Biology subjects

Aoki, Y.

Publications and source records attributed to Aoki, Y..

26 records · Page 2Linked to original sources

bioRxiv2020

Genetic interactions among ADAMTS metalloproteases and basement membrane molecules in cell migration in Caenorhabditis elegans

During development of the Caenorhabditis elegans gonad, the gonadal leader cells, called distal tip cells (DTCs), migrate in a U-shaped pattern to form the U-shaped gonad arms. The ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family metalloproteases MIG-17 and GON-1 are required for correct DTC migration. Mutations in mig-17 result in misshapen gonads due to the misdirected DTC migration, and mutations in gon-1 result in shortened and swollen gonads due to the premature termination of DTC migration. Although the phenotypes shown by mig-17 and gon-1 mutants are very different from one another, mutations that result in amino acid substitutions in the same basement membrane protein genes, emb-9/collagen IV a1, let-2/collagen IV a2 and fbl-1/fibulin-1, were identified as genetic suppressors of mig-17 and gon-1 mutants. To understand the roles shared by these two proteases, we examined the effects of the mig-17 suppressors on gon-1 and the effects of the gon-1 suppressors and enhancers on mig-17 gonadal defects. Some of the emb-9, let-2 and fbl-1 mutations suppressed both mig-17 and gon-1, whereas others acted only on mig-17 or gon-1. These results suggest that mig-17 and gon-1 have their specific functions as well as functions commonly shared between them for gonad formation. The levels of collagen IV accumulation in the DTC basement membrane were significantly higher in the gon-1 mutants as compared with wild type and were reduced to the wild-type levels when combined with suppressor mutations, but not with enhancer mutations, suggesting that the ability to reduce collagen IV levels is important for gon-1 suppression.

developmental biology↗

bioRxiv2020

Species-specific assembly of root-associated bacterial microbiota mediated by a combination of plant specialized metabolites

Plant specialized metabolites (PSMs) influence the taxonomic compositions of the root-associated microbiota; however, the underlying molecular mechanisms and evolutionary trajectories remain elusive. Here, we show that the bacterial genus Arthrobacter is predominant in the tobacco endosphere, and that its enrichment is mediated by a combination of two tobacco-specific PSMs, santhopine and nicotine The isolation and whole genome sequencing of a representative set of Arthrobacter strains identified independent genomic features, including but not limited to genes for santhopine and nicotine catabolism, which are associated with the colonization competence of tobacco roots. Taken together, these data suggest that plant species-specific root microbiota assembly is mediated by bacterial catabolism of a cocktail of PSMs synthesized by the host plant.

microbiology↗

bioRxiv2020

Japonica Array NEO with increased genome-wide coverage and abundant disease risk SNPs

BackgroundIncreasing the power of genome-wide association studies in diverse populations is important for understanding the genetic determinants of disease risks, and large-scale genotype data are collected by genome cohort and biobank projects all over the world. In particular, ethnic-specific SNP arrays are becoming more important because the use of universal SNP arrays has some limitations in terms of cost-effectiveness and throughput. As part of the Tohoku Medical Megabank Project, which integrates prospective genome cohorts into a biobank, we have been developing a series of Japonica Arrays for genotyping participants based on reference panels constructed from whole-genome sequence data of the Japanese population. ResultsWe designed a novel version of the SNP Array for the Japanese population, called Japonica Array NEO, comprising a total of 666,883 SNPs, including tag SNPs of autosomes and X chromosome with pseudoautosomal regions, SNPs of Y chromosome and mitochondria, and known disease risk SNPs. Among them, 654,246 tag SNPs were selected from an expanded reference panel of 3,552 Japanese using pairwise r2 of linkage disequilibrium measures. Moreover, 28,298 SNPs were included for the evaluation of previously identified disease risk SNPs from the literature and databases, and those present in the Japanese population were extracted using the reference panel. The imputation performance of Japonica Array NEO was assessed by genotyping 286 Japanese samples. We found that the imputation quality r2 and INFO score in the minor allele frequency bin >2.5%-5% were >0.9 and >0.8, respectively, and >12 million markers were imputed with an INFO score >0.8. After verification, Japonica Arrays were used to efficiently genotype cohort participants from the sample selection to perform a quality assessment of the raw data; approximately 130,000 genotyping data of >150,000 participants has already been obtained. ConclusionsJaponica Array NEO is a promising tool for genotyping the Japanese population with genome-wide coverage, contributing to the development of genetic risk scores for this population and further identifying disease risk alleles among individuals of East Asian ancestry.

genomics↗

bioRxiv2020

Diurnal metabolic regulation of isoflavones and soyasaponins in soybean roots

Isoflavones and soyasaponins are major specialized metabolites accumulated in soybean roots and secreted into the rhizosphere. Unlike the biosynthetic pathway, the transporters involved in metabolite secretion remain unknown. The developmental regulation of isoflavone and soyasaponin secretions has been recently reported, but the diurnal regulation of their biosynthesis and secretion still needs to be further studied. To address these challenges, we conducted transcriptome and metabolite analysis using hydroponically grown soybean plants at 6-hour intervals for 48 hours in a 12-h-light/12-h-dark condition. Isoflavone and soyasaponin biosynthetic genes showed opposite patterns in the root tissues; that is, the former genes are highly expressed in daytime, while the latter ones are strongly induced at nighttime. GmMYB176 encoding a transcription factor of isoflavone biosynthesis was upregulated from ZT0 (6:00 am) to ZT6 (12:00 am), followed by the induction of isoflavone biosynthetic genes at ZT6. The isoflavone aglycone content in the roots accordingly increased from ZT6 to ZT18 (0:00 am), accompanied by an increase in glucoside levels that peaked at ZT0. The isoflavone aglycone content in root exudates was kept consistent throughout the day, whereas that of glucosides increased at ZT6, which reflected the decreased expression of the gene encoding beta-glucosidase involved in the hydrolysis of apoplast-localized isoflavone conjugates. Co-expression analysis revealed that those isoflavone and soyasaponin biosynthetic genes formed separate clusters, which exhibited a correlation to ABC and MATE transporter genes. As summary, the results in this study indicated the diurnal regulation of isoflavone biosynthesis in soybean roots and the putative transporter genes responsible for isoflavone and soyasaponin transport.

plant biology↗

bioRxiv2019

Cortisol levels adter cold exposure are independent of adrenocorticotropic hormone stimulation

We previously showed that postmortem serum levels of adrenocorticotropic hormone (ACTH) were significantly higher in cases of hypothermia (cold exposure) than other causes of death. This study examined how the human hypothalamic-pituitary-adrenal axis, and specifically cortisol, responds to hypothermia.\n\nHuman samplesAutopsies on 205 subjects (147 men and 58 women; age 15-98 years, median 60 years) were performed within 3 days of death. Cause of death was classified as either hypothermia (cold exposure, n=14) or non-cold exposure (controls; n=191). Cortisol levels were determined in blood samples obtained from the left and right cardiac chambers and common iliac veins using a chemiluminescent enzyme immunoassay. Adrenal gland tissue samples were stained for cortisol using a rabbit anti-human polyclonal antibi.\n\nCell cultureAtT20, a mouse ACTH secretory cell line, and Y-1, a corticosterone secretory cell line derived from a mouse adrenal tumor, were analyzed in mono-and co-culture, and times courses of ACTH (in AtT20) and corticosterone (in Y-1) secretion were assessed after low temperature exposure mimicking hypothermia and compared with data for samples collected postmortem for other causes of death. However, no correlation between ACTH concentration and cortisol levels was observed in hypothermia cases. Immunohistologic analyses of samples from hypothermia cases showed that cortisol staining was localized primarily to the nucleus rather than the cytoplasm of cells in the zona fasciculata of the adrenal gland. During both mono-culture and co-culture, AtT20 cells secreted high levels of ACTH after 10-15 minutes of cold exposure, whereas corticosterone secretion by Y-1 cells increased slowly during the first 15-20 minutes of cold exposure. Similar to autopsy results, no correlation was detected between ACTH levels and corticosterone secretion, either in mono-culture or co-culture experiments. These results suggested that ACTH-independent cortisol secretion may function as a stress response during cold exposure.

biochemistry↗

bioRxiv2019

White matter alterations in autism spectrum disorder and attention-deficit/hyperactivity disorder in relation to sensory profile

BackgroundAutism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) have high rates of co-occurrence and share atypical behavioral characteristics, including sensory problems. The present diffusion tensor imaging (DTI) study was conducted to examine whether and how white matter abnormalities are observed in adult populations with developmental disabilities (DD) and to determine how brain-sensory relationships are either shared between or distinct to ASD and ADHD.\n\nMethodsWe collected DTI data from adult developmental disorder (DD) populations (a primary diagnosis of ASD: n=105, ADHD: n=55) as well as age and sex matched typically developed (TD) participants (n=58). Voxel-wise fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity (RD) were analyzed using tract-based spatial statistics. The severities of sensory problems were assessed using the Adolescent/Adult Sensory Profile (AASP).\n\nResultsCategorical analyses identified voxel clusters showing significant effects of DD on FA and RD in the posterior portion of the corpus callosum and its extension in the right hemisphere. Furthermore, regression analyses using the AASP scores revealed that slopes in relationships of FA or RD with the degree of sensory problems were parallel between the two DDs in large parts of the affected corpus callosum regions, although a small but significant cluster did exist showing interaction between the diagnosis of DD and an AASP subscale score on RD.\n\nConclusionsThese results indicate that white matter abnormalities and their relationships to sensory problems are largely shared between ASD and ADHD, with localized abnormalities showing significant between-diagnosis differences within DD. (247 words)

neuroscience↗

bioRxiv2019

Cortical surface architecture endophenotype and correlates of clinical diagnosis of autism spectrum disorder

AimPrior structural MRI studies demonstrated atypical gray matter characteristics in siblings of individuals with autism spectrum disorder (ASD). However, they did not clarify which aspect of gray matter presents the endophenotype. Further, because they did not enroll siblings of TD people, they underestimated the difference between individuals with ASD and their unaffected siblings. The current study aimed to solve these questions.\n\nMethodsWe recruited 30 pairs of adult male siblings (15 of them have an ASD endophenotype, other 15 pairs not) and focused on four gray matter parameters: cortical volume and three surface-based parameters (cortical thickness, fractal dimension, and sulcal depth [SD]). First, we sought to identify a pattern of an ASD endophenotype, comparing the four parameters. Then, we compared individuals with ASD and their unaffected siblings in the cortical parameters to identify neural correlates for the clinical diagnosis accounting for the difference between TD siblings.\n\nResultsA sparse logistic regression with a leave-one-pair-out cross-validation showed the highest accuracy for the identification of an ASD endophenotype (73.3%) with the SD compared with the other three parameters. A bootstrapping analysis accounting for the difference in the SD between TD siblings showed a significantly large difference between individuals with ASD and their unaffected siblings in six out of 68 regions-of-interest accounting for multiple comparisons.\n\nConclusionsThis proof-of-concept study suggests that an ASD endophenotype emerges in SD and that neural correlates for the clinical diagnosis can be dissociated from the endophenotype when we accounted for the difference between TD siblings. (248/250 words)

neuroscience↗

bioRxiv2018

Machine learning approach to identify resting-state functional connectivity pattern serving as an endophenotype of autism spectrum disorder

Endophenotype refers to a measurable and heritable component between genetics and diagnosis and exists in both individuals with a diagnosis and their unaffected siblings. We aimed to identify a pattern of endophenotype consisted of multiple connections. We enrolled adult male individuals with autism spectrum disorder (ASD) endophenotype (i.e., individuals with ASD and their unaffected siblings) and individuals without ASD endophenotype (i.e., pairs of typical development (TD) siblings) and utilized a machine learning approach to classify people with and without endophenotypes, based on resting-state functional connections (FCs). A sparse logistic regression successfully classified people as to the endophenotype (area under the curve=0.78, classification accuracy=75%), suggesting the existence of endophenotype pattern. A binomial test identified that nine FCs were consistently selected as inputs for the classifier. The least absolute shrinkage and selection operator with these nine FCs predicted severity of communication impairment among individuals with ASD (r=0.68, p=0.021). In addition, two of the nine FCs were statistically significantly correlated with the severity of communication impairment (r=0.81, p=0.0026 and r=-0.60, p=0.049). The current findings suggest that an ASD endophenotype pattern exists in FCs with a multivariate manner and is associated with clinical ASD phenotype.

neuroscience↗