Elevation of basal intracellular calcium as a central element in the activation of brain macrophages (microglia): suppression of receptor-evoked calcium signaling and control of release function

Microglia-brain macrophages are immune-competent cells of the CNS and respond to pathologic events. Using bacterial lipopolysaccharide (LPS) as a tool to activate cultured mouse microglia, we studied alterations in the intracellular calcium concentration ([Ca 2+]i) and in the receptor-evoked generation of transient calcium signals. LPS treatment led to a chronic elevation of basal [Ca 2+]i along with a suppression of evoked calcium signaling, as indicated by reduced [Ca 2+]i transients during stimulation with UTP and complement factor 5a. Presence of the calcium chelator BAPTA prevented the activation-associated changes in [Ca 2+]i and restored much of the signaling efficacy. We also evaluated downstream consequences of a basal [Ca 2+]i lifting during microglial activation and found BAPTA to strongly attenuate the LPS-induced release of nitric oxide (NO) and certain cytokines and chemokines. Furthermore, microglial treatment with ionomycin, an ionophore elevating basal [Ca 2+]i, mimicked the activation-induced calcium signal suppression but failed to induce release activity on its own. Our findings suggest that chronic elevation of basal [Ca 2+]i attenuates receptor-triggered calcium signaling. Moreover, increased [Ca 2+]i is required, but by itself is not sufficient, for release of NO and certain cytokines and chemokines. Elevation of basal [Ca 2+]i could thus prove a central element in the regulation of executive functions in activated microglia

The central engine of GRB 130831A and the energy breakdown of a relativistic explosion

Gamma-ray bursts (GRBs) are the most luminous explosions in the universe, yet the nature and physical properties of their energy sources are far from understood. Very important clues, however, can be inferred by studying the afterglows of these events. We present optical and X-ray observations of GRB 130831A obtained by Swift, Chandra, Skynet, RATIR, Maidanak, ISON, NOT, LT and GTC. This burst shows a steep drop in the X-ray light-curve at $\simeq 10^5$ s after the trigger, with a power-law decay index of $\alpha \sim 6$. Such a rare behaviour cannot be explained by the standard forward shock (FS) model and indicates that the emission, up to the fast decay at $10^5$ s, must be of "internal origin", produced by a dissipation process within an ultrarelativistic outflow. We propose that the source of such an outflow, which must produce the X-ray flux for $\simeq 1$ day in the cosmological rest frame, is a newly born magnetar or black hole. After the drop, the faint X-ray afterglow continues with a much shallower decay. The optical emission, on the other hand, shows no break across the X-ray steep decrease, and the late-time decays of both the X-ray and optical are consistent. Using both the X-ray and optical data, we show that the emission after $\simeq 10^5$ s can be explained well by the FS model. We model our data to derive the kinetic energy of the ejecta and thus measure the efficiency of the central engine of a GRB with emission of internal origin visible for a long time. Furthermore, we break down the energy budget of this GRB into the prompt emission, the late internal dissipation, the kinetic energy of the relativistic ejecta, and compare it with the energy of the associated supernova, SN 2013fu.Comment: Accepted for publication by MNRAS. 21 pages, 3 figures, 8 tables. Extra table with magnitudes in the sourc

Unveiling the Origin of Grb 090709A: Lack of Periodicity in a Reddened Cosmological Long-Duration Gamma-Ray Burst

We present broadband (gamma-ray, X-ray, near-infrared, optical, and radio) observations of the Swift gamma-ray burst (GRB) 090709A and its afterglow in an effort to ascertain the origin of this high-energy transient. Previous analyses suggested that GRB 090709A exhibited quasi-periodic oscillations with a period of 8.06 s, a trait unknown in long-duration GRBs but typical of flares from soft gamma-ray repeaters. When properly accounting for the underlying shape of the power-density spectrum of GRB 090709A, we find no conclusive (>3σ) evidence for the reported periodicity. In conjunction with the location of the transient (far from the Galactic plane and absent any nearby host galaxy in the local universe) and the evidence for extinction in excess of the Galactic value, we consider a magnetar origin relatively unlikely. A long-duration GRB, however, can account for the majority of the observed properties of this source. GRB 090709A is distinguished from other long-duration GRBs primarily by the large amount of obscuration from its host galaxy (A_(K,obs) ≳ 2 mag)

Assessing quality of life in psychosocial and mental health disorders in children:a comprehensive overview and appraisal of generic health related quality of life measures

Background: Mental health problems often arise in childhood and adolescence and can have detrimental effects on people's quality of life (QoL). Therefore, it is of great importance for clinicians, policymakers and researchers to adequately measure QoL in children. With this review, we aim to provide an overview of existing generic measures of QoL suitable for economic evaluations in children with mental health problems. Methods: First, we undertook a meta-review of QoL instruments in which we identified all relevant instruments. Next, we performed a systematic review of the psychometric properties of the identified instruments. Lastly, the results were summarized in a decision tree. Results: This review provides an overview of these 22 generic instruments available to measure QoL in children with psychosocial and or mental health problems and their psychometric properties. A systematic search into the psychometric quality of these instruments found 195 suitable papers, of which 30 assessed psychometric quality in child and adolescent mental health. Conclusions: We found that none of the instruments was perfect for use in economic evaluation of child and adolescent mental health care as all instruments had disadvantages, ranging from lack of psychometric research, no proxy version, not being suitable for young children, no age-specific value set for children under 18, to insufficient focus on relevant domains (e.g. social and emotional domains)

An optical supernova associated with the X-ray flash XRF 060218

Long-duration gamma-ray bursts (GRBs) are associated with type Ic supernovae that are more luminous than average and that eject material at very high velocities. Less-luminous supernovae were not hitherto known to be associated with GRBs, and therefore GRB-supernovae were thought to be rare events. Whether X-ray flashes - analogues of GRBs, but with lower luminosities and fewer gamma-rays - can also be associated with supernovae, and whether they are intrinsically 'weak' events or typical GRBs viewed off the axis of the burst, is unclear. Here we report the optical discovery and follow-up observations of the type Ic supernova SN 2006aj associated with X-ray flash XRF 060218. Supernova 2006aj is intrinsically less luminous than the GRB-supernovae, but more luminous than many supernovae not accompanied by a GRB. The ejecta velocities derived from our spectra are intermediate between these two groups, which is consistent with the weakness of both the GRB output and the supernova radio flux. Our data, combined with radio and X-ray observations, suggest that XRF 060218 is an intrinsically weak and soft event, rather than a classical GRB observed off-axis. This extends the GRB-supernova connection to X-ray flashes and fainter supernovae, implying a common origin. Events such as XRF 060218 are probably more numerous than GRB-supernovae.Comment: Final published versio

The optical identifcation of events with poorly defined locations: The case of the Fermi GBM GRB140801A

We report the early discovery of the optical afterglow of gamma-ray burst (GRB) 140801A in the 137 deg$^2$ 3-$\sigma$ error-box of the Fermi Gamma-ray Burst Monitor (GBM). MASTER is the only observatory that automatically react to all Fermi alerts. GRB 140801A is one of the few GRBs whose optical counterpart was discovered solely from its GBM localization. The optical afterglow of GRB 140801A was found by MASTER Global Robotic Net 53 sec after receiving the alert, making it the fastest optical detection of a GRB from a GBM error-box. Spectroscopy obtained with the 10.4-m Gran Telescopio Canarias and the 6-m BTA of SAO RAS reveals a redshift of $z=1.32$. We performed optical and near-infrared photometry of GRB 140801A using different telescopes with apertures ranging from 0.4-m to 10.4-m. GRB 140801A is a typical burst in many ways. The rest-frame bolometric isotropic energy release and peak energy of the burst is $E_\mathrm{iso} = 5.54_{-0.24}^{+0.26} \times 10^{52}$ erg and $E_\mathrm{p, rest}\simeq280$ keV, respectively, which is consistent with the Amati relation. The absence of a jet break in the optical light curve provides a lower limit on the half-opening angle of the jet $\theta=6.1$ deg. The observed $E_\mathrm{peak}$ is consistent with the limit derived from the Ghirlanda relation. The joint Fermi GBM and Konus-Wind analysis shows that GRB 140801A could belong to the class of intermediate duration. The rapid detection of the optical counterpart of GRB 140801A is especially important regarding the upcoming experiments with large coordinate error-box areas.Comment: in press MNRAS, 201

Dark Bursts in the Swift Era: The Palomar 60 inch-Swift Early Optical Afterglow Catalog

We present multi-color optical observations of long-duration gamma-ray bursts (GRBs) made over a three year period with the robotic Palomar 60 inch telescope (P60). Our sample consists of all 29 events discovered by Swift for which P60 began observations less than one hour after the burst trigger. We were able to recover 80% of the optical afterglows from this prompt sample, and we attribute this high efficiency to our red coverage. Like Melandri et al. (2008), we find that a significant fraction (~ 50%) of Swift events show a suppression of the optical flux with regards to the X-ray emission (so-called "dark" bursts). Our multi-color photometry demonstrates this is likely due in large part to extinction in the host galaxy. We argue that previous studies, by selecting only the brightest and best-sampled optical afterglows, have significantly underestimated the amount of dust present in typical GRB environments.Comment: 49 pages, including 6 figures and 3 tables (one of which is quite long). Re-submitted to ApJ following referee report. Comments welcome. v2: Corrected minor typo

The origin of the early time optical emission of Swift GRB 080310

We present broadband multi-wavelength observations of GRB 080310 at redshift z = 2.43. This burst was bright and long-lived, and unusual in having extensive optical and near IR follow-up during the prompt phase. Using these data we attempt to simultaneously model the gamma-ray, X-ray, optical and IR emission using a series of prompt pulses and an afterglow component. Initial attempts to extrapolate the high energy model directly to lower energies for each pulse reveal that a spectral break is required between the optical regime and 0.3 keV to avoid over predicting the optical flux. We demonstrate that afterglow emission alone is insufficient to describe all morphology seen in the optical and IR data. Allowing the prompt component to dominate the early-time optical and IR and permitting each pulse to have an independent low energy spectral indices we produce an alternative scenario which better describes the optical light curve. This, however, does not describe the spectral shape of GRB 080310 at early times. The fit statistics for the prompt and afterglow dominated models are nearly identical making it difficult to favour either. However one enduring result is that both models require a low energy spectral index consistent with self absorption for at least some of the pulses identified in the high energy emission model.Comment: 24 pages, 12 figures, 12 tables. Accepted to MNRA

Brain energy metabolism: A roadmap for future research

Although we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well as during development, aging, and disease. The focus is on unknowns in metabolism of major brain substrates and associated transporters, the roles of insulin and of lipid droplets, the emerging role of metabolism in microglia, mysteries about the major brain cofactor and signaling molecule NAD+, as well as unsolved problems underlying brain metabolism in pathologies such as traumatic brain injury, epilepsy, and metabolic downregulation during hibernation. It describes our current level of understanding of these facets of brain energy metabolism as well as a roadmap for future research