Distinct expression patterns of ER alpha and ER beta in normal human mammary gland

AIM: Two oestrogen receptors (ERs) have been identified to date—the “classic” ERa and the more recently described ERb. Although much is known about ERa at the mRNA and protein levels, our knowledge of the expression and distribution of ERb protein is much more limited. The aim of this study was to compare the cellular distribution of ERa and ERb in normal human mammary gland. METHODS: Formalin fixed, paraffin wax embedded material was obtained from reduction mammoplasty specimens, normal tissue adjacent to breast tumour, or fibroadenoma. Sections were immunohistochemically stained for ERa, ERb, and the progesterone receptor. The staining pattern for each antibody was evaluated and compared. RESULTS: ERa was restricted to the cell nuclei of epithelial cells lining ducts and lobules. Although ERb was also seen in these cells, additional strong staining was detected specifically in the cell nuclei of myoepithelial cells. Occasional staining was seen in surrounding stromal and endothelial cell nuclei and in lymphocytes. CONCLUSIONS: ER subtypes have distinct distribution patterns in the normal mammary gland. The widespread distribution of ERb suggests that it may be the dominant ER in the mammary gland where it may be acting as a natural suppressor

Maintenance and broadening of the ocean’s salinity distribution by the water cycle

The global water cycle leaves an imprint on ocean salinity through evaporation and precipitation. It has been proposed that observed changes in salinity can be used to infer changes in the water cycle. Here salinity is characterized by the distribution of water masses in salinity coordinates. Only mixing and sources and sinks of freshwater and salt can modify this distribution. Mixing acts to collapse the distribution, making saline waters fresher and fresh waters more saline. Hence, in steady state, there must be net precipitation over fresh waters and net evaporation over saline waters. A simple model is developed to describe the relationship between the breadth of the distribution, the water cycle, and mixing—the latter being characterized by an e-folding time scale. In both observations and a state-of-the-art ocean model, the water cycle maintains a salinity distribution in steady state with a mixing time scale of the order of 50 yr. The same simple model predicts the response of the salinity distribution to a change in the water cycle. This study suggests that observations of changes in ocean salinity could be used to infer changes in the hydrological cycle

Global water cycle amplifying at less than the Clausius-Clapeyron rate

A change in the cycle of water from dry to wet regions of the globe would have far reaching impact on humanity. As air warms, its capacity to hold water increases at the Clausius-Clapeyron rate (CC, approximately 7% °C−1). Surface ocean salinity observations have suggested the water cycle has amplified at close to CC following recent global warming, a result that was found to be at odds with state-of the art climate models. Here we employ a method based on water mass transformation theory for inferring changes in the water cycle from changes in three-dimensional salinity. Using full depth salinity observations we infer a water cycle amplification of 3.0 ± 1.6% °C−1 over 1950–2010. Climate models agree with observations in terms of a water cycle amplification (4.3 ± 2.0% °C−1) substantially less than CC adding confidence to projections of total water cycle change under greenhouse gas emission scenarios

Mediterranean Sea response to climate change in an ensemble of twenty first century scenarios

The Mediterranean climate is expected to become warmer and drier during the twenty-first century. Mediterranean Sea response to climate change could be modulated by the choice of the socio-economic scenario as well as the choice of the boundary conditions mainly the Atlantic hydrography, the river runoff and the atmospheric fluxes. To assess and quantify the sensitivity of the Mediterranean Sea to the twenty-first century climate change, a set of numerical experiments was carried out with the regional ocean model NEMOMED8 set up for the Mediterranean Sea. The model is forced by air–sea fluxes derived from the regional climate model ARPEGE-Climate at a 50-km horizontal resolution. Historical simulations representing the climate of the period 1961–2000 were run to obtain a reference state. From this baseline, various sensitivity experiments were performed for the period 2001–2099, following different socio-economic scenarios based on the Special Report on Emissions Scenarios. For the A2 scenario, the main three boundary forcings (river runoff, near-Atlantic water hydrography and air–sea fluxes) were changed one by one to better identify the role of each forcing in the way the ocean responds to climate change. In two additional simulations (A1B, B1), the scenario is changed, allowing to quantify the socio-economic uncertainty. Our 6-member scenario simulations display a warming and saltening of the Mediterranean. For the 2070–2099 period compared to 1961–1990, the sea surface temperature anomalies range from +1.73 to +2.97 °C and the SSS anomalies spread from +0.48 to +0.89. In most of the cases, we found that the future Mediterranean thermohaline circulation (MTHC) tends to reach a situation similar to the eastern Mediterranean Transient. However, this response is varying depending on the chosen boundary conditions and socio-economic scenarios. Our numerical experiments suggest that the choice of the near-Atlantic surface water evolution, which is very uncertain in General Circulation Models, has the largest impact on the evolution of the Mediterranean water masses, followed by the choice of the socio-economic scenario. The choice of river runoff and atmospheric forcing both have a smaller impact. The state of the MTHC during the historical period is found to have a large influence on the transfer of surface anomalies toward depth. Besides, subsurface currents are substantially modified in the Ionian Sea and the Balearic region. Finally, the response of thermosteric sea level ranges from +34 to +49 cm (2070–2099 vs. 1961–1990), mainly depending on the Atlantic forcing

Challenges in quantifying changes in the global water cycle

Human influences have likely already impacted the large-scale water cycle but natural variability and observational uncertainty are substantial. It is essential to maintain and improve observational capabilities to better characterize changes. Understanding observed changes to the global water cycle is key to predicting future climate changes and their impacts. While many datasets document crucial variables such as precipitation, ocean salinity, runoff, and humidity, most are uncertain for determining long-term changes. In situ networks provide long time-series over land but are sparse in many regions, particularly the tropics. Satellite and reanalysis datasets provide global coverage, but their long-term stability is lacking. However, comparisons of changes among related variables can give insights into the robustness of observed changes. For example, ocean salinity, interpreted with an understanding of ocean processes, can help cross-validate precipitation. Observational evidence for human influences on the water cycle is emerging, but uncertainties resulting from internal variability and observational errors are too large to determine whether the observed and simulated changes are consistent. Improvements to the in situ and satellite observing networks that monitor the changing water cycle are required, yet continued data coverage is threatened by funding reductions. Uncertainty both in the role of anthropogenic aerosols, and due to large climate variability presently limits confidence in attribution of observed changes

Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells

Estrogen receptor α (ERα) is expressed in tissues as diverse as brains and mammary glands. In breast cancer, ERα is a key regulator of tumor progression. Therefore, understanding what activates ERα is critical for cancer treatment in particular and cell biology in general. Using biochemical approaches and superresolution microscopy, we show that estrogen drives membrane ERα into endosomes in breast cancer cells and that its fate is determined by the presence of fibronectin (FN) in the extracellular matrix; it is trafficked to lysosomes in the absence of FN and avoids the lysosomal compartment in its presence. In this context, FN prolongs ERα half-life and strengthens its transcriptional activity. We show that ERα is associated with β1-integrin at the membrane, and this integrin follows the same endocytosis and subcellular trafficking pathway triggered by estrogen. Moreover, ERα+ vesicles are present within human breast tissues, and colocalization with β1-integrin is detected primarily in tumors. Our work unravels a key, clinically relevant mechanism of microenvironmental regulation of ERα signaling.Fil: Sampayo, Rocío Guadalupe. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Toscani, Andrés Martin. Universidad Nacional de Luján; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Rubashkin, Matthew G.. University of California; Estados UnidosFil: Thi, Kate. Lawrence Berkeley National Laboratory; Estados UnidosFil: Masullo, Luciano Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Violi, Ianina Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Lakins, Jonathon N.. University of California; Estados UnidosFil: Caceres, Alfredo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Hines, William C.. Lawrence Berkeley National Laboratory; Estados UnidosFil: Coluccio Leskow, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad Nacional de Luján; ArgentinaFil: Stefani, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Chialvo, Dante Renato. Universidad de Buenos Aires; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro Internacional de Estudios Avanzados; ArgentinaFil: Bissell, Mina J.. Lawrence Berkeley National Laboratory; Estados UnidosFil: Weaver, Valerie M.. University of California; Estados UnidosFil: Simian, Marina. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentin

The slovenian and the cross: Transcending Christianity’s perverse core with Slavoj Žižek

This introductory chapter addresses the questions of why Slavoj Žižek is engaged in the project of creating an atheist or “decaffeinated” theology and how an atheist materialist thinker can be acutely interesting for Christian theology and theologians. It provides an outline of Žižek’s intellectual pursuits, particularly his employment of Lacanian categories of thought in matters political and theological, and focuses on a presentation of Žižek’s multifaceted engagement with Christianity in his works: of the different ways in which he engages with Christianity and of the different strategies one may employ in order to examine his engagement with Christianity, mapping out the theological reception of Žižek’s thought up to now. The chapter also draws attention to Žižek’s political Pneumatology, i.e. to the role of the Holy Spirit in this “decaffeinated” or “atheist theology” as the community of those that have interiorized Christ’s sacrifice, as well as to Žižek’s appropriation of early Christian heresies in his version of Hegelian dialectics. This introductory chapter concludes with a presentation of this volume’s architecture, its authors and chapters, the problems and issues they address and the different strategies they employ, closing with a hint on the scandalous possibility of “caffeine.

Las Maquiladoras Y Su Gente: A Look at the United States-Mexico\u27s Industrial Past, Present, and Future

My Senior Honors Thesis entails a close look at the U.S.- owned sweat shops which reside along the 2,000 mile border between the U.S. and Mexico. In my thesis, I discuss the positive and negative attributes of the Maquiladora Industry, in addition to their history, and a prognostication of what lies ahead for their future

NEMO-ICB (v1.0): interactive icebergs in the NEMO ocean model globally configured at eddy-permitting resolution

An established iceberg module, ICB, is used interactively with the Nucleus for European Modelling of the Ocean (NEMO) ocean model in a new implementation, NEMO–ICB (v1.0). A 30-year hindcast (1976–2005) simulation with an eddy-permitting (0.25°) global configuration of NEMO–ICB is undertaken to evaluate the influence of icebergs on sea ice, hydrography, mixed layer depths (MLDs), and ocean currents, through comparison with a control simulation in which the equivalent iceberg mass flux is applied as coastal runoff, a common forcing in ocean models. In the Southern Hemisphere (SH), drift and melting of icebergs are in balance after around 5 years, whereas the equilibration timescale for the Northern Hemisphere (NH) is 15–20 years. Iceberg drift patterns, and Southern Ocean iceberg mass, compare favourably with available observations. Freshwater forcing due to iceberg melting is most pronounced very locally, in the coastal zone around much of Antarctica, where it often exceeds in magnitude and opposes the negative freshwater fluxes associated with sea ice freezing. However, at most locations in the polar Southern Ocean, the annual-mean freshwater flux due to icebergs, if present, is typically an order of magnitude smaller than the contribution of sea ice melting and precipitation. A notable exception is the southwest Atlantic sector of the Southern Ocean, where iceberg melting reaches around 50% of net precipitation over a large area. Including icebergs in place of coastal runoff, sea ice concentration and thickness are notably decreased at most locations around Antarctica, by up to ~ 20% in the eastern Weddell Sea, with more limited increases, of up to ~ 10% in the Bellingshausen Sea. Antarctic sea ice mass decreases by 2.9%, overall. As a consequence of changes in net freshwater forcing and sea ice, salinity and temperature distributions are also substantially altered. Surface salinity increases by ~ 0.1 psu around much of Antarctica, due to suppressed coastal runoff, with extensive freshening at depth, extending to the greatest depths in the polar Southern Ocean where discernible effects on both salinity and temperature reach 2500 m in the Weddell Sea by the last pentad of the simulation. Substantial physical and dynamical responses to icebergs, throughout the global ocean, are explained by rapid propagation of density anomalies from high-to-low latitudes. Complementary to the baseline model used here, three prototype modifications to NEMO–ICB are also introduced and discussed