Enterococcus faecalis, a gram-positive bacterium, has been implicated in endodontic infections, particularly in chronic apical periodontitis. Proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), are involved in the pathogenesis of these apical lesions. E. faecalis has been reported to stimulate macrophages to produce TNF-α. The present study investigated the mechanisms involved in TNF-α production by a murine macrophage cell line, RAW 264.7 in response to exposure to E. faecalis. Both live and heat-killed E. faecalis induced high levels of gene expression and protein release of TNF-α. Treatment of RAW 264.7 cells with cytochalasin D, an inhibitor of endocytosis, prevented the mRNA up-regulation of TNF-α by E. faecalis. In addition, antioxidant treatment reduced TNF-α production to baseline levels. Inhibition of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinase also significantly attenuated E. faecalis-induced TNF-α expression by RAW 264.7 cells. Furthermore, activation of NF-κB and AP-1 in RAW 264.7 cells was also stimulated by E. faecalis. These results suggest that the phagocytic uptake of bacteria is necessary for the induction of TNF-α in E. faecalis-stimulated macrophages, and that the underlying intracellular signaling pathways involve reactive oxygen species, ERK, p38 MAP kinase, NF-κB, and AP-1.

We perform kinetic simulations of diffusive shock acceleration (DSA) in Type Ia supernova remnants (SNRs) expanding into a uniform interstellar medium (ISM). Bohm-like diffusion due to self-excited Alfven waves is assumed, and simple models for Alfvenic drift and dissipation are adopted. Phenomenological models for thermal leakage injection are considered as well. We find that the preshock gas temperature is the primary parameter that governs the cosmic ray (CR) acceleration efficiency and energy spectrum, while the CR injection rate is a secondary parameter. For SNRs in the warm ISM of T0 ≲ 105K, if the injection fraction is ≳ 10-4, the DSA is efficient enough to convert more than 20% of the SN explosion energy into CRs and the accelerated CR spectrum exhibits a concave curvature flattening to E-1.6, which is characteristic of CR modified shocks. Such a flat source spectrum near the knee energy, however, may not be reconciled with the CR spectrum observed at Earth. On the other hand, SNRs in the hot ISM of T0 ≈106K with a small injection fraction, < 10-4, are inefficient accelerators with less than 10% of the explosion energy getting converted to CRs. Also the shock structure is almost test-particle like and the ensuing CR spectrum can be steeper than E-2. With amplified magnetic field strength of order of 30μG Alfven waves generated by the streaming instability may drift upstream fast enough to make the modified test-particle power-law as steep as E-2.3, which is more consistent with the observed CR spectrum.

Effects of Vegemil® containing soybean proteins and isoflavones on the growth and bone density of broiler chickens were investigated. One-week-old male and female Arbor Acres broiler chickens were fed on Vegemil® A containing 3% soybean proteins and 162 ppm isoflavones, instead of water, for 30 days and their growth indices (body weight, leg weight and femur length) and bone density were analyzed. The body weight gains in male and female chickens were increased by 15.6% and 31.7%, respectively, following feeding Vegemil® A compared to normal water. Vegemil® A increased leg weight as well as femur length of females by 22.9% and 15.0%, respectively. In addition, Vegemil® A feeding enhanced femoral bone density by 21.3% in comparison with water feeding. Therefore, it is suggested that Vegemil® A not only facilitates body growth, but also strengthens bone density of normal chickens, and that it could be a promising candidate for the improvement of infant growth and for the prevention of menopausal osteoporosis.

Porphyromonas gingivalis is a major etiologic agent of chronic periodontitis and cytokines produced by macrophages play important roles in the pathogenesis of periodontal diseases. In this study we investigated the cytokine response of phorbol myristate acetatedifferentiated THP-1 cells exposed to P. gingivalis. Compared with the prominent cell wall components of P. gingivalis (lipopolysaccharide and the major fimbrial protein FimA), live P. gingivalis stimulated much higher levels of cytokine production. In addition, whereas low multiplicity of infection challenges (MOI=10) of P. gingivalis 381 stimulated high levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, high dose challenges with this bacterium (MOI = 100) resulted in a substantially diminished production of MCP-1 and IL-6. Moreover, high MOI P. gingivalis challenges achieved only low levels of induction of MCP-1 and IL-6 mRNA. The decreased production of MCP-1 and IL-6 appeared to be mediated by P. gingivalis proteases, because high MOI challenges with congenic protease mutant strains of this microorganism (MT10 and MT10W) did not result in a diminished production of MCP-1 and IL-6. Similar to its protease mutant strains, leupeptin (a protease inhibitor)- treated P. gingivalis at high doses induced high levels of MCP-1 production. To examine the mechanisms underlying the diminished production of MCP-1 by P. gingivalis proteases, the activation of mitogen-activated protein (MAP) kinases and NF-xB was compared between the 381 and MT10W strains. Whilst high doses of both 381 and MT10W similarly activated the three members of the MAP kinase family, the DNA binding activity of NF-xB, as revealed by gel shift assays, was greatly increased only by MT10W. Taken together, our data indicate that P. gingivalis stimulates the production of high levels of TNF-α, IL-1β, IL-6, and MCP-1 but that high dose challenges with this bacterium result in a diminished production of MCP-1 and IL-6 via the protease-mediated suppression of NF-B activation in THP-1 macrophagic cells.

The gap between the increasing amount of raw sequence data and qualified biological information is widening: it is not possible to provide qualified annotation for new genomes with the same speed at which sequences are generated -- especially with next generation sequencing technologies. Additionally, managing the huge number ofavailable bioinformatics algorithms represents a challenge of its own. Thus, a systemwhich provides maximum annotation quality with approved methods in a minimum of time is absolutely critical as the basis for the R&D pipeline in industrial biotechnology. Also using those various genome annotation, comprehensive knowledge of a fungal’s biosynthetic capacities is the indispensable basis of its usefulness in the biotechnology research. Comparative genomics is on the rise as a potent tool in molecular biology. The publicly available genomes from yeasts and several fungal species are used to comparative genomics method for discovery of functional information in our research. Also we had integrated information from different data sources to dynamically build semantic networks representing up-to-date knowledge, which can then be mined and analyzed. Through those methods, we could inspect the common features and uniques between yeasts and fungal species in the new aspect.