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Biology subjects

Yang, I.

Publications and source records attributed to Yang, I..

12 recordsLinked to original sources
bioRxiv2026

Selective vulnerability of excitatory cortical neurons to ZMYND11 loss reveals cell-type-specific mechanisms of neurodevelopmental disorder risk

Excitation/inhibition (E:I) imbalance is a convergent mechanism in neurodevelopmental disorders (NDDs), yet whether NDD risk genes disrupt excitatory and inhibitory neurons through shared or distinct molecular programs remains poorly understood. Using human pluripotent stem cell-derived cortical projection and medial ganglionic eminence-like inhibitory neurons, we show that loss-of-function mutations in the chromatin reader ZMYND11 produce cell-type-selective vulnerability in cortical excitatory neurons. ZMYND11-deficient excitatory neurons exhibit hyperexcitability accompanied by de-repression of BMP signaling, dysregulation of glutamate receptor expression, and a shift toward non-brain splicing isoforms, whereas these molecular signatures are largely absent in ZMYND11-deficient inhibitory neurons. This cell-type selectivity is associated with differential upregulation of RBFOX family splicing regulators. Structure-function analysis reveals that MYND domain is required for normal progenitor dynamics and neuronal excitability. Together, these findings indicate that E:I imbalance in ZMYND11-associated NDD arises primarily from cell-type-selective vulnerability of excitatory cortical projection neurons and identify MYND domain as a critical determinant of neuronal function. HighlightsO_LIZMYND11-deficient excitatory neurons (ExNs) show hyperexcitability. C_LIO_LIAltered BMP signaling & glutamate receptor levels are implicated in mutant ExNs. C_LIO_LIInhibitory neurons show attenuated response to ZMYND11 loss. C_LIO_LIThe MYND domain in ZMYND11 is a critical regulator of neuronal excitability. C_LI

neuroscience↗
bioRxiv2026

Emotion Representation and Neural Synchrony: Decoding Valence and Arousal with Wearable EEG

Emotions are dynamic experiences that unfold over time, yet most affective neuroscience studies have relied on static stimuli and laboratory-based EEG systems. This study examined whether emotional valence and arousal can be reliably decoded using a consumer-grade wearable EEG device in naturalistic contexts. Forty-three participants viewed video clips designed to elicit four core affect categories including high-arousal positive, low-arousal positive, high-arousal negative, and low-arousal negative, while EEG signals were continuously recorded. Multivariate analyses, including classification, multidimensional scaling (MDS), and intersubject correlation (ISC), were employed to assess affective representation and neural synchrony. Behavioral data demonstrated robust classification of both valence and arousal, whereas EEG data yielded consistent above-chance classification of valence but less stable decoding of arousal, particularly in within-participant analyses. MDS revealed that both behavioral and EEG responses were primarily organized along the valence dimension, with weaker separation along arousal. ISC analyses further indicated frequency- and region-specific neural synchrony, with stronger alignment in left and temporal electrodes, though overall ISC values were modest, likely reflecting the brief duration of stimuli. Taken together, these findings suggest that valence is more stably represented in both subjective and neural domains, whereas arousal may require time-resolved or longer-duration approaches for reliable decoding. This work demonstrates the feasibility and limitations of employing wearable EEG for theory-driven affective neuroscience, underscoring its potential for scalable and ecologically valid emotion research beyond laboratory settings.

neuroscience↗
bioRxiv2025

High-resolution taxonomic profiling and metatranscriptomics identify microbial, biochemical, host and ecological factors in peri-implant disease

Biofilm-associated diseases like peri-implant mucositis (PIM) and peri-implantitis (PI) are significant clinical challenges affecting millions of dental implant patients globally. Although studies have described the role of microbial, host, or environmental factors in disease development, their complex interplay, particularly during dysbiosis remains poorly understood. This cross-sectional study characterized the microbiome composition and metatranscriptomes of 125 peri-implant biofilms from 48 individuals uncovering molecular signatures linked to peri-implant health (PIH), PIM, and PI. Distinct variations were observed in biofilm amount, composition, activity, phage populations and host response. Biofilms were categorized into four community types (CTs) based on the bacterial transcriptional activity: one linked to PIH, one to PI, and two to PIM. PIH and PIM were primarily characterized by aerotolerant taxa with increased anabolic processes, while PI was dominated by obligate anaerobes with complex biofilm morphology, and heightened catabolic activity and virulence. PIM samples, relative to PIH were characterized by biofilm expansion with minimal functional changes, except for the Neisseria-rich PIM subtype showing higher pyruvate and lipoic acid metabolism. The phagome mirrored the bacterial compositional variations across disease states. Furthermore, human transcriptome responses varied indicating increased keratinization in PIH, enhanced expression of ribosome components in PIM, and inflammatory signaling and hypoxia in PI. Additionally, we identified complex species-enzyme, phage-bacteria, and host-microbe associations within the peri-implant ecosystem. Our integrative multi-omics approach provides a comprehensive view of microbial, biochemical, host, and ecological factors associated with dysbiosis, offering novel insights into peri-implant disease dynamics. ImportancePeri-implant mucositis and peri-implantitis are highly prevalent inflammatory conditions that compromise the long-term survival and success of dental implants, yet their underlying biological mechanisms are largely unresolved. While next-generation sequencing has advanced our understanding of microbial composition across health and peri-implant diseases, it falls short of capturing microbial activity and the broader molecular context of peri-implant dysbiosis. Metatranscriptomics overcomes this limitation by profiling actively transcribed genes within the biofilm, offering direct insights into microbial community functions. In this study, we integrated full-length 16S rRNA gene amplicon sequencing with metatranscriptomic profiling to simultaneously assess microbial taxonomy, functional activity, phage dynamics, and host gene expression in peri-implant biofilms. Importantly, we provide a systems-level view and report previously undescribed associations between different molecular signatures in peri-implant ecosystem.

microbiology↗
bioRxiv2025

Invasive species drive polymicrobial resistance to amoxicillin in oral biofilms through beta-lactamase release

Since bacterial biofilms often cause refractory infections, antimicrobial susceptibility testing (AST) is highly desirable even for oral peri-implant biofilms. However, characterization of polymicrobial drug resistance is challenging due to high diversity and complexity of these biofilms. In this work, we developed laser-assisted AST and detected polymicrobial amoxicillin resistance in peri-implantitis. TEM-1 {beta}-lactamase production enabled an Enterobacter sp. strain SPS_532 to protect its otherwise susceptible biofilm cohabitants. To understand the {beta}-lactamase driven cross-protection in the human microbiome we aggregated genomic (n = 200,000) and patient microbial data (n = 27,000), developed a cross-protection assay, studied a representative strain collection (n = 118) and established a complex biofilm in vitro model (with an average of 133 species from 164 found in dental plaque). Multiple oral allochthonous species, e.g., Enterobacter, Klebsiella, Escherichia, Staphylococcus, and only a single typical oral microorganism, Haemophilus, were able to cross-protect. Diverse bla genes conferred activity, via a high expression of chromosomal gene, e.g., blaAmpC gene or by the presence of plasmidic gene, e.g., blaTEM-1 gene. Invaders not only cross-protected the biofilm from the antibiotic, but also supported expansion of opportunistic pathogens like Fusobacterium species. Cross-protection in complex biofilms depended on the diffusion rate and population size of the invader, which could be bio-controlled with a phage. Deciphering polymicrobial resistance might support the development of diagnostic and therapeutic approaches to combat implant-associated biofilm infections in the human mouth.

microbiology↗
bioRxiv2025

Integrative microbiome- and metatranscriptome-based analyses reveal diagnostic biomarkers for peri-implantitis

Peri-implantitis is a severe biofilm-associated infection of the tissues around dental implants that increases the risk of implant failure. The prognosis of peri-implantitis treatment is compromised by the resistance of well-organized and mature bacterial biofilms. Thus, early diagnosis of a pathogenic biofilm would enable treatment at a prognostically favourable stage. However, relatively little is known about how the microbial constitution of the biofilm changes during disease development. The aim of this cross-sectional study was therefore to identify peri-implant taxonomic and functional biomarkers that reliably indicate peri-implantitis using paired data from full length 16S rRNA gene amplicon sequencing (full-16S) and metatranscriptomics (RNAseq). Disease signatures were identified using 24 healthy and 24 peri-implantitis-associated biofilm samples from 32 patients. The taxonomic measurements were validated with 68 additional full-16S samples from another 40 patients. Both full-16S and RNAseq revealed significant differences between healthy and peri-implantitis samples, with respect to both the microbiome and functional profiles. A shift from aerotolerant Gram-positive bacteria to anaerobic Gram-negative bacteria was observed in peri-implantitis. Distinct metabolic pathways were expressed in healthy and peri-implantitis samples. Our results, based on paired taxonomic and functional profiles, provide for the first time important insights into the complex peri-implant biofilm ecology related to amino acid metabolism. Integrating taxonomic and functional information improved the predictive ability (AUC = 0.85) of the machine learning models and revealed diagnostic biomarkers with large effect sizes (Cohens d > 0.8). Primary biomarkers included health-associated Streptococcus, Rothia species and enzymes associated with peri-implantitis (urocanate hydratase, tripeptide aminopeptidase, NADH:ubiquinone reductase, phosphoenolpyruvate carboxykinase and polyribonucleotide nucleotidyltransferase - mostly expressed by Fusobacteriia and Bacteroidia). Thus, biofilm profiling at these two molecular levels reveals highly predictive disease biomarkers and provide the basis for developing early diagnostics and individualized therapy approaches for peri-implant diseases.

microbiology↗
bioRxiv2024

Associations between SARS-CoV-2 Infection or COVID-19 Vaccination and Human Milk Composition: A Multi-Omics Approach

The risk of contracting SARS-CoV-2 via human milk-feeding is virtually non-existent. Adverse effects of COVID-19 vaccination for lactating individuals are not different from the general population, and no evidence has been found that their infants exhibit adverse effects. Yet, there remains substantial hesitation among this population globally regarding the safety of these vaccines. Herein we aimed to determine if compositional changes in milk occur following infection or vaccination, including any evidence of vaccine components. Using an extensive multi-omics approach, we found that compared to unvaccinated individuals SARS-CoV-2 infection was associated with significant compositional differences in 67 proteins, 385 lipids, and 13 metabolites. In contrast, COVID-19 vaccination was not associated with any changes in lipids or metabolites, although it was associated with changes in 13 or fewer proteins. Compositional changes in milk differed by vaccine. Changes following vaccination were greatest after 1-6 hours for the mRNA-based Moderna vaccine (8 changed proteins), 3 days for the mRNA-based Pfizer (4 changed proteins), and adenovirus-based Johnson and Johnson (13 changed proteins) vaccines. Proteins that changed after both natural infection and Johnson and Johnson vaccine were associated mainly with systemic inflammatory responses. In addition, no vaccine components were detected in any milk sample. Together, our data provide evidence of only minimal changes in milk composition due to COVID-19 vaccination, with much greater changes after natural SARS-CoV-2 infection. IMPORTANCEThe impact of the observed changes in global milk composition on infant health remain unknown. These findings emphasize the importance of vaccinating the lactating population against COVID-19, as compositional changes in milk were found to be far less evident after vaccination compared to SARS-CoV-2 infection. Importantly, vaccine components were not detected in milk after vaccination.

molecular biology↗
bioRxiv2024

CCQM-P199: Interlaboratory comparability study of HIV-1 RNA copy number quantification

Infection with human immunodeficiency virus (HIV)-1 leads to acquired immunodeficiency syndrome (AIDS) if left untreated. According to UN figures, approximately 39 million people globally were living with HIV in 2022, with 76% of those individuals accessing antiretroviral therapy. Measurement of plasma viral RNA load using calibrated nucleic acid amplification tests (like reverse transcription quantitative PCR, RT-qPCR) is routinely performed to monitor response to treatment and ultimately prevent viral transmission. RNA quantities measured by commercial tests can vary over many orders of magnitude, from trace single copy levels to, in cases, over 109 /mL of plasma, presenting an analytical challenge for calibrating across a broad measurement range. Interlaboratory study CCQM-P199 "HIV-1 RNA copy number quantification" (April to September 2019) was conducted under the auspices of the Consultative Committee for Amount of Substance (CCQM) Nucleic Acid analysis Working Group (NAWG), with the aims of supporting national metrology institutes (NMIs) and designated institutes (DIs) development of the capacity and evaluating candidate reference measurement procedures for applied viral nucleic acid measurements. Thirteen laboratories participated in CCQM-P199 and were requested to report the RNA copy number concentration, expressed in copies per microliter, of the HIV-1 group specific antigen (gag) gene of in vitro transcribed RNA molecules at low ({approx} 103 /L) and high concentration ({approx} 109 /L) (Study Materials 1 and 2, linked by gravimetric dilution) and purified genomic RNA from cultured virus (Study Material 3). Study Materials 1 and 3 were measured by participants using one-step reverse transcription digital PCR (RT-dPCR) (Bio-Rad reagents) and/or two-step RT-dPCR with alternative cDNA synthesis reagents. Study Material 2 was measured by both RT-dPCR (one-step) (n = 4) and orthogonal methods: single molecule flow cytometric counting (n = 2), high performance liquid chromatograph (HPLC) (n = 1) and isotype dilution-mass spectrometry (ID-MS) (n = 1). Interlaboratory reproducibilities (expressed as %CV) were 21.4 %, 15.3 % and 22.0 % for Study Materials 1, 2 and 3 respectively. Analysis of overdispersion showed that the interlaboratory variation for all three Study Materials was not accounted for in their reported uncertainties, indicating uncharacterized sources of variation remain. Although the mean values of RT-dPCR and orthogonal method results were not statistically significantly different (p = 0.46), the extrapolated mean Study Material 2 results were higher than mean Study Material 1 results (1196 vs. 808 /L; p < 0.05). Follow-up analysis of Study Material 2 purity by ultra-performance liquid chromatography (UPLC) indicated higher molecular weight (MW) impurities constituted 16.6 % of the molecules, which are hypothesised to be the cause of the HPLC and ID-MS results being higher than the majority of Study Material 1 and 2 results. This study demonstrates that reproducible measurement of RNA templates was achieved by metrology laboratories, illustrating the potential of RT-dPCR combined with complimentary orthogonal approaches to support traceability and precision of contemporary methods for RNA quantification. This study also highlighted that detailed characterization of RNA materials and sources of bias affecting measurements such as RT efficiency is needed to further establish RT-dPCR as a primary reference measurement procedure for RNA copy number quantification.

molecular biology↗
bioRxiv2024

Unveiling lipid chemodiversity in root exudates: A comprehensive characterizaton of the exudate metabo-lipidome in Tall Wheatgrass

The rhizosphere, where plant roots meet soil, is a hub of biogeochemical activity with ecosystem impacts on carbon stocks. Root derived carbon has been found to contribute more to soil carbon stocks than aboveground litter. Nonetheless, the molecular chemodiversity of root exudates remains poorly understood due to limited characterization and annotation. Here our goal was to discover the molecular chemodiversity of metabolites and lipids in root exudates to advance our understanding of plant root inputs belowground. We worked with mature, field-grown tall wheatgrass (Thinopyrum ponticum) and optimized exudate collection protocols to enable the capture of non-polar lipids in addition to polar and semi-polar metabolites. Rates of carbon input via hydrophobic exudates were approximately double that of aqueous exudates and carbon/nitrogen ratios were markedly higher in hydrophobic compared to aqueous exudates, emphasizing the importance of lipids, due to their high carbon content. To maximize molecular coverage of exudate chemodiversity, we used liquid chromatography coupled tandem mass-spectrometry for paired untargeted metabolomics and lipidomics or metabo-lipidomics. We substantially increased the characterization of exudate chemodiversity by employing both tandem mass spectral library searching and deep learning-based chemical class assignment. Notably, in this unprecedented characterization of intact lipids in root exudates, we discovered a diverse variety of lipids, including substantial levels of triacylglycerols ([~]19 g/g fresh root per min), fatty acyls, sphingolipids, sterol lipids, and glycerophospholipids. Comparison of the root exudate and tissue lipidomes revealed minimum glycerophospholipids in exudates, suggesting the exudate protocol did not extract lipids from root cell membranes.

plant biology↗
bioRxiv2024

Targeting CD19 for the treatment of B-cell related autoimmune diseases with a novel T cell engager

Autoimmune disorder, affecting more than twenty million in United States and billions of people worldwide, occurs when human immune system mistakenly attacks its own body. Autoreactive B cells, particularly the autoantibodies they produce, play a critical role in the etiology, progress, prognosis, and pathogenesis of multiple autoimmune diseases. While targeting B cells medicines, such as anti-CD19 or anti-CD20 monoclonal antibodies have produced promise in both pre-clinic models and some clinic practices, many patients failed to respond, ended less satisfactory outcome, or relapsed to monoclonal antibody therapies. Novel therapies are desperately needed to fight this challenge. In this study, based upon a symmetrical format, namely fusion of IgG and scFv technology (FIST), an anti-CD19xCD3 T cell engager (TCE) YK012, developed to treat B-cell malignancies such as precursor pre-B acute lymphatic leukemia (ALL) and non-Hodgkins lymphoma (NHL), was expanded to explore the treatment of autoimmune diseases by bringing T cells to CD19 positive B cells, including autoreactive B cell populations. Even as bivalent binding to CD3, YK012 has so significantly reduced binding affinity to TCR compared to other TCEs that, free YK012 alone does activate T cells at all. In contrast, in the presence of CD19-expressing Raji target cells and mediated by YK012, T cells can be activated in a dose-dependent manner, measured by upregulation of NFAT-reporter, CD25, IFN-{gamma} and granzyme B expression. Crosslinking of B cell with T cell by YK012, the conjugation elicited T cell-mediated potent but mild cytotoxicity only to CD19-positive Raji cells. Additionally, YK012 elicited much reduced cytokines release in vitro compared to that of Blincyto(R) biosimilar, implying a potentially me-better therapeutics replacement in clinics for B-cell related diseases. In two in vivo pharmacological studies, YK012 alleviated the pathology symptoms of a collagen-induced arthritis model and almost completely depleted the peripheral B cell in human stem cell-transplanted murine model. In summary, this study demonstrated that YK012, a FIST platform designed TCE, has the potential to treat B cell-mediated diseases including autoimmune indications with possible better efficacy and less side effects in clinical practices.

immunology↗
bioRxiv2023

Fecal microbial transfer and complex carbohydrates mediate protection against COPD

ObjectiveChronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DesignUsing an in vivo mouse model of cigarette smoke-induced COPD and fecal microbial transfer (FMT), we characterized the fecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology, and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in sixteen COPD patients using a randomized, double-blind, placebo-controlled pilot study of inulin supplementation. ResultsFMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in cigarette smoke-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. ConclusionThe gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically. What is already known on this topicO_LIChanges in gut microbiota are associated with COPD but the underlying host and microbial mechanisms are unclear, limiting the therapeutic applications. C_LI What this study addsO_LIMicrobiome composition and metabolism is reproducibly correlated with lung and gastrointestinal pathology in experimental COPD. C_LIO_LIMicrobiome modifying interventions effectively alleviate disease, including protective effects supplementing smoking cessation. C_LIO_LINutritional interventions targeting the microbiome in COPD patients demonstrate efficacy in a small pilot study. C_LI How this study might affect research, practice or policyO_LIMicrobiome-targeting therapeutics and nutritional interventions may be developed for COPD, including as supplements to smoking cessation. C_LI

physiology↗
bioRxiv2019

Human Reference Genome and a High Contiguity Ethnic Genome AK1

Studies have shown that the current human reference genome (GRCh38) might miss information for some populations, but \"exactly what we miss\" is still elusive due to the lower contiguity of non-reference genomes. We juxtaposed the GRCh38 with high contiguity genome assemblies, AK1, to show that [~]1.8% ([~]53.4 Mbp) of AK1 sequences missed in GRCh38 with [~]0.76% ([~]22.2 Mbp) of ectopic chromosomes. The unique AK1 sequences harbored [~]1,390 putative coding elements. We found that [~]5.3Mb ([~]0.2%) of the AK1 sequences aligned and recovered the \"unmapped\" reads of fourteen individuals (5 East-Asians, 4 Europeans, and 5 Africans) as a reference. The regions that \"unmapped\" reads aligned included 110 common (shared between [&ge;]2 individuals) and 38 globally ([&ge;]7 individuals) missing regions with 25 candidate coding elements. We verified that many of the common missing regions exist in multiple populations and chimpanzees DNA. Our study illuminates not only the discovery of missing information but the use of highly precise ethnic genomes in understanding human genetics.

genomics↗