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941.
Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells 总被引:1,自引:0,他引:1
Snippert HJ van der Flier LG Sato T van Es JH van den Born M Kroon-Veenboer C Barker N Klein AM van Rheenen J Simons BD Clevers H 《Cell》2010,143(1):134-144
Intestinal stem cells, characterized by high Lgr5 expression, reside between Paneth cells at the small intestinal crypt base and divide every day. We have carried out fate mapping of individual stem cells by generating a multicolor Cre-reporter. As a population, Lgr5(hi) stem cells persist life-long, yet crypts drift toward clonality within a period of 1-6 months. We have collected short- and long-term clonal tracing data of individual Lgr5(hi) cells. These reveal that most Lgr5(hi) cell divisions occur symmetrically and do not support a model in which two daughter cells resulting from an Lgr5(hi) cell division adopt divergent fates (i.e., one Lgr5(hi) cell and one transit-amplifying [TA] cell per division). The cellular dynamics are consistent with a model in which the resident stem cells double their numbers each day and stochastically adopt stem or TA fates. Quantitative analysis shows that stem cell turnover follows a pattern of neutral drift dynamics. 相似文献
942.
Yoshikazu Shimada Setsuko Yasuda Masayuki Takahashi Takashi Hayashi Norihiro Miyazawa Ikutaro Sato Yasuhiro Abiru Shigeto Uchiyama Haretsugu Hishigaki 《Applied and environmental microbiology》2010,76(17):5892-5901
Equol is a metabolite produced from daidzein by enteric microflora, and it has attracted a great deal of attention because of its protective or ameliorative ability against several sex hormone-dependent diseases (e.g., menopausal disorder and lower bone density), which is more potent than that of other isoflavonoids. We purified a novel NADP(H)-dependent daidzein reductase (L-DZNR) from Lactococcus strain 20-92 (Lactococcus 20-92; S. Uchiyama, T. Ueno, and T. Suzuki, international patent WO2005/000042) that is involved in the metabolism of soy isoflavones and equol production and converts daidzein to dihydrodaidzein. Partial amino acid sequences were determined from purified L-DZNR, and the gene encoding L-DZNR was cloned. The nucleotide sequence of this gene consists of an open reading frame of 1,935 nucleotides, and the deduced amino acid sequence consists of 644 amino acids. L-DZNR contains two cofactor binding motifs and an 4Fe-4S cluster. It was further suggested that L-DZNR was an NAD(H)/NADP(H):flavin oxidoreductase belonging to the old yellow enzyme (OYE) family. Recombinant histidine-tagged L-DZNR was expressed in Escherichia coli. The recombinant protein converted daidzein to (S)-dihydrodaidzein with enantioselectivity. This is the first report of the isolation of an enzyme related to daidzein metabolism and equol production in enteric bacteria.Isoflavones are flavonoids present in various plants and are known to be abundant in soybeans and legumes. These compounds have been called phytoestrogens because their chemical structure is similar to that of the female sex hormone, estrogen. Isoflavones have an ability to bind to estrogen receptors and show protection against or improvement in several sex hormone-dependent diseases, such as breast cancer, prostate cancer, menopausal disorder, lower bone density, and hypertension, due to their weak agonistic or antagonistic effects (1, 19, 27).Daidzein is one of the main soy isoflavonoids produced from daidzin by the glucosidase of intestinal bacteria (17). Equol is a metabolite produced from daidzein by the enterobacterial microflora (5). Recently, equol has attracted a great deal of attention because its estrogenic activity is more potent than that of other isoflavonoids, including daidzein (27). It is well known that individual variation exists in the ability of these enteric microflora to produce equol and that less than half the human population is capable of producing equol after ingesting soy isoflavones (3). Therefore, to increase the production of equol in the enteric environment of each individual, the development of probiotics using safe bacteria which have the ability to produce equol from daidzein is ongoing.Lactococcus strain 20-92 (Lactococcus 20-92; 30a) is an equol-producing lactic acid bacterium isolated from the feces of healthy humans by Uchiyama et al. (30). This bacterium is spherical and Gram positive and is a strain of L. garvieae. The application of Lactococcus 20-92 in probiotics is advantageous because L. garvieae is not pathogenic or toxic to humans.To date, other bacterial strains that are capable of transforming daidzein to dihydrodaidzein or equol have been isolated (9, 21, 22, 23, 29, 32, 36, 37). Daidzein is thought to be metabolized by human intestinal bacteria to equol or to O-desmethylangolensin via dihydrodaidzein and tetrahydrodaidzein (14, 15, 22, 32); however, neither the enzymes involved in the metabolism of daidzein to equol nor even the metabolic pathway has been clarified fully for equol-producing bacteria.In this study, we purified an enzyme from Lactococcus 20-92 that assisted in the conversion of daidzein to dihydrodaidzein. Furthermore, we cloned the L-DZNR gene and expressed the active recombinant enzyme in E. coli. 相似文献
943.
Sato Y Suzuki H Sato T Suda T Yoda T Iwakura Y Chida D 《Biochemical and biophysical research communications》2010,403(3-4):253-257
Glucocorticoids are extensively used in anti-inflammatory therapy and are thought to contribute to the steady-state regulation of hematopoiesis and lymphopoiesis. We have previously established MC2R(-/-) mice, a model of familial glucocorticoid deficiency, that show several similarities to patients with this disease, including undetectable levels of corticosterone, despite high levels of ACTH and unresponsiveness to ACTH. In this study, we analyzed the possible roles of endogenous glucocorticoids in hematopoiesis and lymphopoiesis in MC2R(-/-) and CRH(-/-) mice as models of chronic adrenal insufficiency. Our analysis of total peripheral blood cell counts revealed that the number of lymphocytes was increased and the number of erythrocytes was slightly, but significantly, decreased in MC2R(-/-) mice. Numbers of immature double negative (CD4(-) CD8(-)) thymocytes, transitional type 1 B cells in the spleen, and pre-B cells in the bone marrow, were significantly increased in MC2R(-/-) mice, suggesting that endogenous glucocorticoids contribute to steady-state regulation of lymphopoiesis. Oral glucocorticoid supplementation reversed peripheral blood cell counts and reduced numbers of T and B cells in the thymus and the spleen. T cells in the thymus and B cells in the spleen were also increased in CRH(-/-) mice, another animal model of chronic adrenal insufficiency. MC2R(-/-) mice were sensitive to age-related thymic involution, but they were resistant to fasting-associated thymic involution. Our data support the idea that endogenous glucocorticoids contribute to stress-induced as well as steady-state regulation of hematopoiesis and lymphopoiesis. 相似文献
944.
Yosuke Ueki Yuhei Uda Masaaki Sato 《Biochemical and biophysical research communications》2010,395(3):441-446
Fluid shear stress (FSS) acting on the apical surface of endothelial cells (ECs) can be sensed by mechano-sensors in adhesive protein complexes found in focal adhesions and intercellular junctions. This sensing occurs via force transmission through cytoskeletal networks. This study quantitatively evaluated the force transmitted through cytoskeletons to the mechano-sensors by measuring the FSS-induced strain on SFs using live-cell imaging for actin stress fibers (SFs). FSS-induced bending of SFs caused the SFs to align perpendicular to the direction of the flow. In addition, the displacement vectors of the SFs were detected using image correlation and the FSS-induced axial strain of the SFs was calculated. The results indicated that FSS-induced strain on SFs spanned the range 0.01-0.1% at FSSs ranging from 2 to 10 Pa. Together with the tensile property of SFs reported in a previous study, the force exerted on SFs was estimated to range from several to several tens of pN. 相似文献
945.
Jesudason R Sato S Parameswaran H Araujo AD Majumdar A Allen PG Bartolák-Suki E Suki B 《Biophysical journal》2010,99(9):3076-3083
Many fundamental cellular and extracellular processes in the body are mediated by enzymes. At the single molecule level, enzyme activity is influenced by mechanical forces. However, the effects of mechanical forces on the kinetics of enzymatic reactions in complex tissues with intact extracellular matrix (ECM) have not been identified. Here we report that physiologically relevant macroscopic mechanical forces modify enzyme activity at the molecular level in the ECM of the lung parenchyma. Porcine pancreatic elastase (PPE), which binds to and digests elastin, was fluorescently conjugated (f-PPE) and fluorescent recovery after photobleach was used to evaluate the binding kinetics of f-PPE in the alveolar walls of normal mouse lungs. Fluorescent recovery after photobleach indicated that the dissociation rate constant (koff) for f-PPE was significantly larger in stretched than in relaxed alveolar walls with a linear relation between koff and macroscopic strain. Using a network model of the parenchyma, a linear relation was also found between koff and microscopic strain on elastin fibers. Further, the binding pattern of f-PPE suggested that binding sites on elastin unfold with strain. The increased overall reaction rate also resulted in stronger structural breakdown at the level of alveolar walls, as well as accelerated decay of stiffness and decreased failure stress of the ECM at the macroscopic scale. These results suggest an important role for the coupling between mechanical forces and enzyme activity in ECM breakdown and remodeling in development, and during diseases such as pulmonary emphysema or vascular aneurysm. Our findings may also have broader implications because in vivo, enzyme activity in nearly all cellular and extracellular processes takes place in the presence of mechanical forces. 相似文献
946.
Tae Sato Satoshi Ito Yasushi Mitsuda Norihisa Soen 《Landscape and Ecological Engineering》2010,6(1):89-98
We examined the impacts of land-use history on the species composition and diversity of a warm-temperate riparian forest landscape
in Kyushu, southern Japan, focusing on the relationship between evergreen oaks and deciduous trees in natural and seminatural
forests. The species composition of 59 plots was classified into four types (A to D). Type A, which showed a significant bias
towards sites not subject to nonforest land use since 1947, had high species diversity consisting of (1) many lucidophyllous
components of the region, including the rare indigenous oak Quercus hondae, and (2) summergreen tree species of varying dominance and number representing unique or locally rare elements of the riparian
landscape in this warm-temperate region. Type B was dominated by a common species of oak, Q. glauca, and displayed less clear distribution bias with land-use history. In contrast to types A and B, types C and D, which were
characterized by high dominance of deciduous trees, had negative bias away from sites that had been under forest land use
in 1947. Presumably, intensive anthropogenic disturbances associated with nonforest land uses had expanded the habitats for
deciduous trees. This phenomenon was represented by the establishment of forests (type D) dominated by Ulmus davidiana var. japonica (UDJ) after it had been released from the suppression of evergreen forest trees during a period of nonforest land use that
prevents the successful recovery of evergreen trees. From these results we conclude that the impacts of land-use history on
the diversity of warm-temperate riparian forest landscape are multiphased: a period of nonforest land use has a strong negative
impact on lucidophyllous forest trees represented by the rare indigenous oak Q. hondae; release from the suppressive effects of the lucidophyllous species then encourages establishment of locally rare deciduous
tree flora represented by UDJ, which continue to persist for decades after abandonment of nonforest land use. 相似文献
947.
Cycloartane glycosides (1-9) were isolated from rhizomes of Curculigo orchioides (Hypoxidaceae), and this structures were determined by spectroscopic analysis and a few chemical transformations. Cytotoxic activity of glycosides (1-9) and their common aglycone (1a) against HL-60 human promyelocytic leukemia cells was also examined. 相似文献
948.
949.
950.
Mitsuhiro Obara Wataru Tamura Takeshi Ebitani Masahiro Yano Tadashi Sato Tomoyuki Yamaya 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,121(3):535-547
Root system development is an important target for improving yield in cereal crops. Active root systems that can take up nutrients
more efficiently are essential for enhancing grain yield. In this study, we attempted to identify quantitative trait loci
(QTL) involved in root system development by measuring root length of rice seedlings grown in hydroponic culture. Reliable
growth conditions for estimating the root length were first established to renew nutrient solutions daily and supply NH4
+ as a single nitrogen source. Thirty-eight chromosome segment substitution lines derived from a cross between ‘Koshihikari’,
a japonica variety, and ‘Kasalath’, an indica variety, were used to detect QTL for seminal root length of seedlings grown in 5 or 500 μM NH4
+. Eight chromosomal regions were found to be involved in root elongation. Among them, the most effective QTL was detected
on a ‘Kasalath’ segment of SL-218, which was localized to the long-arm of chromosome 6. The ‘Kasalath’ allele at this QTL,
qRL6.1, greatly promoted root elongation under all NH4
+ concentrations tested. The genetic effect of this QTL was confirmed by analysis of the near-isogenic line (NIL) qRL6.1. The seminal root length of the NIL was 13.5–21.1% longer than that of ‘Koshihikari’ under different NH4
+ concentrations. Toward our goal of applying qRL6.1 in a molecular breeding program to enhance rice yield, a candidate genomic region of qRL6.1 was delimited within a 337 kb region in the ‘Nipponbare’ genome by means of progeny testing of F2 plants/F3 lines derived from a cross between SL-218 and ‘Koshihikari’. 相似文献