Biology subjects

Sekine, Y.

Publications and source records attributed to Sekine, Y..

9 recordsLinked to original sources

bioRxiv2026

Food intake habits and preference affects the activity of medial frontal cortex during eating; functional near-infrared spectroscopy is potential biosensor for appetite study.

Even if they have no dementia, some elderly people find it difficult to imagine the food they may want to eat. However, research into treatments for anorexia in elderly people has not progressed sufficiently due to the lack of a method that can easily measure brain function in clinical settings. In this study, we aim to clarify the relationship of food-dependent medial prefrontal cortex (MPFC) activity with food preference and intake frequency by functional near-infrared spectroscopy (fNIRS) to determine ways to treat the appetite loss and have difficulty in explain what they want to eat. For this purpose, we firstly establish the methodology using young participants experiment. All young participants were asked about their food preferences and intake frequency using a questionnaire, and they were instructed to look and then eat the control dish (CD: typical Japanese home-cooked meal) and their preferred dish (PD: each participant purchased the dish themselves on the day of the experiments) on separate days, and activity of MPFC in each participant was recorded by fNIRS. We found that activity of MPFC during "just-looking" and "eating" were affected by food intake habits and preference. Especially, activity of MPFC during CD eating was affected by food preference (has dislike food or not). We concluded that the activity of MPFC during eating of dishes varies depending on the food intake habits and fNIRS could be a potential technique for estimating such activity.

neuroscience↗

bioRxiv2025

Axon Regeneration and Functional Recovery after Spinal Cord Injury is Enhanced by Allele-Specific ApoE Neuronal Action through LRP8

Adult CNS trauma frequently causes neuronal disconnection and persistent deficits due to failed axon regeneration. While model system screening has identified multiple candidate neural repair pathways, ApoE-LRP8 signaling is unique in being implicated clinically. Here, we show that cortical axon regeneration requires LRP8 and is modified by APOE variants. ApoE2-expressing mice show reparative corticospinal and raphespinal axon growth with greater motor function than controls after spinal cord injury. Distinct from ApoE in other settings, there is no change in inflammation or scarring. After axotomy, ApoE exerts allele-specific effects on LRP8 localization and signaling in cortical neurons. APOE alleles regulate synaptic organization gene expression by cortical neurons after injury, with little effect on glial gene expression. AAV-mediated overexpression of ApoE2 in mice after spinal trauma increases locomotor recovery and reparative axon growth. Thus, ApoE-LRP8 signaling for axon regrowth following CNS trauma provides a potential therapeutic intervention site.

neuroscience↗

bioRxiv2025

Compositional selection of phospholipid compartments in icy environments drives the inheritance of encapsulated genetic information

The lipid world hypothesis proposes that both intracellular components and the chemical composition of the membrane compartment carry heritable information that contributes to protocellular fitness. However, there are few experimental demonstrations of membrane compositional selection and no study has shown that phospholipids--the primary membrane components of modern cells--can support selection of this type. As lipid compartments generally grow in size before fission, faster-growing compartments should enjoy a selective advantage that favors both the membrane itself and the contents it hosts. When situated in icy environments undergoing cycles of freezing and thawing (F/T), we found that the growth of phospholipid vesicles depends on their phospholipid composition: Vesicles with more unsaturated bonds in the acyl chain showed higher growth efficiency. When vesicles composed of lipids with either one or two unsaturated bonds were mixed and subjected to F/T cycles, a selective enrichment of the lipid with two unsaturated bonds was observed. Moreover, selection acting on lipid composition was propagated to the encapsulated genetic material, which was also enriched while selectively neutral. We conclude that phospholipid composition can be a direct target of selection for grown vesicles under an icy environment leading to indirect but concurrent enrichment of compartmentalized genetic molecules.

synthetic biology↗

bioRxiv2024

Synchronous processing of temporal information across the hippocampus, striatum, and orbitofrontal cortex

Information processing for interval timing is supported by several brain regions, including the hippocampus, basal ganglia, and frontal cortical areas. However, little is known about the mechanism by which temporal information is processed cooperatively in the distributed brain network. Here, we investigated the neuronal processing of temporal information in the hippocampal CA1, dorsal striatum, and orbitofrontal cortex by simultaneously recording neuronal activity during a temporal bisection task. We found time cells representing elapsed time during the interval period across all three regions. Seeking a potential mechanism for the correlative representation of time, we found that theta oscillations were dominant in these areas and modulated the activity of these time cells. Moreover, the synchronization of the time cell pairs across the areas was also regulated by theta oscillations. Taken together, these results demonstrated the presence of synchronous activity of time cells across the three areas on a fine time scale, which was supported by theta oscillations. In addition, decoding analysis revealed that the activity of the time cells in these areas correlated with the rats decisions based on their internal time estimation, with the decoded time also showing correlations across the three regions. Thus, the cooperative activity of time-cell assemblies in the three regions reflected the recognition of elapsed time in the rats. In conclusion, these results demonstrate the pivotal role of neuronal synchronization of time cells in supporting temporal processing in the distributed brain network.

neuroscience↗

bioRxiv2022

VR-based real-time imaging reveals abnormal cortical dynamics during behavioral transitions in a mouse model of autism

Functional connectivity (FC) can provide insight into cortical circuit dysfunction in neuropsychiatric disorders. However, dynamic changes in FC related to locomotion with sensory feedback remain unexplored. To investigate FC dynamics in locomoting mice, we developed mesoscopic Ca2+ imaging with a virtual reality (VR) environment. We find rapid reorganization of cortical FC in response to changing behavioral states. Using machine learning classification, behavioral states are accurately decoded. We then use our VR-based imaging system to study cortical FC in a mouse model of autism and find that locomotion states are associated with altered FC dynamics. Furthermore, we identify FC patterns involving the motor area as the most distinguishing features of the autism mice from wild-type mice during behavioral transitions, which might correlate with motor clumsiness in patients with autism. Our VR-based real-time imaging system provides invaluable information to understand FC dynamics linked to a behavioral abnormality of neuropsychiatric disorders.

neuroscience↗

bioRxiv2022

The contribution of Kaposis sarcoma-associated herpesvirus ORF7 and its zinc-finger motif to viral genome cleavage and capsid formation

Kaposis sarcoma-associated herpesvirus (KSHV) is the causative agent of endothelial and B cell malignancies. During KSHV lytic infection, lytic-related proteins are synthesized, viral genomes are replicated as a tandemly repeated form, and subsequently, capsids are assembled. The herpesvirus terminase complex is proposed to package an appropriate genome unit into an immature capsid, by cleavage of terminal repeats (TRs) flanking tandemly linked viral genomes. Although the mechanism of capsid formation in - and {beta}-herpesviruses are well-studied, in KSHV, it remains largely unknown. It has been proposed that KSHV ORF7 is a terminase subunit, and ORF7 harbors a zinc-finger motif, which is conserved among other herpesviral terminases. However, the biological significance of ORF7 is unknown. We previously reported that KSHV ORF17 is essential for the cleavage of inner scaffold proteins in capsid maturation, and ORF17 knockout (KO) induced capsid formation arrest between the procapsid and B-capsid stages. However, it remains unknown if ORF7-mediated viral DNA cleavage occurs before or after ORF17-mediated scaffold collapse. We analyzed the role of ORF7 during capsid formation using ORF7-KO-, ORF7&17-double-KO (DKO)-, and ORF7-zinc-finger motif mutant-KSHVs. We found that ORF7 acted after ORF17 in the capsid formation process, and ORF7-KO-KSHV produced incomplete capsids harboring non-spherical internal structures, which resembled soccer balls. This soccer ball-like capsid was formed after ORF17-mediated B-capsid formation. Moreover, ORF7-KO- and zinc-finger motif KO-KSHV failed to appropriately cleave the TR on replicated genome and had a defect in virion production. Thus, our data revealed that ORF7 contributes to terminase-mediated viral genome cleavage and capsid formation. IMPORTANCEIn herpesviral capsid formation, the viral terminase complex cleaves the TR sites on newly synthesized tandemly repeating genomes and inserts an appropriate genomic unit into an immature capsid. Herpes simplex virus 1 (HSV-1) UL28 is a subunit of the terminase complex that cleaves the replicated viral genome. However, the physiological importance of the UL28 homolog, KSHV ORF7, remains poorly understood. Here, using several ORF7-deficent KSHVs, we found that ORF7 acted after ORF17-mediated scaffold collapse in the capsid maturation process. Moreover, ORF7 and its zinc-finger motif were essential for both cleavage of TR sites on the KSHV genome and virus production. ORF7-deficient KSHVs produced incomplete capsids that resembled a soccer ball. To our knowledge, this is the first report showing ORF7-KO-induced soccer ball-like capsids production and ORF7 function in the KSHV capsid assembly process. Our findings provide insights into the role of ORF7 in KSHV capsid formation.

microbiology↗

bioRxiv2022

A mitochondrial iron-sensing pathway regulated by DELE1

The heme-regulated kinase HRI is activated under heme/iron deficient conditions; however, the underlying molecular mechanism is incompletely understood. Here, we show that iron deficiency-induced HRI activation involves a heme-independent mechanism that requires the mitochondrial protein DELE1. Notably, mitochondrial import of DELE1 and its subsequent protein stability are regulated by iron availability. Under steady state conditions, DELE1 is degraded by the mitochondrial matrix-resident protease LONP1 soon after mitochondrial import. Upon iron chelation, DELE1 import is arrested, thereby stabilizing DELE1 on the mitochondrial surface to activate the HRI-mediated integrated stress response (ISR). Moreover, depletion of the mitochondrial ABC transporter ABCB7 that is involved in iron-sulfur cluster (ISC) metabolism markedly abrogates iron deficiency-induced ISR activation, suggesting the possible involvement of ISC-related molecules in this activation. Our findings highlight mitochondrial import regulation of DELE1 as the core component of a previously unrecognized iron monitoring system that connects the mitochondria to the cytosol.

cell biology↗

bioRxiv2021

Discovery of bactericides as an acute mitochondrial membrane damage inducer

Mitochondria evolved from endosymbiotic bacteria to become essential organelles of eukaryotic cells. The defined lipid composition and structure of mitochondrial membranes are critical for the proper functioning of mitochondria. However, mitochondrial stress responses that help maintain the integrity of mitochondrial membranes against internal or external insults are not well understood. One reason for this lack of insight is the absence of efficient tools to specifically damage mitochondrial membranes. Here, through a compound screen originally aimed at identifying inhibitors of the inner mitochondrial membrane (IMM)-resident protease OMA1, we found that two bis-biguanide compounds, Chlorhexidine and Alexidine, modified OMA1 activity by altering the integrity of the IMM. Interestingly, these compounds are well-known bactericides whose mechanism of action has centered on their damage-inducing activity on bacterial membranes. We found Alexidine binds to the IMM likely through the electrostatic interaction driven by the membrane potential as well as an affinity for anionic phospholipids. Electron microscopic analysis revealed that Alexidine severely perturbated the IMM, especially the cristae structure. Along with this, we observed the altered localization of IMM-resident membrane-shaping proteins, including Mic60. Notably, Alexidine evoked a specific transcriptional/proteostasis signature that was not induced by other typical mitochondrial stressors, highlighting the unique property of Alexidine as a novel mitochondrial membrane stressor. Our findings provide a chemical-biological tool that can induce acute and selective perturbation of the IMM integrity, which should enable the delineation of mitochondrial stress-signaling pathways required to maintain the mitochondrial membrane homeostasis.

cell biology↗

bioRxiv2020

Acetylation-mediated phase control of the nucleolus regulates cellular acetyl-CoA responses

The metabolite acetyl-CoA serves as an essential element for a wide range of cellular functions including ATP production, lipid synthesis and protein acetylation. Intracellular acetyl-CoA concentrations are associated with nutrient availability, but the mechanisms by which a cell responds to fluctuations in acetyl-CoA levels remain elusive. Here, we generate a cell system to selectively manipulate the nucleo-cytoplasmic levels of acetyl-CoA using CRISPR-mediated gene editing and acetate supplementation of the culture media. Using this system and quantitative omics analyses, we demonstrate that acetyl-CoA depletion alters the integrity of the nucleolus, impairing ribosomal RNA synthesis and evoking the ribosomal protein-dependent activation of p53. This nucleolar remodeling appears to be mediated through the class IIa HDAC deacetylases regulating the phase state of the nucleolus. Our findings highlight acetylation-mediated control of the nucleolus as an important hub linking acetyl-CoA fluctuations to cellular stress responses.

cell biology↗