Biology subjects

Ogawa, K.

Publications and source records attributed to Ogawa, K..

29 records · Page 2Linked to original sources

bioRxiv2023

UBL3 Interacts with Alpha-synuclein in Cells and the Interaction is Downregulated by the EGFR Pathway Inhibitor Osimertinib

Ubiquitin-like 3 (UBL3) acts as a post-translational modification (PTM) factor and regulates protein sorting into small extracellular vesicles (sEVs). sEVs have been reported as vectors for the pathology propagation of neurodegenerative diseases, such as -synucleinopathies. Alpha-synuclein (-syn) has been widely studied for its involvement in -synucleinopathies. However, it is still unknown whether UBL3 interacts with -syn, and is influenced by drugs or compounds. In this study, we investigated the interaction between UBL3 and -syn, and any ensuing possible functional and pathological implications. We found that UBL3 can interact with -syn by the Gaussia princeps based split luciferase complementation assay in cells and immunoprecipitation, while cysteine residues at its C-terminal, which are considered important as PTM factors for UBL3, were not essential for the interaction. The interaction was upregulated by 1-methyl-4-phenylpyridinium exposure. In drug screen results, the interaction was significantly downregulated by the treatment of osimertinib. These results suggest that UBL3 interacts with -syn in cells and be significantly downregulated by epidermal growth factor receptor (EGFR) pathway inhibitor osimertinib. Therefore, the UBL3 pathway may be a new therapeutic target for -synucleinopathies in the future.

molecular biology↗

bioRxiv2023

A macroevolutionary role for chromosomal fusion and fission in Erebia butterflies

The impact of large-scale chromosomal rearrangements, such as fusions and fissions, on speciation is a long-standing conundrum. We assessed whether bursts of change in chromosome numbers resulting from chromosomal fusion and fission are related to increased speciation rates in Erebia, one of the most species-rich and karyotypically variable butterfly groups. We established a genome-based phylogeny and employed state-dependent birth-death models to infer trajectories of karyotype evolution across this genus. We demonstrated that rates of anagenetic chromosomal changes (i.e. along phylogenetic branches) exceed cladogenetic changes (i. e. at speciation events), but when cladogenetic changes occur, they are mostly associated with chromosomal fissions rather than fusions. Moreover, we found that the relative importance of fusion and fission differs among Erebia clades of different ages, where especially in younger, more karyotypically diverse clades, speciation is more frequently associated with chromosomal changes. Overall, our results imply that chromosomal fusions and fissions have contrasting macroevolutionary roles and that large-scale chromosomal rearrangements are associated with bursts of species diversification.

evolutionary biology↗

bioRxiv2022

Supramodal representation of the sense of body ownership in the human parieto-premotor and extrastriate cortices

The sense of body ownership, defined as the sensation that ones body belongs to oneself, is a fundamental component of bodily self-consciousness. Several studies have shown the importance of multisensory integration for the emergence of the sense of body ownership, together with the involvement of the parieto-premotor and extrastriate cortices in bodily awareness. However, whether the sense of body ownership elicited by different sources of signal, especially visuotactile and visuomotor inputs, is represented by common neural patterns remains to be elucidated. We used functional magnetic resonance imaging (fMRI) to investigate the existence of neural correlates of the sense of body ownership independent of the sensory modalities. Participants received tactile stimulation or executed finger movements while given synchronous and asynchronous visual feedback of their hand. We used multi-voxel patterns analysis (MVPA) to decode the synchronous and asynchronous conditions with cross-classification between two modalities: the classifier was first trained in the visuotactile sessions and then tested in the visuomotor sessions and vice versa. Regions of interest-based and searchlight analyses revealed significant above-chance cross-classification accuracies in the bilateral intraparietal sulcus (IPS), the bilateral ventral premotor cortex (PMv), and the left extrastriate body area (EBA). Moreover, we observed a significant positive correlation between the cross-classification accuracy in the left PMv and the difference in subjective ratings of the sense of body ownership between the synchronous and asynchronous conditions. Our findings revealed the neural representations of the sense of body ownership in the IPS, PMv, and EBA that is invariant to the sensory modalities. Significance StatementPrevious studies have shown neural correlates of the sense of body ownership in parieto-premotor and extrastriate cortices. However, whether the sense of body ownership induced by different sensory inputs is represented in common neural patterns remains unelucidated. Using functional magnetic resonance imaging (fMRI) with multi-voxel pattern analysis (MVPA), we investigated neural representations of the sense of body ownership invariant to modalities. Decoding neural patterns for visuotactile and visuomotor modalities revealed successful cross-classification accuracies in intraparietal sulcus (IPS), ventral premotor cortex (PMv), and extrastriate body area (EBA). Furthermore, cross-classification accuracy in PMv was positively correlated with subjective ratings of the sense of body ownership. These findings demonstrate that supramodal representations in parieto-premotor and extrastriate cortices underlie the sense of body ownership.

neuroscience↗

bioRxiv2022

Thoracic crop formation is spatiotemporally coordinated with flight muscle histolysis during claustral colony foundation of a Lasius japonicus queen

In a majority of ants, a newly mated queen independently founds a colony and claustrally raises her first brood without foraging outside the nest. During claustral independent colony foundation (ICF) in several ants, the esophagus of the founding queen expands and develops into a thoracic crop, which is then filled with a liquid substrate for larval feeding. It has been suggested that these substrates are converted from her body reserves (e.g., histolyzed flight muscles) or redistributed from a gastral crop. Here, we examined thoracic crop development in Lasius japonicus during claustral ICF. The foundresses claustrally fed their larvae from week 2 to 5 after ICF onset, and the first worker emerged at week 6. The development proceeded as follows: in week 0, foundress dorsal esophagus wall was pleated and thickened. Then, from week 2 to 5, the esophagus expanded dorsally toward where flight muscles had been present, following flight muscle histolysis. Gastral crop expansion followed esophagus expansion. Thus, thoracic crop formation may be spatiotemporally coordinated with flight muscle histolysis in Lasius japonicus queens, and similar developmental regulations might be common in other claustral ICF ants.

zoology↗

bioRxiv2022

Cardiac and gastric interoception have distinct neural substrates

Interoception, or an awareness of the internal body state, guides agents in adaptive behavior by informing them of ongoing bodily signals, such as heart rate or energy status. However, it is still unclear whether the human brain represents the differences in the subjective experience of interoception differently. Hence, we directly compared the neural activation for cardiac (awareness related to heartbeats) and gastric (awareness related to the stomach) interoception in the same population (healthy human, N = 31). Participants were asked to focus on their heart and stomach sensations to be aware of interoception in a magnetic resonance imaging scanner. The results indicated that neural activation underlying gastric interoception encompassed larger brain regions, including the occipitotemporal visual cortices, bilateral primary motor cortex, primary somatosensory cortex, left orbitofrontal cortex, and bilateral hippocampal regions. Cardiac interoception, however, selectively activated the right anterior insula extending to the frontal operculum more compared to gastric interoception. Moreover, our detailed analyses focusing on the insula, the most relevant region for interoception, revealed that the left dorsal middle insula encoded cardiac and gastric interoception in different activation patterns but not the posterior insula. Our results demonstrate that cardiac and gastric interoception have distinct neural substrates; in particular, the selective brain activation may reflect differences in the functional roles of cardiac and gastric interoception. Significance statementInteroception, subjective senses that arise from within the body, plays a critical role in maintaining adaptive behavior by informing of the ongoing bodily states, such as heart rate and energy status. Although interoception has various characteristics depending on its source signals, previous neuroimaging studies have extensively used cardiac interoception (senses related to heartbeats), making it unclear whether the brain differently encodes diverse experiences of interoception. Here, we demonstrate that cardiac interoception and gastric interoception (senses related to the stomach) have distinct neural substrates by combining mass-univariate analysis with multivoxel pattern analysis for fMRI data. Our findings suggest that the selective brain activation may reflect differences in the functional roles of cardiac and gastric interoception.

neuroscience↗

bioRxiv2022

Heterogeneity of social cognition in temporo-parietal junction: Overlapping yet distinct representation between visual perspective-taking and theory of mind

Visual perspective taking (VPT), particularly level 2 VPT (VPT2), which allows an individual to understand that the same object can be seen differently by others, is related to the theory of mind (ToM), because both functions require a decoupled representation from oneself. Although previous neuroimaging studies have shown that VPT and ToM activate the temporo-parietal junction (TPJ), it is unclear whether common neural substrates are involved in VPT and ToM. To clarify this point, the present study directly compared the TPJ activation patterns of individual participants performing VPT2 and ToM tasks using functional magnetic resonance imaging and within-subjects design. VPT2-induced activations were compared with activations observed during a mental rotation task as a control task, whereas ToM-related activities were identified with a standard ToM localizer using false-belief stories. A whole-brain analysis revealed that VPT2 and ToM activated overlapping areas in the posterior part of the TPJ. By comparing the activations induced by VPT2 and ToM in individual participants, we found that the peak voxels induced by ToM were located significantly more anteriorly and dorsally within the bilateral TPJ than those measured during the VPT2 task. We further confirmed that these activity areas were spatially distinct from the nearby extrastriate body area (EBA), visual motion area (MT+), and the posterior superior temporal sulcus (pSTS) using independent localizer scans. Our findings revealed that VPT2 and ToM have distinct representations, albeit partially overlapping, indicating the functional heterogeneity of social cognition within the TPJ. Significance StatementThe temporo-parietal junction (TPJ) is consistently activated by social cognitive tasks such as visual perspective taking (VPT) and theory of mind (ToM) tasks. The present study investigated whether VPT and ToM have the same neural substrates within the TPJ using functional magnetic resonance imaging (fMRI) with a within-subjects design. While VPT and ToM tasks activated overlapping areas in the posterior part of the TPJ, the individual peak voxels induced by ToM were located significantly more anteriorly and dorsally compared with those observed during the VPT task. Moreover, they were spatially distinct from the nearby functional modules, such as the extrastriate body area, visual motion area, and posterior superior temporal sulcus. Our findings reveal the heterogeneity of social cognition representation within the TPJ.

neuroscience↗

bioRxiv2021

Neural basis for adaptive motor behavior during car driving

Car driving is supported by motor skills trained through continuous daily practice. One of the skills unique to expert drivers is the ability to detect abrupt changes in the driving environment and then quickly adapt their operation mode to the changes. Previous functional neuroimaging studies on motor control investigated the mechanisms underlying behaviors adaptive to changes in control properties of simple experimental devices such as a computer mouse or a joystick. The switching of multiple internal models mainly engages adaptive behaviors and underlies the interplay between the cerebellum and frontoparietal network (FPN) regions as the neural process. However, it remains unclear whether the neural mechanisms identified through an experimental paradigm using such simple devices also underlie practical driving behaviors. In the current study, we measure functional magnetic resonance imaging (fMRI) activities while participants control a realistic driving simulator inside the MRI scanner. Here, the accelerator sensitivity of a virtual car is abruptly changed, requiring participants to respond to this change as quickly as possible. We first compare brain activities before and after the sensitivity change. As a result, sensorimotor areas, including the left cerebellum, increase their activities after the sensitivity change. Moreover, after the change, activity significantly increases in the inferior parietal lobe and dorsolateral prefrontal cortex, parts of the FPN regions. By contrast, the posterior cingulate cortex, a part of the default mode network, deactivates after the sensitivity change. Our results suggest that the neural bases found in previous experiments using the simpler devices can serve as the foundation of adaptive car driving. At the same time, this study also highlights the unique contribution of non-motor-related regions to addressing the high cognitive demands of driving.

neuroscience↗

bioRxiv2021

Mapping origins of variation in neural trajectories of human pluripotent stem cells

Variability between human pluripotent stem cell (hPSC) lines remains a challenge and opportunity in biomedicine. We identified differences in the early lineage emergence across hPSC lines that mapped on the antero-posterior axis of embryonic development. RNA-seq analysis revealed dynamic transcriptomic patterns that defined the emergence of mesendodermal versus neuroectodermal lineages conserved across hPSC lines and cell line-specific transcriptional signatures that were invariant across differentiation. The stable cell line-specific transcriptomic patterns predicted the retinoic acid (RA) response of the cell lines, resulting in distinct bias towards fore-versus hind-brain fates. Replicate hPSC lines and paired adult donor tissue demonstrated that cells from individual humans expressed unique and long-lasting transcriptomic signatures associated with evolutionarily recent genes. In addition to this genetic contribution, we found that replicate lines from a single donor showed divergent brain regional fates linked to distinct chromatin states, indicating that epigenetic mechanisms also contribute to neural fate differences. This variation in lineage bias and its correlation with RA responsive gene expression was also observed in a large collection of hPSC lines. These results define transcriptomic differences in hPSCs that initiate a critical early step specifying anterior or posterior neural fates.

neuroscience↗

bioRxiv2020

Tongue thickness measured by ultrasonography is associated with tongue pressure in the Japanese elderly

The term "oral frailty" reflects the fact that oral health is associated with physical frailty and mortality. Tongue thickness measurement is one of the evaluations for swallowing function. The aim of this study was to investigate the relationship between tongue thickness and tongue pressure in the Japanese elderly. We evaluated 254 elderly patients; all the participants underwent tongue ultrasonography and tongue pressure measurement. To determine tongue thickness, we measured the vertical distance from the surface of the mylohyoid muscle to the tongue dorsum using ultrasonography. Result analyses revealed that tongue thickness was linearly associated with tongue pressure in both sexes. In male participants, dyslipidemia, lower leg circumference, and tongue pressure were independently significantly associated with tongue thickness. In female participants, body mass index and tongue pressure were independently significantly associated with tongue thickness. Tongue thickness was significantly decreased by age for both men and women. The optimal cutoff for tongue thickness to predict the tongue pressure of < 20 kPa was 41.3 mm in males, and 39.3 mm in females. In the Japanese elderly, tongue thickness using ultrasonography is associated with tongue pressure. Tongue thickness and tongue pressure, which are sensitive markers for oral frailty, decrease in aging. The tongue ultrasonography provides a less invasive technique for determining tongue thickness and related aspiration risks for elderly patients.

neuroscience↗

bioRxiv2018

Self-agency built with sensorimotor processing: Decoding self-other action attribution in the human brain

A sense of agency can be defined as a subjective experience that I am the one who is causing or generating an action. Several brain regions have been proposed as neural substrates of the subjective experience; however, how the information is processed and organized by each region to achieve the sense of agency still remains unclear. In this study, we have clarified the neural representations corresponding to three processes namely, sensorimotor error, feeling of agency, and judgment of agency. Specifically, we found that the widespread sensorimotor areas represent sensorimotor error information. The right inferior parietal lobe represents the information solely on self-/other-attribution even during movements, which corresponds to the feeling of agency. Finally, the right inferior frontal gyrus shows a distinct representation between self- and other-attribution immediately before reporting the judgment on the movement attribution. These results suggest that the brain builds a sense of agency by developing distinct types of information each corresponding to the three processes with the passage of time.

neuroscience↗

bioRxiv2018

Cas9/CRISPR genome editing to demonstrate the contribution of Cyp51A Gly138Ser to azole resistance in Aspergillus fumigatus

Azole resistance in Aspergillus fumigatus is predominantly associated with increased expression of Cyp51A (lanosterol 14-demethylase), the target enzyme of azole antifungal agents, or with single-nucleotide polymorphisms (SNPs) in cyp51A. Although several SNPs that may be linked to low susceptibility in azole-resistant isolates have previously been reported, few studies have been conducted to conclusively demonstrate the contribution of SNPs to decreased azole susceptibility. An A. fumigatus strain was isolated from the sputum of a 74-year-old male receiving long-term voriconazole treatment for chronic progressive pulmonary aspergillosis. Etest antifungal susceptibility testing showed low susceptibility to voriconazole, itraconazole, and posaconazole. Nucleotide sequencing of cyp51A from this isolate revealed the mutations Gly138Ser (GGC[->]AGC) and Asn248Lys (AAT[->]AAA) compared with the cyp51A of azole-susceptible isolates. PCR-amplified DNA fragments containing cyp51A with or without the mutations of interest and a hygromycin marker were simultaneously introduced along with the Cas9 protein and in vitro-synthesized single-guide RNA into protoplasts of the azole-resistant/susceptible strains. Etest azole susceptibility testing of recombinant strains showed an increased susceptibility via the replacement of Ser138 by glycine. In contrast, azole susceptibility was slightly decreased when a Ser138 mutation was introduced into the azole-susceptible strain AfS35, indicating that the serine at position 138 of Cyp51A contributes to low susceptibility in the azole-resistant isolate. Genetic recombination, which has been hampered thus far in clinical isolates, can now be achieved using Cas9/CRISPR genome editing. This technique could be useful to investigate the contribution of other SNPs of cyp51A to azole resistance.

microbiology↗