Heterotrimeric G proteins consisting of Gα, Gβ and Gγ are conserved signaling hubs in eukaryotes. Without analogs to canonical animal G protein‐coupled receptors, plant cells are thought to use RGS1 ...and a yet unknown mechanism to regulate the activity of Gα. Meanwhile, the exact role of canonical Gα in plant innate immunity remains controversial. Here, we report multiple immune deficiencies in the null allele of Arabidopsis Gα (GPA1) in response to bacterial flg22 elicitor, clarifying a positive regulatory role of GPA1 in flg22 signaling. We also detect overall increased phosphorylation of GPA1 but reduced phosphorylation at Thr19 upon flg22 elicitation. Interestingly, flg22 could not induce phosphorylation of GPA1T19A and GPA1T19D, suggesting that the dynamic Thr19 phosphorylation is required for GPA1 to respond to flg22. Moreover, flg22‐induced GPA1 phosphorylation is largely abolished in the absence of BAK1 in vivo, and BAK1 could phosphorylate GPA1 but not GPA1T19A in vitro at the phosphorylation sites identified in vivo, suggesting BAK1 is likely the kinase for GPA1 phosphorylation in response to flg22. Furthermore, the T19A mutation could promote flg22‐induced association, rather than dissociation, between GPA1 and RGS1. Taken together, our findings shed new insights into the function and regulation of GPA1 in Arabidopsis defense signaling.
Canonical G protein alpha (GPA1) is thought to play a negligible role in Arabidopsis immunity. Here we show genetic and phosphoproteomic evidence that GPA1 positively regulates immunity. Bacterial flagellin can enhance GPA1 phosphorylation through the co‐receptor BAK1, where dynamic phosphorylation of Thr19 is indispensable for GPA1 to respond to flagellin.
The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and ...characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models. Remarkably, immunization of mice and rhesus macaques with a single dose of ChinZIKV elicits robust and long-lasting immune responses, and confers complete protection against ZIKV challenge. Significantly, female mice immunized with ChinZIKV are protected against placental and fetal damage upon ZIKV challenge during pregnancy. Overall, our study provides an alternative vaccine platform in response to the ZIKV emergency, and the safety, immunogenicity, and protection profiles of ChinZIKV warrant further clinical development.
Fungal pathogens are major destructive microorganisms for land plants and pose growing challenges to global crop production. Chitin is a vital building block for fungal cell walls and also a broadly ...effective elicitor of plant immunity. Here we review the rapid progress in understanding chitin perception and signaling in plants and highlight similarities and differences of these processes between arabidopsis and rice. We also outline moonlight functions of CERK1, an indispensable chitin coreceptor conserved across the plant kingdom, which imply potential crosstalk between chitin signaling and symbiotic or biotic/abiotic stress signaling in plants via CERK1. Moreover, we summarize current knowledge about fungal counterstrategies for subverting chitin-triggered plant immunity and propose open questions and future directions in this field.
Chitin perception systems in both arabidopsis and rice consist of multiple LysM-containing proteins, which undergo chitin-induced oligomerization to trigger intracellular signaling. An oligomer size-dependent chitin sensing mechanism is conserved across plants and mammals.Receptor-like cytoplasmic kinase VII members are essential players of chitin signaling in both arabidopsis and rice.Both arabidopsis and rice CERK1 proteins play multifaceted functions beyond chitin signaling and may mediate the crosstalk between chitin signaling and symbiotic or other biotic or abiotic stress signaling.Most uncovered fungal countermeasures to subvert chitin-triggered plant immunity involve blocking the generation and perception of chitin oligomers in plant apoplast, whereas fungal cytoplasmic effector-mediated strategies to disrupt chitin signaling inside plant cells remain poorly understood.
The amplitude of low-frequency fluctuation (ALFF) measures resting-state functional magnetic resonance imaging (RS-fMRI) signal of each voxel. However, the unit of blood oxygenation level-dependent ...(BOLD) signal is arbitrary and hence ALFF is sensitive to the scale of raw signal. A well-accepted standardization procedure is to divide each voxel's ALFF by the global mean ALFF, named mALFF. Although fractional ALFF (fALFF), a ratio of the ALFF to the total amplitude within the full frequency band, offers possible solution of the standardization, it actually mixes with the fluctuation power within the full frequency band and thus cannot reveal the true amplitude characteristics of a given frequency band. The current study borrowed the percent signal change in task fMRI studies and proposed percent amplitude of fluctuation (PerAF) for RS-fMRI. We firstly applied PerAF and mPerAF (i.e., divided by global mean PerAF) to eyes open (EO) vs. eyes closed (EC) RS-fMRI data. PerAF and mPerAF yielded prominently difference between EO and EC, being well consistent with previous studies. We secondly performed test-retest reliability analysis and found that (PerAF ≈ mPerAF ≈ mALFF) > (fALFF ≈ mfALFF). Head motion regression (Friston-24) increased the reliability of PerAF, but decreased all other metrics (e.g. mPerAF, mALFF, fALFF, and mfALFF). The above results suggest that mPerAF is a valid, more reliable, more straightforward, and hence a promising metric for voxel-level RS-fMRI studies. Future study could use both PerAF and mPerAF metrics. For prompting future application of PerAF, we implemented PerAF in a new version of REST package named RESTplus.
High‐efficiency electromagnetic (EM) functional materials are the core building block of high‐performance EM absorbers and devices, and they are indispensable in various fields ranging from ...industrial manufacture to daily life, or even from national defense security to space exploration. Searching for high‐efficiency EM functional materials and realizing high‐performance EM devices remain great challenges. Herein, a simple solution‐process is developed to rapidly grow gram‐scale organic–inorganic (MAPbX3, X = Cl, Br, I) perovskite microcrystals. They exhibit excellent EM response in multi bands covering microwaves, visible light, and X‐rays. Among them, outstanding microwave absorption performance with multiple absorption bands can be achieved, and their intrinsic EM properties can be tuned by adjusting polar group. An ultra‐wideband bandpass filter with high suppression level of −71.8 dB in the stopband in the GHz band, self‐powered photodetectors with tunable broadband or narrowband photoresponse in the visible‐light band, and a self‐powered X‐ray detector with high sensitivity of 3560 µC Gyair−1 cm−2 in the X‐ray band are designed and realized by precisely regulating the physical features of perovskite and designing a novel planar device structure. These findings open a door toward developing high‐efficiency EM functional materials for realizing high‐performance EM absorbers and devices.
A facile one‐step solution processing method is developed to rapidly prepare gram‐scale MAPbX3 microcrystals. Utilizing its intrinsic electromagnetic (EM) properties, a series of EM devices is designed and fabricated, which can be applied in the fields of ultra‐wideband bandpass filters and multi‐band photodetection covering X‐rays, UV, visible light, and microwaves.
The distant metastasis of cancer cells is a risk factor for tumor lethality and poor prognosis in non-small-cell lung carcinoma (NSCLC). Increased SOX9 expression has been associated with clinical ...stage and poor prognosis in NSCLC, but the molecular mechanisms by which SOX9 promotes metastasis in NSCLC are still unknown.
The relationship between SOX9 expression and T, N, M classification was assessed using the χ
test and Spearman's analysis in 142 immunohistochemically diagnosed specimens of NSCLC. We also generated SOX9-overexpression and SOX9-knockdown cells lines and their corresponding control cell lines by transfection with lentiviral constructs. In vivo assay, SOX9-overexpressing and SOX9-knockdown NSCLC cells were injected in zebrafish to examine distance metastasis. Gene set enrichment analysis (GSEA) was applied to analysis the correlation between SOX9 overexpression and Wnt/β-catenin pathway. Luciferase assay was used to check transcriptional activity of TCF/LEF and western blot and immunofluorescence was employed to detect β-catenin translocation in SOX9-overexpression, SOX9-knockdown and their corresponding control cell lines.
We found that SOX9 overexpression correlates with the T, N and M stage significantly (p = 0.03, 0.000, and 0.032 respectively) in 142 immunohistochemically diagnosed specimens of NSCLC. SOX9 overexpression was found to decrease the expression of the epithelial cell markers E-cadherin and γ-catenin and increase the expression of the mesenchymal cell markers N-cadherin and vimentin. An in vivo assay showed distant metastasis of the SOX9-overexpressing cells, which was not observed in the SOX9-knockdown cells. These findings indicate that SOX9 promotes distant metastasis by promoting EMT in NSCLC cells. GSEA showed that SOX9 overexpression was significantly correlated with the Wnt/β-catenin pathway which was corroborated by the expression of EMT-associated proteins in this pathway and its downstream target genes. SOX9 overexpression was also found to enhance the transcriptional activity of TCF/LEF, promote the nuclear translocation of β-catenin and increase the phosphorylation of GSK3β at Ser9. Further, inhibition of β-catenin suppressed the metastasis-promoting effects of SOX9 overexpression.
This study is the first to report that SOX9 is associated with clinical TNM stage and indicates that SOX9 promotes migration, invasion and the EMT process through the Wnt/β-catenin pathway.
SUMMARY
Lysin motif (LysM) is a carbohydrate‐binding module often found in secreted or transmembrane proteins in living organisms from prokaryotes to eukaryotes. Thus far, all characterized ...LysM‐containing proteins in plants are plasma membrane‐resident receptors or co‐receptors playing roles in plant–microbe interactions. Here, we interrogate the Arabidopsis LysM/F‐box‐containing protein InLYP1 and reveal its function in glycine metabolism. InLYP1 was mainly expressed by vigorously growing tissues, encoding a nuclear‐cytoplasmic protein. We validated InLYP1 as part of the SKP1‐CULLIN1‐F‐box E3 complex for mediating protein degradation. The glycine decarboxylase P‐protein 1 (GLDP1) was identified as an InLYP1‐interacting protein by both immunoprecipitation/mass spectrometry and yeast two‐hybrid library screening. InLYP1 could also interact with GLDP2, a paralog of GLDP1 with weaker catalytic activity, and could mediate the degradation of GLDP2 but not GLDP1. Interestingly, both GLDPs could be O‐glycosylated and form homodimers or heterodimers. Overexpression of InLYP1L9A encoding a dominant‐negative variant could cause seedling germination retardation on the medium containing glycine. Collectively, these results shed light on the function of plant intracellular LysM‐containing proteins, and suggest that InLYP1 may deplete GLDP2 to facilitate glycine decarboxylation in Arabidopsis.
Significance Statement
Lysin motif (LysM) is a carbohydrate‐binding module often found in secreted or transmembrane proteins in living organisms, and all LysM‐containing proteins characterized so far in plants are transmembrane receptors or co‐receptors regulating plant–microbe interactions. This work reveals a role of InLYP1, an Arabidopsis intracellular LysM‐containing protein, in regulating glycine metabolism and assigns additional function to the LysM module in plants beyond binding to microbe‐associated carbohydrate molecules.
Abstract
The integrated CO
2
capture and conversion (iCCC) technology has been booming as a promising cost-effective approach for Carbon Neutrality. However, the lack of the long-sought molecular ...consensus about the synergistic effect between the adsorption and in-situ catalytic reaction hinders its development. Herein, we illustrate the synergistic promotions between CO
2
capture and in-situ conversion through constructing the consecutive high-temperature Calcium-looping and dry reforming of methane processes. With systematic experimental measurements and density functional theory calculations, we reveal that the pathways of the reduction of carbonate and the dehydrogenation of CH
4
can be interactively facilitated by the participation of the intermediates produced in each process on the supported Ni–CaO composite catalyst. Specifically, the adsorptive/catalytic interface, which is controlled by balancing the loading density and size of Ni nanoparticles on porous CaO, plays an essential role in the ultra-high CO
2
and CH
4
conversions of 96.5% and 96.0% at 650 °C, respectively.
Tumour lineage plasticity is an emerging hallmark of aggressive tumours. Tumour cells usually hijack developmental signalling pathways to gain cellular plasticity and evade therapeutic targeting. In ...the present study, the secreted protein growth and differentiation factor 1 (GDF1) is found to be closely associated with poor tumour differentiation. Overexpression of GDF1 suppresses cell proliferation but strongly enhances tumour dissemination and metastasis. Ectopic expression of GDF1 can induce the dedifferentiation of hepatocellular carcinoma (HCC) cells into their ancestral lineages and reactivate a broad panel of cancer testis antigens (CTAs), which further stimulate the immunogenicity of HCC cells to immune-based therapies. Mechanistic studies reveal that GDF1 functions through the Activin receptor-like kinase 7 (ALK7)-Mothers against decapentaplegic homolog 2/3 (SMAD2/3) signalling cascade and suppresses the epigenetic regulator Lysine specific demethylase 1 (LSD1) to boost CTA expression. GDF1-induced tumour lineage plasticity might be an Achilles heel for HCC immunotherapy. Inhibition of LSD1 based on GDF1 biomarker prescreening might widen the therapeutic window for immune checkpoint inhibitors in the clinic.
This paper proposes a multi-round e-purchasing mode. The theory of procurement decision traditionally assumes that the offered quantity and quality is fixed prior to source selection. Multi-attribute ...procurement allows negotiation over price and other quantitative or qualitative attributes such as color, weight, or delivery time. It promises higher market efficiency that more effective information of buyer's preferences and supplier's offerings exchanges. It's focused that applying case-based reasoning from offers to winner determination in multi-attribute e-purchasing decision. Our contribution is fourfold: first, the winner determination problem is analyzed in case of multiple sourcing include new unfamiliar suppliers; second, the concept of multi-attribute procurement is extended to allow for configurable offers by suppliers following buyer's preference; third, buyer and suppliers may on-line learn preferences from each other in the e-purchasing process through case-based reasoning. Fourth, the models and decision algorithm are provided and illustrated with an example. These extensions provide buyer with more flexibility in the specification of their procurement request and allow for an efficient information exchange among participants, and finally, the buyer can enhance his profit.
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