Prokineticin ligands and receptors are expressed in the human fetal ovary and regulate germ cell expression of COX2

CONTEXT: Fetal ovarian development and primordial follicle formation underpin future female fertility. Prokineticin (PROK) ligands regulate cell survival, proliferation and angiogenesis in adult reproductive tissues including the ovary. However, their expression and function during fetal ovarian development remains unclear.OBJECTIVE: To investigate expression and localization of the PROK ligands, receptors and their downstream transcriptional targets in the human fetal ovary.SETTING: This study was conducted at the University of Edinburgh.PARTICIPANTS: Ovaries were collected from 37 morphologically normal human fetuses.DESIGN AND MAIN OUTCOME MEASURES: mRNA and protein expression of PROK ligands and receptors was determined in human fetal ovaries using qRT-PCR, immunoblotting and immunohistochemistry. Functional studies were performed using a human germ tumour cell line (TCam-2) stably transfected with PROKR1.RESULTS: Expression of PROK1 and PROKR1 was significantly higher in mid-gestation ovaries (17-20 weeks) than at earlier gestations (8-11 and 14-16 weeks). PROK2 significantly increased across the gestations examined. PROKR2 expression remained unchanged. PROK ligand and receptor proteins were predominantly localised to germ cells (including oocytes within primordial follicles) and endothelial cells, indicating these cell types to be the targets of PROK signalling in the human fetal ovary. PROK1 treatment of a germ cell line stably-expressing PROKR1 resulted in ERK phosphorylation, and elevated COX2 expression.CONCLUSIONS: Developmental changes in expression and regulation of COX2 and pERK by PROK1 suggest that PROK ligands may be novel regulators of germ cell development in the human fetal ovary, interacting within a network of growth and survival factors prior to primordial follicle formation.</p

Ovarian leydig cell hyperplasia: an unusual case of virilization in a postmenopausal woman.

Objective. To report an unusual case of ovarian Leydig cell hyperplasia resulting in virilization in a postmenopausal woman. Methods. Patient\u27s medical history and pertinent literature were reviewed. Results. A 64-year-old woman presented with virilization with worsening hirsutism, deepening of her voice, male musculature, and male pattern alopecia. Her pertinent past medical history included type 1 diabetes, hyperlipidemia, and hypertension. Her pertinent past surgical history included hysterectomy due to fibroids. On further work-up, her serum total testosterone was 506 ng/dL (nl range: 2-45) and free testosterone was 40 pg/mL (nl range: 0.1-6.4). After ruling out adrenal causes, the patient underwent an empiric bilateral oophorectomy that showed Leydig cell hyperplasia on pathology. Six weeks postoperatively, serum testosterone was undetectable with significant clinical improvement. Conclusion. Postmenopausal hyperandrogenism can be the result of numerous etiologies ranging from normal physiologic changes to ovarian or rarely adrenal tumors. Our patient was found to have Leydig cell hyperplasia of her ovaries, a rarely reported cause of virilization

Do Multinational enterprises push up wages of domestic firms in the Italian Manufacturing sector?

This paper analyzes the effects of foreign direct investment on wages paid by domestic firms in the Italian manufacturing sector over the period 2002–2007. In particular, the authors investigate the im-pact of multinational enterprises on wages paid by local firms which operate in the same industry, known and horizontal wage spillovers, or have linkages with multinational enterprises in both downstream and upstream industries, known as vertical wage spillovers. By using a large panel dataset, consisting of 551,000 observations, the authors find evidence of wage spillovers only at inter-industry level and, more specifically, for those firms who supply their goods to multinational enterprises, described as backward wage spillovers. Moreover, findings suggest that the wage spillover effect is strongly affected by the technological gap between local and foreign firms: only workers employed in domestic firms with a low-medium technological absorptive capacity seem to benefit from the presence of multinational enterprises in terms of higher wages

Regional innovation and spillover effects of foreign direct investment in China: a threshold approach

Using a data set on twenty-nine Chinese provinces for the period 1985–2008, this paper establishes a threshold model to analyse the relationship between spillover effects of foreign direct investment (FDI) and regional innovation in China. There is clear evidence of double-threshold effects of regional innovation on productivity spillovers from FDI. Specifically, only when the level of regional innovation reaches the minimum innovation threshold will FDI in the region begin to produce positive productivity spillovers. Furthermore, positive productivity spillovers from FDI will be substantial only when the level of regional innovation attains a higher threshold. The double threshold divides Chinese provinces into three super-regions in terms of innovation, with most provinces positioned within the middle-level innovation super-region. Policy implications are discussed

Changes in capital allocation practices – ERM and organisational change

This paper aims to study changes in capital allocation routines following the introduction of a new risk management system, enterprise risk management (ERM). Based on an institutional framework and empirical evidence from multiple sources in a large UK insurance company, we evaluated the extent and nature of organisational change. ERM was seen as an external driver to the change in the existing routines, which in turn led to internal changes in new capital allocation routines. The change was extreme, which signifies that existing capital allocation routines were not strong enough to deal with ERM as a key driver of change

Caspase Inhibitors of the P35 Family Are More Active When Purified from Yeast than Bacteria

Many insect viruses express caspase inhibitors of the P35 superfamily, which prevent defensive host apoptosis to enable viral propagation. The prototypical P35 family member, AcP35 from Autographa californica M nucleopolyhedrovirus, has been extensively studied. Bacterially purified AcP35 has been previously shown to inhibit caspases from insect, mammalian and nematode species. This inhibition occurs via a pseudosubstrate mechanism involving caspase-mediated cleavage of a “reactive site loop” within the P35 protein, which ultimately leaves cleaved P35 covalently bound to the caspase's active site. We observed that AcP35 purifed from Saccharomyces cerevisae inhibited caspase activity more efficiently than AcP35 purified from Escherichia coli. This differential potency was more dramatic for another P35 family member, MaviP35, which inhibited human caspase 3 almost 300-fold more potently when purified from yeast than bacteria. Biophysical assays revealed that MaviP35 proteins produced in bacteria and yeast had similar primary and secondary structures. However, bacterially produced MaviP35 possessed greater thermal stability and propensity to form higher order oligomers than its counterpart purified from yeast. Caspase 3 could process yeast-purified MaviP35, but failed to detectably cleave bacterially purified MaviP35. These data suggest that bacterially produced P35 proteins adopt subtly different conformations from their yeast-expressed counterparts, which hinder caspase access to the reactive site loop to reduce the potency of caspase inhibition, and promote aggregation. These data highlight the differential caspase inhibition by recombinant P35 proteins purified from different sources, and caution that analyses of bacterially produced P35 family members (and perhaps other types of proteins) may underestimate their activity

Robust evidence for bisexual orientation among men

The question whether some men have a bisexual orientation—that is, whether they are substantially sexually aroused and attracted to both sexes—has remained controversial among both scientists and laypersons. Skeptics believe that male sexual orientation can only be homosexual or heterosexual, and that bisexual identification reflects nonsexual concerns, such as a desire to deemphasize homosexuality. Although most bisexual-identified men report that they are attracted to both men and women, self-report data cannot refute these claims. Patterns of physiological (genital) arousal to male and female erotic stimuli can provide compelling evidence for male sexual orientation. (In contrast, most women provide similar physiological responses to male and female stimuli.) We investigated whether men who self-report bisexual feelings tend to produce bisexual arousal patterns. Prior studies of this issue have been small, used potentially invalid statistical tests, and produced inconsistent findings. We combined nearly all previously published data (from eight previous studies in the United States, United Kingdom, and Canada), yielding a sample of 474 to 588 men (depending on analysis). All participants were cisgender males. Highly robust results showed that bisexual-identified men’s genital and subjective arousal patterns were more bisexual than were those who identified as exclusively heterosexual or homosexual. These findings support the view that male sexual orientation contains a range, from heterosexuality, to bisexuality, to homosexuality