Identification of the NIMA family kinases NEK6/7 as regulators of the p70 ribosomal S6 kinase

AbstractBackground: The p70 S6 kinase, like several other AGC family kinases, requires for activation the concurrent phosphorylation of a site on its activation loop and a site carboxyterminal to the catalytic domain, situated in a hydrophobic motif site FXXFS/TF/Y, e.g.,Thr412 in p70 S6 kinase (α1). Phosphorylation of the former site is catalyzed by PDK1, whereas the kinase responsible for the phosphorylation of the latter site is not known.Results: The major protein kinase that is active on the p70 S6 kinase hydrophobic regulatory site, Thr412, was purified from rat liver and identified as the NIMA-related kinases NEK6 and NEK7. Recombinant NEK6 phosphorylates p70 S6 kinase at Thr412 and other sites and activates the p70 S6 kinase in vitro and in vivo, in a manner synergistic with PDK1. Kinase-inactive NEK6 interferes with insulin activation of p70 S6 kinase. The activity of recombinant NEK6 is dependent on its phosphorylation, but NEK6 activity is not regulated by PDK1 and is only modestly responsive to insulin and PI-3 kinase inhibitors.Conclusion: NEK6 and probably NEK7 are novel candidate physiologic regulators of the p70 S6 kinase

The First Very Long Baseline Interferometric SETI Experiment

The first Search for Extra-Terrestrial Intelligence (SETI) conducted with Very Long Baseline Interferometry (VLBI) is presented. By consideration of the basic principles of interferometry, we show that VLBI is efficient at discriminating between SETI signals and human generated radio frequency interference (RFI). The target for this study was the star Gliese 581, thought to have two planets within its habitable zone. On 2007 June 19, Gliese 581 was observed for 8 hours at 1230-1544 with the Australian Long Baseline Array. The dataset was searched for signals appearing on all interferometer baselines above five times the noise limit. A total of 222 potential SETI signals were detected and by using automated data analysis techniques, were ruled out as originating from the Gliese 581 system. From our results we place an upper limit of 7 MW/Hz on the power output of any isotropic emitter located in the Gliese 581 system, within this frequency range. This study shows that VLBI is ideal for targeted SETI, including follow-up observations. The techniques presented are equally applicable to next-generation interferometers, such as the long baselines of the Square Kilometre Array (SKA).Comment: 34 pages, 6 figures, 2 tables. Accepted on 25/05/2012 for publication in The Astronomical Journa

Mammalian STE20-like kinase 2, not kinase 1, mediates photoreceptor cell death during retinal detachment

Photoreceptor cell death is the definitive cause of vision loss in retinal detachment (RD). Mammalian STE20-like kinase (MST) is a master regulator of both cell death and proliferation and a critical factor in development and tumorigenesis. However, to date the role of MST in neurodegeneration has not been fully explored. Utilizing MST1−/− and MST2−/− mice we identified MST2, but not MST1, as a regulator of photoreceptor cell death in a mouse model of RD. MST2−/− mice demonstrated significantly decreased photoreceptor cell death and outer nuclear layer (ONL) thinning after RD. Additionally, caspase-3 activation was attenuated in MST2−/− mice compared to control mice after RD. The transcription of p53 upregulated modulator of apoptosis (PUMA) and Fas was also reduced in MST2−/− mice post-RD. Retinas of MST2−/− mice displayed suppressed nuclear relocalization of phosphorylated YAP after RD. Consistent with the reduction of photoreceptor cell death, MST2−/− mice showed decreased levels of proinflammatory cytokines such as monocyte chemoattractant protein 1 and interleukin 6 as well as attenuated inflammatory CD11b cell infiltration during the early phase of RD. These results identify MST2, not MST1, as a critical regulator of caspase-mediated photoreceptor cell death in the detached retina and indicate its potential as a future neuroprotection target

LOFAR tied-array imaging and spectroscopy of solar S bursts

Context. The Sun is an active source of radio emission that is often associated with energetic phenomena ranging from nanoflares to coronal mass ejections (CMEs). At low radio frequencies (<100 MHz), numerous millisecond duration radio bursts have been reported, such as radio spikes or solar S bursts (where S stands for short). To date, these have neither been studied extensively nor imaged because of the instrumental limitations of previous radio telescopes. Aims. Here, LOw Frequency ARray (LOFAR) observations were used to study the spectral and spatial characteristics of a multitude of S bursts, as well as their origin and possible emission mechanisms. Methods. We used 170 simultaneous tied-array beams for spectroscopy and imaging of S bursts. Since S bursts have short timescales and fine frequency structures, high cadence (~50 ms) tied-array images were used instead of standard interferometric imaging, that is currently limited to one image per second. Results. On 9 July 2013, over 3000 S bursts were observed over a time period of ~8 h. S bursts were found to appear as groups of short-lived (<1 s) and narrow-bandwidth (~2.5 MHz) features, the majority drifting at ~3.5 MHz s-1 and a wide range of circular polarisation degrees (2−8 times more polarised than the accompanying Type III bursts). Extrapolation of the photospheric magnetic field using the potential field source surface (PFSS) model suggests that S bursts are associated with a trans-equatorial loop system that connects an active region in the southern hemisphere to a bipolar region of plage in the northern hemisphere. Conclusions. We have identified polarised, short-lived solar radio bursts that have never been imaged before. They are observed at a height and frequency range where plasma emission is the dominant emission mechanism, however, they possess some of the characteristics of electron-cyclotron maser emission

Lofar low-band antenna observations of the 3C 295 and boötes fields : Source counts and ultra-steep spectrum sources

© 2018 The American Astronomical Society. All rights reserved.We present Low Frequency Array (LOFAR) Low Band observations of the Boötes and 3C 295 fields. Our images made at 34, 46, and 62 MHz reach noise levels of 12, 8, and 5 mJy beam-1, making them the deepest images ever obtained in this frequency range. In total, we detect between 300 and 400 sources in each of these images, covering an area of 17-52 deg2. From the observations, we derive Euclidean-normalized differential source counts. The 62 MHz source counts agree with previous GMRT 153 MHz and Very Large Array 74 MHz differential source counts, scaling with a spectral index of -0.7. We find that a spectral index scaling of -0.5 is required to match up the LOFAR 34 MHz source counts. This result is also in agreement with source counts from the 38 MHz 8C survey, indicating that the average spectral index of radio sources flattens toward lower frequencies. We also find evidence for spectral flattening using the individual flux measurements of sources between 34 and 1400 MHz and by calculating the spectral index averaged over the source population. To select ultra-steep spectrum (α < -1.1) radio sources that could be associated with massive high-redshift radio galaxies, we compute spectral indices between 62 MHz, 153 MHz, and 1.4 GHz for sources in the Boötes field. We cross-correlate these radio sources with optical and infrared catalogs and fit the spectral energy distribution to obtain photometric redshifts. We find that most of these ultra-steep spectrum sources are located in the 0.7 ≲ z ≲ 2.5 range.Peer reviewe

GSK3-mediated raptor phosphorylation supports amino acid-dependent Q2 mTORC1-directed signalling

The mammalian or mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a ubiquitously expressed multimeric protein kinase complex that integrates nutrient and growth factor signals for the co-ordinated regulation of cellular metabolism and cell growth. Herein, we demonstrate that suppressing the cellular activity of glycogen synthase kinase-3 (GSK3), by use of pharmacological inhibitors or shRNA-mediated gene silencing, results in substantial reduction in amino acid (AA)-regulated mTORC1-directed signalling, as assessed by phosphorylation of multiple downstream mTORC1 targets. We show that GSK3 regulates mTORC1 activity through its ability to phosphorylate the mTOR-associated scaffold protein raptor (regulatory-associated protein of mTOR) on Ser(859). We further demonstrate that either GSK3 inhibition or expression of a S859A mutated raptor leads to reduced interaction between mTOR and raptor and under these circumstances, irrespective of AA availability, there is a consequential loss in phosphorylation of mTOR substrates, such as p70S6K1 (ribosomal S6 kinase 1) and uncoordinated-51-like kinase (ULK1), which results in increased autophagic flux and reduced cellular proliferation

First LOFAR observations at very low frequencies of cluster-scale non-thermal emission: the case of Abell 2256

Abell 2256 is one of the best known examples of a galaxy cluster hosting large-scale diffuse radio emission that is unrelated to individual galaxies. It contains both a giant radio halo and a relic, as well as a number of head-tail sources and smaller diffuse steep-spectrum radio sources. The origin of radio halos and relics is still being debated, but over the last years it has become clear that the presence of these radio sources is closely related to galaxy cluster merger events. Here we present the results from the first LOFAR Low band antenna (LBA) observations of Abell 2256 between 18 and 67 MHz. To our knowledge, the image presented in this paper at 63 MHz is the deepest ever obtained at frequencies below 100 MHz in general. Both the radio halo and the giant relic are detected in the image at 63 MHz, and the diffuse radio emission remains visible at frequencies as low as 20 MHz. The observations confirm the presence of a previously claimed ultra-steep spectrum source to the west of the cluster center with a spectral index of -2.3 \pm 0.4 between 63 and 153 MHz. The steep spectrum suggests that this source is an old part of a head-tail radio source in the cluster. For the radio relic we find an integrated spectral index of -0.81 \pm 0.03, after removing the flux contribution from the other sources. This is relatively flat which could indicate that the efficiency of particle acceleration at the shock substantially changed in the last \sim 0.1 Gyr due to an increase of the shock Mach number. In an alternative scenario, particles are re-accelerated by some mechanism in the downstream region of the shock, resulting in the relatively flat integrated radio spectrum. In the radio halo region we find indications of low-frequency spectral steepening which may suggest that relativistic particles are accelerated in a rather inhomogeneous turbulent region.Comment: 13 pages, 13 figures, accepted for publication in A\&A on April 12, 201

LOFAR Sparse Image Reconstruction

Context. The LOw Frequency ARray (LOFAR) radio telescope is a giant digital phased array interferometer with multiple antennas distributed in Europe. It provides discrete sets of Fourier components of the sky brightness. Recovering the original brightness distribution with aperture synthesis forms an inverse problem that can be solved by various deconvolution and minimization methods Aims. Recent papers have established a clear link between the discrete nature of radio interferometry measurement and the "compressed sensing" (CS) theory, which supports sparse reconstruction methods to form an image from the measured visibilities. Empowered by proximal theory, CS offers a sound framework for efficient global minimization and sparse data representation using fast algorithms. Combined with instrumental direction-dependent effects (DDE) in the scope of a real instrument, we developed and validated a new method based on this framework Methods. We implemented a sparse reconstruction method in the standard LOFAR imaging tool and compared the photometric and resolution performance of this new imager with that of CLEAN-based methods (CLEAN and MS-CLEAN) with simulated and real LOFAR data Results. We show that i) sparse reconstruction performs as well as CLEAN in recovering the flux of point sources; ii) performs much better on extended objects (the root mean square error is reduced by a factor of up to 10); and iii) provides a solution with an effective angular resolution 2-3 times better than the CLEAN images. Conclusions. Sparse recovery gives a correct photometry on high dynamic and wide-field images and improved realistic structures of extended sources (of simulated and real LOFAR datasets). This sparse reconstruction method is compatible with modern interferometric imagers that handle DDE corrections (A- and W-projections) required for current and future instruments such as LOFAR and SKAComment: Published in A&A, 19 pages, 9 figure