Leptin promotes cell proliferation and survival of trophoblastic cells

Leptin, the 16-kDa protein product of the obese gene, was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta. In the present work, we studied a possible effect of leptin on trophoblastic cell proliferation, survival, and apoptosis. Recombinant human leptin added to JEG-3 and BeWo choriocarcinoma cell lines showed a stimulatory effect on cell proliferation up to 3 and 2.4 times, respectively, measured by 3H-thymidine incorporation and cell counting. These effects were time and dose dependent. Maximal effect was achieved at 250 ng leptin/ml for JEG-3 cells and 50 ng leptin/ml for BeWo cells. Moreover, by inhibiting endogenous leptin expression with 2 μM of an antisense oligonucleotide (AS), cell proliferation was diminished. We analyzed cell population distribution during the different stages of cell cycle by fluorescence-activated cell sorting, and we found that leptin treatment displaced the cells towards a G2/M phase. We also found that leptin upregulated cyclin D1 expression, one of the key cell cycle-signaling proteins. Since proliferation and death processes are intimately related, the effect of leptin on cell apoptosis was investigated. Treatment with 2 μM leptin AS increased the number of apoptotic cells 60 times, as assessed by annexin V-fluorescein isothiocyanate/propidium iodide staining, and the caspase-3 activity was increased more than 2 fold. This effect was prevented by the addition of 100 ng leptin/ml. In conclusion, we provide evidence that suggests that leptin is a trophic and mitogenic factor for trophoblastic cells by virtue of its inhibiting apoptosis and promoting proliferation. © 2007 by the Society for the Study of Reproduction, Inc.Fil:Kotler, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Calvo, J.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Varone, C.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

17Beta-estradiol enhances leptin expression in human placental cells through genomic and nongenomic actions

The process of embryo implantation and trophoblast invasion is considered the most limiting factor in the establishment of pregnancy. Leptin was originally described as an adipocyte-derived signaling molecule for the central control of metabolism. However, it has been suggested that leptin is involved in other functions during pregnancy, particularly in the placenta, where it was found to be expressed. In the present work, we have found a stimulatory effect of 17beta-estradiol (E2) on endogenous leptin expression, as analyzed by Western blot, in both the BeWo choriocarcinoma cell line and normal placental explants. This effect was time and dose dependent. Maximal effect was achieved at 10 nM in BeWo cells and 1 nM in placental explants. The E 2 effects involved the estrogen receptor, as the antagonist ICI 182 780 inhibited E2-induced leptin expression. Moreover, E2 treatment enhanced leptin promoter activity up to 4-fold, as evaluated by transient transfection with a plasmid construction containing the leptin promoter region and the reporter gene luciferase. This effect was dose dependent. Deletion analysis demonstrated that a minimal promoter region between - 1951 and -1847 bp is both necessary and sufficient to achieve E2 effects. Estradiol action involved estrogen receptor 1, previously known as estrogen receptor alpha, as cotransfection with a vector encoding estrogen receptor 1 potentiated the effects of E2 on leptin expression. Moreover, E2 action probably involves membrane receptors too, as treatment with an estradiol-bovine serum albumin complex partially enhanced leptin expression. The effects of E2 could be blocked by pharmacologic inhibition of MAPK and the phosphoinositide-3-kinase (PI3K) pathways with 50 μM PD98059 and 0.1 μM Wortmannin, respectively. Moreover, cotransfection of dominant negative mutants of MAP2K or MAPK blocked E 2 induction of leptin promoter. On the other hand, E2 treatment promoted MAPK1/MAPK3 and AKT phosphorylation in placental cells. In conclusion, we provide evidence suggesting that E2 induces leptin expression in trophoblastic cells, probably through genomic and nongenomic actions via crosstalk between estrogen receptor 1 and MAPK and PI3K signal transduction pathways. © 2010 by the Society for the Study of Reproduction, Inc.Fil:Gambino, Y.P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Maymó, J.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Calvo, J.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Varone, C.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Tunable Lyapunov exponent in inverse magnetic billiards

The stability properties of the classical trajectories of charged particles are investigated in a two dimensional stadium-shaped inverse magnetic domain, where the magnetic field is zero inside the stadium domain and constant outside. In the case of infinite magnetic field the dynamics of the system is the same as in the Bunimovich billiard, i.e., ergodic and mixing. However, for weaker magnetic fields the phase space becomes mixed and the chaotic part gradually shrinks. The numerical measurements of the Lyapunov exponent (performed with a novel method) and the integrable/chaotic phase space volume ratio show that both quantities can be smoothly tuned by varying the external magnetic field. A possible experimental realization of the arrangement is also discussed.Comment: 4 pages, 6 figure

Tune in to your emotions: a robust personalized affective music player

The emotional power of music is exploited in a personalized affective music player (AMP) that selects music for mood enhancement. A biosignal approach is used to measure listeners’ personal emotional reactions to their own music as input for affective user models. Regression and kernel density estimation are applied to model the physiological changes the music elicits. Using these models, personalized music selections based on an affective goal state can be made. The AMP was validated in real-world trials over the course of several weeks. Results show that our models can cope with noisy situations and handle large inter-individual differences in the music domain. The AMP augments music listening where its techniques enable automated affect guidance. Our approach provides valuable insights for affective computing and user modeling, for which the AMP is a suitable carrier application

A statistical correlation of sunquakes based on their seismic and white-light emission

Several mechanisms have been proposed to explain the transient seismic emission, i.e. “sunquakes,” from some solar flares. Some theories associate high-energy electrons and/or white-light emission with sunquakes. High-energy charged particles and their subsequent heating of the photosphere and/or chromosphere could induce acoustic waves in the solar interior. We carried out a correlative study of solar flares with emission in hard X-rays, enhanced continuum emission at 6173 Å, and transient seismic emission. We selected those flares observed by the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) with a considerable flux above 50 keV between 1 January 2010 and 26 June 2014. We then used data from the Helioseismic and Magnetic Imager onboard the Solar Dynamic Observatory to search for excess visible-continuum emission and new sunquakes not previously reported. We found a total of 18 sunquakes out of 75 flares investigated. All of the sunquakes were associated with an enhancement of the visible continuum during the flare. Finally, we calculated a coefficient of correlation for a set of dichotomic variables related to these observations. We found a strong correlation between two of the standard helioseismic detection techniques, and between sunquakes and visible-continuum enhancements. We discuss the phenomenological connectivity between these physical quantities and the observational difficulties of detecting seismic signals and excess continuum radiation

Is It Rational to Assume that Infants Imitate Rationally? A Theoretical Analysis and Critique

It has been suggested that preverbal infants evaluate the efficiency of others' actions (by applying a principle of rational action) and that they imitate others' actions rationally. The present contribution presents a conceptual analysis of the claim that preverbal infants imitate rationally. It shows that this ability rests on at least three assumptions: that infants are able to perceive others' action capabilities, that infants reason about and conceptually represent their own bodies, and that infants are able to think counterfactually. It is argued that none of these three abilities is in place during infancy. Furthermore, it is shown that the idea of a principle of rational action suffers from two fallacies. As a consequence, is it suggested that it is not rational to assume that infants imitate rationally. Copyright (C) 2012 S. Karger AG, Base

The influence of climate and land-cover scenarios on dam management strategies in a highwater pressure catchment in Northeast Spain

Altres ajuts: EU LIFE (LIFE12ENV/ES/000536)This paper evaluates the response of streamflow in a Mediterranean medium-scaled basin under land-use and climate change scenarios and its plausible implication on the management of Boadella-Darnius reservoir (NE Spain). Land cover and climate change scenarios supposed over the next several decades were used to simulate reservoir inflow using the Regional Hydro-Ecologic Simulation System (RHESsys) and to analyze the future impacts on water management (2021-2050). Results reveal a clear decrease in dam inflow (-34%) since the dam was operational from 1971 to 2013. The simulations obtained with RHESsys show a similar decrease (-31%) from 2021 to 2050. Considering the ecological minimum flow outlined by water authorities and the projected decrease in reservoir's inflows, different water management strategies are needed to mitigate the effects of the expected climate change

Variation in antiosteoporotic drug prescribing and spending across Spain. A population-based ecological cross-sectional study

Introduction: Evidence has shown that utilization of antiosteoporotic medications does not correspond with risk, and studies on other therapies have shown that adequacy of pharmaceutical prescribing might vary between regions. Nevertheless, very few studies have addressed the variability in osteoporotic drug consumption. We aimed to describe variations in pharmaceutical utilization and spending on osteoporotic drugs between Health Areas (HA) in Spain. Methods: Population-based cross-sectional ecological study of expenditure and utilization of the five therapeutic groups marketed for osteoporosis treatment in Spain in 2009. Small area variation analysis (SAVA) methods were used. The units of analysis were the 168 HA of 13 Spanish regions, including 7.2 million women aged 50 years and older. The main outcomes were the defined daily dose (DDD) per 1000 inhabitants and day (DDD/1000/Day) dispensed according to the pharmaceutical claims reimbursed, and the expenditure on antiosteoporotics at retail price per woman =50 years old and per year. Results: The average osteoporosis drug consumption was 116.8 DDD/1000W/Day, ranging from 78.5 to 158.7 DDD/1000W/Day between the HAs in the 5th and 95th percentiles. Seventy-five percent of the antiosteoporotics consumed was bisphosphonates, followed by raloxifene, strontium ranelate, calcitonins, and parathyroid hormones including teriparatide. Regarding variability by therapeutic groups, biphosphonates showed the lowest variation, while calcitonins and parathyroid hormones showed the highest variation. The annual expenditure on antiosteoporotics was €426.5 million, translating into an expenditure of €59.2 for each woman =50 years old and varying between €38.1 and €83.3 between HAs in the 5th and 95th percentiles. Biphosphonates, despite accounting for 79% of utilization, only represented 63% of total expenditure, while parathyroid hormones with only 1.6% of utilization accounted for 15% of the pharmaceutical spending. Conclusion: This study highlights a marked geographical variation in the prescription of antiosteoporotics, being more pronounced in the case of costly drugs such as parathyroid hormones. The differences in rates of prescribing explained almost all of the variance in drug spending, suggesting that the difference in prescription volume between territories, and not the price of the drugs, is the main source of variation in this setting. Data on geographical variation of prescription can help guide policy proposals for targeting areas with inadequate antiosteoporotic drug use

The perseverative worry bout: a review of cognitive, affective and motivational factors that contribute to worry perseveration

This paper reviews the cognitive, affective and attentional factors that contribute to individual perseverative worry bouts. We describe how automatic biases in attentional and interpretational processes contribute to threat detection and to the inclusion of negative intrusive thoughts into the worry stream typical of the “what if …?” thinking style of pathological worriers. The review also describes processes occurring downstream from these perceptual biases that also facilitate perseveration, including cognitive biases in beliefs about the nature of the worry process, the automatic deployment of strict goal-directed responses for dealing with the threat, the role of negative mood in facilitating effortful forms of information processing (i.e. systematic information processing styles), and in providing negative information for evaluating the success of the worry bout. We also consider the clinical implications of this model for an integrated intervention programme for pathological worrying