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41.
One of the possible pathways of the formation of mutagens in heated foods is through the pyrazine cation radical generated in the early stage of the Maillard reaction. The aim of the present study was to elucidate how food reductones contribute to the pyrazine cation radical generation in the reaction of glucose (Glc) and glycine (Gly), and to the formation of the mutagens in the reaction of Glc, Gly and creatinine. Electron spin resonance (ESR) studies showed that fragrant reductones, 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) and 4-hydroxy-2(or 5)-ethyl-5(or 2)-methyl-3(2H)-furanone (HEMF), generated in the Maillard reactions, enhanced the generation of the pyrazine cation radical in the reaction of Glc and Gly, and the reaction of DMHF or HEMF with Gly generated a larger amount of the pyrazine cation radical than the reaction of Glc and Gly, indicating that the furanones were intermediates of the pyrazine cation radical. By contrast, food antioxidants, ascorbic acid and erythorbic acid, effectively scavenged the pyrazine cation radical generated in the reaction of Glc and Gly. DMHF and HEMF were not effective to modulate the mutagen formation in the reaction of Glc, Gly and creatinine, and the mutagenicity produced in the reaction of DMHF or HEMF, Gly and creatinine was lower than that produced in the reaction of Glc, Gly and creatinine. On the other hand, ascorbic acid and erythorbic acid were effective to decrease the mutagen formation in the reaction of Glc, Gly and creatinine. 相似文献
42.
Makinae K Kobayashi T Kobayashi T Shinkawa H Sakagami H Kondo H Tashiro F Miyazaki J Obata K Tamura S Yanagawa Y 《Journal of neurochemistry》2000,75(4):1429-1437
GABA is synthesized by glutamate decarboxylase (GAD), which has two forms, GAD65 and GAD67. To elucidate the molecular mechanisms of mouse GAD65 (mGAD65) gene expression, we isolated and characterized the mGAD65 gene. The mGAD65 gene was found to be divided into 16 exons and spread over 75 kb. The sequence of the first exon and the 5'-flanking region indicated the presence of potential neuron-specific cis-regulatory elements. We used transgenic mice to examine the expression pattern conferred by a 9.2-kb promoter-proximal DNA fragment of the mGAD65 gene fused to the bacterial lacZ reporter gene. Transgenic mice showed high beta-galactosidase activity specifically in brain and testis. They also showed characteristic patterns of transgene expression in olfactory bulb, cerebellar cortex, and spinal cord, a similar expression pattern to that of endogenous mGAD65. However, no transgene expression was observed in the ventral thalamus or hypothalamus, in which high mGAD65 gene expression levels have been observed. These results suggest that the 9.2-kb DNA fragment of the mGAD65 gene is associated with its tissue-specific expression and its targeted expression in GABAergic neurons of specific brain regions but that additional regulatory elements are necessary to obtain fully correct expression. 相似文献
43.
Origins of globular structure in proteins 总被引:1,自引:0,他引:1
Since natural proteins are the products of a long evolutionary process, the structural properties of present-day proteins should depend not only on physico-chemical constraints, but also on evolutionary constraints. Here we propose a model for protein evolution, in which membranes play a key role as a scaffold for supporting the gradual evolution from flexible polypeptides to well-folded proteins. We suggest that the folding process of present-day globular proteins is a relic of this putative evolutionary process. To test the hypothesis that membranes once acted as a cradle for the folding of globular proteins, extensive research on membrane proteins and the interactions of globular proteins with membranes will be required. 相似文献
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46.
Maiko Matsushita Yoshie Ozaki Yuka Hasegawa Fukiko Terada Noriko Tabata Hirokazu Shiheido Hiroshi Yanagawa Tsukasa Oikawa Koichi Matsuo Wenlin Du Taketo Yamada Masashi Hozumi Daiju Ichikawa Yutaka Hattori 《PloS one》2015,10(1)
Despite the recent advances in the treatment of multiple myeloma (MM), MM patients with high-risk cytogenetic changes such as t(4;14) translocation or deletion of chromosome 17 still have extremely poor prognoses. With the goal of helping these high-risk MM patients, we previously developed a novel phthalimide derivative, TC11. Here we report the further characterization of TC11 including anti-myeloma effects in vitro and in vivo, a pharmacokinetic study in mice, and anti-osteoclastogenic activity. Intraperitoneal injections of TC11 significantly delayed the growth of subcutaneous tumors in human myeloma-bearing SCID mice. Immunohistochemical analyses showed that TC11 induced apoptosis of MM cells in vivo. In the pharmacokinetic analyses, the Cmax was 2.1 μM at 1 h after the injection of TC11, with 1.2 h as the half-life. TC11 significantly inhibited the differentiation and function of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts in mouse osteoclast cultures using M-CSF and RANKL. We also revealed that TC11 induced the apoptosis of myeloma cells accompanied by α-tubulin fragmentation. In addition, TC11 and lenalidomide, another phthalimide derivative, directly bound to nucleophosmin 1 (NPM1), whose role in MM is unknown. Thus, through multiple molecular interactions, TC11 is a potentially effective drug for high-risk MM patients with bone lesions. The present results suggest the possibility of the further development of novel thalidomide derivatives by drug designing. 相似文献
47.
Ryutaro Kakinuma Noriyuki Moriyama Yukio Muramatsu Shiho Gomi Masahiro Suzuki Hirobumi Nagasawa Masahiko Kusumoto Tomohiko Aso Yoshihisa Muramatsu Takaaki Tsuchida Koji Tsuta Akiko Miyagi Maeshima Naobumi Tochigi Shun-ichi Watanabe Naoki Sugihara Shinsuke Tsukagoshi Yasuo Saito Masahiro Kazama Kazuto Ashizawa Kazuo Awai Osamu Honda Hiroyuki Ishikawa Naoya Koizumi Daisuke Komoto Hiroshi Moriya Seitaro Oda Yasuji Oshiro Masahiro Yanagawa Noriyuki Tomiyama Hisao Asamura 《PloS one》2015,10(12)
48.
Richard Lu Bobby Brooke Herrera Heather D. Eshleman Yang Fu Alexander Bloom Zhigang Li David B. Sacks Marcia B. Goldberg 《PLoS pathogens》2015,11(10)
The intracellular bacterial pathogen Shigella infects and spreads through the human intestinal epithelium. Effector proteins delivered by Shigella into cells promote infection by modulating diverse host functions. We demonstrate that the effector protein OspB interacts directly with the scaffolding protein IQGAP1, and that the absence of either OspB or IQGAP1 during infection leads to larger areas of S. flexneri spread through cell monolayers. We show that the effect on the area of bacterial spread is due to OspB triggering increased cell proliferation at the periphery of infected foci, thereby replacing some of the cells that die within infected foci and restricting the area of bacterial spread. We demonstrate that OspB enhancement of cell proliferation results from activation of mTORC1, a master regulator of cell growth, and is blocked by the mTORC1-specific inhibitor rapamycin. OspB activation of mTORC1, and its effects on cell proliferation and bacterial spread, depends on IQGAP1. Our results identify OspB as a regulator of mTORC1 and mTORC1-dependent cell proliferation early during S. flexneri infection and establish a role for IQGAP1 in mTORC1 signaling. They also raise the possibility that IQGAP1 serves as a scaffold for the assembly of an OspB-mTORC1 signaling complex. 相似文献
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Use of digital webcam images to track spring green-up in a deciduous broadleaf forest 总被引:6,自引:0,他引:6
Richardson AD Jenkins JP Braswell BH Hollinger DY Ollinger SV Smith ML 《Oecologia》2007,152(2):323-334
Understanding relationships between canopy structure and the seasonal dynamics of photosynthetic uptake of CO2 by forest canopies requires improved knowledge of canopy phenology at eddy covariance flux tower sites. We investigated whether
digital webcam images could be used to monitor the trajectory of spring green-up in a deciduous northern hardwood forest.
A standard, commercially available webcam was mounted at the top of the eddy covariance tower at the Bartlett AmeriFlux site.
Images were collected each day around midday. Red, green, and blue color channel brightness data for a 640 × 100-pixel region-of-interest
were extracted from each image. We evaluated the green-up signal extracted from webcam images against changes in the fraction
of incident photosynthetically active radiation that is absorbed by the canopy (f
APAR), a broadband normalized difference vegetation index (NDVI), and the light-saturated rate of canopy photosynthesis (A
max), inferred from eddy flux measurements. The relative brightness of the green channel (green %) was relatively stable through
the winter months. A steady rising trend in green % began around day 120 and continued through day 160, at which point a stable
plateau was reached. The relative brightness of the blue channel (blue %) also responded to spring green-up, although there
was more day-to-day variation in the signal because blue % was more sensitive to changes in the quality (spectral distribution)
of incident radiation. Seasonal changes in blue % were most similar to those in f
APAR and broadband NDVI, whereas changes in green % proceeded more slowly, and were drawn out over a longer period of time. Changes
in A
max lagged green-up by at least a week. We conclude that webcams offer an inexpensive means by which phenological changes in
the canopy state can be quantified. A network of cameras could offer a novel opportunity to implement a regional or national
phenology monitoring program. 相似文献