Biology subjects

Nagamori, A.

Publications and source records attributed to Nagamori, A..

4 recordsLinked to original sources

bioRxiv2026

Novel cell wall-associated genes that enable Cryptococcus neoformans to evade dectin-1-mediated innate immune recognition.

The fungal pathogen Cryptococcus neoformans contains about 200 {micro}g of {beta}-1,3-glucan (1,3BG) per 1 mg of dry cell weight when grown under standard culture conditions (YPD medium at 30 {degrees}C under aerobic conditions). However, 1,3BG exposure is tightly suppressed, even in capsule-deficient strains, allowing the fungus to evade recognition by the immune receptor dectin-1 and anti-1,3BG antibodies. Although other pathogenic fungi mask 1,3BG with -1,3-glucan (1,3AG) to evade dectin-1 recognition, the factors responsible for 1,3BG masking and dectin-1 evasion in C. neoformans remain incompletely understood. To identify capsule-independent 1,3BG masking and dectin-1-evasion factors, we generated a series of cell wall-related gene deletion strains in the capsule-deficient strain cap59{Delta} by using CRISPR-Cas9 and screened for mutants that failed to evade dectin-1 binding. We found eight deletants (cap59{Delta}/mpk1{Delta}, cap59{Delta}/chs3{Delta}, cap59{Delta}/kre5{Delta}, cap59{Delta}/crz1{Delta}, cap59{Delta}/kre6{Delta}/skn1{Delta}, cap59{Delta}/hxl1{Delta}, cap59{Delta}/uge1{Delta}, and cap59{Delta}/ugt1{Delta}) that exhibited increased binding to dectin-1 or anti-1,3BG antibody, or both. As a similar phenotype was not observed in cap59{Delta}/ags1{Delta}, 1,3AG-mediated masking of 1,3BG appears to play a limited role in C. neoformans. These eight deletants induced significantly greater secretion of IL-6 and IL-1{beta} from dendritic cells (DCs) than did cap59{Delta}. This enhanced inflammatory response was markedly attenuated in dectin-1-deficient DCs, indicating that the increased immunogenicity was driven by 1,3BG exposure and subsequent dectin-1 recognition. Collectively, these findings demonstrate that multiple genes involved in maintaining cell wall integrity--including those involved in {beta}-1,6-glucan and chitosan biosynthesis--are essential for regulating 1,3BG exposure and enabling C. neoformans to evade dectin-1-mediated immune recognition. HighlightsO_LIWe identified new capsule-independent {beta}-1,3-glucan-masking genes in C. neoformans C_LIO_LIGene deletants had higher dectin-1 deposition than parental acapsular cap59{Delta} C_LIO_LIDeletion of these genes enhanced IL-6 and IL-1{beta} secretion by dendritic cells C_LIO_LIThe enhanced cytokine response was suppressed in dendritic cells lacking dectin-1. C_LIO_LIDeletant strains may serve as new whole-cell antigens for cryptococcal vaccines C_LI

microbiology↗

bioRxiv2026

Adaptive Charge Modulation Enables Focal, Selective Spinal Cord Stimulation

Clinical neuromodulation primarily employs near-field low frequency electrical stimulation to activate neurons in the immediate vicinity of the electrode. We introduce Adaptive Charge Modulation (ACM), a spatiotemporal, charge-balanced stimulation strategy that focuses activation at deep tissue sites distant from the stimulating contacts. We apply ACM to stimulate deep regions of the spinal cord, distant from dorsal root entry zones which are preferentially activated during low frequency stimulation (LFS). ACM applies multipolar, biphasic rectangular pulses to exceed activation thresholds in deeper neuronal populations, with reduced surface activation, potentially due to high-frequency suppression of neural activity. In epidural spinal cord stimulation in rats, ACM achieved single-muscle selectivity among fourteen monitored muscles with minimal co-activation of other muscles. Using simultaneous, high spatiotemporal resolution, 2,112-channel brain-spine recordings, we characterized the response latencies and pathways consistent with focal recruitment at depth. We observed chronic stability of the electrode and ACM in freely behaving animals over 68 days post-implantation. By enabling focal activation with epidural surface electrodes, ACM may expand the reach and precision of neuromodulation and neural interfaces.

bioengineering↗

bioRxiv2025

Cerebellar outputs for rapid directional refinement of forelimb movement

Much of our interaction with the world relies on the ability to move our limbs with speed and precision. The cerebellum is critical for movement coordination, yet how outputs from the cerebellum continually guide the limb and whether discrete pathways differentially contribute to adjusting motor output remain unclear. Using intersectional viral approaches in mice, we identify two spatially intermingled yet anatomically distinct cerebellar populations that drive the forelimb either toward or away from the body. Neural recordings reveal cerebellar activity that correlates with and precedes these opposing directional changes in limb movement. Both cerebellar output pathways influence motor neuron and muscle activity within milliseconds, producing reliable effects on limb trajectory despite substantial underlying variability in muscle recruitment patterns. Our findings disentangle a subtype organization to cerebellar limb control, revealing a subcortical circuit basis for online directional refinement during movement execution.

neuroscience↗

bioRxiv2025

The spinal premotor network driving scratching flexor and extensor alternation

Rhythmic motor behaviors are generated by neural networks termed central pattern generators (CPGs). Although locomotor CPGs have been extensively characterized, it remains unknown how the neuronal populations composing them interact to generate adaptive rhythms. We explored the non-linear cooperation dynamics among the three main populations of ipsilaterally projecting spinal CPG neurons - V1, V2a, V2b neurons - in scratch reflex rhythmogenesis. Ablation of all three neuronal subtypes reduced the oscillation frequency. Activation of excitatory V2a neurons enhanced the oscillation frequency, while activating inhibitory V1 neurons caused atonia. These findings required the development of a novel neuromechanical model that consists of flexor and extensor modules coupled via inhibition, in which rhythm in each module is generated by self-bursting excitatory populations and accelerated by intra-module inhibition. Inter-module inhibition coordinates the phases of flexor and extensor activity and slows the oscillations, while facilitation mechanisms in excitatory neurons explain the V2a activation-driven increase in frequency.

neuroscience↗