Biology subjects

Iwasa, Y.

Publications and source records attributed to Iwasa, Y..

6 recordsLinked to original sources

bioRxiv2024

Thymic involution as an adaptive schedule for combating diverse pathogens.

Diverse naive T cells, produced in the thymus, migrate to peripheral tissues and help suppress pathogens upon activation. As we age, the thymus shrinks, reducing both the supply and diversity of naive T cells, which increases the time required to establish immunity against new pathogens. This process, called thymic involution, is considered a form of aging. In this study, we explore whether thymic involution might be an adaptive strategy. Over time, the immune system accumulates memory cells, reducing the need for new naive T cells to combat unfamiliar pathogens. We examine how the optimal rate of naive T cell production, h(t), declines with age, taking into account the cost of maintaining thymic activity. When pathogen encounter rates are equal, h(t) decreases exponentially with age. As pathogen encounter rates rise, the initial value h(0) increases, but the rate declines more rapidly with age, reducing overall production. A higher pathogen diversity, a greater cost of fighting new pathogens, and a lower cost of maintenance increase h(t). When pathogen encounter rates vary, h(t) decreases with age according to a power function. HighlightsO_LIThe thymus generates diverse naive T cells to recognize a wide range of pathogens. C_LIO_LIThymic involution is considered an adaptive strategy, factoring in maintenance cost. C_LIO_LIIf pathogen encounters are frequent, the rate starts high but quickly declines. C_LIO_LIThe rate increases with the pathogen risk and decreases with the thymic cost. C_LIO_LIIf pathogens vary in abundances, the rate decreases as a power function of age. C_LI

immunology↗

bioRxiv2024

Genetic diversity within a tree and alternative indexes for different evolutionary effects

Trees, living for centuries, accumulate somatic mutations in their growing trunks and branches, causing genetic divergence within a single tree. Stem cell lineages in a shoot apical meristem accumulate mutations independently and diverge from each other. In plants, somatic mutations can alter the genetic composition of reproductive organs and gametes, impacting future generations. To evaluate the genetic variation among a trees reproductive organs, we consider three indexes: mean pairwise phylogenetic distance [Formula], phylogenetic diversity (PD; sum of branch lengths in molecular phylogeny), and parent-offspring phylogenetic distance (DPO). The tissue architecture of trees facilitated the accumulation of somatic mutations, which have various evolutionary effects, including enhancing fitness under strong sib competition and intense host-pathogen interactions, efficiently eliminating deleterious mutations through epistasis, and increasing genetic variance in the population. Choosing appropriate indexes for the genetic diversity of somatic mutations depends on the specific aspect of evolutionary influence being assessed.

genetics↗

bioRxiv2023

Branching architecture affects genetic diversity within an individual tree

PremiseWhile a tree grows over many years, somatic mutations accumulate and generate a genetically diverse individual. Trees can transmit such mutations to subsequent generations, potentially enhancing the genetic diversity of the population. We study a mathematical model to understand the relationship between within-individual genetic variation and branching architecture. MethodsWe generate branching architecture by repeatedly adding two new branches (main and lateral daughter branches) to each terminal branch (mother branch). Tree shape is determined by two key parameters: daughter-mother ratio (DM) and main-lateral ratio (ML). During branch elongation, somatic mutations accumulate in the stem cells of a shoot apical meristem (SAM) at the tip of each branch. In branching, all the stem cells are passed on from the mother to the main daughter branch, but only one stem cell is chosen for the lateral daughter branch. We evaluate genetic variation by [Formula], the mean genetic differences between all pairs of branches of a tree, and examine how [Formula] varies with DM and ML while keeping the total branch length constant. Key results and Conclusions(1) [Formula] attains the maximum for an intermediate DM, when stem cells in the SAM are genetically homogeneous; (2) [Formula] decreases monotonically with DM when stem cells are genetically heterogeneous; and (3) [Formula] increases monotonically with ML. Even though the total branch length remains constant, the within-individual genetic variation differs substantially. The results demonstrate the importance of branching architecture in storing genetic diversity.

evolutionary biology↗

bioRxiv2022

The genetic structure within a single tree is determined by the behavior of the stem cells in the meristem

Genomic sequencing revealed that somatic mutations cause a genetic differentiation of the cells in a single tree. In this study, we consider a mathematical model for stem cell proliferation in the shoot apical meristem (abbrev. SAM), which results in genetic diversification between the cells differing in the distance along the shoot and the angle around a shoot axis. The assumptions are as follows. Stem cells in the SAM normally undergo asymmetric cell division and produce successor stem cells and differentiated cells. The differentiated cells proliferate and contribute to shoot elongation. Occasionally, a stem cell is replaced by a copy of an adjacent stem cell. We discuss the "coalescent length" between cells indicating their genetic difference with respect to neutral mutations. A mathematical analysis revealed the following. The genetic diversity of cells sampled at the same position along the shoot increases with the distance from the bottom of the shoot. Stem cells hold a larger variation if they are replaced only by the nearest neighbors than if they are replaced by any cells. The coalescent length between two cells increases not only with the difference in the position along the shoot but also in the angle around the shoot axis. The dynamics of stem cells at the SAM determine the genetic pattern of the entire shoot.

evolutionary biology↗

bioRxiv2022

The voltage-gated Cav Ca2+ channel subunit α2δ-4 is required for locomotor behavior and sensorimotor gating in mice

Voltage-gated Cav Ca2+ channels are critical for the development and mature function of the nervous system. Variants in the CACNA2D4 gene encoding the 2{delta}-4 auxiliary subunit of these channels are associated with neuropsychiatric and neurodevelopmental disorders. 2{delta}-4 is prominently expressed in the retina and is crucial for vision, but extra-retinal functions of 2{delta}-4 have not been investigated. Here, we sought to fill this gap by analyzing the behavioral phenotypes of 2{delta}-4 knockout (KO) mice. 2{delta}-4 KO mice (both males and females) exhibited significant impairments in prepulse inhibition that were unlikely to result from the modestly elevated auditory brainstem response thresholds. Whereas 2{delta}-4 KO mice of both sexes were hyperactive in various assays, only females showed impaired motor learning/coordination in the rotarod assay. Female but not male 2{delta}-4 KO mice exhibited anxiolytic and anti-depressive behaviors in the elevated plus maze and tail suspension tests, respectively. Our results reveal an unexpected role for 2{delta}-4 in cognitive and motor function and identify 2{delta}-4 KO mice as a novel model for studying the pathophysiology associated with CACNA2D4 variants.

neuroscience↗

bioRxiv2017

Interactions between immunotoxicants and parasite stress: implications for host health

Many organisms face a wide variety of biotic and abiotic stressors which reduce individual survival, interacting synergistically to further reduce fitness. Here we studied the effects of two such synergistically interacting stressors; immunotoxicant exposure and parasite infection. We model the dynamics of a within-host infection and the associated immune response of an individual. We consider both the indirect sub-lethal effects on immunosuppression and the direct effects on health and mortality of individuals exposed to toxicants. We demonstrate that sub-lethal exposure to toxicants can promote infection through the suppression of the immune system. This happens through the depletion of the immune response which causes rapid proliferation in parasite load. In addition, high toxicant exposure can alter cellular regulation and cause the breakdown of normal healthy tissue, from which we infer higher mortality risk of the host. We classify this breakdown into three phases of increasing toxicant stress, and demonstrate the range of conditions under which toxicant exposure causes failure at the within-host level. These phases are determined by the relationship between the immunity status, overall cellular health and the level of toxicant exposure. We discuss the implications of our model in the context of individual honey bee health. Our model provides an assessment of how pesticide stress and infection interact to cause the synergistic breakdown of the within-host dynamics of individual honey bees.

epidemiology↗