The effect of clomiphene citrate

Faculty of Science School of Anatomical Sciences 9901061h [email protected] citrate (CC), a synthetic estrogen, is an efficient superovulator used in infertility treatment. However pregnancy rates resulting from CC treatment are low. Research has suggested that this may be due to an aberrant effect on implantation; CC binds to estrogen receptors (ER) and may affect estrogen responsive gene expression and thus implantation. This study investigates the effect of CC on ERa, 90kDa heat shock protein (Hsp90) and Hoxa10 expression in the rat uterus. Hsp90 binds to ERa in the absence of ligand and is involved in inducing a high affinity ligand binding conformation in the ER and in transactivation of the ER. Hoxa10 has been shown to be essential for uterine receptivity to implantation. CC (0.25mg) was given to ovariectomized rats, either alone or prior to a hormonal regime known to induce uterine receptivity for implantation. Expression of ERa, Hsp90 and Hoxa10 was determined by Western blotting, fluorescence immunocytochemistry and reverse transcription polymerase chain reaction. The single dose CC treated rats were compared to the controls as well as to ovariectomized rats treated with 0.5mg 17b estradiol (E2). The CC treated pseudopregnant rats (CCPPPE treated) were compared to 5½ day pregnant and pseudopregnant rats without CC (PPPE treated), to determine CCs effect at implantation. E2 upregulated ERa and Hsp90 expression in the rat uterus compared to controls (p<0.05). The finding for ERa was unexpected as other studies have shown that E2 decreases ERa levels a few hours after administration in the uterus. The present study therefore suggests a biphasic effect of E2 on ERa expression in the rat uterus. The effect of E2 on Hsp90 and ERa also proposes a balance between the levels of these two proteins in the uterus, to keep ERa in its optimal state and suggests that too high and too low a concentration of Hsp90 may both be inhibitory to ERa functioning. No significant difference was found in ERa and Hsp90 expression between the non-receptive (vehicle treated) and the receptive (PPPE treated) rat uteri, suggesting that these two genes are not markers for receptivity. However E2 is known to induce implantation of donor blastocysts in progesterone (P4) primed uteri. Therefore it is still essential for ERa to be present at implantation. It is of interest that CC downregulated ERa levels both in ii the absence of ovarian hormones and at implantation in the rat uterus. It is therefore proposed that this antiestrogenic effect would render the uterus less sensitive to the E2 required to induce implantation, thus accounting for low pregnancy rates with CC use. Although CC did not alter the expression of Hsp90 in this study, the reduction in ERa levels in response to CC may also upset the balance in the expression of these two genes, which may affect the transcriptional activity of ERa, and further prevent implantation. No clear results were obtained for Hoxa10 expression with the Western blots. However based on the ICC results, CC did not appear to affect Hoxa10 expression. Since P4 and not E2 is known to have the predominant effect on Hoxa10 expression, it is likely that E2 analogs, such as CC, would also not affect Hoxa10 expression to a significant degree. Future work will aim to separate the different uterine compartments and to determine the effects of CC on the expression of other implantation specific genes in the uterus

Self-Defense and Rights

This is the text of The Lindley Lecture for 1976, given by Judith Jarvis Thomson, an American philosopher

Applying patterns to hypermedia instructional design (APHID)

This research addresses the issue of automatically generating instructional hypermedia documents (in the form of web sites). Our hypothesis is that, for certain types of hypermedia, an automated approach can produce satisfactory hypermedia applications more efficiently than humans are able to create them. We propose a method (APHID) that guides a hypermedia creator through the design process and partially automates the creation of hypermedia applications. Our method uses concept maps and instructional design patterns, as well as the more common domain and presentation models, to support partial automation for creating instructional hypermedia. Most hypermedia application developers follow basic graphical design principles, but few commonly accepted principles exist for the structuring of hypermedia applications. The design of instructional hypermedia imposes the additional requirement that the designer be expert both in hypermedia design and in instructional design. APHID supports designers through the use of patterns to describe and clarify design concepts for both instructional design and interface design. This thesis describes the design and development of the APHID approach and a prototype software tool that supports the development of instructional hypermedia using the APHID approach. The thesis also presents a study in which web sites created with APHID are compared (by an independent evaluator) to web sites created by instructional technologists. The study shows that good instructional web sites can be generated semi-automatically with less expenditure of time on the part of the instructional designer

High frame-rate resolution of cell division during Candida albicans filamentation

Acknowledgements: Strain YMG7139 was supplied by Peter Sudbery, University of Sheffield. DDT was funded by a BBSRC-DTG, BB/F016964/1, at Aberdeen. ACB is funded by a Royal Society URFUF080611 and a MRC NIRG90671. JB was funded by the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) REA grant agreement number 303635; by an European Research Council Advanced Award, number 340087, RAPLODAPT, and an award from the Israel Science foundation (340/13).Peer reviewedPublisher PD

Reconceptualising post-PhD research pathways: a model to create new postdoctoral positions and improve the quality of postdoctoral training in Australia

Focusing on the developmental needs of early career postdoctoral fellows – the lifeblood of an internationally competitive researchintensive university – this paper suggests an inextricably linked, two pronged approach to improving research performance at Australian universities. The first is to reconceptualise post-PhD research pathways and in doing so conceive a mechanism for creating new postdoctoral positions; the second is to develop a coherent programme of policies, processes and practices in postdoctoral education and training. In this way, Australian universities will increase their success in attracting and retaining the brightest and best postdoctoral students from all over the world and thereby improve research performanc

Uma defesa do aborto

Resumo O artigo analisa os argumentos contrários ao direito da mulher à interrupção voluntária da gravidez, fundamentando assim sua posição em defesa do direito ao aborto. A análise das contradições nos discursos do “direito à vida” ultrapassa as situações nas quais há risco de morte da mãe ou nas quais a gravidez decorreu de estupro. A consideração da mãe como pessoa moral inclui, na posição sustentada no texto, o direito a assegurar a própria vida e a escolher como esta vida será vivida. Nesta análise, o aborto é discutido em suas implicações políticas, morais e filosóficas. Palavras-chave:&nbsp;aborto; direito à vida; indivíduo; obrigação moral; gestação; escolha. &nbsp; Abstract The article examines arguments opposing women’s right to voluntary interruption of pregnancy, thus basing its own stance in favor of the right to abortion.&nbsp; Examination of contradictions in “right to life” discourses goes beyond life-threatening situations or pregnancies resulting from rape. Considering the mother as a moral person includes, in the stance sustained in the text, the right to guarantee her own life and to choose how it is going to be lived. In this analysis, abortion is debated for its political, moral, and philosophical implications. Key words:&nbsp;abortion; right to life; individual; moral obligation; pregnancy; choice.&nbsp