Effect of female sex hormones on Chlamydia trachomatis growth and gene expression

Transmissible diseases are re-emerging as a global problem, with Sexually Transmitted Diseases (STDs) becoming endemic. Chlamydia trachomatis is the leading cause of bacterially-acquired STD worldwide, with the Australian cost of infection estimated at $90 - $160 million annually. Studies using animal models of genital tract Chlamydia infection suggested that the hormonal status of the genital tract epithelium at the time of exposure may influence the outcome of infection. Oral contraceptive use also increased the risk of contracting chlamydial infections compared to women not using contraception. Generally it was suggested that the outcome of chlamydial infection is determined in part by the hormonal status of the epithelium at the time of exposure. Using the human endolmetrial cell line ECC-1 this study investigated the effects of C. trachomatis serovar D infection, in conjunction with the female sex hormones, 17β-estradiol and progesterone, on chlamydial gene expression. While previous studies have examined the host response, this is the first study to examine C.trachomatis gene expression under different hormonal conditions. We have highlighted a basic model of C. trachomatis gene regulation in the presence of steroid hormones by identifying 60 genes that were regulated by addition of estradiol and/or progesterone. In addition, the third chapter of this thesis discussed and compared the significance of the current findings in the context of data from other research groups to improve our understanding of the molecular basis of chlamydial persistence under hormonal different conditions. In addition, this study analysed the effects of these female sex hormones and C. trachomatis Serovar D infection, on host susceptibility and bacterial growth. Our results clearly demonstrated that addition of steroid hormones not only had a great impact on the level of infectivity of epithelial cells with C.trachomatis serovar D, but also the morphology of chlamydial inclusions was affected by hormone supplementation.

Insulin-like growth factor-i : vitronectin complex-induced changes in gene expression effect breast cell survival and migration

Recent studies have demonstrated that IGF-I associates with VN through IGF-binding proteins (IGFBP) which in turn modulate IGF-stimulated biological functions such as cell proliferation, attachment and migration. Since IGFs play important roles in transformation and progression of breast tumours, we aimed to describe the effects of IGF-I:IGFBP:VN complexes on breast cell function and to dissect mechanisms underlying these responses. In this study we demonstrate that substrate-bound IGF-I:IGFBP:VN complexes are potent stimulators of MCF-7 breast cell survival, which is mediated by a transient activation of ERK/MAPK and sustained activation of PI3-K/AKT pathways. Furthermore, use of pharmacological inhibitors of the MAPK and PI3-K pathways confirms that both pathways are involved in IGF-I:IGFBP:VN complex-mediated increased cell survival. Microarray analysis of cells stimulated to migrate in response to IGF-I:IGFBP:VN complexes identified differential expression of genes with previously reported roles in migration, invasion and survival (Ephrin-B2, Sharp-2, Tissue-factor, Stratifin, PAI-1, IRS-1). These changes were not detected when the IGF-I analogue (\[L24]\[A31]-IGF-I), which fails to bind to the IGF-I receptor, was substituted; confirming the IGF-I-dependent differential expression of genes associated with enhanced cell migration. Taken together, these studies have established that IGF-I:IGFBP:VN complexes enhance breast cell migration and survival, processes central to facilitating metastasis. This study highlights the interdependence of ECM and growth factor interactions in biological functions critical for metastasis and identifies potential novel therapeutic targets directed at preventing breast cancer progression.

Effect of 5′UTR introns on gene expression in Arabidopsis thaliana

Background The majority of introns in gene transcripts are found within the coding sequences (CDSs). A small but significant fraction of introns are also found to reside within the untranslated regions (5′UTRs and 3′UTRs) of expressed sequences. Alignment of the whole genome and expressed sequence tags (ESTs) of the model plant Arabidopsis thaliana has identified introns residing in both coding and non-coding regions of the genome. Results A bioinformatic analysis revealed some interesting observations: (1) the density of introns in 5′UTRs is similar to that in CDSs but much higher than that in 3′UTRs; (2) the 5′UTR introns are preferentially located close to the initiating ATG codon; (3) introns in the 5′UTRs are, on average, longer than introns in the CDSs and 3′UTRs; and (4) 5′UTR introns have a different nucleotide composition to that of CDs and 3′UTR introns. Furthermore, we show that the 5′UTR intron of the A. thaliana EFIα-A3 gene affects the gene expression and the size of the 5′UTR intron influences the level of gene expression. Conclusion Introns within the 5′UTR show specific features that distinguish them from introns that reside within the coding sequence and the 3′UTR. In the EFIα-A3 gene, the presence of a long intron in the 5′UTR is sufficient to enhance gene expression in plants in a size dependent manner.

Overexpression of the kiwifruit SVP3 gene affects reproductive development and suppresses anthocyanin biosynthesis in petals, but has no effect on vegetative growth, dormancy, or flowering time

SVP-like MADS domain transcription factors have been shown to regulate flowering time and both inflorescence and flower development in annual plants, while having effects on growth cessation and terminal bud formation in perennial species. Previously, four SVP genes were described in woody perennial vine kiwifruit (Actinidia spp.), with possible distinct roles in bud dormancy and flowering. Kiwifruit SVP3 transcript was confined to vegetative tissues and acted as a repressor of flowering as it was able to rescue the Arabidopsis svp41 mutant. To characterize kiwifruit SVP3 further, ectopic expression in kiwifruit species was performed. Ectopic expression of SVP3 in A. deliciosa did not affect general plant growth or the duration of endodormancy. Ectopic expression of SVP3 in A. eriantha also resulted in plants with normal vegetative growth, bud break, and flowering time. However, significantly prolonged and abnormal flower, fruit, and seed development were observed, arising from SVP3 interactions with kiwifruit floral homeotic MADS-domain proteins. Petal pigmentation was reduced as a result of SVP3-mediated interference with transcription of the kiwifruit flower tissue-specific R2R3 MYB regulator, MYB110a, and the gene encoding the key anthocyanin biosynthetic step, F3GT1. Constitutive expression of SVP3 had a similar impact on reproductive development in transgenic tobacco. The flowering time was not affected in day-neutral and photoperiod-responsive Nicotiana tabacum cultivars, but anthesis and seed germination were significantly delayed. The accumulation of anthocyanin in petals was reduced and the same underlying mechanism of R2R3 MYB NtAN2 transcript reduction was demonstrated.

The effect of the histological properties of tumors on transfection efficiency of electrically assisted gene delivery to solid tumors in mice

Uniform DNA distribution in tumors is a prerequisite step for high transfection efficiency in solid tumors. To improve the transfection efficiency of electrically assisted gene delivery to solid tumors in vivo, we explored how tumor histological properties affected transfection efficiency. In four different tumor types (B16F1, EAT, SA-1 and LPB), proteoglycan and collagen content was morphometrically analyzed, and cell size and cell density were determined in paraffin-embedded tumor sections under a transmission microscope. To demonstrate the influence of the histological properties of solid tumors on electrically assisted gene delivery, the correlation between histological properties and transfection efficiency with regard to the time interval between DNA injection and electroporation was determined. Our data demonstrate that soft tumors with larger spherical cells, low proteoglycan and collagen content, and low cell density are more effectively transfected (B16F1 and EAT) than rigid tumors with high proteoglycan and collagen content, small spindle-shaped cells and high cell density (LPB and SA-1). Furthermore, an optimal time interval for increased transfection exists only in soft tumors, this being in the range of 5-15 min. Therefore, knowledge about the histology of tumors is important in planning electrogene therapy with respect to the time interval between DNA injection and electroporation.

The effect of BCMO1 gene variants on macular pigment optical density in young healthy Caucasians

Background Serum lutein (L) and zeaxanthin (Z) positively correlate with macular pigment optical density (MPOD), hence the latter is a valuable indirect tool for measuring L and Z content in the macula. L and Z have been attributed antioxidant capacity and protection from certain retinal diseases but their uptake within the eye is thought to depend on genetic, age and environmental factors. In particular gene variants within beta-carotene monooxygenase (BCMO1) are thought to modulate MPOD in the macula. Objectives: To determine the effect of BCMO1 single nucleotide polymorphisms (SNPs) rs11645428, rs6420424 and rs6464851 on macular pigment optical density (MPOD) in a cohort of young healthy participants of Caucasian origin with normal ocular health. Design In this cohort study, MPOD was assessed in 46 healthy participants (22 male and 24 female) with a mean age of 24 ± 4.0 years (range 19-33). The three SNPs, rs11645428, rs6420424, rs6564851 that have established associations with MPOD were determined using MassEXTEND (hME) Sequenom assay. One-way analysis of variance (ANOVA) was performed on groups segregated into homozygous and heterozygous BCMO1 genotypes. Correlations between body mass index (BMI), iris colour, gender, central retinal thickness (CRT), diet and MPOD were investigated. Results MPOD did not significantly vary with BCMO1 rs11645428 (F2,41 = 0.700, p = 0.503), rs6420424 (F2,41 = 0.210, p = 0.801) nor rs6464851 homozygous or heterozygous genotypes (F2,41 = 0,13, p = 0.88), in this young healthy cohort. The combination of these three SNPs into triple genotypes based on plasma conversion efficiency did not affect MPOD (F2,41 = 0.07, p = 0.9). There was a significant negative correlation with MPOD and central retinal thickness (r = - 0.39, p = 0.01) but no significant correlation between BMI, iris colour, gender and MPOD. Conclusion Our results indicate that macular pigment deposition within the central retina is not dependent on BCMO1 gene variants in young healthy people. We propose that MPOD is saturated in younger persons and/or other gene variant combinations determine its deposition.

Early maternal deprivation reduces prepulse inhibition and impairs spatial learning ability in adulthood: No further effect of post-pubertal chronic corticosterone treatment

Prolonged maternal deprivation leads to long-term alterations in hypothalamic–pituitary–adrenal (HPA) axis activity, disturbances of auditory information processing and neurochemical changes in the adult brain, some of which are similar to that observed in schizophrenia. Here we report the adult behavioural effects of maternal deprivation (12 h on postnatal days 9 and 11) in Wistar rats on paradigms of auditory information processing (prepulse inhibition), sensitivity to dopamimetics (amphetamine-induced hyper-locomotion) and cognition (T-maze delayed alternation and Morris water-maze). In addition, we examined the long-lasting effect of chronic 21-day corticosterone treatment during the post-pubertal period (i.e., postnatal days 56–76) on each of these behavioural paradigms in maternally deprived and control rats. Behavioural testing commenced 2 weeks after the termination of corticosterone treatment. Maternal deprivation led to a significant reduction in PPI and impaired spatial learning ability in adulthood, but did not affect the behavioural response to amphetamine. Post-pubertal chronic corticosterone treatment did not have any major long-lasting effects on any of the behavioural measures in either maternally deprived or control rats. Our findings further support maternal deprivation as an animal model of specific aspects of schizophrenia.

The v-MFG test: Investigating maternal, offspring and maternal-fetal genetic incompatibility effects on disease and viability

The MFG test is a family-based association test that detects genetic effects contributing to disease in offspring, including offspring allelic effects, maternal allelic effects and MFG incompatibility effects. Like many other family-based association tests, it assumes that the offspring survival and the offspring-parent genotypes are conditionally independent provided the offspring is affected. However, when the putative disease-increasing locus can affect another competing phenotype, for example, offspring viability, the conditional independence assumption fails and these tests could lead to incorrect conclusions regarding the role of the gene in disease. We propose the v-MFG test to adjust for the genetic effects on one phenotype, e.g., viability, when testing the effects of that locus on another phenotype, e.g., disease. Using genotype data from nuclear families containing parents and at least one affected offspring, the v-MFG test models the distribution of family genotypes conditional on offspring phenotypes. It simultaneously estimates genetic effects on two phenotypes, viability and disease. Simulations show that the v-MFG test produces accurate genetic effect estimates on disease as well as on viability under several different scenarios. It generates accurate type-I error rates and provides adequate power with moderate sample sizes to detect genetic effects on disease risk when viability is reduced. We demonstrate the v-MFG test with HLA-DRB1 data from study participants with rheumatoid arthritis (RA) and their parents, we show that the v-MFG test successfully detects an MFG incompatibility effect on RA while simultaneously adjusting for a possible viability loss.

The effect of transforming growth factor β1 gene polymorphisms in ankylosing spondylitis

Objectives. To determine whether genetic polymorphisms in or near the transforming growth factor β1 (TGFB1) locus were associated d with susceptibility to or severity of ankylosing spondylitis (AS). Methods. Five intragenic single-nucleotide polymorphisms (SNP) and three microsatellite markers flanking the TGFB1 locus were genotyped. Seven hundred and sixty-two individuals from 184 multiplex families were genotyped for the microsatellite markers and two of the promoter SNPs. One thousand and two individuals from 212 English and 170 Finnish families with AS were genotyped for all five intragenic SNPs. A structured questionnaire was used to assess the age of symptom onset, disease duration and disease severity scores, including the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index). Results. A weak association was noted between the rare TGFB1 + 1632 T allele and AS in the Finnish population (P = 0.04) and in the combined data set (P = 0.03). No association was noted between any other SNPs or SNP haplotype and AS, even among those families with positive non-parametric linkage scores. The TGFB1 +1632 polymorphism was also associated with a younger age of symptom onset (English population, allele 2 associated with age of onset greater by 4.2 yr, P = 0.05; combined data set, allele 2 associated with age of onset greater by 3.2 yr, P = 0.02). A haplotype of coding region SNPs (TGFB1 +869/ +915+1632 alleles 2/1/2) was associated with age of symptom onset in both the English parent-case trios and the combined data set (English data set, haplotype 2/1/2 associated with age of onset greater by 4.9 yr, P = 0.03; combined data set, haplotype 2/1/2 associated with greater age of onset by 4.2 yr, P = 0.006). Weak linkage with AS susceptibility was noted and the peak LOD score was 1.3 at distance 2 cM centromeric to the TGFB1 gene. No other linkage or association was found between quantitative traits and the markers. Conclusion. This study suggests that the polymorphisms within the TGFB1 gene play at most a small role in AS and that other genes encoded on chromosome 19 are involved in susceptibility to the disease.

Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect

Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19 713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64–0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother–offspring (r=0.42; P-value=3.60 × 10−61) than father–offspring correlation (r=0.33; P-value=7.01 × 10−5), and a significant positive association with paternal age at offspring birth (β=0.005; P-value=7.01 × 10−5). Interestingly, a significant and quite substantial correlation in TL between spouses (r=0.25; P-value=2.82 × 10−30) was seen, which appeared stronger in older spouse pairs (mean age ≥55 years; r=0.31; P-value=4.27 × 10−23) than in younger pairs (mean age<55 years; r=0.20; P-value=3.24 × 10−10). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age.

To work or not to work? Child development and maternal labor supply

We estimate the effect of early child development on maternal labor force participation. Mothers of poorly developing children may remain at home to care for their children. Alternatively, mothers may enter the labor force to pay for additional educational and health resources. Which action dominates is the empirical question we answer in this paper. We control for the potential endogeneity of child development by using an instrumental variables approach, uniquely exploiting exogenous variation in child development associated with child handedness. We find that a one unit increase in poor child development decreases maternal labor force participation by approximately 10 percentage points.

Maternal exposure to ambient temperature and the risk of preterm birth and stillbirth in Brisbane, Australia

Almost 10% of all births are preterm and 2.2% are stillbirths globally. Recent research has suggested that environmental factors may be a contributory cause to these adverse birth outcomes. The authors examined the relationship between ambient temperature and preterm birth and stillbirth in Brisbane, Australia between 2005 and 2009 (n = 101,870). They used a Cox proportional hazard model with live birth and stillbirth as competing risks. They also examined if there were periods of the pregnancy where exposure to high temperatures had a greater effect. Exposure to higher ambient temperatures during pregnancy increased the risk of stillbirth. The hazard ratio for stillbirth was 0.3 at 12 °C relative to the reference temperature at 21 °C. The temperature effect was greatest for fetuses of less than 36 weeks of gestation. There was an association between higher temperature and shorter gestation, as the hazard ratio for live birth was 0.96 at 15 °C and 1.02 at 25 °C. This effect was greatest at later gestational ages. The results provide strong evidence of an association between increased temperature and increased risk of stillbirth and shorter gestations.

Composing maternal identities : the living realities of mothers with young adult-children in twenty-first century Australia

There is an abundance of books available on the topic of motherhood and mothering; the majority of these books focus on the vulnerability of babies and young children and the motherwork such vulnerability demands. In particular they focus on what it is right to do in the interests of the child, and particularly his or her growth and development. Such a focus is consistent in Western culture with modern moral frameworks where understandings of goodness have been assimilated to dimensions of human action rather than dimensions of human being, selfhood, or specific forms of life. As Charles Taylor has observed, much modern moral philosophy has focused =on what it is right to do rather than the nature of the good life‘ (1989, 13). The master narratives of motherhood and the prevailing social discourses of intensive1 and sacrificial2 mothering exemplify this view as such narratives and discourses depict =what mothers are expected to do [and] how mothers are supposed to be‘ (Nelson 2001, 140). From such infant/child-focused accounts a canonical maternal identity can be discerned; arguably, it is a restricted one. The majority of these books fail to address questions related to what it means be a mother in particular situated, existing, living realities. For instance, ask a mother with young children what being a mother means to her and she may speak of the challenges she faces balancing paid employment and her role as a mother, or the impact of the demands being made on her time and energy. However, ask a mother with young adult-children3 what being a mother means to her and she may speak in similar tones, but she may also speak in differing tones. For example, a "mature" mother may speak of the "empty nest", the "crowded house" and/or "its revolving front door". She may speak of issues related to the vulnerability of the long term marriage, elder care, or grandparenting, or even disillusionment and disenchantment. The purpose of this research is to explore the identity challenges and prospects of some mothers with young adult-children aged between 18 and 30 years of age in twenty-first century Australia. In interpreting the identity challenges and prospects this particular cohort of mothers encounter in their ordinary, everyday living, a diverse and particular range of maternal experiences.my own included5.have been traced, along with the social and ethical meanings ascribed in them. With an understanding and appreciation of voice as the medium which connects one's inner and outer worlds, this research illuminates the plurality of voices and the multiple layers of meaning in each of these mother's particular living and existing realities. Specifically, this research addresses the narrowly constructed, canonical maternal identity through a critical exploration and reflection on stories, shared in a research context, of the living realities of a group of self-identified "mature", middle-class, Australian mothers with children aged between 18 and 30 years of age6. By appraising the broader familial, historical, social, cultural, institutional, and, importantly, moral contexts in which these mothers are situated, 'thick descriptions' (Geertz 1973, 27)7 of maternal identities, and the challenges and prospects these mothers are negotiating, are provided. In terms of its ethical orientation, the frameworks which support and frame this research reject, repudiate and contest (Nelson 2001) the reduction of ethical concerns to individual or intellectual problems or dilemmas to be solved through the application of a theory derived from reasoned thinking. In dismissing deductive and =theoretical-juridical‘8 approaches, the individualistic orientation entrenched in contemporary Western moral thinking, expressed in the notion of '"what ought I to do" when faced with a problem, issue or dilemma of practical urgency' (Isaacs & Massey 1994, 1), is simultaneously rejected, repudiated and contested (Nelson 2001). In countering such understandings, this research reorients us to the illumination and articulation of who it is good to be, for each of these mothers, in allegiance with those goods which guide and inspire her orientations towards living a good life—a life which embraces and enhances the flourishing of herself and her significant others. With an understanding and appreciation that 'mind is never free of precommitment[—t]here is no innocent eye, nor is there one that penetrates aboriginal reality' (Bruner 1987, 32), this thesis is written with the voices of other interlocutors9. These interlocutors include the voices of my research participants whom I refer to as "research interlocutors", my textual "friends" — those scholars whose work resonates strongly with my orientations—as well as the myriad other voices that speak to mothers, for mothers and about mothers, such as those found in popular and mainstream press and culture. Sometimes these voices resonate; other times dissonance may be heard. In situating this research within these complementary frameworks, this research invites readers to join with me in considering, appreciating and appraising the narrow construction of maternal identity. I seek for this engagement, like the engagements with my research interlocutors, to be 'a meeting of voices, an authentic dialogue that is inclusive of the voices of all concerned participants' (Isaacs 2001, 6). I hope that the voices in this thesis resonate with yours (although, at times, you may feel some dissonance) and that together we can draw closer to the accounting, re-counting and re-stor(y)ing of maternal identities; like concentric circles of witness, the dialogue, ...will thus be expanded rippling into corners where one might both imagine, and least expect. Possibilities, then, are vast; the future exciting (Smith 2007, 397). This research is also shaped and guided by maternal scholarship, a relatively new field of inquiry known as 'motherhood studies' (O'Reilly 2011, xvii) which has its origins within the broader terrain of feminist scholarship. As a work of maternal scholarship, this thesis draws upon and continues the tradition of examining motherhood as it is experienced 'in a social context, as embedded in a political institution: in feminist terms' (Rich 1995, ix). It values mothers, their experiences, their stories, their lives. As such, this research is oriented towards 'matricentric feminism', a particular form of feminist inquiry, politics and theory which is consistent with and receptive to feminist frameworks of care and equal rights (O‘Reilly 2011, 25). A number of complementary conceptual frameworks have been engaged in this research with the thesis presented in three parts: the pre-figurative, configurative and re-configurative. As my particular living experiences provided the initial motivation for this research, an account of the challenges I experienced as a mother with young adult-children are outlined as a Prelude to this thesis. Attention then turns to Part One – Pre-figuring Maternal Identities in which the contextual, conceptual and methodological foundations underpinning this research are explored and outlined. In Chapter One, the prevailing cultural narratives and social discourses supporting and shaping the construction of the canonical maternal identity are outlined. Next, in setting the scholarly context, the critiques — arising from feminist and maternal scholarship — of motherhood as a patriarchal institution, mothering as experience, and mothering as work, are explored. As this research engaged with participants who are embedded in particular middle-class, heterosexual, familial and cultural structures, an exploration of family life cycle theory and main stream media accounts are also incorporated. The terrain in which "mature" mothering within an Australian context is experienced is also outlined, including the notions of "empty nests" and "crowded houses", grandparenting, elder care and women's midlife transition. Chapter Two gives an account of the conceptual ontological, ethical, identity and narrative frameworks underpinning this research. In setting the context for rich interpretations, the characteristics of being human10 are outlined before attention turns to our embodiment and embeddedness in our shared human condition11. From this point, attention then turns to understanding the moral form of human living12. In appreciating the vulnerability inherent in our shared human condition, the ways in which we may experience trouble in our lives is noted. The framing of identity constitution13 as complex, multi-faceted, relationally negotiated and composed is then outlined, followed by an understanding of why narrative is a valuable interpretive tool for interpreting and understanding human experiences. This chapter concludes with an appreciation of the ethical significance of storytelling. The research methodology is then outlined in Chapter Three. The rationale underpinning the adoption of the narrative interviewing technique of in-depth interviewing is explored. In exploring these methodological frameworks, the recruitment and interview processes involved in gathering and interpreting the recorded transcripts of ten Australian mothers with young adult-children are outlined. The method of analysis known as the Listening Guide14 best complements the multi-layered, pluri-vocal nature of narrative accounting. The final section of Chapter Three outlines The Guide, with one mother's recorded transcript used to illustrate this method's step-by-step process. Having gathered an understanding and appreciation of the pluri-vocal, multi-layered nature of narrative and identity constitution, the tone of this thesis changes in Part Two . Configuring Maternal Identities. This section consists of Chapters Four and Five and seeks to find meaning in, and make sense of, the differences and commonalities across these particular accounts. Chapter Four explores the living realities of four Australian mothers with young adult-children: Poppy, Honey, Lily and Heather. In presenting a thick description of these mothers' situated realities, the frameworks.the familial, social, cultural, historical and institutional backgrounds.which have supported and shaped each mother's experiences are illuminated. Simultaneously revealed through these particular accounts are the plurality of goods focusing and moving each mother to the moral form of life, a life of meaning and purpose. The harms challenging some mothers' moral motivations are also revealed in this chapter. Specifically illustrated in Chapter Four are the unique and qualitative differences of particular maternal identity configurations. Chapter Five reveals the commonalities amongst all of the research interlocutors' accounts. This chapter contests the individualistic orientation of many contemporary accounts of motherhood which are aimed at defining or contesting what a "good" mother ought to do. By turning away from such individualistic orientations, the chapter does not seek to define 'the content of obligation' (Taylor 1989, 3) but rather seeks to illuminate and articulate a richer, deeper understanding and appreciation of maternal be-ing and be-coming - that is, who it is good to be, for each of these mothers - in allegiance with those goods that focus and inspire her moral motivations. Part Three - Re-Configuring Maternal Identities, which is comprised of Chapter Six, draws this thesis to a close. In this final chapter, the preconceptions, conditions and aspirations for this mother-centred account of the living realities of a small, local cohort of mothers are reiterated. The insights gathered from the rich, descriptive accounts are illuminated and articulated, and the chapter closes with some suggestions for future research. In a Postlude, I reflect on how this research has been a transformative learning experience in my own life.an experience in which I have been able to not only deeply understand and appreciate the challenges and disorientation I was experiencing but also to identify and reorient my stance in relation to the good. In a practical sense, by offering thick descriptions of the living realities of this cohort of "mature" mothers, this research challenges the canonical maternal identity and questions its relevance for, and effect on, "mature" mothers' identity constitution. By bringing to light the complex existing realities of these particular mothers, this research critiques the canonical maternal identity by illustrating that each mother's life and her identity constitutions are complex, relationally negotiated and composed and that motherhood is an enduring way of being. Through these illustrations, this research engages with and extends understandings of difference feminism. This research, however, not only rejects, repudiates and contests (Nelson 2001) the narrowly defined canonical maternal identity. By illuminating and articulating the goods which shape and inspire these "mature" mothers' motherwork, this research offers a matricentric account which is consistent with and respectful of the particular, situated realities—the broader familial, social, institutional, but most importantly, moral values and frameworks—in which each mother‘s life is embedded and her motherwork oriented. By understanding and appreciating the complex and multiple webs of relationships in which each mother exists, this matricentric re-stor(y)ing of maternal experiences not only understands and appreciates the unique nature of each mother‘s existing realities, it is oriented to the continuing enhancing of the shared pursuit of the good which underpins particular maternal practices and particular maternal ways of being.