Biology subjects

Nishitsuji, K.

Publications and source records attributed to Nishitsuji, K..

4 recordsLinked to original sources

bioRxiv2025

Genomic resources of Ascidiella aspersa and comparative analysis across tunicates reveal conserved class-level features and evolutionary diversification

BackgroundAscidiella aspersa is an invasive tunicate and one of the closest relatives of vertebrates. Despite its ecological nuisance, A. aspersa is anticipated to be a valuable model organism for developmental studies due to its remarkably transparent embryos. However, annotated genome assemblies and transcriptomic resources have not yet been fully established. Although several tunicate genomes have been sequenced, most lack annotations, and a comprehensive analysis across tunicates has not yet been conducted. ResultsWe performed de novo genome assembly and transcriptome analysis of A. aspersa, producing a high-quality 306.5 Mb genome assembly. The transcriptome was derived from nine different organs of adults and embryos at six developmental stages. Ab initio and homology-based gene predictions identified 24,504 genes with a BUSCO score of 92.2%. Functional annotation was added for 18,636 genes in the model. To understand the relative features of this species among tunicates, we conducted genome-wide comparative analysis using publicly available data from 35 other tunicate genomes across three classes, five orders, and 12 families, thus constructing gene models for 27 species with BUSCO scores >80%. Overall, phylogenetic analysis revealed a new hypothesis regarding the relationships among Phlebobranchia and Aplousobranchia families. Gene duplication analysis showed distinct contractions of gene families in some taxa with losses of specific DNA repair related genes that were shared among Thaliacea--these may have contributed to their evolutionary diversification. Tunicate genomes exhibited a high level of variation in genomic GC content (28.0%-42.7%). A. aspersa has the highest GC content in coding regions and the third position of codons among tunicate species, with changes in codon usage bias differing from other Ascidiidae species. We also constructed an online comparative tunicate genome database (TUNOME), that provides functional annotations of gene models and ortholog analyses based on these genomic and transcriptomic data. ConclusionsWe constructed genomic resources for A. aspersa and another 35 tunicate gene models. Comparative analysis reveals a variety in tunicate species genomes and characterizes class-level features. Our resources are expected to be a foundation for experimental studies involving non-model tunicates and for comparative analysis among tunicate species.

genomics↗

bioRxiv2025

Amyloid-β fibrils accumulated in preeclamptic placentas suppress syncytialization of cytotrophoblasts

Cerebral deposition of fibrillar amyloid-{beta} (A{beta}) is a pathological hallmark of Alzheimers disease. While A{beta} is present in human placentas and accumulates in preeclamptic placentas characterized by poor placentation, the production and role of A{beta} in the human placenta remain unclear. Because hypoxia in mid-to-late pregnancy is a risk for preeclampsia, we found that levels of hypoxia-inducible factor 1- and {beta}-secretase (BACE-1) increased concurrently with placental A{beta} deposition in late stage preeclamptic placentas. We also found that a human cytotrophoblast (CTB) model, BeWo cells, actually produced A{beta} species, and that hypoxia increased A{beta} production and BACE-1 protein levels. A{beta}42 fibrils inhibited CTB syncytialization, a critical step in maintaining pregnancy, by inducing loss of membrane localization of cell-cell adhesion molecules. Primary human CTBs confirmed these observations. Taken together, our results suggest that increased A{beta} production in CTBs by hypoxia may lead to the formation of A{beta} fibrils, which inhibit syncytiotrophoblast formation and are detrimental to pregnancy. Thus, our results reveal the novel role of A{beta} fibrils in the pathogenesis of preeclampsia.

biochemistry↗

bioRxiv2023

Structural flexibility of apolipoprotein E-derived arginine-rich peptides improves their cell penetration capability

Amphipathic arginine-rich peptide, A2-17, exhibits moderate perturbation of lipid membranes and the highest cell penetration among its structural isomers. We investigated the direct cell-membrane penetration mechanism of the A2-17 peptide. We designed structurally constrained versions of A2-17, stapled (StpA2-17) and stitched (StchA2-17), whose -helical conformations were stabilized by chemical crosslinking. Circular dichroism confirmed that StpA2-17 and StchA2-17 had higher -helix content than A2-17 in aqueous solution. Upon liposome binding, only A2-17 exhibited a coil-to-helix transition. Confocal microscopy revealed that A2-17 had higher cell penetration efficiency than StpA2-17 in HeLa cells. Partitioning into lipid membranes was more prominent for StchA2-17 than for A2-17 or StpA2-17; StchA2-17 remained on the cell membrane without cell penetration. Tryptophan fluorescence analysis suggested that A2-17 and its analogs had similar membrane-insertion positions between the interface and hydrophobic core. Atomic force microscopy demonstrated that A2-17 reduced the mechanical rigidity of liposomes to a greater extent than StpA2-17 and StchA2-17. Finally, electrophysiological analysis showed that A2-17 induced a higher charge influx through transient pores in a planer lipid bilayer than StpA2-17 and StchA2-17. These findings indicate that structural flexibility, which enables diverse conformations of A2-17, leads to a membrane perturbation mode that contributes to cell membrane penetration.

biophysics↗

bioRxiv2021

Extracellular endosulfatase Sulf-2 harbours a chondroitin/dermatan sulfate chain that modulates its enzyme activity

Sulfs represent a class of unconventional sulfatases, which differ from all other members of the sulfatase family by their structures, catalytic features and biological functions. Through their specific endosulfatase activity in extracellular milieu, Sulfs provide an original post-synthetic regulatory mechanism for heparan sulfate complex polysaccharides and have been involved in multiple physiopathological processes, including cancer. However, Sulfs remain poorly characterized enzymes, with major discrepancies regarding their in vivo functions. Here we show that human Sulf-2 (HSulf-2) features a unique polysaccharide post-translational modification. We identified a chondroitin/dermatan sulfate glycosaminoglycan (GAG) chain, attached to the enzyme substrate binding domain. We found that this GAG chain affects enzyme/substrate recognition and tunes HSulf-2 activity in vitro and in vivo using a mouse model of tumorigenesis and metastasis. In addition, we showed that mammalian hyaluronidase acted as a promoter of HSulf-2 activity by digesting its GAG chain. In conclusion, our results highlight HSulf-2 as a unique proteoglycan enzyme and its newly-identified GAG chain as a critical non-catalytic modulator of the enzyme activity. These findings contribute in clarifying the conflicting data on the activities of the Sulfs and introduce a new paradigm into the study of these enzymes.

biochemistry↗