Internalisation of membrane progesterone receptor-α after treatment with progesterone: Potential involvement of a clathrin-dependent pathway

This article has been made available through the Brunel Open Access Publishing Fund.Internalisation and recycling of seven trans-membrane domain receptors is a critical regulatory event for their signalling. The mechanism(s) by which membrane progesterone receptor-α (mPRα) number is regulated on the cell surface is unclear. In this study, we investigated the cellular distribution of mPRα and mechanisms of mPRα trafficking using a cell line derived from a primary culture of human myometrial cells (M11) as an experimental model. RT-PCR and immunofluorescent analysis demonstrated expression of mPRα in M11 cells with mPRα primarily distributed on the cell surface under basal conditions. For the first time, plasma membrane localisation of mPRα was confirmed using immuno-gold transmission electron microscopy. Stimulation of M11 cells with progesterone (P4, 100 nM) resulted in internalisation of mPRα from the plasma membrane to the cytoplasm (10 min) and subsequent partial translocation back to the cell surface (20 min). We investigated potential endocytotic pathways involved in trafficking of mPRα after its internalisation. Partial co-localisation of clathrin with mPRα was obvious after 10 min of P4 treatment. Of note, chlorpromazine (inhibitor of clathrin-mediated pathway) inhibited the endocytosis of mPRα, whereas treatment with nystatin (inhibitor of caveolae-mediated pathway) did not affect internalisation. Collectively, these data suggest that mPRα is expressed on the cell surface of M11 cells and undergoes endocytosis after P4 stimulation primarily via a clathrin-mediated pathway.This article is available through the Brunel Open Access Publishing Fun

Expression of membrane and nuclear progesterone receptors in two human placental choriocarcinoma cell lines (JEG-3 and BeWo): Effects of syncytialization

This article has been made available through the Brunel Open Access Publishing Fund and is available from the specified link - Copyright @ 2011 Spandidos Publications Ltd.A vital function of the human placenta is to produce steroid hormones such as progesterone, which are essential for the maintenance of pregnancy and the onset of parturition. Although choriocarcinoma cell lines are valuable placental models for investigations of steroid hormone actions, little is known about the expression of progesterone receptors (PRs) in these cell lines. Therefore, in this study, the expression of membrane and nuclear PRs was investigated in cultures of fusigenic (BeWo) and non-fusigenic (JEG-3) human choriocarcinoma cell lines. In addition, the effects of an inducer of syncytialization (forskolin) on the PR expression in BeWo cells were assessed. Quantitative RT-PCR revealed that in fully syncytialized BeWo cells (treated with 50 mu M forskolin for 72 h) there was a significant down-regulation of mPR alpha and up-regulation of mPR beta and of the progesterone membrane component-1 (PGRMC1) when compared with non-syncytialized BeWo cells. Expression of all the mPR and PGRMC1 mRNAs was significantly lower in JEG-3 cells compared to non-syncytialized BeWo cells. Interestingly, expression of PR-B was unaltered between the two BeWo states but was significantly higher in JEG-3 cells. Immunofluorescence analysis revealed that mPR proteins are differentially expressed in these choriocarcinoma cell lines as well as in the human placenta. The data demonstrate that human choriocarcinoma cell lines have a complex system of progesterone signalling involving multiple classes of PRs. The finding that syncytialization is accompanied by changes in the expression of these receptors may suggest that this process influences progesterone signalling

Old Dogs Can Learn to Like New Tricks: One Instructor\u27s Change in Attitude to Online Instruction from 2009-2017

This qualitative case study examined a veteran instructor\u27s change in attitude about university online instruction. After a short review of the literature and explanation of the project, researchers conducted a content analysis of an instructor\u27s annual self-reports about his online teaching of a graduate course in the social sciences. The self-reports were written between 2009 and 2017. The researchers also examined students\u27 end-of-semester evaluation scores about the course and instructor. Results suggest that the teacher began online teaching with a mixed attitude. After four years of teachin ghte online course (delivered once each spring) the instructor reported more about content issues and less about online delivery. In the final the period (2016-17) the researchers found that the instructor was invested fully in online delivery. Although the study is not generalizable, its results suggest that instructors who stay with an online system over an extended period of time may gain more confidence in the efficacy on online delivery. The findings complement previous findings in the literature about faculty attitudes toward technology use in instruction

Education Interrupted: The Growing Use of Suspensions in New York City's Public Schools

The New York Civil Liberties Union analyzed 10 years of discipline data from New York City schools, and found that:*The total number of suspensions in New York City grew at an alarming rate over the last decade: One out of every 14 students was suspended in 2008-2009; in 1999-2000 it was one in 25. In 2008-2009, this added up to more than 73,000 suspensions.*Students with disabilities are four times more likely to be suspended than students without disabilities.*Black students, who comprise 33 percent of the student body, served 53 percent of suspensions over the past 10 years. *Black students with disabilities represent more than 50 percent of suspended students with disabilities.*Black students also served longer suspensions on average and were more likely to be suspended for subjective misconduct, like profanity and insubordination.*Suspensions are becoming longer: More than 20 percent of suspensions lasted more than one week in 2008-2009, compared to 14 percent in 1999-2000. The average length of a long-term suspension is five weeks (25 school days).*Between 2001 and 2010, the number of infractions listed in the schools' Discipline Code increased by 49 percent. During that same period, the number of zero tolerance infractions, which mandate a suspension regardless of the individual facts of the incident, increased by 200 percent.*Thirty percent of suspensions occur during March and June of each school year

Productivity Growth and Convergence in Crop, Ruminant and Non-Ruminant Production: Measurement and Forecasts

There is considerable interest in projections of future productivity growth in agriculture. Whether one is interested in the outlook for global commodity markets, future patterns of international trade, or the interactions between land use, deforestation and ecological diversity, the rate of productivity growth in agriculture is an essential input. Yet solid projections for this variable have proven elusive particularly on a global basis. This is due, in no small part, to the difficulty in measuring historical productivity growth. The purpose of this paper is to report the latest time series evidence on total factor productivity growth for crops, ruminants and non-ruminant livestock, on a global basis. We then follow with tests for convergence amongst regions, providing forecasts for farm productivity growth to the year 2040. The results suggest that most regions in the sample are likely to experience larger productivity gains in livestock than in crops. Within livestock, the non-ruminant sector is expected to continue to be more dynamic than the ruminant sector. Given the rapid rates of productivity growth observed recently, non-ruminant and crop productivity in developing countries may be converging to the productivity levels of developed countries. For ruminants, the results show that productivity levels may be diverging between developed and developing countries.Malmquist index, productivity, convergence, projections, crops, livestock, Productivity Analysis, D24, O13, O47, Q10,

The human myometrium differentially expresses mTOR signalling components before and during pregnancy: Evidence for regulation by progesterone

Emerging studies implicate the signalling of the mammalian target of rapamycin (mTOR) in a number of reproductive functions. To this date, there are no data regarding the expression of mTOR signalling components in the human myometrium during pregnancy. We hypothesized that mTOR-related genes might be differentially expressed in term or preterm labour as well as in labour or non-labour myometria during pregnancy. Using quantitative RT-PCR we demonstrate for first time that there is a significant downregulation of mTOR, DEPTOR, and Raptor in preterm labouring myometria when compared to non-pregnant tissues taken from the same area (lower segment). We used an immortalized myometrial cell line (ULTR) as an in vitro model to dissect further mTOR signalling. In ULTR cells DEPTOR and Rictor had a cytoplasmic distribution, whereas mTOR and Raptor were detected in the cytoplasm and the nucleus, indicative of mTORC1 shuttling. Treatment with inflammatory cytokines caused only minor changes in gene expression of these components, whereas progesterone caused significant down-regulation. We performed a non-biased gene expression analysis of ULTR cells using Nimblegen human gene expression microarray (n = 3), and selected genes were validated by quantitative RT-PCR in progesterone treated myometrial cells. Progesterone significantly down-regulated key components of the mTOR pathway. We conclude that the human myometrium differentially expresses mTOR signalling components and they can be regulated by progesterone. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.This research was funded by National Institutes of Health Grant ESO12961

Differentiating the EdD and the PhD in Higher Education: A Survey of Characteristics and Trends

Purpose: Higher education, as a field of study, is one of the few programmatic areas that offer two doctoral degrees: The Doctor of Education (EdD) and the Doctor of Philosophy (PhD). In the United States, the two degrees are often conflated. Conversations, to this point, have done more to contribute to the theoretical debate than to operationally distinguish between the two degree paths. Method: The current study analyzed data collected from a review of the 188 doctoral programs at 145 institutions listed with the Association for the Study of Higher Education (ASHE). Results: Results suggest that while there is a shift toward operational differences between the EdD and the PhD in higher education, the similarities in entrance requirements, formats, and research expectations, to list a few, suggest that the EdD and PhD still require further refinement to reach the theoretical clarity common in many conversations about the education doctorate

Novel Method of Administering Aspirin and Dosage Forms Containing Same

The invention relates to a novel method of administering aspirin to achieve improved delivery thereof. The invention further relates to novel dosage forms of neutralized aspirin adapted for nasal administration, such as solutions, suspensions, gels and ointments. These dosage forms find utility in the treatment of conditions known to respond to the administration of aspirin, particularly in the treatment of migraine and in the mitigation of cardiovascular damage resulting from heart attack