Explore the vast range of titles available.

All tissue development and replenishment relies upon the breaking of symmetries leading to the morphological and operational differentiation of progenitor cells into more specialized cells. One of the main engines driving this process is the Notch signal transduction pathway, a ubiquitous signalling system found in the vast majority of metazoan cell types characterized to date. Broadly speaking, Notch receptor activity is governed by a balance between two processes: 1) intercellular Notch transactivation triggered via interactions between receptors and ligands expressed in neighbouring cells; 2) intracellular cis inhibition caused by ligands binding to receptors within the same cell. Additionally, recent reports have also unveiled evidence of cis activation. Whilst context-dependent Notch receptor clustering has been hypothesized, to date, Notch signalling has been assumed to involve an interplay between receptor and ligand monomers. In this study, we demonstrate biochemically, through a mutational analysis of DLL4, both in vitro and in tissue culture cells, that Notch ligands can efficiently self-associate. We found that the membrane proximal EGF-like repeat of DLL4 was necessary and sufficient to promote oligomerization/dimerization. Mechanistically, our experimental evidence supports the view that DLL4 ligand dimerization is specifically required for cis-inhibition of Notch receptor activity. To further substantiate these findings, we have adapted and extended existing ordinary differential equation-based models of Notch signalling to take account of the ligand dimerization-dependent cis-inhibition reported here. Our new model faithfully recapitulates our experimental data and improves predictions based upon published data. Collectively, our work favours a model in which net output following Notch receptor/ligand binding results from ligand monomer-driven Notch receptor transactivation (and cis activation) counterposed by ligand dimer-mediated cis-inhibition.

The ubiquitous Notch receptor signalling network is essential for tissue growth and maintenance. Operationally, receptor activity is regulated by two principal, counterposed mechanisms: intercellular Notch transactivation triggered by interactions between receptors and ligands expressed in neighbouring cells; intracellular cis inhibition mediated by ligands binding to receptors expressed in the same cell. Moreover, different Notch receptor/ligand combinations are known to elicit distinct molecular and cellular responses, and together, these phenomena determine the strength, the duration and the specificity of Notch receptor signalling. To date, it has been assumed that these processes involve discrete ligand homomers and not heteromeric complexes composed of more than one ligand species. In this study, we explore the molecular basis of the opposing actions of the Notch ligands, DLL4 and JAG1, which control angiogenic sprouting. Through a combination of experimental approaches and mathematical modelling, we provide evidence that two mechanisms could underpin this process: 1) DLL4 rather than JAG1 induces efficient Notch1 receptor transactivation; 2) JAG1 directly blocks DLL4-dependent cis-inhibition of Notch signalling through the formation of a JAG1/DLL4 complex. We propose a new model of Notch signalling that recapitulates the formation of tip and stalk cells, which is necessary for sprouting angiogenesis.

The incidence of respiratory infections in the population is related to many factors, among which environmental factors such as air quality, temperature, and humidity have attracted much attention. In particular, air pollution has caused widespread discomfort and concern in developing countries. Although the correlation between respiratory infections and air pollution is well known, establishing causality between them remains elusive. In this study, by conducting theoretical analysis, we updated the procedure of performing the extended convergent cross-mapping (CCM, a method of causal inference) to infer the causality between periodic variables. Consistently, we validated this new procedure on the synthetic data generated by a mathematical model. For real data in Shaanxi province of China in the period of 1 January 2010 to 15 November 2016, we first confirmed that the refined method is applicable by investigating the periodicity of influenza-like illness cases, an air quality index, temperature, and humidity through wavelet analysis. We next illustrated that air quality (quantified by AQI), temperature, and humidity affect the daily influenza-like illness cases, and, in particular, the respiratory infection cases increased progressively with increased AQI with a time delay of 11 days.

Infectious diseases attack humans from time to time and threaten the lives and survival of people all around the world. An important strategy to prevent the spatial spread of infectious diseases is to restrict population travel. With the reduction of the epidemic situation, when and where travel restrictions can be lifted, and how to organize orderly movement patterns become critical and fall within the scope of this study. We define a novel diffusion distance derived from the estimated mobility network, based on which we provide a general model to describe the spatiotemporal spread of infectious diseases with a random diffusion process and a deterministic drift process of the population. We consequently develop a multi-source data fusion method to determine the population flow in epidemic areas. In this method, we first select available subregions in epidemic areas, and then provide solutions to initiate new travel flux among these subregions. To verify our model and method, we analyze the multi-source data from mainland China and obtain a new travel flux triggering scheme in the selected 29 cities with the most active population movements in mainland China. The testable predictions in these selected cities show that reopening the borders in accordance with our proposed travel flux will not cause a second outbreak of COVID-19 in these cities. The finding provides a methodology of re-triggering travel flux during the weakening spread stage of the epidemic.

Fusarium wilt of banana ( Musa spp.), a typical vascular wilt disease caused by the soil-borne fungus, Fusarium oxysporum f. sp. cubense race 4 (Foc4), seriously threatens banana production worldwide. Pathogens, including vascular wilt fungi, secrete small cysteine-rich proteins during colonization. Some of these proteins are required for pathogenicity. In this study, 106 small secretory proteins that contain a classic N-terminal signal peptide were identified using bioinformatic methods in Foc4. Among them, 11 proteins were selected to show transient expressions in tobacco. Interestingly, transient expression of FoSsp1 in tobacco, an uncharacterized protein (of 145 aa), induced necrotic cell death reactive oxygen burst, and callous deposition. Furthermore, the expression of FoSSP1 in Foc4 wild type (WT) was up-regulated during the stage of banana roots colonization. A split-marker approach was used to knock out FoSSP1 in the Foc4 WT strain. Compared with the WT, the deletion mutant Fossp1 was normal in growth rate but increased in conidiation and virulence. RT-qPCR analysis showed that the expression of four conidiation regulator genes in the Fossp1 deletion mutant was significantly decreased compared to the WT strain. In addition, the expression of four pathogenesis-related genes of bananas infected with Fossp1 deletion mutant was down-regulated in comparison with that of the WT. In summary, these results suggested that FoSSP1 is a putative elicitor that negatively regulates conidiation and pathogenicity in Foc4.

Wheat stripe rust, caused by the obligate biotrophic fungus Puccinia striiformis f. sp. tritici (Pst), seriously affects wheat production. Here, we report the complete genome sequence and biological characterization of a new mitovirus from P. striiformis strain GS-1, which was designated as “Puccinia striiformis mitovirus 2” (PsMV2). Genome sequence analysis showed that PsMV2 is 2658 nt in length with an AU-rich of 52.3% and comprises a single ORF of 2348 nt encoding an RNA-dependent RNA polymerase (RdRp). Phylogenetic analysis indicated that PsMV2 is a new member of the genus Unuamitovirus within the family Mitoviridae. In addition, PsMV2 multiplied highly during Pst infection and it suppresses programmed cell death (PCD) triggered by Bax. Silencing of PsMV2 in Pst by barley stripe mosaic virus (BSMV)-mediated Host Induced Gene Silencing (HIGS) reduced fungal growth and decreased pathogenicity of Pst. These results indicate PsMV2 promotes host pathogenicity in Pst. Interestingly, PsMV2 was detected among a wide range of field isolates of Pst and may have coevolved with Pst in earlier times. Taken together, our results characterized a novel mitovirus PsMV2 in wheat stripe rust fungus, which promotes the virulence of its fungal host and wide distribution in Pst which may offer new strategies for disease control.

Fusarium head blight caused by Fusarium graminearum is an important disease of wheat and barley worldwide. In a previous study on functional characterization of the F. graminearum kinome, one protein kinase gene important for virulence is orthologous to SCH9 that is functionally related to the cAMP-PKA and TOR pathways in the budding yeast. In this study, we further characterized the functions of FgSCH9 in F. graminearum and its ortholog in Magnaporthe oryzae. The ΔFgsch9 mutant was slightly reduced in growth rate but significantly reduced in conidiation, DON production, and virulence on wheat heads and corn silks. It had increased tolerance to elevated temperatures but became hypersensitive to oxidative, hyperosmotic, cell wall, and membrane stresses. The ΔFgsch9 deletion also had conidium morphology defects and produced smaller conidia. These results suggest that FgSCH9 is important for stress responses, DON production, conidiogenesis, and pathogenesis in F. graminearum. In the rice blast fungus Magnaporthe oryzae, the ΔMosch9 mutant also was defective in conidiogenesis and pathogenesis. Interestingly, it also produced smaller conidia and appressoria. Taken together, our data indicate that the SCH9 kinase gene may have a conserved role in regulating conidium size and plant infection in phytopathogenic ascomycetes.

Trichothecene mycotoxins, such as deoxynivalenol (DON) produced by the fungal pathogen, , are not only important for plant infection but are also harmful to human and animal health. Trichothecene targets the ribosomal protein Rpl3 that is conserved in eukaryotes. Hence, a self-defense mechanism must exist in DON-producing fungi. It is reported that (trichothecene biosynthesis) and are two genes responsible for self-defense against trichothecene toxins in . In this study, however, we found that simultaneous disruption of and has no obvious influence on DON resistance upon exogenous DON treatment in , suggesting that other mechanisms may be involved in self-defense. By using RNA-seq, we identified 253 genes specifically induced in DON-treated cultures compared with samples from cultures treated or untreated with cycloheximide, a commonly used inhibitor of eukaryotic protein synthesis. We found that transporter genes are significantly enriched in this group of DON-induced genes. Of those genes, 15 encode major facilitator superfamily transporters likely involved in mycotoxin efflux. Significantly, we found that genes involved in the metabolism of gamma-aminobutyric acid (GABA), a known inducer of DON production in , are significantly enriched among the DON-induced genes. The GABA biosynthesis gene ( ) is downregulated, while GABA degradation genes are upregulated at least twofold upon treatment with DON, resulting in decreased levels of GABA. Taken together, our results suggest that transporters influencing DON efflux are important for self-defense and that GABA mediates the balance of DON production and self-defense in .

Robbsia andropogonis is one of the most destructive leaf spot disease pathogens of numerous host plants and causes heavy economic damage. In the present study, the complete genome of R. andropogonis strain BLB1, causing the leaf spot disease of areca palm, was generated using a hybrid method combining ONT PromethION long reads and BGISEQ-500 short reads. The resulting genome consists of seven replicons totaling 6,828,120 bp, and 5,808 genes were annotated, including 788 virulence-related genes. Function analysis showed that genes involved in metabolism were the most abundant group. Impressively, the bacteria were well-equipped with four, two, and four sets of type three, four, and six secretion systems, respectively, highlighting the virulence features of R. andropogonis BLB1. As the first complete genome sequence of the species of genus Robbsia , the BLB1 genome provides a solid foundation for investigation of mechanisms underlying the pathogen virulence and disease control, and will promote further discovery and characterization of the genus Robbsia .

Fusarium oxysporum f. sp. cubense ( Foc ) causes Fusarium wilt of banana ( Musa spp.), a notorious soil-borne vascular fungal disease threatening the global banana industry. Phytopathogens secrete effectors to suppress plant immunity. However, little is known about the effectors of Foc race 4 ( Foc4 ). In this study, we built a streamlined screening system (candidate effector prediction, RNA-seq-based expression level analysis, and cell death manipulative activity assessment based on transient expression in Nicotiana benthamiana ) to identify candidate virulence-related effectors. In total, 80 candidate effector genes (CEGs) differentially expressed during plant colonization were predicted; 12 out of 15 characterized CEGs, including FoSSP17 , could suppress BAX-triggered programmed cell death (PCD) in N. benthamiana and were induced during the infection of plants. FoSSP17 encodes a novel protein conserved in the Fusarium genus. FoSSP17 gene deletion mutants were not affected in vegetative growth and conidiation but showed reduced virulence. Furthermore, the deletion mutants triggered higher expression levels of host defense-related genes including PR1, PR3, PR5 , and PR10 . Signal peptide activity assay and subcellular localization assay suggested that FoSSP17 is a conventional secretory protein that exerts cell-death-suppressive activity inside plant cells. In addition, FoSSP17 suppressed pattern-triggered immunity in plants by inhibiting reactive oxygen species (ROS) accumulation, reducing callose deposition, and suppressing the expression of NbLOX and NbERF1 genes related to jasmonic acid (JA)-pathway and ethylene (ET)-pathway, respectively. Overall, a systemic screening of Foc4 candidate effectors reveals that FoSSP17 contributes to the virulence of Foc4 and suppresses pattern-triggered immunity in plants.