Identification of Pip4k2β as a mechanical stimulus responsive gene and its expression during musculoskeletal tissue healing
Sakae SanoAkihiko OkawaArata NakajimaMasamichi TaharaKoji FujitaYuichi WadaMasashi YamazakiHideshige MoriyaTakahisa Sasho
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Activating mutations of fibroblast growth factor receptor 3 (FGFR3) cause various skeletal dysplasias and are also associated with certain cancers.Because there are no known specific pharmaceutical inhibitors of FGFR3, we established a cell-based protein translocation assay system that can monitor FGFR3 activity and be used for high throughput screening of complex mixtures.With this system we identified ethanol extract from a plant as a FGFR3 inhibitor and performed bioassay-guided fractionation to identify potent active fractions.The functionality of extract and active fractions were validated in vitro in FGFR3-activated primary multiple myeloma cells.The therapeutic efficacy and safety of the active fractions were further assessed in FGFR3 ACH mice, an achondroplasia mouse model.Oral administration significantly improved growth and dwarfism-related clinical features of the FGFR3 ACH mice.Our results demonstrate the applicability of this discovery approach.The identified plant extracts and active factions hold therapeutic potential for the treatment of FGFR3-activated skeletal dysplasias and cancers.
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We develop and estimate a small open economy DSGE model to investigate the effectiveness of the Australian fiscal stimulus package introduced in the aftermath of the global financial crisis (GFC). The timing and magnitudes of GFC shocks, fiscal shocks that mimic the stimulus transfers, and accommodative monetary policy shocks are carefully calibrated and fed into various simulation experiments. The results suggest that the stimulus transfers were effective in combating the economic downturn caused by the GFC, however, the scale of the transfer initiative seems to be excessive.
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It has been reported that if two sensory stimuli are presented consecutively with stimulus onset asynchrony (SOA) of as short as several hundreds of milliseconds, the neural activity, elicited by the second stimulus, in the stimulus-sensitive area will be inhibited, say, suppressive phenomenon. Using a paired-stimulus paradigm, in which two visual stimuli were successively presented, we investigated the influence of SOA (200ms, 400ms & 600ms) on suppressive phenomenon in face processing. Twelve subjects were asked to passively view randomly ordered paired stimuli and single stimuli, while their event-related potentials (ERPs) were recorded simultaneously. To evaluate the suppression, we compared the ERPs elicited by the second face stimulus of the paired stimuli with that elicited by the single face stimulus. It was found that, comparing with the ERPs elicited by single faces, in all three SOA conditions, the ERPs elicited by the second face stimulus of the intra-category trials (face_face trials) were more suppressed than those of the inter-category trials (blank_face and building_face trials) in both occipitotemporal and frontal regions. We surmised that these results might support a "domain specific" theory, which suggested that visual processing of faces and non-face objects involve separate and specialized networks in the ventro-lateral temporal cortex. Interestingly, for the face_face trials, as the SOA increased, the ERP suppression in the frontal region diminished gradually. Such phenomenon might be due to the lasting effect of semantic processing for the first face stimulus.
Stimulus (psychology)
Stimulus onset asynchrony
Phenomenon
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Bystander effect
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