HETEROTACTIC POLY(N-ISOPROPYLACRYLAMIDE)

Radical polymerization of N-isopropylacrylamide (NIPAAm) in toluene at low temperatures, in the presence of fluorinated alcohols, produced heterotactic polymer comprising an alternating sequence of meso and racemo dyads. The heterotacticity reached 70% in triads when polymerization was carried out at –40°C using nonafluoro-tert-butanol as the added alcohol. NMR analysis revealed that formation of a 1:1 complex of NIPAAm and fluorinated alcohol through C=O•••H-O hydrogen bonding induces the heterotactic specificity. A mechanism for the heterotactic-specific polymerization is proposed. Examination of the phase transition behavior of aqueous solutions of heterotactic poly(NIPAAm) revealed that the hysteresis of the phase transition between the heating and cooling cycles depended on the average length of meso dyads in poly(NIPAAm)

PABPC1 mediates degradation of C9orf72-FTLD/ALS GGGGCC repeat RNA

Uozumi R., Mori K., Gotoh S., et al. PABPC1 mediates degradation of C9orf72-FTLD/ALS GGGGCC repeat RNA. iScience 27, 109303 (2024); https://doi.org/10.1016/j.isci.2024.109303.GGGGCC hexanucleotide repeat expansion in C9orf72 causes frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Expanded GGGGCC repeat RNA accumulates within RNA foci and is translated into toxic dipeptide repeat proteins; thus, efficient repeat RNA degradation may alleviate diseases. hnRNPA3, one of the repeat RNA-binding proteins, has been implicated in the destabilization of repeat RNA. Using APEX2-mediated proximity biotinylation, here, we demonstrate PABPC1, a cytoplasmic poly (A)-binding protein, interacts with hnRNPA3. Knockdown of PABPC1 increased the accumulation of repeat RNA and RNA foci to the same extent as the knockdown of hnRNPA3. Proximity ligation assays indicated PABPC1-hnRNPA3 and PABPC1-RNA exosomes, a complex that degrades repeat RNA, preferentially co-localized when repeat RNA was present. Our results suggest that PABPC1 functions as a mediator of polyadenylated GGGGCC repeat RNA degradation through interactions with hnRNPA3 and RNA exosome complex

eIF5 stimulates the CUG initiation of RAN translation of poly-GA dipeptide repeat protein (DPR) in C9orf72 FTLD/ALS

Gotoh S., Mori K., Fujino Y., et al. eIF5 stimulates the CUG initiation of RAN translation of poly-GA dipeptide repeat protein (DPR) in C9orf72 FTLD/ALS. Journal of Biological Chemistry 300, 105703 (2024); https://doi.org/10.1016/j.jbc.2024.105703.Tandem GGGGCC repeat expansion in C9orf72 is a genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Transcribed repeats are translated into dipeptide repeat proteins via repeat-associated non-AUG (RAN) translation. However, the regulatory mechanism of RAN translation remains unclear. Here, we reveal a GTPase-activating protein, eukaryotic initiation factor 5 (eIF5), which allosterically facilitates the conversion of eIF2-bound GTP into GDP upon start codon recognition, as a novel modifier of C9orf72 RAN translation. Compared to global translation, eIF5, but not its inactive mutants, preferentially stimulates poly-GA RAN translation. RAN translation is increased during integrated stress response, but the stimulatory effect of eIF5 on poly-GA RAN translation was additive to the increase of RAN translation during integrated stress response, with no further increase in phosphorylated eIF2α. Moreover, an alteration of the CUG near cognate codon to CCG or AUG in the poly-GA reading frame abolished the stimulatory effects, indicating that eIF5 primarily acts through the CUG-dependent initiation. Lastly, in a Drosophila model of C9orf72 FTLD/ALS that expresses GGGGCC repeats in the eye, knockdown of endogenous eIF5 by two independent RNAi strains significantly reduced poly-GA expressions, confirming in vivo effect of eIF5 on poly-GA RAN translation. Together, eIF5 stimulates the CUG initiation of poly-GA RAN translation in cellular and Drosophila disease models of C9orf72 FTLD/ALS

Reconciling biodiversity conservation and flood risk reduction : The new strategy for freshwater protected areas

Aim: Natural disaster risk reduction (DRR) is becoming a more important function of protected area (PAs) for current and future global warming. However, biodiversity conservation and DRR have been handled separately and their interrelationship has not been explicitly addressed. This is mainly because, due of prevailing strategies and criteria for PA placement, a large proportion of PAs are currently located far from human-occupied areas, and habitats in human-occupied areas have been largely ignored as potential sites for conservation despite their high biodiversity. If intensely developed lowland areas with high flooding risk overlap with important sites for biodiversity conservation, it would be reasonable to try to harmonize biodiversity conservation and human development in human-inhabited lowland areas. Here, we examined whether extant PAs can conserve macroinvertebrate and freshwater fish biodiversity and whether human-inhabited lowland flood risk management sites might be suitable to designate as freshwater protected areas (FPAs). Location: Across Japan. Methods: We examined whether extant PAs can conserve macroinvertebrate and freshwater fish biodiversity and analysed the relationship between candidate sites for new FPAs and flood disaster risk and land use intensity at a national scale across Japan based on distribution data for 131 freshwater fish species and 1395 macroinvertebrate species. Results: We found that extant PAs overlapped with approximately 30% of conservation-priority grid cells (1 km2) for both taxa. Particularly for red-listed species, only one species of freshwater fish and three species of macroinvertebrate achieved the representation target within extant PAs. Moreover, more than 40% of candidate conservation-priority grid cells were located in flood risk and human-occupied areas for both taxa. Main conclusions: Floodplain conservation provides suitable habitat for many freshwater organisms and helps control floodwaters, so establishing new FPAs in areas with high flood risk could be a win-win strategy for conserving freshwater biodiversity and enhancing ecosystem-based DRR (eco-DRR)

AFF3, a susceptibility factor for autoimmune diseases, is a molecular facilitator of immunoglobulin class switch recombination

Immunoglobulin class switch recombination (CSR) plays critical roles in controlling infections and inflammatory tissue injuries. Here, we show that AFF3, a candidate gene for both rheumatoid arthritis and type 1 diabetes, is a molecular facilitator of CSR with an isotype preference. Aff3-deficient mice exhibit low serum levels of immunoglobulins, predominantly immunoglobulin G2c (IgG2c) followed by IgG1 and IgG3 but not IgM. Furthermore, Aff3-deficient mice show weak resistance to Plasmodium yoelii infection, confirming that Aff3 modulates immunity to this pathogen. Mechanistically, the AFF3 protein binds to the IgM and IgG1 switch regions via a C-terminal domain, and Aff3 deficiency reduces the binding of AID to the switch regions less efficiently. One AFF3 risk allele for rheumatoid arthritis is associated with high mRNA expression of AFF3, IGHG2, and IGHA2 in human B cells. These findings demonstrate that AFF3 directly regulates CSR by facilitating the recruitment of AID to the switch regions

大規模アンサンブル気候予測データを用いた爆弾低気圧の将来変化

金沢大学理工研究域環境デザイン学系In this study, we evaluated the impact of climate change on explosive cyclone using the large ensembleclimate prediction data (d4PDF) of present climate experiment 3,000 years (60 years × 50 members) and future climate experiment 5,400 years (60 years × 90 members). Explosive cyclones were extracted from sea level pressure and examined. Although the trend of increasing explosive cyclone didn’t have statistical significance from the difference between present- and future-climate around Japan, the strongest explosive cyclone intensified in future-climate, and future change was estimated about -12 hPa. In addition, as a result of analyzing the explosive cyclone going through the coastal area of Japan, the proportion of strong explosive cyclone like the typhoon had increasing trend. 現在気候実験3,000年（60年×50メンバ）および将来気候実験5,400年（60年×90メンバ）の大規模アンサンブル気候予測データ（d4PDF）を用いて，日本海沿岸における低頻度気象災害要因の一つである爆弾低気圧に対する気候変動の影響評価を実施した．現在気候および将来気候からの爆弾低気圧抽出結果から，発生個数にはほとんど将来変化はないが，最低中心気圧の強度は将来的に増加する傾向があることがわかった．また，日本沿岸域に被害を及ぼす可能性がある爆弾低気圧について解析した結果，全体に占める台風並みに発達する爆弾低気圧の割合が増加し，特に中心気圧の強度も増加する傾向を示した

Srsf7 Establishes the Juvenile Transcriptome through Age-Dependent Alternative Splicing in Mice.

The juvenile phase is characterized by continuously progressing physiological processes such as growth and maturation, which are accompanied by transitions in gene expression. The contribution of transcriptome dynamics to the establishment of juvenile properties remains unclear. Here, we investigated alternative splicing (AS) events in postnatal growth and elucidated the landscape of age-dependent alternative splicing (ADAS) in C57BL/6 mice. Our analysis of ADAS in the cerebral cortex, cardiomyocytes, and hepatocytes revealed numerous juvenile-specific splicing isoforms that shape the juvenile transcriptome, which in turn functions as a basis for the highly anabolic status of juvenile cells. Mechanistically, the juvenile-expressed splicing factor Srsf7 mediates ADAS, as exemplified by switching from juvenile to adult forms of anabolism-associated genes Eif4a2 and Rbm7. Suppression of Srsf7 results in "fast-forwarding" of this transcriptome transition, causing impaired anabolism and growth in mice. Thus, juvenile-specific AS is indispensable for the anabolic state of juveniles and differentiates juveniles from adults

English Teaching Methodology from Perspectives on Proactive, Interactive, and Deep Learning: Teaching with Tablets in Middle and High Schools

departmental bulletin pape

Neuroepithelial cell competition triggers loss of cellular juvenescence.

Cell competition is a cell-cell interaction mechanism which maintains tissue homeostasis through selective elimination of unfit cells. During early brain development, cells are eliminated through apoptosis. How cells are selected to undergo elimination remains unclear. Here we aimed to identify a role for cell competition in the elimination of suboptimal cells using an in vitro neuroepithelial model. Cell competition was observed when neural progenitor HypoE-N1 cells expressing RASV12 were surrounded by normal cells in the co-culture. The elimination through apoptosis was observed by cellular changes of RASV12 cells with rounding/fragmented morphology, by SYTOX blue-positivity, and by expression of apoptotic markers active caspase-3 and cleaved PARP. In this model, expression of juvenility-associated genes Srsf7 and Ezh2 were suppressed under cell-competitive conditions. Srsf7 depletion led to loss of cellular juvenescence characterized by suppression of Ezh2, cell growth impairment and enhancement of senescence-associated proteins. The cell bodies of eliminated cells were engulfed by the surrounding cells through phagocytosis. Our data indicates that neuroepithelial cell competition may have an important role for maintaining homeostasis in the neuroepithelium by eliminating suboptimal cells through loss of cellular juvenescence