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Biology subjects

Ishimoto, K.

Publications and source records attributed to Ishimoto, K..

3 recordsLinked to original sources

Self-buckling of undulating flagella: an elastohydrodynamic mechanism for double waves in spermatozoa

The relatively long flagella of spermatozoa from insects, birds, and octopuses display double waves, characterized by two superimposed helical waves. The prevalance of these highly organized waveforms across diverse taxa and distinct flagellar architectures hints at shared underlying physics, motivating a model of the flagellum as an elastic filament immersed in a viscous fluid, actively driven by a single set of internal bending moment waves. Simulations of a clamped filament show that it can buckle under its own activity into whirling and flapping states. A multiple-scales analysis of the elastohydrodynamic equations reveals how nonlinear interactions between fast undulations generate an effective compression driving buckling, and connects wave-driven buckling to classical follower-force instabilities. Extending the model to a swimming spermatozoon, the same instability produces double waves. Parameter estimates across species show that most observed double waves lie within the regime where buckling is permitted, supporting self-buckling as a generic physical mechanism for double waves.

biophysics↗

Alphavirus replicon particle expressing IL-12 reprograms tumor-associated macrophages and neutrophils and induces anti-tumor immunity

Cancers evade anti-tumor immunity by the infiltration of immunosuppressive myeloid cells such as macrophages and neutrophils into the tumor microenvironment (TME). The limited efficacy of current immunotherapy is attributed to the presence of these immunosuppressive cells. Here, we describe a novel immunotherapy approach, using a single-cycle alphavirus replicon particle (VRP) that carries a self-amplifying RNA encoding interleukin-12 (IL-12). Leveraging the natural tropism of alphavirus to myeloid cells, single cell transcriptomic analyses of mouse tumor tissues demonstrated that intratumoral (i.t.) injection of the vector effectively reprogrammed tumor-associated macrophages and neutrophils toward a pro-inflammatory, anti-tumor phenotype via interferon signaling, further enhanced by IL-12 expression. The treatment also induced cytotoxic NK and T cell responses, resulting in a significant reduction of tumor growth and effectively preventing nodal and distant metastases in solid tumor mouse models. By targeting tumor-supporting myeloid cells to transform the TME into an immune-active state, our myeloid modulation approach has the potential to enhance the efficacy of current immunotherapies.

cancer biology↗

Computer-assisted beat-pattern analysis and the flagellar waveforms of bovine spermatozoa

Plagued by hurdles in information extraction, handling, and processing, computer-assisted sperm analysis (CASA) systems have typically neglected the complex flagellar waveforms of spermatozoa, despite their defining role in cell motility. Recent developments in imaging techniques and data processing have produced significantly-improved methods of waveform digitisation. Here, we utilise these improvements to demonstrate that near-complete flagellar capture is realisable on the scale of hundreds of cells, and, further, that meaningful statistical comparisons of flagellar waveforms may be readily performed with widely-available tools. Representing the advent of high-fidelity computer-assisted beat-pattern analysis (CABA), we show how such a statistical approach can distinguish between samples using complex flagellar beating patterns rather than crude summary statistics. Dimensionality-reduction techniques applied to entire samples also reveal qualitatively-distinct components of the beat, and a novel data-driven methodology for the generation of representative synthetic waveform data is proposed.

microbiology↗