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Katagiri, T.

Publications and source records attributed to Katagiri, T..

7 recordsLinked to original sources

Oligo DNA-based quantum dot (QD) single-particle tracking for multicolor single-molecule imaging

Quantum dot single-particle tracking (QD-SPT), a powerful tool for analyzing membrane domains that are critical to various cellular processes, is widely used in membrane molecular dynamics research. QDs, which possess both a broad excitation range and a narrow emission bandwidth, are inherently suited for multicolor imaging at various wavelengths. However, applying multicolor QD-SPT with multiple biomolecular targets has been challenging due to the limited methods for specifically conjugating QDs to biomolecules. Here, we propose a DNA hybridization-based QD labeling method that generates several specific interactions based on sequence. QD fused with 20-mer oligo DNA specifically labeled membrane lipid 1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine (DPPE) covalently bound to complementary oligo DNA, forming a stable label that is suitable for SPT. The combination of polyA-polyT sequence as the linker oligo caused more QDs to fuse to DPPE compared with a random sequence linker. Oligo DNA-based QD-SPT accurately reflected the diffusion dynamics of DPPE measured using the single-fluorescence tracking technique and was compatible with conventional QD-SPT utilizing secondary antibody Fab. Using different pairs of oligo DNA sequences, we successfully achieved multicolor QD-SPT that distinguishes the lateral diffusion of DPPE and a membrane protein, GABAA receptor (GABAAR), within the same cell. The oligo DNA-based QD labeling method developed in this study is anticipated to substantially advance simultaneous multicolor QD-SPT of different living cell membrane molecules specific to DNA sequences.

biophysics↗

LINC01503-MP is a Mitochondrial Microprotein That Promotes Cell Proliferation and Oxidative Metabolism.

Long non-coding RNAs (lncRNAs) are well-established as key regulators of gene expression. However, emerging evidence reveals that some lncRNAs can also encode functional microproteins. In this study, we report the identification of an evolutionarily young microprotein encoded by LINC01503, expressed across several human tissues. This microprotein, designated as LINC01503-MP, localises to the mitochondria and exerts a proliferative effect on HCT116 colorectal cancer (CRC) cells. Functional studies reveal that LINC01503-MP regulates mitochondrial oxygen consumption rate, linking its activity to enhanced metabolic functions and cell proliferation. Interactome analyses identified multiple mitochondrial metabolism-related proteins as potential interaction partners. Our findings show that LINC01503-MP plays a role in the proliferative phenotype associated with LINC01503 upregulation in CRC, suggesting the functional significance of evolutionarily young, lncRNA-derived microproteins in cancer progression.

molecular biology↗

Homeostatic Regulation of Seizure Susceptibility and Cognitive Function by ER Quality Controller Derlin-1 through Maintenance of Adult Neurogenesis

Dysfunction of organelle is closely associated with neurological diseases involving disruption of adult neurogenesis. However, the role of the endoplasmic reticulum (ER)-related molecules in this process remains largely unexplored. Here we show that Derlin-1, an ER quality controller, maintains adult neurogenesis in a spatiotemporal manner. Deletion of Derlin-1 in the mouse central nervous system induces ectopic localization of newborn neurons and impairs neural stem cells (NSCs) transition from active to quiescent states, resulting in early depletion of hippocampal NSCs. As a result, Derlin-1- deficient mice exhibit phenotypes of increased seizure susceptibility and impaired cognitive function. Reduced expression of signal transducer and activator of transcription 5b (Stat5b) was found to be responsible for the impairment of adult neurogenesis in Derlin-1-deficient NSCs. Remarkably, the inhibition of histone deacetylase activity ameliorated seizure susceptibility and cognitive dysfunction in Derlin-1-deficient mice by increasing Stat5b expression and restoring abnormal neurogenesis. Overall, our findings demonstrate that Derlin-1, as its characteristic function, plays an essential role in the homeostasis of adult neurogenesis via Stat5b expression, thus regulating seizure susceptibility and cognitive function.

neuroscience↗

The colonial legacy of herbaria

Herbarium collections shape our understanding of the worlds flora and are crucial for addressing global change and biodiversity conservation. The formation of such natural history collections, however, are not free from sociopolitical issues of immediate relevance. Despite increasing efforts addressing issues of representation and colonialism in natural history collections, herbaria have received comparatively less attention. While it has been noted that the majority of plant specimens are housed in the global North, the extent of this disparity has not been rigorously quantified to date. Here, by analyzing over 85 million specimen records and surveying herbaria across the globe, we assess the colonial legacy of botanical collections and how we may move towards a more inclusive future. We demonstrate that colonial exploitation has contributed to an inverse relationship between where plant biodiversity exists in nature and where it is housed in herbaria. Such disparities persist in herbaria across physical and digital realms despite overt colonialism having ended over half a century ago, suggesting ongoing digitization and decolonization efforts have yet to alleviate colonial-era discrepancies. We emphasize the need for acknowledging the inconvenient history of herbarium collections and the implementation of a more equitable, global paradigm for their collection, curation, and use.

ecology↗

Large scale genome-wide association study in a Japanese population identified 45 novel susceptibility loci for 22 diseases

INTRODUCTORY PARAGRAPHThe overwhelming majority of participants in current genetic studies are of European ancestry1-3, limiting our genetic understanding of complex disease in non-European populations. To address this, we aimed to elucidate polygenic disease biology in the East Asian population by conducting a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 383 independent signals in 331 loci for 30 diseases, among which 45 loci were novel (P < 5 x 10-8). Compared with known variants, novel variants have lower frequency in European populations but comparable frequency in East Asian populations, suggesting the advantage of this study in discovering these novel variants. Three novel signals were in linkage disequilibrium (r2 > 0.6) with missense variants which are monomorphic in European populations (1000 Genomes Project) including rs11235604(p.R220W of ATG16L2, a autophagy-related gene) associated with coronary artery disease. We further investigated enrichment of heritability within 2,868 annotations of genome-wide transcription factor occupancy, andidentified 378 significant enrichments across nine diseases (FDR < 0.05) (e.g. NF-{kappa}B for immune-related diseases). This large-scale GWAS in a Japanese population provides insights into the etiology of common complex diseases and highlights the importance of performing GWAS in non-European populations.

genetics↗

Intense Pulsed Electric Fields Denature Urease Protein

This paper describes the effects of nanosecond pulsed electric fields (nsPEFs) on the structure and enzyme activity of three kinds of proteins. Intense (up to 300 kV/cm), 5-ns-long electrical pulses were applied to solutions of lysozyme (14 kDa, monomer), albumin (67 kDa, monomer), and urease (480 kDa, hexamer). We analyzed the tertiary and quaternary structures of these proteins as well as their enzyme activity. The results indicated the deformation of both the quaternary and tertiary structures of urease upon exposure to an electric field of 250 kV/cm or more, whereas no structural changes were observed in lysozyme or albumin, even at 300 kV/cm. The enzyme activity of urease also decreased at field strengths of 250 kV/cm or more. Our experiments demonstrated that intense nsPEFs physically affect the conformation and function of some kinds of proteins. Such intense electric fields often occur on cell membranes when these are exposed to a moderate pulsed electric field.

biophysics↗

BMPR2 inhibits activin- and BMP-signaling via wild type ALK2

Activin A is a member of the TGF-{beta} superfamily and activates the transcription factors SMAD2/3 through the ALK4 type 1 receptor. Activin A has also been shown to activate SMAD1/5/8 through mutated variants of the type 1 receptor ALK2. Interestingly, we here show that both activin A and activin B could activate SMAD1/5/8 through endogenous wild type ALK2 in multiple myeloma cells. Knockdown of the type 2 receptor BMPR2 strongly potentiated activin A- and activin B-induced SMAD1/5/8 activation and subsequent cell death. Furthermore, activity of BMP6, BMP7 or BMP9, which also signal via ALK2, was potentiated by BMPR2 knockdown. Similar results were seen in HepG2 liver carcinoma cells. We propose that BMPR2 inhibited ALK2-mediated signaling by preventing ALK2 from oligomerizing with the type 2 receptors ACVR2A and ACVR2B, necessary for ALK2 activation by activins and several BMPs in these cells. In conclusion, BMPR2 could be explored as a possible target for therapy in patients with multiple myeloma.\n\nSummary StatementThe activation of SMAD1/5/8 via endogenous wild type ALK2 by activin A, activin B, and certain BMPs was enhanced when BMPR2 levels were knocked down.

cell biology↗