Selective up-regulation of NMDA-NR1 receptor expression in myenteric plexus after TNBS induced colitis in rats

BACKGROUND: N-methyl-D-aspartic acid (NMDA) spinal cord receptors play an important role in the development of hyperalgesia following inflammation. It is unclear, however, if changes in NMDA subunit receptor gene expression in the colonic myenteric plexus are associated with colonic inflammation. We investigated regulation of NMDA-NR1 receptor gene expression in TNBS induced colitis in rats. Male Sprague-Dawley rats (150 g–250 g) were treated with 20 mg trinitrobenzene sulfonic acid (TNBS) diluted in 50% ethanol. The agents were delivered with a 24 gauge catheter inserted into the lumen of the colon. The animals were sacrificed at 2, 7, 14, 21, and 28 days after induction of the colitis, their descending colon was retrieved for reverse transcription-polymerase chain reaction; a subset of animals' distal colon was used for two-dimensional (2-D) western analysis and immunocytochemistry. RESULTS: NR1-exon 5 (N1) and NR1-exon 21 (C1) appeared 14, 21 and 28 days after TNBS treatment. NR1 pan mRNA was up-regulated at 14, 21, and 28 days. The NR1-exon 22 (C2) mRNA did not show significant changes. Using 2-D western analysis, untreated control rats were found to express only NR1(001 )whereas TNBS treated rats expressed NR1(001), NR1(011, )and NR1(111). Immunocytochemistry demonstrated NR1-N1 and NR1-C1 to be present in the myenteric plexus of TNBS treated rats. CONCLUSION: These results suggest a role for colonic myenteric plexus NMDA receptors in the development of neuronal plasticity and visceral hypersensitivity in the colon. Up-regulation of NMDA receptor subunits may reflect part of the basis for chronic visceral hypersensitivity in conditions such as post-infectious irritable bowel syndrome

Low Temperature Precursor Route for Highly Efficient Spherically Shaped LED-Phosphors M2Si5N8:Eu2+ (M = Eu, Sr, Ba)

The highly efficient nitridosilicate phosphors M2Si5N8 (M = Sr, Ba, Eu) for phosphor-converted pc-LEDs were synthesized at low temperatures using a novel precursor route involving metal amides M(NH2)2. These precursors have been synthesized by dissolution of the respective metals in supercritical ammonia at 150°C and 300 bar. The thermal behavior and decomposition process of the amides were investigated with temperature programmed powder X-ray diffractometry and thermoanalytical measurements (DTA/TG). These investigations rendered the amides as suitable intermediates for reaction with silicon diimide (Si(NH)2). Thus, the desired nitridosilicate phosphors were obtained at relatively low temperatures around 1150−1400°C which is approximately 300°C lower compared to common synthetic approaches starting from metals or oxides. The influence of the thermal treatment on the phosphor morphology has been studied extensively. The accessibility of spherical phosphor particles represents another striking feature of this route since it improves light extraction from the crystallites due to decreasing light guiding and decreasing re-absorption inside the phosphor particle. The synthesized luminescent materials M2Si5N8:Eu2+ (M = Sr, Ba) exhibit quantum efficiencies and emission band widths (FWHM 70−90 nm) comparable to standard phosphor powders. Employment of Eu(NH2)2 as dopant reagent for synthesis of Ba2Si5N8:Eu2+ proved favorable for the formation of spherical crystallites compared to doping with Eu metal, halides, or oxide

Multidimensional Conservation Laws: Overview, Problems, and Perspective

Some of recent important developments are overviewed, several longstanding open problems are discussed, and a perspective is presented for the mathematical theory of multidimensional conservation laws. Some basic features and phenomena of multidimensional hyperbolic conservation laws are revealed, and some samples of multidimensional systems/models and related important problems are presented and analyzed with emphasis on the prototypes that have been solved or may be expected to be solved rigorously at least for some cases. In particular, multidimensional steady supersonic problems and transonic problems, shock reflection-diffraction problems, and related effective nonlinear approaches are analyzed. A theory of divergence-measure vector fields and related analytical frameworks for the analysis of entropy solutions are discussed.Comment: 43 pages, 3 figure

Ba3Ga3N5 - A Novel Host Lattice for Eu2+ - Doped Luminescent Materials with Unexpected Nitridogallate Substructure

The alkaline earth nitridogallate Ba3Ga3N5 was synthesized from the elements in a sodium flux at 760°C utilizing weld shut tantalum ampules. The crystal structure was solved and refined on the basis of single-crystal X-ray diffraction data. Ba3Ga3N5 (space group C2/c (No. 15), a = 16.801(3), b = 8.3301(2), c = 11.623(2) Å, β = 109.92 (3)°, Z = 8) contains a hitherto unknown structural motif in nitridogallates, namely, infinite strands made up of GaN4 tetrahedra, each sharing two edges and at least one corner with neighboring GaN4 units. There are three Ba2+ sites with coordination numbers six or eight, respectively, and one Ba2+ position exhibiting a low coordination number 4 corresponding to a distorted tetrahedron. Eu2+ - doped samples show red luminescence when excited by UV irradiation at room temperature. Luminescence investigations revealed a maximum emission intensity at 638 nm (FWHM =2123 cm−1). Ba3Ga3N5 is the first nitridogallate for which parity allowed broadband emission due to Eu2+ - doping has been found. The electronic structure of both Ba3Ga3N5 as well as isoelectronic but not isostructural Sr3Ga3N5 was investigated by DFT methods. The calculations revealed a band gap of 1.53 eV for Sr3Ga3N5 and 1.46 eV for Ba3Ga3N5

Oncolytic adenovirus co-expressing IL-12 and IL-18 improves tumor-specific immunity via differentiation of T cells expressing IL-12Rβ2 or IL-18Rα

The oncolytic adenovirus (Ad) is currently being advanced as a promising antitumor remedy as it selectively replicates in tumor cells and can transfer and amplify therapeutic genes. Interleukin (IL)-12 induces a potent antitumor effect by promoting natural killer (NK) cell and cytotoxic T cell activities. IL-18 also augments cytotoxicity of NK cells and proliferation of T cells. This effect further enhances the function of IL-12 in a synergistic manner. Therefore, we investigated for the first time an effective cancer immunogene therapy of syngeneic tumors via intratumoral administration of oncolytic Ad co-expressing IL-12 and IL-18, RdB/IL-12/IL-18. Intratumoral administration of RdB/IL-12/IL-18 improved antitumor effects, as well as increased survival, in B16-F10 murine melanoma model. The ratio of T-helper type 1/2 cytokine as well as the levels of IL-12, IL-18, interferon-γ and granulocyte–macrophage colony-stimulating factor was markedly elevated in RdB/IL-12/IL-18-treated tumors. Mice injected with RdB/IL-12/IL-18 also showed enhanced cytotoxicity of tumor-specific immune cells. Consistent with these results, immense necrosis and infiltration of NK cells, as well as CD4+ and CD8+ T cells, were observed in RdB/IL-12/IL-18-treated tumor tissues. Importantly, tumors treated with RdB/IL-12/IL-18 showed an elevated number of T cells expressing IL-12Rβ2 or IL-18Rα. These results provide a new insight into therapeutic mechanisms of IL-12 plus IL-18 and provide a potential clinical cancer immunotherapeutic agent for improved antitumor immunity

Evolutionary, ecological and biotechnological perspectives on plasmids resident in the human gut mobile metagenome

Numerous mobile genetic elements (MGE) are associated with the human gut microbiota and collectively referred to as the gut mobile metagenome. The role of this flexible gene pool in development and functioning of the gut microbial community remains largely unexplored, yet recent evidence suggests that at least some MGE comprising this fraction of the gut microbiome reflect the co-evolution of host and microbe in the gastro-intestinal tract. In conjunction, the high level of novel gene content typical of MGE coupled with their predicted high diversity, suggests that the mobile metagenome constitutes an immense and largely unexplored gene-space likely to encode many novel activities with potential biotechnological or pharmaceutical value, as well as being important to the development and functioning of the gut microbiota. Of the various types of MGE that comprise the gut mobile metagenome, plasmids are of particular importance since these elements are often capable of autonomous transfer between disparate bacterial species, and are known to encode accessory functions that increase bacterial fitness in a given environment facilitating bacterial adaptation. In this article current knowledge regarding plasmids resident in the human gut mobile metagenome is reviewed, and available strategies to access and characterize this portion of the gut microbiome are described. The relative merits of these methods and their present as well as prospective impact on our understanding of the human gut microbiota is discussed

CD40 Is Essential in the Upregulation of TRAF Proteins and NF-KappaB-Dependent Proinflammatory Gene Expression after Arterial Injury

Despite extensive investigations, restenosis, which is characterized primarily by neointima formation, remains an unsolved clinical problem after vascular interventions. A recent study has shown that CD40 signaling through TNF receptor associated factor 6 (TRAF6) plays a key role in neointima formation after carotid artery injury; however, underlying mechanisms are not clearly elucidated. Because neointima formation may vary significantly depending on the type of injury, we first assessed the effect of CD40 deficiency on neointima formation in 2 injury models, carotid artery ligation and femoral artery denudation injury. Compared with wild-type mice, CD40 deficiency significantly reduced neointima formation and lumen stenosis in two different models. Further, we investigated the mechanism by which CD40 signaling affects neointima formation after arterial injury. In wild-type mice, the expression levels of CD40, several TRAF proteins, including TRAF1, TRAF2, TRAF3, TRAF5, and TRAF6, as well as total NF-kB p65 and phospho-NF-kB p65, in the carotid artery were markedly upregulated within 3–7 days after carotid ligation. Deficiency of CD40 abolished the injury-induced upregulation of TRAFs including TRAF6 and NF-kB-p65 in the injured vessel wall. Further, CD40−/− mice showed a significant decrease in the recruitment of neutrophils (at 3, 7d) and macrophages (at 7, 21d) into injured artery; this effect was most likely attributed to inhibition of NF-kB activation and marked downregulation of NF-kB-related gene expression, including cytokines (TNFα, IL-1β, IL-6), chemokines (MCP-1), and adhesion molecules (ICAM-1, VCAM-1). Moreover, neutrophil recruitment in a model of thioglycollate-induced peritonitis is impaired in CD40-deficient mice. In vitro data revealed that CD40 deficiency blocked CD40L-induced NF-kB p65 nuclear translocation in leukocytes. Altogether, our data identified for the first time that CD40 is essential in the upregulation of TRAF6, NF-kB activation, and NF-kB-dependent proinflammatory genes in vivo. Our findings firmly established the role for CD40 in neointima formation in 2 distinct injury models

Technical summary

Human interference with the climate system is occurring. Climate change poses risks for human and natural systems. The assessment of impacts, adaptation, and vulnerability in the Working Group II contribution to the IPCC's Fifth Assessment Report (WGII AR5) evaluates how patterns of risks and potential benefits are shifting due to climate change and how risks can be reduced through mitigation and adaptation. It recognizes that risks of climate change will vary across regions and populations, through space and time, dependent on myriad factors including the extent of mitigation and adaptation