Conserved and novel functions of programmed cellular senescence during vertebrate development

Cellular senescence, a form of stable cell cycle arrest that is traditionally associated with tumour suppression, has been recently found to occur during mammalian development. Here, we show that cell senescence is an intrinsic part of the developmental programme in amphibians. Programmed senescence occurs in specific structures during defined time windows during amphibian development. It contributes to the physiological degeneration of the amphibian pronephros and to the development of the cement gland and oral cavity. In both contexts, senescence depends on TGFβ but is independent of ERK/MAPK activation. Furthermore, elimination of senescent cells through temporary TGFβ inhibition leads to developmental defects. Our findings uncover conserved and new roles of senescence in vertebrate organogenesis and support the view that cellular senescence may have arisen in evolution as a developmental mechanism

TLR9 regulates adipose tissue inflammation and obesity-related metabolic disorders

ObjectiveRecent studies have revealed a link between Toll-like receptor (TLR) signaling and the adipose tissue inflammation associated with obesity. Although TLR9 is known to play an important role in inflammation and innate immunity, its role in mediating adipose tissue inflammation has not yet been investigated. Thus, the objective of this study was to determine the role of TLR9 in regulating immune cells in visceral adipose tissue and maintaining the metabolic homeostasis. MethodsWild-type and TLR9-deficient mice were fed with a high-fat diet, and the body weight gain, glucose tolerance, insulin sensitivity, and adipose tissue inflammation were examined. ResultsTLR9-deficient mice gained significantly more weight and body fat under a high-fat diet than wild-type mice and exhibited more severe glucose intolerance and insulin resistance. We also found a dramatic increase of M1 macrophages as well as T(H)1 cells in the adipose tissue of TLR9-deficient mice compared to wild-type mice. Furthermore, the levels of various proinflammatory cytokines and chemokines were higher in TLR9-deficient mice. ConclusionsTLR9 signaling is involved in regulating adipose tissue inflammation and controlling obesity and the metabolic syndrome.1174Ysciescopu

Sub-microsecond temporal evolution of edge density during edge localized modes in KSTAR tokamak plasmas inferred from ion cyclotron emission

During edge localised mode (ELM) crashes in KSTAR deuterium plasmas, bursts of spectrally structured ion cyclotron emission (ICE) are detected. Usually the ICE spectrum chirps downwards during an ELM crash, on sub-microsecond timescales. For KSTAR ICE where the separation of spectral peak frequencies is close to the proton cyclotron frequency Omega(cp) at the outer plasma edge, we show that the driving population of energetic ions is likely to be a subset of the 3 MeV fusion protons, born centrally on deeply passing orbits which drift from the core to the edge plasma. We report first principles modelling of this scenario using a particle-in-cell code, which evolves the full orbit dynamics of large numbers of energetic protons, thermal deuterons, and electrons self-consistently with the electric and magnetic fields. The Fourier transform of the excited fields in the nonlinear saturated regime of the simulations is the theoretical counterpart to the measured ICE spectra. Multiple simulation runs for different, adjacent, values of the plasma density under KSTAR edge conditions enable us to infer the theoretical dependence of ICE spectral structure on the local electron number density. By matching this density dependence to the observed time-dependence of chirping ICE spectra in KSTAR, we obtain sub-microsecond time resolution of the evolving local electron number density during the ELM crash.116Ysciescopu

Oral immunization of haemaggulutinin H5 expressed in plant endoplasmic reticulum with adjuvant saponin protects mice against highly pathogenic avian influenza A virus infection

Pandemics in poultry caused by the highly pathogenic avian influenza (HPAI) A virus occur too frequently globally, and there is growing concern about the HPAI A virus due to the possibility of a pandemic among humans. Thus, it is important to develop a vaccine against HPAI suitable for both humans and animals. Various approaches are underway to develop such vaccines. In particular, an edible vaccine would be a convenient way to vaccinate poultry because of the behaviour of the animals. However, an edible vaccine is still not available. In this study, we developed a strategy of effective vaccination of mice by the oral administration of transgenic Arabidopsis plants (HA-TG) expressing haemagglutinin (HA) in the endoplasmic reticulum (ER). Expression of HA in the ER resulted in its high-level accumulation, N-glycosylation, protection from proteolytic degradation and long-term stability. Oral administration of HA-TG with saponin elicited high levels of HA-specific systemic IgG and mucosal IgA responses in mice, which resulted in protection against a lethal influenza virus infection with attenuated inflammatory symptoms. Based on these results, we propose that oral administration of freeze-dried leaf powders from transgenic plants expressing HA in the ER together with saponin is an attractive strategy for vaccination against influenza A virus.X111411Ysciescopu

Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist

Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the Delta dblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4(+) T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1 beta. Moreover, small intestinal eosinophils isolated from IL-1Ra-deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra.open111815sciescopu

Association between Helicobacter pylori infection and interleukin 1β polymorphism predispose to CpG island methylation in gastric cancer [4]

published_or_final_versio

Toxic Epidermal Necrolysis after Pemetrexed and Cisplatin for Non-Small Cell Lung Cancer in a Patient with Sharp Syndrome

Background: Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-effect profile includes fatigue, hematological and gastrointestinal toxicity, an increase in hepatic enzymes, sensory neuropathy, and pulmonary and cutaneous toxicity in various degrees. Case Report: We present the case of a 58-year-old woman with history of Sharp's syndrome and adenocarcinoma of the lung, who developed toxic epidermal necrolysis after the first cycle of pemetrexed, including erythema, bullae, extensive skin denudation, subsequent systemic inflammation and severe deterioration in general condition. The generalized skin lesions occurred primarily in the previous radiation field and responded to immunosuppressive treatment with prednisone. Conclusion: Although skin toxicity is a well-known side effect of pemetrexed, severe skin reactions after pemetrexed administration are rare. Caution should be applied in cases in which pemetrexed is given subsequent to radiation therapy, especially in patients with pre-existing skin diseases

Top-up operation at Pohang Light Source-II

After three years of upgrading work, PLS-II (S. Shin, Commissioning of the PLS-II, JINST, January 2013) is now successfully operating. The top-up operation of the 3 GeV linear accelerator had to be delayed because of some challenges encountered, and PLS-II was run in decay mode at the beginning in March 2012. The main difficulties encountered in the top-up operation of PLS-II are different levels between the linear accelerator and the storage ring, the 14 narrow gap in-vacuum undulators in operation, and the full energy injection by 3 GeV linear accelerator. Large vertical emittance and energy jitter of the linac were the major obstacles that called for careful control of injected beam to reduce beam loss in the storage ring during injection. The following measures were taken to resolve these problems: (1) The high resolution Libera BPM (see http://www.i-tech.si) was implemented to measure the beam trajectory and energy. (2) Three slit systems were installed to filter the beam edge. (3) De-Qing circuit was applied to the modulator system to improve the energy stability of injected beam. As a result, the radiation by beam loss during injection is reduced drastically, and the top-up mode has been successfully operating since 19th March 2013. In this paper, we describe the experimental results of the PLS-II top-up operation and the improvement plan. (C) 2014 AIP Publishing LLC.open111011sciescopu

Atom chip based generation of entanglement for quantum metrology

Atom chips provide a versatile `quantum laboratory on a microchip' for experiments with ultracold atomic gases. They have been used in experiments on diverse topics such as low-dimensional quantum gases, cavity quantum electrodynamics, atom-surface interactions, and chip-based atomic clocks and interferometers. A severe limitation of atom chips, however, is that techniques to control atomic interactions and to generate entanglement have not been experimentally available so far. Such techniques enable chip-based studies of entangled many-body systems and are a key prerequisite for atom chip applications in quantum simulations, quantum information processing, and quantum metrology. Here we report experiments where we generate multi-particle entanglement on an atom chip by controlling elastic collisional interactions with a state-dependent potential. We employ this technique to generate spin-squeezed states of a two-component Bose-Einstein condensate and show that they are useful for quantum metrology. The observed 3.7 dB reduction in spin noise combined with the spin coherence imply four-partite entanglement between the condensate atoms and could be used to improve an interferometric measurement by 2.5 dB over the standard quantum limit. Our data show good agreement with a dynamical multi-mode simulation and allow us to reconstruct the Wigner function of the spin-squeezed condensate. The techniques demonstrated here could be directly applied in chip-based atomic clocks which are currently being set up

First Measurement of Transferred Polarization in the Exclusive e p --> e' K+ Lambda Reaction

The first measurements of the transferred polarization for the exclusive ep --> e'K+ Lambda reaction have been performed in Hall B at the Thomas Jefferson National Accelerator Facility using the CLAS spectrometer. A 2.567 GeV electron beam was used to measure the hyperon polarization over a range of Q2 from 0.3 to 1.5 (GeV/c)2, W from 1.6 to 2.15 GeV, and over the full center-of-mass angular range of the K+ meson. Comparison with predictions of hadrodynamic models indicates strong sensitivity to the underlying resonance contributions. A non-relativistic quark model interpretation of our data suggests that the s-sbar quark pair is produced with spins predominantly anti-aligned. Implications for the validity of the widely used 3P0 quark-pair creation operator are discussed.Comment: 6 pages, 4 figure