Biology subjects

Huang, I.

Publications and source records attributed to Huang, I..

11 recordsLinked to original sources

bioRxiv2026

An expansive animal gut microbiome dataset elucidates major compositional shifts across bilaterian evolution

Animal gut microbiomes provide key physiological functions and are critical for host health. They vary dramatically across the animal kingdom, and are shaped by factors including host diet, evolutionary history and environment. However, analyses of gut microbiomes spanning the entire metazoan clade are lacking, limiting our understanding of the fundamental principles governing gut microbiomes. Here we present the Gut Microbiome Tree of Life (GMToL), a curated 16S amplicon dataset of 17,366 samples from 1,553 host species across 26 host classes from 284 studies, enabling analysis of large-scale evolutionary trends. Using ancestral state reconstruction, we provide a critical baseline calculation of major compositional shifts in gut microbiomes throughout animal evolution. We show that the ancestral animal gut was likely dominated by Pseudomonadota. A major shift to Bacteroidota occurred during the evolution of tetrapods, followed by the emergence of Bacillota-dominated guts in mammals and birds. We identify conserved core gut microbes and demonstrate how GMToL can be leveraged to contextualize the evolutionary history of specific microbial taxa. Ultimately, this framework enables the predictive mapping of microbial symbionts across uncharacterized host lineages, and establishes a quantitative baseline for comparative microbiome research at scale.

microbiology↗

bioRxiv2026

HIRA-mediated H3.3 deposition preserves hepatocyte cell identity during liver aging

Age-associated functional decline is partly driven by progressive chromatin degeneration. Maintenance of chromatin integrity preserves cell identity and promotes healthy aging, but through different mechanisms in proliferating and non-proliferating cells. However, specific mechanisms of chromatin maintenance and their compensatory capacity in proliferating and non-proliferating cells are undefined. The histone chaperone HIRA deposits the histone variant H3.3 in a DNA replication-independent manner, leading to its accumulation in aging, non-proliferating cells. Here, we show that hepatocyte-specific loss of HIRA causes loss of cell identity, metabolic dysfunction, and accelerated fibrotic pathology with age. Transcriptomic and epigenomic analyses indicate that HIRA-H3.3 preserves chromatin integrity and sustains transcription of highly expressed genes, including cell identity genes. Partial hepatectomy, associated with induced proliferation, restores identity of HIRA knockout livers with compensatory deposition of canonical histones H3.1/2. Together, these results demonstrate that HIRA-mediated H3.3 deposition is essential for safeguarding cell identity and tissue function during aging of non-proliferating cells, but this function can be rescued by tissue regeneration and associated cell proliferation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/710643v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@a2a26aorg.highwire.dtl.DTLVardef@154e5aeorg.highwire.dtl.DTLVardef@b315a7org.highwire.dtl.DTLVardef@152bca4_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2025

Post-Ictal Gamma Oscillations Predict Hippocampal Structural Integrity in Mesial Temporal Lobe Epilepsy

The underlying histopathology and epileptic network of patients with mesial temporal lobe epilepsy (mTLE) are difficult to ascertain. Here, we report a novel electrical activity following seizure termination, termed post-ictal gamma oscillations (PIGOs), recorded in mice with intrahippocampal kainic acid injection and a patient with mTLE. PIGOs are characterized by a spectral shift of increased power in gamma frequencies relative to decreased power in other frequencies, generating a gamma peak. PIGOs are accompanied by increased intracellular calcium levels among parvalbumin-positive interneurons and a direct current shift. Only a subgroup of animals in the study had PIGOs. These animals had less pronounced hippocampal sclerosis (HS) than those without PIGOs. To illustrate the translational potential of these findings, we analyzed data from two patients with unilateral mTLE, one with PIGOs and the other without. The patient with PIGOs had symmetrical hippocampi on neuroimaging, whereas the other exhibited overly decreased interictal glucose uptake in left hippocampus, suggesting left-sided HS. After receiving laser ablation of mesial temporal regions, the patient with PIGOs became seizure-free, whereas the other did not. Our results suggest that PIGOs may serve as a biomarker for a milder form of HS in patients with mTLE and for predicting treatment outcomes.

neuroscience↗

bioRxiv2024

Order among chaos: high throughput MYCroplanters can distinguish interacting drivers of host infection in a highly stochastic system

While microbiomes provide diverse benefits for their host, they are notoriously variable in structure and function. As a result, substantial experimental replication and scalability are required to identify the contributions of and interactions between microbiota, the host and the environment. Here, we describe a novel high throughput plant growth system (MYCroplanters) to test how multiple host, microbiota, and pathogen variables predict host health. Using an Arabidopsis-Pseudomonas host-microbiome-pathogen model, we found that host genotype and order of arrival predict competition outcome between strains in the rhizosphere, but pathogen and microbiota dose can overwhelm these effects. Regardless of host or inoculation conditions, final microbial community structure emerged as a consistent predictor of host health. We demonstrate that high-throughput tools like MYCroplanters can isolate interacting drivers of host health. Increasing the scale at which we can screen components of microbiome-mediated host benefits will facilitate building microbiome engineering solutions for medicine and agricultural applications.

ecology↗

bioRxiv2024

Breaking free from the clocks tyranny restores memory to brain damaged flies

The relationship between sleep and memory is an active topic of investigation. In this context, we demonstrate that enhancing sleep restores memory to flies with ablated Mushroom Bodies (MB), a key memory center; this is consistent across several memory assays. Mapping the underlying circuitry reveals circadian modulation of a subset of Dopaminergic neurons (DANs) that modulate aversive learning. Using imaging, we show that MB-ablation disrupts, and sleep restores the time of day these neurons are most responsive. Knocking down the receptor for the clock output signal, Pigment-dispersing factor (Pdfr), in this subset of DANs restores memory to MB-ablated flies. Crucially, MB-ablation does not result in memory impairments in the absence of a functioning clock. Our results reveal neuromodulations key role in cognitive restoration, where sleep aids memory in damaged brains, but a functioning clock unexpectedly hinders this process.

neuroscience↗

bioRxiv2023

Distinct and interdependent functions of three RING proteins regulate recombination during mammalian meiosis

During meiosis, each pair of homologous chromosomes becomes connected by at least one crossover, as required for accurate segregation at the first division, and adjacent crossovers are widely separated thereby limiting total numbers. In coarsening models, crossover patterning results from nascent recombination sites competing to accrue a limiting pro-crossover RING-domain protein (COR) that diffuses between synapsed chromosomes. Here we delineate the localization dynamics of three mammalian CORs in mouse and determine their interdependencies. RNF212, HEI10 and a new member RNF212B show divergent spatiotemporal dynamics along synapsed chromosomes, including profound differences in spermatocytes and oocytes, that are not easily reconciled by elementary coarsening models. Contrasting mutant phenotypes and genetic requirements indicate that RNF212B, RNF212, and HEI10 play distinct but interdependent functions in regulating meiotic recombination and coordinating the events of meiotic prophase-I by integrating signals from DNA breaks, homolog synapsis, the cell-cycle, and incipient crossover sites. SIGNIFICANCEMeiosis produces haploid gametes by precisely halving the chromosome complement. Crossing over between homologous chromosomes (homologs) is essential for their accurate segregation and defects are associated with infertility, miscarriage, and congenital disease. Factors that ensure crossing over between each pair of homologs include mammalian RING-domain proteins RNF212, HEI10, and RNF212B, alleles of which are linked to infertility and heritable variation in crossover rate. This study focuses on understanding the functions and relationships between pro-crossover RING proteins (CORs) in mouse, providing important insights into their roles in regulating recombination, the DNA repair process that gives rise to crossovers. Notably, chromosomal localization dynamics of the three CORs are distinct and show striking sexual dimorphism with important implications for models of crossover control.

genetics↗

bioRxiv2023

Sleep Deprivation, Sleep Fragmentation and Social Jet Lag increase temperature preference in Drosophila

Despite the fact that sleep deprivation substantially affects the way animals regulate their body temperature, the specific mechanisms behind this phenomenon are not well understood. In both mammals and flies, neural circuits regulating sleep and thermoregulation overlap, suggesting an interdependence that may be relevant for sleep function. To investigate this relationship further, we exposed flies to 12 h of sleep deprivation, or 48 h of sleep fragmentation and evaluated temperature preference in a thermal gradient. Flies exposed to 12 h of sleep deprivation chose warmer temperatures after sleep deprivation. Importantly, sleep fragmentation, which prevents flies from entering deeper stages of sleep, but does not activate sleep homeostatic mechanisms nor induce impairments in short-term memory also resulted in flies choosing warmer temperatures. To identify the underlying neuronal circuits, we used RNAi to knock down the receptor for Pigment dispersing factor, a peptide that influences circadian rhythms, temperature preference and sleep. Expressing UAS-PdfrRNAi in subsets of clock neurons prevented sleep fragmentation from increasing temperature preference. Finally, we evaluated temperature preference after flies had undergone a social jet lag protocol which is known to disrupt clock neurons. In this protocol, flies experience a 3 h light phase delay on Friday followed by a 3 h light advance on Sunday evening. Flies exposed to social jet lag exhibited an increase in temperature preference which persisted for several days. Our findings identify specific clock neurons that are modulated by sleep disruption to increase temperature preference. Moreover, our data indicate that temperature preference may be a more sensitive indicator of sleep disruption than learning and memory.

neuroscience↗

bioRxiv2022

Avian and Human Influenza Viruses Exhibit Distinct Glycoconjugate Receptor Specificities in Human Lung Cells

IAV utilize sialic acid (Sia) containing cell surface glycoconjugates for host cell infection, and IAV strains from different host species show preferences for structurally distinct Sia at the termini of glycoconjugates. Various types of cell surface glycoconjugates (N-glycans, O-glycans, glycolipids) display significant diversity in both structure and carbohydrate composition. To define the types of glycoconjugates that facilitate IAV infection, we utilized the CRISPR/Cas9 technique to truncate different types of glycoconjugates, either individually or in combination, by targeting glycosyltransferases essential to glycan biosynthesis in a human lung epithelial cell line. Our studies show that both human and avian IAV strains do not display strict preferences for a specific type of glycoconjugate. Interestingly, truncation of all three types of glycoconjugates significantly decreased the replication of human IAV strains, yet did not impact the replication of avian IAV strains. Taken together, our studies demonstrate that avian IAV strains utilize a broader repertoire of glycoconjugates for host cell infection as compared to human IAV strains. Author SummaryIt is well known that influenza A viruses (IAV) initiate host cell infection by binding to sialic acid, a sugar molecule present at the ends of various sugar chains called glycoconjugates. These glycoconjugates can vary in chain length, structure, and composition. However, it remains unknown if IAV strains preferentially bind to sialic acid on specific glycoconjugates for host cell infection. Here, we utilized CRISPR gene editing to abolish sialic acid on different glycoconjugate types in human lung cells, and evaluated human versus avian IAV infections. Our studies show that both human and avian IAV strains can infect human lung cells by utilizing any of the three major sialic acid-containing glycoconjugate types, specifically N-glycans, O-glycans, and glycolipids. Interestingly, simultaneous elimination of sialic acid on all three glycoconjugate types in human lung cells dramatically decreased human IAV infection, yet had little effect on avian IAV infection. Our studies indicate that avian IAV strains can utilize a wide variety of glycoconjugates for infection, whereas human IAV strains display restrictions in glycoconjugate type usage. These novel studies show distinct differences in host glycoconjugate preferences between human and avian IAV strains.

microbiology↗

bioRxiv2022

Firefly-inspired vocabulary generator for communication in multi-agent systems

Fireflies dazzling light displays are courtship rituals: flying males announce their presence as suitable mates to the females on the ground. Their light signal is composed of a species-specific on/off light sequence repeated periodically. However, thousands of fireflies flashing in a swarm can create immense visual clutter that hinders the detection of potential mates. A partial solution to this visual clutter problem is to flash according to sequences that are more distinct and detectable than those of other individuals. Here, we investigate how distinguishable flash sequences can co-evolve by developing a method for simulating sequences that minimize their mutual similarity with each other while minimizing their energetic cost and predation risk. This simple set of rules produces flash sequences that are remarkably similar to those of real fireflies. In particular, we observe an emergent periodicity in the resulting sequences, despite the lack of any periodicity requirements on the sequences. In addition, we demonstrate a method of reconstructing the evolutionary pressures acting on sets of firefly species. We do so by carrying out simulations that follow known phylogenetic relationships of extant species alongside their characteristic flash patterns.

animal behavior and cognition↗

bioRxiv2021

Host Factor Rab11a is Critical for Efficient Assembly of Influenza A Virus Genomic Segments

It is well documented that influenza A viruses selectively package 8 distinct viral ribonucleoprotein complexes (vRNPs) into each virion; however, the role of host factors in genome assembly is not completely understood. To evaluate the significance of cellular factors in genome assembly, we generated a reporter virus carrying a tetracysteine tag in the NP gene (NP-Tc virus) and assessed the dynamics of vRNP localization with cellular components by fluorescence microscopy. At early time points, vRNP complexes were preferentially exported to the MTOC; subsequently, vRNPs associated on vesicles positive for cellular factor Rab11a and formed distinct vRNP bundles that trafficked to the plasma membrane on microtubule networks. In Rab11a deficient cells, however, vRNP bundles were smaller in the cytoplasm with less co-localization between different vRNP segments. Furthermore, Rab11a deficiency increased the production of non-infectious particles with higher RNA copy number to PFU ratios, indicative of defects in specific genome assembly. These results indicate that Rab11a+ vesicles serve as hubs for the congregation of vRNP complexes and enable specific genome assembly through vRNP:vRNP interactions, revealing the importance of Rab11a as a critical host factor for influenza A virus genome assembly.

microbiology↗

bioRxiv2019

Recombinant Expression of Aldehyde Dehydrogenase 2 (ALDH2) in Escherichia coli Nissle 1917 for Oral Delivery in ALDH2-Deficient Individuals

Turning red after consuming alcohol may seem like a mere social inconvenience. Yet, this flushing response is caused by an accumulation of acetaldehyde, a carcinogenic intermediate of alcohol metabolism. Aldehyde dehydrogenase 2 (ALDH2) deficiency, the result of a point mutation, produces a less efficient ALDH2. The resulting accumulation of acetaldehyde greatly increases the risk of developing esophageal and head and neck cancers. In this study, we produced recombinant ALDH2 in the probiotic E. coli Nissle 1917, which successfully reduces acetaldehyde levels in simulated oral conditions. Packaged in a hard candy, the ALDH2-probiotic would remain in the mouth to specifically target salivary acetaldehyde. Using mathematical modeling, we also determined how much recombinant ALDH2 is needed to reduce elevated acetaldehyde levels.\n\nFinancial DisclosureThis work was funded by Taipei American School. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\n\nCompeting InterestsThe authors have declared that no competing interests exist.\n\nEthics StatementN/A\n\nData AvailabilityYes - all data are fully available without restriction. Sequences for the plasmids used in this study are available through the Registry of Standard Biological Parts. Links to raw data are included in Supplementary Information.

synthetic biology↗