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

Southern Arizona riparian habitat: Spatial distribution and analysis

The objectives of this study were centered around the demonstration of remote sensing as an inventory tool and researching the multiple uses of riparian vegetation. Specific study objectives were to: (1) map riparian vegetation along the Gila River, San Simon Creek, San Pedro River, Pantano Wash, (2) determine the feasibility of automated mapping using LANDSAT-1 computer compatible tapes, (3) locate and summarize existing mpas delineating riparian vegetation, (4) summarize data relevant to Southern Arizona's riparian products and uses, (5) document recent riparian vegetation changes along a selected portion of the San Pedro River, (6) summarize historical changes in composition and distribution of riparian vegetation, and (7) summarize sources of available photography pertinent to Southern Arizona

Determination of Frequency and Distribution of Hessian Fly (Diptera: Cecidomyiidae) Biotypes in the Northeastern Soft Wheat Region

Fifteen collections of Hessian flies from the northern soft winter wheat region of the United States were used to determine the composition and frequency of biotypes. The wheat cultivars \u27Seneca\u27 (H7Hs), \u27Monon\u27 (H3), \u27Knox 62\u27 (~, H7Hg), and \u27Abe\u27 (Hs) were used as differentials. Biotypes J and L replaced biotype B as the prevalent biotype in Indiana, since wheat cultivars having the Hs and the H6 genes have been grown. Biotype GP, the least virulent of any Hessian fly biotypes, was still present in New York indicating that wheat cuItivars with no genes for resistance are still being grown there. The genetic variability of Hessian fly biotypes that enables them to overcome the resistance in wheat cultivars is discussed

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

Drugs for neglected diseases: a failure of the market and a public health failure?

Infectious diseases cause the suffering of hundreds of millions of people, especially in tropical and subtropical areas. Effective, affordable and easy-to-use medicines to fight these diseases are nearly absent. Although science and technology are sufficiently advanced to provide the necessary medicines, very few new drugs are being developed. However, drug discovery is not the major bottleneck. Today's R&D-based pharmaceutical industry is reluctant to invest in the development of drugs to treat the major diseases of the poor, because return on investment cannot be guaranteed. With national and international politics supporting a free market-based world order, financial opportunities rather than global health needs guide the direction of new drug development. Can we accept that the dearth of effective drugs for diseases that mainly affect the poor is simply the sad but inevitable consequence of a global market economy? Or is it a massive public health failure, and a failure to direct economic development for the benefit of society? An urgent reorientation of priorities in drug development and health policy is needed. The pharmaceutical industry must contribute to this effort, but national and international policies need to direct the global economy to address the true health needs of society. This requires political will, a strong commitment to prioritize health considerations over economic interests, and the enforcement of regulations and other mechanisms to stimulate essential drug development. New and creative strategies involving both the public and the private sector are needed to ensure that affordable medicines for today's neglected diseases are developed. Priority action areas include advocating an essential medicines R&D agenda, capacity-building in and technology transfer to developing countries, elaborating an adapted legal and regulatory framework, prioritizing funding for essential drug development and securing availability, accessibility, distribution and rational use of these drugs

Clustering Phase Transitions and Hysteresis: Pitfalls in Constructing Network Ensembles

Ensembles of networks are used as null models in many applications. However, simple null models often show much less clustering than their real-world counterparts. In this paper, we study a model where clustering is enhanced by means of a fugacity term as in the Strauss (or "triangle") model, but where the degree sequence is strictly preserved -- thus maintaining the quenched heterogeneity of nodes found in the original degree sequence. Similar models had been proposed previously in [R. Milo et al., Science 298, 824 (2002)]. We find that our model exhibits phase transitions as the fugacity is changed. For regular graphs (identical degrees for all nodes) with degree k > 2 we find a single first order transition. For all non-regular networks that we studied (including Erdos - Renyi and scale-free networks) we find multiple jumps resembling first order transitions, together with strong hysteresis. The latter transitions are driven by the sudden emergence of "cluster cores": groups of highly interconnected nodes with higher than average degrees. To study these cluster cores visually, we introduce q-clique adjacency plots. We find that these cluster cores constitute distinct communities which emerge spontaneously from the triangle generating process. Finally, we point out that cluster cores produce pitfalls when using the present (and similar) models as null models for strongly clustered networks, due to the very strong hysteresis which effectively leads to broken ergodicity on realistic time scales.Comment: 13 pages, 11 figure

The Adsorption and Collapse Transitions in a Linear Polymer Chain near an Attractive Wall

We deduce the qualitative phase diagram of a long flexible neutral polymer chain immersed in a poor solvent near an attracting surface using phenomenological arguments. The actual positions of the phase boundaries are estimated numerically from series expansion up to 19 sites of a self-attracting self avoiding walk in three dimensions. In two dimensions, we calculate analytically phase boundaries in some cases for a partially directed model. Both the numerical as well as analytical results corroborate the proposed qualitative phase diagram.Comment: 8 pages, 8 figures, revte

DEVELOPMENT OF A STOCHASTIC MODEL TO EVALUATE PLANT GROWERS' ENTERPRISE BUDGETS

Increased domestic concentration and international competition in the floricultural industry are forcing growers to improve resource management efficiency. Cost management and cost accounting methods are becoming key tools as growers attempt to reduce costs. These tools allow growers to allocate costs for each crop, increasing their greenhouse planning abilities. Growers have a relative high degree of risk due to potential crop and market failure. Individual growers have different tolerance for risk and risk bearing capacity. Growers need a cost accounting system that incorporates production and market risk, a system that allows them to make informed business decisions. The research reported in this paper developed a greenhouse budgeting model that incorporated risk to allow growers to compare production costs for flowers with different genetics and production technologies. This enables greenhouse growers to make production management decisions that incorporate production and market risk. The model gives growers the option of imputing their own production data to evaluate how various yield and price assumptions influence income and expense projections, and ultimately, profit. The model allows growers to compare total production cost and revenue varying grower type, production time, geographical location, operation size, and cost structure. The model evaluates budgets for growers who market to mass-market retail operations or wholesale intermediaries who sell to merchandisers or flower shops distribution channels. The model was demonstrated with sample data to illustrate how incorporating risk analysis into a grower's greenhouse budget model effects resource allocation and production decisions as compare to a budget model that does not incorporate risk. Deterministic and stochastic models were used to demonstrate differences in production decisions under various assumptions. The stochastic model introduced prices and flowering characteristics variability. The @Risk software was used to generate the random number simulation of the stochastic model, and stochastic dominance analysis was used to rank the alternatives. The result for both the deterministic and stochastic models identified the same cultivar as most profitable. However, there were differences in crop profits levels and rankings for subsequent cultivars that could influence growers' production choice decisions. The grower's risk aversion level influenced his/her choice of the most profitable cultivars in the stochastic model. The model summarizes the sources of variability that affect cost and revenue. The model enables the grower to measure effects that change in productivity might have on profit. Growers can identify items in their budget that have a greater effect on profitability, and make adjustments. The model can be used to allocate cost across activities, so the grower would be able to measure the economic impact of an item on the budget.Crop Production/Industries,

An Ammonia Spectral Atlas of Dense Cores in Perseus

We present ammonia observations of 193 dense cores and core candidates in the Perseus molecular cloud made using the Robert F. Byrd Green Bank Telescope. We simultaneously observed the NH3(1,1), NH3(2,2), CCS (2_1 -> 1_0) and CC34S (2_1 -> 1_0) transitions near 23 GHz for each of the targets with a spectral resolution of dv ~ 0.024 km/s. We find ammonia emission associated with nearly all of the (sub)millimeter sources as well as at several positions with no associated continuum emission. For each detection, we have measured physical properties by fitting a simple model to every spectral line simultaneously. Where appropriate, we have refined the model by accounting for low optical depths, multiple components along the line of sight and imperfect coupling to the GBT beam. For the cores in Perseus, we find a typical kinetic temperature of T=11 K, a typical column density of N(NH3)~ 10^14.5 /cm^2 and velocity dispersions ranging from sigma_v = 0.07 km/s to 0.7 km/s. However, many cores with velocity dispersions > 0.2 km/s show evidence for multiple velocity components along the line of sight.Comment: 19 pages; Accepted to ApJS; version with high resolution figures available at http://www.cfa.harvard.edu/COMPLETE/papers/nh3-paper1.pdf ; online data at http://www.cfa.harvard.edu/COMPLETE/data_html_pages/GBT_NH3.htm

Prompt energization of relativistic and highly relativistic electrons during a substorm interval: Van Allen Probes observations

Abstract On 17 March 2013, a large magnetic storm significantly depleted the multi-MeV radiation belt. We present multi-instrument observations from the Van Allen Probes spacecraft Radiation Belt Storm Probe A and Radiation Belt Storm Probe B at ~6 Re in the midnight sector magnetosphere and from ground-based ionospheric sensors during a substorm dipolarization followed by rapid reenergization of multi-MeV electrons. A 50% increase in magnetic field magnitude occurred simultaneously with dramatic increases in 100 keV electron fluxes and a 100 times increase in VLF wave intensity. The 100 keV electrons and intense VLF waves provide a seed population and energy source for subsequent radiation belt enhancements. Highly relativistic (\u3e2 MeV) electron fluxes increased immediately at L* ~ 4.5 and 4.5 MeV flux increased \u3e90 times at L* = 4 over 5 h. Although plasmasphere expansion brings the enhanced radiation belt multi-MeV fluxes inside the plasmasphere several hours postsubstorm, we localize their prompt reenergization during the event to regions outside the plasmasphere. Key Points Substorm dynamics are important for highly relativistic electron energization Cold plasma preconditioning is significant for rapid relativistic energization Relativistic / highly relativistic electron energization can occur in \u3c 5 hrs