Inhibition of ERN1 (endoplasmic reticulum to nuclei 1), the major signalling pathway of endoplasmic reticulum stress, significantly decreases tumor growth. We have studied the expression of tumor ...protein 53 (TP53)- related genes such as TOPORS (topoisomerase I binding, arginine/serine-rich, E3 ubiquitin protein ligase), TP53BP1 (TP53 binding protein 1), TP53BP2, SESN1 (sestrin 1), NME6 (non-metastatic cells 6), and ZMAT3 (zinc finger, Matrin-type 3) in glioma cells expressing dominantnegative ERN1 under baseline and hypoxic conditions. We demonstrated that inhibition of ERN1 function in U87 glioma cells resulted in increased expression of RYBP, TP53BP2, and SESN1 genes, but decreased expression of TP53BP1, TOPORS, NME6, and ZMAT3 genes. Moreover, inhibition of ERN1 affected hypoxia-mediated changes in expression of TP53-related genes and their magnitude. Indeed, hypoxia has no effect on expression of TP53BP1 and SESN1 in control cells, while resulted in increased expression of these genes in cells with inhibited ERN1 function. Magnitude of hypoxia-mediated changes in expression levels of RYBP and TP53BP2 was gene specific and more robust in the case of TP53BP2. Hypoxiamediated decrease in expression levels of TOPORS was more prominent if ERN1 was inhibited. Present study demonstrates that fine-tuning of the expression of TP53- associated genes depends upon endoplasmic reticulum stress signaling under normal and hypoxic conditions. Inhibition of ERN1 branch of endoplasmic reticulum stress response correlates with deregulation of p53 signaling and slower tumor growth.
The High Energy Stereoscopic System (H.E.S.S.) is one of the three arrays of imaging atmospheric Cherenkov telescopes (IACTs) currently in operation. It is composed of four 12-meter telescopes and a ...28-meter one, and is sensitive to gamma rays in the energy range ~ 30 GeV – 100 TeV. The cameras of the 12-m telescopes recently underwent a substantial upgrade, with the goal of improving their performance and robustness. The upgrade involved replacing all camera components except for the photomultiplier tubes (PMTs). This meant developing new hardware for the trigger, readout, power, cooling and mechanical systems, and new software for camera control and data acquisition. Several novel technologies were employed in the cameras: the readout is built around the new NECTAr digitizer chip, developed for the next generation of IACTs; the camera electronics is fully controlled and read out via Ethernet using a combination of FPGA and embedded ARM computers; the software uses modern libraries such as Apache Thrift, ØMQ and Protocol buffers. This work describes in detail the design and the performance of the upgraded cameras.
We studied the expression mRNA of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2 (PFKFB-2) in the rat lung and kidney in experimental diabetes mellitus. For investigation we select two ...isoforms of PFKFB-2 with different C-terminus. The level of the expression of both PFKFB-2 mRNA isoforms is decreased in the kidney and lung in rats with experimental diabetes mellitus respect to the control animals. Moreover, four new alternative splice variants of PFKFB-2 mRNA were identified in the rat kidney. These splice variants of PFKFB-2 mRNA have different inserts and/or deletions in 6-phosphofructo-2-kinase as well as in fructose-2,6-bisphosphatase part of PFKFB-2. Three alternative splice variants cannot encode active 6-phosphofructo-2-kinase as a result of deletion of two catalytic domains (E and F). They encode fructose-2,6-bisphosphatase. It was shown that these alternative splice variants express in the kidney and lung and that this expression changes in rats with experimental diabetes mellitus with respect to the control animals. The results of this investigation clearly demonstrated that diabetes mellitus significantly affects the expression and alternative splicing of PFKFB-2 in the kidney and lungs and showed the complexity of regulatory mechanisms of glucose metabolism in this disease.
Context. Microquasars are potential γ-$\gamma$ray emitters. Indications of transient episodes of $\gamma$-ray emission were recently reported in at least two systems: Cyg X-1 and Cyg X-3. The ...identification of additional $\gamma$-ray-emitting microquasars is required to better understand how $\gamma$-ray emission can be produced in these systems.Aim. Theoretical models have predicted very high-energy (VHE) $\gamma$-ray emission from microquasars during periods of transient outburst. Observations reported herein were undertaken with the objective of observing a broadband flaring event in the $\gamma$-ray and X-ray bands.Methods. Contemporaneous observations of three microquasars, GRS 1915+105, Circinus X-1, and V4641 Sgr, were obtained using the High Energy Spectroscopic System (H.E.S.S.) telescope array and the Rossi X-ray Timing Explorer (RXTE) satellite. X-ray analyses for each microquasar were performed and VHE $\gamma$-ray upper limits from contemporaneous H.E.S.S. observations were derived.Results. No significant $\gamma$-ray signal has been detected in any of the three systems. The integral $\gamma$-ray photon flux at the observational epochs is constrained to be $I$(>560 GeV) < 7.3 × $10^{−13} cm^{−2} s^{−1}$, $I$(>560 GeV ) < 1.2 × $10^{−12} cm^{−2} s^{−1}$, and $I$(>240 GeV) < 4.5 × $10^{−12} cm^{−2} s^{−1}$ for GRS 1915+105, Circinus X-1, and V4641 Sgr, respectively.Conclusions. The $\gamma$-ray upper limits obtained using H.E.S.S. are examined in the context of previous Cherenkov telescope observations of microquasars. The effect of intrinsic absorption is modelled for each target and found to have negligible impact on the flux of escaping $\gamma$-rays. When combined with the X-ray behaviour observed using RXTE, the derived results indicate that if detectable VHE $\gamma$-ray emission from microquasars is commonplace, then it is likely to be highly transient.
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