Some of the most devastating agricultural diseases are caused by root-infecting pathogens, yet the majority of studies on these interactions to date have focused on the host responses of aerial tissues rather than those belowground. Fusarium oxysporum is a root-infecting pathogen that causes wilt disease on several plant species including Arabidopsis thaliana. To investigate and compare transcriptional changes triggered by F. oxysporum in different Arabidopsis tissues, we infected soil-grown plants with F. oxysporum and subjected root and leaf tissue harvested at early and late timepoints to RNA-seq analyses. At least half of the genes induced or repressed by F. oxysporum showed tissue-specific regulation. Regulators of auxin and ABA signalling, mannose binding lectins and peroxidases showed strong differential expression in root tissue. We demonstrate that ARF2 and PRX33, two genes regulated in the roots, promote susceptibility to F. oxysporum. In the leaves, defensins and genes associated with the response to auxin, cold and senescence were strongly regulated while jasmonate biosynthesis and signalling genes were induced throughout the plant.
SummaryBread wheat (Triticum aestivum L.) is an allopolyploid species containing three ancestral genomes. Therefore, three homoeologous copies exist for the majority of genes in the wheat genome. Whether different homoeologs are differentially expressed (homoeolog expression bias) in response to biotic and abiotic stresses is poorly understood. In this study, we applied a RNA‐seq approach to analyse homoeolog‐specific global gene expression patterns in wheat during infection by the fungal pathogen Fusarium pseudograminearum, which causes crown rot disease in cereals. To ensure specific detection of homoeologs, we first optimized read alignment methods and validated the results experimentally on genes with known patterns of subgenome‐specific expression. Our global analysis identified widespread patterns of differential expression among homoeologs, indicating homoeolog expression bias underpins a large proportion of the wheat transcriptome. In particular, genes differentially expressed in response to Fusarium infection were found to be disproportionately contributed from B and D subgenomes. In addition, we found differences in the degree of responsiveness to pathogen infection among homoeologous genes with B and D homoeologs exhibiting stronger responses to pathogen infection than A genome copies. We call this latter phenomenon as ‘homoeolog induction bias’. Understanding how homoeolog expression and induction biases operate may assist the improvement of biotic stress tolerance in wheat and other polyploid crop species.
We
report the design, synthesis, and biological evaluation of some
potent small-molecule neuropilin-1 (NRP1) antagonists. NRP1 is implicated
in the immune response to tumors, particularly in Treg cell fragility,
required for PD1 checkpoint blockade. The design of these compounds
was based on a previously identified compound EG00229. The design
of these molecules was informed and supported by X-ray crystal structures.
Compound 1 (EG01377) was identified as having properties
suitable for further investigation. Compound 1 was then
tested in several in vitro assays and was shown to have antiangiogenic,
antimigratory, and antitumor effects. Remarkably, 1 was
shown to be selective for NRP1 over the closely related protein NRP2.
In purified Nrp1+, FoxP3+, and CD25+ populations of Tregs from mice, 1 was able to block
a glioma-conditioned medium-induced increase in TGFβ production.
This comprehensive characterization of a small-molecule NRP1 antagonist
provides the basis for future in vivo studies.
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