Communities of Lifelong Learning [2]: Social Dialogue: Exchanges Shaping Learning Experiences

Social Dialogues discussed in this paper are the learning exchanges that develop in structured adult learning activities and essential communities of lifelong learning. Social dialogues, Social Justice and Social Territories and Borders (Session 1) are topics essential to the development of communities of lifelong learning. They provide the scaffolding critical to the professional and policy discourses shaping lifelong learning and educational opportunities over the adult life course in diverse social communities of practice

IL-15 Activates the Jak3/STAT3 Signaling Pathway to Mediate Glucose Uptake in Skeletal Muscle Cells

Myokines are specialized cytokines that are secreted from skeletal muscle (SKM) in response to metabolic stimuli, such as exercise. Interleukin-15 (IL-15) is a myokine with potential to reduce obesity and increase lean mass through induction of metabolic processes. It has been previously shown that IL-15 acts to increase glucose uptake in SKM cells. However, the downstream signals orchestrating the link between IL-15 signaling and glucose uptake have not been fully explored. Here we employed the mouse SKM C2C12 cell line to examine potential downstream targets of IL-15-induced alterations in glucose uptake. Following differentiation, C2C12 cells were treated overnight with 100 ng/ml of IL-15. Activation of factors associated with glucose metabolism (Akt and AMPK) and known downstream targets of IL-15 (Jak1, Jak3, STAT3, and STAT5) were assessed with IL-15 stimulation. IL-15 stimulated glucose uptake and GLUT4 translocation to the plasma membrane. IL-15 treatment had no effect on phospho-Akt, phospho-Akt substrates, phospho-AMPK, phospho-Jak1, or phospho-STAT5. However, with IL-15, phospho-Jak3 and phospho-STAT3 levels were increased along with increased interaction of Jak3 and STAT3. Additionally, IL-15 induced a translocation of phospho-STAT3 from the cytoplasm to the nucleus. We have evidence that a mediator of glucose uptake, HIF1α, expression was dependent on IL-15 induced STAT3 activation. Finally, upon inhibition of STAT3 the positive effects of IL-15 on glucose uptake and GLUT4 translocation were abolished. Taken together, we provide evidence for a novel signaling pathway for IL-15 acting through Jak3/STAT3 to regulate glucose metabolism

IL-15 Activates the Jak3/STAT3 Signaling Pathway to Mediate Glucose Uptake in Skeletal Muscle Cells

Myokines are specialized cytokines that are secreted from skeletal muscle (SKM) in response to metabolic stimuli, such as exercise. Interleukin-15 (IL-15) is a myokine with potential to reduce obesity and increase lean mass through induction of metabolic processes. It has been previously shown that IL-15 acts to increase glucose uptake in SKM cells. However, the downstream signals orchestrating the link between IL-15 signaling and glucose uptake have not been fully explored. Here we employed the mouse SKM C2C12 cell line to examine potential downstream targets of IL-15-induced alterations in glucose uptake. Following differentiation, C2C12 cells were treated overnight with 100 ng/ml of IL-15. Activation of factors associated with glucose metabolism (Akt and AMPK) and known downstream targets of IL-15 (Jak1, Jak3, STAT3, and STAT5) were assessed with IL-15 stimulation. IL-15 stimulated glucose uptake and GLUT4 translocation to the plasma membrane. IL-15 treatment had no effect on phospho-Akt, phospho-Akt substrates, phospho-AMPK, phospho-Jak1, or phospho-STAT5. However, with IL-15, phospho-Jak3 and phospho-STAT3 levels were increased along with increased interaction of Jak3 and STAT3. Additionally, IL-15 induced a translocation of phospho-STAT3 from the cytoplasm to the nucleus. We have evidence that a mediator of glucose uptake, HIF1α, expression was dependent on IL-15 induced STAT3 activation. Finally, upon inhibition of STAT3 the positive effects of IL-15 on glucose uptake and GLUT4 translocation were abolished. Taken together, we provide evidence for a novel signaling pathway for IL-15 acting through Jak3/STAT3 to regulate glucose metabolism

A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway

The pluripotency factor Lin28 blocks the expression of let-7 microRNAs (miRNAs) in undifferentiated cells during development and functions as an oncogene in a subset of cancers1. Lin28 binds to let-7 precursor RNAs and recruits 3′ terminal uridylyl transferases (TUTases) to selectively inhibit let-7 biogenesis2–4. Uridylated pre-let-7 is refractory to processing by Dicer and is rapidly degraded by an unknown ribonuclease5. Here we identify Dis3l2 as the 3′-5′ exonuclease responsible for the decay of uridylated pre-let-7. Biochemical reconstitution assays reveal that 3′ oligouridylation stimulates Dis3l2 activity in vitro, and knockdown of Dis3l2 in mouse embryonic stem cells leads to the stabilization of pre-let-7. Our study establishes 3′ oligouridylation as an RNA decay signal for Dis3l2 and identifies the first physiological RNA substrate of this novel exonuclease that is mutated in the Perlman syndrome of fetal overgrowth and predisposition to Wilms’ tumor6

The Host Galaxy and Central Engine of the Dwarf AGN POX 52

We present new multi-wavelength observations of the dwarf Seyfert 1 galaxy POX 52 in order to investigate the properties of the host galaxy and the active nucleus, and to examine the mass of its black hole, previously estimated to be ~ 10^5 M_sun. Hubble Space Telescope ACS/HRC images show that the host galaxy has a dwarf elliptical morphology (M_I = -18.4 mag, Sersic index n = 4.3) with no detected disk component or spiral structure, confirming previous results from ground-based imaging. X-ray observations from both Chandra and XMM show strong (factor of 2) variability over timescales as short as 500 s, as well as a dramatic decrease in the absorbing column density over a 9 month period. We attribute this change to a partial covering absorber, with a 94% covering fraction and N_H = 58^{+8.4}_{-9.2} * 10^21 cm^-2, that moved out of the line of sight in between the XMM and Chandra observations. Combining these data with observations from the VLA, Spitzer, and archival data from 2MASS and GALEX, we examine the spectral energy distribution (SED) of the active nucleus. Its shape is broadly similar to typical radio-quiet quasar SEDs, despite the very low bolometric luminosity of L_bol = 1.3 * 10^43 ergs/s. Finally, we compare black hole mass estimators including methods based on X-ray variability, and optical scaling relations using the broad H-beta line width and AGN continuum luminosity, finding a range of black hole mass from all methods to be M_bh = (2.2-4.2) * 10^5 M_sun, with an Eddington ratio of L_bol/L_edd = 0.2-0.5.Comment: 19 pages, 16 figures, accepted for publication in Ap

Sotto Voce: Exploring the Interplay of Conversation and Mobile Audio Spaces

In addition to providing information to individual visitors, electronic guidebooks have the potential to facilitate social interaction between visitors and their companions. However, many systems impede visitor interaction. By contrast, our electronic guidebook, Sotto Voce, has social interaction as a primary design goal. The system enables visitors to share audio information - specifically, they can hear each other's guidebook activity using a technologically mediated audio eavesdropping mechanism. We conducted a study of visitors using Sotto Voce while touring a historic house. The results indicate that visitors are able to use the system effectively, both as a conversational resource and as an information appliance. More surprisingly, our results suggest that the technologically mediated audio often cohered the visitors' conversation and activity to a far greater degree than audio delivered through the open air.Comment: 8 page

The Spring 1985 high precision baseline test of the JPL GPS-based geodetic system

The Spring 1985 High Precision Baseline Test (HPBT) was conducted. The HPBT was designed to meet a number of objectives. Foremost among these was the demonstration of a level of accuracy of 1 to 2:10 to the 7th power, or better, for baselines ranging in length up to several hundred kilometers. These objectives were all met with a high degree of success, with respect to the demonstration of system accuracy in particular. The results from six baselines ranging in length from 70 to 729 km were examined for repeatability and, in the case of three baselines, were compared to results from colocated VLBI systems. Repeatability was found to be 5:10 to the 8th power (RMS) for the north baseline coordinate, independent of baseline length, while for the east coordinate RMS repeatability was found to be larger than this by factors of 2 to 4. The GPS-based results were found to be in agreement with those from colocated VLBI measurements, when corrected for the physical separations of the VLBI and CPG antennas, at the level of 1 to 2:10 to the 7th power in all coordinates, independent of baseline length. The results for baseline repeatability are consistent with the current GPA error budget, but the GPS-VLBI intercomparisons disagree at a somewhat larger level than expected. It is hypothesized that these differences may result from errors in the local survey measurements used to correct for the separations of the GPS and VLBI antenna reference centers

Lin28A and Lin28B Inhibit let-7 MicroRNA Biogenesis by Distinct Mechanisms

SummaryLin28A and Lin28B selectively block the expression of let-7 microRNAs and function as oncogenes in a variety of human cancers. Lin28A recruits a TUTase (Zcchc11/TUT4) to let-7 precursors to block processing by Dicer in the cell cytoplasm. Here we find that unlike Lin28A, Lin28B represses let-7 processing through a Zcchc11-independent mechanism. Lin28B functions in the nucleus by sequestering primary let-7 transcripts and inhibiting their processing by the Microprocessor. The inhibitory effects of Zcchc11 depletion on the tumorigenic capacity and metastatic potential of human cancer cells and xenografts are restricted to Lin28A-expressing tumors. Furthermore, the majority of human colon and breast tumors analyzed exclusively express either Lin28A or Lin28B. Lin28A is expressed in HER2-overexpressing breast tumors, whereas Lin28B expression characterizes triple-negative breast tumors. Overall our results illuminate the distinct mechanisms by which Lin28A and Lin28B function and have implications for the development of new strategies for cancer therapy