Biology subjects

He, T.

Publications and source records attributed to He, T..

At least 19 recordsLinked to original sources

bioRxiv2026

Spatial Tumour Tissue Distribution Dynamics of a Bicycle Peptide-MMAE Toxin Conjugate Profiled by Targeted Mass Spectrometry

A highly specific-NECTIN-4 binding bicyclic peptide covalently linked to the cytotoxin monomethyl auristatin E (MMAE) via a valine-citrulline cleavable linker (zelenectide pevedotin, BT8009) is a promising modality to treat cancer patients with solid tumours. Although the pharmacokinetics and biodistribution of zelenectide pevedotin have been well characterised, a more precise view of tumour delivery and intra-tumoural distribution of its released payload is lacking. To address this, we have developed an approach to profile the spatial tumour and healthy tissue distribution of this anti-cancer agent using laser capture microdissection coupled to targeted liquid chromatography parallel reaction monitoring (LCM-LC-PRM) mass spectrometry. This LCM-assisted spatial pharmacology workflow enables the precise isolation of specific tissue regions, followed by high-resolution analysis of MMAE distribution at sub-tissue-specific levels. By identifying and optimising MS/MS-specific fragmentation ions for accurate and sensitive detection and quantitation of MMAE released from zelenectide pevedotin within tumour tissues, we observed progressive accumulation and sustained retention of MMAE in mouse tumour tissues over a period of 24 h. Conversely, in plasma, liver and muscle tissues, MMAE levels generally declined following early exposure, although inter-animal variability was observed. LCM-based intra-tumour spatial profiling revealed heterogeneous MMAE distribution between tumour cell-rich and stroma-rich regions, with distinct temporal patterns across compartments. Together, our spatial targeted MS method provided valuable insights into zelenectide pevedotin's payload distribution dynamics in vivo, thereby enhancing our understanding of its therapeutic potential and guiding the development of next-generation Bicycle Drug Conjugate (BDC).

cancer biology↗

bioRxiv2026

Simultaneous multi-area recordings in macaque frontoparietal cortex during a manual object-interaction task

Dexterous hand control is essential for daily activities and a top restoration priority for people with tetraplegia, yet neurophysiological datasets suitable for studying and decoding naturalistic hand behavior remain scarce. Most available recordings constrain movements to a small number of degrees of freedom or cover only a single stereotypical grasp-and-hold structure. Moreover, previous brain-computer interface (BCI) studies have largely relied on signals from a single cortical area, even though dexterous hand control is distributed across an interconnected frontoparietal network. To address these limitations, we designed a paradigm that elicits rich hand movements across 40 distinct hand-object interaction conditions. We recorded simultaneous frontoparietal activity with hand kinematics from a rhesus macaque performing them. Neural activity was recorded from the primary motor cortex, anterior intraparietal area, and ventral premotor cortex using microelectrode arrays spanning 1,920 channels, while a multi-camera markerless motion-capture system acquired video from which kinematics were extracted offline. The dataset comprises data from 20 sessions, including processed neural features, synchronized 3D coordinates of hand and elbow keypoints, and trial-level metadata including task conditions and event timing. We further provide technical validation, including a neural decoding benchmark with multiple algorithms for continuous keypoint coordination reconstruction. We found that cross-day and cross-task decoding performance varied among algorithms. Variation in channel availability leads to different performance degradation curves in different algorithms. This task-rich dataset offers a valuable resource for investigating the neural mechanisms of dexterous hand control and for advancing the performance of motor BCIs.

neuroscience↗

bioRxiv2026

End-to-end bimodal anti-counterfeiting by informational DNA nanoparticles

The superior stealth properties and high information density make DNA a sought-after candidate in the field of molecular steganography. Here, we developed the InfinMark end-to-end DNA steganography framework for anti-counterfeiting applications by combining the characteristics of both the Internet of Things (IoT) and DNA-of-Things (DoT). InfinMark includes five modules: Information Transcoding, Fingerprint Writing, Nano-encapsulation, Invisible Marking, and Multi-level Rapid Authentication. It ensures precise anti-counterfeiting information reading and writing through a dynamic DNA-compatible transcoding algorithm, achieves seamless embedding by developing scalable nanoparticle manufacture methods, and supports cross-scenario on-site verification, ultimately granting it comprehensive anti-counterfeiting capabilities spanning from source labeling to terminal tracing. By addressing the bottlenecks in IoT and DoT integration, lifecycle tracking, as well on-site product authentication, this research constructs a full-chain bimodal anti-counterfeiting system, thereby showcasing the practical application of informational DNA nanoparticles in various aspects of production and daily life.

synthetic biology↗

bioRxiv2026

Divergent condensates tune transcriptional responses during stress

Dynamic reorganization of the transcription machinery within nuclear membrane-less compartments is an emergent feature of mammalian stress response, associated with critical cellular decisions. However, mechanisms governing the subcellular formation of these stress-induced condensates and their role in transcription regulation remain poorly understood. Here, we find that heat shock factor 1 (HSF1), transcriptional mediator of protein and cellular homeostasis, forms condensates during various adverse conditions, but these assemblies exhibit context-dependent divergent transcriptional outcomes. During heat shock, HSF1 orchestrates the coordinated assembly of transcription hubs via canonical activation, including post-translational modifications (PTMs), trimerization, and DNA binding. While HSF1s disordered regions restrict condensate formation in unstressed situations, they promote stress-induced condensate maturation to transcriptionally active states. Strikingly, HSF1 condensates that form during other environmental and chemotherapeutic stresses stall at distinct stages of hub formation, assemble independent of PTMs, and exhibit reduced sub-condensate dynamics. These aspects culminate in attenuated genomic occupancy and transcriptional output at HSF1-associated loci, consistent with functional impairment of HSF1 and the transcription machinery via sequestration. Our work suggests that stress-induced transcription factor condensates drive conserved responses during physiological perturbations, but can be inactivated during pathological insults, rationalizing HSF1 and transcriptional dysfunction across degenerative diseases and toxic exposures.

molecular biology↗

bioRxiv2026

Fibroblast-specific Deletion of Yap/Taz Impairs Mouse Postnatal Dermal Development by Suppressing Collagen Production and Deposition

The Hippo pathway effectors YAP and TAZ are key regulators of cell proliferation, apoptosis, and differentiation, thereby maintaining tissue homeostasis and controlling organ size. While their roles in epithelial tissues and cancer are well established, their role in dermal fibroblast extracellular matrix (ECM) regulation is less understood. Here, we investigated the role of Yap/Taz during postnatal skin dermis development. During postnatal growth, mouse skin steadily grows and undergoes significant surface expansion. Postnatal deletion of Yap/Taz in dermal fibroblasts, the primary cells responsible for dermal ECM homeostasis, significantly impaired dermal maturation, as evidenced by marked deficiencies in collagen synthesis and deposition. Isolated fibroblasts from Yap/Taz knockout mice showed reduced proliferation and diminished expression of Yap/Taz target genes (Ccn2, Col1a1), which were rescued by reintroduction of active Yap/Taz. RNA-seq, and spatial transcriptomics and proteomics of Yap/Taz knockout skin revealed substantial downregulation of matrisome genes, including type I (Col1a1, Col1a2) and type III (Col1a3) collagens, which together constitute more than 90% of the skins collagen content. These findings demonstrate that Yap/Taz are essential for dermal ECM homeostasis, highlighting their therapeutic potential in skin regeneration, fibrosis, and aging-related ECM decline.

cell biology↗

bioRxiv2025

Plasmid dependent phage eliminate pathogenic bacteria and antibiotic resistance plasmids from the chicken gut microbiome

Conjugative plasmids are a key reservoir of antimicrobial resistance (AMR) in commensal and pathogenic bacteria within the gut microbiome. Plasmid-dependent phage (PDPs) are a promising therapeutic option directly targeting AMR plasmids, but the efficacy of PDP therapy in vivo is poorly understood. Here, we show that treatment with the PRD1 phage eliminated Salmonella enterica carrying a broad-host range IncP AMR plasmid (RP4) from the chicken gut microbiome. Moreover, PRD1 treatment prevented the transfer of the RP4 plasmid to other members of the gut microbiome, whilst causing only minimal disruption to microbiome composition. Our results demonstrate that PDP therapy rapidly eliminates AMR from a natural gut microbiome by killing pathogenic bacteria and blocking AMR plasmid transmission to commensals, highlighting the conjugative pilus as a promising antimicrobial target.

microbiology↗

bioRxiv2025

Brain Dynamics of Mental Manipulation

Humans effortlessly juggle their internal thoughts, but the neuronal dynamics that support mental manipulation are largely unknown. Leveraging the high spatiotemporal fidelity of intracranial recordings in humans (N = 30), we provide evidence that mental sound manipulation involves the inhibition of sensory cortex and the coordinated engagement of memory and control networks. This modulation manifests in two ways. First, there is a shift in the balance between faster (> 30 Hz) and slower (< 30 Hz) dynamics in primary and secondary auditory areas, suggesting a decrease in local excitability. Second, there is a distributed increase in oscillatory synchrony (6-10 Hz), which predicts imagery vividness and task performance. This evidence points to a key role of local excitability and inter-areal synchrony in the manipulation of thought.

neuroscience↗

bioRxiv2025

Integrating genomics and metabolomics to accelerate the discovery of anti-MRSA natural products from the endophytic fungus Neocucurbitaria sp. VM-36

Endophytic fungi in medicinal plants are a rich source of bioactive natural products. Herein, we performed a comprehensive genomic and metabolic analysis of an uncharacterized endophytic fungus Neocucurbitaria sp. VM-36. Whole-genome sequencing and comparative analysis of the encoded biosynthetic gene clusters with six Cucurbitariaceae strains predicted its potential to produce compounds related to griseofulvin, usnic acid, hypothemycin, and phomasetin. Untargeted metabolomics confirmed several of these predictions with the presence of phomasetin analogs and isousnic acid, and uncovered a diverse range of other secondary metabolites, including specialized lipids, amino acids, and peptides, such as cyclic hexapeptides. We successfully isolated the main compound (1), a phomasetin analog, and show that it has bactericidal activity against different methicillin-resistant and -sensitive Staphylococcus aureus strains comparable in strength to vancomycin and daptomycin. Checkerboard assays with these compounds revealed mostly indifferent interactions. These findings demonstrate the antibacterial potential of compound 1 and Neocucurbitaria sp. VM-36. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=69 SRC="FIGDIR/small/681339v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@19326aeorg.highwire.dtl.DTLVardef@1d078adorg.highwire.dtl.DTLVardef@1a2ba46org.highwire.dtl.DTLVardef@737ed1_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

Trade-offs between phage resistance and conjugative ability shape the ecological and evolutionary response of a multidrug resistance plasmid to plasmid-dependent phage

Phage therapy is a promising alternative to antibiotics to treat multidrug resistant infections. Plasmid dependent phages (PDPs) are particularly attractive as therapeutics because they can both kill targeted pathogen cells, whilst also potentially preventing the further spread of antibiotic resistance genes encoded by plasmids. However, we lack experimental studies of the ecological and evolutionary response of multidrug resistance plasmids against plasmid dependent phage treatment under ecologically relevant scenarios allowing plasmid conjugation. We experimentally evolved populations of E. coli carrying the multidrug resistance RP4 plasmid with the PRD1 PDP under conditions where conjugation was associated with either strong or weak benefits. When opportunities for conjugation were rare, PRD1 only transiently suppressed the conjugative plasmid population due to the rapid evolution of PRD1 resistant plasmids that lacked conjugative ability. Increasing the ecological opportunity for conjugation enhanced plasmid suppression and delayed the evolution of PRD1 resistant plasmids. PRD1 resistance was associated with reduced conjugative ability, but this trade-off was complex due to the heterogeneous impacts of resistance mutations on pilus production and conjugative ability. Mutations and IS element insertions in conjugation genes caused a wide range of PRD1 resistance phenotypes, ranging from complete resistance (virB4) to partial resistance (trbB, trbL). Bioinformatic analysis of publicly available IncP plasmid sequences showed that truncated variants of VirB4 protein are common in natural populations, suggesting that plasmid-dependent phages are an important selective pressure in microbial communities. Our results demonstrate an evolutionary trade-off between conjugative ability and phage resistance that cannot be easily circumvented by plasmids. Targeting multidrug resistance plasmids with PDPs is likely to drive loss of conjugation limiting the transfer of antibiotic resistance genes in bacterial communities.

evolutionary biology↗

bioRxiv2025

Comprehensive analysis of pseudogene expression in human and macaque brains compared with other tissues

Although gene expression in the brain has been extensively investigated and compared to other tissues, the activity of pseudogenes has not been comprehensively surveyed. Here, leveraging large-scale RNA-seq data, we construct consistent pseudogene expression profiles in human and macaque brains and compare them to 29 other tissues. We further annotate pseudogenes with potential cellular roles based on co-clustering them with protein-coding genes. Notably, the majority of the expressed pseudogenes show elevated expression in the brain relative to other tissues, and these pseudogenes show broad and consistent expression patterns across brain subregions. Furthermore, spatiotemporal analyses reveal that pseudogenes in different brain subregions have greatly varying temporal trajectories (e.g., increasing vs. decreasing), in contrast to protein-coding genes that tend to be more uniform. Finally, we identify a set of pseudogenes exhibiting significant changes in neuropsychiatric disorders, some of which overlap with known brain eGenes (genes whose expression is associated with expression quantitative trait loci, eQTLs), as well as with genes implicated by genome-wide association studies (GWAS). Together, our study provides a public resource of pseudogene expression in human and macaque brains (in comparison to other tissues) and highlights aspects of pseudogene expression in brain development and pathogenesis.

bioinformatics↗

bioRxiv2025

A monophyletic origin of domesticated barley

The origin of domesticated barley has been debated extensively over the past century. Early botanical and comparative morphological research and recent genetic research supported a polyphyletic origin. A monophyletic origin was proposed after the discovery that a single genetic locus controls the presence of hull-less grains in all domesticated barley. Interpreting the origin of domesticated barley is further complicated by the archaeological record showing that the first domesticates had two rows of grain on the inflorescence, as does its wild progenitor. However, these two-rowed types effectively disappeared from the record for thousands of years, and they were replaced by derived six-rowed types that dominated barleys cultivation history and only reappeared in the record around one thousand years ago. Here, we used two independent datasets with large sample sizes and genome-wide genetic markers to re-evaluate barley cultivation history. We unequivocally demonstrate that modern domesticated barley has a monophyletic origin. Phylogenetic reconstruction and examination of current archaeological records suggests that the west Fertile Crescent was most likely where barley was first domesticated. Modern two-rowed types were likely derived from six-rowed domesticated types not earlier than 3,500 years ago in modern Turkiye and Iran. We conclude that the two distinct non-brittle rachis haplotypes, coinciding with distinct row types in cultivated barley, are likely the results of two chronological events along the same evolutionary line. Our results provide a reconcilable framework for explaining genetic and phytogeographic patterns and pave the way for a consensus on the origin of barley domestication.

evolutionary biology↗

bioRxiv2025

Single-Cell Sequencing Identifies the Crucial Role of Mitochondrial Fission-Fusion Balance in Cardiac Hypertrophy Progression

BackgroundThe heart undergoes growth in response to both pathological and physiological stimuli. Pathological hypertrophy often leads to cardiomyocyte loss and heart failure (HF), whereas physiological hypertrophy paradoxically protects the heart and enhances cardiomyogenesis. The molecular mechanisms that distinguish these two forms of hypertrophy remain unclear. MethodsIn this study, we utilized single-cell transcriptomics from transverse aortic constriction (TAC) models at 2, 5, 8, and 11 weeks (GSE120064), along with bulk RNA sequencing from mice subjected to 12 months of exercise-induced physiological hypertrophy and cardiomyogenesis (CRA007207), to investigate the molecular differences between pathological and physiological hypertrophy. ResultsOur results reveal the following. Mitochondrial-related pathways are the primary drivers of the pathological changes that occur following TAC. The mitochondrial fission and fusion pathways exhibited increased activity at 2 weeks but decreased activity at 5, 8, and 11 weeks post TAC. The expression pattern of exercise-induced physiological hypertrophy was similar to that of 2-week TAC-induced changes, indicating that the early stage of TAC represents an adaptive physiological response or physiological hypertrophy. Notably, during HF, the fission genes Fis1 and Dnm1l increase, in contrast to the expected decrease in fusion genes. These findings were experimentally validated, indicating that the mitochondrial fission genes Fis1 and Dnm1l are key promoters of HF. ConclusionsOur data indicate that the balance between mitochondrial fission and fusion plays a critical role in the transition from physiological to pathological hypertrophy. The fission-related genes Fis1 and Dnm1l have emerged as key drivers of pathological hypertrophy and heart failure. These findings suggest that targeting fission genes, particularly Fis1 and Dnm1l, may represent promising therapeutic strategies for managing heart failure.

bioinformatics↗

bioRxiv2025

WormID-Benchmark: Extracting Whole-Brain Neural Dynamics of C. elegans At the Neuron Resolution

The nematode C. elegans is a premier model organism for studying neural circuit function due to its fully mapped connectome and genetically identifiable neurons. Recent advances in 3D light microscopy and fluorescent protein tagging have enabled whole-brain imaging at single-neuron resolution. However, extracting meaningful neural dynamics from these high-resolution recordings requires addressing three fundamental challenges: (i) accurate detection of individual neurons in fluorescence images, (ii) precise identification of neuron classes based on anatomical and colorimetric cues, and (iii) robust tracking of neurons over time in calcium imaging videos. To systematically evaluate these challenges, we introduce WormID-Bench, a large-scale, multi-laboratory dataset comprising 118 worms from five distinct research groups, along with standardized evaluation metrics for detection, identification, and tracking. Our benchmark reveals that existing computational approaches show substantial room for improvement in sensitivity, specificity, and generalization across diverse experimental conditions. By providing an open and reproducible benchmarking framework1, WormID-Bench aims to accelerate the development of high-throughput and scalable computational tools for whole-brain neural dynamics extraction in C. elegans, setting the stage for broader advancements in functional connectomics.

neuroscience↗

bioRxiv2024

The endophytic fungus Cosmosporella sp. VM-42 from Vinca minor is a source of bioactive compounds with potent activity against drug-resistant bacteria

Medicinal plants serve as valuable resources for the isolation of endophytic fungi. Vinca minor is a well-known producer of important vinca alkaloids and emerges as a promising source of endophytic fungi with antibacterial potential and biosynthetic capacity. In this study, we isolated an endophytic fungus from V. minor and identified it as Cosmosporella sp. VM-42. To date, relatively little is known about this fungal genus. The ethyl acetate extract of this isolate selectively inhibited Gram-positive bacteria, such as methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA). Therefore, we isolated the most abundant compound from the crude extract and identified it as nectriapyrone with MIC and MBC values ranging from 125 to 62.5 {micro}g/mL against MSSA and MRSA strains. We further sequenced and annotated the 39.07 Mb genome of the isolate, revealing that it encodes 9,842 protein-coding genes, including 415 genes for carbohydrate-active enzymes and various biosynthetic gene clusters. Our untargeted metabolomic analysis shows that the fungus produces various secondary metabolites, including cyclodepsipeptides, dimeric naphtho-{gamma}-pyrones, and macrolactones, which are known to have antifungal and antibacterial activities. In addition, we used small-molecule epigenetic modulators to activate the expression of silent biosynthetic gene clusters to broaden the chemical profile of Cosmosporella sp. VM-42. Taken together, we provide a first systematic analysis of Cosmosporella sp. VM-42, and our results show that it is a promising source of compounds with pharmacological potential against drug resistant bacteria. HighlightsO_LIFirst comprehensive study of Cosmosporella sp. VM-42 by genomics and metabolomics C_LIO_LIThe fungus produces chemically-diverse secondary metabolites with antibacterial activity C_LIO_LINectriapyrone, the main compound, shows bactericidal activity against MSSA and MRSA C_LIO_LISmall-molecule epigenetic modulators trigger production of putatively new secondary metabolites. C_LIO_LIOther secondary metabolites of Cosmosporella may present novel bioactivities. C_LI

biochemistry↗

bioRxiv2024

Plant-induced transcriptional plasticity diverges between generalist and specialist herbivores

Most herbivores are specialized on particular host plants but some are generalists that can exploit distinct hosts. Generalists may have evolved adaptive transcriptional plasticity to cope with the defenses of the different hosts. However, the fundamental differences in plant-induced transcriptional plasticity between generalists and specialists remain poorly understood. Here, we investigated transcriptional plasticity of the generalist aphid Myzus persicae and two specialist aphids, Brevicoryne brassicae and Rhopalosiphum padi, by transferring them between Brassica napus (a host for B. brassicae but not for R. padi) and Zea mays (a host for R. padi but not for B. brassicae), both suitable hosts for M. persicae. Generalist and specialist aphids exhibited transcriptional plasticity coordinately in response to different plant species, but their gene expression patterns often diverged. Generalists suppressed plant-defense salicylic acid (SA) signaling in the host plants, while specialist aphids provoked it in nonhost plants. SA signaling had limited effects on gene expression in the generalist aphids, but significantly shaped transcriptional responses of the specialists. These findings underscore the fundamental differences in plant-induced transcriptional plasticity between generalists and specialists and highlight the critical role of plasticity directionality in insect adaptation. Significance statementMost insects specialize in feeding on just a few specific plants, but some generalists can thrive on many plant species. This study compares the gene expression of green peach aphid Myzus persicae, a generalist, with two specialist aphids in response to different types of plants. Generalists showed adaptive plasticity in their gene responses, while specialists often exhibited opposite gene expression changes. Interestingly, generalists appeared to suppress plant defense signals like salicylic acid, while specialists tended to trigger them. These findings highlight how gene expression plasticity enables generalists to adapt and survive, providing new insights into the evolution of insect-plant interactions.

plant biology↗

bioRxiv2024

Effective metabarcoding of endophytic fungi through host-exclusive primer design for nanopore long-read sequencing

Metabarcoding is a powerful tool to simultaneously identify multiple taxa within a habitat. However, its application to host-associated microbiomes is challenged by substantial co-amplification of host DNA. Here we developed a host-exclusive primer design workflow, to selectively generate amplicons from target taxa while excluding the host. This workflow is centered around a new computational tool, mbc-prime, that can generate a list of discriminative candidate primers and score them. We showcase the use of this tool in the design of primers for long-read metabarcoding of endophytic fungi in Vinca minor. Mbc-prime streamlines the design of fungus-specific primers, enabling efficient and plant-free amplification of fungal rDNA from mixed DNA samples. Our workflow can be used to study the composition of complex host-associated microbiomes. It should be universally applicable for the design of discriminative primers in a user-friendly and practical manner and thus be of use for various researchers in microbiome research.

molecular biology↗

bioRxiv2024

Divergent effects of 3-nitrooxypropanol on enteric methane emissions in Holstein and Brown Swiss cows, and its lack of synergy with Acacia mearnsii tannin extract

The objectives of this study were to investigate the combined effects of 3-nitrooxypropanol (3-NOP) and Acacia mearnsii tannin extract (TAN), and their interactions with dairy cattle breed [Brown Swiss (BS) vs. Holstein Friesian (HF)], on lactational performance, and enteric methane (CH4) emissions. Sixteen multiparous mid-lactation cows, including 8 BS and 8 HF cows were used in a split-plot design, with breed as the main plot. Cows within each subplot were arranged in a replicated 4 x 4 Latin Square design with a 2 x 2 factorial arrangement of treatments across four 24-d periods. The experimental diets were: 1) CON (basal total mixed ration), 2) 3-NOP (60 mg/kg DM), 3) TAN (3% of DM), and 4) 3-NOP + TAN. Spot samples of urine, feces, and gas emissions (via GreenFeed) were collected at the end of each period 8 times over 3 days. No 3-NOP x TAN x Breed interactions were observed for DM intake (DMI), milk production, or enteric gas emissions, except for CH4 yield (g/kg DMI) and CO2 production. Breed influenced DMI, milk production, and component yields, with HF cows consuming 3.7 kg/d more DMI, producing 9.3 kg/d more milk, and achieving greater feed efficiency and higher milk component yields than BS cows. Milk yield and energy-corrected milk (ECM) tended to increase in HF but tended to decrease in BS cows by 3-NOP. Cows fed TAN had 1 kg/d lower DMI with the tendency for 3-NOP x TAN showed greater reduction when TAN was fed alone, but milk yield, ECM, and feed efficiency remained unchanged. Cows fed TAN exhibited 18% lower milk urea nitrogen (N) concentration and 23.0% lower urinary N but 36.7% greater fecal N excretions as a percentage of daily N intake. A 3-NOP x Breed interaction was observed in CH4 production (g/d), with a 21.7% reduction in HF, and a 13.0% reduction in BS. Similarly, there were 3-NOP x Breed tendencies in CH4 yield and intensity (g/kg ECM), with reductions in HF cows of 21.8% and 23.4%, respectively, compared to 11.0% and 10.8% in BS cows. In conclusion, there were no synergistic or additive effects between 3-NOP and TAN on enteric CH4 mitigation. The enteric CH4 emission mitigating effect of 3-NOP was more pronounced in HF cows than in BS cows. Further research is needed to understand breed-specific responses and to optimize CH4 mitigation strategies for inclusion in national greenhouse gas inventories. ImplicationsThis study demonstrated that the feed additive 3-nitrooxypropanol reduces enteric methane emissions in dairy cows, with a greater reduction observed in Holsteins (22%) compared to Brown Swiss (13%) cows. While combining 3-NOP with Acacia mearnsii tannin extract did not further reduce methane. Feeding Acacia mearnsii extract decreased nitrogen excretion, potentially reducing environmental nitrogen pollution from manure. Neither additive substantially impacted milk production; however, 3-nitrooxypropanol tended to increase milk yield in Holsteins while reducing it in Brown Swiss. Overall, this study suggests that enteric methane mitigation efficacy of dietary strategies for different cattle breeds should be further investigated.

animal behavior and cognition↗

bioRxiv2024

The Whole Proteome, Phosphoproteome, and Glycoproteome Landscape of Pan-Cancer Cell Lines Profiled by Mass Spectrometry and Reverse Phase Protein Array

Mammalian cancer cell lines are essential model systems in biomedical research. We conducted multi-level proteomics analyses on 54 widely used cancer cell lines derived from various tissue-of-origins using two prominent proteomics technologies: mass spectrometry (MS) and reverse-phase protein array (RPPA). Our analysis identified 10,088 proteins, 33,609 phosphorylation sites across 7,289 phosphoproteins, and 56,350 site-specific glycans on 16,296 glycosylation sites from 5,966 glycoproteins, along with 305 drug-relevant protein and phosphoprotein targets. Our results reveal both consistent and distinct patterns in protein expression and modification between MS and RPPA, underscoring their complementary strengths as discovery tools. Additionally, we identified protein features that distinguish tissue origins across different cell line lineages. This dataset supports model system selection for drug target-related studies in vitro and provides valuable insights into key signaling pathways. Overall, this comprehensive resource enables new opportunities for exploration in cancer biology and offers significant value to research communities focused on biomarker profiling, drug target discovery, and understanding mechanisms across diverse cancer types.

cancer biology↗