Riluzole is the only drug approved for the treatment of amyotrophic lateral sclerosis (ALS) but its precise mode of action is not properly understood. Damage to axonal transport of neurofilaments is ...believed to be part of the pathogenic mechanism in ALS and this has been linked to defective glutamate handling and increased phosphorylation of neurofilament side-arm domains. Here, we show that riluzole protects against glutamate-induced slowing of neurofilament transport. Protection is associated with decreased neurofilament side-arm phosphorylation and inhibition of the activities of two neurofilament kinases, ERK and p38 that are activated in ALS. Thus, the anti-glutamatergic properties of riluzole include protection against glutamate-induced changes to neurofilament phosphorylation and transport.
Gaia16aye was a binary microlensing event discovered in the direction towards the northern Galactic disc and was one of the first microlensing events detected and alerted to by the
Gaia
space ...mission. Its light curve exhibited five distinct brightening episodes, reaching up to
I
= 12 mag, and it was covered in great detail with almost 25 000 data points gathered by a network of telescopes. We present the photometric and spectroscopic follow-up covering 500 days of the event evolution. We employed a full Keplerian binary orbit microlensing model combined with the motion of Earth and
Gaia
around the Sun to reproduce the complex light curve. The photometric data allowed us to solve the microlensing event entirely and to derive the complete and unique set of orbital parameters of the binary lensing system. We also report on the detection of the first-ever microlensing space-parallax between the Earth and
Gaia
located at L2. The properties of the binary system were derived from microlensing parameters, and we found that the system is composed of two main-sequence stars with masses 0.57 ± 0.05
M
⊙
and 0.36 ± 0.03
M
⊙
at 780 pc, with an orbital period of 2.88 years and an eccentricity of 0.30. We also predict the astrometric microlensing signal for this binary lens as it will be seen by
Gaia
as well as the radial velocity curve for the binary system. Events such as Gaia16aye indicate the potential for the microlensing method of probing the mass function of dark objects, including black holes, in directions other than that of the Galactic bulge. This case also emphasises the importance of long-term time-domain coordinated observations that can be made with a network of heterogeneous telescopes.
We report the occurrence of a deep low state in the eclipsing short-period cataclysmic variable (CV) IR Com, lasting more than two years. Spectroscopy obtained in this state shows the system as a ...detached white dwarf plus low-mass companion, indicating that accretion has practically ceased. The spectral type of the companion derived from the SDSS spectrum is M6–7, somewhat later than expected for the orbital period of IR Com. Its radial velocity amplitude, K
2 = 419.6 ± 3.4 km s−1, together with the inclination of 75°–90° implies 0.8 < Mwd <1.0 M⊙. We estimate the white dwarf temperature to be ≃15 000 K, and the absence of Zeeman splitting in the Balmer lines rules out magnetic fields in excess of ≃5 MG. IR Com still defies an unambiguous classification, in particular the occurrence of a deep, long low state is so far unique among short-period CVs that are not strongly magnetic.
We present early results from the JCMT (James Clerk Maxwell Telescope) Plane Survey (JPS), which has surveyed the northern inner Galactic plane between longitudes ℓ = 7° and ℓ = 63° in the 850-μm ...continuum with SCUBA-2 (Submm Common-User Bolometer Array 2), as part of the JCMT Legacy Survey programme. Data from the ℓ = 30° survey region, which contains the massive-star-forming regions W43 and G29.96, are analysed after approximately 40 per cent of the observations had been completed. The pixel-to-pixel noise is found to be 19 mJy beam−1 after a smooth over the beam area, and the projected equivalent noise levels in the final survey are expected to be around 10 mJy beam−1. An initial extraction of compact sources was performed using the FellWalker method, resulting in the detection of 1029 sources above a 5σ surface-brightness threshold. The completeness limits in these data are estimated to be around 0.2 Jy beam−1 (peak flux density) and 0.8 Jy (integrated flux density) and are therefore probably already dominated by source confusion in this relatively crowded section of the survey. The flux densities of extracted compact sources are consistent with those of matching detections in the shallower APEX (Atacama Pathfinder Experiment) Telescope Large Area Survey of the Galaxy (ATLASGAL) survey. We analyse the virial and evolutionary state of the detected clumps in the W43 star-forming complex and find that they appear younger than the Galactic-plane average.
Neurofilaments are the intermediate filaments of neurons and are synthesised in neuronal cell bodies and then transported through axons. Neurofilament light chain (NFL) is a principal component of ...neurofilaments, and phosphorylation of NFL head domain is believed to regulate the assembly of neurofilaments. However, the role that NFL phosphorylation has on transport of neurofilaments is poorly understood. To address this issue, we monitored axonal transport of phosphorylation mutants of NFL. We mutated four known phosphorylation sites in NFL head domain to either preclude phosphorylation, or mimic permanent phosphorylation. Mutation to preclude phosphorylation had no effect on transport but mutation of three sites to mimic permanent phosphorylation inhibited transport. Mutation of all four sites together to mimic permanent phosphorylation proved especially potent at inhibiting transport and also disrupted neurofilament assembly. Our results suggest that NFL head domain phosphorylation is a regulator of neurofilament axonal transport.
Available evidence indicates that B cell tolerance is attained by receptor editing, anergy, or clonal deletion. Here, we describe a
p-azophenylarsonate (Ars)-specific immunoglobulin transgenic mouse ...in which B cells become anergic as a consequence of cross-reaction with autoantigen in the bone marrow. Developing bone marrow B cells show no evidence of receptor editing but transiently upregulate activation markers and appear to undergo accelerated development. Mature B cells are present in normal numbers but are refractory to BCR-mediated induction of calcium mobilization, tyrosine phosphorylation, and antibody responses. Activation marker expression and acquisition of the anergic phenotype is prevented in bone marrow cultures by monovalent hapten. In this model, it appears that induction of anergy in B cells can be prevented by monovalent hapten competing with autoantigen for the binding site.
Neurofilaments are synthesised in neuronal cell bodies and then transported through axons. Damage to neurofilament transport is seen in amyotrophic lateral sclerosis (ALS). Here, we show that PKN1, a ...neurofilament head–rod domain kinase is cleaved and activated in SOD1G93A transgenic mice that are a model of ALS. Moreover, we demonstrate that glutamate, a proposed toxic mechanism in ALS leads to caspase cleavage and disruption of PKN1 in neurons. Finally, we demonstrate that a cleaved form of PKN1 but not wild-type PKN1 disrupts neurofilament organisation and axonal transport. Thus, deregulation of PKN1 may contribute to the pathogenic process in ALS.
We present early results from the JCMT (James Clerk Maxwell Telescope) Plane Survey (JPS), which has surveyed the northern inner Galactic plane between longitudes ... = 7... and ... = 63... in the ...850-...m continuum with SCUBA-2 (Submm Common-User Bolometer Array 2), as part of the JCMT Legacy Survey programme. Data from the ... = 30... survey region, which contains the massive-star-forming regions W43 and G29.96, are analysed after approximately 40 per cent of the observations had been completed. The pixel-to-pixel noise is found to be 19 mJy beam... after a smooth over the beam area, and the projected equivalent noise levels in the final survey are expected to be around 10 mJy beam... An initial extraction of compact sources was performed using the FellWalker method, resulting in the detection of 1029 sources above a 5... surface-brightness threshold. The completeness limits in these data are estimated to be around 0.2 Jy beam... (peak flux density) and 0.8 Jy (integrated flux density) and are therefore probably already dominated by source confusion in this relatively crowded section of the survey. The flux densities of extracted compact sources are consistent with those of matching detections in the shallower APEX (Atacama Pathfinder Experiment) Telescope Large Area Survey of the Galaxy (ATLASGAL) survey. We analyse the virial and evolutionary state of the detected clumps in the W43 star-forming complex and find that they appear younger than the Galactic-plane average. (ProQuest: ... denotes formulae/symbols omitted.)
Abstract We describe the spectroscopic data processing pipeline of the Dark Energy Spectroscopic Instrument (DESI), which is conducting a redshift survey of about 40 million galaxies and quasars ...using a purpose-built instrument on the 4 m Mayall Telescope at Kitt Peak National Observatory. The main goal of DESI is to measure with unprecedented precision the expansion history of the universe with the baryon acoustic oscillation technique and the growth rate of structure with redshift space distortions. Ten spectrographs with three cameras each disperse the light from 5000 fibers onto 30 CCDs, covering the near-UV to near-infrared (3600–9800 Å) with a spectral resolution ranging from 2000 to 5000. The DESI data pipeline generates wavelength- and flux-calibrated spectra of all the targets, along with spectroscopic classifications and redshift measurements. Fully processed data from each night are typically available to the DESI collaboration the following morning. We give details about the pipeline’s algorithms, and provide performance results on the stability of the optics, the quality of the sky background subtraction, and the precision and accuracy of the instrumental calibration. This pipeline has been used to process the DESI Survey Validation data set, and has exceeded the project’s requirements for redshift performance, with high efficiency and a purity greater than 99% for all target classes.
Context. One-opposition near-Earth asteroids (NEAs) are growing in number, and they must be recovered to prevent loss and mismatch risk, and to improve their orbits, as they are likely to be too ...faint for detection in shallow surveys at future apparitions. Aims. We aimed to recover more than half of the one-opposition NEAs recommended for observations by the Minor Planet Center (MPC) using the Isaac Newton Telescope (INT) in soft-override mode and some fractions of available D-nights. During about 130 h in total between 2013 and 2016, we targeted 368 NEAs, among which 56 potentially hazardous asteroids (PHAs), observing 437 INT Wide Field Camera (WFC) fields and recovering 280 NEAs (76% of all targets). Methods. Engaging a core team of about ten students and amateurs, we used the THELI, Astrometrica, and the Find_Orb software to identify all moving objects using the blink and track-and-stack method for the faintest targets and plotting the positional uncertainty ellipse from NEODyS. Results. Most targets and recovered objects had apparent magnitudes centered around V ~ 22.8 mag, with some becoming as faint as V ~ 24 mag. One hundred and three objects (representing 28% of all targets) were recovered by EURONEAR alone by Aug. 2017. Orbital arcs were prolonged typically from a few weeks to a few years; our oldest recoveries reach 16 years. The O−C residuals for our 1854 NEA astrometric positions show that most measurements cluster closely around the origin. In addition to the recovered NEAs, 22 000 positions of about 3500 known minor planets and another 10 000 observations of about 1500 unknown objects (mostly main-belt objects) were promptly reported to the MPC by our team. Four new NEAs were discovered serendipitously in the analyzed fields and were promptly secured with the INT and other telescopes, while two more NEAs were lost due to extremely fast motion and lack of rapid follow-up time. They increase the counting to nine NEAs discovered by the EURONEAR in 2014 and 2015. Conclusions. Targeted projects to recover one-opposition NEAs are efficient in override access, especially using at least two-meter class and preferably larger field telescopes located in good sites, which appear even more efficient than the existing surveys.
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