Loss of Hippo signaling in Drosophila leads to tissue overgrowth as a result of increased cell proliferation and decreased cell death. YAP (a homolog of Drosophila Yorkie and target of the Hippo pathway) was recently implicated in control of organ size, epithelial tissue development, and tumorigenesis in mammals. However, the role of the mammalian Hippo pathway in such regulation has remained unclear. We now show that mice with liver-specific ablation of WW45 (a homolog of Drosophila Salvador and adaptor for the Hippo kinase) manifest increased liver size and expansion of hepatic progenitor cells (oval cells) and eventually develop hepatomas. Moreover, ablation of WW45 increased the abundance of YAP and induced its localization to the nucleus in oval cells, likely accounting for their increased proliferative capacity, but not in hepatocytes. Liver tumors that developed in mice heterozygous for WW45 deletion or with liver-specific WW45 ablation showed a mixed pathology combining characteristics of hepatocellular carcinoma and cholangiocarcinoma and seemed to originate from oval cells. Together, our results suggest that the mammalian Hippo-Salvador pathway restricts the proliferation of hepatic oval cells and thereby controls liver size and prevents the development of oval cellderived tumors.T he mammalian Hippo signaling pathway has been implicated in regulation of contact inhibition, organ size, and tumorigenesis (1-4). Such regulation is thought to be mediated by control of the expression level or localization of YAP, a major target of the Hippo pathway. YAP is overexpressed in certain mammalian cancers, and YAP transgenic mice show increased liver size and intestinal dysplasia and eventually develop liver tumors. The role of YAP in control of organ size and tumorigenesis prompted us to examine whether upstream components of the Hippo pathway indeed function to regulate YAP in this context. However, embryonic mortality (WW45 −/− , LATS2 −/− , MST1 −/− MST2 −/− , or YAP −/− ) or the absence of any overt enlargement of specific organs (LATS1 −/− ) in mice lacking such components has hampered this investigation (5-9). The generation of conditional knockout mice would thus seem to be warranted for investigation of the role of the mammalian Hippo pathway in the control of liver size and tumorigenesis.Primary liver tumors have been categorized into two major types: hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), which originate from hepatocytes and cholangiocytes, respectively. However, some primary hepatomas exhibit an intermediate or combined (HCC/CC) phenotype and are thought to be derived from transformed progenitor (oval) cells or by dedifferentiation of mature cells (10-16). Oval cells are thought to be bipotential progenitor cells that can differentiate into either hepatocytes or ductal cholangiocytes but do so only if proliferation of hepatocytes is inhibited (17-19). However, the precise mechanism responsible for regulation of oval cell proliferation and how its deregulation contributes to tumor ...
To determine the effect of weight ball throw training as a preparatory exercise before golf practice for 8 weeks on back muscle strength, weight shifting of lower body, head speed of club, and driving distance of amateur golfers.
PURPOSE: The purpose of present study was to ascertain how the activity of the serratus anterior muscle, the upper trapezius muscle and the pectoral major muscle was affected while the upper arm was being flexed at 70, 90 and 110 degrees respectively in a closed kinetic chain exercise (wall push up plus) and an open kinetic chain exercise (static hug). METHODS: Sixteen healthy young men subjects participated in the study. Surface electromyography (EMG) data were collected from the dominant-side muscles during a closed kinetic chain exercise and an open kinetic chain exercise. The activity of each muscle was measured quantitatively, and by the use of the two-way repeated ANOVA, the data were compared with each other according to exercises and shoulder flexion angles. RESULTS: Results indicated that the closed kinetic chain exercise did not interact with the open kinetic chain exercise (p>.05). In both the closed kinetic chain exercise and the open
The purpose of this study is to investigate the effectiveness of the way-finding exercise using a map in rehabilitation of cognitive function and activities of daily living in patients with a stroke. For the seven patients diagnosed with hemiplegia from a stroke, we executed the way-finding exercise using a map in the hospital, three times a week for two weeks. Loewenstein Occupational Therapy Cognitive Assessment(LOTCA) and Functional Independence Measure(FIM) were used to measure the cognitive function and performance of activities of daily living before and after intervention. For the visual perception area and the spatial relations of the spatial perception area of LOTCA, scores were significantly higher than before intervention(p<.05). For the walk/wheelchair of locomotion area and the problem solving of the social cognition area of FIM, scores were significantly higher than before intervention(p<.05). The results of this study show that a way-finding exercise for patients with a stroke is a useful therapeutic approach by enhancing cognitive function and performance of activities of daily living.■ keyword :|Activities of Daily Living|Cognitive Function|Way-Finding Exercise|Map|Stroke|
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