Fasting enhances pyroglutamyl peptidase II activity in tanycytes of the mediobasal hypothalamus of male adult rats

Fasting down-regulates the hypothalamus-pituitary-thyroid (HPT) axis activity through a reduction of TRH synthesis in neurons of the parvocellular paraventricular nucleus of the hypothalamus (PVN). These TRH neurons project to the median eminence (ME), where TRH terminals are close to the cytoplasmic extensions of β2 tanycytes. Tanycytes express pyroglutamyl peptidase II (PPII), the TRH-degrading ectoenzyme that controls the amount of TRH that reaches the anterior pituitary. We tested the hypothesis that regulation of ME PPII activity is another mechanism by which fasting affects the activity of the HPT axis. Semiquantitative in situ hybridization histochemistry data indicated that PPII and deiodinase 2 mRNA levels increased in tanycytes after 48 hours of fasting. This increase was transitory, followed by an increase of PPII activity in the ME, and a partial reversion of the reduction in PVN pro-TRH mRNA levels and the number of TRH neurons detected by immunohistochemistry. In fed animals, adrenalectomy and corticosterone treatment did not change ME PPII activity 72 hours later. Methimazole-induced hypothyroidism produced a profound drop in tanycytes PPII mRNA levels, which was reverted by 3 days of treatment with T4. The activity of thyroliberinase, the serum isoform of PPII, was increased at most fasting time points studied. We conclude that delayed increases in both the ME PPII as well as the thyroliberinase activities in fasted male rats may facilitate the maintenance of the deep down-regulation of the HPT axis function, despite a partial reactivation of TRH expression in the PVN

Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition

Acknowledgments This work was funded in part by the William and Melinda Gates Foundation, award 42917 to JPN and OCS; US National Institutes of Health grants 5R01HG005220 to HCB, 5R01HG004885 to MP; US National Science Foundation Graduate Research Fellowship award DGE0750616 to JNP; AWW and JP are funded by The Wellcome Trust (Grant No. WT098051).Peer reviewedPublisher PD

Novel temperatures are already widespread beneath the world’s tropical forest canopies

Tropical forest biodiversity is potentially at high risk from climate change, but most species reside within or below the canopy, where they are buffered from extreme temperatures. Here, by modelling the hourly below-canopy climate conditions of 300,000 tropical forest locations globally between 1990 and 2019, we show that recent small increases in below-canopy temperature (<1 °C) have led to highly novel temperature regimes across most of the tropics. This is the case even within contiguous forest, suggesting that tropical forests are sensitive to climate change. However, across the globe, some forest areas have experienced relatively non-novel temperature regimes and thus serve as important climate refugia that require urgent protection and restoration. This pantropical analysis of changes in below-canopy climatic conditions challenges the prevailing notion that tropical forest canopies reduce the severity of climate change impacts

Luminous Type II Short-Plateau Supernovae 2006Y, 2006ai, and 2016egz: A Transitional Class from Stripped Massive Red Supergiants

The diversity of Type II supernovae (SNe II) is thought to be driven mainly by differences in their progenitor's hydrogen-rich (H-rich) envelope mass, with SNe IIP having long plateaus ($\sim100$ days) and the most massive H-rich envelopes. However, it is an ongoing mystery why SNe II with short plateaus (tens of days) are rarely seen. Here we present optical/near-infrared photometric and spectroscopic observations of luminous Type II short-plateau SNe 2006Y, 2006ai, and 2016egz. Their plateaus of about $50$--$70$ days and luminous optical peaks ($\lesssim-18.4$ mag) indicate significant pre-explosion mass loss resulting in partially-stripped H-rich envelopes and early circumstellar material (CSM) interaction. We compute a large grid of MESA+STELLA single-star progenitor and light-curve models with various progenitor zero-age main-sequence (ZAMS) masses, mass-loss efficiencies, explosion energies, $^{56}$Ni masses, and CSM densities. Our model grid shows a continuous population of SNe IIP--IIL--IIb-like light-curve morphology in descending order of H-rich envelope mass. With large $^{56}$Ni masses ($\gtrsim0.05\,M_\odot$), short-plateau SNe II lie in a confined parameter space as a transitional class between SNe IIL and IIb. For SNe 2006Y, 2006ai, and 2016egz, our findings suggest high-mass red supergiant (RSG) progenitors ($M_{\rm ZAMS} \simeq 18$--$22\,M_{\odot}$) with small H-rich envelope masses ($M_{\rm H_{\rm env}} \simeq 1.7\,M_{\odot}$) that experience enhanced mass loss ($\dot{M} \simeq 10^{-2}\,M_{\odot}\,{\rm yr}^{-1}$) for the last few decades before the explosion. If high-mass RSGs result in rare short-plateau SNe II, then these events might ease some of the apparent under-representation of higher-luminosity RSGs in observed SN II progenitor samples.Comment: 26 pages, 16 figures, submitted to Ap

SN 2021zny: an early flux excess combined with late-time oxygen emission suggests a double white dwarf merger event

We present a photometric and spectroscopic analysis of the ultra-luminous and slowly evolving 03fg-like Type Ia SN 2021zny. Our observational campaign starts from $\sim5.3$ hours after explosion (making SN 2021zny one of the earliest observed members of its class), with dense multi-wavelength coverage from a variety of ground- and space-based telescopes, and is concluded with a nebular spectrum $\sim10$ months after peak brightness. SN 2021zny displayed several characteristics of its class, such as the peak brightness ($M_{B}=-19.95$ mag), the slow decline ($\Delta m_{15}(B) = 0.62$ mag), the blue early-time colours, the low ejecta velocities and the presence of significant unburned material above the photosphere. However, a flux excess for the first $\sim1.5$ days after explosion is observed in four photometric bands, making SN 2021zny the third 03fg-like event with this distinct behavior, while its $+313$ d spectrum shows prominent [O I] lines, a very unusual characteristic of thermonuclear SNe. The early flux excess can be explained as the outcome of the interaction of the ejecta with $\sim0.04\:\mathrm{M_{\odot}}$ of H/He-poor circumstellar material at a distance of $\sim10^{12}$ cm, while the low ionization state of the late-time spectrum reveals low abundances of stable iron-peak elements. All our observations are in accordance with a progenitor system of two carbon/oxygen white dwarfs that undergo a merger event, with the disrupted white dwarf ejecting carbon-rich circumstellar material prior to the primary white dwarf detonation.Comment: 19 pages, 16 figures, accepted for publication in MNRA

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death