Biology subjects

Sasaki, T.

Publications and source records attributed to Sasaki, T..

At least 73 records · Page 4Linked to original sources

bioRxiv2021

Gene recruitments and dismissals in argonaut octopus genome provide insights to pelagic lifestyle adaptation and shell-like eggcase reacquisition

The paper nautilus, Argonauta argo, also known as the greater argonaut, is a species of octopods distinctly characterized by its pelagic lifestyle and by the presence of a spiral-shaped shell-like eggcase in females. The eggcase functions by protecting the eggs laid inside it, and by building and keeping air intakes for buoyancy. To reveal the genomic background of the species adaptation to pelagic lifestyle and the acquisition of its shell-like eggcase, we sequenced the draft genome sequence of the species. The genome size was 1.1 Gb, which is the smallest among the cephalopods known to date, with the top 215 scaffolds (average length 5,064,479 bp) covering 81% (1.09 Gb) of the total assembly. A total of 26,433 protein-coding genes were predicted from 16,802 assembled scaffolds. From these, we identified nearly intact HOX, Parahox, Wnt clusters and some gene clusters probably related to the pelagic lifestyle, such as reflectin, tyrosinase, and opsin. For example, opsin might have undergone an extensive duplication in order to adapt to the pelagic lifestyle, as opposed to other octopuses, which are mostly the benthic. Our gene models also discovered several genes homologous to those related to calcified shell formation in Conchiferan Mollusks, such as Pif-like, SOD, and TRX. Interestingly, comparative genomics analysis revealed that the homologous genes for such genes were also found in the genome of the octopus, which does not have a shell, as well as the basal cephalopods Nautilus. Therefore, the draft genome sequence of A. argo we presented here had not only helped us to gain further insights into the genetic background of the dynamic recruitment and dismissal of genes for the formation of an important, converging extended phenotypic structure such as the shell and the shell-like eggcase, but also the evolution of lifestyles in Cephalopods and the octopods, from benthic to pelagic.

genomics↗

bioRxiv2021

Prefrontal-amygdalar oscillations related to social interaction behavior in mice

The medial prefrontal cortex and amygdala are involved in the regulation of social behavior and associated with psychiatric diseases but their detailed neurophysiological mechanisms at a network level remain unclear. We recorded local field potentials (LFPs) from the dorsal medial PFC (dmPFC) and basolateral amygdala (BLA) while mice engaged on social behavior. We found that in wild-type mice, both the dmPFC and BLA increased 4-7 Hz oscillation power and decreased 30-60 Hz power when they needed to attend to another target mouse. In mouse models with reduced social interactions, dmPFC 4-7 Hz power further increased especially when they exhibited social avoidance behavior. In contrast, dmPFC and BLA decreased 4-7 Hz power when wild-type mice socially approached a target mouse. Frequency-specific optogenetic manipulations of replicating social approach-related LFP patterns restored social interaction behavior in socially deficient mice. These results demonstrate a neurophysiological substrate of the prefrontal cortex and amygdala related to social behavior and provide a unified pathophysiological understanding of neuronal population dynamics underlying social behavioral deficits.

neuroscience↗

bioRxiv2021

Weak representation of awake/sleep states by local field potentials in aged mice

Senescence affects various aspects of sleep, and it remains unclear how sleep-related neuronal network activity is altered by senescence. Here, we recorded local field potential signals from multiple brain regions covering the forebrain in young (10-week-old) and aged (2-year-old) mice. Interregional LFP correlations across these brain regions showed smaller differences between awake and sleep states in aged mice. Multivariate analyses with machine learning algorithms with uniform manifold approximation and projection (UMAP) and robust continuous clustering (RCC) demonstrated that these LFP correlational patterns in aged mice less represented awake/sleep states than those in young mice. By housing aged mice in an enriched environment, the LFP patterns were restored to those observed in young mice. Our results demonstrate senescence-induced changes in neuronal activity at the network level and provide insight into the prevention of pathological symptoms associated with sleep disturbance in senescence.

neuroscience↗

bioRxiv2021

Sequestration and efflux largely account for Cd and Cu resistance in the deep sea Epsilonproteobacterium Nitratiruptor sp. SB155 2

In deep sea hydrothermal vent environments, metal- and metalloid-enriched fluids and sediments abound, making these habitats ideal to study metal resistance in prokaryotes. In this investigation, the architecture of the epsilonproteobacterium, Nitratiruptor sp. SB155-2 transcriptome in combination with sub-cellular analysis using scanning transmission electron microscopy and energy-dispersive X-ray spectroscopy (STEM-EDX) was examined to better understand mechanisms of tolerance for cadmium (Cd) and copper (Cu) at stress-inducing concentrations. Transcriptomic expression profiles were remarkably different in the presence of these two metals, displaying 385 (19%) and 629 (31%) genes differentially expressed (DE) in the presence of Cd and Cu, respectively, while only 7% of DE genes were shared, with genes for non-specific metal transporters and genes involved in oxidative stress-response predominating. The principal metal-specific DE pathways under Cu stress, including those involving sulfur, cysteine, and methionine, are likely required for high-affinity efflux systems, while flagella formation and chemotaxis were over-represented under Cd stress. Consistent with these differences, STEM-EDX analysis revealed that polyphosphate-like granules (pPLG), the formation of CdS particles, and the periplasmic space may be crucial for Cd sequestration. Overall, this study provides new insights regarding metal-specific adaptations of Epsilonproteobacteria to deep sea hydrothermal vent environments. Significance originality statementDeep sea hydrothermal vents are unique environments in which metals and metalloids abound. Despite being a dominant phylum in these environments, adaptations enabling Epsilonproteobacteria to thrive in metal-rich environments remain poorly understood. In this study, a combination of high-throughput, whole-transcriptome RNA-seq analysis, scanning transmission electron microscopy, and energy-dispersive X-ray spectroscopy provide a comprehensive picture of molecular and morphological adaptations controlling metal efflux and sequestration systems of this bacterium in response to cadmium and copper. Many of these responses are metal-specific.

microbiology↗

bioRxiv2021

Independent adoptions of a set of proteins found in the matrix of the mineralized shell-like eggcase of Argonaut octopuses

The Argonaut octopus, commonly called the paper nautilus, has a spiral-coiled shell-like eggcase. As the main characteristics, the eggcase has no internal septum, is composed entirely of calcite with chitosan being the main polycarbonate and is reportedly formed by organic materials secreted from the membranes of the arms. Meanwhile, the biomineralized external "true" shells of the Mollusks, which includes the Cephalopods, are secreted from the mantle tissue. Therefore, the histological origin of the two shells is completely different. The question of how the Argonauts, which phylogenetically diverged from the completely shell-less octopuses, could form a converging shell-like external structure has thus intrigued biologists for a long time. To answer this question, we performed a multi-omics analysis of the transcriptome and proteome of the two congeneric Argonaut species, Argonauta argo and A. hians. Our result indicates that the shell-like eggcase is not a homolog of the shell, even at the protein level, because the Argonauts apparently recruited a different set of protein repertoires to as eggcase matrix proteins (EcMPs). However, we also found the homologs of three shell matrix proteins (SMPs) of the Conchiferan Mollusks, Pif-like, SOD, and TRX, in the eggcase matrix. The proteins were also found in the only surviving shelled Cephalopods, the nautiloid Nautilus pompilius. Phylogenetic analysis revealed that homologous genes of the Conchiferan SMPs and EcMPs were found in the draft genome of shell-less octopuses. Our result reported here thus suggests that the SMP-coding genes are conserved in both shelled and shell-less Cephalopods. Meanwhile, the Argonauts adopted some of the SMP-coding genes and other non-SMP-coding genes, to form a convergent, non-homologous biomineralized external structure, the eggcase, which is autapomorphic to the group.

evolutionary biology↗

bioRxiv2021

Humanized substitutions of Vmat1 in mice induce changes in amygdala-dependent behaviors associated with the evolution of anxiety in humans

The human vesicular monoamine transporter 1 (VMAT1) harbors unique substitutions (Asn136Thr/Ile) that affect monoamine uptake into synaptic vesicles. These substitutions are absent in all known mammals, suggesting their contributions to distinct aspects of human behavior modulated by monoaminergic transmission, such as emotion and cognition. To directly test the impact of these human-specific mutations, we introduced the humanized residues into mouse Vmat1 via CRISPR/Cas9-mediated genome editing and examined changes at the behavioral, neurophysiological and molecular levels. Behavioral tests revealed reduced anxiety-related traits of Vmat1Ile mice, consistent with human studies, and electrophysiological recordings showed altered oscillatory activity in the amygdala under anxiogenic conditions. Transcriptome analyses further identified amygdala-specific changes in the expression of genes involved in neurodevelopment and emotional regulation, which may corroborate the observed phenotypes. This knock-in mouse model hence provides compelling evidence that the mutations affecting monoaminergic signaling and amygdala circuits have contributed to the evolution of human socio-emotional behaviors.

evolutionary biology↗

bioRxiv2021

Naïve individuals promote collective exploration in homing pigeons

Group-living animals that rely on stable foraging or migratory routes can develop behavioural traditions to pass route information down to inexperienced individuals. Striking a balance between exploitation of social information and exploration for better alternatives is essential to prevent the spread of maladaptive traditions. We investigated this balance during cumulative route development in the homing pigeon Columba livia. We quantified information transfer within pairs of birds in a transmission-chain experiment and determined how birds with different levels of experience contributed to the exploration- exploitation trade-off. Newly introduced naive individuals were initially more likely to initiate exploration than experienced birds, but the pair soon settled into a pattern of alternating leadership with both birds contributing equally. Experimental pairs showed an oscillating pattern of exploration over generations that might facilitate the discovery of more efficient routes. Our results introduce a new perspective on the roles of leadership and information pooling in the context of collective learning.

animal behavior and cognition↗

bioRxiv2021

Integrated population genomic analysis and numerical simulation to estimate larval dispersal of Acanthaster cf. solaris between Ogasawara and other Japanese regions

The estimation of larval dispersal of marine species occurring on an ecological timescale is significant for conservation. In 2018, a semi-population outbreak of crown of thorns starfish, Acanthaster cf. solaris was observed on a relatively isolated oceanic island, Ogasawara. The aim of this study was to assess whether this population outbreak was caused by large-scale larval recruitment (termed secondary outbreak) from the Kuroshio region. We estimated larval dispersal of the coral predator A. cf. solaris between the Kuroshio and Ogasawara regions using both population genomic analysis and oceanographic dispersal simulation. Population genomic analysis revealed overall genetically homogenized patterns among Ogasawara and other Japanese populations, suggesting that the origin of the populations in the two regions is the same. In contrast, a simulation of 26-year oceanographic dispersal indicated that larvae are mostly self-seeded in Ogasawara populations and have difficulty reaching Ogasawara from the Kuroshio region within one generation. However, a connectivity matrix produced by the larval dispersal simulation assuming a Markov chain indicated gradual larval dispersal migration from the Kuroshio region to Ogasawara in a stepping-stone manner over multiple years. These results suggest that, while large-scale larval dispersal from an outbreak of the Kuroshio population spreading to the Ogasawara population within one generation is unlikely. This study also highlighted the importance of using both genomic and oceanographic methods to estimate larval dispersal, which provides significant insight into larval dispersal that occurs on ecological and evolutionary timescales.

ecology↗

bioRxiv2021

TNF Blockade Reduces Prostatic Hyperplasia and Inflammation while Limiting BPH Diagnosis in Patients with Autoimmune Disease

Benign prostatic hyperplasia (BPH) is ostensibly linked to autoimmune (AI) diseases, but whether the prostate is a target of systemic inflammation associated with AI conditions is unknown. Prostatic inflammation is linked to fibrosis, hyperplasia, and reduced responses to BPH-related medical therapies. This study was conducted to determine if AI disease correlates with BPH diagnosis and whether systemic targeting of an inflammatory mediator limits prostatic inflammation and hyperplasia. Patient medical records (n=112,152) were evaluated to determine BPH prevalence among different AI diseases. Inflammatory cells from human BPH tissues were analyzed by single-cell (sc)RNA-seq and the tumor necrosis factor (TNF)-antagonist etanercept was tested in two murine models of prostatic enlargement. BPH prevalence was significantly higher among patients with AI disease compared to unaffected individuals. However, AI patients treated with TNF-antagonists had a significantly reduced incidence of BPH. Data from scRNA- seq identified macrophages as a dominant source of TNF and in vitro assays confirmed that TNF stimulates BPH-derived fibroblast proliferation. In the AI patient cohort and murine models, systemic treatment with TNF-antagonists decreased prostatic epithelial proliferation, macrophage infiltration, and epithelial NF{kappa}B activation compared to control tissues. These studies are the first to show that patients with AI diseases have a heightened susceptibility to BPH and that the TNF-signaling axis is important for BPH pathogenesis. Macrophage-secreted TNF may mechanistically drive BPH via chronic activation of the signaling axis and NF{kappa}B. TNF blockade appears to be a promising new pharmacological approach to target inflammation and suppress BPH. One sentence summaryPatient data and mouse models suggest that repurposing tumor necrosis factor alpha blockade reduces inflammation-mediated prostatic hyperplasia.

cell biology↗

bioRxiv2021

Temporally and Spatially Regulated Collagen XVIII Isoforms Impact Ureteric Patterning Through Their TSP1-like Domain

Collagen XVIII (ColXVIII) is a component of the extracellular matrix implicated in embryogenesis and control of homeostasis. We provide evidence that ColXVIII has a specific role in kidney ontogenesis by regulating the interaction between mesenchymal and epithelial tissues as observed in analyses of total and isoform-specific knockout embryos, mice, and ex vivo organ primordia. ColXVIII deficiency, both temporally and spatially, impacts the 3D pattern of ureteric tree branching morphogenesis via its specific isoforms. Proper development of ureteric tree depends on a tight control of the nephron progenitor cells (NPCs). ColXVIII-deficient NPCs are leaving the NPC pool faster than in controls. Moreover, the data suggests that ColXVIII mediates the kidney epithelial tree patterning via its N-terminal domains, and especially the Thrombospondin-1-like domain, and that this morphogenetic effect involves ureteric epithelial integrins. Altogether, the results propose a significant role for ColXVIII in a complex signalling network regulating renal progenitors and kidney development.

developmental biology↗

bioRxiv2021

Comprehensive analysis of male-free reproduction in Monomorium triviale (Formicidae: Myrmicinae)

We report comprehensive evidence for obligatory thelytokous parthenogenesis in an ant Monomorium triviale. This species is characterized by distinct queen-worker dimorphism with strict reproductive division of labor: queens produce both workers and new queens without mating, whereas workers are completely sterile. We collected 333 nests of this species from 14 localities and three laboratory-reared populations in Japan. All wild queens dissected had no sperm in their spermathecae. Laboratory observation confirmed that virgin queens produced workers without mating. Furthermore, microsatellite genotyping showed identical heterozygous genotypes between mothers and their respective daughters, suggesting an extremely low probability of sexual reproduction. Microbial analysis detected no bacterial genera that are known to induce thelytokous parthenogenesis in Hymenoptera. Finally, the lack of variation in partial sequences of mitochondrial DNA among individuals sampled from across Japan suggests recent rapid spread or selective sweep. M. triviale would be a promising model system of superorganism-like adaptation through comparative analysis with well-studied sexual congeners, including the pharaoh ant M. pharaonis.

zoology↗

bioRxiv2021

Cohesin-mediated loop anchors confine the location of human replication origins

DNA replication occurs through an intricately regulated series of molecular events and is fundamental for genome stability across dividing cells in metazoans. It is currently unknown how the location of replication origins and the timing of their activation is determined in the human genome. Here, we dissect the role for G1 phase topologically associating domains (TADs), subTADs, and loops in the activation of replication initiation zones (IZs). We identify twelve subtypes of self-interacting chromatin domains distinguished by their degree of nesting, the presence of corner dot structures indicative of loops, and their co-localization with A/B compartments. Early replicating IZs localize to boundaries of nested corner-dot TAD/subTADs anchored by high density arrays of co-occupied CTCF+cohesin binding sites with divergently oriented motifs. By contrast, late replicating IZs localize to weak TADs/subTAD boundaries devoid of corner dots and most often anchored by singlet CTCF+cohesin sites. Upon global knock-down of cohesin-mediated loops in G1, early wave focal IZs replicate later in S phase and convert to diffuse placement along the genome. Moreover, IZs in mid-late S phase are delayed to the final minutes before entry into G2 when cohesin-mediated dot-less boundaries are ablated. We also delete a specific loop anchor and observe a sharp local delay of an early wave IZ to replication in late S phase. Our data demonstrate that cohesin-mediated loops at genetically-encoded TAD/subTAD boundaries in G1 phase are an essential determinant of the precise genomic placement of human replication origins in S phase.

genomics↗

bioRxiv2020

Characterization of human embryonic stem cells in animal component-free medium

Clinical use of human embryonic stem cells (ESCs) as a raw material requires good manufacturing practice-compliant axillary materials such as culture medium. To this end, animal components should not be used and contamination of virus/bacteria/fungus and allergens are a concern. In addition, animal components such as albumin and fetal bovine serum pose difficulties such as a lot-to-lot variation. However, only a limited number of animal component-free media have been developed to date. In this study, we investigated whether SEES2 ESCs can be stably propagated for 16 passages (54 population doublings) over a period of 60 days in a newly established Stem-Partner(R) ACF medium. SEES2 ESC maintained their intact karyotype, i.e. 46,XX, and their undifferentiated phenotypes after long-term culture. An in vitro differentiation assay revealed that SEES2 ESCs exhibited multipotency, i.e. endodermal, mesodermal and ectodermal differentiation. Subcutaneous implantation of SEES2 ESCs generated mature teratomas without malignant transformation. These results show that SEES2 ESCs in the Stem-Partner(R) ACF medium can be used to establish master cell banks for future regenerative medicine as well as other ESCs in the previously reported culture medium.

cell biology↗

bioRxiv2020

Hydrophilic Shell Matrix Proteins of Nautilus pompilius and The Identification of a Core Set of Conchiferan Domains

Despite being a member of the shelled mollusks (Conchiferans), most members of extant cephalopods have lost their external biomineralized shells, except for the Nautiloids. Here, we report the result of our study to identify major Shell Matrix Proteins and their domains in the Nautiloid Nautilus pompilius, in order to gain a general insight into the evolution of Conchiferan Shell Matrix Proteins. In order to do so, we conducted transcriptomics of the mantle, and proteomics of the shell of N. pompilius simultaneously. Analyses of obtained data identified 61 distinct shell-specific sequences. Of the successfully annotated 27 sequences, protein domains were predicted in 19. Comparative analysis of Nautilus sequences with four Conchiferans for which Shell Matrix Protein data were available (the pacific oyster, the pearl oyster, the limpet, and the Euhadra snail) revealed that three proteins and six domains of the shell proteins are conserved in all Conchiferans. Interestingly, when the terrestrial Euhadra snail was excluded, another five proteins and six domains were found to be shared among the four marine Conchiferans. Phylogenetic analyses indicated that most of these proteins and domains were present in the ancestral Conchiferan, but employed in shell formation later and independently in most clades. Although further studies utilizing deeper sequencing techniques to obtain genome and full-length sequences, and functional analyses, must be done in the future, our results here provide important pieces of information for the elucidation of the evolution of Conchiferan shells at the molecular level.

zoology↗

bioRxiv2020

Perception of and anxiety about COVID-19 infection and risk behaviors for spreading infection: An international comparison

To control the spread of the newly developed corona viral infection diseases (COVID-19), peoples appropriate precautionary behaviors should be promoted. We conducted a series of online questionnaire survey, to gather a total of 8,000 citizens responses on March 27-28, 2020 in Japan and April 17-21 in the UK and Spain. Compared to Japan, the knowledge and anxiety level and the frequency of precautionary behaviors were higher in the UK and Spain. Participants with infected acquaintances were more concerned about COVID-19. However, participants in the UK rarely wore a medical mask. Participants in the UK and Spain were eager to get information about COVID-19 compared to those in Japan. The participants in Spain tended not to trust official information and to believe specialists' comments instead. The urgency of the spread of COVID-19, cultural backgrounds, and recent political situations appear to contribute to the differences among countries revealed herein.

scientific communication and education↗

bioRxiv2020

Promoter activity-based case-control association study on SLC6A4 highlighting hypermethylation and altered amygdala volume in male patients with schizophrenia

Associations between altered DNA methylation of the serotonin transporter (5-HTT)-encoding gene SLC6A4 and early life adversity, mood and anxiety disorders, and amygdala reactivity have been reported. However, few studies have examined epigenetic alterations of SLC6A4 in schizophrenia (SZ). We examined CpG sites of SLC6A4, whose DNA methylation levels have been reported to be altered in bipolar disorder, using three independent cohorts of patients with SZ and age-matched controls. We found significant hypermethylation of a CpG site in SLC6A4 in male patients with SZ in all three cohorts. We showed that chronic administration of risperidone did not affect the DNA methylation status at this CpG site using common marmosets, and that in vitro DNA methylation at this CpG site diminished the promoter activity of SLC6A4. We then genotyped the 5-HTT-linked polymorphic region (5-HTTLPR) and investigated the relationship among 5-HTTLPR, DNA methylation, and amygdala volume using brain imaging data. We found that patients harboring low-activity 5-HTTLPR alleles showed hypermethylation and they showed a negative correlation between DNA methylation levels and left amygdala volumes. These results suggest that hypermethylation of the CpG site in SLC6A4 is involved in the pathophysiology of SZ, especially in male patients harboring low-activity 5-HTTLPR alleles.

genetics↗

bioRxiv2020

Prioritized experience replays on a hippocampal predictive map for learning

Hippocampal cells are central to spatial and predictive representations, and experience replays by place cells are crucial for learning and memory. Nonetheless, how hippocampal replay patterns dynamically change during the learning process remains to be largely elucidated. We found that when rats updated their behavioral strategies in response to a novel salient location, place cells increased theta sequences and sharp wave ripple-associated synchronous spikes that preferentially replayed salient locations and reward-related contexts in reverse order. The directionality and contents of the replays progressively varied with learning, including an optimized path that had never been exploited by the animals. Realtime suppression of sharp wave ripples during learning inhibited the rapid stabilization of optimized behavior. Our results suggest that hippocampal replays prioritize salient experiences and support the reinforcement of new behavioral policies. One-Sentence SummaryNeuronal network mechanisms to internally rehearse learned information for updating behavioral strategy are revealed

neuroscience↗

bioRxiv2020

SPIN reveals genome-wide landscape of nuclear compartmentalization

Chromosomes segregate differentially relative to distinct subnuclear structures, but this genome-wide compartmentalization, pivotal for modulating genome function, remains poorly understood. New genomic mapping methods can reveal chromosome positioning relative to specific nuclear structures. However, computational methods that integrate their results to identify overall intranuclear chromo-some positioning have not yet been developed. We report SPIN, a new method to identify genome-wide nuclear spatial localization patterns. As a proof-of-principle, we use SPIN to integrate nuclear compartment mapping (TSA-seq and DamID) and chromatin interaction data (Hi-C) from K562 cells to identify 10 spatial compartmentalization states genome-wide relative to nuclear speckles, lamina, and nucleoli. These SPIN states show novel patterns of genome spatial organization and their relation to genome function (transcription and replication timing). Comparisons of SPIN states with Hi-C sub-compartments and lamina-associated domains (LADs) from multiple cell types suggest constitutive compartmentalization patterns. By integrating different readouts of higher-order genome organization, SPIN provides critical insights into nuclear spatial and functional compartmentalization.

bioinformatics↗