Dwarf AGNs from Variability for the Origins of Seeds (DAVOS): Optical Variability of Broad-line Dwarf AGNs from the Zwicky Transient Facility

We study the optical variability of a sample of candidate low-mass (dwarf ang Seyfert) active galactic nuclei (AGNs) using Zwicky Transient Facility g-band light curves. Our sample is compiled from broad-line AGNs in dwarf galaxies reported in the literature with single-epoch virial black hole (BH) masses in the range $M_{\rm{BH}} \sim 10^{4}$--$10^{8}\ M_{\odot}$. We measure the characteristic ``damping'' timescale of the optical variability $\tau_{\rm{DRW}}$, beyond which the power spectral density flattens, of a final sample of 79 candidate low-mass AGNs with high-quality light curves. Our results provide further confirmation of the $M_{\rm{BH}} - \tau_{\rm{DRW}}$ relation from Burke et al. 2022 within $1\sigma$ agreement, adding 78 new low-mass AGNs to the relation. The agreement suggests that the virial BH mass estimates for these AGNs are generally reasonable. We expect that the optical light curve of an accreting intermediate-mass black hole (IMBH) to vary with a rest-frame damping timescale of $\sim$ tens of hours, which could enable detection and direct mass estimation of accreting IMBHs in wide-field time-domain imaging surveys with sufficient cadence like with the Vera C. Rubin Observatory.Comment: 9 pages plus 6 appendix, 7 figure

Possible large phase in psi(2S) -> 1-0- Decays

The strong and the electromagnetic amplitudes are analyzed on the basis of the measurements of J/psi, psi(2S) -> 1-0- in e+e- experiments. The currently available experimental information is revised with inclusion of the contribution from e+e- -> gamma * -> 1-0- . The study shows that a large phase around minus 90 degree between the strong and the electromagnetic amplitudes could not be ruled out by the experimental data for psi(2S).Comment: 4 page

Dwarf AGNs from Variability for the Origins of Seeds (DAVOS): Intermediate-mass black hole demographics from optical synoptic surveys

We present a phenomenological forward Monte Carlo model for forecasting the population of active galactic nuclei (AGNs) in dwarf galaxies observable via their optical variability. Our model accounts for expected changes in the spectral energy distribution of AGNs in the intermediate-mass black hole (IMBH) mass range and uses observational constraints on optical variability as a function of black hole (BH) mass to generate mock light curves. Adopting several different models for the BH occupation function, including one for off-nuclear IMBHs, we quantify differences in the predicted local AGN mass and luminosity functions in dwarf galaxies. As a result, we are able to model the variable fraction of AGNs as a function of physical host properties, such as host galaxy stellar mass, in the presence of complex selection effects. We find that our adopted occupation fractions for the "heavy" and "light" initial BH seeding scenarios can be distinguished with variability data at the $2-3 \sigma$ level for galaxy host stellar masses below $\sim 10^8 M_\odot$ with the Vera C. Rubin Observatory. We demonstrate the prevalence of a selection bias whereby recovered IMBH masses fall, on average, above the predicted value from the local host galaxy - BH mass scaling relation with the strength of the bias dependent on the survey sensitivity. The methodology developed in this work can be used more broadly to forecast and correct for selection effects for AGN demographic studies in synoptic surveys. Finally, we show that a targeted $\sim$ hourly cadence program over a few nights with the Rubin Observatory can provide strong constraints on IMBH masses given their expected rapid variability timescales.Comment: 26 pages, 16 figures incl. 5 appendices; re-submitted to MNRAS following referee repor

Mitochondrial Ca(2+) uptake by the voltage-dependent anion channel 2 regulates cardiac rhythmicity.

Tightly regulated Ca(2+) homeostasis is a prerequisite for proper cardiac function. To dissect the regulatory network of cardiac Ca(2+) handling, we performed a chemical suppressor screen on zebrafish tremblor embryos, which suffer from Ca(2+) extrusion defects. Efsevin was identified based on its potent activity to restore coordinated contractions in tremblor. We show that efsevin binds to VDAC2, potentiates mitochondrial Ca(2+) uptake and accelerates the transfer of Ca(2+) from intracellular stores into mitochondria. In cardiomyocytes, efsevin restricts the temporal and spatial boundaries of Ca(2+) sparks and thereby inhibits Ca(2+) overload-induced erratic Ca(2+) waves and irregular contractions. We further show that overexpression of VDAC2 recapitulates the suppressive effect of efsevin on tremblor embryos whereas VDAC2 deficiency attenuates efsevin\u27s rescue effect and that VDAC2 functions synergistically with MCU to suppress cardiac fibrillation in tremblor. Together, these findings demonstrate a critical modulatory role for VDAC2-dependent mitochondrial Ca(2+) uptake in the regulation of cardiac rhythmicity

Delayed Wound Closure in Fibromodulin-Deficient Mice Is Associated with Increased TGF-β3 Signaling

Fibromodulin (FMOD), a small leucine-rich proteoglycan, mediates scarless fetal skin wound repair through, in part, transforming growth factor-Β (TGF-Β) modulation. Using an adult fmod-null (fmod -/-) mouse model, this study further elucidates the interplay between FMOD and TGF-Β expression during cutaneous repair and scar formation. Full-thickness skin wounds on fmod -/- and wild-type (WT) mice were closed primarily and analyzed. Histomorphometry revealed delayed dermal cell migration leading to delayed wound closure and significantly increased scar size in fmod -/- mice relative to WT, which was partially rescued by exogenous FMOD administration. In addition, fmod -/- wounds exhibited early elevation (within 24 hours post-wounding) of type I and type II TGF-Β receptors as well as unexpectedly high fibroblast expression of TGF-Β3, a molecule with reported antifibrotic and antimigratory effects. Consistent with elevated fibroblastic TGF-Β3, fmod -/- fibroblasts were significantly less motile than WT fibroblasts. fmod -/- fibroblasts were also more susceptible to migration inhibition by TGF-Β3, leading to profound delays in dermal cell migration. Increased scarring in fmod -/- mice indicates that TGF-Β3\u27s antimotility effects predominate over its antifibrotic effects when high TGF-Β3 levels disrupt early fibroblastic wound ingress. These studies demonstrate that FMOD presence is critical for proper temporospatial coordination of wound healing events and normal TGF-Β bioactivity. © 2011 The Society for Investigative Dermatology

Measurements of ψ(2S)\psi(2S) decays into Vector- Tensor final states

Decays of the $\psi(2S)$ into vector plus tensor meson final states have been studied with 14 million $\psi(2S)$ events collected with the BESII detector. Branching fractions of \psi(2S) \rt \omega f_{2}(1270), $\rho a_2(1320)$, $K^*(892)^0\bar{K}^*_2(1430)^0+c.c.$ and $\phi f_2^{\prime}(1525)$ are determined. They improve upon previous BESI results and confirm the violation of the "12%" rule for $\psi(2S)$ decays to VT channels with higher precision.Comment: 7 pages, 7 figures and 2 table

Measurement of ψ(2S)\psi(2S) decays to baryon pairs

A sample of 3.95M $\psi(2S)$ decays registered in the BES detector are used to study final states containing pairs of octet and decuplet baryons. We report branching fractions for $\psi(2S)\to p\bar{p}$, $\Lambda\bar{\Lambda}$, $\Sigma^0\bar{\Sigma}{}^0$, $\Xi^-\bar{\Xi}{}^+$, $\Delta^{++}\bar{\Delta}{}^{--}$, $\Sigma^+(1385)\bar{\Sigma}{}^-(1385)$, $\Xi^0(1530)\bar{\Xi}{}^0(1530)$, and $\Omega^-\bar{\Omega}{}^+$. These results are compared to expectations based on the SU(3)-flavor symmetry, factorization, and perturbative QCD.Comment: 22 pages, 21 figures, 4 table

The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

LncRNA GAS5 inhibits microglial M2 polarization and exacerbates demyelination

The regulation of inflammation is pivotal for preventing the development or reoccurrence of multiple sclerosis (MS). A biased ratio of high-M1 versus low-M2 polarized microglia is a major pathological feature of MS Here, using microarray screening, we identify the long noncoding RNA (lncRNA) GAS5 as an epigenetic regulator of microglial polarization. Gain- and loss-of-function studies reveal that GAS5 suppresses microglial M2 polarization. Interference with GAS5 in transplanted microglia attenuates the progression of experimental autoimmune encephalomyelitis (EAE) and promotes remyelination in a lysolecithin-induced demyelination model. In agreement, higher levels of GAS5 are found in amoeboid-shaped microglia in MS patients. Further, functional studies demonstrate that GAS5 suppresses transcription of TRF4, a key factor controlling M2 macrophage polarization, by recruiting the polycomb repressive complex 2 (PRC2), thereby inhibiting M2 polarization. Thus, GAS5 may be a promising target for the treatment of demyelinating diseases.Research in the author’s laboratory is supported by the National Natural Science Foundation of China (81461138035, 31130024, 81371326, 31371068, 31571066) and core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute