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Biology subjects

Kanazawa, H.

Publications and source records attributed to Kanazawa, H..

6 recordsLinked to original sources

Complete post-transcriptional modification profiles in individual Staphylococcus aureus tRNA species

Transfer RNAs play a critical role in protein synthesis by matching mRNA codons to their corresponding amino acids. Their post-transcriptional modifications, shaping structure, stability, and codon decoding, are now recognized as key regulators of translation and cellular adaptation, including in bacterial pathogens. Here, we provide a comprehensive analysis of tRNA modifications in Staphylococcus aureus using extensive oligonucleotide mass spectrometry and deep-sequencing methods, generating a high-confidence modification map for each individual tRNA species, including the non-proteogenic tRNAGly. While the overall tRNA modification landscape is conserved among Gram-positive bacteria, our data uncovered unexpected S. aureus-specific features. These include the absence of [m2A]37 in tRNAs despite the presence of the methyltransferase RlmN, a single multi-site DusB2 enzyme catalyzing all tRNA dihydrouridylation, and a dedicated pseudouridine synthase responsible for [{Psi}]32 formation. Besides, heterogenous modification patterns were observed in tRNALeu(UAA) and tRNALys(CAA), highlighting a complex interplay in anticodon hypermodification. Integration of ribosome profiling and Nanopore tRNA sequencing offered a global view of the decoding properties of the reduced S. aureus tRNA set, revealing efficient four-way wobble recognition, slower translation of rare codons by low abundant tRNAs, and distinctive decoding dynamics of Gly codons potentially influenced by the unusual modification status of tRNAGly(UCC). This work establishes a framework for future research aimed at dissecting the role of specific tRNA modifications in S. aureus physiology and pathogenesis.

molecular biology↗

A core driver of somatic markers: Interoception controls the transition of decision making

The somatic marker hypothesis proposes that internal bodily activity (IBA) is a prerequisite for rationality. However, the underlying mechanism remains unclear. First, we reveal that IBAs directly switch or lock the output of a neural circuit involved in decision-making, through human and computational studies of binocular rivalry, which is a form of perceptual decision-making. Then, through computational studies of a gambling task, we demonstrate that, if the IBA parameter is updated appropriately based on a subjective evaluation of the decision outcome, a neural network coupled with IBA can converge to rational decisions. Throughout the entire decision-making process, "Brownian ratchet" emerges, forcing unprofitable options to change while enabling rational and profitable decisions to persist. This ratchet enables intersubjective rationality to self-organize beyond subjective reasonings.

neuroscience↗

A reservoir model of respiration-induced perceptual alternation in binocular rivalry

Perceptual alternation in human binocular rivalry is more likely to occur during certain respiratory phases. In this paper, we show that the respiration dependence of perceptual alternations can be reproduced by a randomly connected recurrent neural network coupled with respiration relevant information via a neuromodulator of norepinephrine (NA). We considered two models of NA modulations; NA increases or decreases the nonlinearity of the activation function of neurons, and we found that the shape of the likelihood function of perceptual alternation depends only on respiratory phase, regardless of whether NA increases or decreases neural nonlinearity. Our results suggest that periodic neuromodulation facilitates the switching of competing neural states in specific phases and that this effect is independent of the excitatory or inhibitory effect of NA.

neuroscience↗

Synthesising robot behaviour through reinforcement learning for homeostasis

Homeostasis is a fundamental property for the survival of animals. Computational reinforcement learning provides a theoretically sound framework for learning autonomous agents. However, the definition of a unified motivational signal (i.e., reward) for integrated survival behaviours has been largely underexplored. Here, we present a novel neuroscience-inspired algorithm for synthesising robot survival behaviour without the need for complicated reward design and external feedback. Our agent, the Embodied Neural Homeostat, was trained solely with feedback generated by its internal physical state and optimised its behaviour to stabilise these internal states: homeostasis. To demonstrate the effectiveness of our concept, we trained the agent in a simulated mechano-thermal environment and tested it in a real robot. We observed the synthesis of integrated behaviours, including walking, navigating to food, resting to cool down the motors, and shivering to warm up the motors, through the joint optimisation for thermal and energy homeostasis. The Embodied Neural Homeostat successfully achieved homeostasis-based integrated behaviour synthesis, which has not previously been accomplished at the motor control level. This demonstrates that homeostasis can be a motivating principle for integrated behaviour generation in robots and can also elucidate the behavioural principles of living organisms.

neuroscience↗

Flow zoometry of Drosophila

Drosophila serves as a highly valuable model organism across numerous fields including genetics, immunology, neuroscience, cancer biology, and developmental biology. Central to Drosophila-based biological research is the ability to perform comprehensive genetic or chemical screens. However, this research is often limited by its dependence on laborious manual handling and analysis, making it prone to human error and difficult to discern statistically significant or rare events amid the noise of individual variations resulting from genetic and environmental factors. In this article we present flow zoometry, a whole-animal equivalent of flow cytometry for large-scale, individual-level, high-content screening of Drosophila. Our flow zoometer automatically clears the tissues of Drosophila melanogaster, captures three-dimensional (3D) multi-color fluorescence tomograms of single flies with single-cell volumetric resolution at an unprecedented throughput of over 1,000 animals within 48 hours (24 hr for clearing; 24 hr for imaging), and performs AI-enhanced data-driven analysis - a task that would traditionally take months or years with manual techniques. To demonstrate its broad applications, we employed the flow zoometer in various laborious screening assays, including those in toxicology, genotyping, and tumor screening. Flow zoometry represents a pivotal evolution in high-throughput screening technology: previously from molecules to cells, now from cells to whole animals. This advancement serves as a foundational platform for "statistical spatial biology", to improve empirical precision and enable serendipitous discoveries across various fields of biology.

bioengineering↗

A neuromodulatory model for determining the effect of emotion-respiration-cognition coupling on the time-to-respond

Respiration and emotional stimuli modulate cognitive ability and the reaction time to generate bodily movement. To understand mechanisms for emotion-respiration-cognition coupling, first, we considered a schematic feed-forward neural network, in which neurons was biased by respiratory-relevant sensory input and the activation function of a neuron was modulated by a neuromodulator, such as norepinephrine (NE). Furthermore, we assumed that the neural model received a stimulus input and generated a response action upon the activity of the output neuron exceeding a certain threshold. Time-to-respond (TTR) was equivalently modulated by the intensity of the input bias and the neuromodulator strength for small action execution threshold; however, it was dominantly modulated by only the neuromodulator for high threshold. Second, we implemented a comprehensive model comprising a cardio-respiration relevant neuromechanical-gas system, a respiratory central pattern generator (CPG), NE dynamics to modulate neurocognitive dynamics, and a locus coeruleus (LC) circuit, which was the primary nucleus for controlling NE. The LC neurons received pCO2 or synaptic current from an inspiratory neurons, which resulted in shortened TTR by a stimulus input during inhalation. By contrast, upon receiving pulmonary stretch information, the TTR was shortened by a stimulus input during exhalation. In humans, TTR is shortened when a fear-related stimulus is presented during inhalation, and likewise, TTR is weakly-shortened when surprise-related stimulus is presented during exhalation. Hence, we conclude that emotional stimuli in humans may switch the gating strategies of information and the inflow to LC to change the attention or behavior strategy.

neuroscience↗