Biology subjects

Tani, M.

Publications and source records attributed to Tani, M..

8 recordsLinked to original sources

bioRxiv2026

Predictive coding of visual feedback of actions in human parieto-frontal circuits

Executing visually guided movements requires integrating motor commands with visual feedback of the moving hand. Yet, how the motor and visual systems interact during movement remains unquantified. Using real-time motion tracking in immersive virtual reality during fMRI (MOTUM), we manipulated motor execution and hand visual feedback orthogonally in 24 human participants performing reach-to-grasp actions. Execution and hand visual feedback converged in a bilateral parieto-frontal network, including the anterior intraparietal sulcus (aIPS), anterior superior parietal lobule (aSPL), and premotor cortex. In the left aIPS extending into aSPL, combining movement with visual feedback elicited a subadditive response-less activity than predicted by the sum of movement and visual feedback alone-revealing circuitry tuned to the predicted visual consequences of action. Conversely, the posterior cerebellum showed a superadditive response, consistent with internal model updating. Dynamic causal modeling demonstrated a dynamic reversal in information flow along the dorsal parieto-frontal pathway (aSPL-PMd): effective connectivity was excitatory from parietal to frontal cortex when the moving hand was visible, but reversed from frontal to parietal cortex when visual feedback was removed. These findings show that the human parieto-frontal network integrates action and visual feedback predictively, suppressing activity when feedback matches internal predictions and dynamically reconfiguring information flow based on visual availability.

neuroscience↗

bioRxiv2026

Segregation and integration between visuo-spatial attention and semantic memory across large-scale brain networks

Visuo-spatial attention and semantic memory are supported by distinct, largely competing brain networks, yet they are frequently engaged together in daily life. How these networks interact during combined tasks remains unexplored. We conducted a factorial fMRI experiment in which 25 participants performed a novel task requiring visuo-spatial attention, semantic judgment, or both. Covert shifts of attention towards cued lateral location activated bilateral parietal (PEF), frontal eye fields (FEF), and anterior insula. Categorizing a word as referring to a living or non-living entity activated a lateral parietal region (LaP) between the dorsal tip of the angular gyrus and the lateral bank of the intraparietal sulcus, along with the left inferior frontal gyrus (IFG), superior temporal sulcus, inferior temporal lobe and bilateral anterior insula. Notably, the anterior insula was active in both conditions. Dynamic causal modeling showed excitatory-inhibitory parieto-frontal loops driving attention (PEF[->]FEF) and semantic processing (LaP[->]IFG) separately, but in the combined condition frontal-to-parietal feedback became excitatory, reflecting stronger integration, with the anterior insula driving overall connectivity. These findings identify LaP as a novel region supporting semantic processing of linguistic stimuli, and highlight the anterior insula as a key hub integrating attentional and semantic networks under concurrent cognitive demands. HighlightsVisuo-spatial attention and semantic memory rely on segregated parieto-frontal circuits. However, concurrent demands induce a large-scale reconfiguration centered on the left anterior insula, which acts as an integrative hub between the two networks.

neuroscience↗

bioRxiv2026

Enzyme activity as an actionable axis for small-molecule precision oncology

Current precision oncology--molecular targeted therapies and immunotherapies--relies on genomic or expressed biomarkers, yet most cancer patients remain ineligible for these treatments. Here, we establish enzyme activity as an actionable and orthogonal axis for precision cancer medicine. Strategic activity-based screening of mouse organs and human clinical specimens with a panel of enzyme-reactive fluorescence probes identified {beta}-galactosidase 1 (GLB1) and {beta}-hexosaminidases (HEX) as broadly elevated tumor-selective biomarkers. Leveraging these activities, we developed 7-ethyl-10-hydroxycamptothecin (SN38)-based GLB1-and HEX-reactive prodrugs. These prodrugs exhibited dramatically reduced systemic toxicities and improved therapeutic windows, compared to a clinically used SN38-based prodrug, irinotecan (CPT-11). Both prodrugs demonstrated activity-dependent therapeutic efficacy, affording a dramatic reduction of tumor volumes across multiple in vivo models, including a subcutaneous patient-derived xenograft (PDX) of lung squamous cell carcinoma that lacked genetic alterations targeted by current precision medicine. Furthermore, this strategy is broadly applicable across various cytotoxic payloads, establishing a generalizable platform for small-molecule precision medicines. Our results define an enzyme-targeting paradigm for precision oncology, in which fluorescence probes serve as companion diagnostic tools to guide development and selection of appropriately targeted prodrugs, which are expected to provide safer and more efficacious treatment options for cancer patients with elevated enzyme activities.

cancer biology↗

bioRxiv2026

Regulation of sphingolipid synthesis by the C2H2 zinc finger transcription factor Com2 through ubiquitin-proteasome mediated degradation pathway

Membrane lipid synthesis is globally coordinated by a limited set of master transcription factors that regulate broad gene networks encoding lipid-metabolic enzymes and their regulators. Here, we identify the C2H2 zinc-finger transcription factor Com2 as a regulator of sphingolipid homeostasis in Saccharomyces cerevisiae that promotes transcription of downstream targets, including the protein kinase Ypk1, a key activator of sphingolipid synthesis. Com2 protein abundance increased upon treatment with myriocin, an inhibitor of sphingolipid synthesis, but rapidly decreased after addition of phytosphingosine (PHS), a precursor of complex sphingolipids; this decrease was blocked by proteasome inhibitors. These results suggest that Com2 is regulated in a sphingolipid-dependent manner through proteasome-mediated degradation. Moreover, a Com2 mutant in which lysine residues putatively involved in ubiquitination were replaced with arginine exhibited attenuated PHS-dependent degradation and elevated phosphorylation. Likewise, a mutant in which putative phosphorylation sites were replaced with alanine showed reduced PHS-dependent degradation. Together, these findings indicate that Com2 undergoes phosphorylation-dependent degradation via the ubiquitin-proteasome system in response to sphingolipid levels.

cell biology↗

bioRxiv2025

Force Scaling in Active Swarm of Microtubules via Magnetic Manipulation

Scalability refers to the ability of a system to enhance performance with increasing size. This ability is a defining feature of natural swarms such as ant and bee colonies. Extending this principle to artificial active matter has motivated the creation of molecular swarms composed of myosin-driven actin filaments and kinesin-driven microtubules (MTs). While these swarms exhibit cooperative transport behaviors that surpass the abilities of individual filaments, their collective force generation has remained unquantified. Here, we introduce a straightforward electromagnetic tweezer approach to directly measure the forces generated by MT swarms propelled by surface-bound kinesin motors. We find that force output changes with swarm size, demonstrating quantitative scalability and linking collective organization to mechanical performance. These results establish MT swarms as a model system for scalable, force-producing active matter and provide a foundation for designing biomolecular devices that exploit collective dynamics for microscale actuation and transport. Significance StatementThe cooperative activity of multiple motile agents is observed in nature, known as swarming. In artificial systems, swarming has been demonstrated using active agents like kinesin and MTs, successfully enabling efficient cargo transportation. However, the force generated by the swarm remains unexplored, which is one of the keys to understanding the principles underlying swarm systems. This study introduces a simple method employing electromagnetic tweezers and magnetic beads to measure the force of the MT swarm accurately. The measured forces within the microtubule swarms of different sizes unveil the scaling effect, the additive nature of force generation as the kinesin unit increases. The force study sheds light on the fundamental properties, work performance, efficiency, and execution of the MT swarm.

biophysics↗

bioRxiv2025

MOTUM: a system for Motion Online Tracking Under MRI

Attempts to implement realistic body-environment interactions during functional magnetic resonance imaging (fMRI) experiments have developed expensive, hardly reproducible, and task-specific setups. Here, we introduce MOTUM (Motion Online Tracking Under MRI), a novel system that combines real-time kinematic tracking with immersive virtual reality, enabling participants to perform naturalistic movements inside the scanner. As a proof-of-concept, we tested MOTUM during a reach-to-grasp task with and without visual feedback of ones hand (N = 7). The system achieved high-fidelity motion tracking, induced an intense immersive experience, evoked expected sensorimotor brain activations, and maintained high fMRI data quality. Standard fMRI control metrics were below the critical threshold in 99% of volumes, indicating that participants arm movements had minimal impact on head motion and data quality. While hand movements had little to no effect on brain activity, arm movements resulted in sparse spurious correlations that were easily controlled for. Critically, MOTUM allowed us to extract rich kinematic indices and link them directly to brain activity on a trial-by-trial basis. Parametric modulation analyses revealed that natural variations in movement dynamics significantly influenced neural responses in parietal, frontal, and occipital regions. In sum, MOTUM is a robust method to study motor control and beyond, enabling a new class of fMRI experiments that bridge ecological realism and experimental control, pushing current neuroimaging research towards real-life neuroscience.

neuroscience↗

bioRxiv2021

Transcriptional regulation of sphingolipid metabolism in budding yeast

Global control for the synthesis of lipids constituting a bilayer of cell membranes is known to be with a small number of transcription factors called master transcriptional regulators, which target a wide range of genes encoding lipid metabolism enzymes and/or their regulators. Although master transcriptional regulators of glycerophospholipids and sterols have been identified in both yeast and mammals, this aspect of sphingolipid metabolism is not yet understood. In the present study, we identified the C2H2-type zinc finger transcription factor, Com2, as a master transcriptional regulator of sphingolipid metabolism in the budding yeast, Saccharomyces cerevisiae. The target of rapamycin complex 2 (TORC2)-activated protein kinase Ypk1 is known to regulate sphingolipid metabolism. Activated Ypk1 stimulates the activity of serine palmitoyl transferase (SPT), the first-step enzyme in sphingolipid biosynthesis, by phosphorylating and inhibiting Orm1/2, a negative regulator of SPT. This regulation of SPT activity is thought to be a major pathway in the regulation of sphingolipid metabolism. In the present study, we found that inhibition of sphingolipid synthesis upregulates the expression of Com2, which in turn leads to the concomitant expression of Ypk1. The upregulation of Ypk1 expression was found to be dependent on a putative Com2-binding site in the YPK1 promoter. Our results also suggested that Com2 senses intracellular sphingolipid levels through a pathway independent of TORC2-Ypk1-mediated sensing of sphingolipids. Our results revealed an additional layer of mechanistic regulation that allows cells to maintain appropriate levels of sphingolipid biosynthesis and to rapidly induce this process in response to environmental stresses. Significance StatementOne of the major regulatory mechanisms involved in the control of lipid metabolism in bilayers of biological membranes is regulation at the transcriptional level by master transcriptional regulators that control the transcription of genes encoding lipid metabolism enzymes and/or their regulators. In the present study, we identified the C2H2-type zinc finger transcription factor Com2 as a master transcriptional regulator in sphingolipid metabolism. We found that Com2 regulates sphingolipid metabolism by transcriptionally controlling the expression of Ypk1, which regulates Orm1/2, a negative regulator of serine palmitoyl transferase, the first-step enzyme in sphingolipid biosynthesis, through phosphorylation. Our study revealed a new layer of regulation that allows the maintenance of an appropriate level of sphingolipid biosynthesis for a rapid response to environmental stresses.

cell biology↗

bioRxiv2017

Aberrant cerebellar-default-mode functional connectivity underlying auditory verbal hallucinations in schizophrenia revealed by multi-voxel pattern analysis of resting-state functional connectivity MRI data

Past neuroimaging studies have reported that aberrant functional connectivity (FC) underlying auditory verbal hallucinations (AVHs) in schizophrenia is highly distributed over multiple functional networks. There is thus a need for exploratory approaches without limiting analysis to particular seed regions or functional networks, to identify FC alterations underlying AVH. We applied a multi-voxel pattern analysis (MVPA) of FC together with a series of post-hoc FC analyses to resting-state fMRI data acquired from 25 patients with schizophrenia and 25 matched healthy controls. First, the MVPA revealed multiple clusters exhibiting altered FC patterns in schizophrenia. Subsequent multiple linear regression analysis using scores of these clusters identified that FC alteration in the right cerebellum crus I was significantly associated with the severity of AVH. Furthermore, post-hoc FC analysis with the right crus I as a seed revealed significant FC alterations with regions distributed across multiple functional networks, including speech, default-mode, thalamus, and cerebellum. Subsequent linear regression analyses further demonstrated that, among these regions, only reduced FC in the left precuneus was significantly associated with the severity of AVH. Our unbiased exploratory analysis of FC data revealed a novel evidence for the crucial role of FC between cerebellar and default-mode networks in AVH. (198 words)

neuroscience↗