The diversity of Type II supernova versus the similarity in their progenitors

High-quality collections of Type II supernova (SN) light curves are scarce because they evolve for hundreds of days, making follow-up observations time consuming and often extending over multiple observing seasons. In light of these difficulties, the diversity of SNe II is not fully understood. Here we present ultraviolet and optical photometry of 12 SNe II monitored by the Las Cumbres Observatory Global Telescope Network during 2013 to 2014, and compare them with previously studied SNe having well-sampled light curves. We explore SN II diversity by searching for correlations between the slope of the linear light-curve decay after maximum light (historically used to divide SNe II into IIL and IIP) and other measured physical properties. While SNe IIL are found to be on average more luminous than SNe IIP, SNe IIL do not appear to synthesize more $^{56}$Ni than SNe IIP. Finally, optical nebular spectra obtained for several SNe in our sample are found to be consistent with models of red supergiant progenitors in the 12–16 M$_{⊙}$ range. Consequently, SNe IIL appear not to account for the deficit of massive red supergiants as SN II progenitors.The authors acknowledge the ASASSN, La Silla Quest, and LOSS surveys for discovering new SNe that made this study possible. This material is based upon work supported by the National Science Foundation (NSF) under Grant No. 1313484. MDS gratefully acknowledges generous support provided by the Danish Agency for Science and Technology and Innovation realized through a Sapere Aude Level 2 grant. MF is supported by the European Union FP7 programme through ERC grant number 320360. SJS acknowledges funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement No. [291222] and STFC grants ST/I001123/1 and ST/L000709/1. AVF's group at UC Berkeley is grateful for financial assistance from NSF grant AST-1211916, the TABASGO Foundation, Gary and Cynthia Bengier, and the Christopher R. Redlich Fund. This work was supported by the NSF under grants PHY-1125915 and AST-1109174. M.S. acknowledges support from EU/FP7-ERC grant no [615929]. This paper is based on observations made with the Swift, LCOGT, Gemini, and Keck Observatories; we thank their respective staffs for excellent assistance. The W. M. Keck Observatory is operated as a scientific partnership among the California Institute of Technology, the University of California, and NASA; the observatory was made possible by the generous financial support of the W. M. Keck Foundation. Based on observations collected at the European Organization for Astronomical Research in the Southern hemisphere, Chile as part of PESSTO, (the Public ESO Spectroscopic Survey for Transient Objects Survey) ESO program ID 188.D-3003.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/mnras/stw87

Immune-Mobilizing Monoclonal T Cell Receptors Mediate Specific and Rapid Elimination of Hepatitis B-Infected Cells

Background and Aims: Therapies for chronic hepatitis B virus (HBV) infection are urgently needed because of viral integration, persistence of viral antigen expression, inadequate HBV‐specific immune responses, and treatment regimens that require lifelong adherence to suppress the virus. Immune mobilizing monoclonal T Cell receptors against virus (ImmTAV) molecules represent a therapeutic strategy combining an affinity‐enhanced T Cell receptor with an anti‐CD3 T Cell‐activating moiety. This bispecific fusion protein redirects T cells to specifically lyse infected cells expressing the target virus‐derived peptides presented by human leukocyte antigen (HLA). Approach and Results: ImmTAV molecules specific for HLA‐A*02:01‐restricted epitopes from HBV envelope, polymerase, and core antigens were engineered. The ability of ImmTAV‐Env to activate and redirect polyclonal T cells toward cells containing integrated HBV and cells infected with HBV was assessed using cytokine secretion assays and imaging‐based killing assays. Elimination of infected cells was further quantified using a modified fluorescent hybridization of viral RNA assay. Here, we demonstrate that picomolar concentrations of ImmTAV‐Env can redirect T cells from healthy and HBV‐infected donors toward hepatocellular carcinoma (HCC) cells containing integrated HBV DNA resulting in cytokine release, which could be suppressed by the addition of a corticosteroid in vitro. Importantly, ImmTAV‐Env redirection of T cells induced cytolysis of antigen‐positive HCC cells and cells infected with HBV in vitro, causing a reduction of hepatitis B e antigen and specific loss of cells expressing viral RNA. Conclusions: The ImmTAV platform has the potential to enable the elimination of infected cells by redirecting endogenous non‐HBV‐specific T cells, bypassing exhausted HBV‐specific T cells. This represents a promising therapeutic option in the treatment of chronic hepatitis B, with our lead candidate now entering trials

The role of dobutamine stress cardiovascular magnetic resonance in the clinical management of patients with suspected and known coronary artery disease

BACKGROUND: Recent studies have demonstrated the consistently high diagnostic and prognostic value of dobutamine stress cardiovascular magnetic resonance (DCMR). The value of DCMR for clinical decision making still needs to be defined. Hence, the purpose of this study was to assess the utility of DCMR regarding clinical management of patients with suspected and known coronary artery disease (CAD) in a routine setting. METHODS AND RESULTS: We prospectively performed a standard DCMR examination in 1532 consecutive patients with suspected and known CAD. Patients were stratified according to the results of DCMR: DCMR-positive patients were recommended to undergo invasive coronary angiography and DCMR-negative patients received optimal medical treatment. Of 609 (40%) DCMR-positive patients coronary angiography was performed in 478 (78%) within 90 days. In 409 of these patients significant coronary stenoses ≥ 50% were present (positive predictive value 86%). Of 923 (60%) DCMR-negative patients 833 (90%) received optimal medical therapy. During a mean follow-up period of 2.1 ± 0.8 years (median: 2.1 years, interquartile range 1.5 to 2.7 years) 8 DCMR-negative patients (0.96%) sustained a cardiac event.In 131 DCMR-positive patients who did not undergo invasive angiography, 20 patients (15%) suffered cardiac events. In 90 DCMR-negative patients (10%) invasive angiography was performed within 2 years (range 0.01 to 2.0 years) with 56 patients having coronary stenoses ≥ 50%. CONCLUSION: In a routine setting DCMR proved a useful arbiter for clinical decision making and exhibited high utility for stratification and clinical management of patients with suspected and known CAD

The effect of lengthening contractions on neuromuscular junction structure in adult and old mice

Skeletal muscles of old mice demonstrate a profound inability to regenerate fully following damage. Such a failure could be catastrophic to older individuals where muscle loss is already evident. Degeneration and regeneration of muscle fibres following contraction-induced injury in adult and old mice are well characterised, but little is known about the accompanying changes in motor neurons and neuromuscular junctions (NMJs) following this form of injury although defective re-innervation of muscle following contraction-induced damage has been proposed to play a role in sarcopenia. This study visualised and quantified structural changes to motor neurons and NMJs in Extensor digitorum longus (EDL) muscles of adult and old Thy1-YFP transgenic mice during regeneration following contraction-induced muscle damage. Data demonstrated that the damaging contraction protocol resulted in substantial initial disruption to NMJs in muscles of adult mice, which was reversed entirely within 28 days following damage. In contrast, in quiescent muscles of old mice, ∼15 % of muscle fibres were denervated and ∼80 % of NMJs showed disruption. This proportion of denervated and partially denervated fibres remained unchanged following recovery from contraction-induced damage in muscles of old mice although ∼25 % of muscle fibres were completely lost by 28 days post-contractions. Thus, in old mice, the failure to restore full muscle force generation that occurs following damage does not appear to be due to any further deficit in the percentage of disrupted NMJs, but appears to be due, at least in part, to the complete loss of muscle fibres following damag

S-adenosylmethionine and S-adenosylhomocysteine levels in the aging brain of APP/PS1 Alzheimer mice

Hyperhomocysteinemia and factors of homocysteine metabolism, S-adenosylhomocysteine (AdoHcy) and S-adenosylmethionine (AdoMet), may play a role in Alzheimer’s disease (AD). With liquid-chromatography-tandem-mass-spectrometry AdoMet and AdoHcy were determined in brains of 8- and 15-month-old APP/PS1 Alzheimer mice, and their possible roles in AD brains investigated. The finding that AdoMet levels do not differ between the genotypes in (young) 8-month-old mice, but are different in (older) 15-month-old APP/PS1 mice compared to their wild-type littermates, suggests that alterations in AdoMet are a consequence of AD pathology rather than a cause. During aging, AdoMet levels decreased in the brains of wild-type mice, whereas AdoHcy levels diminished in both wild type and APP/PS1 mice. The finding that AdoMet levels in APP/PS1 mice are not decreased during aging (in contrast to wild-type mice), is probably related to less demand due to neurodegeneration. No effect of the omega-3 fatty acid docosahexaenoic acid (DHA) or cholesterol-enriched diets on AdoMet or AdoHcy levels were found

Use of vitamin supplements and risk of total cancer and cardiovascular disease among the Japanese general population: A population-based survey

<p>Abstract</p> <p>Background</p> <p>Despite the popular use of vitamin supplements and several prospective cohort studies investigating their effect on cancer incidence and cardiovascular disease (CVD), scientific data supporting their benefits remain controversial. Inconsistent results may be partly explained by the fact that use of supplements is an inconsistent behavior in individuals. We examined whether vitamin supplement use patterns affect cancer and CVD risk in a population-based cohort study in Japan.</p> <p>Methods</p> <p>A total of 28,903 men and 33,726 women in the Japan Public Health Center-based Prospective Study cohort, who answered questions about vitamin supplement use in the first survey from 1990-1994 and the second survey from 1995-1998, were categorized into four groups (never use, past use, recent use, and consistent use) and followed to the end of 2006 for cancer and 2005 for CVD. Sex-specific hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to describe the relative risks of cancer and CVD associated with vitamin supplement use.</p> <p>Results</p> <p>During follow-up, 4501 cancer and 1858 CVD cases were identified. Multivariate adjusted analysis revealed no association of any pattern of vitamin supplement use with the risk of cancer and CVD in men. In women, consistent use was associated with lower risk of CVD (HR 0.60, 95% CI 0.41-0.89), whereas past (HR 1.17, 95% CI 1.02-1.33) and recent use (HR 1.24, 95% CI 1.01-1.52) were associated with higher risk of cancer.</p> <p>Conclusions</p> <p>To our knowledge, this is the first prospective cohort study to examine simultaneously the associations between vitamin supplement use patterns and risk of cancer and CVD. This prospective cohort study demonstrated that vitamin supplement use has little effect on the risk of cancer or CVD in men. In women, however, consistent vitamin supplement use might reduce the risk of CVD. Elevated risk of cancer associated with past and recent use of vitamin supplements in women may be partly explained by preexisting diseases or unhealthy background, but we could not totally control for this in our study.</p

Low luminosity Type II supernovae - IV. SN 2020cxd and SN 2021aai, at the edges of the sub-luminous supernovae class

Photometric and spectroscopic data for two Low Luminosity Type IIP Supernovae (LL SNe IIP) 2020cxd and 2021aai are presented. SN 2020cxd was discovered 2 d after explosion at an absolute magnitude of M-r = -14.02 +/- 0.21 mag, subsequently settling on a plateau which lasts for similar to 120 d. Through the luminosity of the late light curve tail, we infer a synthesized Ni-56 mass of (1.8 +/- 0.5) x 10(-3) M-circle dot. During the early evolutionary phases, optical spectra show a blue continuum (T > 8000 K) with broad Balmer lines displaying a P Cygni profile, while at later phases, Ca II, Fe II, Sc II, and Ba II lines dominate the spectra. Hydrodynamical modelling of the observables yields R similar or equal to 575 R-circle dot for the progenitor star, with M-ej = 7.5 M-circle dot and E similar or equal to 0.097 foe emitted during the explosion. This low-energy event originating from a low-mass progenitor star is compatible with both the explosion of a red supergiant (RSG) star and with an Electron Capture Supernova arising from a super asymptotic giant branch star. SN 2021aai reaches a maximum luminosity of M-r = -16.57 +/- 0.23 mag (correcting for A(V) = 1.92 mag), at the end of its remarkably long plateau (similar to 140 d). The estimated Ni-56 mass is (1.4 +/- 0.5) x 10(-2) M-circle dot. The expansion velocities are compatible with those of other LL SNe IIP (few 10(3) km s(-1)). The physical parameters obtained through hydrodynamical modelling are R similar or equal to 575 R-circle dot, M-ej = 15.5 M-circle dot, and E = 0.4 foe. SN 2021aai is therefore interpreted as the explosion of an RSG, with properties that bridge the class of LL SNe IIP with standard SN IIP events.</p

A Rapid Crosstalk of Human γδ T Cells and Monocytes Drives the Acute Inflammation in Bacterial Infections

Vγ9/Vδ2 T cells are a minor subset of T cells in human blood and differ from other T cells by their immediate responsiveness to microbes. We previously demonstrated that the primary target for Vγ9/Vδ2 T cells is (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), an essential metabolite produced by a large range of pathogens. Here we wished to study the consequence of this unique responsiveness in microbial infection. The majority of peripheral Vγ9/Vδ2 T cells shares migration properties with circulating monocytes, which explains the presence of these two distinct blood cell types in the inflammatory infiltrate at sites of infection and suggests that they synergize in anti-microbial immune responses. Our present findings demonstrate a rapid and HMB-PP-dependent crosstalk between Vγ9/Vδ2 T cells and autologous monocytes that results in the immediate production of inflammatory mediators including the cytokines interleukin (IL)-6, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and oncostatin M (OSM); the chemokines CCL2, CXCL8, and CXCL10; and TNF-related apoptosis-inducing ligand (TRAIL). Moreover, under these co-culture conditions monocytes differentiate within 18 hours into inflammatory dendritic cells (DCs) with antigen-presenting functions. Addition of further microbial stimuli (lipopolysaccharide, peptidoglycan) induces CCR7 and enables these inflammatory DCs to trigger the generation of CD4+ effector αβ T cells expressing IFN-γ and/or IL-17. Importantly, our in vitro model replicates the responsiveness to microbes of effluent cells from peritoneal dialysis (PD) patients and translates directly to episodes of acute PD-associated bacterial peritonitis, where Vγ9/Vδ2 T cell numbers and soluble inflammatory mediators are elevated in patients infected with HMB-PP-producing pathogens. Collectively, these findings suggest a direct link between invading pathogens, microbe-responsive γδ T cells, and monocytes in the inflammatory infiltrate, which plays a crucial role in the early response and the generation of microbe-specific immunity

Low luminosity Type II supernovae - IV. SN 2020cxd and SN 2021aai, at the edges of the sub-luminous supernovae class

Photometric and spectroscopic data for two Low Luminosity Type IIP Supernovae (LL SNe IIP) 2020cxd and 2021aai are presented. SN 2020cxd was discovered 2 d after explosion at an absolute magnitude of Mr = -14.02 ± 0.21 mag, subsequently settling on a plateau which lasts for ∼120 d. Through the luminosity of the late light curve tail, we infer a synthesized 56Ni mass of (1.8 ± 0.5) × 10-3 M⊙. During the early evolutionary phases, optical spectra show a blue continuum (T >8000 K) with broad Balmer lines displaying a P Cygni profile, while at later phases, Ca ii, Fe ii, Sc ii, and Ba ii lines dominate the spectra. Hydrodynamical modelling of the observables yields R ~ 575 R⊙ for the progenitor star, with Mej = 7.5 M⊙ and E ~ 0.097 foe emitted during the explosion. This low-energy event originating from a low-mass progenitor star is compatible with both the explosion of a red supergiant (RSG) star and with an Electron Capture Supernova arising from a super asymptotic giant branch star. SN 2021aai reaches a maximum luminosity of Mr = -16.57 ± 0.23 mag (correcting for AV = 1.92 mag), at the end of its remarkably long plateau (∼140 d). The estimated 56Ni mass is (1.4 ± 0.5) × 10-2 M⊙. The expansion velocities are compatible with those of other LL SNe IIP (few 103 km s-1). The physical parameters obtained through hydrodynamical modelling are R ~575 R⊙, Mej = 15.5 M⊙, and E = 0.4 foe. SN 2021aai is therefore interpreted as the explosion of an RSG, with properties that bridge the class of LL SNe IIP with standard SN IIP events