The activation of NF-kappaB has been shown to be regulated by multiple phosphorylations of IkappaBs and the NF-kappaB p65 subunit. Here, we characterized the intracellular signaling pathway leading to phosphorylation of p65 on Ser-536 using a novel anti-phospho-p65 (Ser-536) antibody. The Ser-536 of endogenous p65 was rapidly phosphorylated in response to a wide variety of NF-kappaB stimulants including TNF-alpha in the cytoplasm and rapidly dephosphorylated in the nucleus. The TNF-alpha-but not IL-1beta-induced Ser-536 phosphorylation was severely impaired in murine embryonic fibroblasts derived from traf2-/-traf5-/- mice. Bay 11-7082, an inhibitor of IkappaB phosphorylation, inhibited the TNF-alpha-induced phosphorylation in vivo. In addition, overexpression of TGF-beta-activated kinase 1 (TAK1), IKKalpha and IKKbeta stimulated the phosphorylation, and their dominant negative mutants blocked the TNF-alpha-induced phosphorylation. Moreover, small interfering RNAs (siRNAs) against TAK1, IKKalpha and IKKbeta blocked the phosphorylation of endogenous p65. On the other hand, calyculin-A, a protein phosphatase inhibitor, blocked the dephosphorylation in the nucleus in vivo. These results indicate that similar signaling pathways were utilized for the phosphorylations of IkappaBalpha and p65, which further support the idea that both IkappaB and NF-kappaB are substrates for the IKK complex in the activation of NF-kappaB.

A more precise quantitative analysis of precipitates in Ti-bearing Interstitial-Free (IF) steel is made through the combination of both a Field-Emission Transmission Electron Microscope (FE-TEM) analysis and an analysis based upon chemical extraction and isolation. The non-stoichiometry of precipitates is precisely determined using either Energy Dispersive X-ray spectroscopy (EDX) or a new method by plasmon energy in Electron Energy-Loss Spectroscopy (EELS) attached to FE-TEM. The non-stoichiometric compositions of each precipitate are taken into consideration in the quantitative analysis.The precise quantitative method is applied to both the hot-rolled and the annealed steels in the process condition : the reheating temperature : 1220 deg . C , the finishing hot-rolling temperature : 890 deg . C , the hot-rolling coiling temperature : 680 deg . C and the annealing temperature : 770 deg . C . The precipitates are quantitatively analyzed from the viewpoint of the interstitial elements ; nitrogen , sulfur and carbon . All the nitrogen is precipitated as TiN when hot-rolling is completed. Most of the sulfur-related precipitate is TiS1.25 in the hot-rolled steel. The rest are Ti4C2S2 and (Mn , Fe) 51.25. After annealing , TiS1.25 decreases , while Ti4C2S2 increases significantly and (Mn , Fe) S1.25 slightly increases. Not all the carbon is combined with Ti in the hot-rolled steel and a lot of "free carbon" still remains even after the hot-rolling process is finished. After the annealing process, both TiC085 and Ti4C2S2 increase in quantity dramatically .

No abstract

Glossodynia is often refractory to conventional medicine, and there is only limited evidence to guide clinicians in its management. Patients with refractory glossodynia are often introduced to Japanese traditional herbal (Kampo) medicine experts under such circumstances because Kampo medicine has become known in Japan to be effective in treating a wide variety of symptoms refractory to conventional medicine. Herein, we report our single-institution 5-year experience treating patients with Kampo medicine for primary glossodynia that was refractory to conventional medicine. We found that 69.2% of patients reported a beneficial effect of Kampo medicine on glossodynia, and the average onset of improvement was 8.0 ± 7.7 weeks after starting Kampo treatment. The top two frequently used Kampo medicines for glossodynia were seinetsuhokito and mibakuekkito among high responders who showed a decrease of severity by 50% or more. The top four most overlapped herbs among effective Kampo medicines for glossodynia were Glycyrrhiza Root, Ginseng Root, Hoelen, and Atractylodes (lancea) Rhizome, which compose an essential Kampo prescription called shikunshito. Although more research is required to further clarify the effectiveness of Kampo medicine, it has valid efficacy even in cases of glossodynia that remain incurable by conventional treatments.