Coronal radiation belts

The magnetic field of the solar corona has a large-scale dipole character, which maps into the bipolar field in the solar wind. Using standard representations of the coronal field, we show that high-energy ions can be trapped stably in these large-scale closed fields. The drift shells that describe the conservation of the third adiabatic invariant may have complicated geometries. Particles trapped in these zones would resemble the Van Allen Belts and could have detectable consequences. We discuss potential sources of trapped particles

The first products made in space: Monodisperse latex particles

The preparation of large particle size 3 to 30 micrometer monodisperse latexes in space confirmed that original rationale unequivocally. The flight polymerizations formed negligible amounts of coagulum as compared to increasing amounts for the ground-based polymerizations. The number of offsize large particles in the flight latexes was smaller than in the ground-based latexes. The particle size distribution broadened and more larger offsize particles were formed when the polymerizations of the partially converted STS-4 latexes were completed on Earth. Polymerization in space also showed other unanticipated advantages. The flight latexes had narrower particle size distributions than the ground-based latexes. The particles of the flight latexes were more perfect spheres than those of the ground-based latexes. The superior uniformity of the flight latexes was confirmed by the National Bureau of Standards acceptance of the 10 micrometer STS-6 latex and the 30 micrometer STS-11 latexes as Standard Reference Materials, the first products made in space for sale on Earth. The polymerization rates in space were the same as those on Earth within experimental error. Further development of the ground-based polymerization recipes gave monodisperse particles as large as 100 micrometer with tolerable levels of coagulum, but their uniformity was significantly poorer than the flight latexes. Careful control of the polymerization parameters gave uniform nonspherical particles: symmetrical and asymmetrical doublets, ellipsoids, egg-shaped, ice cream cone-shaped, and popcorn-shaped particles

Evidence for collapsing fields in corona and photosphere during the 15 February 2011 X2.2 flare: SDO AIA and HMI Observations

We use high-resolution images of the sun obtained by the SDO/AIA instrument to study the evolution of the coronal loops in a flaring solar active region. During 15 February 2011 a X-2.2 class flare occurred in NOAA 11158, a $\beta\gamma\delta$ sunspot complex. We identify three distinct phases of the coronal loop dynamics during this event: (i) {\it Slow rise phase}: slow rising motion of the loop-tops prior to the flare in response to slow rise of the underlying flux rope, (ii) {\it Collapse phase}: sudden contraction of the loop-tops with lower loops collapsing earlier than the higher loops, and (iii) {\it Oscillation phase}: the loops exhibit global kink oscillations after the collapse phase at different periods, with period decreasing with decreasing height of the loops. The period of these loop oscillations is used to estimate the field strength in the coronal loops of different loop lengths in this active region. Further, we also use SDO/HMI observations to study the photospheric changes close to the polarity inversion line (PIL). The longitudinal magnetograms show step-wise permanent decrease in the magnetic flux after the flare over a coherent patch along the PIL. Further, we examine the HMI Stokes I,Q,U,V profiles over this patch and find that the Stokes-V signal systematically decreases while the Stokes-Q and U signal increases after the flare. These observations suggest that close to the PIL the field configuration became more horizontal after the flare. We also use HMI vector magnetic field observations to quantify the changes in the field inclination angle and found an inward collapse of the field lines towards the polarity inversion line (PIL) by $\sim$ 10$^\circ$. These observations are consistent with the "coronal implosion" scenario and its predictions about flare related photospheric field changes.Comment: 27 pages, 7 figures, in press (Astrophysical Journal

The WW Domain of Neural Protein FE65 Interacts with Proline-rich Motifs in Mena, the Mammalian Homolog of Drosophila Enabled*

The neural protein FE65 contains two types of protein-protein interaction modules: one WW binding domain and two phosphotyrosine binding domains. The carboxyl-terminal phosphotyrosine binding domain of FE65 interacts in vivo with the beta-amyloid precursor protein, which is implicated in Alzheimer disease. To understand the function of this adapter protein, we identified binding partners for the FE65 WW domain. Proline-rich sequences sharing a proline-proline-leucine-proline core motif were recovered by screening expression libraries for ligands of the FE65 WW domain. Five proteins of molecular masses 60, 75, 80, 140, and 200 kDa could be purified from mouse brain lysates by affinity to the FE65 WW domain. We identified two of these five proteins as the 80- and 140-kDa isoforms encoded by Mena, the mammalian homolog of the Drosophila Enabled gene. Using the SPOTs technique of peptide synthesis, we identified the sequences in Mena that interact with the FE65 WW domain and found that they contain the signature proline-proline-leucine-proline motif. Finally, we demonstrated that Mena binds to FE65 in vivo by coimmunoprecipitation assay from COS cell extracts. The specificity of the Mena-FE65 WW domain association was confirmed by competition assays. Further characterization of the FE65-Mena complex may identify a physiological role for these proteins in beta-amyloid precursor protein biogenesis and may help in understanding the mechanism of molecular changes that underlie Alzheimer disease

Agave negatively regulates YAP and TAZ transcriptionally and post-translationally in osteosarcoma cell lines

Osteosarcoma (OS) is the most aggressive type of primary solid tumor that develops in bone. Whilst conventional chemotherapy can improve survival rates, the outcome for patients with metastatic or recurrent OS remains poor, so novel treatment agents and strategies are required. Research into new anticancer therapies has paved the way for the utilisation of natural compounds as they are typically less expensive and less toxic compared to conventional chemotherapeutics. Previously published works indicate that Agave exhibits anticancer properties, however potential molecular mechanisms remain poorly understood. In the present study, we investigate the anticancer effects of Agave leaf extract in OS cells suggesting that Agave inhibits cell viability, colony formation, and cell migration, and can induce apoptosis in OS cell lines. Moreover, Agave sensitizes OS cells to cisplatin (CDDP) and radiation, to overcome chemo- and radio-resistance. We demonstrate that Agave extract induces a marked decrease of Yes Associated Protein (YAP) and Tafazzin (TAZ) mRNA and protein expression upon treatment. We propose an initial mechanism of action in which Agave induces YAP/TAZ protein degradation, followed by a secondary event whereby Agave inhibits YAP/TAZ transcription, effectively deregulating the Nuclear Factor kappa B (NF-\u3baB) p65:p50 heterodimers responsible for transcriptional induction of YAP and TAZ

WW Domains of the Yes-Kinase-Associated-Protein (YAP) Transcriptional Regulator Behave as Independent Units with Different Binding Preferences for PPxY Motif-Containing Ligands

YAP is a WW domain-containing effector of the Hippo tumor suppressor pathway, and the object of heightened interest as a potent oncogene and stemness factor. YAP has two major isoforms that differ in the number of WW domains they harbor. Elucidating the degree of co-operation between these WW domains is important for a full understanding of the molecular function of YAP. We present here a detailed biophysical study of the structural stability and binding properties of the two YAP WW domains aimed at investigating the relationship between both domains in terms of structural stability and partner recognition. We have carried out a calorimetric study of the structural stability of the two YAP WW domains, both isolated and in a tandem configuration, and their interaction with a set of functionally relevant ligands derived from PTCH1 and LATS kinases. We find that the two YAP WW domains behave as independent units with different binding preferences, suggesting that the presence of the second WW domain might contribute to modulate target recognition between the two YAP isoforms. Analysis of structural models and phage-display studies indicate that electrostatic interactions play a critical role in binding specificity. Together, these results are relevant to understand of YAP function and open the door to the design of highly specific ligands of interest to delineate the functional role of each WW domain in YAP signaling.This work was supported by the Spanish Ministry of Education and Science [grant BIO2009-13261-CO2], the Spanish Ministry of Economy and Competitivity [grant BIO2012-39922-CO2] including FEDER (European Funds for Regional Development) funds and the Governement of Andalusia [grant CVI-5915]. Marius Sudol was supported by PA Breast Cancer Coalition Grants (#60707 and #920093) plus the Geisinger Clinic

Functional complexes between YAP2 and ZO-2 are PDZ domain-dependent, and regulate YAP2 nuclear localization and signalling

he Hippo pathway regulates the size of organs by controlling two opposing processes: proliferation and apoptosis. YAP2 (Yes kinase-associated protein 2), one of the three isoforms of YAP, is a WW domain-containing transcriptional co-activator that acts as the effector of the Hippo pathway in mammalian cells. In addition to WW domains, YAP2 has a PDZ-binding motif at its C-terminus. We reported previously that this motif was necessary for YAP2 localization in the nucleus and for promoting cell detachment and apoptosis. In the present study, we show that the tight junction protein ZO (zonula occludens)-2 uses its first PDZ domain to form a complex with YAP2. The endogenous ZO-2 and YAP2 proteins co-localize in the nucleus. We also found that ZO-2 facilitates the nuclear localization and pro-apoptotic function of YAP2, and that this activity of ZO-2 is PDZ-domain-dependent. The present paper is the first report on a PDZ-based nuclear translocation mechanism. Moreover, since the Hippo pathway acts as a tumour suppressor pathway, the YAP2-ZO-2 complex could represent a target for cancer therapy

A spatio-temporal description of the abrupt changes in the photospheric magnetic and Lorentz-force vectors during the 2011 February 15 X2.2 flare

The active region NOAA 11158 produced the first X-class flare of Solar Cycle 24, an X2.2 flare at 01:44 UT on 2011 February 15. Here we analyze SDO/HMI magnetograms covering a 12-hour interval centered at the time of this flare. We describe the spatial distributions of the photospheric magnetic changes associated with this flare, including the abrupt changes in the field vector, vertical electric current and Lorentz force vector. We also trace these parameters' temporal evolution. The abrupt magnetic changes were concentrated near the neutral line and in two neighboring sunspots. Near the neutral line, the field vectors became stronger and more horizontal during the flare and the shear increased. This was due to an increase in strength of the horizontal field components near the neutral line, most significant in the horizontal component parallel to the neutral line but the perpendicular component also increased in strength. The vertical component did not show a significant, permanent overall change at the neutral line. The increase in total flux at the neutral line was accompanied by a compensating flux decrease in the surrounding volume. In the two sunspots near the neutral line the azimuthal flux abruptly decreased during the flare but this change was permanent in only one of the spots. There was a large, abrupt, downward vertical Lorentz force change during the flare, consistent with results of past analyses and recent theoretical work. The horizontal Lorentz force acted in opposite directions along each side of neutral line, with the two sunspots at each end subject to abrupt torsional forces. The shearing forces were consistent with field contraction and decrease of shear near the neutral line, whereas the field itself became more sheared as a result of the flux collapsing towards the neutral line from the surrounding volume.Comment: DOI 10.1007/s11207-012-0071-0. Accepted for publication in Solar Physics SDO3 Topical Issue. Some graphics missing due to 15MB limi

ZO Proteins Redundantly Regulate the Transcription Factor DbpA/ZONAB

The localization and activities of DbpA/ZONAB and YAP transcription factors are in part regulated by the density-dependent assembly of epithelial junctions. DbpA activity and cell proliferation are inhibited by exogenous overexpression of the tight junction (TJ) protein ZO-1, leading to a model whereby ZO-1 acts by sequestering DbpA at the TJ. However, mammary epithelial cells and mouse tissues knock-out for ZO-1 do not show increased proliferation, as predicted by this model. To address this discrepancy, we examined the localization and activity of DbpA and YAP in Madin-Darby canine kidney cells depleted either of ZO-1, or one of the related proteins ZO-2 and ZO-3 (ZO proteins), or all three together. Depletion of only one ZO protein had no effect on DbpA localization and activity, whereas depletion of ZO-1 and ZO-2, which is associated with reduced ZO-3 expression, resulted in increased DbpA localization in the cytoplasm. Only depletion of ZO-2 reduced the nuclear import of YAP. Mammary epithelial (Eph4) cells KO for ZO-1 showed junctional DbpA, demonstrating that ZO-1 is not required to sequester DbpA at junctions. However, further depletion of ZO-2 in Eph4 ZO-1KO cells, which do not express ZO-3, caused decreased junctional localization and expression of DbpA, which were rescued by the proteasome inhibitor MG132. In vitro binding assays showed that full-length ZO-1 does not interact with DbpA. These results show that ZO-2 is implicated in regulating the nuclear shuttling of YAP, whereas ZO proteins redundantly control the junctional retention and stability of DbpA, without affecting its shuttling to the nucleus

Imaging Spectroscopy of a White-Light Solar Flare

We report observations of a white-light solar flare (SOL2010-06-12T00:57, M2.0) observed by the Helioseismic Magnetic Imager (HMI) on the Solar Dynamics Observatory (SDO) and the Reuven Ramaty High-Energy Solar Spectroscopic Imager (RHESSI). The HMI data give us the first space-based high-resolution imaging spectroscopy of a white-light flare, including continuum, Doppler, and magnetic signatures for the photospheric FeI line at 6173.34{\AA} and its neighboring continuum. In the impulsive phase of the flare, a bright white-light kernel appears in each of the two magnetic footpoints. When the flare occurred, the spectral coverage of the HMI filtergrams (six equidistant samples spanning \pm172m{\AA} around nominal line center) encompassed the line core and the blue continuum sufficiently far from the core to eliminate significant Doppler crosstalk in the latter, which is otherwise a possibility for the extreme conditions in a white-light flare. RHESSI obtained complete hard X-ray and \Upsilon-ray spectra (this was the first \Upsilon-ray flare of Cycle 24). The FeI line appears to be shifted to the blue during the flare but does not go into emission; the contrast is nearly constant across the line profile. We did not detect a seismic wave from this event. The HMI data suggest stepwise changes of the line-of-sight magnetic field in the white-light footpoints.Comment: 14 pages, 7 figures, Accepted by Solar Physic