Search for a Light Sterile Neutrino at Daya Bay

published_or_final_versio

The muon system of the Daya Bay Reactor antineutrino experiment

postprin

Independent measure of the neutrino mixing angle θ13 via neutron capture on hydrogen at Daya Bay

published_or_final_versio

AMP-Activated Kinase AMPK Is Expressed in Boar Spermatozoa and Regulates Motility

The main functions of spermatozoa required for fertilization are dependent on the energy status and metabolism. AMP-activated kinase, AMPK, acts a sensor and regulator of cell metabolism. As AMPK studies have been focused on somatic cells, our aim was to investigate the expression of AMPK protein in spermatozoa and its possible role in regulating motility. Spermatozoa from boar ejaculates were isolated and incubated under different conditions (38,5°C or 17°C, basal medium TBM or medium with Ca2+ and bicarbonate TCM, time from 1–24 hours) in presence or absence of AMPK inhibitor, compound C (CC, 30 µM). Western blotting reveals that AMPK is expressed in boar spermatozoa at relatively higher levels than in somatic cells. AMPK phosphorylation (activation) in spermatozoa is temperature-dependent, as it is undetectable at semen preservation temperature (17°C) and increases at 38,5°C in a time-dependent manner. AMPK phosphorylation is independent of the presence of Ca2+ and/or bicarbonate in the medium. We confirm that CC effectively blocks AMPK phosphorylation in boar spermatozoa. Analysis of spermatozoa motility by CASA shows that CC treatment either in TBM or in TCM causes a significant reduction of any spermatozoa motility parameter in a time-dependent manner. Thus, AMPK inhibition significantly decreases the percentages of motile and rapid spermatozoa, significantly reduces spermatozoa velocities VAP, VCL and affects other motility parameters and coefficients. CC treatment does not cause additional side effects in spermatozoa that might lead to a lower viability even at 24 h incubation. Our results show that AMPK is expressed in spermatozoa at high levels and is phosphorylated under physiological conditions. Moreover, our study suggests that AMPK regulates a relevant function of spermatozoa, motility, which is essential for their ultimate role of fertilization

Redox Regulation of the AMP-Activated Protein Kinase

Redox state is a critical determinant of cell function, and any major imbalances can cause severe damage or death

Exploring the molecular mechanisms underlying the potentiation of exogenous growth hormone on alcohol-induced fatty liver diseases in mice

<p>Abstract</p> <p>Background</p> <p>Growth hormone (GH) is an essential regulator of intrahepatic lipid metabolism by activating multiple complex hepatic signaling cascades. Here, we examined whether chronic exogenous GH administration (via gene therapy) could ameliorate liver steatosis in animal models of alcoholic fatty liver disease (AFLD) and explored the underlying molecular mechanisms.</p> <p>Methods</p> <p>Male C57BL/6J mice were fed either an alcohol or a control liquid diet with or without GH therapy for 6 weeks. Biochemical parameters, liver histology, oxidative stress markers, and serum high molecular weight (HMW) adiponectin were measured. Quantitative real-time PCR and western blotting were also conducted to determine the underlying molecular mechanism.</p> <p>Results</p> <p>Serum HMW adiponectin levels were significantly higher in the GH1-treated control group than in the control group (3.98 ± 0.71 μg/mL vs. 3.07 ± 0.55 μg/mL; <it>P </it>< 0.001). GH1 therapy reversed HMW adiponectin levels to the normal levels in the alcohol-fed group. Alcohol feeding significantly reduced hepatic adipoR2 mRNA expression compared with that in the control group (0.71 ± 0.17 vs. 1.03 ± 0.19; <it>P </it>< 0.001), which was reversed by GH therapy. GH1 therapy also significantly increased the relative mRNA (1.98 ± 0.15 vs. 0.98 ± 0.15) and protein levels of SIRT1 (2.18 ± 0.37 vs. 0.99 ± 0.17) in the alcohol-fed group compared with those in the control group (both, <it>P </it>< 0.001). The alcohol diet decreased the phosphorylated and total protein levels of hepatic AMP-activated kinase-α (AMPKα) (phosphorylated protein: 0.40 ± 0.14 vs. 1.00 ± 0.12; total protein: 0.32 ± 0.12 vs. 1.00 ± 0.14; both, <it>P </it>< 0.001) and peroxisome proliferator activated receptor-α (PPARα) (phosphorylated protein: 0.30 ± 0.09 vs. 1.00 ± 0.09; total protein: 0.27 ± 0.10 vs. 1.00 ± 0.13; both, <it>P </it>< 0.001), which were restored by GH1 therapy. GH therapy also decreased the severity of fatty liver in alcohol-fed mice.</p> <p>Conclusions</p> <p>GH therapy had positive effects on AFLD and may offer a promising approach to prevent or treat AFLD. These beneficial effects of GH on AFLD were achieved through the activation of the hepatic adiponectin-SIRT1-AMPK and PPARα-AMPK signaling systems.</p

RNA interference as a key to knockdown overexpressed cyclooxygenase-2 gene in tumour cells

Silencing those genes that are overexpressed in cancer and contribute to the survival and progression of tumour cells is the aim of several researches. Cyclooxygenase-2 (COX-2) is one of the most intensively studied genes since it is overexpressed in most tumours, mainly in colon cancer. The use of specific COX-2 inhibitors to treat colon cancer has generated great enthusiasm. Yet, the side effects of some inhibitors emerging during long-term treatment have caused much concern. Genes silencing by RNA interference (RNAi) has led to new directions in the field of experimental oncology. In this study, we detected sequences directed against COX-2 mRNA, that potently downregulate COX-2 gene expression and inhibit phorbol 12-myristate 13-acetate-induced angiogenesis in vitro in a specific, nontoxic manner. Moreover, we found that the insertion of a specific cassette carrying anti-COX-2 short hairpin RNA sequence into a viral vector (pSUPER.retro) greatly increased silencing potency in a colon cancer cell line (HT29) without activating any interferon response. Phenotypically, COX-2 deficient HT29 cells showed a significant impairment of their in vitro malignant behaviour. Thus, the retroviral approach enhancing COX-2 knockdown, mediated by RNAi, proved to be an useful tool to better understand the role of COX-2 in colon cancer. Furthermore, the higher infection efficiency we observed in tumour cells, if compared to normal endothelial cells, may disclose the possibility to specifically treat tumour cells without impairing endothelial COX-2 activity

STM-induced light emission from thin films of perylene derivatives on the HOPG and Au substrates

We have investigated the emission properties of N,N'-diheptyl-3,4,9,10-perylenetetracarboxylic diimide thin films by the tunneling-electron-induced light emission technique. A fluorescence peak with vibronic progressions with large Stokes shifts was observed on both highly ordered pyrolytic graphite (HOPG) and Au substrates, indicating that the emission was derived from the isolated-molecule-like film condition with sufficient π-π interaction of the perylene rings of perylenetetracarboxylic diimide molecules. The upconversion emission mechanism of the tunneling-electron-induced emission was discussed in terms of inelastic tunneling including multiexcitation processes. The wavelength-selective enhanced emission due to a localized tip-induced surface plasmon on the Au substrate was also obtained

HSP60 as a Target of Anti-Ergotypic Regulatory T Cells

The 60 kDa heat shock protein (HSP60) has been reported to influence T-cell responses in two ways: as a ligand of toll-like receptor 2 signalling and as an antigen. Here we describe a new mechanism of T-cell immuno-regulation focused on HSP60: HSP60 is up-regulated and presented by activated T cells (HSP60 is an ergotope) to regulatory (anti-ergotypic) T cells. Presentation of HSP60 by activated T cells was found to be MHC-restricted and dependent on accessory molecules - CD28, CD80 and CD86. Anti-ergotypic T cells responded to T-cell HSP60 by proliferation and secreted IFNγ and TGFβ1. In vitro, the anti-ergotypic T cells inhibited IFNγ production by their activated T-cell targets. In vivo, adoptive transfer of an anti-ergotypic HSP60-specific T-cell line led to decreased secretion of IFNγ by arthritogenic T cells and ameliorated adjuvant arthritis (AA). Thus, the presentation of HSP60 by activated T cells turns them into targets for anti-ergotypic regulatory T cells specific for HSP60. However, the direct interaction between the anti-ergotypic T regulators (anti-HSP60) and the activated T cells also down-regulated the regulators. Thus, by functioning as an ergotope, HSP60 can control both the effector T cells and the regulatory HSP60-specific T cells that control them