Dysregulation of the mTOR Pathway Mediates Impairment of Synaptic Plasticity in a Mouse Model of Alzheimer's Disease

Background: The mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr protein kinase that plays a pivotal role in multiple fundamental biological processes, including synaptic plasticity. We explored the relationship between the mTOR pathway and b-amyloid (Ab)-induced synaptic dysfunction, which is considered to be critical in the pathogenesis of Alzheimer’s disease (AD). Methodology/Principal Findings: We provide evidence that inhibition of mTOR signaling correlates with impairment in synaptic plasticity in hippocampal slices from an AD mouse model and in wild-type slices exposed to exogenous Ab1-42. Importantly, by up-regulating mTOR signaling, glycogen synthase kinase 3 (GSK3) inhibitors rescued LTP in the AD mouse model, and genetic deletion of FK506-binding protein 12 (FKBP12) prevented Ab-induced impairment in long-term potentiation (LTP). In addition, confocal microscopy demonstrated co-localization of intraneuronal Ab42 with mTOR. Conclusions/Significance: These data support the notion that the mTOR pathway modulates Ab-related synaptic dysfunctio

An elliptical accretion disk following the tidal disruption event AT 2020zso

Aims. The modelling of spectroscopic observations of tidal disruption events (TDEs) to date suggests that the newly formed accretion disks are mostly quasi-circular. In this work we study the transient event AT 2020zso, hosted by an active galactic nucleus (AGN; as inferred from narrow emission line diagnostics), with the aim of characterising the properties of its newly formed accretion flow.Methods. We classify AT 2020zso as a TDE based on the blackbody evolution inferred from UV/optical photometric observations and spectral line content and evolution. We identify transient, double-peaked Bowen (N III), He I, He II, and H alpha emission lines. We model medium-resolution optical spectroscopy of the He II (after careful de-blending of the N III contribution) and H alpha lines during the rise, peak, and early decline of the light curve using relativistic, elliptical accretion disk models.Results. We find that the spectral evolution before the peak can be explained by optical depth effects consistent with an outflowing, optically thick Eddington envelope. Around the peak, the envelope reaches its maximum extent (approximately 10(15) cm, or similar to 3000-6000 gravitational radii for an inferred black hole mass of 5-10 x 10(5) M-circle dot) and becomes optically thin. The H alpha and He II emission lines at and after the peak can be reproduced with a highly inclined (i  = 85 +/- 5 degrees), highly elliptical (e  = 0.97 +/- 0.01), and relatively compact (R-in = several 100 R-g and R-out = several 1000 R-g) accretion disk.Conclusions. Overall, the line profiles suggest a highly elliptical geometry for the new accretion flow, consistent with theoretical expectations of newly formed TDE disks. We quantitatively confirm, for the first time, the high inclination nature of a Bowen (and X-ray dim) TDE, consistent with the unification picture of TDEs, where the inclination largely determines the observational appearance. Rapid line profile variations rule out the binary supermassive black hole hypothesis as the origin of the eccentricity; these results thus provide a direct link between a TDE in an AGN and the eccentric accretion disk. We illustrate for the first time how optical spectroscopy can be used to constrain the black hole spin, through (the lack of) disk precession signatures (changes in inferred inclination). We constrain the disk alignment timescale to > 15 days in AT2020zso, which rules out high black hole spin values (a  < 0.8) for M-BH  similar to  10(6) M-circle dot and disk viscosity alpha  greater than or similar to  0.1.</p

Transitional events in the spectrophotometric regime between stripped envelope and superluminous supernovae

The division between stripped-envelope supernovae (SE-SNe) and superluminous supernovae (SLSNe) is not well-defined in either photometric or spectroscopic space. While a sharp luminosity threshold has been suggested, there remains an increasing number of transitional objects that reach this threshold without the spectroscopic signatures common to SLSNe. In this work, we present data and analysis on four SNe transitional between SE-SNe and SLSNe; the He-poor SNe 2019dwa and 2019cri, and the He-rich SNe 2019hge and 2019unb. Each object displays long-lived and variable photometric evolution with luminosities around the SLSN threshold of M-r < -19.8 mag. Spectroscopically however, these objects are similar to SE-SNe, with line velocities lower than either SE-SNe and SLSNe, and thus represent an interesting case of rare transitional events

Transitional events in the spectrophotometric regime between stripped envelope and superluminous supernovae

The division between stripped-envelope supernovae (SE-SNe) and superluminous supernovae (SLSNe) is not well-defined in either photometric or spectroscopic space. While a sharp luminosity threshold has been suggested, there remains an increasing number of transitional objects that reach this threshold without the spectroscopic signatures common to SLSNe. In this work, we present data and analysis on four SNe transitional between SE-SNe and SLSNe; the He-poor SNe 2019dwa and 2019cri, and the He-rich SNe 2019hge and 2019unb. Each object displays long-lived and variable photometric evolution with luminosities around the SLSN threshold of Mr < -19.8 mag. Spectroscopically however, these objects are similar to SE-SNe, with line velocities lower than either SE-SNe and SLSNe, and thus represent an interesting case of rare transitional events

SN 2022joj: A Peculiar Type Ia Supernova Possibly Driven by an Asymmetric Helium-shell Double Detonation

We present observations of SN 2022joj, a peculiar Type Ia supernova discovered by the Zwicky Transient Facility. SN 2022joj exhibits an unusually red g ZTF − r ZTF color at early times and a rapid blueward evolution afterward. Around maximum brightness, SN 2022joj shows a high luminosity ( M g ZTF , max ≃ − 19.7 mag), a blue broadband color (g ZTF − r ZTF ≃ −0.2 mag), and shallow Si ii absorption lines, consistent with those of overluminous, SN 1991T-like events. The maximum-light spectrum also shows prominent absorption around 4200 Å, which resembles the Ti ii features in subluminous, SN 1991bg-like events. Despite the blue optical-band colors, SN 2022joj exhibits extremely red ultraviolet minus optical colors at maximum luminosity (u − v ≃ 0.6 mag and uvw1 − v ≃ 2.5 mag), suggesting a suppression of flux at ∼2500-4000 Å. Strong C ii lines are also detected at peak. We show that these unusual spectroscopic properties are broadly consistent with the helium-shell double detonation of a sub-Chandrasekhar mass (M ≃ 1 M ⊙) carbon/oxygen white dwarf from a relatively massive helium shell (M s ≃ 0.04-0.1 M ⊙), if observed along a line of sight roughly opposite to where the shell initially detonates. None of the existing models could quantitatively explain all the peculiarities observed in SN 2022joj. The low flux ratio of [Ni ii] λ7378 to [Fe ii] λ7155 emission in the late-time nebular spectra indicates a low yield of stable Ni isotopes, favoring a sub-Chandrasekhar mass progenitor. The significant blueshift measured in the [Fe ii] λ7155 line is also consistent with an asymmetric chemical distribution in the ejecta, as is predicted in double-detonation models

A precursor plateau and pre-maximum [O II] emission in the superluminous SN2019szu: a pulsational pair-instability candidate

We present a detailed study on SN2019szu, a Type I superluminous supernova at z = 0.213 that displayed unique photometric and spectroscopic properties. Pan-STARRS and ZTF forced photometry show a pre-explosion plateau lasting ∼40 d. Unlike other SLSNe that show decreasing photospheric temperatures with time, the optical colours show an apparent temperature increase from ∼15 000 to ∼20 000 K over the first 70 d, likely caused by an additional pseudo-continuum in the spectrum. Remarkably, the spectrum displays a forbidden emission line (likely attributed to λλ7320,7330) visible 16 d before maximum light, inconsistent with an apparently compact photosphere. This identification is further strengthened by the appearances of [O III] λλ4959, 5007, and [O III] λ4363 seen in the spectrum. Comparing with nebular spectral models, we find that the oxygen line fluxes and ratios can be reproduced with ∼0.25 M☉ of oxygen-rich material with a density of ∼ 10−15 g cm−3. The low density suggests a circumstellar origin, but the early onset of the emission lines requires that this material was ejected within the final months before the terminal explosion, consistent with the timing of the precursor plateau. Interaction with denser material closer to the explosion likely produced the pseudo-continuum bluewards of ∼5500 Å. We suggest that this event is one of the best candidates to date for a pulsational pair-instability ejection, with early pulses providing the low density material needed for the formation of the forbidden emission line, and collisions between the final shells of ejected material producing the pre-explosion plateau

A Systematic Study of Ia-CSM Supernovae from the ZTF Bright Transient Survey

Among the supernovae (SNe) that show strong interaction with a circumstellar medium (CSM), there is a rare subclass of Type Ia supernovae, SNe Ia-CSM, which show strong narrow hydrogen emission lines much like SNe IIn but on top of a diluted Type Ia spectrum. The only previous systematic study of this class identified 16 SNe Ia-CSM, eight historic and eight from the Palomar Transient Factory (PTF). Now using the successor survey to PTF, the Zwicky Transient Facility (ZTF), we have classified 12 additional SNe Ia-CSM through the systematic Bright Transient Survey (BTS). Consistent with previous studies, we find these SNe to have slowly evolving optical light curves with peak absolute magnitudes between −19.1 and −21, spectra having weak Hβ and large Balmer decrements of ∼7. Out of the 10 SNe from our sample observed by NEOWISE, nine have 3σ detections, with some SNe showing a reduction in the red wing of Hα, indicative of newly formed dust. We do not find our SN Ia-CSM sample to have a significantly different distribution of equivalent widths of He i λ5876 than SNe IIn as observed in Silverman et al. The hosts tend to be late-type galaxies with recent star formation. We derive a rate estimate of 29 − 21 + 27 Gpc−3 yr−1 for SNe Ia-CSM, which is ∼0.02%-0.2% of the SN Ia rate. We also identify six ambiguous SNe IIn/Ia-CSM in the BTS sample and including them gives an upper limit rate of 0.07%-0.8%. This work nearly doubles the sample of well-studied Ia-CSM objects in Silverman et al., increasing the total number to 28

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer's disease, about the therapeutic strategies in Alzheimer's research

Experimental models that faithfully mimic the developmental pathology of sporadic Alzheimer's disease (sAD) in humans are important for testing the novel therapeutic approaches in sAD treatment. Widely used transgenic mice AD models have provided valuable insights into the molecular mechanisms underlying the memory decline but, due to the particular β-amyloid-related gene manipulation, they resemble the familial but not the sporadic AD form, and are, therefore, inappropriate for this purpose. In line with the recent findings of sAD being recognised as an insulin resistant brains state (IRBS), a new, non-transgenic, animal model has been proposed as a representative model of sAD, developed by intracerebroventricular application of the betacytotoxic drug streptozotocin (STZ-icv). The STZ-icv-treated animals (mostly rats and mice) develop IRBS associated with memory impairment and progressive cholinergic deficits, glucose hypometabolism, oxidative stress and neurodegeneration that share many features in common with sAD in humans. The therapeutic strategies (acetylcholinesterase inhibitors, antioxidants and many other drugs) that have been tested until now on the STZ-icv animal model have been reviewed and the comparability of the drugs' efficacy in this non-transgenic sAD model and the results from clinical trials on sAD patients, evaluated