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Yokota, H.

Publications and source records attributed to Yokota, H..

9 recordsLinked to original sources
bioRxiv2026

Task-specific ISS reduction and network balance during Stroop task performance in older adults

Declines in the cognitive inhibition that comes with aging impacts daily life and independence. It is still debated whether overactivation during cognitive inhibition tasks in older adults is due to compensation or neural noise. To address this question, we examined age-related changes in inter-subject similarity (ISS) of functional connectivity from task-based and resting-state fMRI. Using Bayesian hierarchical modeling, we identified 27 Stroop task-related regions of interest and found that ISS in these regions was significantly reduced in older adults during task performance. Furthermore, aging is associated with a loss of consistent functional connectivity patterns in frontal regions, accompanied by the emergence of a convergent compensatory mechanism within visual attention regions. Principal component analysis of individual activation deviations from the group-mean pattern showed that task performance in older adults cannot be explained by overall task-related brain activation, but rather by a specific spatial component involving suppression of the default mode network and increased activity in visual attention regions. These findings indicate that task-related brain overactivation in older adults is not due to uniform noise or uniform compensation, but rather a spatially specific pattern of functional reorganization.

neuroscience↗
bioRxiv2026

Increased Interstitial Flow and Elastic Lamina Degradation Precede Aortic Dissection

AimsTo elucidate the relationship between interstitial flow (IF) and structural changes in the aortic media during the development of aortic dissection (AD). MethodsApolipoprotein E-deficient (ApoE[-/-]) mice infused with angiotensin II (AngII) were used as an AD model, in which AD develops exclusively in the thoracoabdominal aorta but not in the thoracic aorta. To capture characteristics present prior to AD onset, the duration of AngII infusion was shortened to generate Pre-AD group. Normal C57BL/6 mice (Normal group) and ApoE(-/-) mice without AngII infusion (Control group) were also included for comparison. Thoracic and thoracoabdominal aortas were excised from all groups, and IF was measured in vitro in accordance with our previously established methods. ResultsIF velocity was generally smaller than 4 m/s across all groups; however, velocities exceeding 4 m/s was observed predominantly in the thoracoabdominal region of the Pre-AD group. Although mean IF velocity did not differ significantly among groups, the standard deviation differed significantly and was the highest in the thoracoabdominal region of the Pre-AD group. In this region, IF velocity tended to increase with more prolonged AngII administration, indicating acceleration of IF prior to AD onset. Three-dimensional internal structural microscopy revealed fragmentation of the elastic lamina (ELs) and a reduction in elastin density only in the thoracoabdominal region of the Pre-AD group. ConclusionsOur findings suggest that increased IF and EL degradation occur in parallel and together contribute to the initiation of AD.

bioengineering↗
bioRxiv2025

Data-Driven Feed Optimization for Sustainable Aquaculture through Integrated Omics Analysis and Two-stage Bayesian optimization

In aquaculture and livestock farming, developing feed that promotes efficient growth while minimizing environmental impact is crucial for sustainability. We developed a data-driven feed optimization system (DFOS) that integrates omics analysis with machine learning-based optimization technologies. First, DFOS employed Bayesian optimization (BO) to identify the optimal proportions of proteins and lipids, which are crucial feed components. Simultaneously, omics analysis was conducted to assess the physiological response of the targets to a given feed and identify key dietary components essential for growth. Next, BO was used to efficiently modify the combination and proportion of the specific additives identified in the first stage. We demonstrated the efficacy of DFOS by applying it to develop a new feed for the high-demand leopard coral grouper (Plectropomus leopardus) in Southeast Asia. This system provides an efficient data-driven framework for feed optimization across aquaculture and livestock, contributing significantly to more sustainable and productive farming practices.

ecology↗
bioRxiv2023

Different Physical Parameters in the Bonds between Platelet Glycoprotein Ibalpha with von Willebrand factor and with Coagulant Factor XI -Results from the Molecular Dynamic Simulation-

BackgroundBoth von Willebrand factor (VWF) and coagulation factor XI (FXI) bind with platelet membrane glycoprotein (GP) Ib. However, the differences in the physical parameters in the bonds between VWF-GPIb and FXI-GPIb mediating different biological functions are unclear. MethodsThe FXI molecule was arranged in 9 different initial positions around the structure of GPIb bound to VWF. The position coordinate and velocity vectors of all atoms constructing VWF, GPIb, and FXI were calculated in each 2 femto (10-15) second using the Chemistry at HARvard Macromolecular Mechanics (CHARMM) force field. The physical parameters of VWF-GPIb and FXI-GPIb bonds were calculated by molecular dynamic (MD) simulations. ResultsMD calculation revealed 2.8 to 11.3 times greater positional fluctuations in atoms constructing FXI-GPIb as compared to those constructing VWF-GPIb (RMSDs: 5.9{+/-}1.5 to 18.1{+/-}7.9 [A] for FXI-GPIb vs 1.6{+/-}0.1 to 2.1{+/-}0.3 [A] for VWF-GPIb). The absolute value of non-covalent binding energy generated in FXI-GPIb (65.5{+/-}79.7 to 517.6{+/-}54.2 kcal/mol) was smaller than that generated in VWF-GPIb (678.5{+/-}58.3 to 1000.4{+/-}75.1 kcal/mol). The binding structure of VWF-GPIb was stable and was only minimally influenced by the presence of FXI-GPIb binding. ConclusionsOur MD calculation results revealed that atoms constructing the VWF-GPIb bond are physically more stable and produce more non-covalent binding energy than the bond of FXI-GPIb. The physical parameters in the VWF-GPIb bond were not largely influenced by FXI binding with GPIb.

bioengineering↗
bioRxiv2022

Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins

Osteosarcoma (OS) is the common primary bone cancer that affects mostly children and young adults. To augment the standard-of-care chemotherapy, we examined the possibility of protein-based therapy using mesenchymal stem cells (MSCs)-derived proteomes and osteosarcoma-elevated proteins. While a conditioned medium (CM), collected from MSCs, did not present tumor-suppressing ability, the activation of PKA converted MSCs into induced tumor-suppressing cells (iTSCs). In a mouse model, the direct and hydrogel-assisted administration of CM inhibited tumor-induced bone destruction, and its effect was additive with Cisplatin. CM was enriched with proteins such as Calreticulin, which acted as an extracellular tumor suppressor by interacting with CD47. Notably, the level of Calr transcripts was elevated in OS tissues, together with other tumor-suppressing proteins, including histone H4, and PCOLCE. PCOLCE acted as an extracellular tumor-suppressing protein by interacting with amyloid precursor protein (APP), a prognostic OS marker with poor survival. The results supported the possibility of employing a paradoxical strategy of utilizing OS transcriptomes for the treatment of OS.

cancer biology↗
bioRxiv2020

Receptor-linked environment-sensitive probe monitors the local membrane environment surrounding the insulin receptor

Functional membrane proteins in the plasma membrane are suggested to have specific membrane environments that play important roles to maintain and regulate the function of proteins. However, the local membrane environments of membrane proteins remain largely unexplored due to the lack of techniques allowing to monitor them in living cells. We have developed a method to probe the local membrane environment surrounding a membrane protein in the plasma membrane by covalently tethering a solvatochromic, environment-sensitive dye, Nile red, to a membrane protein via a flexible linker. Our direct imaging reported on the spatio-temporal properties of membrane fluidity of the local environment surrounding the insulin receptor. The local environment was distinct from the average plasma membrane fluidity and was quite dynamic and heterogeneous. Upon addition of insulin, the local membrane environment surrounding the receptor increased in fluidity in an insulin receptor-kinase dependent manner. This new technology should allow researchers to examine changes in membrane properties caused by receptor activation and devise ways to address the role of these changes in physiological processes.

cell biology↗
bioRxiv2020

APC mutant cells exploit compensatory chromosome alterations to restore tumour cell fitness

Cancer cells tolerate copy number alterations (CNAs) of genomic regions that are lethal to non-cancer cells. Certain CNAs are preferentially associated with specific cancer types and lineages, but the mechanisms underlying the emergence and selection of specific CNAs remain unclear. Adenomatous polyposis coli (APC) mutations induce mitotic errors, but their impact on tumor evolution remains elusive. We investigated APC function in cultured cells and tumors and found that its loss led to {beta}-catenin accumulation at centrosomes, suppressing its maturation through inhibition of key centrosome regulators, including Aurora kinase A (AURKA) that promotes tumor growth. These defects collectively reduced cellular fitness, leading to impaired mitotic fidelity and delayed cell cycle progression. However, in APC-mutant tumors, AURKA activity was maintained, at least in part, through the amplification of chromosomes harboring AURKA and its activator genes, yet this alone was insufficient to fully restore proliferation: aberrant chromosomal reorganization also emerged and contributed to the adaptive fitness of APC-mutant cells. Such a process of adaptive CNA selection provides a framework for understanding how specific CNAs are selected to counteract disadvantages imposed by genetic alterations during tumor progression, providing one key insight into how specific CNAs are selected in this context.

cell biology↗
bioRxiv2020

Evaluation of origin of driving force for loop formation in a chromatin fiber

Chromosome condensation results from the formation of consecutive chromatin loops in which excluded volume interactions lead to chromosome stiffness. Formation of chromatin loops requires energy, but the source of such energy remains controversial. Here, we quantified the energy balance during chromatin loop formation by calculating the free energies of unlooped and looped chromatins using a lattice model of polymer chains. We tested two hypothetical energy sources: thermal fluctuation and ATP hydrolysis. We evaluated the free energy difference of the chain loop model without accounting for excluded volume interactions (phantom loop model), and integrated those interactions by employing the mean-field theory (interacting loop model), where we introduced the parameter of excluded volume interaction within a single loop vex. Using our strategy, we confirmed that loop-growth efficiency calculated by the phantom loop model is too high to explain the experimental data. Comparing loop-growth efficiencies for each energy source, and using the interacting loop model, we found that excluded volume interaction is essential for chromatins resistance to looping, regardless of the energy source. We predict that the quantitative measurement of vex determines which energy source is more plausible. Author summaryBefore mitosis, the chromatin fibers of eukaryotic cells fold into consecutive loop structures and condense into rod-like chromosomes. Chromosome stiffness results from the interaction of the excluded volume between chromatin loops. The driving force of loop formation and growth is still controversial, despite the many efforts undertaken to clarify it. Two possible origins can be considered: the energy provided by thermal fluctuations or the energy gained from ATP hydrolysis. To discuss the validity of each, we constructed a theoretical model of chromatin loop formation that includes excluded volume interactions. Using this model, we calculated the free energy difference before and after chromatin loop formation, which corresponds to the energy that fuels chromatin looping. By comparing the results for each energy source, we conclude that the spatial distribution of chromatin loops should be relatively wide, given the large excluded volume interaction within a single loop, irrespective of which energy source is valid. Moreover, our results imply that intra-loop interactions are key to determine the driving force of chromatin loop formation.

biophysics↗