Identification of non-canonical Wnt receptors required for Wnt-3a-induced early differentiation of human neural stem cells

Wnt proteins preferentially activate either β-catenin-dependent or β-cateninindependent signals, but the activity of a particular Wnt also depends on cellular context and receptor availability. We previously reported that Wnt-3a induces neural differentiation of human embryonic stem cell-derived neural stem cells (NSCs) in a β-catenin-independent manner by activating a signal involving JNK and the AP-1 family member ATF-2. Here, we report the results of a gene silencing approach to identify the Wnt receptors that mediate this response to Wnt-3a. Silencing of ROR2 increased neuronal differentiation, as measured by expression of the genes DCX, NEUROD1 and NGN1, suggesting ROR2 signals normally prevent differentiation. Silencing of the other Wnt receptors singly did not affect Wnt-3ainduced neuronal differentiation. However, pair-wise silencing of ROR1 and FZD4 or FZD5 and of LRP6 and FZD4 or FZD5 inhibited neuronal differentiation, as detected by reductions in the expression of neuronal genes and immunocytochemical detection of DCX and NEUROD1 and DCX. Ectopic expression of these receptors in HEK 293 cells increased ATF2-dependent transcription. In addition, ROR1 co-immunoprecipitated with FZD4 and LRP6 in transfected HEK 293 cells and colocalized with FZD4 and with LRP6 at the cell surface of transfected L cells. Wnt-3a did not appear to affect these interactions but did alter the interactions between LRP6 and FZD4/5. Together, these observations highlight roles for ROR1, LRP6, FZD4 and FZD5 in neural stem cell differentiation and provide support for a model in which dynamic interactions among these receptors mediate Wnt-3a activation of ATF2 signaling

Hand posture, but not vision of the hand, affects tactile spatial resolution in the grating orientation discrimination task

The grating orientation discrimination task (GOT) is a sensitive and reliable measure of tactile spatial resolution, or acuity. We used the GOT in three experiments to investigate the effects of hand posture and hand visibility on spatial acuity. Participant sex and experimental design were also manipulated. Healthy adult participants received brief touches to their index fingertips of grated, domed objects. Their task was to decide whether the gratings ran 'along' or 'across' their finger. Measures of the smallest grating width for which participants could reliably discriminate between orientations were recorded as threshold. Experiment 1 evaluated the effect of two- versus one-interval discrimination, hand used and participant sex. Experiments 2 and 3 evaluated the effects of hand visibility (visible or covered) and hand posture (in front or to the side). Females were better than males; the two-interval task resulted in lower thresholds than the one-interval task; and left and right hand thresholds were not significantly different. Most importantly, while hand visibility did not have a significant effect on the task, thresholds were affected by hand posture—worse when the hand was oriented to the side of the body than in front. These results replicate previously reported effects of sex (or finger size), but failed to replicate the so-called ‘visual enhancement of touch’ (VET) effect. We also report a meta-analysis of 27 VET studies, finding a significant effect of ‘non-informative’ vision on tactile perception. Our novel finding is that hand posture affects tactile acuity

Unresolved Gamma-Ray Sky through its Angular Power Spectrum

The gamma-ray sky has been observed with unprecedented accuracy in the last decade by the Fermi -large area telescope (LAT), allowing us to resolve and understand the high-energy Universe. The nature of the remaining unresolved emission [unresolved gamma-ray background (UGRB)] below the LAT source detection threshold can be uncovered by characterizing the amplitude and angular scale of the UGRB fluctuation field. This Letter presents a measurement of the UGRB autocorrelation angular power spectrum based on eight years of Fermi-LAT Pass 8 data products. The analysis is designed to be robust against contamination from resolved sources and noise systematics. The sensitivity to subthreshold sources is greatly enhanced with respect to previous measurements. We find evidence (with ∼3.7σ significance) that the scenario in which two classes of sources contribute to the UGRB signal is favored over a single class. A double power law with exponential cutoff can explain the anisotropy energy spectrum well, with photon indices of the two populations being 2.55±0.23 and 1.86±0.15

High-energy emission from a magnetar giant flare in the Sculptor galaxy

Magnetars are the most highly magnetized neutron stars in the cosmos (with magnetic field 1013–1015 G). Giant flares from magnetars are rare, short-duration (about 0.1 s) bursts of hard X-rays and soft γ rays1,2. Owing to the limited sensitivity and energy coverage of previous telescopes, no magnetar giant flare has been detected at gigaelectronvolt (GeV) energies. Here, we report the discovery of GeV emission from a magnetar giant flare on 15 April 2020 (refs. 3,4 and A. J. Castro-Tirado et al., manuscript in preparation). The Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope detected GeV γ rays from 19 s until 284 s after the initial detection of a signal in the megaelectronvolt (MeV) band. Our analysis shows that these γ rays are spatially associated with the nearby (3.5 megaparsecs) Sculptor galaxy and are unlikely to originate from a cosmological γ-ray burst. Thus, we infer that the γ rays originated with the magnetar giant flare in Sculptor. We suggest that the GeV signal is generated by an ultra-relativistic outflow that first radiates the prompt MeV-band photons, and then deposits its energy far from the stellar magnetosphere. After a propagation delay, the outflow interacts with environmental gas and produces shock waves that accelerate electrons to very high energies; these electrons then emit GeV γ rays as optically thin synchrotron radiation. This observation implies that a relativistic outflow is associated with the magnetar giant flare, and suggests the possibility that magnetars can power some short γ-ray bursts

Search for Early Gamma-ray Production in Supernovae Located in a Dense Circumstellar Medium with the Fermi LAT

Supernovae (SNe) exploding in a dense circumstellar medium (CSM) are hypothesized to accelerate cosmic rays in collisionless shocks and emit GeV gamma rays and TeV neutrinos on a time scale of several months. We perform the first systematic search for gamma-ray emission in Fermi LAT data in the energy range from 100 MeV to 300 GeV from the ensemble of 147 SNe Type IIn exploding in dense CSM. We search for a gamma-ray excess at each SNe location in a one year time window. In order to enhance a possible weak signal, we simultaneously study the closest and optically brightest sources of our sample in a joint-likelihood analysis in three different time windows (1 year, 6 months and 3 months). For the most promising source of the sample, SN 2010jl (PTF10aaxf), we repeat the analysis with an extended time window lasting 4.5 years. We do not find a significant excess in gamma rays for any individual source nor for the combined sources and provide model-independent flux upper limits for both cases. In addition, we derive limits on the gamma-ray luminosity and the ratio of gamma-ray-to-optical luminosity ratio as a function of the index of the proton injection spectrum assuming a generic gamma-ray production model. Furthermore, we present detailed flux predictions based on multi-wavelength observations and the corresponding flux upper limit at 95% confidence level (CL) for the source SN 2010jl (PTF10aaxf).Comment: Accepted for publication in ApJ. Corresponding author: A. Franckowiak ([email protected]), updated author list and acknowledgement

Search for extended gamma-ray emission from the Virgo galaxy cluster with Fermi-LAT

Galaxy clusters are one of the prime sites to search for dark matter (DM) annihilation signals. Depending on the substructure of the DM halo of a galaxy cluster and the cross sections for DM annihilation channels, these signals might be detectable by the latest generation of $\gamma$-ray telescopes. Here we use three years of Fermi Large Area Telescope (LAT) data, which are the most suitable for searching for very extended emission in the vicinity of nearby Virgo galaxy cluster. Our analysis reveals statistically significant extended emission which can be well characterized by a uniformly emitting disk profile with a radius of 3\deg that moreover is offset from the cluster center. We demonstrate that the significance of this extended emission strongly depends on the adopted interstellar emission model (IEM) and is most likely an artifact of our incomplete description of the IEM in this region. We also search for and find new point source candidates in the region. We then derive conservative upper limits on the velocity-averaged DM pair annihilation cross section from Virgo. We take into account the potential $\gamma$-ray flux enhancement due to DM sub-halos and its complex morphology as a merging cluster. For DM annihilating into $b\overline{b}$, assuming a conservative sub-halo model setup, we find limits that are between 1 and 1.5 orders of magnitude above the expectation from the thermal cross section for $m_{\mathrm{DM}}\lesssim100\,\mathrm{GeV}$. In a more optimistic scenario, we exclude $\langle \sigma v \rangle\sim3\times10^{-26}\,\mathrm{cm^{3}\,s^{-1}}$ for $m_{\mathrm{DM}}\lesssim40\,\mathrm{GeV}$ for the same channel. Finally, we derive upper limits on the $\gamma$-ray-flux produced by hadronic cosmic-ray interactions in the inter cluster medium. We find that the volume-averaged cosmic-ray-to-thermal pressure ratio is less than $\sim6\%$.Comment: 15 pages, 11 figures, 4 tables, accepted for publication in ApJ; corresponding authors: T. Jogler, S. Zimmer & A. Pinzk

Fermi and Swift Observations of GRB 190114C: Tracing the Evolution of High-energy Emission from Prompt to Afterglow

We report on the observations of gamma-ray burst (GRB) 190114C by the Fermi Gamma-ray Space Telescope and the Neil Gehrels Swift Observatory. The prompt gamma-ray emission was detected by the Fermi GRB Monitor (GBM), the Fermi Large Area Telescope (LAT), and the Swift Burst Alert Telescope (BAT) and the long-lived afterglow emission was subsequently observed by the GBM, LAT, Swift X-ray Telescope (XRT), and Swift UV Optical Telescope. The early-time observations reveal multiple emission components that evolve independently, with a delayed power-law component that exhibits significant spectral attenuation above 40 MeV in the first few seconds of the burst. This power-law component transitions to a harder spectrum that is consistent with the afterglow emission observed by the XRT at later times. This afterglow component is clearly identifiable in the GBM and BAT light curves as a slowly fading emission component on which the rest of the prompt emission is superimposed. As a result, we are able to observe the transition from internal-shock- to external-shock-dominated emission. We find that the temporal and spectral evolution of the broadband afterglow emission can be well modeled as synchrotron emission from a forward shock propagating into a wind-like circumstellar environment. We estimate the initial bulk Lorentz factor using the observed high-energy spectral cutoff. Considering the onset of the afterglow component, we constrain the deceleration radius at which this forward shock begins to radiate in order to estimate the maximum synchrotron energy as a function of time. We find that even in the LAT energy range, there exist high-energy photons that are in tension with the theoretical maximum energy that can be achieved through synchrotron emission from a shock. These violations of the maximum synchrotron energy are further compounded by the detection of very high-energy (VHE) emission above 300 GeV by MAGIC concurrent with our observations. We conclude that the observations of VHE photons from GRB 190114C necessitates either an additional emission mechanism at very high energies that is hidden in the synchrotron component in the LAT energy range, an acceleration mechanism that imparts energy to the particles at a rate that is faster than the electron synchrotron energy-loss rate, or revisions of the fundamental assumptions used in estimating the maximum photon energy attainable through the synchrotron process

Multiwavelength Evidence for Quasi-periodic Modulation in the Gamma-ray Blazar PG 1553+113

We report for the first time a gamma-ray and multi-wavelength nearly-periodic oscillation in an active galactic nucleus. Using the Fermi Large Area Telescope (LAT) we have discovered an apparent quasi-periodicity in the gamma-ray flux (E >100 MeV) from the GeV/TeV BL Lac object PG 1553+113. The marginal significance of the 2.18 +/-0.08 year-period gamma-ray cycle is strengthened by correlated oscillations observed in radio and optical fluxes, through data collected in the OVRO, Tuorla, KAIT, and CSS monitoring programs and Swift UVOT. The optical cycle appearing in ~10 years of data has a similar period, while the 15 GHz oscillation is less regular than seen in the other bands. Further long-term multi-wavelength monitoring of this blazar may discriminate among the possible explanations for this quasi-periodicity.Comment: 8 pages, 5 figures. Accepted to The Astrophysical Journal Letters. Corresponding authors: S. Ciprini (ASDC/INFN), S. Cutini (ASDC/INFN), S. Larsson (Stockholm Univ/KTH), A. Stamerra (INAF/SNS), D. J. Thompson (NASA GSFC