Biology subjects

Kang, G.

Publications and source records attributed to Kang, G..

At least 19 recordsLinked to original sources

bioRxiv2026

OMICON: a community resource for studying gene coexpression networks in normal and neoplastic human brain samples

Genome-wide coexpression analysis of intact tissue samples is a powerful approach for identifying reproducible signatures of cell types and states, since it can survey vast numbers of individuals, cells, and transcripts. However, it can be difficult to optimize gene coexpression network construction and compare results from independent analyses. To address these challenges, we developed OMICON (theomicon.ucsf.edu) for research on human brain gene coexpression networks. OMICON contains gene expression data from >17K normal and neoplastic human brain samples with standardized metadata. Systematic analysis of independent datasets identified >250K gene coexpression modules, which were characterized and compared via enrichment analysis with >40K gene sets. All modules are discoverable via an advanced search engine that can filter by genes, metadata, and enrichment results. Analyses can also be browsed with an interactive workflow visualization tool, and users can communicate within OMICON using @mention functionality to support communal research on human brain gene coexpression networks.

neuroscience↗

bioRxiv2026

Tau-Mediated Cytoskeletal Stabilization Modulates Cell Mechanics and Vulnerability to Mechanical Strain

Cells experience mechanical loading across a broad range of loading rates, from low strain rates that are generated during morphogenesis and tissue remodelling, to high and injurious strain rates that are sustained during ventilation-induced lung injury, blast-induced injury, and impact-induced traumatic brain injury. Cell survival under high strain rate loading conditions depends on the ability of the cytoskeleton and plasma membrane to sustain mechanical load without permanent damage. The activity of different cytoskeletal and membrane regulatory proteins could therefore modulate cell susceptibility to injury, but the underlying mechanisms of injury at high strain rate are poorly understood. Tau is a microtubule-associated protein best known for its role in stabilizing microtubules in neurons and as a marker of neurodegenerative disease. Here, we investigated how Tau expression, phosphorylation, and microtubule binding modulates cell viscoelastic behaviour and membrane integrity during high strain-rate uniaxial stretch. We show that Tau expression and de-phosphorylation stabilize microtubules and causes increases in cell stiffness, suppresses cytoskeletal fluidity, and heightens susceptibility to stretch-induced membrane poration. Interestingly, we also find that these effects cannot be explained by microtubule stabilization by Tau alone. Actin architecture acts as a key determinant of injury vulnerability at high strain rate, highlighting the importance of cytoskeletal fluidity and microtubule-actin crosstalk for rapid force dissipation. Significance StatementCells must rapidly adapt to mechanical stress during high strain rate deformation. This study shows that Tau, a microtubule-associated protein, modulates cellular mechanics by increasing stiffness, decreasing viscoelastic fluidity, and enhancing susceptibility to membrane poration under rapid stretch. While Tau-mediated microtubule stabilization contributes to these effects, actin architecture and microtubule-actin crosstalk are also critical determinants of injury vulnerability in Tau-expressing cells.

biophysics↗

bioRxiv2026

Circulating miR-10b-5p drives Kawasaki vasculitis through endothelial reprogramming and nominates CXCL8 as an early diagnostic biomarker

BackgroundKawasaki disease (KD) is an acute systemic vasculitis of unknown etiology and the leading cause of acquired heart disease in children. Coronary artery aneurysm formation represents its most serious complication, yet no specific biomarker exists for early diagnosis at emergency department (ED) presentation. We sought to define the molecular mechanisms driving KD vasculitis and to identify a clinically actionable early diagnostic marker. MethodsWhole microRNA sequencing was performed on buffy coat specimens from KD patients and febrile controls presenting to the ED. Disease-associated miRNA candidates were validated in two independent murine KD-like vasculitis models: Lactobacillus casei cell wall extract (LCWE; n=12-20) and Candida albicans water-soluble fraction (CAWS; n=12). The functional role of miR-10b-5p was assessed by antagomir-mediated inhibition in the LCWE model. Transcriptomic and chromatin-level reprogramming were characterized by single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, and assay for transposase-accessible chromatin with sequencing (ATAC-seq) in human coronary artery endothelial cells (HCAECs). Transcription factor binding was validated by in vitro binding assays and chromatin immunoprecipitation. Serum chemokine (C-X-C motif) ligand 8 (CXCL8) was quantified by enzyme-linked immunosorbent assay. ResultsForty miRNAs were upregulated in KD patients and fourteen miRNAs were prioritized for further analysis. miR-10b-5p was consistently elevated across both vasculitis models, and its antagomir-mediated inhibition attenuated aortic root inflammation in vivo. In HCAECs, miR-10b-5p suppressed its direct targets marker of proliferation Ki-67 (MKI67)/Chromobox5 (CBX5), driving a cell-state transition from proliferative/metabolic programs toward a pro-inflammatory phenotype. Consistently, analyses of bulk RNA-seq supported cell-cycle arrest and altered chromatin remodeling. ATAC-seq revealed increased chromatin accessibility at the CXCL8 and Matrix metalloproteinases 10 (MMP10) promoters, and motif analysis identified CCAAT/enhancer-binding protein alpha (CEBPA) as the key transcriptional activator; CEBPA knockdown abrogated miR-10b-5p-induced CXCL8 and MMP10 upregulation. Serum CXCL8 was markedly elevated in KD patients relative to febrile controls at first ED presentation, prior to definitive diagnosis, and declined significantly at 8-week follow-up. ConclusionsWe define a miR-10b-5p-MKI67/CBX5-CEBPA-CXCL8 axis as a mechanistic driver of endothelial reprogramming and neutrophil-recruiting inflammation in KD. Serum CXCL8 emerges as a candidate early diagnostic biomarker that may facilitate timely KD recognition at ED presentation.

molecular biology↗

bioRxiv2026

Biophysical trade-offs in antibody evolution are resolved by conformation-mediated epistasis

Protein evolution is constrained by multidimensional biophysical factors, in which mutations that enhance one property often compromise another. Antibodies represent an extreme case: they evolve rapidly to bind diverse antigens, yet mutations that improve affinity can disrupt folding, reduce cell-surface trafficking, or promote self-reactivity, and are typically selected against during affinity maturation. Though biophysical characterization of individual antibodies suggests that such trade-offs are pervasive, their impact on antibody evolutionary trajectories remains unclear, in part because existing high-throughput biophysical methods rely on heterologous systems that are often poorly suited for human proteins. Here, we develop a high-throughput platform to quantify multiple biophysical parameters of large libraries of full-length proteins that are natively synthesized, processed, and displayed on human cells. We apply this approach to a human antibody lineage that matures to recognize divergent SARS-CoV-2 variants by measuring the surface expression, antigen affinity, and self-reactivity for all 213 possible evolutionary intermediates between the unmutated and mature sequences. These measurements reveal that mutations differentially affect these biophysical properties - in some cases, improving one property at the expense of another. We leverage these data to compute the likelihood of all possible evolutionary paths, finding that very few paths can navigate these multidimensional requirements. The few accessible paths acquire mutations in a specific order that either circumvent trade-offs between biophysical properties or offset deleterious effects on one property with beneficial effects on another. By determining the structures of the ancestral and evolved antibodies, we find that these coordinated mutational effects arise from a conformational rearrangement that alleviates steric clashes and reshapes the biophysical landscape, enabling otherwise inaccessible mutational paths. Together, this work defines the multidimensional biophysical constraints and structural mechanisms that govern antibody evolution and establishes a general framework for mapping and predicting the biophysical effects of mutations in human proteins.

evolutionary biology↗

bioRxiv2026

Neonatal social communication and single genes predict the variability of post-pubertal social behavior in a mouse model of paternal 15q11-13 duplication

Mental illnesses associated with high-risk copy number variations (CNVs) are characterized by incomplete penetrance and variable severity, with their underlying mechanisms remaining inadequately understood. We hypothesized that such phenotypic variability is evident from the neonatal stage and is, at least in part, attributable to individual differences in the expression levels of CNV-encoded genes in the brain. We conducted an analysis of the quantitative and functional structure of neonatal social communication, assessed post-pubertal social interaction, and evaluated the brain expression levels of genes within the same cohort of a mouse model of paternal human 15q11-13 duplication, a high-risk factor variably associated with neurodevelopmental disorders. Subsequently, computational methods were utilized to identify predictive variables for the variability of post-pubertal social interaction. Mice harboring the 15q11-13 duplication exhibited distinctive call sequences characterized by diverse connections, which lacked the incentive value necessary for effective social communication with mother mice. The neonatal call sequences and the expression levels of Magel2, along with, to a lesser extent, Herc2 and Ndn, in the prefrontal cortex of the 15q11-13 duplication model were predictive of post-pubertal social interaction. Our findings demonstrate that variability in post-pubertal social interaction--a dimensional characteristic of neurodevelopmental disorders--can be predicted by the variability of neonatal social communication and is influenced by the expression levels of specific CNV-encoded genes in the prefrontal cortex. This computational approach has the potential to predict the developmental trajectories of various dimensions of mental illness among CNV carriers in humans and to identify CNV-encoded driver genes in preclinical models, thereby providing potential mechanistic bases for the development of gene-based therapeutic strategies.

neuroscience↗

bioRxiv2025

Tbx1 heterozygosity in the oligodendrocyte lineage has distinct effects on myelinated axons in the fimbria and on behaviors related to neurodevelopmental disorders in mice.

Constitutive heterozygosity of Tbx1, a T-box transcription factor gene located within the 22q11.2 deletion region, results in behavioral deficits and altered composition of myelinated axons in the fimbria, together with reduced levels of an oligodendrocyte precursor cell (OPC) marker, in mice. However, the cellular origins of these effects and the extent to which axonal changes causally contribute to behavioral impairments remain unclear. We hypothesized that Tbx1 deficiency specifically within the oligodendrocyte lineage contributes to myelin and behavioral phenotypes. To test this hypothesis, we first demonstrated through in vitro siRNA knockdown that Tbx1 regulates both OPCs and mature oligodendrocytes. Subsequently, we assessed the impact of Tbx1 heterozygosity initiated in OPCs on behavioral and myelin phenotypes in male conditional PdgfrCre;Tbx1+/flox mice. These mice exhibited Cre-mediated recombination in Pdgfr-expressing brain regions and in the OPC progeny within the fimbria. At one month of age, the mutants displayed a higher rate of spontaneous alternation at the longest inter-trial interval in the T-maze compared to their wild-type littermates--an effect that was dissipated at two months. No significant phenotypic abnormalities were observed in conditional PdgfrCre;Tbx1+/flox mice regarding neonatal ultrasonic vocalizations, social interaction, novel object approach, anxiety-like behavior (elevated plus maze), or open-field locomotion and thigmotaxis. Electron microscopic analysis revealed a compositional shift in myelinated axons within the fimbria of adult male mutants, characterized by an increased number of myelinated axons in the 300-800 nm diameter range and a decreased number in the [~]1,200 nm and [~]1,400 nm ranges, with myelin thickness remaining unchanged across diameters. These findings indicate that Tbx1 heterozygosity in the oligodendrocyte lineage leads to a selective shift towards smaller myelinated axons in the fimbria and a transiently higher level of capacity for working memory and cognitive flexibility. However, it does not replicate the full spectrum of myelination abnormalities or the broader cognitive and social deficits observed in constitutive Tbx1 heterozygotes, suggesting that Tbx1 deficiency in non-oligodendrocyte lineage cells may lead to altered myelination and neurodevelopmental behavioral impairments.

neuroscience↗

bioRxiv2025

Conserved early steps of stemmadenine biosynthesis

Stemmadenine acetate is a pivotal intermediate in the production of pharmacologically active monoterpene indole alkaloids. Here, we identify orthologs of stemmadenine acetate pathway genes (SGD, GS, GO, Redox1, Redox2, SAT) from Tabernanthe iboga. We characterize these enzymes in vitro, and additionally, we reconstitute stemmadenine acetate biosynthesis in Nicotiana benthamiana, comparing the formation of intermediates and shunt products that are produced when previously characterized orthologs from the related plant Catharanthus roseus are used. Ortholog pairs are catalytically indistinguishable, except in the case of GS. Surprisingly, the T. iboga ortholog catalyzes formation of an alternate stereoisomer 19Z-geissoschizine, seeding a low-flux Z-series in heterologous reconstitution systems in vitro and in planta. We additionally characterize the major shunt products that arose during reconstitution of stemmadenine acetate biosynthesis. We show that the substrate promiscuity of Redox2 results in formation of the shunt products 16(R/S)-isositsirikines, hampering pathway flux and yields. Additionally, we show that stemmadenine can be oxidized by endogenous N. benthamiana enzymes, leading to the shunt product condylocarpine. Nevertheless, we could produce stemmadenine at a 6 mg yield from 19E-geissoschizine by heterologous expression in N. benthamiana. Overall, we highlight the prospects for milligram production of important biosynthetic intermediates in N. benthamiana.

biochemistry↗

bioRxiv2025

An extensive forward genetic screen identifies the HWS-AGO1 axis as pivotal for target mimicry-mediated miRNA degradation in Arabidopsis

Target RNAs have emerged as key regulators of miRNA stability, thereby influencing development and physiological processes in both plants and animals. The F-box protein HAWAIIAN SKIRT (HWS) has been characterized as a crucial factor in targeted miRNA degradation in plants (pTMD), a process triggered by a specific type of target RNA called target mimicry. However, the precise mechanism by which HWS functions is still poorly understood. We previously established a genetic reporter system based on Short Tandem Target Mimicry of miR160 (STTM160) triggered miR160 degradation, resulting in pleiotropic developmental defects that are easy to monitor. Here, through an extensive forward genetic screen, we identified fourteen additional hws alleles that near-completely restored STTM160-induced developmental defects, highlighting a central role for HWS in pTMD. Intriguingly, we discovered two adjacent amino acid substitutions (R421K and G422D) in the PAZ domain of AGO1 that significantly suppressed the STTM160 phenotype. Similar to HWS dysfunction, the AGO1 R421K substitution caused a significant retention of target mimicry RNAs in AGO1 immunoprecipitates, suggesting that the R421 residue of AGO1 may cooperate with HWS for the clearance of AGO1-miRNA-target mimicry complexes. Although the R/G mutations only impacted a small set of endogenous miRNA levels, they were sufficient to rescue the developmental defects caused by HWS overexpression (HWS-OE), suggesting that the developmental abnormalities caused by HWS-OE largely depend on the AGO1-miRNA pathway. Taken together, our findings provide a solid genetic evidence for the coordination of HWS and AGO1 in pTMD.

plant biology↗

bioRxiv2025

Cortical organoids reveal human-specific roles of METTL5 in neurodevelopment via regulation of CHCHD2

METTL5 is a conserved methyltransferase responsible for catalyzing N6-methyladenosine (m6A) modification on 18S ribosomal RNA. Human patients with mutations in METTL5 show severe microcephaly and intellectual disability, which has not been fully recapitulated in animal models. Given its emerging role in neurodevelopment, we sought to investigate METTL5 function in a human-specific context using cortical forebrain organoids derived from human induced pluripotent stem cells. We generated METTL5 knockout organoids and observed a marked delay in neural stem cell proliferation and the timing of neuronal differentiation, suggesting a critical role for METTL5 in the temporal regulation of neurogenesis. Though METTL5 methylates rRNA near the decoding center, the mechanism of this methylation remains highly contested. In our cortical organoids, broad translational changes mirror stress response rather than transcript-specific regulation of translation. Transcriptomic analysis further revealed a significant downregulation of CHCHD2, a nuclear-encoded mitochondrial gene linked to cellular energy metabolism and neurodevelopmental processes. Overexpression of CHCHD2 rescued proliferation defects of METTL5-KO neural progenitor cells, suggesting dysregulation of CHCHD2 is heavily involved in the phenotypes of METTL5 mutant patient brains. These findings highlight a previously uncharacterized link between METTL5, ribosomal RNA modification, and cellular metabolism essential for proper human brain development.

molecular biology↗

bioRxiv2025

Dimethyl fumarate reprograms cervical cancer cells to enhance antitumor immunity by activating mtDNA-cGAS-STING pathway

BackgroundCervical cancer (CC) remains a significant global health challenge for women, especially in advanced stages where effective treatments are limited. Current immunotherapies, including PD-1/PD-L1 blockades and adoptive T cell therapies, show limited response rates and durability. Dimethyl fumarate (DMF), an FDA-approved drug for autoimmune diseases, has demonstrated that it might exhibit direct antitumor activity in several cancers. However, its influence on anti-tumor immunity and its function in CC remain poorly understood. This study aims to investigate the therapeutic potential of DMF in CC models and elucidate its underlying mechanisms of action. MethodsCC cell lines and mouse models were treated with DMF. Transcriptional level changes in cervical cancer cells following DMF treatment were analyzed by RNA-seq. Mitochondrial DNA (mtDNA) release, and cGAS-STING activation were assessed via qPCR, immunofluorescence, immunoblotting and ELISA. CD8+ T cell recruitment was analyzed by flow cytometry. Combinatorial therapies (DMF + anti-PD-1/TILs) were tested in syngeneic or patient-derived xenografts (PDX) models. ResultsDMF treatment induces mitochondrial dysfunction in tumor cells, resulting in the release of mtDNA into the cytosol. The cytosolic mtDNA activates the cGAS-STING-TBK1 pathway and type I interferon response, leading to the secretion of CCL5 and CXCL10, thereby enhancing CD8 T cell infiltration. Additionally, DMF exhibits synergistic effect with PD-1 blockade in murine CC model, and can enhance the therapeutic efficacy of adoptively transferred T cells toward CC patient-derived xenografts model. ConclusionThis work elucidated that DMF reprograms CC cells to activate the mtDNA-cGAS-STING pathway, fostering a chemokine-rich microenvironment that recruits CD8+ T cells. Its synergy with PD-1 blockade or TIL therapy underscores its potential as an immunomodulatory adjuvant. These findings suggest that DMF holds promise as a novel immunotherapeutic strategy for improving clinical outcomes in CC.

immunology↗

bioRxiv2025

Fast and accessible morphology-free functional fluorescence imaging analysis

Optical calcium imaging is a powerful tool for recording neural activity across a wide range of spatial scales, from dendrites and spines to whole-brain imaging through two-photon and widefield microscopy. Traditional methods for analyzing functional calcium imaging data rely heavily on spatial features, such as the compact shapes of somas, to extract regions of interest and their associated temporal traces. This spatial dependency can introduce biases in time trace estimation and limit the applicability of these methods across different neuronal morphologies and imaging scales. To address these limitations, the Graph Filtered Temporal Dictionary Learning (GraFT) uses a graph-based approach to identify neural components based on shared temporal activity rather than spatial proximity, enhancing generalizability across diverse datasets. Here we present significant advancements to the GraFT algorithm, including the integration of a more efficient solver for the L1 least absolute shrinkage and selection operator (LASSO) problem and the application of compressive sensing techniques to reduce computational complexity. By employing random projections to reduce data dimensionality, we achieve substantial speedups while maintaining analytical accuracy. These advancements significantly accelerate the GraFT algorithm, making it more scalable for larger and more complex datasets. Moreover, to increase accessibility, we developed a graphical user interface to facilitate running and analyzing the outputs of GraFT. Finally, we demonstrate the utility of GraFT to imaging data beyond meso-scale imaging, including vascular and axonal imaging.

bioinformatics↗

bioRxiv2025

Senolytics Restore Hematopoietic Stem Cells Function in Sickle Cell Disease

Sickle Cell Disease (SCD) is a blood disorder affecting millions worldwide. Emerging evidence reveals that SCD pathophysiology increases risk of myeloid malignancies and hematopoietic stem cell (HSC) dysfunction, possibly due to pathological stress on bone marrow. To investigate this further, we interrogated mice and individuals with SCD and observed extended cell cycle times, oxidative stress, DNA damage, senescence, and dysregulation of molecular programs associated with these processes in bone marrow hematopoietic stem and progenitor cells (HSPCs). Human SCD HSPCs displayed poor hematopoietic potential ex vivo. SCD mice displayed a dramatic loss of transplantable bone marrow HSPCs, which was reversed upon treatment of SCD mice with the senolytic agent, ABT-263 (navitoclax). Thus, senolytics restore bone marrow function during SCD in mice and represent a novel strategy to improve bone marrow health in individuals with SCD and improve the safety of potentially curative gene therapies that utilize autologous HSPCs from individuals with SCD.

cell biology↗

bioRxiv2024

Innovative Strategies for Enhancing Signal-to-Noise Ratio in Single-molecule Imaging: The Influence of Molecular Motion

Single-molecule fluorescence imaging has extensively revealed the dynamic and structural characteristics of biomolecules. However, its application is limited by the upper concentration of fluorophore-tagged biomolecules, which is in the sub-ten nanomolar range. We found that the signal-to-noise ratio (SNR) in single-molecule fluorescence imaging is strongly influenced by the size of fluorophore-labeled molecules in solution. Our computational simulations suggest that the faster diffusion of background fluorophores can enhance the SNR of target molecules. Moreover, we identified that the molecular motion through fluid flow can improve SNR. This study provides a novel perspective by emphasizing the importance of molecular motion in SNR and propose a rapid barrier-free method to increase the upper concentration limit in single-molecule imaging.

biophysics↗

bioRxiv2024

2.6-A resolution cryo-EM structure of a class Ia ribonucleotide reductase trapped with mechanism-based inhibitor N3CDP

Ribonucleotide reductases (RNRs) reduce ribonucleotides to deoxyribonucleotides using radical-based chemistry. For class Ia RNRs, the radical species is stored in a separate subunit ({beta}2) from the subunit housing the active site (2), requiring the formation of a short-lived 2{beta}2 complex and long-range radical transfer (RT). RT occurs via proton-coupled electron transfer (PCET) over a long distance (~32-[A]) and involves the formation and decay of multiple amino acid radical species. Here, we use cryogenic-electron microscopy and a mechanism-based inhibitor 2'-azido-2'-deoxycytidine-5'-diphosphate (N3CDP) to trap a wild-type 2{beta}2 complex of E. coli class Ia RNR. We find that one subunit has turned over and that the other is trapped, bound to {beta} in a mid-turnover state. Instead of N3CDP in the active site, forward RT has resulted in N2 loss, migration of the third nitrogen from the ribose C2' to C3' positions, and attachment of this nitrogen to the sulfur of cysteine-225. To the best of our knowledge, this is the first time an inhibitor has been visualized as an adduct to an RNR. Additionally, this structure reveals the positions of PCET residues following forward RT, complementing the previous structure that depicted a pre-turnover PCET pathway and suggesting how PCET is gated at the -{beta} interface. This N3CDP-trapped structure is also of sufficient resolution (2.6 [A]) to visualize water molecules, allowing us to evaluate the proposal that water molecules are proton acceptors and donors as part of the PCET process. Significance StatementSeveral FDA-approved cancer drugs target human ribonucleotide reductase (RNR), a radical enzyme that produces the requisite deoxyribonucleotides for DNA biosynthesis and repair. Human RNR is a class Ia enzyme that requires radical transfer (RT) from a {beta}2 subunit to an 2 subunit on every round of turnover. Long-range RT is both a remarkable feature and an Achilles heel, given that inhibitors can intercept the radical species. Here we present a cryogenic electron microscopy (cryo-EM) structure of the best studied class Ia RNR, the enzyme from E. coli, in which 2 and {beta}2 subunits have been trapped together using a mechanism-based inhibitor. This structure provides insight into both the mechanism of RNR inhibition and the mechanism of long-range RT.

biophysics↗

bioRxiv2024

microRNA-1 Regulates Metabolic Flexibility in Skeletal Muscle via Pyruvate Metabolism

MicroRNA-1 (miR-1) is the most abundant miRNA in adult skeletal muscle. To determine the function of miR-1 in adult skeletal muscle, we generated an inducible, skeletal muscle-specific miR-1 knockout (KO) mouse. Integration of RNA-sequencing (RNA-seq) data from miR-1 KO muscle with Argonaute 2 enhanced crosslinking and immunoprecipitation sequencing (AGO2 eCLIP-seq) from human skeletal muscle identified miR-1 target genes involved with glycolysis and pyruvate metabolism. The loss of miR-1 in skeletal muscle induced cancer-like metabolic reprogramming, as shown by higher pyruvate kinase muscle isozyme M2 (PKM2) protein levels, which promoted glycolysis. Comprehensive bioenergetic and metabolic phenotyping combined with skeletal muscle proteomics and metabolomics further demonstrated that miR-1 KO induced metabolic inflexibility as a result of pyruvate oxidation resistance. While the genetic loss of miR-1 reduced endurance exercise performance in mice and in C. elegans, the physiological down-regulation of miR-1 expression in response to a hypertrophic stimulus in both humans and mice causes a similar metabolic reprogramming that supports muscle cell growth. Taken together, these data identify a novel post-translational mechanism of adult skeletal muscle metabolism regulation mediated by miR-1.

physiology↗

bioRxiv2024

Childhood brain morphometry in children with persistent stunting and catch-up growth

BackgroundEarly childhood stunting affects around 150 million young children worldwide and leads to suboptimal human potential in later life. However, there is limited data on the effects of early childhood stunting and catch-up growth on brain morphometry. MethodsWe evaluated childhood brain volumes at nine years of age in a community-based birth-cohort follow-up study in Vellore, south India among four groups based on anthropometric assessments at two, five, and nine years namely Never Stunted (NS), Stunted at two years and caught up by five years (S2N5), Stunted at two and five years and caught up by nine years (S2N9), and Always Stunted (AS). T1-weighted magnetic resonance imaging (MRI) images were acquired using a 3T MRI scanner, and brain volumes were quantified using FreeSurfer software. FindingsAmongst 251 children from the overall cohort, 178 children with a mean age of 9.54 were considered for further analysis. The total brain volume, subcortical volume, bilateral cerebellar white matter, and posterior corpus callosum showed a declining trend from NS to AS. Regional cortical brain analysis showed significant lower bilateral lateral occipital volumes, right pallidum, bilateral caudate, and right thalamus volumes between NS and AS. InterpretationTo the best of our knowledge, this first neuroimaging analysis to investigate the effects of persistent childhood stunting and catch-up growth on brain volumetry indicates impairment at different brain levels involving total brain and subcortical volumes, networking/connecting centres (thalamus, basal ganglia, callosum, cerebellum) and visual processing area of lateral occipital cortex.

neuroscience↗

bioRxiv2024

Microbial-Derived Exerkines Prevent Skeletal Muscle Atrophy

Regular exercise yields a multitude of systemic benefits, many of which may be mediated through the gut microbiome. Here, we report that cecal microbial transplants (CMTs) from exercise-trained vs. sedentary mice have modest benefits in reducing skeletal muscle atrophy using a mouse model of unilaterally hindlimb-immobilization. Direct administration of top microbial-derived exerkines from an exercise-trained gut microbiome preserved muscle function and prevented skeletal muscle atrophy.

physiology↗

bioRxiv2023

A highly contiguous hexaploid wheat genome assembly facilitates analysis of 1RS translocation and mining of a new adult plant resistance locus to yellow rust disease

High-quality genome information is essential for efficiently deciphering and improving crop traits. Here we report a highly contiguous hexaploid genome assembly for the key wheat breeding parent Zhou8425B, an elite 1BL/1RS translocation line with durable adult plant resistance (APR) against rust diseases. By using HiFi and Hi-C sequencing reads, a 14.75 Gb genome assembly, with contig N50 and scaffold N50 values reaching 70.94 and 735.11 Mb, respectively, was developed. Comparison with 16 previously sequenced common wheat cultivars revealed unique chromosomal structural features in Zhou8425B. Notably, the 1RS translocation in Zhou8425B was apparently longer and carried more genes encoding AP2/ERF-ERF and B3 transcription factors relative to its counterpart in several genome sequenced 1BL/1RS varieties and rye lines. Aided by Zhou8425B genome assembly, a new APR locus (i.e., YrZH3B) against yellow rust (YR) disease was finely mapped to a 1 - 2 Mb interval on chromosome 3BS. Analysis with 212 Zhou8425B derivative varieties showed that pyramiding of YrZH3B with two other APR loci (YrZH22 and YrZH84) significantly decreased YR severity and enhanced grain yield, with triple combination (YrZH3B/YrZH22/YrZH84) having the highest effects. Our data demonstrate the high value of Zhou8425B assembly in studying wheat genome and agronomically important genes.

genomics↗