STAT1 regulates interferon-γ-induced angiotensinogen and MCP-1 expression in a bidirectional manner in primary cultured mesangial cells

Objective: Intrarenal interferon-γ significantly contributes to the development of glomerular injury in which angiotensinogen and monocyte chemoattractant protein 1 levels are elevated. However, the exact nature of the role that interferon-γ plays in regulating angiotensinogen and monocyte chemoattractant protein 1 expression has not been fully delineated. Therefore, the aim of this study was to investigate the role that interferon-γ plays in angiotensinogen and monocyte chemoattractant protein 1 expression. Methods: Primary cultured rat mesangial cells were treated with 0–20 ng/mL interferon-γ for 2, 8 or 24 hours. Expression levels of angiotensinogen, monocyte chemoattractant protein 1, suppressors of cytokine signaling 1, an intracellular suppressor of Janus kinase-signal transducers and activators of transcription signaling and activity of the Janus kinase-signal transducers and activators of transcription pathway were evaluated by reverse transcriptase polymerase chain reaction and western blot analysis. Results: Interferon-γ increased angiotensinogen expression in mesangial cells with maximal augmentation observed following 5 ng/mL interferon-γ at 8 hours of treatment (1.87 ± 0.05, mRNA, relative ratio). Further increases were reduced or absent using higher concentrations of interferon-γ. Following treatments, monocyte chemoattractant protein 1 expression was induced in a linear dose-dependent manner (6.85 ± 0.62-fold by 20 ng/mL interferon-γ at 24 hours). In addition, interferon-γ induced STAT1 phosphorylation and suppressors of cytokine signaling 1 expression in a linear dose-dependent manner. The suppression of STAT1 and suppressors of cytokine signaling 1 expression by small interference RNAs facilitated an increase in interferon-γ-induced angiotensinogen expression, indicating that these two factors negatively regulate angiotensinogen expression. In contrast, the increase in interferon-γ-induced monocyte chemoattractant protein 1 expression was attenuated in STAT1-deficient mesangial cells, suggesting that STAT1 positively regulates monocyte chemoattractant protein 1 expression in mesangial cells. Conclusion: These results demonstrate that while interferon-γ increases both angiotensinogen and monocyte chemoattractant protein 1 expression, STAT1 plays an opposing role in the regulation of each factor in mesangial cells

Development of Coaxial Type flow microwave reactor

[EN] We have developed a flow microwave reactor with a coaxial cavity. It comprises a cylindrical cavity of 100 mm inside diameter, a metal rod along its center axis, and a spiral glass tube for flowing solvents and reactants, as shown in Fig.1. When the input port of microwave is placed at the end of the metal rod, the TEM mode is excited in the cylindrical chamber due to the presence of the metal rod. Simulations of the electric field and the magnetic field within the coaxial cavity are shown in Fig.2. This configuration was confirmed suitable for rapid and continuous microwave syntheses of various functional metal complexes. Experimental results are presented of Ir(Ⅲ) complexes for OLED dopants and Ru(Ⅱ) complexes for various sensors. The application to rapid and continuous microwave synthesis of various functional metal complexes were performed in success. In the similar manner as the coaxial reaction chamber of 2.45GHz, a coaxial reaction chamber for 5.8GHz IMS band, dimension of 51mm in diameter and 50mm in height,　is designed The electric field distributions in the chamber and the temperature profiles of solvent are simulated using the commercial simulator (COMSOL Multiphysics) for 5.8 GHz, 5W microwave input. Using the simulation results appropriate dimensions of the chamber are determined for the 5.8 GHz operation. When water is used as a solvent the simulation shows that the temperature rises from20℃ to 95℃ after 300 seconds of the microwave irradiation.Matsumura, T.; Kishihara, M.; Urushihara, U. (2019). Development of Coaxial Type flow microwave reactor. En AMPERE 2019. 17th International Conference on Microwave and High Frequency Heating. Editorial Universitat Politècnica de València. 487-491. https://doi.org/10.4995/AMPERE2019.2019.9897OCS48749

dictyBase update 2011: web 2.0 functionality and the initial steps towards a genome portal for the Amoebozoa

dictyBase (http://www.dictybase.org), the model organism database for Dictyostelium, aims to provide the broad biomedical research community with well integrated, high quality data and tools for Dictyostelium discoideum and related species. dictyBase houses the complete genome sequence, ESTs, and the entire body of literature relevant to Dictyostelium. This information is curated to provide accurate gene models and functional annotations, with the goal of fully annotating the genome to provide a ‘reference genome’ in the Amoebozoa clade. We highlight several new features in the present update: (i) new annotations; (ii) improved interface with web 2.0 functionality; (iii) the initial steps towards a genome portal for the Amoebozoa; (iv) ortholog display; and (v) the complete integration of the Dicty Stock Center with dictyBase

Involvement of glomerular renin−angiotensin system (RAS) activation in the development and progression of glomerular injury

Recently, there has been a paradigm shift away from an emphasis on the role of the endocrine (circulating) renin−angiotensin system (RAS) in the regulation of the sodium and extracellular fluid balance, blood pressure, and the pathophysiology of hypertensive organ damage toward a focus on the role of tissue RAS found in many organs, including kidney. A tissue RAS implies that RAS components necessary for the production of angiotensin II (Ang II) reside within the tissue and its production is regulated within the tissue, independent of the circulating RAS. Locally produced Ang II plays a role in many physiological and pathophysiological processes such as hypertension, inflammation, oxidative stress, and tissue fibrosis. Both glomerular and tubular compartments of the kidney have the characteristics of a tissue RAS. The purpose of this article is to review the recent advances in tissue RAS research with a particular focus on the role of the glomerular RAS in the progression of renal disease

Hydrogen Susceptibility of Nanostructured Bainitic Steels

Abstract Nanostructured steels with an ultimate tensile strength of 1.6 GPa were produced with austenite content varying from 0 to 35 vol pct. The effect on the mechanical properties was assessed after saturating the steel with hydrogen. Elongation was reduced to 2 to 5 pct and UTS to 65 to 70 pct of prior value. Thermal desorption measurements confirmed the higher solubility of hydrogen in the steel with higher austenite content. The level of hydrogen saturation was found to correlate to the total area of grain boundaries rather than to the volume fraction of retained austenite.This is the final version of the article. It was first available from Springer via http://dx.doi.org/10.1007/s11661-015-3221-

Comparative genome and transcriptome analyses of the social amoeba Acytostelium subglobosum that accomplishes multicellular development without germ-soma differentiation

Background Social amoebae are lower eukaryotes that inhabit the soil. They are characterized by the construction of a starvation-induced multicellular fruiting body with a spore ball and supportive stalk. In most species, the stalk is filled with motile stalk cells, as represented by the model organism Dictyostelium discoideum, whose developmental mechanisms have been well characterized. However, in the genus Acytostelium, the stalk is acellular and all aggregated cells become spores. Phylogenetic analyses have shown that it is not an ancestral genus but has lost the ability to undergo cell differentiation. Results We performed genome and transcriptome analyses of Acytostelium subglobosum and compared our findings to other available dictyostelid genome data. Although A. subglobosum adopts a qualitatively different developmental program from other dictyostelids, its gene repertoire was largely conserved. Yet, families of polyketide synthase and extracellular matrix proteins have not expanded and a serine protease and ABC transporter B family gene, tagA, and a few other developmental genes are missing in the A. subglobosum lineage. Temporal gene expression patterns are astonishingly dissimilar from those of D. discoideum, and only a limited fraction of the ortholog pairs shared the same expression patterns, so that some signaling cascades for development seem to be disabled in A. subglobosum. Conclusions The absence of the ability to undergo cell differentiation in Acytostelium is accompanied by a small change in coding potential and extensive alterations in gene expression patterns

Kin discrimination and possible cryptic species in the social amoeba Polysphondylium violaceum

Abstract Background The genetic diversity of many protists is unknown. The differences that result from this diversity can be important in interactions among individuals. The social amoeba Polysphondylium violaceum, which is a member of the Dictyostelia, has a social stage where individual amoebae aggregate together to form a multicellular fruiting body with dead stalk cells and live spores. Individuals can either cooperate with amoebae from the same clone, or sort to form clonal fruiting bodies. In this study we look at genetic diversity in P. violaceum and at how this diversity impacts social behavior. Results The phylogeny of the ribosomal DNA sequence (17S to 5.8S region) shows that P. violaceum is made up of at least two groups. Mating compatibility is more common between clones from the same phylogenetic group, though matings between clones from different phylogenetic groups sometimes occurred. P. violaceum clones are more likely to form clonal fruiting bodies when they are mixed with clones from a different group than when they are mixed with a clone of the same group. Conclusion Both the phylogenetic and mating analyses suggest the possibility of cryptic species in P. violaceum. The level of divergence found within P. violaceum is comparable to the divergence between sibling species in other dictyostelids. Both major groups A/B and C/D/E/F show kin discrimination, which elevates relatedness within fruiting bodies but not to the level of clonality. The diminished cooperation in mixes between groups suggests that the level of genetic variation between individuals influences the extent of their cooperation

Glomerular angiotensinogen protein is enhanced in pediatric IgA nephropathy

Enhanced intrarenal renin-angiotensin system (RAS) is implicated in the development and progression of renal injury. To investigate whether angiotensinogen (AGT) expression is involved in glomerular RAS activity and glomerular injury, we examined glomerular AGT expression and its correlation with expression of other RAS components, and levels of glomerular injury in samples from patients with immunoglobulin A nephropathy (IgAN) (23) and minor glomerular abnormalities (MGA) (8). Immunohistochemistry showed that AGT protein was highly expressed by glomerular endothelial cells (GEC) and mesangial cells in nephritic glomeruli of IgAN compared with glomeruli of MGA. Levels of glomerular AGT protein were well correlated with levels of glomerular angiotensin II (ang II), transforming growth factor-β (TGF-β), α-smooth-muscle actin, glomerular cell number, and glomerulosclerosis score but not with those of glomerular angiotensin-converting enzyme and ang II type 1 receptor. Real-time polymerase chain reaction (RT-PCR) and Western blot analyses using cultured human GEC indicated that ang II upregulated AGT messenger ribonucleic acid (mRNA) and protein expression in a dose- and time-dependent manner. These data suggest that activated glomerular AGT expression is likely involved in elevated local ang II production and, thereby, may contribute to increased TGF-β production and development of glomerular injury in IgAN. Augmentation of GEC-AGT production with ang II stimulation might drive further glomerular injury in a positive-feedback loop

Brain Deletion of Insulin Receptor Substrate 2 Disrupts Hippocampal Synaptic Plasticity and Metaplasticity

Diabetes mellitus is associated with cognitive deficits and an increased risk of dementia, particularly in the elderly. These deficits and the corresponding neurophysiological structural and functional alterations are linked to both metabolic and vascular changes, related to chronic hyperglycaemia, but probably also defects in insulin action in the brain. To elucidate the specific role of brain insulin signalling in neuronal functions that are relevant for cognitive processes we have investigated the behaviour of neurons and synaptic plasticity in the hippocampus of mice lacking the insulin receptor substrate protein 2 (IRS-2)