Biology subjects

Nakayama, A.

Publications and source records attributed to Nakayama, A..

7 recordsLinked to original sources

bioRxiv2026

Lasp family proteins generated by teleost-specific genome duplication

Two rounds of whole-genome duplication (2R-WGD) in the vertebrate lineage are thought to have driven gene diversification. Mammals have four genes encoding five nebulin superfamily proteins (LASP1, LASP2/NEBL, NEB, and NRAP) hypothesised to have arisen from invertebrate LASP via WGD. Here, we examined the evolutionary fate of the nebulin superfamily after an additional WGD, teleost-specific genome duplication (TGD). Genome and transcriptome analysis of zebrafish (Danio rerio) and medaka (Oryzias latipes), of which the complete genomes were recently determined, showed only lasp family genes retained duplicate copies. Zebrafish retained two LASP2/NEBL-derived ohnologs; one (LASP2L) had been misidentified as a nebulette gene in the Zebrafish Information Network (ZFIN) despite lacking nebulette-specific exons. Another (LASP2/NEBL) is newly identified in this study because it lies in a newly determined region of the latest genome assembly. Contrastingly, medaka retained two LASP1 ohnologs and one LASP2/NEBL. The duplicated lasp family proteins showed overlapping and specific tissue expression patterns. We confirmed all three zebrafish lasp proteins bound actin and co-localized with actin-rich structures when ectopically expressed in cultured fibroblasts. This supports that TGD-derived lasp duplicates underwent lineage-specific retention and expression divergence in teleosts whilst conserving core actin-binding properties.

evolutionary biology↗

bioRxiv2026

Organ-resolved endothelial regulatory programs link aging and metabolic overload to vascular immune remodeling

Systemic aging and metabolic overload remodel the vasculature; however, how endothelial cells integrate these stresses across organs remains unclear. Using multi-organ single-cell and spatial transcriptomics with functional validation, we mapped endothelial and hematopoietic responses in adipose tissue, skeletal muscle, liver, and heart. Organ-specific endothelial transcriptional features were relatively preserved, whereas chronic stress selectively reconfigured regulatory programs: aging induced a conserved Irf/Stat-centered endothelial program, while high-fat diet engaged organ-biased lipid and remodeling programs. Spatial analysis revealed perivascular niches centered on aging-associated interferon-stimulated endothelial activation, with neighboring immune and stromal cells expressing C3 and LRP1-associated signals. Rather than simply amplifying inflammation, these niches contained mechanisms that restrained IFN activation, as C3 depletion upregulated vascular IRF7 expression. In parallel, the IFN downstream effector BST2 promoted anti-inflammatory macrophage differentiation and suppressed atherosclerosis. These findings define vascular inflammaging as an organ-resolved niche process in which endothelial IFN activation is coupled to local inflammatory restraint. HighlightsO_LIAging induces a shared endothelial type I IFN program across organs. C_LIO_LIA high-fat diet triggers organ-biased endothelial remodeling programs. C_LIO_LIPerivascular interferon niches couple inflammation with local restraint. C_LIO_LIIFN-induced endothelial BST2 promotes CD200R-associated macrophage regulatory features. C_LI

cell biology↗

bioRxiv2025

Integrated Antibody and DIA Based Plasma Proteomics Uncover Temporal Host Responses to SARS CoV 2 Infection

This is a single-case longitudinal study in which we monitored antibody responses and plasma proteome dynamics over a 310-day period in a single individual who underwent COVID-19 vaccination and SARS-CoV-2 infection. To evaluate COVID-19 antibody responses, human plasma samples collected over 310 days (August 18, 2021, to June 22, 2022) were analyzed by DIA-LC-MS/MS proteomics. This led to the acquisition of a quantitative protein profile and allowed validation of the temporal behavior of expressed proteins within the samples. A total of 1,502 proteins were identified from the plasma samples. Before vaccination, after the first dose, after the second dose, and during the period after contracting the novel coronavirus, protein quantification values during each event interval were compared. Despite minimal changes before and after COVID-19 vaccination, notable proteins exhibiting distinct high-expression and low-expression patterns were identified after SARS-CoV-2 infection.

molecular biology↗

bioRxiv2025

Longitudinal analysis of antibody titers after primary and booster mRNA COVID-19 vaccination can identify individuals at risk for breakthrough infection

A key issue in the post-COVID-19 era is the ongoing administration of COVID-19 vaccines. Repeated vaccination is essential for preparing against currently circulating and newly emerging SARS-CoV-2 variants while enabling people to continue with daily life. Optimizing vaccination strategies is crucial to efficiently manage medical resources and establish an effective vaccination framework. Therefore, it is important to quantitatively understand vaccine-induced immunity dynamics and to be able to identify poor responders with lower sustained antibody titers as potential priorities for revaccination. We investigated longitudinal antibody titer data in a cohort of 2,526 people in Fukushima, Japan, from April 2021 to November 2022 for whom basic demographic and health information was available. Using mathematical modeling and machine learning, we stratified the time-course patterns of antibody titers after 2 primary doses and 1 booster dose of mRNA COVID-19 vaccines. We identified 3 notable populations, which we refer to as the durable, the vulnerable, and the rapid-decliner populations, approximately half of which remained in the same population after the booster dose. Notably, the rapid-decliner population experienced earlier infections than the others. Furthermore, when comparing IgG(S) titers, IgA(S) titers, and T-spot counts between participants who experienced breakthrough infections after booster vaccination and those who did not, we found that IgA(S) titers were significantly lower in breakthrough infected participants during the early stage after booster vaccination. Our computational approach is adaptable to various types of vaccinations. This flexibility can inform policy decisions on vaccine distribution to enhance immunity both in future pandemics and in the post-COVID-19 era.

immunology↗

bioRxiv2023

Deep proteome analysis of time-series human plasma samples applied to Covid-19 antibody test

For the purpose of Covid-19 antibody testing, the human plasma samples acquired over a period of 310 days from August 18, 2021, to June 22, 2022, were subjected to DIA LC-MS proteome analysis. This process led to the acquisition of a quantitative protein profile and allowed for the validation of the temporal behavior of expressed proteins within the samples. A total of 1502 proteins were identified from the plasma samples. Before vaccination, after the first dose, after the second dose, and during the period after contracting the novel coronavirus, protein quantification values during each event interval were compared. Despite minimal changes observed before and after Covid-19 vaccination, notable proteins exhibiting distinct high-expression and low-expression patterns were identified after contracting the novel coronavirus infection.

molecular biology↗

bioRxiv2023

A hyperpolarizing neuron recruits undocked innexin hemichannels to transmit neural information in Caenorhabditis elegans

While depolarization of neuronal membrane is known to evoke the neurotransmitter release from synaptic vesicles, hyperpolarization is regarded as a resting state of chemical neurotransmission. Here we report that hyperpolarizing neurons can actively signal neural information by employing undocked hemichannels. We show that UNC-7, a member of the innexin family in Caenorhabditis elegans, functions as a hemichannel in thermosensory neurons and transmits temperature information from the thermosensory neurons to their post-synaptic interneurons. By monitoring neural activities in freely behaving animals, we find that hyperpolarizing thermosensory neurons inhibit the activity of the interneurons and that UNC-7 hemichannels regulate this process. UNC-7 is required to control thermotaxis behavior and functions independently of synaptic vesicle exocytosis. Our findings suggest that innexin hemichannels mediate neurotransmission from hyperpolarizing neurons in a manner that is distinct from the synaptic transmission, expanding the way of neural circuitry operations.

neuroscience↗

bioRxiv2022

Genetic screens identified dual roles of MAST kinase and CREB within a single thermosensory neuron in the regulation of C. elegans thermotaxis behavior

Animals integrate sensory stimuli presented at the past and present, assess the changes in their surroundings and navigate themselves toward preferred environment. Identifying the molecular and circuit mechanisms of such sensory integration is pivotal to understand how the nervous system generates perception and behavior. Previous studies on thermotaxis behavior of Caenorhabditis elegans suggested that a single thermosensory neuron AFD plays an essential role in integrating the past and present temperature information and is essential for the neural computation that drives the animal toward the preferred temperature region. However, the molecular mechanisms by which AFD executes this neural function remained elusive. Here we report multiple forward genetic screens to identify genes required for thermotaxis. We reveal that kin-4, which encodes the C. elegans homolog of MAST kinase, plays dual roles in thermotaxis and can promote both cryophilic and thermophilic drives. We also uncover that a thermophilic defect of mutants for mec-2, which encodes a C. elegans homolog of stomatin, can be suppressed by a loss-of-function mutation in the gene crh-1, encoding a C. elegans homolog CREB transcription factor. Calcium imaging analysis from freely-moving animals suggest that mec-2 and crh-1 function in AFD and regulate the neuronal activity of its post-synaptic interneuron AIY. Our results suggest that a stomatin family protein can control the dynamics of neural circuitry through the transcriptional regulation within a sensory neuron.

genetics↗