Biology subjects

Nishiyama, H.

Publications and source records attributed to Nishiyama, H..

5 recordsLinked to original sources

bioRxiv2026

Multimodal phenotyping reveals plant-food-related dietary information in serum Raman spectra of community-dwelling Japanese adults

Healthy dietary patterns are associated with long-term health, but diet-quality scores do not reveal how habitual dietary information is represented in human biological phenotypes. Here we linked habitual dietary assessment with preceding health records and contemporaneous clinical chemistry, serum metabolomics and serum Raman spectra in community-dwelling Japanese adults. Higher diet quality corresponded to a more favorable preceding health profile, but did not define discrete states across contemporary multivariate phenotypes. Instead, specific dietary information was recoverable across these layers: Raman spectra provided predictive information complementary to clinical and metabolomic measurements for multiple dietary variables. Raman variation corresponding to {beta}-carotene equivalent could be traced to carotenoid-assigned bands and aligned with a broader plant-food-related dietary dimension. These findings show that habitual diet is represented not as a single biological state but through biologically traceable dietary dimensions distributed across complementary phenotypic layers.

bioinformatics↗

bioRxiv2024

A novel mouse model for developmental and epileptic encephalopathy by Purkinje cell-specific deletion of Scn1b

Loss of function variants of SCN1B are associated with a range of developmental and epileptic encephalopathies (DEEs), including Dravet syndrome. These DEEs feature a wide range of severe neurological disabilities, including changes to social, motor, mood, sleep, and cognitive function which are notoriously difficult to treat, and high rates of early mortality. While the symptomology of SCN1B-associated DEEs indicates broad changes in neural function, most research has focused on epilepsy-related brain structures and function. Mechanistic studies of SCN1B/Scn1b have delineated diverse roles in development and adult maintenance of neural function, via cell adhesion, ion channel regulation, and other intra- and extra-cellular actions. However, use of mouse models is limited as knockout of Scn1b, globally and even in some cell-specific models (e.g., Parvalbumin+ interneuron-specific knockout) in adult mice, leads to severe and progressive epilepsy, health deterioration, and 100% mortality within weeks. Here, we report findings of a novel transgenic mouse line in which Scn1b was specifically deleted in cerebellar Purkinje cells. Unlike most existing models, these mice did not show failure to thrive or early mortality. However, we quantified marked decrements to Purkinje cell physiology as well as motor, social, and cognitive dysfunction. Our data indicate that cerebellar Purkinje cells are an important node for dysfunction and neural disabilities in SCN1B-related DEEs, and combined with previous work identify this as a potentially vital site for understanding mechanisms of DEEs and developing therapies that can treat these disorders holistically.

neuroscience↗

bioRxiv2023

Loss of Purkinje cells in the developing cerebellum strengthens the cerebellothalamic synapses

Cerebellar damage early in life often causes long-lasting motor, social, and cognitive impairments, suggesting the roles of the cerebellum in developing a broad spectrum of behaviors. This recent finding has promoted research on how cerebellar damage affects the development of the cerebral cortex, the brain region responsible for higher-order control of all behaviors. However, the cerebral cortex is not directly connected to the cerebellum. The thalamus is the direct postsynaptic target of the cerebellum, sending cerebellar outputs to the cerebral cortex. Despite its crucial position in cerebello-cerebral interaction, thalamic susceptibility to cerebellar damage remains largely unclear. Here, we studied the consequences of early cerebellar perturbation on thalamic development. Whole-cell patch-clamp recordings showed that the synaptic organization of the cerebellothlamic circuit is similar to that of the primary sensory thalamus, in which aberrant sensory activity alters synaptic circuit formation. The hemizygous deletion of the tuberous sclerosis complex-1 (Tsc1) gene in the Purkinje cell--known to cause Purkinje cell hypoactivity and autistic behaviors--did not alter cerebellothalamic synapses or intrinsic membrane properties of thalamic neurons. However, the ablation of Purkinje cells in the developing cerebellum strengthened the cerebellothalamic synapses and enhanced thalamic suprathreshold activities. These results suggest that the cerebellothalamic circuit is resistant to moderate perturbation in the developing cerebellum, such as the reduced firing rate of Purkinje cells, and that autistic behaviors are not necessarily linked to thalamic abnormality. Still, Purkinje cell loss alters the thalamic circuit, suggesting the vulnerability of the thalamus to substantial disturbance in the developing cerebellum.

neuroscience↗

bioRxiv2020

Aberrant claudin-6-adhesion signal promotes endometrial cancer progression via estrogen receptor α

Cell adhesion proteins not only maintain tissue integrity but also possess signaling abilities to organize diverse cellular events in physiological and pathological processes; however, the underlying mechanism remains obscure. Among cell adhesion molecules, the claudin (CLDN) family often possesses aberrant expression in various cancers, but the biological relevance and molecular basis have not yet been established. Here, we show that high CLDN6 expression promotes endometrial cancer progression and represents the poor prognostic marker. The second extracellular domain and Y196/200 of CLDN6 were required to recruit and activate Src-family kinases (SFKs) and to stimulate malignant phenotypes. Importantly, we demonstrate that the CLDN6/SFK/PI3K-dependent AKT and SGK (serum- and glucocorticoid-regulated kinase) signalings target Ser518 in the human estrogen receptor and ligand-independently activate target genes in endometrial cancer cells, resulting in cancer development. The identification of this machinery highlights regulation of the transcription factors by cell adhesion to advance tumor progression.

cancer biology↗

bioRxiv2018

CTCF looping is established during gastrulation in medaka embryos

AbstractGenome architecture plays a critical role in gene regulation, but how the structures seen in mature cells emerge during embryonic development remains poorly understood. Here, we study early development in medaka (the Japanese killifish, Oryzias latipes) at 12 time points before, during, and after gastrulation which is the most dramatic event in early embryogenesis, and characterize transcription, protein binding, and genome architecture. We find that gastrulation is most associated with drastic changes in genome architecture, including the formation of the first loops between sites bound by the insulator protein CTCF and great increase in the size of contact domains. However, the position of CTCF is fixed throughout medaka embryogenesis. Interestingly, genome-wide transcription precedes the emergence of mature domains and CTCF-CTCF loops.

genomics↗