Impact of Permeable Structures on Salinity Intrusion in the Abashiri River

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

Next-Generation Cancer Immunotherapy Targeting Glypican-3

Glypican-3 (GPC3), a 65 kD protein consisting of 580 amino acids, is a heparan sulfate proteoglycan bound to the cell membrane by glycosylphosphatidylinositol. This protein is expressed in the liver and the kidney of healthy fetuses but is hardly expressed in adults, except in the placenta. Contrarily, GPC3 is specifically expressed in hepatocellular carcinoma (HCC), ovarian clear cell carcinoma, melanoma, squamous cell carcinoma of the lung, hepatoblastoma, nephroblastoma (Wilms tumor), yolk sac tumor, and some pediatric cancers. Although the precise function of GPC3 remains unclear, it has been strongly suggested that it is related to the malignant transformation of HCC. We identified GPC3 as a promising target for cancer immunotherapy and have been working on the development of cancer immunotherapeutic agents targeting it through clinical trials. In some trials, it was revealed that the GPC3 peptide vaccines we developed using human leukocyte antigen-A24- and A2-restricted GPC3-derived peptides could induce GPC3-specific cytotoxic T cells in most vaccinated patients and thereby improve their prognosis. To further improve the clinical efficacy of cancer immunotherapy targeting GPC3, we are also developing next-generation therapeutic strategies using T cells engineered to express antigen-specific T-cell receptor or chimeric antigen receptor. In addition, we have successfully monitored the levels of serum full-length GPC3 protein, which is somehow secreted in the blood. The utility of GPC3 as a biomarker for predicting tumor recurrence and treatment efficacy is now being considered. In this review article, we summarize the results of clinical trials carried out by our team and describe the novel agent targeting the cancer-specific shared antigen, GPC3

Bilateral Cataract in a Cynomolgus Monkey

Severe bilateral cataract was found in a 7 year-old naïve female cynomolgus monkey (Macaca fascicularis) 3 months before necropsy. During macroscopic examination, severe opacity and thinning of the lens were observed in both eyes. Histopathology revealed that the lens nuclei and majority of cortex lens fibers had disappeared and become excavated, while the lens fibers in the subcapsular area were swollen and distorted. Other observations included atrophy and vacuolation in the lens epithelial cells and proliferation of spindle cells and collagen fiber beneath the anterior capsule of the right eye. Immunohistochemical staining of these spindle cells revealed the presence of vimentin, cytokeratin and α-smooth muscle actin (α-SMA), which were considered to be derived from lens epithelial cells. This is a rare case of spontaneous, bilateral, hypermature cataract in a cynomolgus monkey

BSEの危機をめぐって

総研大レクチャー「科学と社会的合意形成」講義録第6章　BSEの危機をめぐって 吉川 泰弘[東京大学大学院農学生命研究科教授

Behavioral Alterations in Response to Fear-Provoking Stimuli and Tranylcypromine Induced by Perinatal Exposure to Bisphenol A and Nonylphenol in Male Rats

The purpose of this study was to examine whether perinatal exposure to two major environmental endocrine-disrupting chemicals, bisphenol A (BPA; 0.1 mg/kg/day orally) and nonylphenol [NP; 0.1 mg/kg/day (low dose) and 10 mg/kg/day (high dose) orally] daily from gestational day 3 to postnatal day 20 (transplacental and lactational exposures) would lead to behavioral alterations in the male offspring of F344 rats. Neither BPA nor NP exposure affected behavioral characteristics in an open-field test (8 weeks of age), in a measurement of spontaneous motor activity (12 weeks of age), or in an elevated plus-maze test (14 weeks of age). A passive avoidance test (13 weeks of age) showed that both BPA- and NP-treated offspring tended to delay entry into a dark compartment. An active avoidance test at 15 weeks of age revealed that BPA-treated offspring showed significantly fewer avoidance responses and low-dose NP-treated offspring exhibited slightly fewer avoidance responses. Furthermore, BPA-treated offspring significantly increased the number of failures to avoid electrical unconditioned stimuli within 5-sec electrical shock presentation compared with the control offspring. In a monoamine-disruption test using 5 mg/kg (intraperitoneal) tranylcypromine (Tcy), a monoamine oxidase inhibitor, both BPA-treated and low-dose NP-treated offspring at 22–24 weeks of age failed to show a significant increment in locomotion in response to Tcy, whereas control and high-dose NP-treated offspring significantly increased locomotion behavior after Tcy injection. In addition, when only saline was injected during a monoamine-disruption test, low-dose NP-treated offspring showed frequent rearing compared with the control offspring. The present results indicate that perinatal low-dose BPA or NP exposure irreversibly influenced the reception of fear-provoking stimuli (e.g., electrical shock), as well as monoaminergic neural pathways

Characterization of the lasing properties of a 5%Yb doped Lu_2SiO_5 crystal along its three principal dielectric axes

The laser performance of a 5% Yb doped Lu2SiO5 (Yb:LSO) has been investigated in quasi continuous-wave pumping regime along the three principal dielectric axes of the crystal, to obtain a complete characterization of its laser properties. The comparison among the obtained results for differently polarized lasers, in term of relative slope efficiency and absolute efficiency, allows the exploitability of different orientations of the material in order to be determined to obtain efficient laser sources. The laser slope efficiency and the energy conversion efficiency were similar for emission polarized along the three indicatrix axes, with noticeable maximum values of slope efficiency around 90% for polarization along the Y and Z axes. Tunable laser action has been obtained in the range 990 nm - 1084 nm, with sizeable differences in the shape of the tuning curve for polarization along the X, Y and Z axes. In particular, the tuning for polarization along the Z axis is relatively flat and uniform in the range 1023 nm - 1083 nm

脳皮質静脈梗塞ラットモデルを用いた脳静脈虚血による神経細胞および神経前駆細胞の発現と分布

Neurogenesis in the subventricular zone (SVZ), subgranular zone (SGZ), and cerebral cortex is now a familiar event to confirm by cerebral arterial ischemia in rat models. However, it remains unclear whether cerebral venous ischemia (CVI) alone causes neurogenesis, and where that neurogenesis occurs. After creating CVI rat models via a two-vein occlusion (2-VO) method, neurogenesis was immunohistochemically evaluated by doublelabeling 5-bromo-2′ -deoxyuridine (BrdU)-positive cells with neuronal nuclei (NeuN) or doublecortin (DCX) antibody. Fifty Wistar rats were divided into two major groups (BrdU-NeuN and BrdU-DCX) and then separated into two subgroups (2-VO or sham). The total number of double-positive cells expressed inside a predefined region of interest (ROI) covering the ischemic area was compared between the two subgroups. Then, we divided the ROI into six sections to evaluate and compare the distribution of double-positive cells generated in each section between the two subgroups. The 2-VO subgroup presented more double-positive cells than the sham group in both BrdU-NeuN and BrdU-DCX groups, while the BrdU-DCX+2-VO group showed a characteristic distribution of double-positive cells in ROI 2 and ROI 3, suggesting areas of the ischemic core and penumbra, with a significant difference compared to the BrdU-DCX+sham group. This study demonstrates that CVI has the potential to induce endogenous neurogenesis, with significant numbers of both newly generated neurons and precursors observed in the ischemic area. The distribution of these cells suggests that the cortex could be the main origin of neurogenesis after cortical CVI.博士（医学）・甲第872号・令和5年3月15

Fetal and Neonatal Goiter in Cynomolgus Monkeys Following Administration of the Antithyroid Drug Thiamazole at High Doses to Dams During Pregnancy

To evaluate morphologic alterations in the thyroid gland in the second generation in cynomolgus monkeys, pregnant dams were exposed to high doses of thiamazole. In Experiment A, dams received thiamazole intragastrically via a nasogastric catheter from gestation day (GD) 50 to GD 150 or on the day before delivery. Initially, the dose level was 20 mg/kg/day (10 mg/kg twice daily); however, the dose level was subsequently decreased to 5 mg/kg/day (2.5 mg/kg twice daily), since deteriorated general conditions were observed in two dams. Six out of seven neonates died on the day of birth. The cause of neonatal death was tracheal compression and suffocation from goiter. The transplacental exposure to thiamazole affected the fetal thyroid glands and induced goiter in all neonates. The surviving neonate was necropsied 767 days after discontinuation of thiamazole exposure and showed reversibility of the induced changes. In Experiment B, dams were intragastrically administered thiamazole at 5 mg/kg/day (2.5 mg/kg twice daily) for treatment periods from GDs 51 to 70, 71 to 90, 91 to 110, 111 to 130 and 131 to 150. All fetuses showed enlarged thyroid glands but were viable. Histopathologically, hypertrophy and/or hyperplastic appearance of the follicular epithelium of the thyroid gland was observed at the end of each treatment period. The most active appearance of the follicular epithelium, consisting of crowded pedunculated structure, was demonstrated at end of the treatment period from GD 131 to 150. This is the first report on the morphology of fetal and neonatal goiter in the cynomolgus monkey

Quantification of Warming Climate-Induced Changes in Terrestrial Arctic River Ice Thickness and Phenology

A land process model [the coupled hydrological and biogeochemical model (CHANGE)] is used to quantitatively assess changes in the ice phenology, thickness, and volume of terrestrial Arctic rivers from 1979 to 2009. The CHANGE model was coupled with a river routing and discharge model enabling explicit representation of river ice and water temperature dynamics. Model-simulated river ice phenological dates and thickness were generally consistent with in situ river ice data and landscape freeze–thaw (FT) satellite observations. Climate data indicated an increasing trend in winter surface air temperature (SAT) over the pan-Arctic during the study period. Nevertheless, the river ice thickness simulations exhibited a thickening regional trend independent of SAT warming, and associated with less insulation and cooling of underlying river ice by thinning snow cover. Deeper snow depth (SND) combined with SAT warming decreased simulated ice thickness, especially for Siberian rivers, where ice thickness is more strongly correlated with SND than SAT. Overall, the Arctic river ice simulations indicated regional trends toward later fall freezeup, earlier spring breakup, and consequently a longer annual ice-free period. The simulated ice phenological dates were significantly correlated with seasonal SAT warming. It is found that SND is an important factor for winter river ice growth, while ice phenological timing is dominated by seasonal SAT. The mean total Arctic river ice volume simulated from CHANGE was 54.1 km3 based on the annual maximum ice thickness in individual grid cells, while river ice volume for the pan-Arctic rivers decreased by 2.82 km3 (0.5%) over the 1979–2009 record. Arctic river ice is shrinking as a consequence of regional climate warming and coincident with other cryospheric components, including permafrost, glaciers, and sea ice