Selective recruitment and concentration of signaling proteins within membraneless compartments is a ubiquitous mechanism for subcellular organization 1 – 3 . The dynamic flow of molecules into and out of these compartments occurs on faster timescales than for membrane-enclosed organelles, presenting a possible mechanism to control spatial patterning within cells. Here, we combined single-molecule tracking and super-resolution microscopy, light-induced subcellular localization, reaction-diffusion modeling, and a spatially-resolved promoter activation assay to study signal exchange in and out of the 200 nm cytoplasmic PopZ microdomain at the cell pole of the asymmetrically dividing bacterium Caulobacter crescentus 4 – 8 . Two phospho-signaling proteins, the transmembrane histidine kinase CckA and the cytoplasmic phosphotransferase ChpT, provide the only phosphate source for the cell fate-determining transcription factor CtrA ( Fig. 1a ) 9 – 18 . We found that all three proteins exhibit restricted rates of entry into and escape from the microdomain and enhanced phospho-signaling within, leading to a submicron gradient of activated CtrA~P 19 that is stable and sublinear. Entry into the microdomain is selective for cytosolic proteins and requires a binding pathway to PopZ. Our work demonstrates how nanoscale protein assemblies can modulate signal propagation with fine spatial-resolution, and that in Caulobacter , this modulation serves to reinforce asymmetry and differential cell fate of the two daughter cells.

Pathogens from the fastidious, phloem-restricted 'Candidatus Liberibacter' species cause the devastating Huanglongbing (HLB) disease in citrus worldwide and cause diseases on many solanaceous crops and plants in the Apiaceae family. However, little is known about the pathogenic mechanisms due to the difficulty in culturing the corresponding 'Ca. Liberibacter' species. Here, we report that the citrus HLB pathogen 'Ca. L. asiaticus' uses an active salicylate hydroxylase SahA to degrade salicylic acid (SA) and suppress plant defenses. Purified SahA protein displays strong enzymatic activity to degrade SA and its derivatives. Overexpression of SahA in transgenic tobacco plants abolishes SA accumulation and hypersensitive response (HR) induced by nonhost pathogen infection. By degrading SA, 'Ca. L. asiaticus' not only enhances the susceptibility of citrus plants to both nonpathogenic and pathogenic Xanthomonas citri but also attenuates the responses of citrus plants to exogenous SA. In addition, foliar spraying of 2,1,3-benzothiadiazole and 2,6-dichloroisonicotinic acid, SA functional analogs not degradable by SahA, displays comparable (and even better) effectiveness with SA in suppressing 'Ca. L. asiaticus' population growth and HLB disease progression in infected citrus trees under field conditions. This study demonstrates one or more pathogens suppress plant defenses by degrading SA and establish clues for developing novel SA derivatives-based management approaches to control the associated plant diseases.

Background:Recently, the prognostic value of the platelet-to-lymphocyte ratio (PLR) has been identified in multiple cancers. However, the prognostic significance of the PLR in prostate cancer (PCa) remains conflicting. We therefore searched relevant studies and conducted a meta-analysis.Methods:Papers from the databases of PubMed, Web of Science, and the Cochrane Library were retrieved. Six studies comprising 1324 patients were included.Results:The pooled analysis demonstrated that an elevated PLR predicted poor overall survival (OS; HR = 1.85, 95% CI = 1.51–2.25, P < .001) and disease-free survival (DFS; HR = 1.4, 95% CI = 1.1–1.79, P = .007). Subgroup analyses showed that the PLR remained a significant prognostic factor for OS irrespective of ethnicity, tumor stage, or cut-off value. The PLR was an indicator of poor DFS in Asian patients, but not in Caucasian patients. No significant publication bias was detected.Conclusion:This meta-analysis showed that a high PLR was correlated with poor DFS and OS in patients with prostate cancer. Due to this meta-analysis being derived from a few studies, the results should be validated in clinical practice.