The RENO experiment has analyzed about 500 live days of data to observe an energy dependent disappearance of reactor νe by comparison of their prompt signal spectra measured in two identical near and far detectors. In the period between August 2011 and January 2013, the far (near) detector observed 31541 (290775) electron antineutrino candidate events with a background fraction of 4.9% (2.8%). The measured prompt spectra show an excess of reactor νe around 5 MeV relative to the prediction from a most commonly used model. A clear energy and baseline dependent disappearance of reactor νe is observed in the deficit of the observed number of νe. Based on the measured far-to-near ratio of prompt spectra, we obtain sin 2 2θ13 = 0. The reactor ν e disappearance has been firmly observed to determine the smallest neutrino mixing angle θ 13 [1-3]. All of the three mixing angles in the Pontecorvo-MakiNakagawa-Sakata matrix [4,5] have been measured to provide a comprehensive picture of neutrino transformation. The successful measurement of a rather large θ 13 value opens the possibility of searching for CP violation in the leptonic sector and determining the neutrino mass ordering. Appearance of ν e from an accelerator ν µ beam is also observed by the T2K [6] and NOνA [7] experiments.Using the ν e survival probability P [8], reactor experiments with a baseline distance of ∼1 km can determine the mixing angle θ 13 and an effective squared-massdifference ∆m where ∆ ij ≡ 1.267∆m 2 ij L/E, E is the ν e energy in MeV, and L is the distance between the reactor and detector in meters.The first measurement of θ 13 by RENO was based on the rate-only analysis of deficit found in ∼220 live days of data [1]. The oscillation frequency |∆m 2 ee | in the measurement was approximated by the measured value |∆m 2 31 | assuming the normal ordering in the ν µ disappearance [10]. In this Letter, we present a more precisely measured value of θ 13 and our first determination of |∆m 2 ee |, based on the rate, spectral and baseline information (rate+spectrum analysis) of reactor ν e disappearance using ∼500 live days of data. The Daya Bay collaboration has also reported spectral measurements [11].The RENO uses identical near and far ν e detectors located at 294 m and 1383 m, respectively, from the center of six reactor cores of the Hanbit (known as Yonggwang) Nulcear Power Plant. The far (near) detector is under a 450 m (120 m) of water equivalent overburden. Six pressurized water reactors, each with maximum thermal output of 2.8 GW th , are situated in a linear array spanning 1.3 km with equal spacings. The reactor flux-weighted baseline is 410.6 m for the near detector and 1445.7 m for the far detector.The reactor ν e is detected through the inverse beta decay (IBD) interaction, ν e + p → e + + n, with free protons in hydrocarbon liquid scintillator (LS) with 0.1% Gadolinium (Gd) as a target. The coincidence of a prompt positron signal and a mean time of ∼28 µs delayed signal from neutron capture by Gd (n-Gd) provides the distinctive IBD signatur...

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease characterized by type 2 cytokines secreted by T helper type 2 cells and group 2 innate lymphoid cells. Despite a high degree of heterogeneity, AD is still explained by type 2 immunity, and the role of IL-17A, which is increased in acute, pediatric, or Asian patients with AD, remains poorly understood. Here, we aimed to investigate the role of IL-17Aeproducing group 3 innate lymphoid cells (ILC3s), which are unexplored immune cells, in the pathogenesis of AD. We found that the numbers of ILC3s in the skin of AD-induced mice were increased, and that neutralizing IL-17A delayed development of AD. Moreover, adoptive transfer of ILC3s accelerated the symptoms of AD. Mechanically, ILC3s induced IL-33 production by nonimmune skin cells, keratinocytes, and fibroblasts, which promoted type 2 immune responses. Because AD has a complex pathophysiology and a broad spectrum of clinical phenotypes, the presence of ILC3s in the skin and their interaction with nonimmune skin cells could explain the pathogenesis of cutaneous AD.

Background Skin ageing is caused by numerous factors that result in structural and functional changes in cutaneous components. Research has shown that senescent cells are known to accumulate in skin ageing, however, the role of senescent cells in skin ageing has not been defined. Objectives To elucidate the role of the senescent cell in skin ageing, we evaluated the effect of known senolytic drugs on senescent dermal fibroblasts. Methods Primary human dermal fibroblasts (HDFs) were induced to senescence by long‐term passaging, UV irradiation, and H2O2 treatment. Cell viability was measured after treatment of ABT‐263 and ABT‐737 on HDFs. Young and aged hairless mice were intradermally injected with drugs or vehicle on the dorsal skin for 10 days. Skin specimens were obtained and reverse‐transcription quantitative PCR, western blotting, and histological analysis were performed. Results We found that ABT‐263 and ABT‐737 induced selective clearance of senescent dermal fibroblasts, regardless of the method of senescence induction. Aged mouse skin treated with ABT‐263 or ABT‐737 showed increased collagen density, epidermal thickness, and proliferation of keratinocytes, as well as decreased senescence‐associated secretory phenotypes, such as MMP‐1 and IL‐6. Conclusions Taken together, our results indicate that selective clearance of senescent skin cells can attenuate and improve skin ageing phenotypes and that senolytic drugs may be of potential use as new therapeutic agents for treating ageing of the skin.

The superoxide dismutase (SOD) family functions as a reactive oxygen species (ROS)-scavenging system by converting superoxide anions into hydrogen peroxide in the cytosol (SOD1), mitochondria (SOD2), and extracellular matrix (SOD3). In this study, we examined the potential roles of SOD family members in skin aging. We found that SOD3 expression levels were significantly more reduced in the skin tissues of old mice and humans than in young counterparts, but SOD1 and SOD2 expression levels remained unchanged with aging. Accordingly, we analyzed the effects of SOD3 on intracellular ROS levels and the integrity of the extracellular matrix in fibroblasts. The treatment of foreskin fibroblasts with recombinant SOD3 reduced the intracellular ROS levels and secretion of MMP-1 while increasing the secretion of type I collagen. The effects of SOD3 were greater in fibroblasts treated with the TNF-α. SOD3 treatment also decreased the mRNA levels and promoter activity of MMP-1 while increasing the mRNA levels and promoter activities of COL1A1 and COL1A2. SOD3 treatment reduced the phosphorylation of NF-κB, p38 MAPK, ERK, and JNK, which are essential for MMP-1 transactivation. In a three-dimensional culture of fibroblasts, SOD3 decreased the amount of type I collagen fragments produced by MMP-1 and increased the amount of nascent type I procollagen. These results demonstrate that SOD3 reduces intracellular ROS levels, suppresses MMP-1 expression, and induces type I collagen expression in fibroblasts. Therefore, SOD3 may play a role in delaying or preventing skin aging.