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

Charge radii and electromagnetic moments of 195-211At

Hyperfine-structure parameters and isotope shifts of At195-211 have been measured for the first time at CERN-ISOLDE, using the in-source resonance-ionization spectroscopy method. The hyperfine structures of isotopes were recorded using a triad of experimental techniques for monitoring the photo-ion current. The Multi-Reflection Time-of-Flight Mass Spectrometer, in connection with a high-resolution electron multiplier, was used as an ion-counting setup for isotopes that either were affected by strong isobaric contamination or possessed a long half-life; the ISOLDE Faraday cups were used for cases with high-intensity beams; and the Windmill decay station was used for short-lived, predominantly α-decaying nuclei. The electromagnetic moments and changes in the mean-square charge radii of the astatine nuclei have been extracted from the measured hyperfine-structure constants and isotope shifts. This was only made possible by dedicated state-of-the-art large-scale atomic computations of the electronic factors and the specific mass shift of atomic transitions in astatine that are needed for these extractions. By comparison with systematics, it was possible to assess the reliability of the results of these calculations and their ascribed uncertainties. A strong deviation in the ground-state mean-square charge radii of the lightest astatine isotopes, from the trend of the (spherical) lead isotopes, is interpreted as the result of an onset of deformation. This behavior bears a resemblance to the deviation observed in the isotonic polonium isotopes. Cases for shape coexistence have been identified in At197,199, for which a significant difference in the charge radii for ground (9/2-) and isomeric (1/2+) states has been observed

Inverse odd-even staggering in nuclear charge radii and possible octupole collectivity in $^217,218,219At revealed by in-source laser spectroscopy

International audienceHyperfine-structure parameters and isotope shifts for the 795-nm atomic transitions in $^{217,218,219}$At have been measured at CERN-ISOLDE, using the in-source resonance-ionization spectroscopy technique. Magnetic dipole and electric quadrupole moments, and changes in the nuclear mean-square charge radii, have been deduced. A large inverse odd-even staggering in radii, which may be associated with the presence of octupole collectivity, has been observed. Namely, the radius of the odd-odd isotope $^{218}$At has been found to be larger than the average of its even-$N$ neighbors, $^{217,219}$At. The discrepancy between the additivity-rule prediction and experimental data for the magnetic moment of $^{218}$At also supports the possible presence of octupole collectivity in the considered nuclei

Neurovascular dysfunction in vascular dementia, Alzheimer’s and atherosclerosis

Efficient blood supply to the brain is of paramount importance to its normal functioning and improper blood flow can result in potentially devastating neurological consequences. Cerebral blood flow in response to neural activity is intrinsically regulated by a complex interplay between various cell types within the brain in a relationship termed neurovascular coupling. The breakdown of neurovascular coupling is evident across a wide variety of both neurological and psychiatric disorders including Alzheimer’s disease. Atherosclerosis is a chronic syndrome affecting the integrity and function of major blood vessels including those that supply the brain, and it is therefore hypothesised that atherosclerosis impairs cerebral blood flow and neurovascular coupling leading to cerebrovascular dysfunction. This review will discuss the mechanisms of neurovascular coupling in health and disease and how atherosclerosis can potentially cause cerebrovascular dysfunction that may lead to cognitive decline as well as stroke. Understanding the mechanisms of neurovascular coupling in health and disease may enable us to develop potential therapies to prevent the breakdown of neurovascular coupling in the treatment of vascular brain diseases including vascular dementia, Alzheimer’s disease and stroke

The young and the restless: Socializing trumps sleep, fear of missing out, and technological distractions in first-year college students

College students are a sleep-deprived population, with first-year students facing a number of specific challenges to sleep. As students transition into and through the first year of college, sleep may be sacrificed for a variety of reasons. Semi-structured interviews were conducted with fifteen first-year students, exploring factors that impacted sleep during the first semester of college. Study participants identified three unique but related themes that impacted their sleep: socializing trumps sleep; fear of missing out; and social/technological distractions. Implications are provided for balancing social, academic and biological demands in emerging adulthood

A nuclear fluorescent dye identifies pericytes at the neurovascular unit

Perivascular pericytes are key regulators of the blood–brain barrier, vascular development, and cerebral blood flow. Deciphering pericyte roles in health and disease requires cellular tracking; yet, pericyte identification remains challenging. A previous study reported that the far-red fluorophore TO-PRO-3 (642/661), usually employed as a nuclear dye in fixed tissue, was selectively captured by live pericytes from the subventricular zone. Herein, we validated TO-PRO-3 as a specific pericyte tracer in the nervous system (NS). Living pericytes from ex vivo murine hippocampus, cortex, spinal cord, and retina robustly incorporated TO-PRO-3. Classical pericyte immunomarkers such as chondroitin sulphate proteoglycan neuron-glial antigen 2 (NG2) and platelet-derived growth factor receptor beta antigen (PDGFrβ) and the new pericyte dye NeuroTrace 500/525 confirmed cellular specificity of dye uptake. The TO-PRO-3 signal enabled quantification of pericytes density and morphometry; likewise, TO-PRO-3 labeling allowed visualization of pericytes associated with other components of the neurovascular unit. A subset of TO-PRO-3 stained cells expressed the contractile protein α–SMA, indicative of their ability to control the capillary diameter. Uptake of TO-PRO-3 was independent of connexin/pannexin channels but was highly sensitive to temperature and showed saturation, suggesting that a yet unidentified protein-mediated active transport sustained dye incorporation. We conclude that TO-PRO-3 labeling provides a reliable and simple tool for the bioimaging of pericytes in the murine NS microvasculature.Comisión Sectorial de Investigación Científica. Proyecto de Investigación y Desarrollo CSIC I+D 2014.Agencia Nacional de Investigación e Innovación FCE_1_2017_1_13610