Stress can exert long-lasting changes on the brain that contribute to vulnerability to mental illness, yet mechanisms underlying this long-term vulnerability are not well understood. We hypothesized ...that stress may alter the production of oligodendrocytes in the adult brain, providing a cellular and structural basis for stress-related disorders. We found that immobilization stress decreased neurogenesis and increased oligodendrogenesis in the dentate gyrus (DG) of the adult rat hippocampus and that injections of the rat glucocorticoid stress hormone corticosterone (cort) were sufficient to replicate this effect. The DG contains a unique population of multipotent neural stem cells (NSCs) that give rise to adult newborn neurons, but oligodendrogenic potential has not been demonstrated in vivo. We used a nestin-CreER/YFP transgenic mouse line for lineage tracing and found that cort induces oligodendrogenesis from nestin-expressing NSCs in vivo. Using hippocampal NSCs cultured in vitro, we further showed that exposure to cort induced a pro-oligodendrogenic transcriptional program and resulted in an increase in oligodendrogenesis and decrease in neurogenesis, which was prevented by genetic blockade of glucocorticoid receptor (GR). Together, these results suggest a novel model in which stress may alter hippocampal function by promoting oligodendrogenesis, thereby altering the cellular composition and white matter structure.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We present constraints on the progenitor metallicities of core-collapse supernovae. To date, nearly all metallicity constraints have been inferred from indirect methods such as metallicity gradients ...in host galaxies, luminosities of host galaxies or derived global galaxy metallicities. Here, progenitor metallicities are derived from optical spectra taken at the sites of nearby supernovae, from the ratio of strong emission lines found in their host H ii regions. We present results from the spectra of 74 host H ii regions and discuss the implications that these have on the nature of core-collapse supernova progenitors. Overall, while we find that the mean metallicity of Type Ibc environments is higher than that of Type II events, this difference is smaller than observed in previous studies. There is only a 0.06 dex difference in the mean metallicity values, at a statistical significance of ∼1.5σ, while using a Kolmogorov–Smirnov test we find that the two metallicity distributions are marginally consistent with being drawn from the same parent population (probability >10 per cent). This argues that progenitor metallicity is not a dominant parameter in deciding supernovae type, with progenitor mass and/or binarity playing a much more significant role. The mean derived oxygen metallicities 12+log(O/H) for the different supernova types, on the Pettini & Pagel scale, are 8.580 (standard error on the mean of 0.027) for the 46 Type II supernovae (dominated by Type II plateau), 8.616 (0.040) for 10 Type Ib and 8.626 (0.039) for 14 Type Ic. Overall, the Type Ibc supernovae have a mean metallicity of 8.635 (0.026, 27 supernovae). Hence, we find a slight suggestion of a metallicity sequence, in terms of increasing progenitor metallicity going from Type II through Ib and finally Ic supernovae arising from the highest metallicity progenitors. Finally we discuss these results in the context of all current literature progenitor metallicity measurements, and discuss biases and selection effects that may affect the current sample compared to overall supernova and galaxy samples.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
We present DES13S2cmm, the first spectroscopically-confirmed superluminous supernova (SLSN) from the Dark Energy Survey (DES). We briefly discuss the data and search algorithm used to find this event ...in the first year of DES operations, and outline the spectroscopic data obtained from the European Southern Observatory (ESO) Very Large Telescope to confirm its redshift (z = 0.663 ± 0.001 based on the host-galaxy emission lines) and likely spectral type (Type I). Using this redshift, we find
$M^{\rm peak}_U=-21.05^{+0.10}_{-0.09}$
for the peak, rest-frame U-band absolute magnitude, and find DES13S2cmm to be located in a faint, low-metallicity (sub-solar), low stellar-mass host galaxy (log (M/M⊙) = 9.3 ± 0.3), consistent with what is seen for other SLSNe-I. We compare the bolometric light curve of DES13S2cmm to 14 similarly well-observed SLSNe-I in the literature and find that it possesses one of the slowest declining tails (beyond +30 d rest-frame past peak), and is the faintest at peak. Moreover, we find the bolometric light curves of all SLSNe-I studied herein possess a dispersion of only 0.2–0.3 mag between +25 and +30 d after peak (rest frame) depending on redshift range studied; this could be important for ‘standardizing’ such supernovae, as is done with the more common Type Ia. We fit the bolometric light curve of DES13S2cmm with two competing models for SLSNe-I – the radioactive decay of 56Ni, and a magnetar – and find that while the magnetar is formally a better fit, neither model provides a compelling match to the data. Although we are unable to conclusively differentiate between these two physical models for this particular SLSN-I, further DES observations of more SLSNe-I should break this degeneracy, especially if the light curves of SLSNe-I can be observed beyond 100 d in the rest frame of the supernova.
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease, where even surgical resection and aggressive chemotherapy produce dismal outcomes. Immunotherapy is a promising alternative to ...conventional treatments, possessing the ability to elicit T cell-mediated killing of tumor cells and prevent disease recurrence. Immunotherapeutic approaches thus far have seen limited success in PDAC due to a poorly immunogenic and exceedingly immunosuppressive tumor microenvironment, which is enriched with dysfunctional and immunosuppressed antigen-presenting cells (APCs). We developed a highly potent immunostimulatory nanoparticle (immuno-NP) to activate and expand APCs in the tumor and induce local secretion of interferon β (IFNβ), which is a pro-inflammatory cytokine that plays a major role in APC recruitment. The effectiveness of the immuno-NP stems from its dual cargo of two synergistic immune modulators consisting of an agonist of the stimulator of interferon genes (STING) pathway and an agonist of the Toll-like receptor 4 (TLR4) pathway. We show the functional synergy of the dual-agonist cargo can be tweaked by adjusting the ratio of the two agonists loaded in the immuno-NP, leading to an increase in IFNβ production (11-fold) compared to any single agonist immuno-NP variant. Using the orthotopic murine Panc02 model of PDAC, we show that systemic administration allowed immuno-NPs to deposit into the perivascular regions of the tumor, which coincided with the APC-rich tumor areas leading to predominant uptake of immuno-NPs by APCs. The immuno-NPs were effectively taken up by a significant portion of dendritic cells in the tumor (>56%). This led to a significant expansion of APCs, resulting in an 11.5-fold increase of dendritic cells and infiltration of lymphocytes throughout the pancreatic tumor compared to untreated animals.
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•Nanoparticle is loaded with two potent innate immune agonists.•The dual-agonist cargo provides remarkable functional synergy.•Systemic delivery enables uptake by APCs in perivascular regions of tumors.•Significant activation and expansion of APCs in pancreatic tumor.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Impaired regulation of emotional memory is a feature of several affective disorders, including depression, anxiety and post-traumatic stress disorder. Such regulation occurs, in part, by interactions ...between the hippocampus and the basolateral amygdala (BLA). Recent studies have indicated that within the adult hippocampus, newborn neurons may contribute to support emotional memory, and that regulation of hippocampal neurogenesis is implicated in depressive disorders. How emotional information affects newborn neurons in adults is not clear. Given the role of the BLA in hippocampus-dependent emotional memory, we investigated whether hippocampal neurogenesis was sensitive to emotional stimuli from the BLA. We show that BLA lesions suppress adult neurogenesis, while lesions of the central nucleus of the amygdala do not. Similarly, we show that reducing BLA activity through viral vector-mediated overexpression of an outwardly rectifying potassium channel suppresses neurogenesis. We also show that BLA lesions prevent selective activation of immature newborn neurons in response to a fear-conditioning task. These results demonstrate that BLA activity regulates adult hippocampal neurogenesis and the fear context-specific activation of newborn neurons. Together, these findings denote functional implications for proliferation and recruitment of new neurons into emotional memory circuits.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
ABSTRACT We report the discovery of eight new Milky Way companions in of optical imaging data collected during the first year of the Dark Energy Survey (DES). Each system is identified as a ...statistically significant over-density of individual stars consistent with the expected isochrone and luminosity function of an old and metal-poor stellar population. The objects span a wide range of absolute magnitudes (MV from to ), physical sizes ( ), and heliocentric distances ( ). Based on the low surface brightnesses, large physical sizes, and/or large Galactocentric distances of these objects, several are likely to be new ultra-faint satellite galaxies of the Milky Way and/or Magellanic Clouds. We introduce a likelihood-based algorithm to search for and characterize stellar over-densities, as well as identify stars with high satellite membership probabilities. We also present completeness estimates for detecting ultra-faint galaxies of varying luminosities, sizes, and heliocentric distances in the first-year DES data.
ABSTRACT We describe the operation and performance of the difference imaging pipeline (DiffImg) used to detect transients in deep images from the Dark Energy Survey Supernova program (DES-SN) in its ...first observing season from 2013 August through 2014 February. DES-SN is a search for transients in which ten 3 deg2 fields are repeatedly observed in the g, r, i, z passbands with a cadence of about 1 week. The observing strategy has been optimized to measure high-quality light curves and redshifts for thousands of Type Ia supernovae (SNe Ia) with the goal of measuring dark energy parameters. The essential DiffImg functions are to align each search image to a deep reference image, do a pixel-by-pixel subtraction, and then examine the subtracted image for significant positive detections of point-source objects. The vast majority of detections are subtraction artifacts, but after selection requirements and image filtering with an automated scanning program, there are ∼130 detections per deg2 per observation in each band, of which only ∼25% are artifacts. Of the ∼7500 transients discovered by DES-SN in its first observing season, each requiring a detection on at least two separate nights, Monte Carlo (MC) simulations predict that 27% are expected to be SNe Ia or core-collapse SNe. Another ∼30% of the transients are artifacts in which a small number of observations satisfy the selection criteria for a single-epoch detection. Spectroscopic analysis shows that most of the remaining transients are AGNs and variable stars. Fake SNe Ia are overlaid onto the images to rigorously evaluate detection efficiencies and to understand the DiffImg performance. The DiffImg efficiency measured with fake SNe agrees well with expectations from a MC simulation that uses analytical calculations of the fluxes and their uncertainties. In our 8 "shallow" fields with single-epoch 50% completeness depth ∼23.5, the SN Ia efficiency falls to 1/2 at redshift z 0.7; in our 2 "deep" fields with mag-depth ∼24.5, the efficiency falls to 1/2 at z 1.1. A remaining performance issue is that the measured fluxes have additional scatter (beyond Poisson fluctuations) that increases with the host galaxy surface brightness at the transient location. This bright-galaxy issue has minimal impact on the SNe Ia program, but it may lower the efficiency for finding fainter transients on bright galaxies.
ABSTRACT We describe an algorithm for identifying point-source transients and moving objects on reference-subtracted optical images containing artifacts of processing and instrumentation. The ...algorithm makes use of the supervised machine learning technique known as Random Forest. We present results from its use in the Dark Energy Survey Supernova program (DES-SN), where it was trained using a sample of 898,963 signal and background events generated by the transient detection pipeline. After reprocessing the data collected during the first DES-SN observing season (2013 September through 2014 February) using the algorithm, the number of transient candidates eligible for human scanning decreased by a factor of 13.4, while only 1.0% of the artificial Type Ia supernovae (SNe) injected into search images to monitor survey efficiency were lost, most of which were very faint events. Here we characterize the algorithm's performance in detail, and we discuss how it can inform pipeline design decisions for future time-domain imaging surveys, such as the Large Synoptic Survey Telescope and the Zwicky Transient Facility. An implementation of the algorithm and the training data used in this paper are available at at http://portal.nersc.gov/project/dessn/autoscan.
Background:
Chronic kidney disease (CKD) is a global health problem. As it progresses to end stages, renal replacement therapy is required but ultimately, the best treatment is transplantation. ...Decreased renal function has been associated with an inflammatory state associated to primary CKD and in kidney transplant recipients (KTRs).
Objective:
To establish how the serum concentrations of some cytokines, such as interleukin (IL)-2, IL-8, IL-22, IL-17α, interferon-gamma, IL-4, and transforming growth factor-β, correlate with various CKD stages.
Methods:
One hundred and forty-one KTRs between the ages of 18 and 75 years were included in the study. We also included 112 live kidney donors, 37 CKD PGCKD+3, and 76 GPhealthy. Participants were grouped according to their glomerular filtration rate (GFR) and their circulating cytokine levels, previously quantified by ELISA.
Results:
By linear regression analysis, we established the relation of each cytokine with the GFR. Transforming growth factor-β correlated positively with the GFR in the study population, except in healthy individuals. A negative correlation of IL-8 and IL-17α and GFR was found in all cases.
Conclusions:
Whether these cytokines (IL-8 and IL-17α) could be used as inflammatory biomarkers indicating CKD progression, regardless of the type of population, remains to be prospectively determined.
The Australian Dark Energy Survey (OzDES) is a five-year, 100-night, spectroscopic survey on the Anglo-Australian Telescope, whose primary aim is to measure redshifts of approximately 2500 Type Ia ...supernovae host galaxies over the redshift range 0.1 < z < 1.2, and derive reverberation-mapped black hole masses for approximately 500 active galactic nuclei and quasars over 0.3 < z < 4.5. This treasure trove of data forms a major part of the spectroscopic follow-up for the Dark Energy Survey for which we are also targeting cluster galaxies, radio galaxies, strong lenses, and unidentified transients, as well as measuring luminous red galaxies and emission line galaxies to help calibrate photometric redshifts. Here, we present an overview of the OzDES programme and our first-year results. Between 2012 December and 2013 December, we observed over 10 000 objects and measured more than 6 000 redshifts. Our strategy of retargeting faint objects across many observing runs has allowed us to measure redshifts for galaxies as faint as mr
= 25 mag. We outline our target selection and observing strategy, quantify the redshift success rate for different types of targets, and discuss the implications for our main science goals. Finally, we highlight a few interesting objects as examples of the fortuitous yet not totally unexpected discoveries that can come from such a large spectroscopic survey.
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