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Biology subjects

Horikawa, K.

Publications and source records attributed to Horikawa, K..

5 recordsLinked to original sources

Male and female Drosophila suzukii maintain extended, stable flight headings to a discrete sun stimulus.

Long-distance movement in insects has crucial impacts on agriculture, human health, and biodiversity. Although it was long assumed that only large, specialist insects had the navigation capacity to support long-distance dispersal, recent studies have demonstrated that smaller insects, such as the tiny fruit fly Drosophila melanogaster, can maintain extended, straight paths while flying or walking. This raises the question of whether other Drosophila species possess the navigation capacity to support extended dispersal. Resolving this question is particularly important for Drosophila suzukii (spotted-wing drosophila), a potent pest species that causes enormous damage worldwide to ripe fruit and berries. Spotted-wing drosophila has been thought to lack a capacity for long-distance dispersal, as prior studies have estimated maximal daily dispersal distances of less than 90 m. We developed a system to continuously track the flight trajectories of magnetically tethered D. suzukii relative to a discrete, overhead LED that mimicked the sun. We found that flies maintained remarkably straight flight headings that varied unpredictably across individuals. Male and female D. suzukii exhibited a similar navigation capacity; both sexes responded to rotation of a discrete sun stimulus with compensatory turns to maintain a stable relative heading. Our results suggest that D. suzukii has an underappreciated capacity for rapid, radial dispersal, which could exceed 250 m in 15 min. This capacity may contribute to the pest species invasiveness and its reliable, annual re-establishment in seasonally intolerable climates. Our findings highlight the importance of developing area-wide, regional strategies to manage the impacts of D. suzukii.

zoology↗

A rare human TNFAIP3 variant reveals how A20 abundance is regulated by TAX1BP1

Variants in TNFAIP3 (encoding A20) are among the most consistent non-MHC genetic associations with human autoimmune disease. Moreover, TNFAIP3 haploinsufficiency confers an autosomal dominant autoinflammatory and autoimmune disease. Whilst these findings strongly suggest that quantitative changes in A20 predispose to pathology, there is currently no evidence that post-transcriptional modifications regulate A20 abundance. We used human reverse genetics approach to investigate this question. From a cohort of patients with complex immune diseases, we identified an ultrarare hypomorphic TNFAIP3 variant (A20S254R) that is both hypomorphic and prone to phosphorylation. One of five carriers of this variant was distinguished by autoimmunity and an NF-kB gain-of-function transcriptional signature. A search for modifiers identified a variant in TAX1BP1 (p.Leu207Ile). We discovered that TAX1BP1 normally retrains A20 phosphorylation. Furthermore, TAX1BP1 preferentially binds phospho-A20, which explains the enhanced interaction between TAX1BP1L207I and A20S254R. A20 phosphorylation regulates its abundance, not by MALT1-mediated degradation, but probably via autophagy. Thus, while A20 phosphorylation has been implicated in A20 protease activity, an epistatic interaction between rare human genetic variants reveals how phosphorylation also regulates A20 abundance.

immunology↗

Trans-scale-scope to find rare cellular activity in sub-million cells

In many phenomena of biological systems, not a majority, but a minority of cells act on the entire multicellular system causing drastic changes in the system properties. To understand the mechanisms underlying such phenomena, it is essential to observe the spatiotemporal dynamics of a huge population of cells at sub-cellular resolution, which is difficult with conventional tools such as microscopy and flow cytometry. Here, we describe an imaging system named AMATERAS that enables optical imaging with an over-one-centimeter field-of-view and a-few-micrometer spatial resolution. This trans-scale-scope has a simple configuration, composed of a low-power lens for machine vision and a hundred-megapixel image sensor. We demonstrated its high cell-throughput, capable of simultaneously observing more than one million cells. We applied it to dynamic imaging of calcium ions in HeLa cells and cyclic-adenosine-monophosphate in Dictyostelium discoideum, and successfully detected less than 0.01% of rare cells and observed multicellular events induced by these cells.

cell biology↗

Cellular logics bringing the symmetry breaking in spiral nucleation revealed by trans-scale imaging

SummaryThe spiral wave is a commonly observed spatio-temporal order in diverse signal relaying systems. Although properties of generated spirals have been well studied, the mechanisms for their spontaneous generation in living systems remain elusive. By the newly developed imaging system for trans-scale observation of the intercellular communication among ∼130,000 cells of social amoeba, we investigated the onset dynamics of cAMP signaling and identified mechanisms for the self-organization of the spiral wave at three distinct scalings: At the population-level, the structured heterogeneity of excitability fragments traveling waves at its high/low boundary, that becomes the generic source of the spiral wave. At the cell-level, both the pacemaking leaders and pulse-amplifying followers regulate the heterogeneous growth of the excitability. At the intermediate-scale, the essence of the spontaneous wave fragmentation is the asymmetric positioning of the pacemakers in the high-excitability territories, whose critical controls are operated by a small number of cells, pulse counts, and pulse amounts.Competing Interest StatementThe authors have declared no competing interest.View Full Text

systems biology↗

Phospho-tuning immunity through Denisovan, modern human, and mouse TNFAIP3 gene variants

Resisting or tolerating microbes are alternative strategies to survive infection, but little is known about the evolutionary mechanisms controlling this balance. Here, genomic analyses of anatomically modern humans, extinct Denisovan hominins, and mice revealed a series of missense variants in the immune response inhibitor A20 (encoded by TNFAIP3), substituting non-catalytic residues of the ubiquitin protease domain to diminish I{kappa}B-dependent phosphorylation and activation of A20. Two A20 variants with partial phosphorylation deficits appeared beneficial: one originating in Denisovans and introgressed in modern humans throughout Oceania, and another in a mouse strain resistant to Coxsackievirus. By contrast, a variant with 95% loss of phosphorylation caused spontaneous inflammatory disease in humans and mice. Analysis of the partial phosphorylation variant in mice revealed diminished tolerance of bacterial lipopolysaccharide or to poxvirus inoculation as trade-offs for enhanced immunity.\n\nOne Sentence SummaryModern and ancient variants reveal a genetically tunable element for balancing immunity and microbial tolerance.

immunology↗