The emerging role of cellular senescence in renal diseases

Cellular senescence represents the state of irreversible cell cycle arrest during cell division. Cellular senescence not only plays a role in diverse biological events such as embryogenesis, tissue regeneration and repair, ageing and tumour occurrence prevention, but it is also involved in many cardiovascular, renal and liver diseases through the senescence-associated secretory phenotype (SASP). This review summarizes the molecular mechanisms underlying cellular senescence and its possible effects on a variety of renal diseases. We will also discuss the therapeutic approaches based on the regulation of senescent and SASP blockade, which is considered as a promising strategy for the management of renal diseases

Tumor-directed gene therapy in mice using a composite nonviral gene delivery system consisting of the piggyBac transposon and polyethylenimine

<p>Abstract</p> <p>Background</p> <p>Compared with viral vectors, nonviral vectors are less immunogenic, more stable, safer and easier to replication for application in cancer gene therapy. However, nonviral gene delivery system has not been extensively used because of the low transfection efficiency and the short transgene expression, especially <it>in vivo</it>. It is desirable to develop a nonviral gene delivery system that can support stable genomic integration and persistent gene expression <it>in vivo</it>. Here, we used a composite nonviral gene delivery system consisting of the <it>piggyBac </it>(PB) transposon and polyethylenimine (PEI) for long-term transgene expression in mouse ovarian tumors.</p> <p>Methods</p> <p>A recombinant plasmid PB [Act-RFP, HSV-tk] encoding both the herpes simplex thymidine kinase (HSV-tk) and the monomeric red fluorescent protein (mRFP1) under PB transposon elements was constructed. This plasmid and the PBase plasmid were injected into ovarian cancer tumor xenografts in mice by <it>in vivo </it>PEI system. The antitumor effects of HSV-tk/ganciclovir (GCV) system were observed after intraperitoneal injection of GCV. Histological analysis and TUNEL assay were performed on the cryostat sections of the tumor tissue.</p> <p>Results</p> <p>Plasmid construction was confirmed by PCR analysis combined with restrictive enzyme digestion. mRFP1 expression could be visualized three weeks after the last transfection of pPB/TK under fluorescence microscopy. After GCV admission, the tumor volume of PB/TK group was significantly reduced and the tumor inhibitory rate was 81.96% contrasted against the 43.07% in the TK group. Histological analysis showed that there were extensive necrosis and lymphocytes infiltration in the tumor tissue of the PB/TK group but limited in the tissue of control group. TUNEL assays suggested that the transfected cells were undergoing apoptosis after GCV admission <it>in vivo</it>.</p> <p>Conclusion</p> <p>Our results show that the nonviral gene delivery system coupling PB transposon with PEI can be used as an efficient tool for gene therapy in ovarian cancer.</p

Neutron Capture Cross Sections for the Weak s Process

In past decades a lot of progress has been made towards understanding the main s-process component that takes place in thermally pulsing Asymptotic Giant Branch (AGB) stars. During this process about half of the heavy elements, mainly between 90<=A<=209 are synthesized. Improvements were made in stellar modeling as well as in measuring relevant nuclear data for a better description of the main s process. The weak s process, which contributes to the production of lighter nuclei in the mass range 56<=A<=90 operates in massive stars (M>=8Msolar) and is much less understood. A better characterization of the weak s component would help disentangle the various contributions to element production in this region. For this purpose, a series of measurements of neutron-capture cross sections have been performed on medium-mass nuclei at the 3.7-MV Van de Graaff accelerator at FZK using the activation method. Also, neutron captures on abundant light elements with A<56 play an important role for s-process nucleosynthesis, since they act as neutron poisons and affect the stellar neutron balance. New results are presented for the (n,g) cross sections of 41K and 45Sc, and revisions are reported for a number of cross sections based on improved spectroscopic information

Characteristics of DNA-AuNP networks on cell membranes and real-time movies for viral infection

AbstractThis data article provides complementary data for the article entitled “DNA-AuNP networks on cell membranes as a protective barrier to inhibit viral attachment, entry and budding” Li et al. (2016) [1]. The experimental methods for the preparation and characterization of DNA-conjugated nanoparticle networks on cell membranes were described. Confocal fluorescence images, agarose gel electrophoresis images and hydrodynamic diameter of DNA-conjugated gold nanoparticle (DNA-AuNP) networks were presented. In addition, we have prepared QDs-labeled RSV (QDs-RSV) to real-time monitor the RSV infection on HEp-2 cells in the absence and presence of DNA-AuNP networks. Finally, the cell viability of HEp-2 cells coated by six types of DNA-nanoparticle networks was determined after RSV infection

Mass spectrometry analysis of the variants of histone H3 and H4 of soybean and their post-translational modifications

Abstract Background Histone modifications and histone variants are of importance in many biological processes. To understand the biological functions of the global dynamics of histone modifications and histone variants in higher plants, we elucidated the variants and post-translational modifications of histones in soybean, a legume plant with a much bigger genome than that of Arabidopsis thaliana. Results In soybean leaves, mono-, di- and tri-methylation at Lysine 4, Lysine 27 and Lysine 36, and acetylation at Lysine 14, 18 and 23 were detected in HISTONE H3. Lysine 27 was prone to being mono-methylated, while tri-methylation was predominant at Lysine 36. We also observed that Lysine 27 methylation and Lysine 36 methylation usually excluded each other in HISTONE H3. Although methylation at HISTONE H3 Lysine 79 was not reported in A. thaliana, mono- and di-methylated HISTONE H3 Lysine 79 were detected in soybean. Besides, acetylation at Lysine 8 and 12 of HISTONE H4 in soybean were identified. Using a combination of mass spectrometry and nano-liquid chromatography, two variants of HISTONE H3 were detected and their modifications were determined. They were different at positions of A31F41S87S90 (HISTONE variant H3.1) and T31Y41H87L90 (HISTONE variant H3.2), respectively. The methylation patterns in these two HISTONE H3 variants also exhibited differences. Lysine 4 and Lysine 36 methylation were only detected in HISTONE H3.2, suggesting that HISTONE variant H3.2 might be associated with actively transcribing genes. In addition, two variants of histone H4 (H4.1 and H4.2) were also detected, which were missing in other organisms. In the histone variant H4.1 and H4.2, the amino acid 60 was isoleucine and valine, respectively. Conclusion This work revealed several distinct variants of soybean histone and their modifications that were different from A. thaliana, thus providing important biological information toward further understanding of the histone modifications and their functional significance in higher plants.</p

Activation of Serotonin 2C Receptors in Dopamine Neurons Inhibits Binge-like Eating in Mice

Acknowledgments and Disclosures This work was supported by the National Institutes of Health (Grant Nos. R01DK093587 and R01DK101379 [to YX], R01DK092605 to [QT], R01DK078056 [to MM]), the Klarman Family Foundation (to YX), the Naman Family Fund for Basic Research (to YX), Curtis Hankamer Basic Research Fund (to YX), American Diabetes Association (Grant Nos. 7-13-JF-61 [to QW] and 1-15-BS-184 [to QT]), American Heart Association postdoctoral fellowship (to PX), Wellcome Trust (Grant No. WT098012 [to LKH]), and Biotechnology and Biological Sciences Research Council (Grant No. BB/K001418/1 [to LKH]). The anxiety tests (e.g., open-field test, light-dark test, elevated plus maze test) were performed in the Mouse Neurobehavior Core, Baylor College of Medicine, which was supported by National Institutes of Health Grant No. P30HD024064. PX and YH were involved in experimental design and most of the procedures, data acquisition and analyses, and writing the manuscript. XC assisted in the electrophysiological recordings; LV-T assisted in the histology study; XY, KS, CW, YY, AH, LZ, and GS assisted in surgical procedures and production of study mice. MGM, QW, QT, and LKH were involved in study design and writing the manuscript. YX is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors report no biomedical financial interests or potential conflicts of interest.Peer reviewedPublisher PD

Petrographic characterization to build an accurate rock model using micro-CT: Case study on low-permeable to tight turbidite sandstone from Eocene Shahejie Formation

Pore scale flow simulations heavily depend on petrographic characterizing and modeling of reservoir rocks. Mineral phase segmentation and pore network modeling are crucial stages in micro-CT based rock modeling. The success of the pore network model (PNM) to predict petrophysical properties relies on image segmentation, image resolution and most importantly nature of rock (homogenous, complex or microporous). The pore network modeling has experienced extensive research and development during last decade, however the application of these models to a variety of naturally heterogenous reservoir rock is still a challenge. In this paper, four samples from a low permeable to tight sandstone reservoir were used to characterize their petrographic and petrophysical properties using high-resolution micro-CT imaging. The phase segmentation analysis from micro-CT images shows that 5-6% microporous regions are present in kaolinite rich sandstone (E3 and E4), while 1.7-1.8% are present in illite rich sandstone (El and E2). The pore system percolates without micropores in El and E2 while it does not percolate without micropores in E3 and E4. In El and E2, total MICP porosity is equal to the volume percent of macrospores determined from micro-CT images, which indicate that the macropores are well connected and microspores do not play any role in non-wetting fluid (mercury) displacement process. Whereas in E3 and E4 sandstones, the volume percent of micropores is far less (almost 50%) than the total MICP porosity which means that almost half of the pore space was not detected by the micro-CT scan. PNM behaved well in El and E2 where better agreement exists in PNM and MICP measurements. While E3 and E4 exhibit multiscale pore space which cannot be addressed with single scale PNM method, a multiscale approach is needed to characterize such complex rocks. This study provides helpful insights towards the application of existing micro-CT based petrographic characterization methodology to naturally complex petroleum reservoir rocks

Egy 14. századi új Salamon: V. (Bölcs) Károly francia király

The result of in-hospital all mortality (P < 0.001; RR 3.23; 95% CI 2.28–4.57). (DOCX 54 kb

Influence of uniaxial tensile stress on the mechanical and piezoelectric properties of short-period ferroelectric superlattice

Tetragonal ferroelectric/ferroelectric BaTiO3/PbTiO3 superlattice under uniaxial tensile stress along the c axis is investigated from first principles. We show that the calculated ideal tensile strength is 6.85 GPa and that the superlattice under the loading of uniaxial tensile stress becomes soft along the nonpolar axes. We also find that the appropriately applied uniaxial tensile stress can significantly enhance the piezoelectricity for the superlattice, with piezoelectric coefficient d33 increasing from the ground state value by a factor of about 8, reaching 678.42 pC/N. The underlying mechanism for the enhancement of piezoelectricity is discussed