Primordial follicles are the first small follicles to appear in the mammalian ovary. Women are born with a fixed number of primordial follicles in the ovaries. Once formed, the pool of primordial follicles serves as a source of developing follicles and oocytes. The first aim of this thesis was to investigate the functional role of the intra-oocyte signaling pathways, especially the phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin complex 1 (mTORC1) pathways in the regulation of primordial follicle activation and survival. We found that a primordial follicle remains dormant when the PI3K and mTORC1 signaling in its oocyte is activated to an appropriate level, which is just sufficient to maintain its survival, but not sufficient for its growth initiation. Hyperactivation of either of these signaling pathways causes global activation of the entire pool of primordial follicles leading to the exhaustion of all the follicles in young adulthood in mice. Mammalian oocytes, while growing within the follicles, remain arrested at prophase I of meiosis. Oocytes within the fully-grown antral follicles resume meiosis upon a preovulatory surge of leutinizing hormone (LH), which indicates that LH mediates the resumption of meiosis. The prophase I arrest in the follicle-enclosed oocyte is the result of low maturation promoting factor (MPF) activity, and resumption of meiosis upon the arrival of hormonal signals is mediated by activation of MPF. MPF is a complex of cyclin dependent kinase 1 (Cdk1) and cyclin B1, which is essential and sufficient for entry into mitosis. Although much of the mitotic cell cycle machinery is shared during meiosis, lack of Cdk2  in mice leads to a postnatal loss of all oocytes, indicating that Cdk2 is important for oocyte survival, and probably oocyte meiosis also. There have been conflicting results earlier about the role of Cdk2 in metaphase II arrest of Xenopus  oocytes. Thus the second aim of the thesis was to identify the specific Cdk that is essential for mouse oocyte meiotic maturation. We generated mouse models with oocytespecific deletion of Cdk1  or Cdk2  and studied the specific requirements of Cdk1 and Cdk2 during resumption of oocyte meiosis. We found that only Cdk1 is essential and sufficient for the oocyte meiotic maturation. Cdk1 does not only phosphorylate the meiotic phosphoproteins during meiosis resumption but also phosphorylates and suppresses the downstream protein phosphatase 1, which is essential for protecting the Cdk1 substrates from dephosphorylation.

No description available.

Parent child communications about sex play an important role in influencing adolescent’s sexual behaviors and attitudes. The present study was conducted to examine how sexual communications between African American mothers and their children change over a period of three years in the areas of sex education, communication about risk reduction, and child and parent report of responsiveness. Hierarchical linear modeling (HLM) analyses found significant linear or curvilinear trajectory in communication with sons and daughters in all areas. Gender differences were found such that daughters received more communication than sons. Furthermore, daugthers’ sexual maturation was found to be associated with a decrease in the rate of decline of communication about general sex information. For sons, mothers decreased in rates of responsiveness as sons got older; however, as sons’ sexual maturation increased, rates of declining responsiveness slowed down.

Sexual maturation during commercial culture of Atlantic cod (Gadus morhua L.) represents a significant production bottleneck restricting the profitability of the industry. Such problems in other species have traditionally been addressed by artificial manipulation of photoperiod cycles, however little research exists in this field in cod. This thesis therefore investigates the interactions between artificial photoperiod manipulation, sexual maturation and somatic growth in this species. In the first experiment, populations of Atlantic cod (hatched, spring 1999) were maintained on either a simulated natural photoperiod (SNP) or continuous illumination (LL) from approximately 15 months post hatch (MPH) (July 2000) in an enclosed tank system. Growth performance was recorded monthly along with observations of reproductive activity over the subsequent 2 years (up to July 2002). At both 2 and 3 years of age the entire population raised under SNP matured and spawned, during which time mean weight reduced by 13% and 24% respectively. No spawning individuals were recorded at 2 years of age in the LL population and only 18% were observed to spawn at 3. However, observations of both changes in gonadal morphology (observed via ultrasound scanning) and a suppression in growth rate at 2 years of age in the LL population alluded to a maturation “dummy run” regulated by an endogenous clock. Despite this phenomenon, the LL treatment realised a 39% and 43% improvement in wet weight following 1 and 2 years of exposure to LL respectively. When the diel cycle of plasma melatonin was compared between the treatments in February 2001 (23MPH) the SNP population displayed an A-profile diel rhythm ranging between 20 and 50 pg/ml while the LL treatment did not display any rhythm. In the second experiment of this work, two populations of cod (hatched, spring 2001) were reared in commercial open cage systems, one of which experienced continuous additional artificial illumination between July 2002 (15MPH) and October 2003 (30MPH) provided by four, 400W submerged lighting units. Growth and maturation were assessed in both populations throughout. In March 2003 (24MPH) it was apparent that spawning individuals were present in both the SNP and LL populations though a significantly lower number of spawning individuals in the LL treatment suggested that the peak in spawning activity was delayed by about 1 to 2 months. With both populations apparently maturing at 2 years of age, there was no significant difference in weight between the populations at the end of the trial. In comparison to experiments I and IV of this work, these results would suggest that in comparison to salmonids for example, Atlantic cod appear to have a heightened sensitivity to light allowing individuals to differentiate the ambient photoperiod signal from the application of continuous artificial light. In the third experiment, 6 populations of approximately 20 tagged individuals (hatched spring 1999) were maintained, from December 2000 to July 2002, under either SNP, LL or one of four, out of season “square wave” photoperiod regimes (repeating cycles with a 12 month period, consisting of a 6 month window of LL followed by six months of short day lengths [SD, 7L:17D] which had been staggered to start over a six month period). Each individual was monitored monthly for maturation status. Out of season “square wave” photoperiods were demonstrated to successfully entrain maturation and hence significantly alter the spawning profiles in these populations. Application of LL from December 2000 failed to inhibit maturation in the spring of 2001 and, in fact, advanced the spawning season by 1 month while those that experienced SD from the same date showed significant extension of the subsequent spawning season. Interestingly, the males maintained on LL throughout the experiment matured both in the spring of 2001 and one year later in the spring of 2002 while females under the same treatment only matured and spawned in 2001. In the fourth experiment, a total of 830 tagged individuals were raised either under SNP or one of 7 photoperiod treatments, consisting of 5 groups transferred from SNP to LL at 3 monthly intervals between 6 and 18 MPH where they remained and a further two groups maintained on LL from 6 to 15MPH and 6 to 21 MPH respectively before being returned to SNP. Both the gonadic and somatic axes were monitored at the physiological and endocrinological level at three monthly intervals from 6 to 27 MPH. The results demonstrated that it is the falling autumnal photoperiod signal after the summer solstice, more specifically after October, that is responsible for recruiting individuals to enter the sexual maturation cycle. Furthermore, in all treatments where this signal was masked i.e. those which experienced LL starting at or prior to 15MPH, except for some restricted spermatogenic activity in the males testis observed at 27MPH, there was no significant reproductive activity and growth was improved by up to 60% at 27 MPH. While providing evidence for direct photic stimulation of somatic growth, the growth results were also correlated with the measurement of plasma IGF-I and demonstrated its potential as a tool to assess growth rates in the species. Plasma melatonin measured at 15MPH, as in experiment I, was suppressed in all populations which were under LL photoperiods. By identifying the photoperiod “window of opportunity” which recruits individuals into the sexual maturation cycle, this work was able to conclude that the application of LL from the summer solstice prior to maturation is the most efficient photoperiod strategy to be adopted by the aquaculture industry to realise maximum growth potential from their cultured stocks.

Indien är en tillväxtmarknad med många möjligheter; det är en plats för nytänkande och frugala innovationer. Frugala innovationer är ett fenomen som Indien är välkänt för. I grunden uppstår frugala innovationer genom sparsamhet i processen för att ta fram effektiva lösningar. Kunskapen om frugala innovationer och dess förhållningssätt kopplat till svenska energiföretag som är inom branschen för förnybara energikällor är dock begränsad. Därför är innovationsmyndigheten Vinnova och Energimyndigheten intresserade av att se om det finns potential för ett antal svenska energiteknikföretag att lyckas etablera sig på Indiens marknad för förnybara energikällor, där effektivitet och sparsamhet är viktigt. Undersökningen har skett genom en kvalitativ forskningsmetod i form av intervjuer med de företag som har varit tillgängliga och även med en expert med kunskap om den Indiska marknaden. Teorier har främst hämtats ifrån tryckt litteratur och vetenskapliga artiklar. Under studiens gång arbetade författarna fram en modell som kan användas för att bedöma ett företags förmåga att etablera sig på en främmande marknad. I modellen ingår ett antal viktiga aspekter inom områden som ekonomi, innovation, marknad och tillväxt. Forskningen har kommit fram till slutsatser om samtliga undersökta företags potential att lyckas i Indien. I studien fann författarna att om man ska ha potential att lyckas på den Indiska marknaden, ska man bland annat ha en aktuell och effektiv produkt, stark ekonomi, konkurrenskraftighet samt marknadsmöjligheter. / India is an emerging market with many opportunities; it's a place for rethinking and frugal innovations. Frugal innovation is a phenomenon that India is well known for. Frugal innovations arise by thrift in the process of developing effective solutions. Knowledge about the frugal innovations and its approach linked to Swedish energy companies that is in the business of renewable energy is limited. Therefore, the innovation agency Vinnova and the Swedish Energy Agency (Energimyndigheten) are interested to see if there is potential for a number of Swedish energy companies to establish in the Indian market for renewable energy, where efficiency and economy are important. The survey was done by a qualitative research in the form of interviews with the companies that have been available and also an expert with knowledge of the Indian market. Theories were mainly collected from printed literature and scientific articles. During the study, the authors came up with a model that can be used to estimate a company's ability to establish itself in a foreign market. The model includes a number of important aspects, such as financial aspects, innovation, market and growth. The research has come to conclusions about all the studied companies potential to succeed in India. In the study, the authors found that if you're going to have the potential to succeed in the Indian market, you should have an up-to-date and effective product, strong economy, competitiveness and market opportunities.

Conifer species are subjected to major time constraints in tree improvement because of their long regeneration cycle and large sizes. However, integration of developing biotechnologies could significantly reduce this time limitation in tree breeding programs. In this regard, somatic embryogenesis (SE) offers a great potential in commercially important Turkish red pine (Pinus brutia TEN.) for rapid production of larger number of clones as well as capture of greater genetic gains. In this study, seven collections were done to sample precotyledonar zygotic embryos for induction of embryogenic tissue (ET) from 15 clones located in Antalya. Afterwards, abscisic acid, carbohydrates, polyethylene glycol (PEG), and gellan gum were tested to obtain mature somatic embryos in maturation experiments. Analyses of variance showed a significant variation among collection dates (43.1% of total variance) and clones studied (18.8% of total variance) for induction of ETs. Overall initiation frequency of ET in this study was 11.6% with clonal range of 4.7 &amp / #8211 / 24.1%. Of those tested maturation treatments, 80&amp / #956 / M ABA, sucrose and maltose at 3 and 6%, 3.75% PEG combined with 1% gellan gum were found to be suitable for maturation of somatic embryos in Turkish red pine. Sixty nine somatic embryos were obtained from Clone 22, which was one of tested clones. Induction frequencies could be further improved by using different basal media and/or manipulating media components, such as plant growth regulators. For proper maturation of somatic embryos, embryogenic lines need to be screened to find suitable lines, which are developmentally responsive to ABA treatment.

Female gametes, or oocytes grow and mature in a niche environment maintained by the somatic cells of the ovarian follicle. At ovulation ovarian follicle cells respond to the luteinising hormone (LH) surge coordinating the final maturation, meiotic resumption and release of oocytes. Simultaneously, production of a unique “mucified” extracellular matrix surrounding the oocyte through synthesis of Hyaluronan (HA) and HA cross-linking proteins produces an “expanded” and stabilised cumulus oocyte matrix with a specific composition, structure and function. In vitro maturation (IVM) of oocytes is a procedure by which cumulus oocyte complexes (COCs) are stimulated to produce cumulus matrix and undergo oocyte maturation ex vivo. In vitro maturation is a useful procedure for studying oocyte competence as well as offering health benefits for patients undergoing assisted reproduction. Oocytes derived from IVM have much lower developmental competence than in vivo matured oocytes, likely as a result of altered environmental conditions and gene expression leading to suboptimal maturation and/or inappropriate metabolic control in oocytes. Cumulus matrix expansion is widely used as an indicator of good oocyte developmental potential, however, the mechanism(s) that endow oocyte quality and how these may be influenced by the cumulus matrix are poorly understood. To better understand the process by which cumulus matrix is linked to the final stages of oocyte maturation, I undertook investigation of mouse COC matrix composition and function after in vivo maturation in comparison to IVM. The gene responsible for Hyaluronan synthesis, Has2, was not impaired under IVM conditions. In contrast, two key extracellular matrix proteins; Versican and Adamts1, which are normally selectively incorporated into periovulatory COCs in vivo, were greater than 10-fold reduced in IVM whether stimulated with Egf and/or FSH. This work is the first to show that commonly used IVM conditions result in altered gene expression in cumulus cells. Furthermore, the absence of Adamts1 and Versican suggest that COC matrix may be functionally insufficient. Although associated with good developmental potential, the function of the COC matrix in oocyte maturation is unknown. I assessed the properties of COC matrix that control metabolite supply to oocytes by examining transport of fluorescently labelled glucose and cholesterol across mouse COCs. Profound differences in the control of metabolite supply to oocytes in IVM were observed. In vivo matured complexes were capable of excluding glucose from the entire COC and cholesterol was excluded from oocytes. Conversely IVM COCs were more permissive to rapid equilibration of glucose and cholesterol concentrations across the complex and in oocytes. In fact both metabolites accumulated rapidly in IVM oocytes resulting in inverse gradient patterns of glucose and cholesterol abundance with highest concentrations accumulating in the oocyte after IVM vs highest concentrations surrounding the COC after in vivo maturation conditions. As oocytes are highly sensitive to high glucose my results indicate that metabolic balance in IVM may be disrupted due to impaired molecular filtration properties of the mucified COC matrix that controls supply of hydrophilic and lipophylic substrates. Importantly these novel findings can explain the glucose sensitivity of IVM oocytes and identifies a mechanism by which IVM may lead to poorer oocyte developmental competence. To translate these findings into the improvement of IVM I generated recombinant expression plasmid constructs for several Adamts1 and Versican functional domains. The efficacy of Versican as an IVM supplement that activates cumulus cell signal transduction was proved in principle, by showing enhanced COC matrix expansion when added to mouse IVM cultures. Similar mechanisms are likely to be functional in human COCs since I demonstrated VERSICAN and ADAMTS1 expression in human in vivo matured cumulus and granulosa cells. This work has advanced our understanding of oocyte maturation and will lead to improvements in IVM and healthier outcomes from reproductive therapies. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1342419 / Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2008

Female gametes, or oocytes grow and mature in a niche environment maintained by the somatic cells of the ovarian follicle. At ovulation ovarian follicle cells respond to the luteinising hormone (LH) surge coordinating the final maturation, meiotic resumption and release of oocytes. Simultaneously, production of a unique “mucified” extracellular matrix surrounding the oocyte through synthesis of Hyaluronan (HA) and HA cross-linking proteins produces an “expanded” and stabilised cumulus oocyte matrix with a specific composition, structure and function. In vitro maturation (IVM) of oocytes is a procedure by which cumulus oocyte complexes (COCs) are stimulated to produce cumulus matrix and undergo oocyte maturation ex vivo. In vitro maturation is a useful procedure for studying oocyte competence as well as offering health benefits for patients undergoing assisted reproduction. Oocytes derived from IVM have much lower developmental competence than in vivo matured oocytes, likely as a result of altered environmental conditions and gene expression leading to suboptimal maturation and/or inappropriate metabolic control in oocytes. Cumulus matrix expansion is widely used as an indicator of good oocyte developmental potential, however, the mechanism(s) that endow oocyte quality and how these may be influenced by the cumulus matrix are poorly understood. To better understand the process by which cumulus matrix is linked to the final stages of oocyte maturation, I undertook investigation of mouse COC matrix composition and function after in vivo maturation in comparison to IVM. The gene responsible for Hyaluronan synthesis, Has2, was not impaired under IVM conditions. In contrast, two key extracellular matrix proteins; Versican and Adamts1, which are normally selectively incorporated into periovulatory COCs in vivo, were greater than 10-fold reduced in IVM whether stimulated with Egf and/or FSH. This work is the first to show that commonly used IVM conditions result in altered gene expression in cumulus cells. Furthermore, the absence of Adamts1 and Versican suggest that COC matrix may be functionally insufficient. Although associated with good developmental potential, the function of the COC matrix in oocyte maturation is unknown. I assessed the properties of COC matrix that control metabolite supply to oocytes by examining transport of fluorescently labelled glucose and cholesterol across mouse COCs. Profound differences in the control of metabolite supply to oocytes in IVM were observed. In vivo matured complexes were capable of excluding glucose from the entire COC and cholesterol was excluded from oocytes. Conversely IVM COCs were more permissive to rapid equilibration of glucose and cholesterol concentrations across the complex and in oocytes. In fact both metabolites accumulated rapidly in IVM oocytes resulting in inverse gradient patterns of glucose and cholesterol abundance with highest concentrations accumulating in the oocyte after IVM vs highest concentrations surrounding the COC after in vivo maturation conditions. As oocytes are highly sensitive to high glucose my results indicate that metabolic balance in IVM may be disrupted due to impaired molecular filtration properties of the mucified COC matrix that controls supply of hydrophilic and lipophylic substrates. Importantly these novel findings can explain the glucose sensitivity of IVM oocytes and identifies a mechanism by which IVM may lead to poorer oocyte developmental competence. To translate these findings into the improvement of IVM I generated recombinant expression plasmid constructs for several Adamts1 and Versican functional domains. The efficacy of Versican as an IVM supplement that activates cumulus cell signal transduction was proved in principle, by showing enhanced COC matrix expansion when added to mouse IVM cultures. Similar mechanisms are likely to be functional in human COCs since I demonstrated VERSICAN and ADAMTS1 expression in human in vivo matured cumulus and granulosa cells. This work has advanced our understanding of oocyte maturation and will lead to improvements in IVM and healthier outcomes from reproductive therapies. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1342419 / Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2008

Background. Despite extensive research the etiology of schizophrenia remains unclear. Whilst a substantial body of research points to a developmental component where early risk factors and maturational processes interact to culminate in psychosis during adulthood, key components and processes are yet to be confirmed. Prospective birth cohort studies, with their longitudinal data drawn from the general population, are vital to better understanding these pathways. To date, birth cohort (BC) studies have found that compared to healthy individuals, those who develop schizophrenia are more likely to display subtle deviations in certain developmental domains during infancy, childhood or adolescence. Yet there had been no recent review of these findings to identify areas of agreement, disagreement or where information was lacking. Aims. The overall aim of this dissertation is two-fold: firstly to identify and consolidate the current literature related to the antecedents of schizophrenia based on birth cohort studies; and secondly to undertake empirical studies based on an Australian birth cohort to address specific issues raised in the preceding review. Methods. The following three papers present empirical studies which use common methods based on an Australian birth cohort. Each study was based on a birth cohort of 3801 young adults born between 1981 and 1984, as part of the Mater University Study of Pregnancy and its outcomes. An extensive range of behavioural, cognitive, physical and social measures had been taken at various stages during their development namely, antenatally, at birth and six months, and at 5, 14 and 21 year follow-ups. Psychiatric diagnoses were obtained at age 21 follow-up from the Composite International Diagnostic Interview (CIDI), or, if this was not available, on a self-report health outcomes checklist; this produced the outcome variable ‘screen-positive non-affective psychosis’ (SP-NAP). The association between antecedents and later SP-NAP were examined using logistic regression adjusted for potentially confounding variables (such as actual age at assessment, cannabis use in adolescence, and gender). Each study also (a) examined differences in case vs. noncase maturation over time; and (b) conducted planned sensitivity and post hoc analyses, such as for source of diagnoses and predictive validity. Analyses were performed using SAS 9.2 (SAS). Results. The main findings of the review were that BC studies of schizophrenia provide important insights into both the maturational antecedents of schizophrenia and putative risk modifying factors. Yet while some antecedents, such as neurocognitive dysfunction, have been well documented, others are less certain (such as postnatal physical growth). There are no studies based on pre-morbid attentional measures. In addition, there were no studies of developmental pathways where continuity of maturation was based on within-individual scores rather than group means. These findings led to three empirical studies based on an Australian birth cohort previously untapped in psychosis research. The first study found that higher levels childhood and adolescent general psychopathology increased the risk of SP-NAP. This effect was less clear for females and when adolescent psychopathology had been rated by mothers at the 14-year follow-up. In contrast, self-reported hallucinations at the 14 year follow-up increased the risk of SP-NAP in both sexes. Males with high psychopathology scores in both childhood and adolescence were at greatest risk, followed by males and females whose ‘social, attention and thought’ scores were either consistently dysfunctional or worsened from childhood to adolescence (3- to 13-fold risk). The second study found that altered physical growth in infancy and adulthood (increased head circumference and height) raised the risk of SP-NAP for females but not males. For cases, there was no evidence of ‘catch-up growth’, i.e., growth retardation at birth being followed by a period of rapid growth. There was also no group difference in pubertal maturation for males or females. The final study found that dysfunction in childhood and adolescent intelligence, attention and speech increased the risk of SP-NAP for males but not females. Males with persistently high scores or who worsened on measures related to childhood and adolescent attentional problems were at greatest risk of SP-NAP. Discussion. While there are some caveats, disturbed developmental antecedents – particularly psychopathology and impaired cognition in males – were more frequently identified in cohort members who developed non-affective psychosis than their peers. More specifically, this disturbed development appeared be in domains which reflect those of the adult disorder and include the possible endophenotypes of psychosis-like experiences, inattention and visuospatial dysfunction. Of interest, self-rated items during adolescence were associated with increased risk of later psychosis. Finally, developmental pathways associated with non-affective psychosis were not uniform in timing but varied depending on such factors as domain and gender. These findings stress that understanding the heterogeneity in developmental pathways is crucial to understanding the heterogeneous nature of the subsequent disorder.

Auditory processing is the ability of the brain to manipulate and utilise the neural output of the ear based on the frequency, intensity, and temporal features of the incoming acoustic signal. An auditory processing disorder (APD) is a deficiency in this ability. One category of tests that examine auditory processing ability are the various versions of the "filtered words test" (FWT), whereby a monaural, low-redundancy speech sample is distorted by using filtering to modify its frequency content. Due to the richness of the neural pathways in the auditory system and the redundancy of acoustic information in spoken language, a normal listener is able to recognize speech even when parts of the signal are missing, whereas this ability is often impaired in listeners with APD. One limitation of the various versions of the FWT is that they are carried out using a constant level of low-pass filtering (e.g. a corner frequency of 1000 Hz), which is prone to ceiling and floor effects. The purpose of this study was to counter these effects by modifying the FWT to use a computer-based adaptive procedure, to improve the sensitivity of the test over its constant-level counterparts. The University of Canterbury Monosyllabic Adaptive Speech Test (UC MAST) was performed on 23 normal adults, and 32 normal children (7 to 11 years of age). The child participants also underwent the SCAN-C test for APD in Children (Revised). Findings indicated a significant maturational effect on the UC MAST. Adult participants performed significantly better on the UC MAST in comparison to the child participants. In addition, adult participants performed the UC MAST more reliably than their younger counterparts. No correlation was found between performance on the UC MAST and SCAN-C test. The development of the UC MAST is discussed and the clinical implications of the findings are explored.