Biology subjects

Tanaka, D.

Publications and source records attributed to Tanaka, D..

7 recordsLinked to original sources

bioRxiv2026

A Novel Metric for Quantifying the Sustainability of Phage-Mediated Bacterial Suppression

The global spread of antimicrobial-resistant (AMR) bacteria represents one of the greatest threats to modern medicine, making the development of novel therapeutic strategies increasingly urgent. Phage therapy, which exploits bacteriophages (phages, viruses that specifically infect and kill bacteria) has regained attention as a therapeutic approach for multidrug-resistant infections. One critical determinant of treatment outcome is the capacity of phages to sustain bacterial growth suppression; however, no metric has previously existed to directly quantify the duration of effective lytic activity. Here, we propose the Sustainability Index (SusI), a novel metric that quantifies both the duration and extent of phage-mediated bacterial growth suppression, which is restricted to the primary lysis period from lysis initiation to resistance emergence. Evaluation of individual phages and two-phage cocktails against both laboratory and clinical isolates of Escherichia coli demonstrated that SusI provides information independent of the Virulence Index, which primarily reflects bactericidal activity during the initial phase of infection, and serves as a complementary metric to the Suppression Index, which may incorporate behavior beyond primary lysis. Cocktails composed of phages targeting different receptors specificities consistently exhibited higher SusI values, consistent with the notion that multifaceted selective pressure delays resistance emergence. Furthermore, in a mouse model of systemic infection established by intraperitoneal administration, cocktails with higher SusI values demonstrated superior therapeutic efficacy. These results confirm SusI as a practical metric for rational phage cocktail design. As phage therapy advances toward clinical implementation, standardized quantitative metrics such as SusI are expected to facilitate evidence-based selection of therapeutic phages across diverse pathogens and infection conditions. ImportanceThe global spread of antimicrobial-resistant bacteria is making bacterial infections increasingly difficult to treat. Phage therapy, which uses bacteriophages (viruses that specifically infect bacteria), has re-emerged as a therapeutic alternative; however, reliable methods to determine in advance which phages will be therapeutically effective remain limited. Current evaluation metrics are well-suited for quantifying how rapidly phages kill bacteria but were not designed to directly measure how long lytic activity is sustained before resistant bacteria emerge. Here, we developed the Sustainability Index (SusI), a novel metric that specifically quantifies the duration of effective bacterial growth suppression. Evaluation of multiple phages and their combinations (cocktails) against both laboratory and clinical bacterial isolates demonstrated that SusI can distinguish phage combinations that existing metrics fail to differentiate. Moreover, in a mouse model of lethal bacterial infection, higher SusI values correlated with improved therapeutic outcomes. SusI has potential as a practical tool for selecting phages with greater likelihood of therapeutic success.

microbiology↗

bioRxiv2024

Healthy dietary choices involve prefrontal mechanisms associated with long-term reward maximization but not cognitive control

Taste and health are critical factors to be considered when choosing foods. Prioritizing healthiness over tastiness requires self-control. It has also been suggested that self-control is guided by cognitive control. We then hypothesized that neural mechanisms underlying healthy food choice are associated with both self-control and cognitive control. Human participants performed a food choice task and a working memory (WM) task during functional MRI scanning. Their degree of self-control was assessed behaviorally by the value discount of delayed monetary rewards in intertemporal choice. Prioritizing healthiness in food choice was associated with greater activity in the superior, dorsolateral, and medial prefrontal cortices. Importantly, the prefrontal activity was greater in individuals with smaller delay discounting (i.e., high self-control) who preferred a delayed larger reward to an immediate smaller reward in intertemporal choice. On the other hand, WM activity did not show a correlation with delay discounting or food choice activity, which was further supported by supplementary results that analyzed data from the Human Connectome Project. Our results suggest that the prefrontal cortex plays a critical role in healthy food choice, which requires self-control, but not cognitive control, for maximization of reward attainments in a remote future.

neuroscience↗

bioRxiv2023

The microcephaly gene ASPM is required for the timely generation of human outer-radial glia progenitors by controlling mitotic spindle orientation

Abnormal spindle-like, microcephaly-associated (ASPM) is the most commonly mutated gene in primary microcephaly (MCPH), characterized by reduced brain size and intellectual deficiency. The mechanisms underlying MCPH have remained unclear, as ASPM disruption leads to distinct phenotypes depending on the species studied. Here, we studied the impact of ASPM pathogenic mutations on human corticogenesis in organoid models. We found that at earliest stages of neurogenesis, ASPM mutant cortical progenitors, located at the apical surface of the neuroepithelium, display transient mitotic spindle randomization. The mutant progenitors then delaminate basally to adopt precociously the characteristics of outer radial glia cells (oRGC), a population of progenitors selectively amplified in human corticogenesis. Subsequently, cortical progenitors are depleted through decreased amplification and increased apoptosis. Thus, ASPM regulates the timely generation of oRGC by controlling mitotic spindle orientation, shedding light on how species-specific features of neurogenesis may confer vulnerability to neurodevelopmental diseases.

neuroscience↗

bioRxiv2022

Subjectivity of time perception alters choice preference for future rewards through fronto-striatal value signal dynamics

Our preference for a reward depends on the time of delay for its delivery. Here we show that changes in the external environment can manipulate the perceived duration of time, which alters the formation of the choice preference through value signals in the cortical and subcortical brain regions. Humans anticipated a real liquid reward delayed by tens of seconds, during which colors of visually presented panels gradually changed. The color-change delay was perceived as shorter than a control color-constant delay. Interestingly, participants with greater perceptual bias of the delay showed stronger preference for rewards with the color-change delay. The ventrolateral prefrontal cortex (vlPFC) and ventral striatum (VS) showed dynamic neural signatures of value components that were modulated by subjectively perceived duration. Crucially, these effects were specifically observed while a future reward was anticipated, and moreover, the vlPFC activity was weaker in participants with greater bias in the duration perception. These results demonstrate that subjective time experience leads to biased choice preference of delayed rewards, which is regulated by dynamic value signals of future rewards and accurate perception of the external world in the vlPFC-VS systems.

neuroscience↗

bioRxiv2022

An excitatory-inhibitory fronto-cerebellar loop resolves the Stroop effect

The Stroop effect is a well-known behavioral phenomenon in humans that refers to robust interference between language and color information. Although this effect has long been studied, it remains unclear when the interference occurs and how it is resolved in the brain. By manipulating the verbality of stimulus perception and response generation, here we show that the Stroop effect occurs during perception of color-word stimuli and is resolved by a cross-hemispheric, excitatory-inhibitory functional loop involving the lateral prefrontal cortex and cerebellum. Humans performed a Stroop task and a control task in which the stimulus did not contain verbal information, and made a response either vocally or manually. The resolution of Stroop interference involved the lateral prefrontal cortex in the left hemisphere and the cerebellum in the right hemisphere, independently of whether the response was made vocally or manually. In contrast, such cross-hemispheric lateralization was absent during the non-verbal control task. Moreover, the prefrontal cortex amplified cerebellar activity, whereas the cerebellum suppressed prefrontal activity, and these effects were enhanced during interference resolution. These results suggest that this fronto-cerebellar loop involving language and cognitive systems regulates goal-relevant information to resolve the interference occurring during simultaneous perception of a word and color.

neuroscience↗

bioRxiv2021

Anticipatory dynamics in the human brain guide foraging for primary rewards

Deciding whether to wait for a future reward is crucial for acquiring rewards in an uncertain world and involves anticipating future reward attainment. While seeking for a reward in natural environments, behavioral agents constantly face a trade-off between staying in their current environment or leaving it. It remains unclear, however, how humans make continuous decisions in such situations. Here we show that anticipatory brain activity in the anterior prefrontal cortex (aPFC) and hippocampus underpins continuous stay-leave decision making. Human participants awaited for real liquid rewards available after tens of seconds, and continuous decision was tracked by monitoring dynamic patterns of brain activity. Participants stopped waiting more frequently and sooner after they experienced longer delays and received smaller rewards. When dynamic activity reflecting the anticipation of a future reward was enhanced in the aPFC, participants remained in their current environment, but when this activity diminished, they left the environment for a new one. The anticipatory activity in the aPFC and hippocampus was associated with distinct decision strategies; aPFC activity was enhanced in participants adopting a leave strategy, whereas those remaining stationary showed enhanced activity in the hippocampus. Our results suggest that fronto-hippocampal anticipatory dynamics underlie continuous decision making while anticipating a future reward.

neuroscience↗

bioRxiv2018

ReALLEN: structural variation discovery in cancer genome by sensitive analysis of single-end reads.

BackgroundThe structural abnormalities in chromosomes are important issues in cancer genomics. Next generation sequencing technologies have big potentials to detect the structural variations precisely and comprehensively. Nevertheless, it is still difficult problem to detect large structural variations from short read sequence data. Major efforts have been achieved with paired-end reads, since discordant pairs directly reflect the existence of large rearrangement. Furthermore, approaches to detect structural variations from single-end reads are still worthwhile challenge because they allow wide choices of sequencing platforms.\n\nResultWe present ReALLEN, a series of tools to detect genomic rearrangement with base-pair resolution from single-end reads provided by next generation sequencing. We examined the performance of ReALLEN using simulated dataset and real dataset sequenced by Ion Torrent systems. In most cases on the simulated dataset, ReALLEN showed nearly 100% precision and better sensitivity than other major tools. Notably, ReALLEN showed stable scores even if it was on some unfavorable conditions, for example, low coverage or small variant size. On the real dataset sequenced by Ion Torrent systems, ReALLEN accurately found an insertional translocation that was crucial for the diagnosis of chronic myeloid leukemia.\n\nConclusionReALLEN is useful to researchers in finding genomic rearrangements. It will contribute to discovery of cancer-specific fusion proteins, precise diagnosis of known types of cancers, and understanding of genetic diseases caused by abnormal chromosomes.

bioinformatics↗