Biology subjects

Qiu, D.

Publications and source records attributed to Qiu, D..

At least 19 recordsLinked to original sources

bioRxiv2026

Interspecific hybrids reveal a deeply conserved nuclear role of EIF1A-family proteins in zygotic genome activation

Zygotic genome activation (ZGA) launches inaugural gene expression and autonomous development of the embryo. Yet, conserved regulators of ZGA among different mammals remain poorly defined. Here, we generated interspecific hybrid embryos to place distant mammalian genomes in a shared maternal cytoplasm. These hybrids undergo cleavage and transcriptional activation from divergent parental genomes. Comparative transcriptomics identifies a core set of zygotic genes reproducibly activated across different hybrid contexts, including the Eif1a-like family. Depletion of EIF1A-like proteins disrupts ZGA and preimplantation development in mouse, pig and cattle embryos. Although best known for translation initiation, these proteins contain a conserved nuclear localization signal and translocate to the nucleus at the onset of major ZGA. Further studies revealed that they occupy promoters of nearly all ZGA genes and MERVL/MT2 retrotransposons, required for local chromatin accessibility. These findings uncover a conserved nuclear licensing function for EIF1A-family proteins in zygotic genome activation among divergent mammalian embryos.

developmental biology↗

bioRxiv2026

Ecdysone Antagonizes Growth and Juvenile Hormone-Dependent Soldier Caste Identity in Camponotus floridanus

From tardigrades to lobsters, ecdysone is the critical steroid hormone regulating ecdysis across Panarthropoda. In insects, the sesquiterpenoid hormone called juvenile hormone (JH) prolongs the juvenile state, and together, ecdysone and JH regulate growth and developmental timing. The complex worker caste system in ants has elaborated multiple times and is composed of individuals exhibiting an array of size and allometry variation. While we have accumulated a great deal of knowledge related to the role of JH in influencing size and caste identity in ants, the role of ecdysone in caste development remains poorly understood. Here we show in Camponotus floridanus that ecdysone negatively regulates size, can block soldier determination, and there is an antagonistic relationship between JH and ecdysone. First, we show that during the worker-soldier switchpoint sensitivity window of development, ecdysone is capable of negatively influencing head size, body size, head-to-body allometry, and unexpectedly extends developmental timing. We then show at the molecular level that as expected, developing soldiers upregulate ecdysone degradation, yet surprisingly, developing soldiers also upregulate ecdysone synthesis and the reception of ecdysone signalling. We next investigated the interaction between JH and ecdysone signaling and found that the two hormones antagonize each other at both the molecular and phenotypic levels. Furthermore, in contrast to other insects, we uncovered that ecdysone signaling is negatively regulated by temperature. Beyond its role in size regulation, we also provide preliminary data suggesting that the interaction of JH and ecdysone may have sex inducing properties, generating male-like anomalies. Altogether, our findings show that ecdysone blocks JH-dependent soldier development and we propose that the dynamic regulation of ecdysone synthesis, reception, and degradation may be the basis for the complex sigmoid-like head-to-body allometry found in this species as well as several others across ants. More generally, the evolutionary tinkering of antagonistic growth hormones, their regulation and interaction, and opposing responses to environmental cues, may be a major source for size diversity across developmentally plastic organisms.

developmental biology↗

bioRxiv2026

An 8 Gene Bevacizumab Resistance Signature Predicts Prognosis and Reveals Immunosuppressive Microenvironment in Colorectal Cancer

BackgroundBevacizumab resistance severely limits long-term efficacy in metastatic colorectal cancer (CRC). This study aimed to develop and validate a bevacizumab resistance-associated gene signature for prognosis prediction and immune microenvironment characterization in CRC. MethodsTwo GEO datasets (GSE19862, GSE86582) with bevacizumab response data and TCGA-COAD/READ RNA-seq data were analyzed. Overlapping differentially expressed genes (DEGs) linked to both CRC progression and bevacizumab resistance were identified. An 8-gene signature (AXIN2, PSORS1C1, KRT74, SLC2A3, STIL, IL33, GALNT6, HSD11B2) was constructed via univariate Cox and LASSO-Cox regression. ResultsIn the TCGA cohort, high-risk patients had shorter overall survival (OS; log-rank P < 0.0001). Time-dependent ROC yielded 1-year AUC = 0.638, 3-year AUC = 0.657, and 5-year AUC = 0.757. Multivariate Cox regression confirmed the risk score as an independent prognostic factor. External validation in GSE39582 (optimal cutoff = -1.49) replicated these findings: high-risk patients had inferior OS (P = 0.0016) with acceptable 1/3/5-year AUCs and retained independent prognostic value (HR = 1.634, P = 0.00415). CIBERSORT and ESTIMATE analyses showed that the high-risk group was characterized by increased M2 macrophages and neutrophils, higher immune and stromal scores, and reduced activated memory CD4+ T cells, monocytes, and activated dendritic cells (all P < 0.05). GSEA highlighted enrichment of TNF-/NF-{kappa}B, IL-6/JAK/STAT3, and immune checkpoint pathways in the high-risk group. AXIN2 (HR = 0.829, P = 0.032) was an independent protective factor, while PSORS1C1 (HR = 1.356, P = 0.048) was an independent risk factor. ConclusionThe 8-gene bevacizumab resistance signature robustly predicts prognosis and reflects an immunosuppressive microenvironment closely linked to bevacizumab failure in CRC. These findings provide novel insights into immune-mediated resistance and support clinical risk stratification.

bioinformatics↗

bioRxiv2026

Identification of Reductases Catalyzing Benzyl Alcohol Formation during Salicylic Acid Biosynthesis in Plants

Salicylic acid (SA), a central hormone in plant immunity, is biosynthesized via a recently elucidated phenylalanine-derived pathway in most seed plants. This pathway requires benzyl alcohol as a key substrate for the formation of the SA precursor benzyl benzoate. However, how benzyl alcohol is produced in plants was unclear. Here, we identify a two-step conversion of benzoyl-CoA to benzyl alcohol via benzaldehyde in Nicotiana (N.) benthamiana. From a forward genetic screen for SA-deficient mutants, the and {beta} subunits of heterodimeric benzaldehyde synthase (BalS) involved in the conversion of benzoyl-CoA to benzaldehyde were found to be required for SA biosynthesis in N. benthamiana. Further reverse genetic analysis revealed that the NADPH-dependent benzaldehyde reductase (BalR1) acts downstream of BalS to convert benzaldehyde to benzyl alcohol. Interestingly, OsBalR1, but not OsBalS or OsBalS{beta}, is required for maintaining high basal SA levels in rice, suggesting the presence of redundant benzoyl-CoA-reducing activities or alternative biosynthesis routes for benzyl alcohol production. Together, this work defines the missing enzymatic steps in phenylalanine-derived SA pathway and provides insights into the evolutionary diversification of SA production strategies in plants.

plant biology↗

bioRxiv2026

Temporal-deviation-driven community detection uncovers early-warning signals for critical transitions in complex diseases

Early detection of critical transitions in complex diseases is crucial for timely clinical intervention. However, as patients often provide only a single snapshot, identifying sample-specific early-warning signals (EWS) from a dynamical evolution perspective remains challenging, coupled with high-dimensional noise amplification. Here, we present TD-COM, a framework for detecting personalized EWS of critical transitions via single-sample community detection. By constructing a temporal perturbation map STDN, TD-COM captures latent dynamical perturbations inferred from static individual profiles. Synergizing these temporaldeviation signals with static topological features, TD-COM implements a multilevel node filtering strategy during community detection, effectively suppressing single-sample noise. Validated on hour-scale, multi-year, and multi-decade transcriptomic data, TD-COM robustly detects critical states preceding clinical deterioration and uncovers their underlying molecular mechanisms. Comparative experiments demonstrate that TD-COM outperforms existing methods in accuracy and topological robustness. Thus, TD-COM provides a generalizable framework for personalized early warning of complex diseases, particularly when longitudinal sampling is infeasible.

bioinformatics↗

bioRxiv2026

TcrDesign: De novo design of epitope specific full-length T cell receptors

T cell receptors (TCRs) are essential for adaptive immune recognition. Recently computational tools have been developed to predict the interactions between TCR and epitope, and artificial intelligence models have been proposed to generate the complementarity determining region 3 (CDR3) region of {beta} chain TCR. However, de novo design of experimentally validated, functional, full-length epitope-specific TCRs remains a significant challenge. Here we developed TcrDesign, a deep learning framework based on large-scale unlabeled TCR and epitope datasets to generate epitope-specific, full-length TCRs. TcrDesign comprises two modules: TcrDesign-B for TCR-pMHC binding prediction with state-of-the-art accuracy, and TcrDesign-G for functional full-length TCR sequence generation. Pre-trained on large-scale unlabeled datasets using transformer-based architectures, TcrDesign achieves state-of-the-art performance in both TCR-epitope binding prediction and de novo TCR sequence generation. Furthermore, epitope-major histocompatibility complex (MHC) binding and functional activation of TcrDesign-generated TCRs were experimentally validated. TcrDesign provides an efficient and modular approach for designing epitope-specific full-length TCRs, with experimental validation confirming its utility.

bioinformatics↗

bioRxiv2026

Simultaneous Capillary Electrophoresis - Mass Spectrometry profiling of (p)ppGpp and dinucleoside polyphosphates reveals oscillatory (p)ppGpp dynamics and a potential synchronisation between alarmones

To survive stressful conditions, bacteria enter the stringent response mediated by the magic spot nucleotides (MSN) guanosine 35-bispyrophosphate (ppGpp) and guanosine 3-diphosphate 5-triphosphate (pppGpp). Another group of so-called alarmones elevated under stress are dinucleoside polyphosphates (NpnNs), such as diadenosine triphosphate (Ap3A). How these two groups of alarmones intersect with one another is poorly understood. Here, we present a sensitive method using capillary electrophoresis coupled to mass spectrometry (CE-MS) with heavy isotope labeled internal references to separate and quantify magic spot nucleotides in parallel with NpnNs. This approach uncovered oscillatory fluctuations in MSN and some NpnN during exponential growth, suggesting more dynamic regulation of the stringent response than previously thought. In addition, up to eleven NpnNs were detected after prolonged growth. NpnN levels were also quantified under various amino acid starvation conditions, revealing a pronounced accumulation in late stationary phase. In summary, our parallel assignment and quantification of highly charged signaling molecules in bacteria under stress conditions paves the way to better study and understand the cross-talk between different alarmones.

biochemistry↗

bioRxiv2025

Identification of Vector Organisms and Their Carried Pathogens by Metagenomic Sequencing

Vector surveillance is vital for public health, yet traditional methods often face limitations. This study assessed the use of metagenomic sequencing for analyzing mosquitoes, cockroaches, flies, and rodents from Zhongshan, China. The results revealed a high concordance between metagenomic and Sanger sequencing for species identification (Kappa = 0.667, P = 0.011). Metagenomic analysis identified vector-specific dominant bacteria, including Wolbachia in mosquitoes, Blattabacterium sp. in cockroaches, Bartonella tribocorum and Leptospira interrogans in rodents, and Vagococcus teuberi in flies. It also detected numerous classical pathogens, such as Enterococcus faecalis, L. interrogans, and Klebsiella pneumoniae. Among the identified fungi and viruses, 19 were human pathogens, while seven posed a threat to agriculture, notably Pepper mild mottle virus and Tomato brown rugose fruit virus. These findings systematically characterize the microbial communities associated with various vectors, highlight the potential of metagenomics for broad pathogen screening, and underscore its utility in large-scale vector surveillance and public health protection. ImportanceVectors are major carriers of numerous diseases and present risks fot cross-border transmission. Existing detection methods for vectors and their pathogens remain inefficient, insensitive, and prone to difficulties in species identification. Despite extensive efforts in vector identification, the potential threats posed by their associated pathogens remain unclear, demonstrating the need for more effective diagnostic strategies. Metagenomic sequencing offers a promising solution to this challenge. In this study, we applied metagenomic sequencing to vectors collected from urban and port areas in Zhongshan, China, to evaluate its efficacy in pathogen detection. Overall, our work contributes to a better understanding of the public health risks posed by vector-borne pathogens.

microbiology↗

bioRxiv2025

Juvenile Hormone Signalling Underlies the Switchpoint and Differentiation of Soldiers in Camponotus floridanus

Multicellular organisms are composed of various cell types derived from cellular determination and differentiation, which carry out specialized functions in the individual. Ant societies are composed of various castes of individuals derived from caste determination and differentiation, which divide specialized tasks in the colony. From cells to societies, the underlying mechanisms orchestrating determination and differentiation at different biological levels are fundamental in generating biological diversity. While past work has described the developmental process of caste determination and differentiation in ants, the endocrinological and molecular basis for these processes in the genus Camponotus remains unknown. Here we show that minor worker and soldier development is determined by a Juvenile hormone (JH)-mediated minor-soldier switchpoint in C. floridanus. Hormonal treatments identified a sensitivity period when JH can induce bipotential larvae to become soldiers. Induced soldiers phenocopy natural soldiers in size and soldier-specific head-to-body allometry and this is associated with a heterochronic shift in metamorphosis. Furthermore, we molecularly characterize the activity of the JH pathway at the level of synthesis, degradation, reception, and downstream effectors during caste determination and differentiation. Surprisingly, rather than JH synthesis, we found JH reception and JH degradation are the major signalling processes differentially regulated across castes and RNAi of juvenile hormone degradation enzymes generates soldiers. Finally, our data suggests that the hyperdiverse genus Camponotus has independently evolved a JH-mediated minor-soldier switchpoint similar to that known in Pheidole. More generally, the evolution of plastic hormonal regulation may facilitate the origin of developmental determination and differentiation processes underlying complex adaptive phenotypes. Significance StatementAnts live in complex societies like a superorganism where individuals divide reproductive and various non-reproductive labors, which are analogous to the array of functions of germ cells and highly differentiated somatic cells in an organism. While there are over 1500 species of the hyperdiverse genus Camponotus, a genus whose diversity reflects their complex caste system including minor workers and soldiers, the molecular and endocrinological basis for how these castes develop remains unknown. Here we have identified a juvenile hormone (JH) mediated minor-soldier switchpoint during larval development, and have characterized components of the JH signalling pathway that regulate soldier development. This work enables further understanding of how castes are regulated across ants and social insects more broadly.

developmental biology↗

bioRxiv2025

Integral Synthesis and Clearance Analysis via DIA (ISDia) Reveals Coordinated Protein Dynamics Regulation during Endoplasmic Reticulum Stress

Endoplasmic Reticulum (ER) stress disrupts protein homeostasis, driving cellular responses critical for survival, development and disease. However, systematic proteome-wide analyses of protein synthesis and clearance during ER stress remain limited. In this study, we developed Integral Synthesis and clearance analysis via DIA (ISDia), a robust mass spectrometry (MS)-based workflow that integrates multiple pulsed-SILAC labeling timepoints under one condition into a single sample and utilize data-independent acquisition (DIA) to quantify heavy and light peptide changes across conditions. It enables proteome-wide tracking of protein synthesis and clearance with high coverage by directly comparing light and heavy peptides in pSILAC-DIA experiments across multiple conditions. Using ISDia, we uncover diverse regulatory mechanisms by which protein synthesis and clearance are modulated to regulate protein abundances during ER stress, revealing PERK dependent and independent regulatory mechanisms across subcellular compartments, complexes and isoforms. These findings highlight the potential of ISDia as a powerful and widely applicable workflow for revealing protein abundance regulatory mechanisms.

systems biology↗

bioRxiv2025

Acidocalcisome-like vacuoles constitute a feedback-controlled phosphate buffering system for the cytosol

Cells experience strong variations in the consumption and availability of inorganic phosphate (Pi). Since Pi is an essential macronutrient but excess Pi has negative impacts on nucleotide hydrolysis and metabolism, its concentration must be maintained in a suitable range. Conserved storage organelles, acidocalcisomes, provide this buffering function. We used acidocalcisome-like yeast vacuoles to study how such organelles are set up to for this task. Our combined in vitro and in vivo analyses revealed that their ATP-driven polyphosphate polymerase VTC converts cytosolic Pi into inorganic polyphosphates (polyP), which it transfers into the vacuole lumen. Luminal polyphosphatases immediately hydrolyse this polyP to establish a growing reservoir of vacuolar Pi. Product inhibition by this Pi pool silences the polyphosphatases, caps Pi accumulation, and favours vacuolar polyP storage. Upon cytosolic Pi scarcity, the declining inositol pyrophosphate levels activate the vacuolar Pi exporter Pho91 to replenish cytosolic Pi. In this way, acidocalcisome-like vacuoles constitute a feedback-regulated buffering system for cytosolic Pi, which the cells can switch between Pi accumulation, Pi release, and high-capacity phosphate storage through polyP.

cell biology↗

bioRxiv2025

Engineering novel AAV capsids by global de-targeting and subsequent muscle-specific tropism in mice and NHPs

Recombinant adeno-associated viral (rAAV) vectors are a potent tool, but their clinical application is restricted by insufficient target tissue transduction and liver toxicity. We employed a novel two-step engineering strategy to create novel rAAV capsids with global tissue de-targeting, then produced strong tissue-specific expression by adding a peptide sequence. We created a novel capsid, AAV.Zero1, with globally de-targeted transduction by loop swapping domains from AAV9 into AAV2. Making an R585A substitution (AAV.Zero2) re-targeted tissues but deleting residues 585-587 (AAV.Zero3) abrogated transduction. Inserting a myogenic peptide into AAV.Zero3 produced a novel capsid (AAV.eM) with strong muscle-specific transgene expression while maintaining minimal off-target expression, including in liver, which was conserved in two mouse strains and non-human primates. AAV.eM showed similar expression as the leading myotropic vector MyoAAV.4A but had a more favorable safety profile. Importantly, AAV.eM was able to functionally rescue a mouse model of Duchenne Muscular Dystrophy following systemic delivery of a micro-dystrophin gene. Thus, AAV.eM is an improved myotropic rAAV capsid that de-targets other tissues, especially the liver, and proof-of-concept for a platform to create capsids with specific properties that translate across species by addition of peptides onto low transduction backbones.

bioengineering↗

bioRxiv2025

A biGWAS strategy reveals the genetic architecture of the interaction between wheat and Blumeria graminis f. sp. tritici

BackgroundWheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt) is one of the most significant diseases affecting global wheat production. Breeding for disease resistance (R) genes against Bgt often follows a boom-bust cycles, where cultivars with effective resistance are widely deployed on an expanding area until virulence emerges in the avirulence (Avr) pathogen population. While extensive effort has been devoted to identifying and cloning R genes, Avr genes remain relatively understudied, limiting our understanding of R-Avr interactions. That said, understanding R-Avr interactions is crucial for developing durable resistance strategies. ResultsWe conducted whole genome sequencing on 245 Bgt isolates collected from major wheat-growing regions in China, identifying 120 genetically unique isolates. Each of these unique isolates was inoculated and phenotyped on a diverse panel of wheat germplasm. Through Genome-Wide Association Analysis (GWAS) in both Bgt and wheat, we identified 65 Avr loci and 251 R loci overlapping with nine and eight cloned Avr or R genes, respectively. On average, each isolate carries eight Avr alleles, ranging from one to 17. Little geographical preference for Avr alleles or their combinations was observed, suggesting that disease resistance breeding against this pathogen should be coordinated at the national level. The level of resistance level is positively correlated with the number of R alleles carried by a wheat line, and the average frequency of an R allele is 2% among the wheat panel, indicating the potential for accumulating R alleles in breeding programs. We mapped 212 R-Avr interactions based on joint GWAS using both plant and pathogen genomes and cross-species epistasis, where a network of interactions was formed between wheat and Bgt. These interactions indicate that pyramiding five major R loci has the potential to confer resistance to half of the Avr loci. As a proof of concept, we successfully verified two previously described R-Avr pairs using tobacco experiments. Furthermore, we provided molecular validation evidence for three new Avr genes, including Bgt-50651, BgtE-5826 and BgtE-20009, and two new R-Avr interactions. Among them, Bgt-50651 interacts with Pm1a, Pm2a, and another unidentified R gene located near the Pm6/Pm52 interval. ConclusionOur study provides a framework for understanding the genetic interaction between plants and pathogens. The discovery of novel R/Avr loci and their complex interaction network underscores the need to integrate crop and pathogen genetic background, particularly the R/Avr allele composition, into breeding program design. These findings have significant implications for developing durable resistance strategies in wheat alongside offering valuable insights into the broader dynamics of plant-pathogen interactions.

genomics↗

bioRxiv2025

HISTONE DEACETYLASE COMPLEX 1 modulates sepal length through the ethylene-ROS module

Organ size is precisely regulated during development to ensure proper function. The sepal must maintain an appropriate size throughout its growth to protect the developing flower bud until blooming. Despite its significance, the mechanisms regulating sepal size during its maturation remain poorly understood. Here we identify the HISTONE DEACETYLASE COMPLEX 1 (HDC1) as a positive regulator of sepal size during maturation in Arabidopsis thaliana. hdc1 mutation prolongs sepal elongation due to delayed sepal maturation, thus hindering flowers from opening timely. Transcriptomic and proteomic analyses reveal that both plant hormone ethylene and reactive oxygen species (ROS) signaling are involved in the HDC1s modulation of sepal size during maturation. Further genetic and chemical data show that during sepal maturation, HDC1 upregulates ethylene levels to promote ROS accumulation, thereby regulating the cessation of sepal growth. Collectively, our study revealed that HDC1 integrates ethylene and ROS signaling to regulate sepal maturation, providing new insights into the molecular mechanisms that govern organ size during maturation in plants.

plant biology↗

bioRxiv2025

Single-cell copy number alteration signature analysis reveals masked patterns and potential biomarkers for cancer

Copy number alteration (CNA) is a major type of cancer genome alteration that drives cancer progression. CNA signature analysis can reveal underlying etiology and provide biomarkers for cancer treatment, and existing CNA signature analyzes are all performed using bulk tissue samples. However CNA usually affect large proportion of genome, and the CNA profile of bulk sample does not reflect the actual CNA profiles of the individual cancer cells of the sample, especially in tumors with high heterogeneity, such as hepatocellular carcinoma (HCC). Furthermore, the evolutionary trajectory of CNA mutational processes still remain elusive. Here we build a method to comprehensively analyze the CNA signatures of HCC from single-cell and bulk sample perspective, revealing patterns and potential noise signals from the usually performed bulk tissue CNA signature analysis. Single-cell signature analysis delineated the evolutionary trajectory of HCC CNA signatures, and different CNA signatures consistently emerge in different HCC evolution stages. Single-cell CNA signatures show robust performance in patient prognosis and drug sensitivity prediction. This work not only reveals specific considerations in analyzing CNA signature derived from bulk tissue but also depicts CNA evolution process and provides potential biomarkers for the prognosis and treatment of HCC patients. HighlightSingle-cell analysis reveals CNA signatures masked in bulk tissue. Single-cell analysis delineates the evolutionary trajectory of CNA signature. Small CNAs occur early and large CNAs happens late in HCC evolution. Single-cell CNA signatures show robust performance in guiding cancer clinical treatment.

genomics↗

bioRxiv2024

PfATP2 is an essential flippase on the Plasmodium falciparum surface that influences parasite sensitivity to antiplasmodial compounds

Antimalarials play a crucial role in the fight against malaria. However, resistance of the most virulent malaria parasite, Plasmodium falciparum, to front-line antimalarials is spreading. To identify new antimalarials, millions of compounds have been screened for their ability to inhibit the growth of blood-stage P. falciparum parasites. To gain insight into the mode of action of novel compounds and the ease by which parasites can acquire resistance to them, many have been tested in in vitro evolution experiments, in which parasites are exposed to the compound for a prolonged period of time. In a recent study, parasite resistance to two compounds, MMV007224 and MMV665852, was associated with amplification of the pfatp2 gene, implicating PfATP2, a putative phospholipid flippase, as a parasite drug target or resistance determinant. These two compounds, along with MMV665794 (which is structurally related to MMV007224) had previously been reported to dysregulate pH in parasites. Here, we show that PfATP2 localises to the parasite surface and is essential for parasite growth. We demonstrate that parasites genetically engineered to overexpress PfATP2 display reduced sensitivity to MMV665794, MMV007224 and MMV665852 compared to parasites with a normal expression level of the protein, and that parasites in which PfATP2 is knocked down become hypersensitive to the three compounds. We show that PfATP2 expression level does not affect the cytosolic pH of parasites, or the potency by which MMV665794 or MMV007224 dysregulate parasite pH. We show that PfATP2-overexpressing parasites internalise a fluorescent phosphatidylserine analogue (NBD-PS) at a greater rate than parasites with a normal expression level of PfATP2, and that parasites in which PfATP2 is knocked down have a reduced rate of NBD-PS uptake. Further, we provide evidence that MMV665794 and MMV007224 inhibit both ATP-dependent and ATP-independent NBD-PS internalisation mechanisms, the former at lower concentrations. Together, our data are consistent with PfATP2 serving as a major ATP-dependent phosphatidylserine internalisation mechanism at the parasite plasma membrane, and being a target of MMV665794 and MMV007224.

microbiology↗

bioRxiv2024

A mosaic of whole-body representations in human motor cortex

Understanding how the body is represented in motor cortex is key to understanding how the brain controls movement. The precentral gyrus (PCG) has long been thought to contain largely distinct regions for the arm, leg and face (represented by the "motor homunculus"). However, mounting evidence has begun to reveal a more intermixed, interrelated and broadly tuned motor map. Here, we revisit the motor homunculus using microelectrode array recordings from 20 arrays that broadly sample PCG across 8 individuals, creating a comprehensive map of human motor cortex at single neuron resolution. We found whole-body representations throughout all sampled points of PCG, contradicting traditional leg/arm/face boundaries. We also found two speech-preferential areas with a broadly tuned, orofacial-dominant area in between them, previously unaccounted for by the homunculus. Throughout PCG, movement representations of the four limbs were interlinked, with homologous movements of different limbs (e.g., toe curl and hand close) having correlated representations. Our findings indicate that, while the classic homunculus aligns with each areas preferred body region at a coarse level, at a finer scale, PCG may be better described as a mosaic of functional zones, each with its own whole-body representation.

neuroscience↗

bioRxiv2024

A wheat tandem kinase and NLR pair confers resistance to multiple fungal pathogens

Recently discovered tandem kinase proteins (TKPs) are pivotal to the innate immune systems of cereal plants, yet how they initiate plant immune responses remains unclear. This report identifies the wheat protein WTN1, a non-canonical NLR receptor featuring tandem NB-ARC domains, as crucial for WTK3-mediated disease resistance. Both WTK3 and its allelic variant Rwt4, known for conferring resistance to wheat powdery mildew and blast respectively, are capable of recognizing the blast effector PWT4, and activate WTN1 to form calcium-permeable channels, akin to ZAR1 and Sr35. This study unveils a unique plant defense mechanism wherein TKPs and associated NLRs operate as "sensor-executor" pairs against fungal pathogens. Additionally, evolutionary analyses reveal a co-evolutionary trajectory of the TKP-NLR module, highlighting their synergistic role in triggering plant immunity. One Sentence SummaryAn ancient synergistic TKP-NLR pair triggers innate immunity for multiple disease resistance in wheat.

plant biology↗