indicate a role of this peptide in ovulation in cattle. / O Sistema Renina-Angiotensina (RAS) tem sido relacionado com diversas funções reprodutivas, incluindo a cascata ovulatória. Ao contrário da Angiotensina II (AngII), a função da Angiotensina-(1-7) [Ang-(1-7)] ainda não está caracterizada no ovário de espécies mono-ovulares como a bovina. Este estudo teve por objetivo determinar se os diferentes tipos celulares de folículos pré ovulatórios expressam o receptor MAS para Ang-(1-7) e a enzima conversora de angiotensina 2 (ECA2). Além disso, foi investigado se esses genes são induzidos por LH durante o processo ovulatório. Quarenta vacas foram sincronizadas e aquelas que alcançaram diâmetro folicular ≥ 12 mm receberam uma aplicação IM de GnRH e foram ovariectomizadas via colpotomia em diferentes momentos (0, 3, 6, 12 e 24 h) após o GnRH. O líquido folicular foi recuperado para dosagem de Ang-(1-7). As células da teca e da granulosa foram isoladas e submetidas à extração de RNA e transcrição reversa. A expressão relativa dos genes foi realizada por PCR em tempo real. Em um segundo experimento, utilizando um modelo in vitro de cultivo de células de folículos ≥ 12mm, buscou-se avaliar o efeito da Ang-(1-7) ou do bloqueio de seu receptor (MAS) na expressão de RNAm para epirregulina (Ereg). No terceiro experimento, utilizando o modelo de injeção intrafolicular in vivo, foi testada a hipótese de que Ang-(1-7) é essencial para a ovulação em bovinos. Vinte vacas foram sincronizadas e quando os folículos atingiram um diâmetro mínimo de 12 mm, receberam os tratamentos com A-779 (inibidor do receptor MAS) ou solução salina 0,9% (grupo controle) e foram no momento da injeção intrafolicular desafiados com uma aplicação IM de análogo de GnRH. Foi detectada a presença de Ang-(1-7) no líquido folicular, sendo que seus níveis foram constantes até 12 h após o GnRH e aumentando (P <0,05), às 24 h após o tratamento. A expressão de RNAm para MAS, ECA2, NEP e PEP foi detectada em células da teca e granulosa em todos os períodos após a aplicação de GnRH. A expressão de RNAm para ECA2, NEP e PEP, foi regulada nas células da granulosa em diferentes momentos após tratamento com GnRH (P <0,05). Folículos pré-ovulatórios possuem Ang-(1-7) no líquido folicular, bem como expressam RNAm para MAS, ECA2, NEP e PEP nas células da teca e granulosa durante o processo ovulatório. A suplementação com Ang-(1-7), ou o bloqueio de seu receptor nas doses utilizadas não foi capaz de alterar o padrão de expressão de RNAm para Ereg em nosso sistema de cultivo de pedaços de folículos ≥ 12 mm. A aplicação intrafolicular de A-779 (10-5 M) não bloqueou a ovulação quando realizada antes do início do pico esperado de LH (100% das vacas ovularam nos grupos A-779 e controle). A expressão diferencial das enzimas formadoras da Ang-(1-7) (ECA2, NEP e PEP) nas células da granulosa e o aumento nas concentrações Ang-(1-7) no líquido folicular próximos a ovulação podem indicar um papel desse peptídeo na ovulação em bovinos.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Ovulation is controlled by a complex and dynamic interaction of factors, including endocrine and vasoactive mechanisms, cellular messengers and activating enzymes. It is well established that locally produced factors exert pivotal roles during ovulation. Some peptides such as angiotensin II (Ang II) and Natriuretic Peptides (NPs) have been prominent in local regulation of reproductive functions of mammals, beyond its systemic activities. Unlike angiotensin II (AngII), the role of angiotensin-(1-7) [Ang-(1-7)] has not been characterized in the ovary of mono-ovulatory species. In the first study, was evaluated the effect of Ang-(1-7) and its receptor (MAS) in the regulation of the ovulatory cascade. For this we used an in vitro model of supplementation with Ang- (1-7) or blocking its receptor on EREG mRNA expression in granulosa cells. Using an in vivo model, the intrafollicular injection of Ang-(1-7) antagonist (A-779 - MAS receptor inhibitor) was performed to evaluate the ovulation rate. Results showed that the Ang- (1-7) and A-779 inhibitor when in vitro culture, were not able to regulate to EREG mRNA expression. Likewise, the intrafollicular injection of A-779 did not block ovulation before the expected time of LH peak, suggesting that Ang-(1-7) has no role in the early ovulatory cascade in cattle. In the second experiment, the aim was to evaluate the pattern of mRNA expression in bovine granulosa cells for the Natriuretic Peptides Precursors (NPPs), receptors (NPRs) and key enzymes of this system after GnRH-induced ovulation in vivo. Using in vivo model main results have been shown the presence of several components of NPs system during ovulation in cattle, as well as increased mRNA expression for NPPC (natriuretic peptide precursor C) in granulosa cells after induction of ovulation with GnRH / LH. These results provide the first evidence that the C-type natriuretic peptide (NPC) is upregulated by LH and may be involved in ovulation and bovine luteinizing. Third study was conducted to answer like LH controls the mRNA expression for NPPC if this is up-regulated through EGF receptor (EGF-R). Moreover, we evaluated if the NPC regulates genes in ovulatory cascade and blockade EGF-R is capable of altering ovulation rate. For this we used an in vitro model of granulosa cell culture from large follicles (> 12 mm) and in vivo models to study ovulation, combined with intrafollicular injection and follicular dynamics and / or ovariectomy at strategic times. Our main results were: NPC does not regulate mRNA expression for amphiregulin (AREG) and EREG in vitro; NPPC mRNA coding is regulated by EGF-R but block EGF-R was not able to change the ovulation rate in bovines. These results suggest that the regulation and function of NPs during ovulation may differ between monovular and polyovular species. / A ovulação é controlada por uma complexa e dinâmica interação de fatores, incluindo mecanismos endócrinos e vasoativos, mensageiros celulares e enzimas ativadoras. Fatores produzidos localmente exercem papel essencial durante o período ovulatório. Alguns peptídeos como Angiotensina II (AngII) e os Peptídeos Natriuréticos (NPs) têm se destacado na regulação local das funções reprodutivas, além de suas atividades sistêmicas. Ao contrário da AngII, a função da Angiotensina-(1-7) [Ang-(1-7)] ainda não está caracterizada no ovário de espécies monovulatórias, como o bovino. No primeiro estudo foi avaliado o efeito da Ang-(1-7) e de seu receptor (MAS) na regulação da ovulação. Para isso foi realizada a suplementação com Ang-(1-7) ou bloqueio de seu receptor, em células da granulosa cultivadas in vitro, sobre a expressão de RNAm para epirregulina (EREG marcador inicial do processo de ovulação). Utilizando um modelo in vivo, foi realizada a injeção intrafolicular do inibidor do receptor MAS (A-779) para avaliar a taxa de ovulação. Os resultados demonstraram que a Ang-(1-7) e o inibidor A-779 quando em cultivo in vitro, não foram capazes de regular a expressão de RNAm para EREG. Da mesma forma que injeção intrafolicular de A-779 não inibiu o processo ovulatório, indicando que a Ang-(1-7) não possui papel relevante no início da cascata ovulatória em bovinos. No segundo estudo o objetivo foi caracterizar a expressão dos NPs, seus receptores e enzimas convertases durante a ovulação induzida a partir de GnRH/LH em bovinos. Utilizando modelo in vivo foram demonstrados como principais resultados a presença de vários componentes do sistema NPs durante a ovulação em bovinos, bem como um aumento na expressão de RNAm para NPPC (precursor do peptídeo natriurético tipo C) após indução da ovulação GnRH / LH em células da granulosa. Esses resultados fornecem a primeira evidência que o peptídeo natriurético tipo C (NPC) é regulado positivamente pelo LH e pode estar envolvido na ovulação e luteinização de bovinos. O terceiro estudo foi realizado para responder como ocorre a regulação do RNAm para NPPC pelo LH, se essa regulação é via receptor de EGF (EGF-R). Além disso, avaliamos se o NPC regula genes da cascata ovulatória e se o bloqueio EGF-R é capaz de alterar a taxa de ovulação. Para isso foram utilizados modelos in vitro de cultivo de células da granulosa de folículos grandes (> 12 mm) e modelos in vivo para estudo da ovulação aliados à injeção intrafolicular com ovariectomia em momentos estratégicos e/ou dinâmica folicular. Nossos principais resultados foram: NPC não regula a expressão de RNAm para anfirregulina (AREG) e EREG in vitro; RNAm para NPPC é regulado via EGF-R porém o bloqueio de EGF-R não foi capaz de alterar a taxa de ovulação em bovinos. Estes resultados sugerem que a regulação e função dos NPs durante a ovulação pode diferir entre espécies mono e multiovulatórias.

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No. of bitstreams: 2 Dissertação - Cíntia do Carmo e Silva - 2016.pdf: 1705558 bytes, checksum: f3f7616f0bd9d70c3439ec18c38eef3f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-03-21 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / Previous studies have demonstrated a protective effect of the Ang-(1-7)/Mas receptor axis on pathological cardiac hypertrophy. Also, the involvement of Mas receptor in the exercise-induced cardiac hypertrophy has been suggested. However, the role of the Ang-(1-7)/Mas receptor on pregnancy-induced cardiac remodeling remains unknown. Thus, the aim of this study was to evaluate the participation of the Mas receptor in the development of pregnancy and hypertrophy, fibrosis and cardiac function during pregnancy. Female Wistar rats were randomly shared in 3 groups: control (W-NP), pregnant (W-P), and pregnant treated with A-779 (W-P + A-779). Wild type and Masknockout mice were distributed in non-pregnant (WT and KO) and pregnant (WT-P and KO-P) groups. Gestational parameters such as, maternal weight, placental weight, fetus weight, fetus/placenta ratio, fertility, Loss pre embryonic, Loss pos embryonic were evaluated. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography. The medial part of the left ventricle (LV) was collected for cardiomyocytes morphometry analysis and extracellular matrix proteins deposition. Echocardiographic analysis was used to evaluate the cardiac function. Mas receptor blockade or genetic deletion of Mas did not alter the fertility or embryonic and fetal development. However, the Mas receptor antagonist decreased placental weight and increased fetus placenta ratio in rats. The pregnant KO mice presented a decreased maternal and fetal weight and increased fetus/placenta ratio. SBP was not changed by pregnancy or A-779 treatment in the Wistar rats. Pharmacological blockade or genetic deletion of Mas receptor attenuates the pregnancy-induced myocyte hypertrophy. The A-779 treatment or genetic deletion of the Mas receptor increased the collagen III deposition in LV from pregnant animals. KO mice presented a lower ejection fraction, fraction shortening, stroke volume and higher end systolic volume compared to WT. Interestingly, the pregnancy restored these parameters. In conclusion, these data show that Mas receptor can alter gestational and maternal parameters, and this is involved in the cardiomyocyte hypertrophy and in the control of the collagen III deposition in pregnancy condition. These alterations are associated with improvement of the cardiac function through Mas-independent mechanism. / Estudos anteriores mostraram que o eixo Ang- (1-7) / receptor Mas possue efeito protetor na hipertrofia cardíaca patológica. Além disso, o envolvimento de receptor Mas na hipertrofia cardíaca induzida por exercício tem sido sugerida. No entanto, o papel da Ang- (1-7) / receptor Mas no remodelamento cardíaco induzido pela gestação permanece desconhecido. Diante disto, o objetivo desse estudo foi avaliar a participação do receptor Mas no desenvolvimento da gestação e na hipertrofia, fibrose e função cardíaca durante a gestação. Ratas Wistar foram randomizadas aleatoriamente em 3 grupos: controle (W-NP), gestante (W-P) e gestante tratada com A-779 (W-P + A-779). Camundongas Wild type e Knockout para o receptor Mas foram randominazadas em grupos não-grávidas (WT e KO) e grávidas (WT-P e KO-P). Parâmetros gestacionais como peso materno, peso placentário, peso fetal, razão feto/placenta, fertilidade, perda pré-embrionária e perda pós-embrionária foram avaliados. A pressão arterial sistólica (PAS) foi medida por pletismografia de cauda. A parte medial do ventrículo esquerdo (VE) foi coletado para análise morfométrica do cardiomiócito e deposição de proteínas na matriz extracelular. Análise por ecocardiografia foi utilizada para avaliar a função cardíaca. O bloqueio ou a deleção genética do Mas não altera a fertilidade, o desenvolvimento embrionário ou fetal. No entanto, o bloqueio do Mas reduziu o peso placentário e aumentou a relação feto/placenta nas ratas. Já nos animais KO gestantes foi observado menor ganho de peso materno e fetal, o que acarretou em aumento da razão feto/placenta. A PAS não foi alterada pela gestação ou tratamento com A-779 nas ratas Wistar. O bloqueio farmacológico ou deleção genética de receptor Mas atenuou a hipertrofia dos miócitos induzida pela gravidez. O tratamento A-779 ou deleção genética do receptor Mas aumentou a deposição de colágeno III do VE das gestantes. KO apresentaram uma menor fração de ejeção, fração de encurtamento, volume sistólico e aumento do volume sistólico final em comparação com WT. Curiosamente, a gravidez restaurou esses parâmetros. Em conclusão, estes dados demonstraram que o receptor Mas pode alterar parâmetros maternos e gestacionais, bem como está envolvido na hipertrofia dos cardiomiócitos e no controle da deposição de colágeno III na gestação. Essas alterações estão associadas com a melhora da função cardíaca por meio de mecanismos independente do Mas

No description available.

Im Frühjahr 1956 bildete sich in Leipzig auf private Initiative hin eine Gruppe junger Fotografen und Fotografinnen unter dem kämpferischen Namen „action fotografie“. Fast alle waren Studierende oder Absolventen der Leipziger Hochschule für Grafik und Buchkunst in Fotografie. Nur zwei Ausstellungen veranstaltete die Gruppe 1956 und 1957 in Leipzig, doch bis heute ist sie in der Literatur und Fotografiegeschichte der DDR präsent. Eine Retrospektive der Bildenden Künste in Leipzig vom Beginn der deutschen Teilung bis in die Gegenwart, die für Oktober 2009 als Ausstellungsprojekt im Museum der bildenden Künste Leipzig geplant war, bot die Gelegenheit, sich nach gut fünfzig Jahren mit der Gruppe auseinander zu setzen, nach ihren Zielen zu fragen und Gründe für die kurze Existenz zu suchen. Bei der Recherche im Staatsarchiv und in privaten Künstlernachlässen sowie in zahlreichen Gesprächen mit den Beteiligten ergab sich das komplexe Bild einer sehr heterogenen Fotografengruppe, die engagierte Ziele hatte, sie jedoch nicht auf Dauer frei artikulieren oder künstlerisch umsetzen konnte.

The thesis examines the work of photographer Nick Hedges (b. 1953) who made photographs for the housing charity Shelter between 1968 and 1972. It concentrates on Hedges’ methodology, his representation of the homeless child, and how this was deployed in Shelter’s campaign strategy. Moreover, it examines the wider political, sociological and cultural debates surrounding the conception, production, dissemination and reception of the Shelter photographs. The thesis argues that Hedges’ photographs, although contextualised by an ostensibly radical charity agenda, were shaped by an established photographic and art historical tradition reaching back to the nineteenth century. This is examined in the light of a shifting conception of what constituted an ethically sound representation of homelessness amongst leftist critics in Britain from the 1970s onwards. The thesis equally discusses the archive as a site of photographic accession, interpretation and display, and outlines the issues that face archive professionals charged with the presentation of the Shelter photographs to a contemporary audience. By combining art historical analysis of Hedges’ photographs with research into their current framing in the archive, the thesis offers a distinctive contribution to scholarship, exploring how photographic meaning is shaped, subverted and disseminated by individuals, organisations and institutions alike.

This research project makes use of photographic art practice as an investigative tool, through which a variety of strategies have been employed in order to picture the traditional photographic portrait studio. The thesis provides both a context within which to understand this art practice and expands upon and develops the themes proposed by it. The history of the photographic studio is presented in traditional narrative form and as a discursive formation; being analysed at two specific junctures within this narrative. This historical and cultural contextualisation allows the studio to be viewed in terms of a space and apparatus that embody particular characteristics. It is suggested that whilst these characteristics are explicitly located within discourses relating to class and aesthetics they also incorporate an implicit psychical dimension. The studio as an apparatus is analysed as constituting particular subject positions. These are discussed in relation to ideas drawn from film theory that utilise Lacanian psychoanalytic concepts. The studio is considered as a space in which the presence of the Lacanian Gaze becomes suggested with particular prominence. As an architecture that embodies the presence of the gaze, the studio is discussed in relation to a number of theories around the nature of space and modernity. The possibility of transference as an element of the studio encounter is also posited. Four artists (Helmut Newton, Jemima Stehli, Broomberg and Chanarin and Christopher Williams) are identified as producing work that critically engages the space of the studio. Analysis of this work serves to develop the arguments made so far and provides an extended consideration of the particular subject object relationships that become played out in the studio. This becomes developed further in relation to commercial portrait practices and is demonstrated through analysis of portraits by Mike Disfarmer and Suresh Punjabi both of whom have been the subject of significant theoretical discussion. The thesis concludes with a reflection on how the practice produced for this research has both been conceived and executed in relation to theory but also on how it can be thought of as providing, in itself, a unique and valuable contribution to knowledge. It is argued that the practice not only makes visible a coercive discourse and psychic economy implicit within the studio but that it also promotes a particularly compelling and pertinent consideration of how the two might be related.

The childlike character of ideal femininities has long been critiqued in feminist literature, from Mary Wollstonecraft (1792) to Susan Faludi (1992). Yet, despite the partial gains of feminism the ‘woman-child’ continues to be a prominent subject-position in fashion photography of the West. This thesis builds upon earlier feminist critiques of the infantilisation of women by considering the meaning of childlike femininities in the period spanning 1990 to 2015. In particular, it questions whether representations of childlike femininities can shed their dehumanising, ‘second sex’ connotations and be resignified to a more progressive end in the contemporary context. The possible appeal of ‘girly’ subject-positions to women, following several waves of feminism, is explored through reception studies carried out with female participants in focus groups, as well as theory on the ‘female gaze’. Images were principally drawn from three British fashion magazines: Vogue (UK), i-D, and Lula. Drawing on the work of Michel Foucault and Judith Butler, this thesis demonstrates the ways in which discourses on childhood, girlhood and womanhood overlap and intersect to produce the figure of the ‘woman-child’ in the fashion media and beyond. This subject-position is shown not to be singular but rather as appearing in a number of guises. The many permutations of childlike femininity are subsumed into four overarching categories: the Romantic woman-child; the femme-enfant-fatale; Lolita style; and the Parodic woman-child. This thesis thereby contributes to existing debates in fashion studies by considering in greater detail the different discourses on childhood and femininity that come into play when women are positioned as childlike. A multi-faceted visual methodology is employed, combining visual analysis of imagery with experimental reception studies. Reception studies were conducted in focus groups with female participants and provide insight into the way these women made sense of the ‘woman-child’. In addition, they provide an indication as to whether the participants liked or disliked childlike femininities in the fashion media, thus pointing to the possible investments women might have in childlike subject-positions. Finally, including an element of social research served to challenge and/or reinforce the researcher’s own readings of the imagery, pointing to new avenues of research and expanding the discursive field of enquiry. This aspect of the thesis makes a methodological contribution to literature on the reception of still media imagery in fashion studies, magazine studies and feminist media studies.