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Duong, T.

Publications and source records attributed to Duong, T..

At least 19 recordsLinked to original sources

Deep learning models detect neuromuscular disease and quantify functional impairment from video-derived biomechanics data

Measurements of human movement are critical for evaluating patients with neuromuscular diseases. However, current clinical tools are limited in sensitivity and can fail to detect the full spectrum of movement changes patients may exhibit. These limitations can obscure early signs of decline, delaying interventions that could preserve function and independence. OpenCap, a smartphone application that performs video-based markerless motion capture, can help address this gap by enabling scalable, out-of-lab measurements of human movement. Here, we present a method for both detecting disease and quantifying the severity of impaired movement from smartphone videos of patient motion. We used OpenCap to measure kinematics from 337 individuals with diagnoses spanning 12 rare, genetically-defined neuromuscular diseases and 78 age-matched healthy controls. Our dataset is the largest existing publicly available resource of body segment kinematics for this class of diseases. These data were collected in neuromuscular clinics during regular clinic visits as well as at conferences and community events across the United States. We trained deep learning models on these kinematic time series to differentiate between participants with neuromuscular disease and controls (AUROC = 0.97 [0.93-1.00]). We also developed a movement impairment severity score that correlates with both participant ratings of their own functional abilities ({rho} = -0.81, p < 0.001) and existing clinical tests of movement capabilities such as run speed ({rho} = -0.83, p < 0.001). Our methods for detecting disease and deriving quantitative biomarkers of movement impairment from smartphone videos have the potential to complement clinical assessments, inform screening protocols, and improve clinical trial endpoints.

bioengineering↗

White matter cognition mapping in pediatric cancer survivors: a two-cohort NODDI-Bingham study

Childhood cancer survivors (CS) treated with chemotherapy frequently experience long-term cognitive impairments, commonly referred to as CRCI. Whether these deficits reflect disrupted white matter microstructure, altered relationships between microstructure and cognition, or both remains unclear. Here, we applied the NODDI-Bingham model, which quantifies neurite density (NDI), isotropic free water (ISO), and orientation dispersion along primary (ODIp), secondary (ODIs), and total (ODIt) fiber axes, to characterize biophysically specific white matter microstructure in CS and examine its relationship to cognition. Twenty-one pediatric cancer survivors and 21 age-matched healthy controls (HC) underwent multi-shell diffusion MRI. Voxel-wise NODDI-Bingham analyses were performed within JHU atlas regions. Group differences were tested by ANCOVA, and associations between microstructure and cognition were examined with the NIH Toolbox Crystallized, Fluid, and Early Childhood composites using group-specific regressions. Confirmatory analyses were performed in an age-matched subsample of the HCP (n = 679). Notably, CS showed reduced NDI in the corona radiata, cerebral peduncles, and corpus callosum, with elevated ODIt and ODIp in the middle cerebellar peduncle, pathways that subserve processing speed and interhemispheric integration, cognitive domains among the most vulnerable in CRCI. Group-specific regressions revealed qualitatively different relationships between microstructure and cognition: HC exhibited mixed positive and negative relationships across four of five metrics (138 clusters spanning approximately 305,000 voxels; peak Cohen's d up to 3.00), whereas CS showed a predominantly uniformly negative pattern (67 clusters across 57,000 voxels), with no positive clusters for ISO, ODIt, ODIp, or ODIs, thus highlighting that reduced dispersion and extracellular free water are linked to better cognitive performance in CS. HCP analyses reproduced the HC pattern across all five metrics at proportionally smaller effect sizes, ruling out sample-size effects. NODDI-Bingham identifies two aspects of chemotherapy-related white matter pathology that standard diffusion metrics cannot resolve. First, pediatric cancer survivors show selective elevation of ODIp and ODIt in the cerebellar peduncles and reduced NDI in the corona radiata and corpus callosum, localizing group-level injury to specific fanning and neurite density signatures. Second, whereas in healthy controls white matter shows mixed positive and negative relationships between microstructure and cognition, survivors retain only negative relationships for ODIp and ODIt and a diminished mixed pattern for NDI, such that in the chemotherapy-exposed brain, only reduced neurite density and increased primary-axis fanning relate to cognitive impairment. These findings implicate a biophysically specific restructuring of the relationships between white matter and cognition as a candidate mechanism for CRCI and support NODDI-Bingham as a targeted biomarker panel for monitoring and intervention trials.

neuroscience↗

12-plex DiLeu enables robust quantification of the feeding neuropeptidome

Understanding the feeding-induced neuropeptidome cascade requires analytical strategies capable of quantifying low-abundance, highly modified peptides across multiple tissues and time points. Herein, we apply 12-plex N,N-dimethyl leucine (DiLeu) isobaric labeling to perform the first multiplexed, tissue-wide, temporal quantitation of the Cancer borealis feeding neuropeptidome. This approach enabled sensitive measurement of neuropeptides across five tissues over six timepoints, revealing distinct regulatory patterns. The pericardial organ (PO) showed rapid early upregulation followed by suppression aligned with foregut emptying, whereas the thoracic ganglion (TG) displayed inverse and strongly condition-dependent responses, indicating previously unrecognized neuromodulatory roles. Single-residue variants and post-translational modifications, including pyro-Glu formation and amidation, produced markedly different temporal profiles, underscoring the functional specificity of closely related isoforms. We further identify differential regulation of proctolin and its amidated form, suggesting modified variants may contribute uniquely to feeding physiology. Collectively, these results establish multiplexed DiLeu labeling as a powerful platform for quantitative neuropeptidomics and reveal new dimensions of peptide-mediated feeding regulation.

neuroscience↗

Novel quantitative trait loci conferring broad-based resistance to root-knot nematodes in lima bean (Phaseolus lunatus)

Lima bean (Phaseolus lunatus) is a broadly adapted, economically important leguminous crop and a susceptible host of root-knot nematodes (Meloidogyne spp.; RKN), which are a devastating plant pathogen in agricultural systems worldwide. To date, there have been few studies to elucidate the genetic determinants of RKN resistance in lima beans. Understanding the genetic mechanisms underlying resistance is essential for improving resistance traits and incorporating them into lima bean breeding programs. To assist in marker-assisted selection, we aimed to identify and map quantitative trait loci (QTLs) conferring RKN resistance-related traits. Three recombinant inbred line (RIL) populations were used in this study. Three populations were derived by crossing two RKN-resistant parents with the same RKN-susceptible parent and with each other. All populations were genotyped using genome-wide single-nucleotide polymorphism (SNP) markers. Each population was screened for root galling (RG) and RKN egg reproduction (ER) in response to M. incognita and M. javanica in greenhouse experiments. Three major QTLs were detected and mapped on chromosome Pl04 (QRk-pl04.1), Pl05 (QRk-pl05.1) and Pl10 (QRk-pl10.1) across populations. Among them, QRk-pl05.1 and QRk-pl10.1 affected levels of RG and ER of both RKN species, while QRk-pl04.1 suppressed root galling and reproduction responses of M. incognita but not of M. javanica. These chromosomal regions defined by flanking markers will help guide marker-assisted breeding and gene discovery for broad-based RKN resistance in lima beans.

plant biology↗

Cognitive Control in Pediatric Cancer Survivors: A task-fMRI study

BackgroundChemotherapy-related cognitive impairment is a well-documented concern among cancer survivors, yet the neural mechanisms underlying deficits in cognitive control remain poorly understood. This study examined group differences in brain activation during a flanker task using functional MRI (fMRI) between chemotherapy-exposed participants and healthy controls. MethodsParticipants (21 survivors (24.9 years old; 71.4 % female; 15 years from diagnosis) and 21 healthy controls (26.7 years old; 61.9 % female) completed a flanker task during fMRI, with congruent and incongruent conditions. Reaction time, accuracy, and Flanker scores were collected. Whole-brain group comparisons were performed for congruent, incongruent, and incongruent > congruent contrasts. Associations between the incongruent > congruent contrast and cognitive performance were examined. ResultsCompared to controls, the Chemo group had longer reaction times in both congruent and incongruent conditions (p < .001) and lower NIH Flanker scores (p = .01), with no differences in accuracy. They showed reduced activation in the bilateral inferior frontal gyri, supplementary motor area, and bilateral caudate, but greater activation in the right inferior temporal and cerebellar regions. The incongruent > congruent contrast correlated with increased activation in the orbitofrontal cortex, inferior temporal gyri, and fusiform gyrus with cognitive performance. ConclusionsChemotherapy-exposed participants showed cognitive control deficits and altered neural activation during a flanker task, indicating disrupted recruitment of frontoparietal and subcortical regions key for conflict processing. These findings improve understanding of neural causes of chemotherapy-related cognitive impairment and may help identify at-risk survivors and guide personalized rehabilitation.

neuroscience↗

Dual-Lipa: A sequential multi-omic subcellular landscape map of mouse heart

Spatial multi-omics can provide a unique understanding in molecular organisation and heterogeneity of organs including the heart. Heart function is dependent on the abundance and the spatial arrangement of proteins and lipids. Yet, an integrated multi-omics landscape of the heart at subcellular scale remains unknown. Here, we used a sequential lipid-proteomic analytical pipeline applied to the mouse heart to identify, map, and integrate lipid and protein features, revealing coordinated distinct molecular networks within defined subcellular niches. Here, we benchmark this dual extraction workflow for integrated global proteome-lipidome analyses to demonstrate its performance. We developed conserved subcellular proteome of mouse heart across 14 niches and applied the knowledge of subcellular proteome to spatially resolve the heart lipidome, identifying unique lipid features from different subcellular niches, including mitochondria (e.g., cardiolipin, LPC) and plasma membrane-enriched lipids (e.g., plasmalogens). We identified sex-dependent molecular differences in heart subcellular proteome between male and female, including RNA-protein complexes, mitochondrial calcium handling and immune regulatory pathways. We demonstrate that lipid-protein integrated multi-omics analysis of the heart by dual extraction workflow and mass spectrometry could enable previously unidentified discoveries in heart molecular composition and organisation and spatial cardiac biology. HighlightsO_LIResolved tissue-wide subcellular architecture of cardiac tissue through simultaneous high-resolution proteomics and lipidomics profiling. C_LIO_LISystematically evaluated MS-compatible dual extraction strategies for integrated proteome-lipidome recovery and performance. C_LIO_LIProteomics revealed major sex-dependent differences in mouse left ventricles, primarily involving cellular metabolism, immune regulation, detoxification pathways, and signalling responses. C_LIO_LILipidomics identified strong sex-specific lipid signatures, including differences in omega-3 vs omega-6 fatty-acid containing lipid species, triacylglycerides, and acylcarnitines. C_LIO_LIDeveloped supervised machine-learning models to classify 14 subcellular niches from tissue-wide fractionation proteomics and identified a conserved core subcellular proteome. C_LIO_LIApplied the tissue-wide subcellular proteome model to infer lipid subcellular localisation, revealing mitochondria-enriched lipids (e.g., cardiolipin, LPC) and plasma membrane-enriched lipids (e.g., plasmalogens) in the mouse left ventricle. C_LIO_LIMapped sex-specific subcellular distribution in the heart, highlighting pathways linked to RNA-protein complexes, mitochondrial calcium handling, and immune regulatory networks. C_LI

biochemistry↗

Reconstituting Mouse Embryogenesis Ex Utero from Gastrulation to Fetal Development Reveals Maternally Independent Metabolic Programs

Mammalian development takes place inside the maternal uterus, creating technological constraints that make difficult the study of embryogenesis in live developing embryos. A central challenge for understanding the role of metabolism in mammalian development is discriminating placental and uterine-regulated signals from embryo-intrinsic processes independent of maternal influence, a process that until now has remained inseparable during gastrulation and organogenesis1-3. Ex utero culture systems allowing continuous growth of embryos during pre-gastrulation to organogenesis4,5 offer a promising solution to this challenge. Here, we present optimized ex utero culture platforms that support faithful development of mouse embryos from gastrulation (embryonic day 6.5/7.5) through the fetal period (embryonic day [~]12.5) and harnessed these platforms for dissecting metabolic transitions in vivo during embryogenesis independently of uterus and placenta. We characterized the metabolome of in utero and ex utero whole embryos, fetal organs and culture medium between embryonic days E6.5 and E12.5 by liquid chromatography mass-spectrometry (LC-MS) metabolomics, isotope tracing, and single cell transcriptomics. These datasets present a comprehensive overview of the dynamic embryonic metabolism during gastrulation and organogenesis in utero and ex utero. This analysis revealed that the midgestational metabolic switch occurring at E10.5-E11.5 is faithfully recapitulated ex utero, indicating that this transition is intrinsically programmed in embryonic tissues and does not require direct maternal or placental cues. Notably, oxygen availability modulated the extent of this transition, but elevated oxygen was insufficient to induce it prematurely, demonstrating that the switch is developmentally timed and only partially environmental-responsive. We further harnessed the ex utero platform for identifying and perturbing a mitochondrial redox shift at E7.5-E8.5 that is critical for developmental progress after gastrulation. These findings uncover the remarkable metabolic plasticity of the mammalian embryo, demonstrating its capacity to sustain growth independently of maternal inputs from the establishment of the body plan through the onset of the fetal period. Moreover, they highlight the use of long-term ex utero culture as a unique framework for dissecting the mechanisms that shape embryogenesis under physiological and experimentally perturbed conditions, while functionally uncoupling embryonic programs from maternal and placental influences.

developmental biology↗

Quantitative Neuropeptidomics Reveals Thermal Acclimation-Induced Remodeling of Peptidergic Signaling in the American Lobster Homarus americanus

Global warming and rising ocean temperatures pose substantial challenges to marine ecosystems and crustacean populations. As an ectothermic species, the American lobster (Homarus americanus) relies on physiological and neurochemical mechanisms to maintain homeostasis under varying environmental conditions. To elucidate the role of neuropeptides in neuronal plasticity and systemic adaptation to temperature fluctuations, we employed a quantitative mass spectrometry-based approach to probe key neuropeptides involving thermal adaptation in four lobster neural tissues at three temperatures: 4 {degrees}C (cold), 11 {degrees}C (control), and 18 {degrees}C (warm). Peptidomic profiling revealed a global reduction in peptide abundance during cold exposure, alongside coordinated, tissue-specific reconfigurations of the neuropeptidome between experimental groups. Cold exposure led to a significant downregulation of RFamide, leucokinin, and pyrokinin peptides in the commissural ganglia, whereas B-type allatostatin (AST-B), natalisin, and RYamide peptides were drastically elevated in the brain of warm-acclimated animals, with comparatively fewer detectable peptide abundance changes in the sinus gland and the stomatogastric ganglion. Collectively, our findings elucidate neuropeptide signaling pathways underlying thermal tolerance and adaptive resilience in Homarus americanus, offering insights into the survival mechanism and neurochemical basis of neural circuits in response to thermal acclimation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/710231v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@a3d24borg.highwire.dtl.DTLVardef@1434aaaorg.highwire.dtl.DTLVardef@db11cforg.highwire.dtl.DTLVardef@6e5995_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Aging, dauer, and stature phenotypes are conferred by structure-directed missense mutations in the endogenous AGE-1/phosphatidylinositol 3-kinase catalytic subunit.

Phosphatidylinositol 3-kinase (PI3K) integrates insulin/IGF signaling (IIS) and Ras inputs to control lifespan, metabolism and growth, yet the organismal consequences of selective structural perturbations remain poorly understood. Using structure-guided CRISPR/Cas9-dependent genome editing, we dissected functions of AGE-1, the sole Class IA PI3K catalytic subunit in Caenorhabditis elegans. An endogenously tagged AGE-1, containing a long flexible linker, epitope and fluorescent tag, retained full activity, enabling visualization of native protein dynamics in vivo. A constitutively active E630K substitution, modeled on oncogenic p110 alleles, markedly shortened lifespan and enhanced Ras-dependent induction of primary vulval precursor cell (VPC) fate, confirming evolutionary conservation of PI3K activation mechanisms that directly modulate longevity and development. Structural modeling further guided mutation of AGE-1 residues predicted to mediate Ras binding. Unexpectedly, a putative AGE-1 variant defective in Ras association, together with a complementary Ras effector-binding mutation, produced enlarged animals with reduced dauer formation. These phenotypes reveal a previously unrecognized Ras>PI3K signaling axis that restrains somatic growth and promotes entry into diapause, counter to canonical IIS models. Together, these structure-informed alleles show that discrete PI3K structural perturbations can differentially uncouple lifespan, growth, and developmental outcomes in vivo. By combining structural modeling with genome editing in a tractable aging model, this work establishes a framework for dissecting conserved signaling enzymes at single-residue resolution and uncovers unexpected organismal roles for PI3K structure in coordinating growth and longevity.

developmental biology↗

cpiVAE: Robust and Interpretable Cross-Platform Proteomics Imputation

Large-scale plasma proteomic studies often use different high-throughput affinity platforms, and measurements of the same protein across platforms are often discordant. Discordance hinders cross-study integration. Improving proteomics data integration would enable more powerful meta-analyses, improve statistical power for biomarker discovery, and provide a better understanding of proteome-phenotype relationships. Here we present a cross-platform proteomics imputation variational autoencoder (cpiVAE), a deep generative model for bidirectional imputation of protein abundances between two widely used platforms: Olink and SomaScan. Using a training cohort of paired measurements from the China Kadoorie Biobank (CKB), cpiVAE learns a joint latent representation that enables cross-platform imputation. The cpiVAE method improves benchmarks provided by established methods, k-nearest neighbors (KNN) Weighted Nearest Neighbors (WNN, from Seurat v4). The cpiVAE method achieves up to 30% higher correlation between imputed and true values than KNN and WNN. The cpiVAE method also generalizes well to an independent cohort from the Atherosclerosis Risk in Communities Study (ARIC). Without retraining, cpiVAE maintains high performance compared to benchmarks. Associations of imputed protein levels with clinical phenotypes closely mirror results using the actual measurements and increases power in a meta-analysis scenario. A post-hoc feature importance matrix enables interpretation of this AI model. Protein pair features extracted from cpiVAE have significant overlap with known associations in the Search Tool for the Retrieval of Interacting Genes (STRING) database. In summary, cpiVAE offers an accurate, generalizable, and interpretable solution for cross-platform proteomic imputation, enabling integrated analyses across studies with proteomics measured on different platforms. This user-friendly framework and pre-trained model weights are available under a BSD2 open source license at https://github.com/joelbaderlab/cpiVAE_v1.

bioinformatics↗

A single-component optogenetic toolkit for programmable control of microtubule

Microtubules (MTs) form dynamic cytoskeletal scaffolds essential for intracellular transport, organelle positioning, and spatial organization of signaling. Their architecture and function are continuously remodeled through the concerted actions of microtubule-associated proteins (MAPs), post-translational modifications (PTMs), and molecular motors. To precisely interrogate these processes in living systems, we developed a genetically encoded optogenetic toolkit for spatiotemporal control of MT organization and dynamics. By replacing native multimerization motifs with a blue light-responsive oligoermization domain, we have engineered single-component probes, OptoMT and OptoTIP, that reversibly label MT polymers or track plus-ends with tunable kinetics from seconds to minutes. When coupled to enzymatic effectors, these modules enable localized tubulin acetylation or detyrosination, directly linking PTMs to MT stability. We further engineered OptoMotor, a light-activatable kinesin platform that reconstitutes tail-dependent cargo transport along MTs, and OptoSAW, a light-triggered severing actuator for controlled MT disassembly. Using these tools, we reveal how local MT integrity governs lysosomal trafficking and ER-associated signaling dynamics. Collectively, this versatile single-component toolkit bridges molecular design with cytoskeletal function, offering new avenues to illuminate how dynamic cytoskeletal architectures coordinate intracellular organization, transport, and signaling.

cell biology↗

Pangenome of U.S. ex-PVP and Wild Sorghum Reveals Structural Variants and Selective Sweeps Shaping Adaptation and Trait Improvement

Sorghum is a cereal crop grown for food, feed, and biofuel, yet the genomic diversity of elite commercial lines remains underexplored. Here, we assembled a sorghum pangenome from long-read sequences of 46 U.S. ex-Plant Variety Protection Act (ex-PVP) cultivars and a haplotype-resolved assembly of one wild accession. The pangenome revealed largely conserved genomic architecture across elite lines but identified presence-absence variations (PAVs) in 28% of gene families, including genes involved in stress responses and starch metabolism, such as STARCH BRANCHING ENZYME I (SBE1). Selective sweep analyses detected strong signals at key flowering-time loci (Ma1/SbPRR37, Ma2, Ma6) and circadian/light regulators (PHOT1, DET1, XAP5), with PHYA showing copy number variations (CNVs). Analysis of 24 wild accessions, beyond the core pangenome panel, detected CNVs in MULTIDRUG AND TOXIC COMPOUND EXTRUSION (MATE) transporters, potentially reflecting selection or breeding for enhanced herbicide detoxification. These results highlight breeding-shaped regions and position the pangenome as a resource for sorghum improvement.

genomics↗

HILIC-Enabled Mass Spectrometric Discovery of Novel Endogenous and Glycosylated Neuropeptides in the American Lobster Nervous System

Neuropeptides are a highly conserved and diverse class of intercellular signaling molecules that regulate a broad range of neural and hormonal processes across animal phyla. The American lobster, Homarus americanus, has long served as a powerful invertebrate model for the discovery and functional investigation of neuropeptides. Among common post-translational modifications (PTMs) found in neuropeptides, glycosylation remains underexplored due to the inherently low in vivo abundance and intrinsically complex structural heterogeneity. In this study, we employed hydrophilic interaction liquid chromatography (HILIC) enrichment coupled with oxonium-ion triggered EThcD fragmentation strategy to simultaneously profile novel endogenous and glycosylated neuropeptides across eight distinct neural tissues and neuroendocrine organs of Homarus americanus. This integrative mass spectrometry-based approach led to the identification of 154 endogenous neuropeptides derived from 25 families, approximately one-third of which are newly reported, and uncovered 24 glycosylated neuropeptides in this species for the first time. These peptides exhibit strong tissue-specific expression, distinct proteolytic cleavage patterns, and confidently localized glycosylation sites. Our results highlight the utility of integrated sampling enrichment and hybrid fragmentation strategies for deep neuropeptidomic profiling and provide a valuable resource for future studies on the functional roles of newly identified neuropeptides and glycosylation in crustacean neuromodulation and peptidergic signaling. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/661634v2_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@9a1745org.highwire.dtl.DTLVardef@6decc4org.highwire.dtl.DTLVardef@d34256org.highwire.dtl.DTLVardef@1a83b4c_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Inhibition of Posterior Thalamic Nuclei Attenuates CGRP-induced Migraine-like Behavior in Mice

ObjectiveTo determine whether induction of migraine-like symptoms in mice by calcitonin gene-related peptide (CGRP) requires activation of the posterior thalamic nuclei (PoT) in the brain.BackgroundPrevious research found that both optical activation of the PoT and injection of CGRP into the PoT are sufficient to induce light aversive behavior in mice. The PoT is well known as a sensory integration center of light and pain signals in the brain. However, whether this region is required for touch hypersensitivity and light aversion following peripheral administration of CGRP was not known.MethodsThe PoT was injected in two strains of mice, inbred C57BL/6J and outbred CD-1, with viral vectors expressing inhibitory chemogenetic Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). The inhibitory DREADDs were activated by systemic intraperitoneal (ip) injection of two designer drugs, clozapine N-oxide (CNO) and DREADD agonist compound 21 (C21). We used ip injection of CGRP to induce migraine-like phenotypes and tested whether we could rescue these phenotypes by bilateral chemogenetic inhibition of the PoT. The light/dark assay was used to measure light aversive behavior (a surrogate for photophobia) and the plantar von Frey assay to measure hindpaw touch sensitivity (a surrogate for extracephalic allodynia).ResultsWe successfully induced light aversive and hindpaw touch hypersensitivity phenotypes in mice using ip injections of CGRP. Activation of the inhibitory DREADDs in the PoT using ip CNO (5 mg/kg) was sufficient to partially rescue the touch hypersensitivity phenotype, but with off target effects in the control mice. Lowering the CNO dose to 1 mg/kg alleviated off target effects but was insufficient to rescue the touch hypersensitivity phenotype. On the other hand, C21 (1 mg/kg) fully rescued the touch hypersensitivity phenotype without any off target effects. Treatment with C21 also partially rescued the light aversion phenotype. These results were consistent across both C57BL/6J and CD-1 mouse strains.ConclusionInhibition of the PoT fully rescues CGRP-induced touch hypersensitivity and partially rescues light aversion in mice, indicating that the PoT is necessary for touch hypersensitivity and partially necessary for light aversive behaviors. These data suggest the PoT is part of a central network that receives peripheral CGRP-induced signals and thus could be harnessed for future targeted therapeutics for migraine.Plain language summaryThe posterior thalamus is a central brain region that contributes to migraine pathophysiology when stimulated. In this study, we asked if inhibition of this brain region could alleviate migraine-like phenotypes in mice. We found that inhibition of the posterior thalamus fully rescues touch hypersensitivity and partially rescues light aversive behavior, suggesting that the posterior thalamus is necessary for migraine pathophysiology and could offer a potential therapeutic target for migraine.

neuroscience↗

Triploidy is prominent in the duckweed Lemna minor complex

Duckweeds (Lemnaceae Martinov) are aquatic monocotyledonous flowering plants comprising five genera and 35 recognized species, known for being the smallest and fastest-growing flowering plants on Earth. Many species are morphologically indistinguishable due to their highly reduced structures, yet molecular evidence suggests that visually similar clones may represent distinct species or hybrids. For example, clonal accessions of the globally distributed Lemna minor in the Landolt Duckweed Collection exhibit genome size variations of several hundred megabases (Mb), raising questions about their taxonomic classification and evolutionary origins. We analyzed 58 presumed L. minor clones to resolve these relationships using a comprehensive suite of methods, including whole-genome sequencing (WGS), flow-cytometric genome size measurements, molecular markers, chromosome counting, and genomic in situ hybridization (GISH). Our findings reveal extensive genome plasticity within the "Lemna minor complex," identifying diploid and triploid L. minor clones, as well as di-haploid and triploid interspecific hybrids called L. x japonica (L. minor x L. turionifera), L. x mediterranea (L. minor x L. gibba), and a novel African-clade distinct from known L. minor lineages. Triploidy was prevalent, occurring in 29% of the clones, and was associated with enhanced growth under optimal conditions but reduced performance under high light and temperature. These findings highlight the widespread role of triploidy, cryptic species, and hybridization in the L. minor complex, emphasizing the importance of multiple approaches for accurately classifying duckweed species and understanding their evolutionary trajectories.

plant biology↗

Video-based biomechanical analysis captures disease-specific movement signatures of different neuromuscular diseases

BackgroundAssessing human movement is essential for diagnosing and monitoring movement-related conditions like neuromuscular disorders. Timed function tests (TFTs) are among the most widespread assessments due to their speed and simplicity, but they cannot capture disease-specific movement patterns. Conversely, biomechanical analysis can produce sensitive disease-specific biomarkers but is traditionally confined to laboratory settings. Recent advances in smartphone video-based biomechanical analysis enable quantification of 3D movement with the ease and speed required for clinical settings. However, the potential of this technology to offer more sensitive assessments of human function than TFTs remains untested. MethodsTo compare video-based analysis against TFTs, we collected an observational dataset from 129 individuals: 28 with facioscapulohumeral muscular dystrophy, 58 with myotonic dystrophy, and 43 controls with no diagnosed neuromuscular condition. We used OpenCap, a free open-source software tool, to capture smartphone video-based biomechanics of nine different movements in a median time of 16 minutes per participant. From these recordings we extracted 34 interpretable movement features. Using these features, we evaluated the ability of video-based biomechanics to reproduce four TFTs (10-meter walk, 10-meter run, timed up-and-go, and 5-time sit-to-stand) while capturing additional disease-specific signatures of movement. ResultsVideo-based biomechanical analysis reproduced all four TFTs (r > 0.98) with similar test-retest reliability. In addition, video metrics outperformed TFTs at disease classification (p = 0.021). Unlike TFTs, video-based biomechanical analysis identified disease-specific signatures of movement such as differences in gait kinematics that are not evident in TFTs. ConclusionVideo-based biomechanical analysis can complement existing functional movement assessments by capturing more sensitive, disease-specific outcomes from human movement. This technology enables digital health solutions for assessing and monitoring motor function, complementing traditional clinical outcome measures to enhance care, management, and clinical trial design for movement-related conditions. DescriptionThis study demonstrates that smartphone video-based biomechanical analysis can accurately replicate traditional timed function tests (TFTs) -- commonly used to diagnose and assess movement-related conditions like neuromuscular disorders -- while also capturing disease-specific movement patterns that TFTs fail to detect. By enabling sensitive and interpretable assessments in clinical settings, this approach offers a scalable and objective tool to enhance diagnosis, monitoring, and clinical trial design for neuromuscular disorders.

bioengineering↗

Domesticated cannabinoid synthases amid a wild mosaic cannabis pangenome

Cannabis sativa is a globally significant seed-oil, fiber, and drug-producing plant species. However, a century of prohibition has severely restricted legal breeding and germplasm resource development, leaving potential hemp-based nutritional and fiber applications unrealized. Existing cultivars are highly heterozygous and lack competitiveness in the overall fiber and grain markets, relegating hemp to less than 200,000 hectares globally1. The relaxation of drug laws in recent decades has generated widespread interest in expanding and reincorporating cannabis into agricultural systems, but progress has been impeded by the limited understanding of genomics and breeding potential. No studies to date have examined the genomic diversity and evolution of cannabis populations using haplotype-resolved, chromosome-scale assemblies from publicly available germplasm. Here we present a cannabis pangenome, constructed with 181 new and 12 previously released genomes from a total of 156 biological samples from both male (XY) and female (XX) plants, including 42 trio phased and 36 haplotype-resolved, chromosome-scale assemblies. We discovered widespread regions of the cannabis pangenome that are surprisingly diverse for a single species, with high levels of genetic and structural variation, and propose a novel population structure and hybridization history. Conversely, the cannabinoid synthase genes contain very low levels of diversity, despite being embedded within a variable region containing multiple pseudogenized paralogs and distinct transposable element arrangements. Additionally, we identified variants of acyl-lipid thioesterase (ALT) genes2 that are associated with fatty acid chain length variation and the production of the rare cannabinoids, tetrahydrocannabinol varin (THCV) and cannabidiol varin (CBDV). We conclude the Cannabis sativa gene pool has only been partially characterized, and that the existence of wild relatives in Asia remains likely, while its potential as a crop species remains largely unrealized.

plant biology↗

AMH protects the ovary from doxorubicin by regulating cell fate and the response to DNA damage

Anti-Mullerian hormone (AMH) protects the ovarian reserve from chemotherapy, and this effect is most pronounced with Doxorubicin (DOX). However, the mechanisms of DOX toxicity and AMH rescue in the ovary remain unclear. Herein, we characterize these mechanisms in various ovarian cell types using scRNAseq. In the mesenchyme, DOX activates the intrinsic apoptotic signaling pathway through p53 class mediators, particularly affecting theca progenitors, while co-treament with AMH halts theca differentiation and reduces apoptotic gene expression. In preantral granulosa cells, DOX upregulates the cell cycle inhibitor Cdkn1a and dysregulates Wnt signaling, which are ameliorated by AMH co-treatment. Finally, in follicles, AMH induces Id3, a protein involved in DNA repair, which is necessary to prevent the accumulation of DNA lesions marked by {gamma}-H2AX in granulosa cells. Altogether this study characterizes cell, and follicle stage-specific mechanisms of AMH protection of the ovary, offering promising new avenues for fertility preservation in cancer patients undergoing chemotherapy. HighlightsO_LIDoxorubicin treatment induces DNA damage that activates the p53 pathway in stromal and follicular cells of the ovary. C_LIO_LIAMH inhibits the proliferation and differentiation of theca and granulosa cells and promotes follicle survival following Doxorubicin insult. C_LIO_LIAMH treatment mitigates Doxorubicin-induced DNA damage in the ovary by preventing the accumulation of {gamma}-H2AX-positive unresolved foci, through increased expression of ID3, a protein involved in DNA repair. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC="FIGDIR/small/595356v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@19f6752org.highwire.dtl.DTLVardef@383e74org.highwire.dtl.DTLVardef@8c38f7org.highwire.dtl.DTLVardef@1efe797_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗