Transcellular transport of West Nile virus-like particles across human endothelial cells depends on residues 156 and 159 of envelope protein

<p>Abstract</p> <p>Background</p> <p>West Nile virus (WNV) causes viremia after invasion to the hosts by mosquito bite. Endothelial cells could play an important role in WNV spread from the blood stream into the central nervous system and peripheral tissues. Here, we analyzed the capacity of virus-like particles (VLPs) of the highly virulent NY99 6-LP strain (6-LP VLPs) and the low virulence Eg101 strain (Eg VLPs) to cross cultured human endothelial cells.</p> <p>Results</p> <p>6-LP VLPs were transported from the apical to basolateral side of endothelial cells, whereas Eg VLPs were hardly transported. The localization of tight junction marker ZO-1 and the integrity of tight junctions were not impaired during the transport of 6-LP VLPs. The transport of 6-LP VLPs was inhibited by treatment with filipin, which prevents the formation of cholesterol-dependent membrane rafts, suggesting the involvement of raft-associated membrane transport. To determine the amino acid residues responsible for the transport of VLPs, we produced mutant VLPs, in which residues of E protein were exchanged between the 6-LP and Eg strains. Double amino acid substitution of the residues 156 and 159 greatly impaired the transport of VLPs.</p> <p>Conclusion</p> <p>Our results suggest that a transcellular pathway is associated with 6-LP VLPs transport. We also showed that the combination of the residues 156 and 159 plays an important role in the transport of VLPs across endothelial cells.</p

Impact of cardiac support device combined with slow-release prostacyclin agonist in a canine ischemic cardiomyopathy model

BackgroundThe cardiac support device supports the heart and mechanically reduces left ventricular (LV) diastolic wall stress. Although it has been shown to halt LV remodeling in dilated cardiomyopathy, its therapeutic efficacy is limited by its lack of biological effects. In contrast, the slow-release synthetic prostacyclin agonist ONO-1301 enhances reversal of LV remodeling through biological mechanisms such as angiogenesis and attenuation of fibrosis. We therefore hypothesized that ONO-1301 plus a cardiac support device might be beneficial for the treatment of ischemic cardiomyopathy.MethodsTwenty-four dogs with induced anterior wall infarction were assigned randomly to 1 of 4 groups at 1 week postinfarction as follows: cardiac support device alone, cardiac support device plus ONO-1301 (hybrid therapy), ONO-1301 alone, or sham control.ResultsAt 8 weeks post-infarction, LV wall stress was reduced significantly in the hybrid therapy group compared with the other groups. Myocardial blood flow, measured by positron emission tomography, and vascular density were significantly higher in the hybrid therapy group compared with the cardiac support device alone and sham groups. The hybrid therapy group also showed the least interstitial fibrosis, the greatest recovery of LV systolic and diastolic functions, assessed by multidetector computed tomography and cardiac catheterization, and the lowest plasma N-terminal pro-B-type natriuretic peptide levels (P < .05).ConclusionsThe combination of a cardiac support device and the prostacyclin agonist ONO-1301 elicited a greater reversal of LV remodeling than either treatment alone, suggesting the potential of this hybrid therapy for the clinical treatment of ischemia-induced heart failure

教職を志望する大学生の特別支援教育に関する知識や指導上の不安 : 通常の学級の担当教員を志す学部生を対象として

通常の学級の担当教員を志望する大学生を対象として、特別支援教育に関する基礎的知識、ならびに特別な教育的支援を必要とする児童生徒の指導を担当することの不安等についてアンケート調査を行った。特別支援教育に関する基礎的知識に関しては、特別支援学校のセンター的機能や特別支援教育コーディネーターについての定着度が低かった。特別な教育的支援を必要とする児童生徒の指導を担当することの不安等に関しては、「学習指導」においては「適切な指導ができるか」「知識不足」、「学習環境の整備」においては「知識不足」「適切な整備ができるか」、「生徒指導と学級経営」においては「周囲の児童生徒に対する障害理解教育」「知識不足」「経験不足」「児童生徒どうしの関係づくり」、「保護者や校内外の関係機関との連携」においては、「保護者と良好な関係を築くことができるか」「保護者にむけた障害理解教育」、「その他」においては「漠然とした不安がある」「全般的な知識不足」という回答の数が上位にのぼった。A questionnaire survey was conducted on basic knowledge and concerns about teaching students with special educational needs among undergraduate students who wish to become regular classroom teachers. Regarding basic knowledge of special needs education, the level of familiarity with the central functions of special needs schools and special needs education coordinators was low. Regarding concerns about teaching students with special educational needs, respondents answered as follows: 1) “Insufficient knowledge” and “Can I provide appropriate guidance?” in “Guidance for learning”; 2) “Insufficient knowledge” and “Can I provide appropriate improvement of learning environment?” in “Maintenance of learning environment”; 3) “Education to understand disabilities for surrounding students,” “Insufficient knowledge,” “Lack of experience,” “Building relationships among students” in “Student guidance and classroom management”; 4) “Can I built a good relationship with students’ parents?” and “Education to understand disabilities for students’ parents” in “Cooperation with parents and related organizations inside and outside the school”; 5) “Vague sense of anxiety” and “Overall poor knowledge” in the “others” category.本稿は、日本特殊教育学会第60回大会において発表した内容に加筆・修正を加えたものである

A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from processing of autologous human induced pluripotent stem(-like) cells

As a series of endeavors to establish suitable measures for the sound development of regenerative medicine using human stem cell-based products, we studied scientific principles, concepts, and basic technical elements to ensure the quality and safety of therapeutic products derived from autologous human iPS cells or iPS cell-like cells, taking into consideration scientific and technological advances, ethics, regulatory rationale, and international trends in human stem cell-derived products. This led to the development of the Japanese official Notification No. 0907-4, “Guideline on Ensuring the Quality and Safety of Pharmaceuticals and Medical Devices Derived from the Processing of Autologous Human Induced Pluripotent Stem(-Like) Cells, ” issued by Pharmaceuticals and Food Safety Bureau, Ministry of Health, Labour and Welfare of Japan, on September 7, 2012. The present paper addresses various aspects of products derived from autologous human iPS cells (or iPS cell-like cells), in addition to similar points to consider that are described previously for autologous human stem cell-based products. Major additional points include (1) possible existence of autologous human iPS cell-like cells that are different from iPS cells in terms of specific biological features; (2) the use of autologous human iPS(-like) cells as appropriate starting materials for regenerative medicine, where necessary and significant; (3) establishment of autologous human iPS(-like) cell lines and their characterization; (4) cell banking and/or possible establishment of intermediate cell lines derived from autologous human iPS(-like) cells at appropriate stage(s) of a manufacturing process, if necessary; and (5) concerns about the presence of undifferentiated cells in the final product; such cells may cause ectopic tissue formation and/or tumorigenesis. The ultimate goal of this guidance is to provide suitable medical opportunities as soon as possible to the patients with severe diseases that are difficult to treat with conventional modalities

Ultrafast isomerization-induced cooperative motions to higher molecular orientation in smectic liquid-crystalline azobenzene molecules

The photoisomerization of molecules is widely used to control the structure of soft matter in both natural and synthetic systems. However, the structural dynamics of the molecules during isomerization and their subsequent response are difficult to elucidate due to their complex and ultrafast nature. Herein, we describe the ultrafast formation of higherorientation of liquid-crystalline (LC) azobenzene molecules via linearly polarized ultraviolet light (UV) using ultrafast time-resolved electron diffraction. The ultrafast orientation is caused by the trans-to-cis isomerization of the azobenzene molecules. Our observations are consistent with simplified molecular dynamics calculations that revealed that the molecules are aligned with the laser polarization axis by their cooperative motion after photoisomerization. This insight advances the fundamental chemistry of photoresponsive molecules in soft matter as well as their ultrafast photomechanical applications