Estrogen/Estrogen Receptor Alpha Signaling in Mouse Posterofrontal Cranial Suture Fusion

BACKGROUND: While premature suture fusion, or craniosynostosis, is a relatively common condition, the cause is often unknown. Estrogens are associated with growth plate fusion of endochondral bones. In the following study, we explore the previously unknown significance of estrogen/estrogen receptor signaling in cranial suture biology. METHODOLOGY/PRINCIPAL FINDINGS: Firstly, estrogen receptor (ER) expression was examined in physiologically fusing (posterofrontal) and patent (sagittal) mouse cranial sutures by quantitative RT-PCR. Next, the cranial suture phenotype of ER alpha and ER beta knockout (alphaERKO, betaERKO) mice was studied. Subsequently, mouse suture-derived mesenchymal cells (SMCs) were isolated; the effects of 17-beta estradiol or the estrogen antagonist Fulvestrant on gene expression, osteogenic and chondrogenic differentiation were examined in vitro. Finally, in vivo experiments were performed in which Fulvestrant was administered subcutaneously to the mouse calvaria. Results showed that increased ERalpha but not ERbeta transcript abundance temporally coincided with posterofrontal suture fusion. The alphaERKO but not betaERKO mouse exhibited delayed posterofrontal suture fusion. In vitro, addition of 17-beta estradiol enhanced both osteogenic and chondrogenic differentiation in suture-derived mesenchymal cells, effects reversible by Fulvestrant. Finally, in vivo application of Fulvestrant significantly diminished calvarial osteogenesis, inhibiting suture fusion. CONCLUSIONS/SIGNIFICANCE: Estrogen signaling through ERalpha but not ERbeta is associated with and necessary for normal mouse posterofrontal suture fusion. In vitro studies suggest that estrogens may play a role in osteoblast and/or chondrocyte differentiation within the cranial suture complex

The Comparative Economics of ICT, Environmental Degradation and Inclusive Human Development in Sub-Saharan Africa

This study examines how information and communication technology (ICT) could be employed to dampen the potentially damaging effects of environmental degradation in order to promote inclusive human development in a panel of 44 Sub-Saharan African countries. ICT is captured with internet and mobile phone penetration rates whereas environmental degradation is measured in terms of CO2 emissions per capita and CO2 intensity. The empirical evidence is based on Fixed Effects and Tobit regressions using data from 2000-2012. In order to increase the policy relevance of this study, the dataset is decomposed into fundamental characteristics of inclusive development and environmental degradation based on income levels (Low income versus (vs.) Middle income); legal origins (English Common law vs. French Civil law); religious domination (Christianity vs. Islam); openness to sea (Landlocked vs. Coastal); resource-wealth (Oil-rich vs. Oil-poor) and political stability (Stable vs. Unstable).Baseline findings broadly show that improvement in both of measures of ICT would significantly diminish the possibly harmful effect of CO2 emissions on inclusive human development. When the analysis is extended with the abovementioned fundamental characteristics, we observe that the moderating influence of both our ICT variables on CO2 emissions is higher in the group of English Common law, Middle income and Oil-wealthy countries than in the French Civil law, Low income countries and Oil-poor countries respectively. Theoretical and practical policy implications are discussed

Trends, Persistence, and Volatility in Energy Markets

This paper makes a threefold contribution to the underlying dynamic properties and causal effects of energy prices. Firstly, the paper makes a study of the underlying trends to help identify the time series path of nonrenewable energy resources, which can have far reaching consequences for economists and policy makers alike. The analysis is extended to also determine the persistence of oil price shocks. Secondly, the study examines the causal relation between oil prices and the macroeconomy allowing for nonlinear models that have been recently advocated in the literature. Finally, this study describes the relation between oil prices and agricultural commodities. From a policy perspective, these interrelationships of agricultural and oil prices warrant careful consideration in the context of the recent energy crisis, which may very well continue in the future

Psychosocial and Sexual Well-Being Following Nipple-Sparing Mastectomy and Reconstruction

Nipple-sparing mastectomy (NSM) is considered an oncologically safe option for select patients. As many patients are candidates for nipple-sparing or skin-sparing mastectomy (SSM), reliable patient-reported outcome data are crucial for decision-making. The objective of this study was to determine whether patient satisfaction and/or health-related quality of life (HRQOL) were improved by preservation of the nipple with NSM compared to SSM and nipple reconstruction. Subjects were identified from a prospectively maintained database of patients who completed the BREAST-Q following mastectomy and breast reconstruction between March and October 2011 at Memorial Sloan Kettering Cancer Center. Fifty-two patients underwent NSM followed by immediate expander-implant reconstruction. A comparison group consisted of 202 patients who underwent SSM followed by immediate expander-implant reconstruction and later nipple reconstruction. HRQOL and satisfaction domains as measured by BREAST-Q scores were compared in multivariate linear regression analyzes that controlled for potential confounding factors. NSM patients reported significantly higher scores in the psychosocial (p = 0.01) and sexual well-being (p = 0.02) domains compared to SSM patients. There was no significant difference in the BREAST-Q physical well-being, satisfaction with breast, or satisfaction with outcome domains between the NSM and SSM groups. NSM is associated with higher psychosocial and sexual well-being compared to SSM and nipple reconstruction. Preoperative discussion of such HRQOL outcomes with patients may facilitate informed decision-making and realistic postoperative expectations

Radiation therapy causes loss of dermal lymphatic vessels and interferes with lymphatic function by TGF-β1-mediated tissue fibrosis

Although radiation therapy is a major risk factor for the development of lymphedema following lymphadenectomy, the mechanisms responsible for this effect remain unknown. The purpose of this study was therefore to determine the effects of radiation on lymphatic endothelial cells (LECs) and lymphatic function. The tails of wild-type or acid sphingomyelinase (ASM)-deficient mice were treated with 0, 15, or 30 Gy of radiation and then analyzed for LEC apoptosis and lymphatic function at various time points. To analyze the effects of radiation fibrosis on lymphatic function, we determined the effects of transforming growth factor (TGF)-β1 blockade after radiation in vivo. Finally, we determined the effects of radiation and exogenous TGF-β1 on LECs in vitro. Radiation caused mild edema that resolved after 12–24 wk. Interestingly, despite resolution of tail edema, irradiated animals displayed persistent lymphatic dysfunction. Radiation caused loss of capillary lymphatics and was associated with a dose-dependent increase in LEC apoptosis. ASM−/− mice had significantly less LEC apoptosis; however, this finding did not translate to improved lymphatic function at later time points. Short-term blockade of TGF-β1 function after radiation markedly decreased tissue fibrosis and significantly improved lymphatic function but did not alter LEC apoptosis. Radiation therapy decreases lymphatic reserve by causing depletion of lymphatic vessels and LECs as well as promoting soft tissue fibrosis. Short-term inhibition of TGF-β1 activity following radiation improves lymphatic function and is associated with decreased soft tissue fibrosis. ASM deficiency confers LEC protection from radiation-induced apoptosis but does not prevent lymphatic dysfunction