Biology subjects

Nakai, R.

Publications and source records attributed to Nakai, R..

8 recordsLinked to original sources

bioRxiv2026

Adolescent prodromal phenotypes of psychiatric disorders: insights from a novel DISC1-perturbed monkey model

Neurodevelopmental deficits frequently lead to mild but significant adolescent social and cognitive changes, representing prodromal manifestations of adult-onset psychiatric disorders in a cross-disease manner. Although experimental medicine utilizes animal models to address the mechanisms, rodent brains lack critical structures for human higher brain functions such as the dorsolateral prefrontal cortex. To fill this translational gap, we generated monkeys with an impaired DISC1 gene locus, targeting the multifunctional protein essential for neurodevelopment and involved in transdiagnostic mental health risks. Here we analyze the F0 animals by minimizing mosaicism. At ages equivalent to human adolescence, these monkeys exhibited blunted responsiveness to social stimuli and increased internal drives, mirroring altered social behaviors in the prodromal stage in humans. Resting-state functional MRI data indicated disrupted global functional connectivity and reorganization of network topology, marked by a shift in the dominance of brain hubs from prefrontal regions to sensory areas. This primate model provides a unique platform for studying psychiatric disorders, such as schizophrenia, across the developmental trajectory.

neuroscience↗

bioRxiv2026

Identity-state expression and switching in co-conscious dissociative identity disorder: a non-traumatic proof-of-concept fMRI study

Dissociative identity disorder (DID) remains debated because identity-state phenomena are privately experienced and may be attributed to suggestion, simulation or role enactment. Most neuroimaging studies rely on symptom provocation or traumatic recall, which complicates interpretation and is poorly suited to co-conscious presentations where simultaneous awareness should make state differences hardest to detect. We applied Identity-State Characterization and Analysis (ID-SCAN), a non-traumatic, identity-cued functional magnetic resonance imaging protocol, to a DSM-5-diagnosed woman with persistent co-consciousness between Adult and Adolescent identity-states. One task used identical insect images that evoked opposite preferences across identity-states; the other used trait judgments about self, the other identity-state and a shared intimate other. Analyses combined Bayesian single-case general linear modelling, generalized psychophysiological interaction connectivity and searchlight representational similarity analysis. Identity-instruction cue epochs were pooled across tasks to assess switch direction. The same insect stimuli engaged different valuation-related configurations across identity-states: Adolescent-selective effects centred on striato-thalamic regions, whereas Adult-selective effects extended to amygdala and orbitofrontal/medial prefrontal cortex, with distinct task-evoked coupling. Adult-as-self and Adolescent-as-self occupied separable positions within canonical self-referential regions. Cue-locked activity differed by switch direction across tasks, with larger reconfiguration when switching to Adult (mean between-cluster beta separation 4.30 versus 0.85; permutation p = 0.0001). Cross-task overlap localized a limited shared task-related substrate mainly to posterior visual and dorsal parietal cortex. Even under persistent co-consciousness and without trauma provocation, identity-state expression and switching showed convergent within-person neural signatures. The findings support non-traumatic mechanistic phenotyping of dissociative presentations and motivate cohort and longitudinal studies, including treatment-tracking work.

neuroscience↗

bioRxiv2026

How the brain represents a romantic partner: dissociable roles of the nucleus accumbens and anterior insula

Humans form selective and enduring pair bonds with romantic partners, a principal feature of human sociality. Neuroimaging studies have shown that romantic partners are differentially represented from other individuals in the nucleus accumbens (NAcc) and anterior insula (aINS), and that the specificity of partner representations in the NAcc diminishes as relationships mature. However, it remains unclear whether such differentiation reflects partner-specific coding or mere differences in familiarity with others, and whether these regions play different roles in romantic bonding. To address these questions, we applied multiple regression representational similarity analysis to fMRI data from 51 heterosexual male participants in early romantic relationships. The data were acquired during a social incentive delay task, in which participants anticipated social approval from their female romantic partner, a female friend, or an unfamiliar female individual. This approach allowed us to dissociate partner-specific representations from familiarity-related effects in the NAcc and aINS. We found that both regions exhibited partner-specific representations that could not be explained by familiarity. Consistent with previous findings, partner specificity in the NAcc was negatively associated with relationship duration, indicating that partner-specific coding in this region is established early in romantic relationships and diminishes as relationships progress. Moreover, greater partner specificity in the aINS was associated with more frequent intrusive thoughts about the partner. Together, these findings demonstrate that romantic partners are represented in the NAcc and aINS in a qualitatively distinct manner from other individuals, and that these regions support dissociable aspects of romantic bonding. Key PointsO_LIMultiple regression representational similarity analysis revealed partner-specific representations in the nucleus accumbens and anterior insula that cannot be explained by familiarity. C_LIO_LIIndividuals in longer relationships showed reduced partner specificity in the nucleus accumbens, consistent with prior findings. C_LIO_LIIndividuals exhibiting greater partner specificity in the anterior insula reported more frequent intrusive thoughts about their partner, indicating dissociable psychological functions across regions. C_LI

neuroscience↗

bioRxiv2023

Microscopic and metatranscriptomic analyses revealed unique cross-domain symbiosis between Candidatus Patescibacteria/candidate phyla radiation (CPR) and methanogenic archaea in anaerobic ecosystems

To verify the parasitic lifestyle of Candidatus Patescibacteria in the enrichment cultures derived from a methanogenic bioreactor, we applied multifaceted approaches combining cultivation, microscopy, metatranscriptomic, and protein structure prediction analyses. Cultivation experiments with the addition of exogenous methanogenic archaea with acetate, amino acids, and nucleoside monophosphates and 16S rRNA gene sequencing confirmed the increase in the relative abundance of Ca. Patescibacteria and methanogens. The predominant Ca. Patescibacteria were Ca. Yanofskybacteria and 32-520 lineages (to which belongs to class Ca. Paceibacteria) and positive linear relationships (r2 [≥] 0.70) between the relative abundance of Ca. Yanofskybacteria and Methanothrix, suggesting that the tendency of the growth rate is similar to that of the host. By fluorescence in situ hybridization (FISH) observations, the FISH signals of Methanothrix and Methanospirillum cells with Ca. Yanofskybacteria and with 32-520 lineages, respectively, were significantly lower than those of the methanogens without Ca. Patescibacteria, suggesting their parasitic interaction. The TEM and SEM observations also support parasitism in that the cell walls and plugs of these methanogens associated with submicron cells were often deformed. In particular, some Methanothrix-like filamentous cells were dented where the submicron cells were attached. Metatranscriptomic and protein structure prediction analyses identified highly expressed secreted genes from the genomes of Ca. Yanofskybacteria and 32-520, and these genes contain adhesion-related domains to the host cells. Considering the results through the combination of microscopic observations, gene expression, and computational protein modeling, we propose that the interactions between Ca. Yanofskybacteria and 32-520 belonging to class Ca. Paceibacteria and methanogenic archaea are parasitism.

microbiology↗

bioRxiv2022

Enhanced Mirror Neuron Network Activity and Effective Connectivity during Live Interaction

Facial expressions are indispensable in daily human communication. Previous neuroimaging studies investigating facial expression processing have presented pre-recorded stimuli and lacked live face-to-face interaction. Our paradigm alternated between presentations of real-time model performance and pre-recorded videos of dynamic facial expressions to participants. Simultaneous functional magnetic resonance imaging (fMRI) and facial electromyography activity recordings, as well as post-scan valence and arousal ratings were acquired from 44 female participants. Live facial expressions enhanced the subjective valence and arousal ratings as well as facial muscular responses. Live performances showed greater engagement of the right posterior superior temporal sulcus (pSTS), right inferior frontal gyrus (IFG), right amygdala and right fusiform gyrus, and modulated the effective connectivity within the right mirror neuron system (IFG, pSTS, and right inferior parietal lobule). A support vector machine algorithm could classify multivoxel activation patterns in brain regions involved in dynamic facial expression processing in the mentalizing networks (anterior and posterior cingulate cortex). These results indicate that live social interaction modulates the activity and connectivity of the right mirror neuron system and enhances spontaneous mimicry, further facilitating emotional contagion. HighlightsO_LIWe alternately presented real-time and pre-recorded dynamic facial expressions. C_LIO_LILive facial expressions enhanced emotion contagion and spontaneous facial mimicry. C_LIO_LILive conditions modulated mirror neuron system activity and effective connectivity. C_LIO_LIThe mentalizing network showed distinctive multivoxel patterns in live conditions. C_LIO_LIThe results support the validity of second-person design in social neuroscience. C_LI

neuroscience↗

bioRxiv2022

Symbiosis between Patescibacteria and Archaea discovered in wastewater-treating bioreactors

Each prokaryotic domain, Bacteria and Archaea, contains a large and diverse group of organisms characterized with ultrasmall cell size and symbiotic lifestyles - Patescibacteria (also known as Candidate Phyla Radiation/CPR) and DPANN archaea. Cultivation-based approaches have revealed that Patesibacteria and DPANN symbiotically interact with bacterial and archaeal partners/hosts respectively, but cross-domain symbiosis/parasitism has never been observed. Here, we discovered physical interaction between ultramicrobacterial Patescibacteria and methanogenic archaea using cultures from anaerobic wastewater treatment sludge. In the cultures, we observed physical attachment of ultramicrobial cells to cells resembling Methanothrix and Methanospirillum using transmission electron microscopy and successfully detected physical association of Ca. Yanofskybacteria and Methanothrix using fluorescence in situ hybridization (FISH) (other ultramicrosized bacterial cells, presumably Patescibacteria, were also observed to attach on Methanospirillum). This was further confirmed to be a symbiosis rather than simple aggregation based on the observation that most ultramicrobacterial cells attached to Methanothrix were Ca. Yanofskybacteria and positive correlation (p < 0.05) between the relative abundance of Patescibacteria lineages and methanogenic archaea (e.g., Ca. Yanofskybacteria-Methanothrix and uncultured clade 32-520-Methanospirillum). The results shed light on a novel cross-domain symbiosis and inspire potential strategies for culturing CPR/DPANN.

microbiology↗

bioRxiv2021

Unique metabolic strategies in Hadean analogues reveal hints for primordial physiology

Primordial microorganisms are postulated to have emerged in H2-rich alkaline Hadean serpentinite-hosted environments with homoacetogenesis as a core metabolism. However, investigation of two modern serpentinization-active analogues of early Earth reveals that conventional H2-/CO2-dependent homoacetogenesis is thermodynamically unfavorable in situ due to picomolar CO2 levels. Through metagenomics and thermodynamics, we discover unique taxa capable of metabolism adapted to the habitat. This included a novel deep-branching phylum, "Ca. Lithoacetigenota", that exclusively inhabits Hadean analogues and harbors genes encoding alternative modes of H2-utilizing lithotrophy. Rather than CO2, these metabolisms utilize reduced carbon compounds detected in situ presumably serpentinization-derived: formate and glycine. The former employs a partial homoacetogenesis pathway and the latter a distinct pathway mediated by a rare selenoprotein - the glycine reductase. A survey of serpentinite-hosted system microbiomes shows that glycine reductases are diverse and nearly ubiquitous in Hadean analogues. "Ca. Lithoacetigenota" glycine reductases represent a basal lineage, suggesting that catabolic glycine reduction is an ancient bacterial innovation for gaining energy from geogenic H2 even under serpentinization-associated hyperalkaline, CO2-poor conditions. This draws remarkable parallels with ancestral archaeal H2-driven methyl-reducing methanogenesis recently proposed. Unique non-CO2-reducing metabolic strategies presented here may provide a new view into metabolisms that supported primordial life and the diversification of LUCA towards Archaea and Bacteria.

microbiology↗

bioRxiv2021

Internal microbial zonation assists in the massive growth of marimo, a lake ball of Aegagropila linnaei in Lake Akan

Marimo (lake ball) is an uncommon ball-like aggregation of the green alga, Aegagropila linnaei. Although A. linnaei is broadly distributed in fresh and brackish waters in the northern hemisphere, marimo colonies are found only in particular habitats. The colonies have been gradually shrinking in recent years. Nevertheless, it is not clear how and why A. linnaei forms such massive spherical aggregations. Here, we report the bacterial microbiomes inside various sizes and aggregating structures of natural marimo collected from Lake Akan, Japan. We observed multi-layers composed of sediment particles only in the sizeable radial-type marimo with a >20 cm diameter, not in the tangled-type marimo. The deeper layers were enriched by Nitrospira, potential novel sulphur-oxidizing bacteria, and sulphate-reducing Desulfobacteraceae bacteria. The sulphur cycle-related bacteria are unique to Lake Akan due to sulphur deposits from the nearby volcanic mountains. Some of them were also recovered from lake sediments. Microorganisms of the multi-layers would form biofilms incorporating nearby sediment, which would function as microbial "seals" within large radial-type marimo. We propose that the layer structure provides habitats for diverse bacterial communities, promotes airtightness of the marimo, and finally contributes to the massive growth of the aggregation. These findings provide a clue to deciphering the massive growth of endangered marimo aggregates.

microbiology↗