Biology subjects

Yao, A.

Publications and source records attributed to Yao, A..

8 recordsLinked to original sources

bioRxiv2026

A genome-wide catalog of sites where peripheral DNA methylation reflects the brain

Epigenetic studies of psychiatric and neurological disorders rely largely on peripheral tissues, yet where peripheral DNA methylation (DNAm) reflects the brain remains unclear. We generated a paired brain and peripheral DNAm dataset from 148 donors in three cohorts and combined it with five published cohorts for consensus brain-peripheral correlations. By cross-validation across cohorts, we defined brain epigenome shared sites (BrESS), more than 100,000 CpGs per tissue at which peripheral DNAm reproducibly predicts brain DNAm. BrESS lay at promoters active in both brain and periphery and in housekeeping genes, and most were not explained by genetic effects. BrESS did not contribute to the heritability of seven disorders, and CpGs from epigenome-wide association studies of these disorders were not enriched at BrESS. Peripheral DNAm reflects the brain mainly in a regulatory compartment shared across tissues, outside which disease signals largely lie, and BrESS separate peripheral signals attributable to the brain from others.

neuroscience↗

bioRxiv2026

Axial Patterning Beyond the Individual: Colony-level Organization in a Siphonophore Colony

Colonial animals composed of clonally produced units can achieve a high degree of functional integration, challenging the distinction between an individual and a higher-order organism. Siphonophores (Cnidaria: Hydrozoa) exemplify this condition, forming highly organized colonies in which genetically identical zooids are specialized for functions such as locomotion, feeding, and reproduction, and are precisely arranged along a shared stem. All zooids arise from two spatially separated budding zones, the nectosomal and siphosomal growth zones, suggesting that positional information along the stem patterns colony organization at the level of the colony rather than individual zooids. However, the molecular basis of this colony-level axial patterning remains poorly understood. Here, we analyze gene expression along the stem of the siphonophore Agalma okenii using RNA sequencing and in situ hybridization chain reaction (HCR). We show that conserved developmental regulators, including Hox and Wnt pathway genes, exhibit region-specific expression corresponding to distinct budding zones and zooid distributions. These results indicate that canonical axial patterning systems are deployed at the level of the colony axis. Our findings demonstrate that developmental gene networks classically associated with anterior-posterior patterning can operate at a higher level of biological organization, providing a mechanistic framework for the evolution of integrated, superorganism-like body plans in colonial animals.

developmental biology↗

bioRxiv2025

HIF1α controls somitogenesis and spine development by regulating levels of intracellular oxygen in the presomitic mesoderm

Embryonic axis extension depends on presomitic mesoderm (PSM) segmentation into somites, which give rise to vertebrae and muscles. The PSM is a highly glycolytic structure. HIF1 is a transcription factor that regulates bioenergetic metabolism by promoting glycolysis and suppressing mitochondrial respiration. Conditional deletion of HIF1 in the PSM resulted in vertebral malformations, including shortened, misshapen vertebrae and additional thoracic segments. These defects correlated with disrupted segmentation clock oscillations, marked by abnormal Hes7 and Lfng expression. HIF1 loss also induced intracellular hypoxia, likely due to increased mitochondrial respiration. Hyperoxic exposure of mutant embryos corrected hypoxia, restoring Hes7 oscillations and somitogenesis. These findings highlight HIF1s essential role in ensuring proper segmentation clock function and somitogenesis by maintaining intracellular oxygen homeostasis through reprogramming of metabolism.

developmental biology↗

bioRxiv2025

Histological transition during ovotestis formation in a female-to-male sex-change fish, the harlequin sandsmelt (Parapercis pulchella)

Many teleost fishes are capable of sex change, and some species possess intersex gonads known as ovotestes, which contain both ovarian and testicular tissues. Uncovering the developmental processes in ovotestis formation is critical for elucidating the mechanisms of intersexuality in vertebrates. However, such developmental processes have been described in only a limited number of species. In this study, we examined the histological structure of juvenile gonads in the harlequin sandsmelt (Parapercis pulchella), a female-to-male sex-change fish in which mature females possess ovotestes. Juveniles measuring up to 32.2 mm in total length exhibited gonads containing cyst-formed developing oogonia and a small number of oocytes. In contrast, larger juveniles possessed more developed ovaries but showed no detectable spermatogenic germ cells. These results suggest that gonads initially differentiate as ovaries and subsequently develop into ovotestes through the emergence of male germ cells. Together with previous studies, our results also indicate that a similar developmental sequence may be shared among sex-change fishes.

zoology↗

bioRxiv2024

Freshwater fish egg dispersal by attaching to waterbirds

Dispersal over geographic barriers plays an essential role in colonization, gene flow, metapopulation dynamics, and invasion (Bowler and Benton 2005). Since dry lands strictly separate freshwater habitats, as expressed by the phrase "islands of water in a sea of dry land" (Faulks, Gilligan, and Beheregaray 2010), dispersal among freshwater waterbodies by themselves is challenging of aquatic organisms. Rumors have existed worldwide that freshwater fish eggs are dispersed by attaching to (ectozoochory) or excretion from (endzoochory) waterbirds (Hirsch et al. 2018). It is well documented that waterbirds disperse aquatic plants, zooplankton, and various aquatic invertebrates, which are co-distributed with fishes (Green et al. 2023). However, there is only two reported cases of empirical evidence of endzoochory in freshwater fishes and no scientific evidence of ectozoochory (Hirsch et al. 2018; Silva et al. 2019; Lovas-Kiss et al. 2020; Green et al. 2023). Here, we show that the southern medaka (Oryzias latipes, hereafter medaka) egg can travel passively by attaching to waterbirds.

ecology↗

bioRxiv2021

Tear miRNAs identified in a murine model of Sjögren's Syndrome as potential diagnostic biomarkers and indicators of disease mechanism

ObjectiveThe tear miRNAome of the male NOD mouse, a model of ocular symptoms of Sjogrens syndrome (SS), was analyzed to identify possible tear biomarkers of the disease. MethodsMale NOD mice, aged 12-14 weeks, were used to identify tear miRNAs associated with development of autoimmune dacryoadenitis. Age-matched female NOD mice that do not develop the autoimmune dacryoadenitis characteristic of SS were used as negative controls while age- and sex-matched male BALB/c mice served as healthy controls. Total RNA was isolated from stimulated tears pooled from 5 mice per sample and tear miRNAs were sequenced and analyzed. Putative miRNA hits were validated using RT-qPCR in a separate mouse cohort, and the pathways influenced by the validated hits were identified using Ingenuity Pathway Analysis. ResultsIn comparison to tears from both healthy (male BALB/c) and negative control (female NOD) mice, initial analysis identified 7 upregulated and 7 downregulated miRNAs in male NOD mouse tears. Of these, 8 were subsequently validated by RT-qPCR in tears from additional mouse cohorts. miRNAs previously implicated in SS pathology included mmu-miR-146a/b-5p, which were significantly downregulated in the male NOD mouse tears, as well as mmu-miR-150-5p and mmu-miR-181a-5p, which were upregulated in the male NOD mouse tears. All other validated hits including the upregulated miR-181b-5p and mmu-miR-203-3p, as well as the downregulated mmu-miR-322-5p and mmu-miR-503-5p, represent novel putative indicators of autoimmune dacryoadenitis in SS. ConclusionsA panel of differentially expressed miRNAs were identified in tears of SS model male NOD mice, including some never previously linked to SS. These may have potential utility as diagnostic biomarkers for ocular symptoms of SS; evaluation of the pathways influenced by these dysregulated miRNAs may also provide further insights into SS pathogenesis.

immunology↗

bioRxiv2020

The Small GTPase OsRac1 forms two distinct immune receptor complexes containing the PRR OsCERK1 and the NLR Pit

Plants employ two different types of immune receptors, cell surface pattern recognition receptors (PRRs) and intracellular nucleotide-binding and Leucine-rich repeat-containing proteins (NLRs), to cope with pathogen invasion. Both immune receptors often share similar downstream components and responses but it remains unknown whether a PRR and an NLR assemble into the same protein complex or two distinct receptor complexes. We have previously found that the small GTPase OsRac1 plays key roles in the signaling of OsCERK1, a PRR for fungal chitin, and of Pit, an NLR for rice blast fungus, and associates directly and indirectly with both of these immune receptors. In this study, using biochemical and bioimaging approaches, we reveal that OsRac1 formed two distinct receptor complexes with OsCERK1 and with Pit. Supporting this result, OsCERK1 and Pit utilized different transport systems for anchorage to the plasma membrane. Activation of OsCERK1 and Pit led to OsRac1 activation and, concomitantly, OsRac1 shifted from a small to a large protein complex fraction. We also found that the chaperone Hsp90 contributed to the proper transport of Pit to the plasma membrane and the immune induction of Pit. These findings illuminate how the PRR OsCERK1 and the NLR Pit orchestrate rice immunity through the small GTPase OsRac1.Competing Interest StatementThe authors have declared no competing interest.View Full Text

plant biology↗

bioRxiv2019

Conservation of an Ancient Oxidation Response That Controls Archaeal Epigenetic Traits Through Chromatin Protein Networks

Epigenetic variants of the archaeon Sulfolobus solfataricus called SARC have evolved heritable traits including extreme acid resistance, enhanced genome integrity and a conserved \"SARC\" transcriptome related to acid resistance. These traits appear to result from altered chromatin protein function related to the heritable hypomethylation of chromatin proteins Cren7 and Sso7D. To clarify how this might occur, ChIPseq and Affinity Purification Mass Spectrometry (AP-MS) were used to compare Cren7 and Sso7D genome binding sites and protein networks between lineages (wild type and SARC) and culture pH (pH 1 and 3). All SARC transcriptome loci were bound by these chromatin proteins but with invariant patterns indicating binding alone was insufficient to mediate the SARC traits. In contrast, chromosome association varied at other loci. Quantitative AP-MS was then used to identify protein interaction networks and these included transcription and DNA repair proteins implicated in the evolved heritable traits that varied in abundance between SARC and wild type strains. Protein networks included most of the S-adenosylmethionine (SAM) synthesis pathway including serine hydroxymethyltransferase (SHMT), whose abundance varied widely with culture pH. Because epigenetic marks are coupled to SAM pools and oxidative stress in eukaryotes, occurrence of a similar process was investigated here. Archaeal SAM pools were depleted by treatment with SAM pathway inhibitors, acid or oxidative stress and, like eukaryotes, levels were raised by vitamin B12 and methionine supplementation. We propose that in archaea, oxidation-induced SAM pool depletion acting through an SHMT sensor, drove chromatin protein hypomethylation and thereby protein network changes that established the evolved SARC epigenetic traits.\n\nSignificance StatementArchaea and eukaryotes share many molecular processes, including chromatin-mediated epigenetic inheritance of traits. As with eukaryotes, archaeal protein complexes were formed between trait-related proteins and chromatin proteins, subject to chromatin protein methylation state. Oxidation-induced depletion of S-adenosylmethionine (SAM) pools likely resulted in chromatin protein hypomethylation. Subsequent chromatin enrichment of serine hydroxymethyltransferase as a response to oxidative stress could modulate methylation at specific genomic loci. The interplay between archaeal metabolism and chromatin appear consistent with patterns observed in eukaryotes and indicate the existence of an ancient oxidation signal transduction pathway controlling epigenetics.

microbiology↗