Biology subjects

Konishi, I.

Publications and source records attributed to Konishi, I..

4 recordsLinked to original sources

bioRxiv2022

Spontaneous myocarditis in mice predisposed to autoimmune disease: Including Vaccination-induced onset

Non-obese diabetic (NOD)/ShiLtJ mice, like biobreeding rats, are used as an animal model for type 1 diabetes. Diabetes develops in NOD mice as a result of insulitis, a leukocytic infiltrate of the pancreatic islets. The onset of diabetes is associated with a moderate glycosuria and a non-fasting hyperglycemia. Previously, in non-obese diabetic (NOD)/ShiLtJ mice spontaneously developing type 1 diabetes, the possible involvement of decreased expression of LMP2/{beta}1i, an immunoproteasome {beta} subunit, and associated decreased expression of NF-{kappa}B1 (also called as p50) in the development of type 1 diabetes was argued between our research team and other research groups. In response to these arguments, we created NOD mice in which NF-{kappa}B1 expression is not consistently observed. Unexpectedly, most NOD Nf{kappa}b1 homozygote mice were found to die by the 8th week of age due to the development of severe myocarditis. Furthermore, in all NOD Nf{kappa}b1 heterozygote mice, the onset of Insulitis was observed from 4 months of age. In addition, in NOD Nf{kappa}b1 heterozygote mice, an increase in cTnT due to vaccination with influenza or HBV vaccine was observed without gender difference. Now, we found a direct involvement of decreased expression of NF-{kappa}B1 in the development of autoimmune diseases in NOD/ShiLtJ mice. Therefore, we would like to introduce new research results on autoimmune diseases, including findings on important risk factors for the development of myocarditis observed after vaccination with mRNA-based COVID-19 vaccine.

immunology↗

bioRxiv2020

Effect of RBD mutation (Y453F) in spike glycoprotein of SARS-CoV-2 on neutralizing antibody affinity

Natural selection "adaptation" in the coronavirus can occur during coronavirus amplification in vivo in farmed minks. Natural selection in such viruses is observed by introduction of mutations in SARS- CoV-2 that are not observed during the growth process in humans. Infection with a mutant (Y453F) of SARS-CoV-2 from farmed minks is known to widely spread among humans. We investigated the virological characteristics of this SARS-CoV-2 mutant (Y453F) using three-dimensional protein structural analysis. Our experimental study suggests that virus variants with the Y453F mutation partially escaped detection by four neutralizing monoclonal antibodies. The spread of SARS-CoV-2 variants mediated by millions of infected farmed minks is uncontrolled; consequently, raising a concern that infection of SARS-CoV-2 mutants that cause serious symptoms in humans may spread globally.

microbiology↗

bioRxiv2020

Impact of COVID-19: Decrease in the Number of Fledging Barn Swallow Chicks in Tokyo

Barn swallows that have crossed the sea from Southeast Asia usually appear in the Kyushu Region of Japan around March after passing through Okinawa Prefecture. When the climate becomes warmer, these birds then move further north, nesting and raising their chicks in various parts of Japan. It is worth noting that barn swallows typically nest on man-made objects, for example, the roofs of houses and barns. It is believed that this is because barn swallows protect their eggs and chicks from foreign enemies such as sparrows and crows so they build their nests in populated areas. The barn swallows behavior of using the presence of people to keep foreign enemies away shows that barn swallows are quite wise. However, it has been reported that from the spring to summer of 2020, barn swallows, nesting and raising their chicks, which were seen every year, were not found in various parts of Japan. Therefore, we investigated the relationship between peoples self-restraint from going out and the fledging of barn swallow chicks in Tokyo metropolitan during the corona virus disease 2019 (COVID-19) era. The results of the survey showed a link between peoples refraining from going out and the fledging of barn swallow chicks. Next spring of 2021, the termination of COVID-19 is an important environment for swallow chick fledging.

ecology↗

bioRxiv2019

Targeting dormant ovarian cancer cells in vitro and in an in vivo model of platinum resistance

ObjectiveOvarian cancer cells often exist in vivo as multicellular spheroids. Spheroid formation in vitro has been used to enrich for cancer stem cell populations from primary tumors. Such spheroids exhibit drug resistance and slow proliferation, suggesting involvement in disease recurrence. Our objectives were to characterize cancer spheroid phenotypes, determine gene expression profiles associated with spheroid forming capacity and to evaluate the responsiveness of spheroids to commonly used and novel therapeutic agents.\n\nMethodsTumorigenic potential was assessed using anchorage independent growth assays in 24 cell lines. Spheroids from cell lines (N=12) and from primary cancers (N=8) were grown on non-adherent tissue culture plates in serum-free media. Cell proliferation was measured using MTT assays and Ki67 immunostaining. Affymetrix HT U133A gene expression data was used to identify differentially expressed genes based on spheroid forming capacity. Matched monolayers and spheroids (N=7 pairs) were tested for response to cisplatin, paclitaxel and 7-hydroxystaurosporine (UCN-01) while mitochondrial inhibition was performed using oligomycin. Xenograft tumors from intraperitoneal injection of CAOV2-GFP/LUC ovarian cancer cells into nude mice were treated with carboplatin to reduce tumor burden followed by secondary treatment with carboplatin, UCN-01, or Oltipraz. Tumor formation and response was monitored using live imaging.\n\nResultsOf 12 cell lines with increased anchorage-independent growth, 8 also formed spheroids under serum-free spheroid culture conditions. Spheroids showed reduced proliferation (p<0.0001) and Ki67 immunostaining (8% versus 87%) relative to monolayer cells. Spheroid forming capacity was associated with increased mitochondrial pathway activity (p [≤] 0.001). The mitochondrial inhibitors, UCN-01 and Oligomycin, demonstrated effectiveness against spheroids, while spheroids were refractory to cisplatin and paclitaxel. By live in vivo imaging, ovarian cancer xenograft tumors were reduced after primary treatment with carboplatin. Continued treatment with carboplatin was accompanied by an increase in tumor signal while there was little or no increase in tumor signal observed with subsequent treatment with UCN-01 or Oltipraz.\n\nConclusionsOur findings suggest that the mitochondrial pathway in spheroids may be an important therapeutic target in preventing disease recurrence.

cancer biology↗