現代日本語における助詞「ト」の研究 : 引用の周辺にある「ト」を中心に

筑波大学 (University of Tsukuba)201

2D or 3D? How cell motility measurements are conserved across dimensions in vitro and translate in vivo

Cell motility is a critical aspect of several processes such as wound healing and immunity; however, it is dysregulated in cancer. Current limitations of imaging tools make it difficult to study cell migration in vivo. To overcome this, and to identify drivers from the microenvironment that regulate cell migration, bioengineers have developed 2D and 3D tissue model systems in which to study cell motility in vitro, with the aim of mimicking elements of the environments in which cells move in vivo. However, there has been no systematic study to explicitly relate and compare cell motility measurements between these geometries or systems. Here, we provide such analysis on our own data, as well as across data in existing literature to understand whether, and which, metrics are conserved across systems. To our surprise, only one metric of cell movement on 2D surfaces significantly and positively correlates with cell migration in 3D environments (percent migrating cells, and cell invasion in 3D has a weak, negative correlation with glioblastoma invasion in vivo. Finally, to compare across complex model systems, in vivo data, and data from different labs, we suggest that groups report an effect size, a statistical tool that is most translatable across experiments and labs, when conducting experiments that affect cellular motility

Serum creatinine as a predictor of functional and anatomical success in diabetic tractional retinal detachment

Pacientes con Desprendimiento de retina traccional diabéticoObjectives: The aim of the study was to evaluate pre-operative, intraoperative, and post-operative factors associated with functional and anatomical success in patients with diabetic tractional retinal detachment (TRD) treated with pars plana vitrectomy (PPV). Material and Methods: We retrospectively reviewed the medical records of patients with diabetic TRD surgically repaired with PPV between March 2014 and February 2015 at the Instituto de Oftalmología Fundación de Asistencia Privada Conde de Valenciana, IAP in Mexico City. A total of 250 records were reviewed and 85 met the inclusion criteria. Pre-operative, intraoperative, and post-operative variables were obtained from all records. Statistical analysis included Fisher’s exact test, Kruskal–Wallis test, and Mann–Whitney U test. Results: A total of 88 eyes of 85 patients were included in the study. The average patient age at the time of the surgery was 51.53 years (SD ± 11.99). At post-operative month (POM) 1, a greater pre-operative serum creatinine value and a greater surgical duration were associated with a worse anatomical success (P = 0.032; P = 0.014). At POM 1, 31% of the eyes with macula-involved TRD and 57.5% of the eyes without macula-involved TRD achieved visual success (P = 0.013, Fisher’s exact test). Conclusion: A greater pre-operative serum creatinine value was associated with a worse visual and anatomical outcome at POM 1. A macula-involved TRD was associated with a worse visual outcome at POM 3. Post-operative complications were associated with a worse functional and/or anatomical success at the final follow-up visit (P < 0.05).https://orcid.org/0000-0002-1310-9852Revista Internacional - No indexadaN

Characteristics of Cricopharyngeal Dysphagia After Ischemic Stroke

ObjectiveTo evaluate the characteristics of cricopharyngeal dysfunction (CPD), the frequency, and correlation with a brain lesion in patients with first-ever ischemic stroke, and to provide basic data for developing a therapeutic protocol for dysphagia management.MethodsWe retrospectively reviewed the medical records of a series of subjects post-stroke who underwent a videofluoroscopic swallowing study (VFSS) from January 2009 to December 2015. VFSS images were recorded on videotape and analyzed. CPD was defined as the retention of more than 25% of residue in the pyriform sinus after swallowing. The location of the brain lesion was assessed using magnetic resonance imaging.ResultsAmong the 262 dysphagic patients with first-ever ischemic stroke, 15 (5.7%) showed CPD on the VFSS. Patients with an infratentorial lesion had a significantly higher proportion of CPD than those with a supratentorial lesion (p=0.003), and lateral medullary infarction was identified as the single independent predictor of CPD (multivariable analysis: odds ratio=19.417; confidence interval, 5.560–67.804; p<0.0001). Compared to patients without CPD, those with CPD had a significantly prolonged pharyngeal transit time, lower laryngeal elevation, and a higher pharyngeal constriction ratio and functional dysphagia scale score.ConclusionOverall, the results support the notion that an impaired upper esopharyngeal opening is likely related to the specific locations of brain lesions. The association of CPD with lateral medullary infarction can be explained based on the regulation of the pharyngolaryngeal motor system by the motor neurons present in the dorsal nucleus ambiguus. Overall, the results reveal the relation between CPD and the problems in the pharyngeal phase as well as the severity of dysphagia

CAGE Binds to Beclin1, Regulates Autophagic Flux and CAGE-Derived Peptide Confers Sensitivity to Anti-cancer Drugs in Non-small Cell Lung Cancer Cells

The objective of this study was to determine the role of CAGE, a cancer/testis antigen, in resistance of non-small cell lung cancers to anti-cancer drugs. Erlotinib-resistant PC-9 cells (PC-9/ER) with EGFR mutations (ex 19 del + T790M of EGFR), showed higher level of autophagic flux than parental sensitive PC-9 cells. Erlotinib and osimertinib increased autophagic flux and induced the binding of CAGE to Beclin1 in PC-9 cells. The inhibition or induction of autophagy regulated the binding of CAGE to Beclin1 and the responses to anti-cancer drugs. CAGE showed binding to HER2 while HER2 was necessary for binding of CAGE to Beclin1. CAGE was responsible for high level of autophagic flux and resistance to anti-cancer drugs in PC-9/ER cells. A peptide corresponding to the DEAD box domain of CAGE, 266AQTGTGKT273, enhanced the sensitivity of PC-9/ER cells to erlotinib and osimertinib, inhibited the binding of CAGE to Beclin1 and regulated autophagic flux in PC-9/ER cells. Mutant CAGE-derived peptide 266AQTGTGAT273 or 266AQTGTGKA273 did not affect autophagic flux or the binding of CAGE to Beclin1. AQTGTGKT peptide showed binding to CAGE, but not to Beclin1. FITC-AQTGTGKT peptide showed co-localization with CAGE. AQTGTGKT peptide decreased tumorigenic potentials of PC-9/ER and H1975 cells, non-small cell lung cancer (NSCLC) cells with EGFR mutation (L885R/T790M), by inhibiting autophagic fluxand inhibiting the binding of CAGE to Beclin1. AQTGTGKT peptide also enhanced the sensitivity of H1975 cells to anti-cancer drugs. AQTGTGKT peptide showed tumor homing potential based on ex vivo homing assays of xenograft of H1975 cells. AQTGTGKT peptide restored expression levels of miR-143-3p and miR-373-5p, decreased autophagic flux and conferred sensitivity to anti-cancer drugs. These results present evidence that combination of anti-cancer drug with CAGE-derived peptide could overcome resistance of non-small cell lung cancers to anti-cancer drugs

Development of a multi-channel NIRS-USG hybrid imaging system for detecting prostate cancer and improving the accuracy of imaging-based diagnosis: a phantom study

Purpose This study aimed to develop a multi-channel near-infrared spectroscopy (NIRS) and ultrasonography (USG) fusion imaging system for imaging prostate cancer and to verify its diagnostic capability by applying the hybrid imaging system to a prostate cancer phantom. Methods A multi-channel NIRS system using the near-infrared 785-nm wavelength with 12 channels and four detectors was developed. After arranging the optical fibers around a USG transducer, we performed NIRS imaging and grayscale USG imaging simultaneously. Fusion imaging was obtained by processing incoming signals and the spatial reconstruction of NIRS, which corresponded with grayscale USG acquired at the same time. The NIRS-USG hybrid system was applied to a silicone-based optical phantom of the prostate gland containing prostate cancer to verify its diagnostic capability qualitatively. Results The NIRS-USG hybrid imaging system for prostate cancer imaging simultaneously provided anatomical and optical information with 2-dimensional registration. The hybrid imaging system showed more NIR attenuation over the prostate cancer model than over the model of normal prostate tissue. Its diagnostic capability to discriminate a focal area mimicking the optical properties of prostate cancer from the surrounding background mimicking the optical properties of normal prostate tissue was verified by applying the hybrid system to a silicone-based optical phantom of prostate cancer. Conclusion This study successfully demonstrated that the NIRS-USG hybrid system may serve as a new imaging method for improving the diagnostic accuracy of prostate cancer, with potential utility for future clinical applications

Extreme glacial cooling likely led to hominin depopulation of Europe in the Early Pleistocene

The oldest known hominin remains in Europe [~1.5 to ~1.1 million years ago (Ma)] have been recovered from Iberia, where paleoenvironmental reconstructions have indicated warm and wet interglacials and mild glacials, supporting the view that once established, hominin populations persisted continuously. We report analyses of marine and terrestrial proxies from a deep-sea core on the Portugese margin that show the presence of pronounced millennial-scale climate variability during a glacial period ~1.154 to ~1.123 Ma, culminating in a terminal stadial cooling comparable to the most extreme events of the last 400,000 years. Climate envelope–model simulations reveal a drastic decrease in early hominin habitat suitability around the Mediterranean during the terminal stadial. We suggest that these extreme conditions led to the depopulation of Europe, perhaps lasting for several successive glacial-interglacial cycles

Extreme glacial cooling likely led to hominin depopulation of Europe in the Early Pleistocene

The oldest known hominin remains in Europe [~1.5 to ~1.1 million years ago (Ma)] have been recovered from Iberia, where paleoenvironmental reconstructions have indicated warm and wet interglacials and mild glacials, supporting the view that once established, hominin populations persisted continuously. We report analyses of marine and terrestrial proxies from a deep-sea core on the Portugese margin that show the presence of pronounced millennial-scale climate variability during a glacial period ~1.154 to ~1.123 Ma, culminating in a terminal stadial cooling comparable to the most extreme events of the last 400,000 years. Climate envelope-model simulations reveal a drastic decrease in early hominin habitat suitability around the Mediterranean during the terminal stadial. We suggest that these extreme conditions led to the depopulation of Europe, perhaps lasting for several successive glacial-interglacial cycles.We gratefully acknowledge financial support from The Leverhulme Trust grant RPG-2014-417 (P.C.T., V.M., and D.A.H.); the Catalan Government, Research Group 2021SGR00986 (J.O.G.); IBS, South Korea grant IBS-R028-D1 (A.T., K.-S.Y., and H.K.); the Human Origins Research Fund (C.B.S.); and the Calleva Foundation (C.B.S., S.A.P., and N.M.A.).Peer reviewe