Biology subjects

Kishi, N.

Publications and source records attributed to Kishi, N..

3 recordsLinked to original sources

bioRxiv2026

MECP2-mutant marmosets exhibit primate-specific phenotypes of Rett syndrome

We used genome editing to generate MECP2-knockout marmosets and establish a new primate model for Rett syndrome (RTT), a neurodevelopmental disorder. MRI analysis of this marmoset model revealed diminished cortico-cortical connections, particularly those originating in the prefrontal cortex. Detailed histological analysis revealed reduced dendritic arborization and synaptic density, particularly in the upper layers of the cerebral cortex. Cortical layer II/III excitatory neurons appeared to be immature based on single-nucleus RNA sequencing and spatial transcriptomics, while PVALB-positive interneurons exhibited upregulation of neuronal maturation-related transcripts. Moreover, the neurodevelopmental disease gene GABAB receptor 2 (GABBR2) emerged as a conserved downstream target of MECP2, illuminating a cellular cascade that could be targeted in preclinical and therapeutic drug development. Many of the gene expression changes observed in the marmoset model are common in RTT patients, thereby highlighting molecular links from cell type-specific phenotypes in the marmoset model to the RTT clinical presentation.

neuroscience↗

bioRxiv2024

Dual fragmentation via collision-induced and oxygen attachment dissociations using water and its radicals for C=C position-resolved lipidomics

Oxygen attachment dissociation (OAD) is a tandem mass spectrometry (MS/MS) technique used to annotate the positions of double bonds (C=C) in complex lipids. Although OAD has been used for untargeted lipidomics, its availability has been limited to the positive-ion mode, requiring the independent use of a collision-induced dissociation (CID) method. In this study, we demonstrated the OAD-MS/MS technique in the negative-ion mode for profiling phosphatidylserines, phosphatidylglycerols, phosphatidylinositols, and sulfatides, where the fragmentation mechanism remained consistent with that in the positive-ion mode. Furthermore, we proposed optimal conditions for the simultaneous acquisition of CID- and OAD-specific fragment ions, termed OAciD. In the collision cell for OAD, oxygen atoms and hydroxy radicals facilitate C=C position-specific fragmentation, while residual water vapor induces cleavage of low-energy covalent bonds, such as ester and peptide bonds, at higher collision energy values, preserving OAD-specific ions under high collision energy conditions. Finally, theoretical fragment ions were implemented in MS-DIAL 5 to accelerate C=C position-resolved untargeted lipidomics. The OAciD methodology was applied to lipid profiling of five marmoset brain regions: the frontal lobe, hippocampus, midbrain, cerebellum, and medulla. Region-specific marmoset lipidomes were characterized with C=C positional information, where the ratios of C=C positional isomers such as delta 9- and delta 11 of fatty acid 18:1 in phosphatidylcholine were also estimated using OAciD-MS/MS. In addition, we characterized the profiles of polyunsaturated fatty acid-containing complex lipids with C=C positional information, where lipids containing omega-3 fatty acids were enriched in the cerebellum, while those containing omega-6 fatty acids were more abundant in the hippocampus and frontal lobe.

bioengineering↗

bioRxiv2022

Multi-modal brain magnetic resonance imaging database covering marmosets with a wide age range

Magnetic resonance imaging (MRI) is a noninvasive neuroimaging method beneficial for the identification of normal developmental and aging processes and data sharing. Marmosets have a relatively shorter life expectancy (approximately 10 years) than other primates, including, humans because they grow and age faster. Hence, the common marmoset model is effective in aging research. The current study investigated the aging process of the marmoset brain and provided an open MRI database on marmosets with a wide age range. The Brain/MINDS Marmoset Brain MRI Dataset contains brain MRI information on 216 marmosets aged between 1 and 10 years. During its release date, it is the largest public dataset worldwide. Further, it comprises multi contrast MRI images. In addition, 91 of 216 animals have corresponding ex vivo high-resolution MRI datasets. Our MRI database, which is available at the Brain/MINDS Data portal might help understand the effects of different factors, such as age, sex, body size, and fixation, on the brain. Moreover, it can contribute to and accelerate brain science studies worldwide.

neuroscience↗