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Erica K. Husser PhD Donna M. Fick PhD Marie Boltz PhD Priyanka Shrestha RN MS Jonathan Siuta MD Shannon Malloy MA Abigail Overstreet MA Douglas L. Leslie PhD Long Ngo PhD Yoojin Jung MS PhD Sharon K. Inouye MD MPH Edward R. Marcantonio MD MSc 《Journal of the American Geriatrics Society》2021,69(5):1349-1356
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Yoojin Kwun Hye Won Park Min-ju Kim Byong Sop Lee Ellen Ai-Rhan Kim 《Journal of Korean medical science》2015,30(4):450-455
This study aimed to evaluate the validity of the ages and stages questionnaire in Korean (ASQ 1st edition, Korean Questionnaires, Seoul Community Rehabilitation Center, 2000) for premature infants. The study population consisted of 90 premature infants born between January 1, 2005, and December 31, 2011, who were tested using the ASQ (Korean) and Bayley Scales of Infant Development (BSID) (II) at a corrected age of 18-24 months. The validity of the ASQ (Korean) using cut-off values set at < -2 SD was examined by comparing it to the BSID (II) components, namely, the mental developmental index (MDI) or psychomotor developmental index (PDI), which were both set at < 85. The calculation of the sensitivities, specificities, positive predictive values, and negative predictive values of the ASQ (Korean) components revealed that they detected infants with neurodevelopmental delay with low sensitivity and positive predictive values, however, the communication domain showed moderate correlations with MDI. The failure in more than one domain of the ASQ (Korean) was significantly correlated with the failure in MDI. The ASQ (Korean) showed low validity for screening neurodevelopmentally delayed premature infants.
Graphical Abstract
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Listeria monocytogenes is a bacterial pathogen that multiplies in the cytosol of host cells and spreads directly from cell to cell by using an actin-based mechanism of motility. The broad-range phospholipase C (PC-PLC) of L. monocytogenes contributes to bacterial escape from vacuoles formed upon cell-to-cell spread. PC-PLC is made as an inactive proenzyme whose activation requires cleavage of an N-terminal propeptide. During infection, PC-PLC is activated specifically in acidified vacuoles. To assess the importance of compartmentalizing PC-PLC activity during infection, we created a mutant that makes constitutively active PC-PLC (the plcBDelta pro mutant). Results from intracellular growth and cell-to-cell spread assays showed that the plcBDelta pro mutant was sensitive to gentamicin, suggesting that unregulated PC-PLC activity causes damage to host cell membranes. This was confirmed by the observation of a twofold increase in staining of live infected cells by a non-membrane-permeant DNA fluorescent dye. However, membrane damage was not sufficient to cause cell lysis and was dependent on bacterial cell-to-cell spread, suggesting that damage was localized to bacterium-containing filopodia. Using an in vivo competitive infection assay, we observed that the plcBDelta pro mutant was outcompeted up to 200-fold by the wild-type strain in BALB/c mice. Virulence attenuation was greater when mice were infected orally than when they were infected intravenously, presumably because the plcBDelta pro mutant was initially outcompeted in the intestines, reducing the number of mutant bacteria reaching the liver and spleen. Together, these results emphasize the importance for L. monocytogenes virulence of compartmentalizing the activity of PC-PLC during infection. 相似文献
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Jiah Lim Yoojin Song Jung-Hee Jang Chul-Ho Jeong Sooyeun Lee Byoungduck Park Young Ho Seo 《Archives of pharmacal research》2018,41(10):967-976
Aspirin is one of the oldest drugs for the treatment of inflammation, fever, and pain. It is reported to covalently modify COX-2 enzyme by acetylating a serine amino acid residue. By virtue of aspirin’s acetylating potential, we for the first time developed novel acetyl-donating HDAC inhibitors. In this study, we report the design, synthesis, in silico docking study, and biological evaluation of acetyl-donating HDAC inhibitors. The exposure of MDA-MB-231 cells with compound 4c significantly promotes the acetylation of α-tubulin and histone H3, which are substrates of HDAC6 and HDAC1, respectively. In silico docking simulation also indicates that compound 4c tightly binds to the deep substrate-binding pocket of HDAC6 by coordinating the active zinc ion in a bidentate manner and forming hydrogen bond interactions with Ser531 and His573 amino acid residues. In particular, compound 4c (GI50?=?147 μM) affords the significant enhancement of anti-proliferative effect on MDA-MB-231 cells, compared with its parent compound 2c (GI50?>?1000 μM) and acetyl-donating group deficient compound 6 (GI50?=?554 μM). Overall, compound 4c presents a novel strategy for developing acetyl-donating HDAC inhibitors. 相似文献
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Yaqing Su Yoojin Chung Dan F. M. Goodman Kenneth E. Hancock Bertrand Delgutte 《Journal of the Association for Research in Otolaryngology》2021,22(3):319
Although pitch is closely related to temporal periodicity, stimuli with a degree of temporal irregularity can evoke a pitch sensation in human listeners. However, the neural mechanisms underlying pitch perception for irregular sounds are poorly understood. Here, we recorded responses of single units in the inferior colliculus (IC) of normal hearing (NH) rabbits to acoustic pulse trains with different amounts of random jitter in the inter-pulse intervals and compared with responses to electric pulse trains delivered through a cochlear implant (CI) in a different group of rabbits. In both NH and CI animals, many IC neurons demonstrated tuning of firing rate to the average pulse rate (APR) that was robust against temporal jitter, although jitter tended to increase the firing rates for APRs ≥ 1280 Hz. Strength and limiting frequency of spike synchronization to stimulus pulses were also comparable between periodic and irregular pulse trains, although there was a slight increase in synchronization at high APRs with CI stimulation. There were clear differences between CI and NH animals in both the range of APRs over which firing rate tuning was observed and the prevalence of synchronized responses. These results suggest that the pitches of regular and irregular pulse trains are coded differently by IC neurons depending on the APR, the degree of irregularity, and the mode of stimulation. In particular, the temporal pitch produced by periodic pulse trains lacking spectral cues may be based on a rate code rather than a temporal code at higher APRs. 相似文献