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Early life adverse experiences, including childhood maltreatment, are major risk factors for psychopathology, including anxiety disorders with dysregulated fear responses. Consistent with human studies, maltreatment by the mother (MALT) leads to increased emotional reactivity in rhesus monkey infants. Whether this persists and results in altered emotion regulation, due to enhanced fear learning or impaired utilization of safety signals as shown in human stress-related disorders, is unclear. Here we used a rhesus model of MALT to examine long-term effects on state anxiety and threat/safety learning in 25 adolescents, using a fear conditioning paradigm (AX+/BX-) with acoustic startle amplitude as the peripheral measure. The AX+/BX- paradigm measures baseline startle, fear-potentiated startle, threat/safety cue discrimination, startle attenuation by safety signals, and extinction. Baseline startle was higher in MALT animals, suggesting elevated state anxiety. No differences in threat learning, or threat/safety discrimination were detected. However, MALT animals showed generalized blunted responses to the conditioned threat cue, regardless of the safety cue presence in the transfer test, and took longer to extinguish spontaneously recovered threat. These findings suggest adverse caregiving experiences have long-term impacts on adolescent emotion regulation, including elevated state anxiety and blunted fear conditioning responses, consistent with reports in children with maltreatment exposure.

The first James Webb Space Telescope (JWST) Near InfraRed Camera imaging in the field of the galaxy cluster PLCK G165.7+67.0 ( z = 0.35) uncovered a Type Ia supernova (SN Ia) at z = 1.78, called “SN H0pe.” Three different images of this one SN were detected as a result of strong gravitational lensing, each one traversing a different path in spacetime, thereby inducing a relative delay in the arrival of each image. Follow-up JWST observations of all three SN images enabled photometric and rare spectroscopic measurements of the two relative time delays. Following strict blinding protocols which oversaw a live unblinding and regulated postunblinding changes, these two measured time delays were compared to the predictions of seven independently constructed cluster lens models to measure a value for the Hubble constant, H _0 = 71.8 + 9.2 − 8.1 km s ^−1 Mpc ^−1 . The range of admissible H _0 values predicted across the lens models limits further precision, reflecting the well-known degeneracies between lens model constraints and time delays. It has long been theorized that a way forward is to leverage a standard candle, but this has not been realized until now. For the first time, the lens models are evaluated by their agreement with the SN absolute magnifications, breaking degeneracies and producing our best estimate, H _0 = ${75.7}_{-5.5}^{+8.1}$ km s ^−1 Mpc ^−1 . This is the first precise measurement of H _0 from a multiply imaged SN Ia and only the second from any multiply imaged SN.

We present multiwavelength data of SN 2020acct, a double-peaked stripped-envelope supernova (SN) in NGC 2981 at ∼150 Mpc. The two peaks are temporally distinct, with maxima separated by 58 rest-frame days and a factor of 20 reduction in flux between. The first is luminous ( M _r = −18.00 ± 0.02 mag) and blue ( g − r = 0.27 ± 0.03 mag) and displays spectroscopic signatures of interaction with hydrogen-free circumstellar material. The second peak is fainter ( M _r = −17.29 ± 0.03 mag) and has some spectroscopic similarities to an evolved stripped-envelope SN, with strong forbidden [Ca ii ] and [O ii ] features. No other known double-peaked SN exhibits a light curve similar to that of SN 2020acct. We find the likelihood of two individual SNe occurring in the same star-forming region within that time to be highly improbable, while an implausibly fine-tuned configuration would be required to produce two SNe from a single binary system. We find that the peculiar properties of SN 2020acct match models of pulsational pair instability (PPI), in which the initial peak is produced by collisions of shells of ejected material, shortly followed by core collapse. Pulsations from a star with a 72 M _⊙ helium core provide an excellent match to the double-peaked light curve. The local galactic environment has a metallicity of 0.4 Z _⊙ , a level where massive single stars are not expected to retain enough mass to encounter the PPI. However, late binary mergers or a low-metallicity pocket may allow the required core mass. We measure the rate of SN 2020acct–like events to be

We present a comprehensive analysis of the photometric and spectroscopic evolution of SN 2021foa, unique among the class of transitional supernovae for repeatedly changing its spectroscopic appearance from hydrogen-to-helium-to-hydrogen dominated (IIn-to-Ibn-to-IIn) within 50 days past peak brightness. The spectra exhibit multiple narrow (≈300–600 km s ^−1 ) absorption lines of hydrogen, helium, calcium, and iron together with broad helium emission lines with a full width at half-maximum (FWHM) of ∼6000 km s ^−1 . For a steady, wind mass-loss regime, light-curve modeling results in an ejecta mass of ∼8 M _⊙ and circumstellar material (CSM) mass below 1 M _⊙ , and an ejecta velocity consistent with the FWHM of the broad helium lines. We obtain a mass-loss rate of ≈2 M _⊙ yr ^−1 . This mass-loss rate is 3 orders of magnitude larger than derived for normal Type II supernovae. We estimate that the bulk of the CSM of SN 2021foa must have been expelled within half a year, about 12 yr ago. Our analysis suggests that SN 2021foa had a helium-rich ejecta that swept up a dense shell of hydrogen-rich CSM shortly after explosion. At about 60 days past peak brightness, the photosphere recedes through the dense ejecta-CSM region, occulting much of the redshifted emission of the hydrogen and helium lines, which results in an observed blueshift (∼−3000 km s ^−1 ). Strong mass-loss activity prior to explosion, such as those seen in SN 2009ip-like objects and SN 2021foa as precursor emission, are the likely origin of a complex, multiple-shell CSM close to the progenitor star.

The AGN STORM 2 Collaboration targeted the Seyfert 1 galaxy Mrk 817 for a year-long multiwavelength, coordinated reverberation mapping campaign including Hubble Space Telescope, Swift, XMM-Newton, NICER, and ground-based observatories. Early observations with NICER and XMM revealed an X-ray state 10 times fainter than historical observations, consistent with the presence of a new dust-free, ionized obscurer. The following analysis of NICER spectra attributes variability in the observed X-ray flux to changes in both the column density of the obscurer by at least one order of magnitude ( N _H ranges from ${2.85}_{-0.33}^{+0.48}\times {10}^{22}\,{\mathrm{cm}}^{-2}$ to ${25.6}_{-3.5}^{+3.0}\times {10}^{22}\,{\mathrm{cm}}^{-2}$ ) and the intrinsic continuum brightness (the unobscured flux ranges from 10 ^−11.8 to 10 ^−10.5 erg s ^−1 cm ^−2 ). While the X-ray flux generally remains in a faint state, there is one large flare during which Mrk 817 returns to its historical mean flux. The obscuring gas is still present at lower column density during the flare, but it also becomes highly ionized, increasing its transparency. Correlation between the column density of the X-ray obscurer and the strength of UV broad absorption lines suggests that the X-ray and UV continua are both affected by the same obscuration, consistent with a clumpy disk wind launched from the inner broad-line region.

We present reverberation mapping measurements for the prominent ultraviolet broad emission lines of the active galactic nucleus Mrk 817 using 165 spectra obtained with the Cosmic Origins Spectrograph on the Hubble Space Telescope. Our ultraviolet observations are accompanied by X-ray, optical, and near-infrared observations as part of the AGN Space Telescope and Optical Reverberation Mapping Program 2 (AGN STORM 2). Using the cross-correlation lag analysis method, we find significant correlated variations in the continuum and emission-line light curves. We measure rest-frame delayed responses between the far-ultraviolet continuum at 1180 Å and Ly α λ 1215 Å ( ${10.4}_{-1.4}^{+1.6}$ days), N v λ 1240 Å ( ${15.5}_{-4.8}^{+1.0}$ days), Si iv + ]O iv λ 1397 Å ( ${8.2}_{-1.4}^{+1.4}$ days), C iv λ 1549 Å ( ${11.8}_{-2.8}^{+3.0}$ days), and He ii λ 1640 Å ( ${9.0}_{-1.9}^{+4.5}$ days) using segments of the emission-line profile that are unaffected by absorption and blending, which results in sampling different velocity ranges for each line. However, we find that the emission-line responses to continuum variations are more complex than a simple smoothed, shifted, and scaled version of the continuum light curve. We also measure velocity-resolved lags for the Ly α and C iv emission lines. The lag profile in the blue wing of Ly α is consistent with virial motion, with longer lags dominating at lower velocities, and shorter lags at higher velocities. The C iv lag profile shows the signature of a thick rotating disk, with the shortest lags in the wings, local peaks at ±1500 km s ^−1 , and a local minimum at the line center. The other emission lines are dominated by broad absorption lines and blending with adjacent emission lines. These require detailed models, and will be presented in future work.

We present near-infrared (NIR) and optical observations of the Type Ic supernova (SN Ic) SN 2021krf obtained between days 13 and 259 at several ground-based telescopes. The NIR spectrum at day 68 exhibits a rising K -band continuum flux density longward of ∼2.0 μ m, and a late-time optical spectrum at day 259 shows strong [O i ] 6300 and 6364 Å emission-line asymmetry, both indicating the presence of dust, likely formed in the SN ejecta. We estimate a carbon-grain dust mass of ∼2 × 10 ^−5 M _⊙ and a dust temperature of ∼900–1200 K associated with this rising continuum and suggest the dust has formed in SN ejecta. Utilizing the one-dimensional multigroup radiation-hydrodynamics code STELLA, we present two degenerate progenitor solutions for SN 2021krf, characterized by C–O star masses of 3.93 and 5.74 M _⊙ , but with the same best-fit ^56 Ni mass of 0.11 M _⊙ for early times (0–70 days). At late times (70–300 days), optical light curves of SN 2021krf decline substantially more slowly than those expected from ^56 Co radioactive decay. Lack of H and He lines in the late-time SN spectrum suggests the absence of significant interaction of the ejecta with the circumstellar medium. We reproduce the entire bolometric light curve with a combination of radioactive decay and an additional powering source in the form of a central engine of a millisecond pulsar with a magnetic field smaller than that of a typical magnetar.

We present observations of a peculiar hydrogen- and helium-poor stripped-envelope (SE) supernova (SN) 2020wnt, primarily in the optical and near-infrared (near-IR). Its peak absolute bolometric magnitude of −20.9 mag ( L _bol, peak = (6.8 ± 0.3) × 10 ^43 erg s ^−1 ) and a rise time of 69 days are reminiscent of hydrogen-poor superluminous SNe (SLSNe I), luminous transients potentially powered by spinning-down magnetars. Before the main peak, there is a brief peak lasting

The unknown cause of the correlation between Type Ia supernova (SN Ia) Hubble residuals and their host-galaxy masses (the “mass step”) may bias cosmological parameter measurements. To better understand the mass step, we develop a SALT3 light-curve model for SN cosmology that uses the host-galaxy masses of 296 low-redshift SNe Ia to derive a spectral energy distribution–host-galaxy mass relationship. The resulting model has larger Ca ii H and K, Ca ii near-infrared triplet, and Si ii equivalent widths for SNe in low-mass host galaxies at 2.2–2.7 σ significance; this indicates higher explosion energies per unit mass in low-mass-hosted SNe. The model has phase-dependent changes in SN Ia colors as a function of host mass, indicating intrinsic differences in mean broadband light curves. Although the model provides a better fit to the SN data overall, it does not substantially reduce data–model residuals for a typical light curve in our sample nor does it significantly reduce Hubble residual dispersion. This is because we find that previous SALT models parameterized most host-galaxy dependencies with their first principal component, although they failed to model some significant spectral variations. Our new model is luminosity and cosmology independent, and applying it to data reduces the mass step by 0.021 ± 0.002 mag (uncertainty accounts for correlated data sets); these results indicate that ∼35% of the mass step can be attributed to luminosity-independent effects. This SALT model version could be trained using alternative host-galaxy properties and at different redshifts, and therefore will be a tool for understanding redshift-dependent correlations between SNe Ia and their host properties as well as their impact on cosmological parameter measurements.

The exact nature of the luminous fast blue optical transient AT 2018cow is still debated. In this first of a two-paper series, we present a detailed analysis of three Hubble Space Telescope (HST) observations of AT 2018cow covering ∼50–60 days post-discovery in combination with other observations throughout the first two months and derive significantly improved constraints of the late thermal properties. By modeling the spectral energy distributions (SEDs), we confirm that the UV–optical emission over 50–60 days was still a smooth blackbody (i.e., optically thick) with a high temperature ( T _BB ∼ 15,000 K) and small radius ( R _BB ≲ 1000 R _⊙ ). Additionally, we report for the first time a break in the bolometric light curve: the thermal luminosity initially declined at a rate of L _BB ∝ t ^−2.40 but faded much faster at t ^−3.06 after day 13. Reexamining possible late-time power sources, we disfavor significant contributions from radioactive decay based on the required ^56 Ni mass and lack of UV line blanketing in the HST SEDs. We argue that the commonly proposed interaction with circumstellar material may face significant challenges in explaining the late thermal properties, particularly the effects of the optical depth. Alternatively, we find that continuous outflow/wind driven by a central engine can still reasonably explain the combination of a receding photosphere, optically thick and rapidly fading emission, and intermediate-width lines. However, the rapid fading may have further implications on the power output and structure of the system. Our findings may support the hypothesis that AT 2018cow and other “Cow-like transients” are powered mainly by accretion onto a central engine.

Natural killer (NK) cells are important innate immune cells with diverse functions. Here the authors use single-cell RNA-sequencing of purified human bone marrow and peripheral blood NK cells to define five populations of NK cells with distinct transcriptomic profile to further our understanding of NK development and heterogeneity.

Abstract Background The spinal cord is limited in its capacity to repair after damage caused by injury or disease. However, propriospinal (PS) neurons in the spinal cord have demonstrated a propensity for axonal regeneration after spinal cord injury. They can regrow and extend axonal projections to re-establish connections across a spinal lesion. We have previously reported differential reactions of two distinct PS neuronal populations—short thoracic propriospinal (TPS) and long descending propriospinal tract (LDPT) neurons—following a low thoracic (T10) spinal cord injury in a rat model. Immediately after injury, TPS neurons undergo a strong initial regenerative response, defined by the upregulation of transcripts to several growth factor receptors, and growth associated proteins. Many also initiate a strong apoptotic response, leading to cell death. LDPT neurons, on the other hand, show neither a regenerative nor an apoptotic response. They show either a lowered expression or no change in genes for a variety of growth associated proteins, and these neurons survive for at least 2 months post-axotomy. There are several potential explanations for this lack of cellular response for LDPT neurons, one of which is the distance of the LDPT cell body from the T10 lesion. In this study, we examined the molecular response of LDPT neurons to axotomy caused by a proximal spinal cord lesion. Results Utilizing laser capture microdissection and RNA quantification with branched DNA technology, we analyzed the change in gene expression in LDPT neurons following axotomy near their cell body. Expression patterns of 34 genes selected for their robust responses in TPS neurons were analyzed 3 days following a T2 spinal lesion. Our results show that after axonal injury nearer their cell bodies, there was a differential response of the same set of genes evaluated previously in TPS neurons after proximal axotomy, and LDPT neurons after distal axotomy (T10 spinal transection). The genetic response was much less robust than for TPS neurons after proximal axotomy, included both increased and decreased expression of certain genes, and did not suggest either a major regenerative or apoptotic response within the population of genes examined. Conclusions The data collectively demonstrate that the location of axotomy in relation to the soma of a neuron has a major effect on its ability to mount a regenerative response. However, the data also suggest that there are endogenous differences in the LDPT and TPS neuronal populations that affect their response to axotomy. These phenotypic differences may indicate that different or multiple therapies may be needed following spinal cord injury to stimulate maximal regeneration of all PS axons.

The transcriptional activation and repression during NK cell ontology are poorly understood. Here, using single-cell RNA-sequencing, we reveal a novel role for T-bet in suppressing the immature gene signature during murine NK cell development. Based on transcriptome, we identified five distinct NK cell clusters and define their relative developmental maturity in the bone marrow. Transcriptome-based machine-learning classifiers revealed that half of the mTORC2-deficient NK cells belongs to the least mature NK cluster. Mechanistically, loss of mTORC2 results in an increased expression of signature genes representing immature NK cells. Since mTORC2 regulates the expression of T-bet through AktS473-FoxO1 axis, we further characterized the T-bet-deficient NK cells and found an augmented immature transcriptomic signature. Moreover, deletion of Foxo1 restores the expression of T-bet and corrects the abnormal expression of immature NK genes. Collectively, our study reveals a novel role for mTORC2-AktS473-FoxO1-T-bet axis in suppressing the transcriptional signature of immature NK cells.

Natural killer (NK) cells are innate lymphocytes that play essential roles in mediating antitumor immunity. NK cells respond to various inflammatory stimuli including cytokines and stress-induced cellular ligands which activate germline-encoded activation receptors (NKRs), such as NKG2D. The signaling molecules activated downstream of NKRs are well defined; however, the mechanisms that regulate these pathways are not fully understood. IQ domain-containing GTPase-activating protein 1 (IQGAP1) is a ubiquitously expressed scaffold protein. It regulates diverse cellular signaling programs in various physiological contexts, including immune cell activation and function. Therefore, we sought to investigate the role of IQGAP1 in NK cells. Development and maturation of NK cells from mice lacking IQGAP1 (Iqgap1−/−) were mostly intact; however, the absolute number of splenic NK cells was significantly reduced. Phenotypic and functional characterization revealed a significant reduction in the egression of NK cells from the bone marrow of Iqagp1−/− mice altering their peripheral homeostasis. Lack of IQGAP1 resulted in reduced NK cell motility and their ability to mediate antitumor immunity in vivo. Activation of Iqgap1−/− NK cells via NKRs, including NKG2D, resulted in significantly reduced levels of inflammatory cytokines compared with wild-type (WT). This reduction in Iqgap1−/− NK cells is neither due to an impaired membrane proximal signaling nor a defect in gene transcription. The levels of Ifng transcripts were comparable between WT and Iqgap1−/−, suggesting that IQGAP1-dependent regulation of cytokine production is regulated by a post-transcriptional mechanism. To this end, Iqgap1−/− NK cells failed to fully induce S6 phosphorylation and showed significantly reduced protein translation following NKG2D-mediated activation, revealing a previously undefined regulatory function of IQGAP1 via the mechanistic target of rapamycin complex 1. Together, these results implicate IQGAP1 as an essential scaffold for NK cell homeostasis and function and provide novel mechanistic insights to the post-transcriptional regulation of inflammatory cytokine production.

FOXC1 loss contributes to Dandy-Walker malformation (DWM), a common human cerebellar malformation. Previously, we found that complete Foxc1 loss leads to aberrations in proliferation, neuronal differentiation and migration in the embryonic mouse cerebellum (Haldipur et al., 2014). We now demonstrate that hypomorphic Foxc1 mutant mice have granule and Purkinje cell abnormalities causing subsequent disruptions in postnatal cerebellar foliation and lamination. Particularly striking is the presence of a partially formed posterior lobule which echoes the posterior vermis DW 'tail sign' observed in human imaging studies. Lineage tracing experiments in Foxc1 mutant mouse cerebella indicate that aberrant migration of granule cell progenitors destined to form the posterior-most lobule causes this unique phenotype. Analyses of rare human del chr 6p25 fetal cerebella demonstrate extensive phenotypic overlap with our Foxc1 mutant mouse models, validating our DWM models and demonstrating that many key mechanisms controlling cerebellar development are likely conserved between mouse and human.