Oncostatin M is a novel glucocorticoid-dependent neuroinflammatory factor that enhances oligodendrocyte precursor cell activity in demyelinated sites

The innate immune reaction to tissue injury is a natural process, which can have detrimental effects in the absence of negative feedbacks by glucocorticoids (GCs). Although acute lipopolysaccharide (LPS) challenge is relatively harmless to the brain parenchyma of adult animals, the endotoxin is highly neurotoxic in animals that are treated with the GC receptor antagonist RU486. This study investigated the role of cytokines of the gp130-related family in these effects, because they are essential components of the inflammatory process that provide survival signals to neurons. Intracerebral LPS injection stimulated expression of several members of this family of cytokines, but oncostatin M (Osm) was the unique ligand to be completely inhibited by the RU486 treatment. OSM receptor (Osmr) is expressed mainly in astrocytes and endothelial cells following LPS administration and GCs are directly responsible for its transcriptional activation in the presence of the endotoxin. In a mouse model of demyelination, exogenous OSM significantly modulated the expression of genes involved in the mobilization of oligodendrocyte precursor cells (OPCs), differentiation of oligodendrocyte, and production of myelin. In conclusion, the activation of OSM signaling is a mechanism activated by TLR4 in the presence of negative feedback by GCs on the innate immune system of the brain. OSM absence is associated with detrimental effects of LPS, whereas exogenous OSM favors repair response to demyelinated regions. (C) 2010 Elsevier Inc. All rights reserved.

Human endogenous RNAs: Implications for the immunomodulation of Toll-like receptor 3

Toll-like receptors (TLRs), a family of mammalian receptors, are able to recognize nucleic acids. TLR3 recognizes double-stranded (ds)RNA, a product of the replication of certain viruses. Polyinosinic-polycytidylic acid, referred to as poly(I:C), an analog of viral dsRNA, interacts with TLR3 thereby eliciting immunoinflammatory responses characteristic of viral infection or down-regulating the expression of chemokine receptor CXCR4. It is known that dsRNA also directly activates interferon (IFN)-induced enzymes, such as the RNA-dependent protein kinase (PKR). In the present study, the mRNA expression of TLR3, CXCR4, IFN gamma and PKR was investigated in a culture of peripheral blood mononuclear cells (PBMCs) stimulated with poly(I:C) and endogenous RNA from human PBMCs. No cytotoxic effect on the cells or on the proliferation of CD3(+), CD4(+) and CD8(+) cells was observed. TLR3 expression in the PBMCs in the presence of poly(I:C) was up-regulated 9.5-fold, and TLR3 expression in the PBMCs treated with endogenous RNA was down-regulated 1.8-fold (p=0.002). The same trend was observed for IFN gamma where in the presence of poly(I:C) an 8.7-fold increase was noted and in the presence of endogenous RNA a 3.1-fold decrease was observed. In the culture activated with poly(1:C), mRNA expression of CXCR4 increased 8.0-fold and expression of PKR increased 33.0-fold. Expression of these genes decreased in the culture treated with endogenous RNA when compared to the culture without stimulus. Thus, high expression of mRNA for TLR3, IFN gamma, CXCR4 and PKR was observed in the presence of poly(I:C) and low expression was observed in the cells cultured with endogenous RNA. In conclusion, TLR3 may play major physiological roles that are not in the context of viral infection. It is possible that RNA released from cells could contain enough double-stranded structures to regulate cell activation. The involvement of endogenous RNA in endogenous gene expression and its implications in the regulation thereof, are still being studied, and will have significant implications in the future.

RE Kevin and the right of transsexual persons to marry in Australia

This article considers the decision of the Family Court of Australia in Re Kevin (Validity of Marriage of a Transsexual) [2001] FamCA 1074, which was upheld by the Full Court of the Family Court of Australia in February 2003. Re Kevin was the first case in Australia to deal directly with the question of whether a transsexual person could marry under Australian law. In the past, Australia had adhered to the judgement of Ormrod J in Corbett v Corbett [1971] P. 83, which set the benchmark for what is ‘male’ and what is ‘female’ under the common law. Prior to Re Kevin the question of what is a man and what is a woman for the purposes of marriage in Australia mirrored the strict biological test established in Corbett. In other words, the Australian courts relied upon biological factors, as espoused by Ormrod J, when determining a person's true sex. In Re Kevin, Chisholm J examined in detail what it is to be a man or woman, but unlike Ormrod J considered ‘brain sex’ to have a significant impact on a person's view of their own innate sexual identity. The Full Court of the Family Court agreed with the powerful and well-reasoned judgement of Chisholm J at first instance.

Moving towards a model of professional identity formation in midwifery through conversations and positioning theory

The disciplines of nursing and midwifery both uphold a powerful oral tradition that can impact upon student learning. Students enrolled in a Graduate Diploma of Midwifery are supervised and assessed by midwives during their placements in midwifery practice settings by a program of 'preceptorship' support and where conversations are innate. Positioning theory, eveloped by Harre and others, is a metaphorical concept in which an individual 'positions' herself/himself within entities of encompassing people, institutions and societies where conversations are conducted either privately or publicly. As construction sites of professional learning, conversations are underpinned by reflective practices.In unravelling conversations, positioning may be applied as an analytical tool by educators to interpret the emerging meanings and themes in their discussions with students, reflective journals by students and in meetings with preceptors/midwives.

Graphical authentication : an architectural design specification

Graphical authentication is proposed as an alternative to password, smartcard, and biometric authentication as it uses the innate ability of humans to recognise visual stimuli. Despite passionate debate surrounding their privacy and invasiveness issues, smartcards and biometrics require an excessive amount of extra hardware for widespread deployment. Conversely graphical authentication extends existing infrastructure as it builds largely on the foundations of passwords with one important difference: it takes humans into account as they are better at recognising visual stimuli than recalling text-based passwords. This paper follows a preceding proof of concept paper and essentially outlines the architectural and technical design for a graphical authentication solution.

Professionalisation and accounting in China: a historical and comparative review

While applied broadly within the setting of accounting and some other occupations, “a profession” is a particularly Western concept with peculiarly British origins. Additionally, the significance of such status and the process of “professionalisation” by which it is acquired remain beset by lingering uncertainties. Examination of the sociology of the accounting occupation within non-Western locations can contribute to exposing and clarifying these problematic and contingent aspects of occupational stratification, as well as assist in redressing the bias towards English-speaking and European countries within the accounting history literature. Proceeding from these theoretical premises, a historical and comparative study of the accounting occupation within China is undertaken. This seeks to integrate the world’s most populous nation into the historical narrative of the professionalisation of accounting, and reinforces – often vividly – that accountants’ work status is not bound to any predetermined trajectory which is innate to the occupation. Instead, the variety of localised and time-specific variables which constitute the occupational context are shown to exert a dominating influence.

Emerging host cell targets for hepatitis C therapy

Chronic hepatitis C virus (HCV) infection is a major burden on humanity. The current HCV therapy has limited efficacy, and there is pressing need for new and more effective therapies. Host cell factors that are required for HCV infection, replication and/or pathogenesis represent potential therapeutic targets. Of particular interest are cellular receptors that mediate HCV entry, factors that facilitate HCV replication and assembly, and intracellular pathways involving lipid biosynthesis, oxidative stress and innate immune response. A crucial challenge now is to manipulate such cellular targets pharmacologically for chronic HCV treatment, without being limited by side effects.

The modelling ability of non-major chemistry students and their understanding of the sub-microscopic level

This case study examined the ability of three first year non-major chemistry students to understand chemical concepts according to Johnstone’s three levels of chemical representations of matter. Students’ background knowledge in chemistry proved to be a powerful factor in their understanding of the submicroscopic level. The results show that modelling ability is not necessarily innate, but it is a skill to be learnt. Each of the students’ modelling abilities with chemical representations improved with instruction and practice. Generally, as modelling skills improved so did students’ understanding of the relevant chemical concept. Modelling ability is described according to Grosslight et al.’s three–tiered level and the ability to traverse the three levels of chemical representation of matter.

Characterization of the zebrafish matrix metalloproteinase 9 gene and its developmental expression pattern

Members of the matrix metalloproteinase (MMP) family are important for the remodeling of the extracellular matrix in a number of biological processes including a variety of immune responses. Two members of the family, MMP2 and MMP9, are highly expressed in specific myeloid cell populations in which they play a role in the innate immune response. To further expand the repertoire of molecular reagents available to study zebrafish myeloid cell development, the matrix metalloproteinase 9 (mmp9) gene from this organism has been identified and characterized. The encoded protein is 680 amino acids with high homology to known MMP9 proteins, particularly those of other teleost fish. Maternal transcripts of mmp9 are deposited in the oocyte and dispersed throughout the early embryo. These are replaced by specific zygotic transcripts in the notochord from 12 h post fertilization (hpf) and also transiently in the anterior mesoderm from 14 to 16 h post fertilization. From 24 h post fertilization, mmp9 expression was detected in a population of circulating white blood cells that are distinct from macrophages, and which migrate to the site of trauma, and so likely represent zebrafish heterophils. In the adult, mmp9 expression was most prominent in the splenic cords, a site occupied by mature myeloid cells in other species. These results suggest that mmp9 will serve as a useful marker of mature myeloid cells in the zebrafish.

Making the pedagogic relay inclusive for indigenous Australian students in mathematics classrooms

Many students are unsuccessful in the study of school mathematics, not because of some innate ability, but because of pedagogical practices. Bernstein (1996) has argued that pedagogy serves as a mechanism for cultural reproduction, so that for those students whose cultures are different from that represented in and through pedagogy, the task of constructing school mathematics is made more difficult. The paper explores the ways in which a teacher changes the pedagogic relay in order to be more inclusive of her students. Her practice is informed by understanding the ways in which pedagogy is a subtle tool for marginalization in mathematics.

UV-induced DNA damage promotes resistance to the biotrophic pathogen Hyaloperonospora parasitica in Arabidopsis

Plant innate immunity to pathogenic microorganisms is activated in response to recognition of extracellular or intracellular pathogen molecules by transmembrane receptors or resistance proteins, respectively. The defense signaling pathways share components with those involved in plant responses to UV radiation, which can induce expression of plant genes important for pathogen resistance. Such intriguing links suggest that UV treatment might activate resistance to pathogens in normally susceptible host plants. Here, we demonstrate that pre-inoculative UV (254 nm) irradiation of Arabidopsis (Arabidopsis thaliana) susceptible to infection by the biotrophic oomycete Hyaloperonospora parasitica, the causative agent of downy mildew, induces dose- and time-dependent resistance to the pathogen detectable up to 7 d after UV exposure. Limiting repair of UV photoproducts by postirradiation incubation in the dark, or mutational inactivation of cyclobutane pyrimidine dimer photolyase, (6-4) photoproduct photolyase, or nucleotide excision repair increased the magnitude of UV-induced pathogen resistance. In the absence of treatment with 254-nm UV, plant nucleotide excision repair mutants also defective for cyclobutane pyrimidine dimer or (6-4) photoproduct photolyase displayed resistance to H. parasitica, partially attributable to short wavelength UV-B (280–320 nm) radiation emitted by incubator lights. These results indicate UV irradiation can initiate the development of resistance to H. parasitica in plants normally susceptible to the pathogen and point to a key role for UV-induced DNA damage. They also suggest UV treatment can circumvent the requirement for recognition of H. parasitica molecules by Arabidopsis proteins to activate an immune response.

Focusing in on structural genomics : the University of Queensland structural biology pipeline

The flood of new genomic sequence information together with technological innovations in protein structure determination have led to worldwide structural genomics (SG) initiatives. The goals of SG initiatives are to accelerate the process of protein structure determination, to fill in protein fold space and to provide information about the function of uncharacterized proteins. In the long-term, these outcomes are likely to impact on medical biotechnology and drug discovery, leading to a better understanding of disease as well as the development of new therapeutics. Here we describe the high throughput pipeline established at the University of Queensland in Australia. In this focused pipeline, the targets for structure determination are proteins that are expressed in mouse macrophage cells and that are inferred to have a role in innate immunity. The aim is to characterize the molecular structure and the biochemical and cellular function of these targets by using a parallel processing pipeline. The pipeline is designed to work with tens to hundreds of target gene products and comprises target selection, cloning, expression, purification, crystallization and structure determination. The structures from this pipeline will provide insights into the function of previously uncharacterized macrophage proteins and could lead to the validation of new drug targets for chronic obstructive pulmonary disease and arthritis.

Apparent in vivo Δ-6 desaturase activity, efficiency, and affinity are affected by total dietary C18 PUFA in the freshwater fish Murray cod

Dietary fatty acids are known to modulate fatty acid metabolism in fish. However, the innate capability of fish to bioconvert short chain fatty acids to health promoting long chain fatty acids (LCPUFA) is insufficient to compensate for a reduced dietary intake. While many studies have focused on the dietary regulation of the fatty acid bioconversion pathways, there is little known regarding the effects of the dietary levels of C18 polyunsaturated fatty acids (PUFA) on fatty acid metabolism. Here, we show a greater degree of apparent enzyme activity (Δ-6 desaturase) in fish fed a diet with higher amounts of dietary C18 PUFA. In particular, fish receiving high amounts of dietary C18 PUFA had a greater amount of Δ-6 desaturase activity acting on 18:3n-3 than 18:2n-6. However, with the gradual reduction of dietary C18 PUFA there was a shift in substrate preference of Δ-6 desaturase from 18:3n-3 to 18:2n-6. This information will provide valuable insight for the implementation of low fish oil diets, which permit the maintenance of n-3 LCPUFA levels in farmed Murray cod.

Bovine Muc1 is a highly polymorphic gene encoding an extensively glycosylated mucin that binds bacteria

The bovine Muc1 protein is synthesized by mammary epithelial cells and shed into milk as an integral component of the milk fat globule membrane; however, the structure and functions of this mucin, particularly in relation to lactation, are poorly defined. The objectives of this investigation were to investigate the Muc1 gene and protein structures in the context of lactation and to test the hypothesis that Muc1 has a role in innate immune defense. Polymerase chain reaction analysis of genomic DNA from 630 cattle revealed extensive polymorphism in the variable number of tandem repeats (VNTR) in the bovine Muc1 gene. Nine allelic
variants spanning 7 to 23 VNTR units, each encoding 20 AA, were identified. Three alleles, containing 11, 14, and 16 VNTR units, respectively, were predominant. In addition, a polymorphism in one of the VNTR units has the potential to introduce a unique site for N-linked glycosylation. Statistical analysis indicated weak associations between the VNTR alleles and milk protein and fat percentages in a progeny-tested population of Holstein-Friesian dairy cattle. No association with somatic cell count could be demonstrated. Bovine Muc1 was purified from milk fat globule membranes and characterized. The protein was highly glycosylated, primarily with O-linked sialylated T-antigen [Neu5Ac(α2–3)-Gal(β1–3)-GalNAcα1] and, to a lesser extent, with N-linked oligosaccharides, which together accounted for approximately 60% of the apparent mass of Muc1. Purified bovine Muc1 directly bound fluorescently labeled Escherichia coli BioParticles (Invitrogen, Mount Waverley, Australia) and inhibited their binding to bovine mammary epithelial cells grown in vitro.

Changing bodies, changing discourses : women's experiences of early menopause

Early menopause has been constructed by discourses of biological determinism as an untimely, but natural, failure of the female body. Medical discourses in particular have interpreted early menopause as a congenital irregularity and a rare anomaly of menopause at midlife. In this thesis I challenge the notion that early menopause is an innate imperfection related only to women’s age. I propose that early menopause is dependent upon the cultural interpretations of individual women and is constituted through the mercurial and multiple discourses of women who have this embodied experience. Moreover, I reveal that early menopause is a contemporary condition and that its location in history is inextricably bound to discourses of risk, naturalism and the self. Further I make the assumption that having an early menopause both affects and is an effect of women’s fertility, sexuality and subjectivity. I have drawn upon a broad range of sources to provide a sociological analysis of early menopause. Literature on early menopause is dominated by positivist discourses, yet many alternate discourses negotiate these influential constructions. I suggest here that the perception of early menopause as a natural fault is merely a construction by medical discourses and does not incorporate the dynamic discourses of early-menopausal women. Moreover, the restriction of early menopause to a genetic female failure excludes the majority of women who have an early menopause through iatrogenisis. This omission occurs through the failure of positivist discourses to accommodate diversity in discourses. Recent sociological and feminist studies have vindicated menopausal women. They have reconstructed menopause through notions of embodiment and have removed the veil of negativity used by the medical sciences to contain menopausal women (Komesaroff, Rothfield and Daly 1997). The visibility of menopausal women, however, remains connected to age. Menopause has been created as a predictable consequence of aging and as such has come to be synonymous with middle age. Nowadays, even men are said to experience menopause at midlife (Carruthers 1996). But early menopause is constituted within the discourses of women who have this experience. Medico-scientific discourses, based upon theories of genetic inevitability, disregard this perspective. Consequently early menopause is subsumed by naturalistic discourses that relate menopause to midlife. Such restraint reflects the unease created by menopause that does not coincide with prescribed life stages. Women's experiences of their changing bodies are largely unheard. Thus, women who have an early menopause are faced with a chasm of ‘cultural non-recognition’ (Fraser 1997). Conjointly with this discursive repression early-menopausal women face social imbalances that are transacted as both cause and consequence of early menopause. In particular the contemporary creation of early menopause is bound to the social and historical location of women as a group. Women are exploited by the institution of medicine, ‘exposure to environmental toxicity’ (Fraser 1997: 11) and commercialization as causes of early menopause. Yet the corporeal effects of practices of risk avoidance (Beck 1993), social practices (Shilling 1993) and Western consumerism (Lupton 1994) fail to be recognized. I address these problematics through a poststructural and feminist critique that assumes moments of commonality among women, while at the same time recognizes shifting and multiple differences (Nicholson 1999). I suggest here that early menopause falls into cultural misrecognition in Fraser's (1997) terms and argue that it is united concurrently with the gender injustice of androcentrism (Fraser 1997: 21). Fraser (1997: 16) suggests that it is only by relating these dual problematics that we are able to make sense of current dilemmas. Thus I have critiqued early menopause through a connection between individual embodied experiences of early menopause and early menopause as a modern phenomenon that is specific to women. I have attempted to unravel these arguments that simultaneously call to ‘... abolish gender differentiation and to valorize gender specificity’ (Fraser 1997: 21) while at the same time acknowledging their interconnectedness. An approach of merely combining women’s discourses with overarching social issues would be inadequate as not only do these problematics intersect but they also can be opposed. As Fraser (1997: 25) notes with her theory, redressing one aspect of cultural or social analysis can further imbalance another. For instance making visible the diversity and uniqueness of individual experiences of early menopause could detract from acknowledging the contemporary construction of early menopause through social inequality. Crucial to this understanding is a destabilizing of the binary construction of differences between the sexes that makes way for a reconstruction of early menopause through ‘sexual slippage’ (Matus 1995). In this thesis I look for a subtlety between the particular and the collective that views early menopause as concurrently a singular and changeable experience as well as imbedded in social practice. I suggest that these concepts are entwined as interactive effects of early menopause. Thus I have analyzed the bivalent problematics of the embodiment and social location of early menopause as imbricated, dynamic and unending discourses. From this perspective I reviewed the literature that was available on early menopause. In Chapter One I look to descriptions of early menopause and note that it has disappeared into a conglomeration of disparate, mostly medical, discourses that are contradictory. Nevertheless medical discourses offer ‘conclusive’ definitions of early menopause that are based on naturalistic views of the body (Shilling 1994). The determinants used are inconsistent and do not include women's discourses of early menopause. Thus, dominant medical discourses obscure women’s embodied experiences of early menopause and ignore the contemporary causes of early menopause. In Chapter Two I examine the causes of early menopause as a way of explaining the disparity between medical discourses and my anecdotal observations of early menopause as a fairly common contemporary occurrence. The relatively recent escalation in gynaecological surgery, especially hysterectomy, appears to account almost single-handedly for early menopause as a current phenomenon. Moreover, the extraordinary number of women who have their uterus removed at hysterectomy can be interpreted as a modern implementation of ancient anxieties. Women's sexuality has been constructed throughout history as problematic and this unease has been translated through women's bodies as dangerous and in need of control (Greer 1992). Thus social concerns which have evolved historically have emerged through the representation of a woman's uterus as an unseen, dark and mysterious risk (Beck 1993). Medical discourses define this risk and are able to negate the so-called dangers of women's sexuality through the surgical removal of their organs. Widespread negotiation of medical discourses is apparent, as hysterectomy in the modern Western world is the most common of all surgical operations (Hufnagel 1989). It is overwhelmingly the most common cause of early menopause as well. I examine also the historical condemnation of infertile women and how this anxiety has been transposed to the modern world through the commercialization of reproduction. Transactions of this social unease can cause early menopause. For instance the medical technology of in-vitro fertilization (I.V.F.) has been offered as a panacea for the infertility of early menopause but, paradoxically, can cause early menopause as well. Conception through technology has been normalized as a viable option for women who are unable to conceive and understandings of I.V.F. have moved into everyday discourse. Medical discourses have constructed fertility as a saleable item and infertile women expect that they can purchase this merchandise. Human eggs have become lucrative commodities that now are available in the market place. Egg ‘donation’ for I.V.F. programs can hasten the attrition rate of eggs and can cause early menopause in some pre-menopausal women (Rowland 1992: 24). Even the recycling of a woman’s uterus supposedly has become a possibility through the transferring of this ‘used’ organ at hysterectomy to a recipient woman who can use the other woman’s uterus as a ‘gestational garage’ (Rogers 1998). In this way women have been disembodied as mechanical systems with inter-changeable body parts and the potentially detrimental consequences of these commercial transactions are ignored. In addition I show how early menopause can be caused by the connection between the self and the social structure. Women's subjectivity is constituted through the cultural discourses available to them and these discourses affect social behaviour (Lupton 1995). For instance smoking and dieting have been identified as causes of early menopause. These activities have been related to the creation of women’s bodies as hetero-sexually desirable and are endemic to young women (Evans-Young 1995). This suggests that cultural causes of early menopause are transactions of sexual politics. Yet there is a paucity of literature that acknowledges the relationship between women’s subjectivity and early menopause. Thus the second chapter exposes a link between sexual politics and causes of early menopause through women's relationships with risk, naturalism and the self. In Chapter Three I deconstruct early menopause through theoretical considerations. I rely on an overarching poststructuralism that embraces the concept of fragmented plural discourses and the subjectivity of menopausal women as a continuous process (Komesaroff 1997: 61). I have woven these variables through broad feminist critiques (Leonard 1997). Through this eclectic approach I hoped to find some loose alignment between the corporeal, ontological and embodied dimensions of early menopause. The recurring themes of sexuality, fertility and subjectivity emerge through deconstructing discourses of sexual difference as immutable and non-negotiable; exposing ‘premature ovarian failure’ as a discursive construction that censures early-menopausal women; and acknowledging the discourses of individual women as unique, diverse and dynamic. I looked to a method of exposing some of these individual discourses and in Chapter Four I describe a critical research process aimed at understanding early menopause as a lived experience. In the remaining chapters I align these ontological arguments with an analysis of the discourses of women who had experienced or were experiencing an early menopause. This section partly relieves the ‘cultural non-recognition’ of the discourses of early-menopausal women. I recorded the narratives of fifty early-menopausal women through in-depth interviews and used this empirical data to direct the study. This data provides the opportunity to understand early menopause as an assortment of embodied experiences. For instance women’s experiences of age at commencement of menopause spanned over three and half decades. They did not reflect the age specifications prescribed by medical discourses. Rather women interpreted their experiences within their own discourses and determined their menopause as early based upon the expectations of their cultural context. Many of the women experienced changes attributed to menopause at midlife. It was not these changes that were significant to early-menopausal women it was how each woman translated these changes that provided meanings of early menopause. In Chapter Five I introduce the women through a table that connects the varying experiences of each woman. This profile shows that, in the main, the women’s experiences of early menopause were unexpected. I suggest that this is due to the disparity between early-menopausal women’s experiences and the current age and social norms of menopause. By bracketing the women into cohorts patterns emerged displaying differences between women who had menopause in their teens, twenties, thirties and forties. Adolescent women had intense feelings of abnormality and despair. Women who were in their twenties were less devastated by menopause than the younger women but described their sexuality and self-identity as changing. And although some women in their thirties were shocked or dismayed to have an early menopause others were ambivalent or happy. These women also described their sexuality and self-identity through changing discourses. A number of the women who were in their forties said that they were ‘too young for the menopause’ but were far less despondent than the younger women. It seemed that the greater the distance between age norms and social norms the more negatively women responded. Age norms that determine the social norms of women's lives through a ‘biological clock’ are constructed to reflect social values. But age is a social construction that changes over time. Thus it would appear that women’s changing bodies and changing discourses of early menopause are in the process of recreating age and social norms around menopause. In Chapter Six I draw upon women’s narratives that describe a connection between early menopause and sexuality. Yet the respondents were not unified in their constructions of sexuality. For instance a number of the women rejected the containment of their sexuality as absolute and defined in terms of bi-lateral hetero-sexual opposition. The discourses of these women constructed their sexuality as continuously flexible. Some early-menopausal women described this sexual mobility as an equivocal relationship between their sexuality, reproductive capacity and female organs. Other women articulated their sexuality as vacillating, ambiguous and unrepresentative of the so-called ‘true woman’. Several felt that they were not meant to have female reproductive organs at all. Nearly one third of the women had had their uterus removed at hysterectomy and the reproductive organs of two women were rudimentary. Women’s narratives showed that the social value of fertility influences constructions of early menopause. In Chapter Seven I record the contrast between the poignant responses of women who wished to have a baby of their own and other women who resisted discourses that entwine reproductivity with being a woman. For instance some women negotiated fertility through economic discourses of consumerism with the expectation that they could purchase conception as a commodity. Other women welcomed their early menopause as freedom from contraceptive concerns and others had no interest in reproduction at all. Thus discord arose through discourses that problematize early-menopausal women as non-reproductive and discourses that value variability. In addition many of the women’s accounts constructed their subjectivity as mobile, challenging the notion that discourses of the self are immutable. Chapter Eight presents narratives which suggest that the subjectivity of many women was altered continuously by early menopause. Yet some of the women rejected the construction of their subjectivity as unfluctuating. These contradictions reflect the uncertainties of the contemporary world. Nevertheless most respondents found that the tethering of menopause to constructions of midlife was incongruous with their own experiences. Many women refused to accept the label of social redundancy attached to middle-aged women. They moved their subjectivity beyond the reproductive body to a shifting and tractable identity of the self. This thesis demonstrates that the medical construction of early menopause as a rare and natural female flaw varies from women's experiences which suggest that early menopause is common and discursively constructed. This disparity has occurred through the privilege placed upon the construction of bodies as immutable and sexually static. This privileging has obscured the multi-dimensional causes of early menopause and given preference to a mono-causal theory. By exposing the variety of causes of early menopause the medical construction of women through a universal and unalterable body of reproduction is challenged. Moreover, women's discourses of early menopause demonstrate that the medical reduction of early menopause to a spontaneous bio-chemical malfunction has ignored the volatility of women’s embodied experiences. Women experience early menopause variously and through mercurial discourses. I suggest here that women's discourses of their experiences of early menopause reflect recurring and restructuring philosophical quandaries of fertility, sexuality and subjectivity. While there can be no representative claims made from this thesis it contributes to an understanding of the embodied experiences of early menopause. It provides an understanding of the creation of early menopause through social practices and goes part way to redressing the problematics of what Fraser terms ‘cultural non-recognition’. But, more importantly, it acknowledges early menopause as a variety of experiences where women interpret their changing bodies through changing discourses.