Mécanisme de l'autorégulation de l'infection secondaire dans la symbiose S. meliloti-Medicago

L'interaction symbiotique entre les rhizobia et les légumineuses repose sur un réseau complexe de boucles de régulation et d'échange de signaux entre les partenaires. Dans le système modèle S.meliloti-Medicago, la nodulation et l'infection bactérienne sont induits par les NFs et des exopolysaccharides de surface bactériens. Lorsque la nodulation est établie, la plante autorégule le nombre de nodosités en activant une boucle de régulation systémique appelée AON. Des mutants de plante déficients pour l'AON sont hypernodulants. Des mutants de plantes présentant un phénotype hyperinfecteux ont été décrits mais ils présentaient également un défaut de nodulation. L'existence d'une autorégulation spécifique de l'infection est donc restée jusqu'ici controversée. Nous décrivons ici une nouvelle boucle de régulation appelée AOI qui régule le nombre d'évènements d'infection secondaire, c'est-à-dire la formation de cordons d'nfection (ITs) sur des plantes déjà nodulées. Nous montrons que l'AOI n'impacte ni la nodulation, ni l'AON ni la fixation de l'azote. Contrairement à l'AON qui est sous le seul contrôle de la plante, l'AOI est également génétiquement contrôlée par la bactérie. Au cours de l'AOI, deux signaux végétaux inconnus 1 et 1' synthétisés au cours du développement du nodule sont perçus par le récepteur NsrA localisé dans la membrane externe des bactéroïdes. En réponse à ces signaux, NsrA active trois adénylate cyclases situées dans la membrane interne induisant la production d'AMPc. Celui-ci, combiné au régulateur transcriptionnel Clr, induit l'expression de gènes bactériens cibles (eg smc02178, smc02177 et smb20495), conduisant à la production d'un signal 2 bactérien. Le signal 2 induit à son tour la production d'éthylène par la plante qui inhibe l'infection secondaire en diminuant la sensibilité de la racine aux NFS. L'implication des bactéries endosymbiotiques dans l'AOI permet vraisemblablement d'assujettir l'AOI à une infection réussie des nodosités. Les résultats de l'équipe suggèrent que le signal 1 est une protéine de haut poids moléculaire. D'après nos résultats, le signal 2 serait un polysaccharide de surface, probablement de type LPS. L'éthylène (signal3) déjà connu pour son rôle régulateur de l'infection primaire aux stades précoces de l'interaction inhibe donc également l'infection secondaire à des stades tardifs de l'interaction. L'AOI est donc une nouvelle boucle de régulation impliquant une combinaison de nouveaux et ancien signaux.The symbiotic interactions between rhizobia and legumes involve complicated regulatory loops and signals exchanges. In the S.meliloti-Medicago symbiosis, nodulation and bacterial infection rely on bacterial NFs and surface polysaccharides EPS. After successful nodulation has occurred, plant autoregulates nodule number by a well-known systemic regulatory mechanism called AON. Plant mutants defective in AON display a hypernodulation phenotype. Some plant mutants display a hyperinfection phenotype yet associated with defects in nodulation or nitrogen fixation ability. Whether ITs formation is also autoregulated independently of nodulation has remained so far unclear. Here we describe a new regulatory pathway that negatively controls secondary infection, ie ITs formation on already nodulated plants at late symbiotic stages (7-14 dpi) in the S.meliloti-Medicago symbiosis. This pathway was called AOI. We show that AOI controls ITs formation without impacting nodulation nor nitrogen fixation. Contrary to AON which is only under plant control, AOI is under both plant and bacteria control. In AOI, unknown plant signals 1 and 1' synthesized during nodule organogenesis are perceived by endosymbiotic bacteria through an outer membrane protein NsrA. NsrA transduces the signals to three receptor-like adenylate cyclases, namely, CyaD1, CyaD2 and CyaK to produce cAMP. cAMP together with the transcriptional regulator Clr drives the expression of target genes, such as smc02178, smc02177 and smb20495, leading to the production of signal 2. Signal 2 then induces the production of ethylene by the plant, which further inhibits secondary infection by decreasing the root susceptibility to NFs. The implication of endosymbiotic bacteria ensures that AOI inhibits ITs formation after successful infection of nodules has occurred. Plant signal 1 has been proved by the group to be a big protein which may act as a new signal in the concert of symbiosis. Signal 2 may be a new surface (lipo)polysaccharide. Signal 3, ethylene, in addition to its well-known role in controlling primary infection at early symbiotic stages, plays a new role in controlling secondary infection at late stages in AOI. Thus, AOI is a new regulatory loop involving new signals

Modeling the Geographic Spread of Rabies in China

Abstract In order to investigate how the movement of dogs affects the geographically inter-provincial spread of rabies in Mainland China, we propose a multi-patch model to describe the transmission dynamics of rabies between dogs and humans, in which each province is regarded as a patch. In each patch the submodel consists of susceptible, exposed, infectious, and vaccinated subpopulations of both dogs and humans and describes the spread of rabies among dogs and from infectious dogs to humans. The existence of the disease-free equilibrium is discussed, the basic reproduction number is calculated, and the effect of moving rates of dogs between patches on the basic reproduction number is studied. To investigate the rabies virus clades lineages, the two-patch submodel is used to simulate the human rabies data from Guizhou and Guangxi, Hebei and Fujian, and Sichuan and Shaanxi, respectively. It is found that the basic reproduction number of the two-patch model could be larger than one even if the isolated basic reproduction number of each patch is less than one. This indicates that the immigration of dogs may make the disease endemic even if the disease dies out in each isolated patch when there is no immigration. In order to reduce and prevent geographical spread of rabies in China, our results suggest that the management of dog markets and trades needs to be regulated, and transportation of dogs has to be better monitored and under constant surveillance. Author Summary In 1999, human rabies cases were reported in about 120 counties in Mainland China, mainly in the southern provinces. Now outbreaks of human rabies have been reported in about 1000 counties and the disease has spread geographically from the south to the north. Phylogeographic analyses of rabies virus strains indicate that prevalent strains in northern provinces are indeed related to the remote southern provinces. It is believed that the geographical spread of rabies virus is caused by the transportation of dogs. In this paper, a multi-patch model is proposed to describe the spatial transmission dynamics of rabies in China and to investigate how the immigration of dogs affects the geographical spread of rabies. The expression and sensitivity analysis of the basic reproduction number indicates that the movement of dogs plays an essential role in the spatial transmission dynamics of rabies. Numerical simulations on the effect of the immigration rate in three pairs of provinces, Guizhou and Guangxi, Hebei and Fujian, Sichuan and Shaanxi, are also performed. It is shown that the immigration of dogs is the main factor for the long-distance inter-provincial spread of rabies and it is necessary to manage such inter-provincial transportation of dogs

The electromagnetic and gravitational-wave radiations of X-ray transient CDF-S XT2

Binary neutron star (NS) mergers may result in remnants of supra-massive or even stable NS, which have been supported indirectly by observed X-ray plateau of some gamma-ray bursts (GRBs) afterglow. Recently, Xue et al. (2019) discovered a X-ray transient CDF-S XT2 that is powered by a magnetar from merger of double NS via X-ray plateau and following stepper phase. However, the decay slope after the plateau emission is a little bit larger than the theoretical value of spin-down in electromagnetic (EM) dominated by losing its rotation energy. In this paper, we assume that the feature of X-ray emission is caused by a supra-massive magnetar central engine for surviving thousands of seconds to collapse black hole. Within this scenario, we present the comparisons of the X-ray plateau luminosity, break time, and the parameters of magnetar between CDF-S XT2 and other short GRBs with internal plateau samples. By adopting the collapse time to constrain the equation of state (EOS), we find that three EOSs (GM1, DD2, and DDME2) are consistent with the observational data. On the other hand, if the most released rotation energy of magnetar is dominated by GW radiation, we also constrain the upper limit of ellipticity of NS for given EOS, and it is range in $[0.32-1.3]\times 10^{-3}$. Its GW signal can not be detected by aLIGO or even for more sensitive Einstein Telescope in the future.Comment: 13 pages, 5 figures,1 table. Accepted for publication by Research in Astronomy and Astrophysic

3D-PreMise: Can Large Language Models Generate 3D Shapes with Sharp Features and Parametric Control?

Recent advancements in implicit 3D representations and generative models have markedly propelled the field of 3D object generation forward. However, it remains a significant challenge to accurately model geometries with defined sharp features under parametric controls, which is crucial in fields like industrial design and manufacturing. To bridge this gap, we introduce a framework that employs Large Language Models (LLMs) to generate text-driven 3D shapes, manipulating 3D software via program synthesis. We present 3D-PreMise, a dataset specifically tailored for 3D parametric modeling of industrial shapes, designed to explore state-of-the-art LLMs within our proposed pipeline. Our work reveals effective generation strategies and delves into the self-correction capabilities of LLMs using a visual interface. Our work highlights both the potential and limitations of LLMs in 3D parametric modeling for industrial applications.Comment: 10 pages, 6 figure

Effects of a traditional Chinese medicine, Longdanxiegan formula granule, on Toll-like receptor pathway in female guinea pigs with recurrent genital herpes

AbstractObjectiveThe aim of the present study was to investigate the effects of Longdanxiegan formula granule (LDXGFG), a Chinese traditional medicine on Toll-like receptor (TLR) pathway in recurrent genital herpes.Materials and MethodsAn experimental recurrent genital herpes model was constructed using herpes guinea pig model. The effect of LDXGFG on expression levels of TLR pathway genes were detected using real-time polymerase chain reaction. Furthermore, the dendritic cells and Langerhans cells were isolated and the TLR pathway genes of these cells were assayed after LDXGFG treatment.ResultsThe result suggested two different expression patterns of TLR pathway genes in genital herpes and recurrent genital herpes, including upregulated genes and downregulated genes. TLR1, TLR4, TLR6, TLR7, TLR8, TLR9, and TLR10 showed a significant decrease while, TLR2, TLR3, and TLR5 increased in genital herpes and recurrent genital herpes guinea pigs. Meanwhile, the downregulated genes in genital herpes and recurrent genital herpes were stimulated by LDXGFG. By contrast, the upregulated genes decreased significantly after LDXGFG treatment. In both dendritic cells and Langerhans cells, the TLR pathway genes exhibited same pattern: the LDXGFG corrected the abnormal expression of TLR pathway genes.ConclusionThe present results suggest that LDXGFG is an alternative, inexpensive, and lasting-effect medicine for herpes simplex virus 2 infection