Biology subjects

Okada, N.

Publications and source records attributed to Okada, N..

25 records · Page 2Linked to original sources

bioRxiv2020

Patterns of functional and structural brain information are preserved over generations

There is clear evidence of intergenerational transmission of life values, cognitive traits, psychiatric disorders, and even aspects of daily decision making. To investigate biological substrates of this phenomenon, brain has received increasing attention as a measurable biomarker and potential target for intervention. However, no previous study has quantitatively and comprehensively investigated the effects of intergenerational transmission on functional and structural brain networks from parents to their children. Here, by employing an unusually large cohort dataset, we show that patterns of functional and structural brain networks are preserved over a generation. We also demonstrate that several demographic and behavioural phenotypes have effects on brain similarity. Collectively, our results provide a comprehensive picture of neurobiological substrates of parent-child similarity, and demonstrate the usability of our dataset for investigating the neurobiological substrates of intergenerational transmission.

neuroscience↗

bioRxiv2020

Intron retention as a new marker of the pre-disease state and its recovery to the normal state by a traditional Japanese multi-herbal medicine

Intron retention (IR) is an important regulatory mechanism that affects gene expression and protein functions. Using klotho mice at the pre-symptomatic state, we discovered that retained-introns accumulated in several organs including the liver and that among these retained introns in the liver a subset was recovered to the normal state by a Japanese traditional herbal medicine. This is the first report of IR recovery by a medicine. IR-recovered genes fell into two categories: those involved in liver-specific metabolism and in splicing. Metabolome analysis of the liver showed that the klotho mice were under starvation stress. In addition, our differentially expressed gene analysis showed that liver metabolism was actually recovered by the herbal medicine at the transcriptional level. By analogy with the widespread accumulation of intron-retained pre-mRNAs induced by heat shock stress, we propose a model in which retained-introns in klotho mice were induced by an aging stress and in which this medicine-related IR recovery is indicative of the actual recovery of liver-specific metabolic function to the healthy state. Accumulation of retained-introns was also observed at the pre-symptomatic state of aging in wild-type mice and may be an excellent marker for this state in general.

molecular biology↗

bioRxiv2019

Time-lapse single-cell transcriptomics reveals modulation of histone H3 for dormancy breaking

How quiescent cells break dormancy is a key issue in eukaryotic cells including cancer. Fungal spores, for example, remain quiescent for long periods until nourished, although the mechanisms by which dormancy is broken remain enigmatic. Transcriptome analysis could provide a clue, but methods to synchronously germinate large numbers of spores are lacking, and thus it remains a challenge to analyse gene expression upon germination. Hence, we developed methods to assemble transcriptomes from individual, asynchronous spore cells of fission yeast undergoing germination to assess transcriptomic changes over time. The virtual time-lapse analyses highlighted one of three copies of histone H3 genes for which transcription fluctuates during the initial stage of germination. Disruption of this temporal fluctuation caused defects in spore germination despite no visible defects in other stages of the life cycle. We conclude that modulation of histone H3 expression is a crucial wake-up trigger at dormancy breaking.

cell biology↗

bioRxiv2019

Functional connectome linking child-parent relationships with psychological problems in adolescence

Paternal- and maternal-child relationships are associated with partly distinct psychobehavioral problems, which often manifest differently between boys and girls. In order to understand neural mechanisms underlying complicated mappings between child-parent relationship and adolescents problems, we used a dataset of early adolescents (N=93) and separately estimated the effects of paternal- and maternal-child relationships on resting-state functional connectivity and problems in boys and girls. General linear models identified the effects of paternal- and maternal-child relationships in different sets of functional connectivity, which we termed functional brain connectomes associated with paternal- and maternal-child relationship (FBCp and FBCm), respectively. Subsequent connectome-based models using these FBCs significantly predicted aggressive behaviors only for boys and internalizing problems selectively only girls. Lastly, a causal discovery method identified causal paths from daughter-mother relationship to FBCm, and then to daughters internalizing problems. These observations highlight sex-dependent mechanisms linking child-parent relationship, brain, and psychobehavioral problems in early adolescence.

neuroscience↗

bioRxiv2019

CLASP2 lattice-binding near microtubule plus ends stabilizes kinetochore attachments

The fine regulation of kinetochore microtubule dynamics during mitosis ensures proper chromosome segregation by promoting error correction and spindle assembly checkpoint (SAC) satisfaction. CLASPs are widely conserved microtubule plus-end-tracking proteins that regulate microtubule dynamics throughout the cell cycle and independently localize to kinetochores during mitosis. Thus, CLASPs are ideally positioned to regulate kinetochore microtubule dynamics, but the underlying molecular mechanism remains unknown. Here we found that human CLASP2 can dimerize through its C-terminal kinetochore-targeting domain, but kinetochore localization was independent of dimerization. CLASP2 kinetochore localization, microtubule plus-end-tracking and microtubule lattice binding through TOG2 and TOG3 (but not TOG1) domains, independently sustained normal spindle length, timely SAC satisfaction, chromosome congression and faithful segregation. Measurements of kinetochore microtubule half-life in living cells expressing RNAi-resistant mutants revealed that CLASP2 kinetochore localization, microtubule plus-end-tracking and lattice binding cooperatively modulate kinetochore microtubule stability during mitosis. Thus, CLASP2 regulates kinetochore microtubule dynamics by integrating distinctive microtubule-binding properties at the kinetochore-microtubule interface to ensure chromosome segregation fidelity.

cell biology↗

bioRxiv2018

Development of the Brief Personal Values Inventory for sense of values in the Japanese general population

The Portrait Values Questionnaire (PVQ) is a widely used questionnaire for assessing sense of values; however, it has limitations, especially for children. Therefore, the present study aims to develop a questionnaire for sense of values, called the Brief Personal Values Inventory (BPVI), consisting of simple questions and a smaller number of items compared to the PVQ. We first created 12 items for the BPVI and then tested their validity and reliability in 167 Japanese general population (81 males, mean age (SD) [range]: 23.4 (8.2) [15-57] years). Each of these items was correlated with one or more values in the PVQ-57. The BPVI items covered all higher-order values in Schwartzs theory (Openness to Change, Self-Enhancement, Conservation, and Self-Transcendence). In sum, the BPVI has an acceptable criterion-related validity and corresponds to higher-order values in Schwartzs value theory. The BPVI is suitable for a reliable and direct comparison of sense of values between children and adults, which may be useful for elucidating the developmental pathway of personal sense of values.

scientific communication and education↗

bioRxiv2018

Harmonization of resting-state functional MRI data across multiple imaging sites via the separation of site differences into sampling bias and measurement bias

When collecting large neuroimaging data associated with psychiatric disorders, images must be acquired from multiple sites because of the limited capacity of a single site. However, site differences represent the greatest barrier when acquiring multi-site neuroimaging data. We utilized a traveling-subject dataset in conjunction with a multi-site, multi-disorder dataset to demonstrate that site differences are composed of biological sampling bias and engineering measurement bias. Effects on resting-state functional MRI connectivity because of both bias types were greater than or equal to those because of psychiatric disorders. Furthermore, our findings indicated that each site can sample only from among a subpopulation of participants. This result suggests that it is essential to collect large neuroimaging data from as many sites as possible to appropriately estimate the distribution of the grand population. Finally, we developed a novel harmonization method that removed only the measurement bias by using traveling-subject dataset and achieved the reduction of the measurement bias by 29% and the improvement of the signal to noise ratios by 40%.

neuroscience↗