Biology subjects

Oishi, K.

Publications and source records attributed to Oishi, K..

14 recordsLinked to original sources

bioRxiv2026

Spatial Patterns of White Matter Hyperintensities and Cognitive Function in Older Adults: A Community-Based Study

Abstract Objectives White matter hyperintensities (WMH) are associated with cognitive decline in older adults. We examined whether anatomically defined spatial WMH patterns are associated with cognitive performance and subsequent decline in a large community-based cohort with approximately six years of follow-up. Methods We analyzed 1,667 participants (mean age 76 years) from the Atherosclerosis Risk in Communities Neurocognitive Study. WMH were segmented from FLAIR images and mapped to 112 white matter regions using deep-learning-based parcellation. Principal component analysis identified dominant WMH distribution patterns; candidate components were selected by Horn's parallel analysis and retained if stable across resampled split samples. Linear mixed-effects models examined associations between WMH patterns and cognitive performance at baseline and follow-up, adjusting for demographic, genomic, and vascular risk factors. Robustness was assessed using analyses accounting for total WMH burden, study center, and selective attrition. Results Of 14 candidate principal components (PCs) identified by parallel analysis, eight met the resampling stability criterion and were retained, together explaining 42% of the variance. Three components were associated with cross-sectional or future cognition. PC3, characterized by deep white matter burden in the corpus callosum and anterior corona radiata with relative preservation of superficial white matter, showed no cross-sectional association at baseline but was associated with accelerated decline across multiple domains. Interpretation A deep spatial pattern of WMH loading on the corpus callosum and anterior corona radiata was associated with subsequent cognitive decline in the absence of a cross-sectional association at baseline, independent of total lesion burden.

neuroscience↗

bioRxiv2024

A Neural Network Approach to Identify Left-Right Orientation of Anatomical Brain MRI

Left-right orientation misidentification in brain MRIs presents significant challenges due to several factors, including metadata loss or ambiguity, which often occurs during the de-identification of medical images for research, conversion between image formats, software operations that strip or overwrite metadata, and the use of older imaging systems that stored orientation differently. This study presents a novel application of deep-learning to enhance the accuracy of left-right orientation identification in anatomical brain MRI scans. A three-dimensional Convolutional Neural Network model was trained using 350 MRIs and evaluated on eight distinct brain MRI databases, totaling 3,384 MRIs, to assess its performance across various conditions, including neurodegenerative diseases. The proposed deep-learning framework demonstrated a 99.6% accuracy in identifying the left-right orientation, thus addressing challenges associated with the loss of orientation metadata. GradCAM was used to visualize areas of the brain where the model focused, demonstrating the importance of the right planum temporale and surrounding areas in judging left-right orientation. The planum temporale is known to exhibit notable left-right asymmetry related to language functions, underscoring the biological validity of the model. More than half of the ten left-right misidentified MRIs involved notable brain feature variations, such as severe temporal lobe atrophy, arachnoidal cysts adjacent to the temporal lobe, or unusual cerebral torque, indicating areas for further investigation. This approach offers a potential solution to the persistent issue of left-right misorientation in brain MRIs and supports the reliability of neuroscientific research by ensuring accurate data interpretation.

neuroscience↗

bioRxiv2023

Neutralizing antibody levels and epidemiological information of patients with breakthrough COVID-19 infection in Toyama, Japan

Breakthrough infection (BI) after coronavirus disease 2019 (COVID-19) vaccination has exploded owing to the emergence of various SARS-CoV-2 variants and has become a major problem at present. In this study, we analyzed the epidemiological information and possession status of neutralizing antibodies in patients with BI using SARS-CoV-2 pseudotyped viruses (SARS-CoV-2pv). Analysis of 44 specimens diagnosed with COVID-19 after two or more vaccinations showed high inhibition of infection by 90% or more against the Wuhan strain and the Alpha and Delta variants of pseudotyped viruses in 40 specimens. In contrast, almost no neutralizing activity was observed against the Omicron BA.1 variant. Many cases without neutralizing activity or BI were immunosuppressed individuals. The results of this study show that BI occurs even when there are sufficient neutralizing antibodies in the blood due to exposure to close contacts at the time of infection. Thus, even after vaccination, sufficient precautions must be taken to prevent infection.

microbiology↗

bioRxiv2023

Evaluation of SARS-CoV-2 isolation in cell culture from nasal/nasopharyngeal swabs or saliva specimens of patients with COVID-19

It has been revealed that SARS-CoV-2 can be efficiently isolated from clinical specimens such as nasal/nasopharyngeal swabs or saliva in cultured cells. In this study, we examined the efficiency of viral isolation including SARS-CoV-2 mutant strains between nasal/nasopharyngeal swab or saliva specimens. Furthermore, we also examined the comparison of viral isolation rates by sample species using simulated specimens for COVID- 19. As a result, it was found that the isolation efficiency of SARS-CoV-2 in the saliva specimens was significantly lower than that in the nasal/nasopharyngeal swab specimens. In order to determine which component of saliva is responsible for the lower isolation rate of saliva specimens, we tested the abilities of lactoferrin, amylase, cathelicidin, and mucin, which are considered to be abundant in saliva, to inhibit the infection of SARS-CoV-2 pseudotyped viruses (SARS-CoV-2pv). Lactoferrin and amylase were found to inhibit SARS-CoV-2pv infection. In conclusion, even if the same number of viral genome copies was detected by the real-time RT-PCR test, infection of SARS-CoV-2 present in saliva is thought to be inhibited by inhibitory factors such as lactoferrin and amylase, compared to nasal/nasopharyngeal swab specimens.

microbiology↗

bioRxiv2022

Multi-modal multi-resolution atlas of the human neonatal cerebral cortex based on microstructural similarity

The neonatal period is a critical window for the development of the human brain and may hold implications for the long-term development of cognition and disorders. Multi-modal connectome studies have revealed many important findings underlying the adult brain but related studies were rare in the early human brain. One potential challenge is the lack of an appropriate and unbiased parcellation that combines structural and functional information in this population. Using 348 multi-modal MRI datasets from the developing human connectome project, we found that the information fused from the structural, diffusion, and functional MRI was relatively stable across MRI features and showed high reproducibility at the group level. Therefore, we generated automated multi-resolution parcellations (300 - 500 parcels) based on the similarity across multi-modal features using a gradient-based parcellation algorithm. In addition, to acquire a parcellation with high interpretability, we provided a manually delineated parcellation (210 parcels), which was approximately symmetric, and the adjacent areas around each boundary were statistically different in terms of the integrated similarity metric and at least one kind of original features. Overall, the present study provided multi-resolution and neonate-specific parcellations of the cerebral cortex based on multi-modal MRI properties, which may facilitate future studies of the human connectome in the early development period.

neuroscience↗

bioRxiv2022

Activation of SARS-CoV-2 by trypsin-like proteases in the clinical specimens of patients with COVID-19

SARS-CoV-2 enters host cells through the angiotensin converting enzyme 2 (ACE2) receptor and/or transmembrane protease, serine 2 (TMPRSS2). Serine proteases, such as TMPRSS2 and trypsin, promote viral entry. In this study, we investigated whether proteases increased SARS-CoV-2 infectivity using pseudotyped viruses and clinical specimens from patients with COVID-19. First, we investigated how trypsin increased infectivity using the pseudotyped virus. Our findings revealed that trypsin increased infectivity after the virus was adsorbed on the cells, but no increase in infectivity was observed when the virus was treated with trypsin. We examined the effect of trypsin on SARS-CoV-2 infection in clinical specimens and found that the infectivity of the SARS-CoV-2 delta variant increased 36,000-fold after trypsin treatment. By contrast, the infectivity of SARS-CoV-2 omicron variant increased to less than 20-fold in the clinical specimens. Finally, infectivity of clinical specimens containing culture supernatants of Fusobacterium necrophorum was increased from several- to 10-fold. Because SARS-CoV-2 infectivity increases in the oral cavity, which may contain anaerobic bacteria, keeping the oral cavities clean may help prevent SARS-CoV-2 infection. ImportanceIn this study, we examined whether trypsin-like proteases increased the infectivity of SARS-CoV-2. We found that trypsin-like proteases increased the infectivity of both the pseudotyped viruses and the live virus in the clinical specimens. The increase in infectivity was significantly higher for the delta than the omicron variant. A large amount of protease in the oral cavity during SARS-CoV-2 infection is expected to increase infectivity. Therefore, keeping the oral cavity clean is important for preventing infection.

microbiology↗

bioRxiv2022

SARS-CoV-2 infection results in lasting and systemic perturbations post recovery

SARS-CoV-2 has been found capable of inducing prolonged pathologies collectively referred to as Long-COVID. To better understand this biology, we compared the short- and long-term systemic responses in the golden hamster following either SARS-CoV-2 or influenza A virus (IAV) infection. While SARS-CoV-2 exceeded IAV in its capacity to cause injury to the lung and kidney, the most significant changes were observed in the olfactory bulb (OB) and olfactory epithelium (OE) where inflammation was visible beyond one month post SARS-CoV-2 infection. Despite a lack of detectable virus, OB/OE demonstrated microglial and T cell activation, proinflammatory cytokine production, and interferon responses that correlated with behavioral changes. These findings could be corroborated through sequencing of individuals who recovered from COVID-19, as sustained inflammation in OB/OE tissue remained evident months beyond disease resolution. These data highlight a molecular mechanism for persistent COVID-19 symptomology and characterize a small animal model to develop future therapeutics.

microbiology↗

bioRxiv2020

The Japan Monkey Centre Primates Brain Imaging Repository of high-resolution postmortem magnetic resonance imaging: the second phase of the archive of digital records

A comparison of neuroanatomical features of the brain between humans and our evolutionary relatives, nonhuman primates, is key to understanding the human brain system and the neural basis of mental and neurological disorders. Although most comparative MRI studies of human and nonhuman primate brains have been based on brains of primates that had been used as subjects in experiments, it is essential to investigate various species of nonhuman primates in order to elucidate and interpret the diversity of neuroanatomy features among humans and nonhuman primates. To develop a research platform for this purpose, it is necessary to harmonize the scientific contributions of studies with the standards of animal ethics, animal welfare, and the conservation of brain information for long-term continuation of the field. In previous research, we first developed an open-resource repository of anatomical images obtained using 9.4-T ex vivo MRI of postmortem brain samples from 12 nonhuman primate species, and which are stored at the Japan Monkey Centre. In the present study, as a second phase, we released a collection of T2-weighted images and diffusion tensor images obtained in nine species: white-throated capuchin, Bolivian squirrel monkey, stump-tailed macaque, Tibet monkey, Sykes monkey, Assamese macaque, pig-tailed macaque, crested macaque, and chimpanzee. Our image repository should facilitate scientific discoveries in the field of comparative neuroscience. This repository can also promote animal ethics and animal welfare in experiments with nonhuman primate models by optimizing methods for in vivo and ex vivo MRI scanning of brains and supporting veterinary neuroradiological education. In addition, the repository is expected to contribute to conservation, preserving information about the brains of various primates, including endangered species, in a permanent digital form.

neuroscience↗

bioRxiv2020

-SATA: A MATLAB based toolbox to estimate Current Density generated by Transcranial Direct Current Stimulation in an Individual Brain

BackgroundTranscranial Direct Current Stimulation (tDCS) is a technique where a weak current is passed through the electrodes placed on the scalp. The distribution of the electric current induced in the brain due to tDCS is provided by simulation toolbox like Realistic-volumetric-Approach-based-Simulator-for-Transcranial-electric-stimulation (ROAST). However, the procedure to estimate the total current density induced at the target and the intermediary region of the cortex is complex. The Systematic-Approach-for-tDCS-Analysis (SATA) was developed to overcome this problem. However, SATA is limited to standardized headspace only. Here we develop individual-SATA (-SATA) to extend it to individual head. MethodT1-weighted images of 15 subjects were taken from two Magnetic Resonance Imaging (MRI) scanners of different strengths. Across the subjects, the montages were simulated in ROAST. -SATA converts the ROAST output to Talairach space. The x, y and z coordinates of the anterior commissure (AC), posterior commissure (PC), and Mid-Sagittal (MS) points are necessary for the conversion. AC and PC are detected using the acpcdetect toolbox. We developed a method to determine the MS in the image and cross-verified its location manually using BrainSight(R). ResultDetermination of points with -SATA is fast and accurate. The -SATA provided estimates of the current-density induced across an individuals cortical lobes and gyri as tested on images from two different scanners. ConclusionResearchers can use -SATA for customizing tDCS-montages. With -SATA it is also easier to compute the inter-individual variation in current-density across the target and intermediary regions of the brain. The software is publicly available.

neuroscience↗

bioRxiv2020

Engineering an RNA-based tissue-specific platform for genetic editing through use of a miRNA-enabled Cas12a

The capacity to edit genomes using CRISPR-Cas systems holds immense potential for countless genetic-based diseases. However, one significant impediment preventing broad therapeutic utilization is in vivo delivery. While genetic editing at a single cell level in vitro can be achieved with high efficiency, the capacity to utilize these same biologic tools in a desired tissue in vivo remains challenging. Non-integrating RNA virus-based vectors constitute efficient platforms for transgene expression and surpass several barriers to in vivo delivery. However, the broad tissue tropism of viral vectors raises the concern for off-target effects. Moreover, prolonged expression of the Cas proteins, regardless of delivery method, can accumulate aberrant RNAs leading to unwanted immunological responses. In an effort to circumvent these shortcomings, here we describe a versatile RNA virus-based technology that can achieve cell-specific activity and self-inactivation by combining host microRNA (miRNA) biology with the CRISPR-Cas12a RNA-guided nuclease. Exploiting the RNase activity of Cas12a, we generated a vector that self-inactivates upon delivery of Cas12a and an accompanying CRISPR RNA (crRNA). Furthermore, we show that maturation of the crRNA can be made dependent on cell-specific miRNAs, which confers cell-specificity. We demonstrate that this genetic editing circuit delivers diminished yet sufficient levels of Cas12a to achieve effective genome editing whilst inducing a minimal immunological response. It can also function in a cell-specific manner thereby facilitating in vivo editing and mitigating the risk of unwanted, off-target effects.

bioengineering↗

bioRxiv2019

Genetic risks of schizophrenia identified in a matched case-control study

BackgroundGenetic association studies of schizophrenia may be confounded by the pathological heterogeneity and multifactorial nature of this disease. We demonstrated previously that combinations of the three functional single nucleotide polymorphisms (SNPs) rs10770141 of tyrosine hydroxylase (TH) gene, rs4680 of catechol-O-methyltransferase (COMT) gene, and rs1800497 of dopamine D2 receptor (DRD2) gene may be associated with schizophrenia onset, and we tested those associations herein. Methods: We conducted a secondary study of 2,542 individuals in age- and sex-matched case-control populations. The schizophrenia diagnosis was based on the DSM-IV. To reduce the influence of confounders (age and sex), we performed a propensity score matching analysis. Genotyping and associative analyses of rs10770141, rs4680, and rs1800497 with schizophrenia were performed. Results: We analyzed 1,271 schizophrenics (male/female: 574/698; age 47.4{+/-}13.9 years) and 1,271 matched controls (male/female: 603/669; age 46.5{+/-}13.4 years). The estimated odds ratios (ORs) were 1.245 (p<0.001) for rs4680, 1.727 (p<0.0001) for rs1800497, and 1.788 (p<0.0001) for rs10770141. Double SNP analyses revealed the ORs of 2.010 (p<0.0001) for the combination of rs4680*rs1800497, 1.871 (p<0.001) for rs1800497*rs10770141, and 1.428 (p=0.068) for rs4680*rs1800497. Among the individuals with any of the three double SNP risk combinations (which accounted for 35.8% of the involved patients), the estimated OR was 2.224 (p<0.0001). Conclusions: In this validation study, the combinations of functional polymorphisms related to dopaminergic genes were associated with the development of schizophrenia. Analyzing combinations of functional polymorphisms with the control of possible confounders may provide new insights for association research.

genetics↗

bioRxiv2018

Genetic combination risk for schizophrenia

Summary ParagraphSchizophrenia is a highly hereditary mental disease1 related to abnormal dopaminergic activities.2,3 To elucidate the mechanisms underlying schizophrenias development, genomic studies have sought to identify the pathogenic genetic polymorphisms. Large-scale genome-wide association studies (GWAS) have reported potential candidate loci that contribute to schizophrenias development.4,5 The risk genetic profiles are not yet established. Here we show that the combination of three functional single nucleotide polymorphisms (SNPs) related to the key factors of dopaminergic signaling can be used to predict the risk of schizophrenias development, though none of the SNPs is known to be associated by itself. These functional SNPs were reported to demonstrate directional influences in their parent gene activity, perhaps characterizing the integrated properties of dopaminergic signaling. Interestingly, the risk combination presented here included the major genotype as well as the minor polymorphisms, suggesting a possible association of unaffected activities of some dopamine-related genes with the disease development. The phenotype speculated based on the allelic status seemed consistent with the conventional pathophysiological hypotheses, although recently developed predictive methods, such as the polygenic risk score, could miss this potent pathogenic role of carrying a normal genotype by evaluating only minor polymorphisms. Our results demonstrate the presence of a subtype in schizophrenia with the favored genetic background related to dopamine signaling. Our findings indicate the possibility that the combinations could characterize integrated biological functions (including neurotransmission) and therefore identify individuals with a disease risk. The biological microenvironment indicated by the functional SNPs could bring an insight to elucidate the pathogenic mechanisms of developing schizophrenia. Furthermore, we believe that our approach will contribute to the development of innovative means to predict disease risks even for other multi-factorial diseases and then, the following preventive medicine.

neuroscience↗

bioRxiv2018

Temporal control of cortico-thalamic neuron specification by regulation of Neurogenin activity and Polycomb repressive complexes

Neural progenitor cells (NPCs) in the embryonic mammalian neocortex generate different neuronal subtypes sequentially. A long-standing hypothesis to account for this temporal fate specification process is that NPCs change their differentiation potential over time. However, the molecular mechanisms underlying these temporal changes in NPC properties are poorly understood. Here we show that Neurogenin1 and Neurogenin2 (Neurog1/2), two proneural transcription factors expressed in NPCs throughout cortical neurogenesis, specify the identity of one of the first cortical neuron subtypes generated, layer 6 cortico-thalamic neurons (CTNs). We found that Neurog1/2 specify the CTN fate through regulation of the cortical fate determinants Fezf2 and Foxp2 and that this Neurog-induced programme becomes inactive after the period of CTN production. Two independent mechanisms contribute to the arrest of CTN neuron generation at the end of layer 6 neurogenesis, including a reduction in the transcriptional activity of Neurog1/2 and the deposition of epigenetic repressive modifications mediated by Polycomb repressive complexes at the Foxp2 gene. Therefore, the duration of production of a cortical neuron subtype is controlled by multiple locking mechanisms involving both transcriptional and epigenetic processes.

neuroscience↗

bioRxiv2018

Molecular typing and macrolide resistance analyses of Treponema pallidumin heterosexuals and men who have sex with men communities in Japan, 2017.

In recent years, syphilis notifications have increased dramatically in Japan. We performed molecular typing and analyzed macrolide resistance of Treponema pallidum samples collected from four clinics and a hospital in Tokyo and Osaka prefectures in 2017.\n\nMacrolide resistant strain type 14d/f was found significantly more in heterosexual syphilis cases compared with those strains identified in men who have sex with men (MSM) syphilis cases. The proportion of 14d/f among heterosexuals was 79% (31/39) compared to 37% (7/19) among MSM [OR, 6.6 (95% CI, 1.7 to 26.7); P=0.002]. 83% (50/60) of the strains were identified as macrolide resistant with an A2058G mutation at the 23S rRNA gene. 90% (35/39) of the heterosexual strains were macrolide resistant, relative to 58% (11/19) of MSM strains; the odds of having the resistant mutation was considerably higher in heterosexuals compared with MSM [OR, 6.4 (95% CI, 1.3 to 33.5); P=0.02]. Heterosexual females and males showed similar distributions, and the results remained the same when restricted to men.\n\nThe strain type distribution and frequency of macrolide resistance differed substantially between heterosexual and MSM syphilis samples, suggesting distinct epidemiologic profiles for the two communities and insight into syphilis transmission dynamics in Japan.

epidemiology↗