Matrix metalloproteinases (MMPs) have been implicated in wound healing. To analyze the roles of MMP-9 and MMP-13 in wound healing, we generated full-thickness cutaneous wounds in MMP-9 knockout (KO), MMP-13 KO, MMP-9/13 double KO, and wild-type mice. Macroscopic wound closure was delayed in all of the KO mice, as compared with wild-type mice. The rate of re-epithelialization was significantly delayed in MMP-9 KO and MMP-13 KO mice and remarkably delayed in MMP-9/13 double KO mice, as compared with wild-type mice. Both MMP-9 and MMP-13 were expressed by the leading edges of epidermal cells in wild-type mice, and the migration of keratinocytes was suppressed by treatment with an MMP inhibitor or transfection of small interfering RNAs for MMP-9 or MMP-13, as compared with controls. The vascular density in wound granulation was significantly lower in both MMP-13 KO and MMP-9/13 double KO mice than in wild-type mice. Degradation of connective tissue growth factor in wound tissue was transiently prevented in MMP-13 KO mice. Morphometric analyses demonstrated a reduction in both wound contraction and myofibroblast formation in both MMP-13 KO and MMP-9/13 double KO mice. Proliferation and transforming growth factor-beta1-induced myofibroblast differentiation of dermal fibroblasts from MMP-13 KO mice were decreased, as compared with wild-type dermal fibroblasts. These data suggest that MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in wound healing, while MMP-9 functions in keratinocyte migration.
which are described as BCN(H) and BC 3 N(H), have been prepared by the interaction of acetonitrile with boron trichloride in a hydrogen and nitrogen atmosphere and acrylonitrile with boron trichloride, respectively. X-ray and electron diffraction analyses indicate that these materials have hexagonal structures similar to that of graphite. ESCA spectra and the possible chemical bonds suggest that the ideal structure of BCN is made of the unit structure of BC 2 N + BN, while BC 3 N is composed of BC 3 N + BNC 3 . A BCN(H) plate has a basal-plane conductivity of 1.28 (Ω cm) -1 at room temperature, while a BC 3 N(H) plate has that of 88.5 (Ω cm) -1 . Thermoelectric measurements indicate that both materials behave as p-type semiconductors and a BCN(H) plate has a high Seebeck coefficient of 300 µV/°K at room temperature in air.
Abstract. We describe our data collection and results on activity recognition with wearable, coin-sized sensor devices. The devices were attached to four different parts of the body: right thigh and wrist, left wrist and to a necklace on 13 different testees. In this experiment, data was from 17 daily life examples from male and female subjects. Features were calculated from triaxial accelerometer and heart rate data within different sized time windows. The best features were selected with forward-backward sequential search algorithm. Interestingly, acceleration mean values from the necklace were selected as important features. Two classifiers (multilayer perceptrons and kNN classifiers) were tested for activity recognition, and the best result (90.61 % aggregate recognition rate for 4-fold cross validation) was achieved with a kNN classifier.
MRP1 is a 190-kDa membrane glycoprotein that confers multidrug resistance (MDR) to tumor cells. MRP1 is characterized by an N-terminal transmembrane domain (TMD 0 ), which is connected to a P-glycoprotein-like core region (⌬MRP) by a cytoplasmic linker domain zero (L 0 ).It has been demonstrated that GSH plays an important role in MRP1-mediated MDR. However, the mechanism by which GSH mediates MDR and the precise roles of TMD 0 and L 0 are not known. We synthesized [125 I]11-azidophenyl agosterol A ([ 125 I]azidoAG-A), a photoaffinity analog of the MDR-reversing agent, agosterol A (AG-A), to photolabel MRP1, and found that the analog photolabeled the C-proximal molecule of MRP1 (C 932-1531) in a manner that was GSH-dependent. The photolabeling was inhibited by anticancer agents, reversing agents and leukotriene C 4 . Based on photolabeling studies in the presence and absence of GSH using membrane vesicles expressing various truncated, co-expressed, and mutated MRP1s, we found that L 0 is the site on MRP1 that interacts with GSH. This study demonstrated that GSH is required for the binding of an unconjugated agent to MRP1 and suggested that GSH interacts with L 0 of MRP1. The photoanalog of AG-A will be useful for identifying the drug binding site within MRP1, and the role of GSH in transporting substrates by MRP1.Following exposure to a natural product chemotherapeutic agent, tumor cells often acquire resistance to several structurally and functionally unrelated drugs, so-called multidrug resistance (MDR).1 MDR is the major obstacle to successful cancer chemotherapy. Two membrane proteins, P-glycoprotein (Pgp) and the human multidrug resistance protein (MRP1) are frequently overexpressed in MDR cells (for reviews see Refs. 1-4). Although both MRP1 (190 kDa) and P-gp (170 kDa) are members of the family of ATP-binding cassette transporters (5), they share only 15% amino acid sequence identity (6). The amino acid sequence suggests that P-gp consists of two homologous halves and a variable linker region. Each half of the protein has six transmembrane segments and one nucleotide binding domain (NBD). MRP1 differs from P-gp by the presence of an extra N-terminal extension with five transmembrane segments (TMD 0 ), which is connected to the P-gp-like core (⌬MRP) by a cytoplasmic linker domain zero (L 0 ) (7, 8).The precise roles of TMD 0 and L 0 are unknown. Although MRP1 and P-gp both confer multidrug resistance by actively effluxing drugs from the cells (9, 10), there is compelling evidence that they function very differently in drug transport (6, 11). P-gp confers multidrug resistance by directly binding and transporting unmodified drugs (12, 13). MRP1, however, is an active transporter of amphiphilic conjugated organic anions, including a number of compounds conjugated with GSH, glucuronide, and sulfate. To date, leukotriene C 4 (LTC 4 ) is the best substrate for MRP1 (14). It has been reported that GSH plays a critical role in MRP1-mediated MDR (15). Reduction of GSH level in MRP1-expressing cells by buthionine su...
Complete mitochondrial cytochrome b sequences of 54 species, including 18 newly sequenced, were analyzed to infer the phylogenetic relationships within the family Cyprinidae in East Asia. Phylogenetic trees were generated using various tree-building methods, including Neighbor-joining (NJ), Maximum Parsimony (MP) and Maximum Likelihood (ML) methods, with Myxocyprinus asiaticus (family Catostomidae) as the designated outgroup. The results from NJ and ML methods were mostly similar, supporting some existing subfamilies within Cyprinidae as monophyletic, such as Cultrinae, Xenocyprinae and Gobioninae (including Gobiobotinae). However, genera within the subfamily "Danioninae" did not form a monophyletic group. The subfamily Leuciscinae was divided into two unrelated groups: the "Leuciscinae" in East Asia forming as a monophyletic group together with Cultrinae and Xenocyprinae, while the Leuciscinae in Europe, Siberia, and North America as another monophyletic group. The monophyly of subfamily Cyprininae sensu Howes was supported by NJ and ML trees and is basal in the tree. The position of Acheilognathinae, a widely accepted monophyletic group represented by Rhodeus sericeus, was not resolved.Keywords: Cyprinidae, cytochrome b, molecular phylogeny, Pisces. DOI: 10.1360/03yc0034Cyprinidae, the largest fish family, comprises approximately 210 recognized genera and 2010 species that are distributed widely in Eurasia, East Indian Island, Africa, and North America [1] . Species richness of this family is the greatest in East Asia, for example, China has 122 genera and more than 600 species. It is difficult to build a comprehensive phylogeny of Cyprinidae due to the large number of genera and species.The classification of this family has been subject to revisions and rearrangements since Cuvier first established it in 1817. Bonaparte [2] , Bleeker [3] , and Gunther [4] recognized various subgroups. On the basis of barbels distribution, morphotype and innervations, Howes [5] recognized the Cyprinidae as containing the subfamilies Cyprininae, Gobioninae, Rasborinae (which lack or sporadically possess barbels), LeuMolecular phylogenetics of Cyprinidae 131 ciscinae, Acheilognathinae, Cultrinae, and Alburninae.In a morphological-based phylogenetic study, Chen et al. [6] proposed that the Cyprinidae could be divided into 10 subfamilies which grouped into two tribes: series Leuciscini, (((Acheilognathinae, Gobioninae) ((Xenocyprinae, Cultrinae) Leuciscinae)) Danioninae), and series Barbini, (Tincinae (Labeoninae (Cyprininae, Barbinae))), with subfamily G obiobotinae included in Gobioninae and Schizothoracinae in Barbinae. The intergeneric relationships of the subfamilies Danioninae and Leuciscinae remained unresolved. Cavender and Coburn [7] presented a phylogenetic hypothesis of cyprinid relationships based on a cladistic analysis. Chen [8] and Yue [9] proposed classifications of Cyprinidae based on morphological characteristics and suggested that further studies on the phylogeny and evolution within the Cyprini...
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