Epithelial-mesenchymal transition (EMT) is an important contributor to the invasion and metastasis of epithelial-derived cancers. While considerable effort has focused in the regulators involved in ...the transition process, we have focused on consequences of EMT to prosurvival signaling. Changes in distinct metastable and ‘epigentically-fixed' EMT states were measured by correlation of protein, phosphoprotein, phosphopeptide and RNA transcript abundance. The assembly of 1167 modulated components into functional systems or machines simplified biological understanding and increased prediction confidence highlighting four functional groups: cell adhesion and migration, metabolism, transcription nodes and proliferation/survival networks. A coordinate metabolic reduction in a cluster of 17 free-radical stress pathway components was observed and correlated with reduced glycolytic and increased oxidative phosphorylation enzyme capacity, consistent with reduced cell cycling and reduced need for macromolecular biosynthesis in the mesenchymal state. An attenuation of EGFR autophosphorylation and a switch from autocrine to paracrine-competent EGFR signaling was implicated in the enablement of tumor cell chemotaxis. A similar attenuation of IGF1R, MET and RON signaling with EMT was observed. In contrast, EMT increased prosurvival autocrine IL11/IL6-JAK2-STAT signaling, autocrine fibronectin-integrin α5β1 activation, autocrine Axl/Tyro3/PDGFR/FGFR RTK signaling and autocrine TGFβR signaling. A relatively uniform loss of polarity and cell-cell junction linkages to actin cytoskeleton and intermediate filaments was measured at a systems level. A more heterogeneous gain of ECM remodeling and associated with invasion and migration was observed. Correlation to stem cell, EMT, invasion and metastasis datasets revealed the greatest similarity with normal and cancerous breast stem cell populations, CD49fhi/EpCAM⁻/lo and CD44hi/CD24lo, respectively.
Abstract
A stellar occultation by the extreme large-perihelion trans-Neptunian object (541132) Leleākūhonua (also known by the provisional designation of 2015 TG
387
) was predicted by the Lucky Star ...project and observed with the Research and Education Collaborative Occultation Network on 2018 October 20 UT. A single detection and a nearby nondetection provide constraints for the size and albedo. When a circular profile is assumed, the radius is
km, corresponding to a geometric albedo
, for an adopted absolute magnitude of
H
V
= 5.6, typical of other objects in dynamically similar orbits. The occultation also provides a high-precision astrometric constraint.
Approximately 6 million youth aged 12 to 20 consume alcohol monthly in the United States. The effect of alcohol consumption in adolescence on behavior and cognition is heavily researched; however, ...little is known about how alcohol consumption in adolescence may alter brain function, leading to long-term developmental detriments. In order to investigate differences in brain connectivity associated with alcohol use in adolescents, brain networks were constructed using resting-state functional magnetic resonance imaging data collected by the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) from 698 youth (12-21 years; 117 hazardous drinkers and 581 no/low drinkers). Analyses assessed differences in brain network topology based on alcohol consumption in eight predefined brain networks, as well as in whole-brain connectivity. Within the central executive network (CEN), basal ganglia network (BGN), and sensorimotor network (SMN), no/low drinkers demonstrated stronger and more frequent connections between highly globally efficient nodes, with fewer and weaker connections between highly clustered nodes. Inverse results were observed within the dorsal attention network (DAN), visual network (VN), and frontotemporal network (FTN), with no/low drinkers demonstrating weaker connections between nodes with high efficiency and increased frequency of clustered nodes compared to hazardous drinkers. Cross-sectional results from this study show clear organizational differences between adolescents with no/low or hazardous alcohol use, suggesting that aberrant connectivity in these brain networks is associated with risky drinking behaviors.
A stellar occultation by the extreme large-perihelion trans-Neptunian object (541132) Lele k honua (also known by the provisional designation of 2015 TG387) was predicted by the Lucky Star project ...and observed with the Research and Education Collaborative Occultation Network on 2018 October 20 UT. A single detection and a nearby nondetection provide constraints for the size and albedo. When a circular profile is assumed, the radius is km, corresponding to a geometric albedo , for an adopted absolute magnitude of HV = 5.6, typical of other objects in dynamically similar orbits. The occultation also provides a high-precision astrometric constraint.
We report on the stellar occultation by (523764) 2014 WC510 observed on 2018 December 1 UT. This occultation campaign was part of the Research and Education Collaborative Occultation Network (RECON), ...a network of small telescopes spread over 2000 km in western USA and Canada. Light curves from six stations revealed three groups of two or more consecutive flux drops correlated in time between adjacent stations. A Bayesian model comparison reveals that a model with a double object occulting a double star is favored over alternative models considered. For the statistically favored model, we determined that the primary component of the object has a diameter dp = 181 16 km and the secondary ds = 138 32 km, assuming identical geometric albedo between the two components. The two components have a projected separation of 349 26 km. Adopting an absolute magnitude for the system of HV = 7.2 from the Minor Planet Center, we derive a geometric albedo of pV = 5.1% 1.7%. This is the smallest resonant object with an occultation size measurement and with a detected secondary from a ground-based stellar occultation, filling a region of the size versus separation parameter space of binary objects that is largely unexplored. The results show the capabilities of the unique design of the RECON experiment sensitive to small objects and close binaries. 2014 WC510 is presently at a low galactic latitude where the high surface density of stars will provide good occultation opportunities in the upcoming years.
The Falcon Solid-state Energetic Electron Detector (SEED) is a single element particle telescope designed to measure 14 to 145 keV electrons in geostationary Earth orbit. The instrument is designed ...to be a low-resource space weather sensor and utilizes commercial-off-the-shelf components to further reduce cost. The instrument is calibrated on-orbit against the Los Alamos National Laboratory Space Atmospheric Burst Report System plasma spectrometer co-located on the same STPSat-6 satellite, as well as electron measurements from NOAA GOES satellites.
In 2019, the Research and Education Collaborative Occultation Network (RECON) obtained multiple-chord occultation measurements of two Centaur objects: 2014 YY49 on 2019 January 28 and 2013 NL24 on ...2019 September 4. RECON is a citizen-science telescope network designed to observe high-uncertainty occultations by outer solar system objects. Adopting circular models for the object profiles, we derive a radius km and a geometric albedo for 2014 YY49 and a radius km and a geometric albedo for 2013 NL24. To the precision of these measurements, no atmosphere or rings are detected for either object. The two objects measured here are among the smallest distant objects measured with the stellar occultation technique. In addition to these geometric constraints, the occultation measurements provide astrometric constraints for these two Centaurs at a higher precision than has been feasible by direct imaging. To supplement the occultation results, we also present an analysis of color photometry from the Pan-STARRS surveys to constrain the rotational light curve amplitudes and spectral colors of these two Centaurs. We recommend that future work focus on photometry to more deliberately constrain the objects' colors and light curve amplitudes and on follow-on occultation efforts informed by this astrometry.
Abstract
In 2019, the Research and Education Collaborative Occultation Network (RECON) obtained multiple-chord occultation measurements of two Centaur objects: 2014 YY
49
on 2019 January 28 and 2013 ...NL
24
on 2019 September 4. RECON is a citizen-science telescope network designed to observe high-uncertainty occultations by outer solar system objects. Adopting circular models for the object profiles, we derive a radius
km and a geometric albedo
for 2014 YY
49
and a radius
km and a geometric albedo
for 2013 NL
24
. To the precision of these measurements, no atmosphere or rings are detected for either object. The two objects measured here are among the smallest distant objects measured with the stellar occultation technique. In addition to these geometric constraints, the occultation measurements provide astrometric constraints for these two Centaurs at a higher precision than has been feasible by direct imaging. To supplement the occultation results, we also present an analysis of color photometry from the Pan-STARRS surveys to constrain the rotational light curve amplitudes and spectral colors of these two Centaurs. We recommend that future work focus on photometry to more deliberately constrain the objects’ colors and light curve amplitudes and on follow-on occultation efforts informed by this astrometry.
The subfornical organ (SFO) plays a pivotal role in body fluid homeostasis through its ability to integrate neurohumoral signals and subsequently alter behavior, neuroendocrine function, and ...autonomic outflow. The purpose of the present study was to evaluate whether selective activation of SFO neurons using virally mediated expression of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) stimulated thirst and salt appetite. Male C57BL/6 mice (12-15 wk) received an injection of rAAV2-CaMKII-HA-hM3D(Gq)-IRES-mCitrine targeted at the SFO. Two weeks later, acute injection of clozapine N-oxide (CNO) produced dose-dependent increases in water intake of mice with DREADD expression in the SFO. CNO also stimulated the ingestion of 0.3 M NaCl. Acute injection of CNO significantly increased the number of Fos-positive nuclei in the SFO of mice with robust DREADD expression. Furthermore, in vivo single-unit recordings demonstrate that CNO significantly increases the discharge frequency of both ANG II- and NaCl-responsive neurons. In vitro current-clamp recordings confirm that bath application of CNO produces a significant membrane depolarization and increase in action potential frequency. In a final set of experiments, chronic administration of CNO approximately doubled 24-h water intake without an effect on salt appetite. These findings demonstrate that DREADD-induced activation of SFO neurons stimulates thirst and that DREADDs are a useful tool to acutely or chronically manipulate neuronal circuits influencing body fluid homeostasis.
In 2019, the Research and Education Collaborative Occultation Network (RECON) obtained multiple-chord occultation measurements of two centaur objects: 2014 YY\(_{49}\) on 2019 January 28 and 2013 ...NL\(_{24}\) on 2019 September 4. RECON is a citizen-science telescope network designed to observe high-uncertainty occultations by outer solar system objects. Adopting circular models for the object profiles, we derive a radius \(r=16^{+2}_{-1}\)km and a geometric albedo \(p_V=0.13^{+0.015}_{-0.024}\) for 2014 YY\(_{49}\), and a radius \(r=66 ^{+5}_{-5}\)km and geometric albedo \(p_V = 0.045^{+0.006}_{-0.008}\) for 2013 NL\(_{24}\). To the precision of these measurements, no atmosphere or rings are detected for either object. The two objects measured here are among the smallest distant objects measured with the stellar occultation technique. In addition to these geometric constraints, the occultation measurements provide astrometric constraints for these two centaurs at a higher precision than has been feasible by direct imaging. To supplement the occultation results, we also present an analysis of color photometry from the Pan-STARRS surveys to constrain the rotational light curve amplitudes and spectral colors of these two centaurs. We recommend that future work focus on photometry to more deliberately constrain the objects' colors and light curve amplitudes, and on follow-on occultation efforts informed by this astrometry.
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