Nucleic Acid-Based Therapy: Development of a Nonviral-Based Delivery Approach

Gene therapy returns to the center stage of medicine to treat patients with diseases that are unable to be cured with the conventional therapeutic strategies. This development is due to various reasons, including vector development and significant achievement in next-generation sequencing. Among the various methodologies of gene therapy, nucleic acid-based therapy has been considered to be promising in various diseases. The development of delivery methods to target cells in vivo, however, remains critical. These include viral vector-based and nonviral vector-based gene delivery methods as well as physical approaches such as hydrodynamic gene delivery (HGD). HGD is a simple and effective in vivo gene transfer method for the functional analysis of therapeutic genes and regulatory elements in small animals. Moreover, this chapter outlines the principle of HGD, gene expression studies in rodents, and recent advances in clinical application of HGD and provides future perspectives in developing a safe and efficient method for nucleic acid-based therapy

Population genetic structure ofYamato-sllijimi clam in Lake Sbinji, Japan

Yamato-shijimiclam Corbicula japonica is the best-known bivalve inhabiting ln brackish estuaries and lakes around Japan and one of the most commercially important species in inland fisheries. Althoughthe amotmt of C japonica from Lake Shinji has accotmted for the large part of the domestic catch, itsamolmt has dramatically fallen in recent years･ This study was conducted to verifythe genetic structtue and reproduction mechanism of C･ japonica, both of which are essential to its stock management in Lake Shinji. Weanalyzed sequence polymorphism of the 588 bp portion ofthemitochondrial DNA cytochrome oxidase subunit I (Col) gene to determinethe population genetic structure of C･ japonica in Lake Shinji･Among a total of 177 C･ japonica specimens collected from 4 colonies, 37 haplotypes were obtained, and 2 major haplotypes were apparent withrelatively highabtmdance in all colonies･ Well correspondingmismatch distributions along the Col gene were determined for the data sets of the individual colonies, and the pairwise population estimates FsT among the individual colonies were also generally low, Such small genetic differentiation of C japonica is derived kom highgeneflow in Lake Shinji, and this could be caused by a lake-wide dispersion of its larvae mediated by the water movements･Article信州大学山地水環境教育研究センター研究報告 6: 115-124(2010)departmental bulletin pape

Magnetic resonance imaging of obesity and metabolic disorders: Summary from the 2019 ISMRM Workshop

More than 100 attendees from Australia, Austria, Belgium, Canada, China, Germany, Hong Kong, Indonesia, Japan, Malaysia, the Netherlands, the Philippines, Republic of Korea, Singapore, Sweden, Switzerland, the United Kingdom, and the United States convened in Singapore for the 2019 ISMRM-sponsored workshop on MRI of Obesity and Metabolic Disorders. The scientific program brought together a multidisciplinary group of researchers, trainees, and clinicians and included sessions in diabetes and insulin resistance; an update on recent advances in water–fat MRI acquisition and reconstruction methods; with applications in skeletal muscle, bone marrow, and adipose tissue quantification; a summary of recent findings in brown adipose tissue; new developments in imaging fat in the fetus, placenta, and neonates; the utility of liver elastography in obesity studies; and the emerging role of radiomics in population-based “big data” studies. The workshop featured keynote presentations on nutrition, epidemiology, genetics, and exercise physiology. Forty-four proffered scientific abstracts were also presented, covering the topics of brown adipose tissue, quantitative liver analysis from multiparametric data, disease prevalence and population health, technical and methodological developments in data acquisition and reconstruction, newfound applications of machine learning and neural networks, standardization of proton density fat fraction measurements, and X-nuclei applications. The purpose of this article is to summarize the scientific highlights from the workshop and identify future directions of work

In-Plane Anisotropy and Temperature Dependence of Oxygen Phonon Modes in YBa₂Cu₃O₆.₉₅

Inelastic pulsed neutron scattering measurements on YBa2Cu3O6.95 single crystals indicate that the sample has a distinct a-b plane anisotropy in the oxygen vibrations. The Cu-O bond-stretching-type phonons, which are suspected to interact strongly with charge, are simultaneously observed along the a and b directions due to a 7-meV splitting arising from the orthorhombicity, even though the sample is twinned. The bond-stretching LO branch with the polarization along a (perpendicular to the chain) loses intensity beyond the middle of the zone, indicating branch splitting as seen in doped nickelates, with the second branch being located at 10 meV below. The mode along b has a continuous dispersion. These modes show temperature dependence, which parallels that of superconductive order parameter, suggesting significant involvement of phonons in the superconductivity of this compound

Effectiveness of vital staining with iodine solution in reducing local recurrence after resection of dysplastic or malignant oral mucosa

The purpose of this retrospective study was to assess the effect of vital staining with iodine solution in reducing local recurrence after resection of dysplastic or malignant oral mucosa. The historical control group had dysplastic or malignant mucosal lesions resected solely on the evidence of direct inspection and palpation. In the vital staining group tissue was resected only after vital staining with iodine solution. Seven of 25 patients in the conventional group developed recurrent dysplastic or cancerous oral mucosa around the primary site, while no patient among 23 reported recurrence in the vital staining group (p < 0.01). Kaplan Meier assessment showed that the 5-year primary control rate was 100% in the vital staining group and 75% in the conventional group. Although this retrospective study has some limitations, the results suggest that vital staining with iodine may be useful in reducing the incidence of recurrence of dysplastic or cancerous epithelium at a primary site. Further well-controlled study is essential.ArticleBRITISH JOURNAL OF ORAL & MAXILLOFACIAL SURGERY. 50(2):109-112 (2012)journal articl

Impact of Normothermic Preservation with Extracellular Type Solution Containing Trehalose on Rat Kidney Grafting from a Cardiac Death Donor

BACKGROUND: The aim of this study was to investigate factors that may improve the condition of a marginal kidney preserved with a normothermic solution following cardiac death (CD) in a model of rat kidney transplantation (RTx). METHODS: Post-euthanasia, Lewis (LEW) donor rats were left for 1 h in a 23°C room. These critical kidney grafts were preserved in University of Wisconsin (UW), lactate Ringer's (LR), or extracellular-trehalose-Kyoto (ETK) solution, followed by intracellular-trehalose-Kyoto (ITK) solution at 4, 23, or 37°C for another 1 h, and finally transplanted into bilaterally nephrectomized LEW recipient rats (n = 4-6). Grafts of rats surviving to day 14 after RTx were evaluated by histopathological examination. The energy activity of these marginal rat kidneys was measured by high-performance liquid chromatography (HPLC; n = 4 per group) and fluorescence intensity assay (n = 6 per group) after preservation with UW or ETK solutions at each temperature. Finally, the transplanted kidney was assessed by an in vivo luciferase imaging system (n = 2). RESULTS: Using the 1-h normothermic preservation of post-CD kidneys, five out of six recipients in the ETK group survived until 14 days, in contrast to zero out of six in the UW group (p<0.01). Preservation with ITK rather than ETK at 23°C tended to have an inferior effect on recipient survival (p = 0.12). Energy activities of the fresh donor kidneys decreased in a temperature-dependent manner, while those of post-CD kidneys remained at the lower level. ETK was superior to UW in protecting against edema of the post-CD kidneys at the higher temperature. Luminescence intensity of successful grafts recovered within 1 h, while the intensity of grafts of deceased recipients did not change at 1 h post-reperfusion. CONCLUSIONS: Normothermic storage with extracellular-type solution containing trehalose might prevent reperfusion injury due to temperature-dependent tissue edema

Swelling of a lava plug associated with a Vulcanian eruption at Sakurajima Volcano, Japan, as revealed by infrasound record: Case study of the eruption on January 2, 2007

In order to clarify the time relation of the expansion of a gas pocket and failure of its overlying plug of lava during Vulcanian eruptions, infrasound records and video images of the Vulcanian eruption that occurred at Sakurajima volcano on January 2, 2007 were analyzed with respect to their origin times. Weak (≤ 3 Pa) and slowly increasing air pressure preceded the impulsive compression phase by 0.25-0.32 s, and a longer-period rarefaction phase of infrasound waves was recognized at all microphone stations. The velocity of the compression phase was assumed to be supersonic (ca. 400 m/s) up to 850 m above the crater bottom from other recent explosions. On the other hand, the propagation velocity of the preceding weak signal was regarded to be similar to the air sound velocity because the lack of impulsiveness is unlikely to be related to the main compression phase. Therefore, the estimated origin time of the main compression phase was delayed by 0.5-0.7 s from the preceding phase. The origin time of the preceding phase coincided with the onset of the isotropic expansion process of the pressurized gas pocket, which was obtained by the waveform inversion of the explosion earthquake. In contrast, the origin time of the main impulsive phase coincided with the time when the expansion rate reached its peak. This observation suggests that the volumetric increase of the gas pocket caused swelling of the surface of the crater bottom and its subsequent failure. When the expansion velocity exceeded a threshold level, the main impulsive compression phase radiated with a high velocity by the sudden releases of the pressurized gases. The volumetric change at the source was estimated to be 280-560 m3 from the preceding phase of the infrasound. This volume change indicates that the vertical displacement of the swelling ground was on the order of 1.0 m, assuming the radius of the lava plug was ca. 10 m