Modulation of plasmacytoid dendritic cell and CD4+ T cell differentiation accompanied by upregulation of the cholinergic anti-inflammatory pathway induced by enterovirus 71.

Enterovirus 71 (EV71) is a neurotropic enterovirus associated with hand, foot, and mouth disease (HFMD) fatalities. In this study, we investigated the impact of EV71 on plasmacytoid dendritic cells (pDCs) and CD4+ T cells. The results showed that pDCs were promptly activated, secreting interferon (IFN)-α and inducing CD4+ T cell proliferation and differentiation during early EV71 infection. This initiated adaptive immune responses and promoted proinflammatory cytokine production by CD4+ T cells. Over time, viral nucleic acids and proteins were synthesized in pDCs and CD4+ T cells. Concurrently, the cholinergic anti-inflammatory pathway (CAP) was activated, exhibiting an anti-inflammatory role. With constant viral stimulation, pDCs and CD4+ T cells showed reduced differentiation and cytokine secretion. Defects in pDCs were identified as a key factor in CD4+ T cell tolerance. CAP had a more significant regulatory effect on CD4+ T cells than on pDCs and was capable of inhibiting inflammation in these cells.

Repression of rRNA gene transcription by endothelial SPEN deficiency normalizes tumor vasculature via nucleolar stress.

Human cancers induce a chaotic, dysfunctional vasculature that promotes tumor growth and blunts most current therapies; however, the mechanisms underlying the induction of a dysfunctional vasculature have been unclear. Here, we show that split end (SPEN), a transcription repressor, coordinates rRNA synthesis in endothelial cells (ECs) and is required for physiological and tumor angiogenesis. SPEN deficiency attenuated EC proliferation and blunted retinal angiogenesis, which was attributed to p53 activation. Furthermore, SPEN knockdown activated p53 by upregulating noncoding promoter RNA (pRNA), which represses rRNA transcription and triggers p53-mediated nucleolar stress. In human cancer biopsies, a low endothelial SPEN level correlated with extended overall survival. In mice, endothelial SPEN deficiency compromised rRNA expression and repressed tumor growth and metastasis by normalizing tumor vessels, and this was abrogated by p53 haploinsufficiency. rRNA gene transcription is driven by RNA polymerase I (RNPI). We found that CX-5461, an RNPI inhibitor, recapitulated the effect of Spen ablation on tumor vessel normalization and combining CX-5461 with cisplatin substantially improved the efficacy of treating tumors in mice. Together, these results demonstrate that SPEN is required for angiogenesis by repressing pRNA to enable rRNA gene transcription and ribosomal biogenesis and that RNPI represents a target for tumor vessel normalization therapy of cancer.

Corrigendum: Genetic Mapping of a Light-Dependent Lesion Mimic Mutant Reveals the Function of Coproporphyrinogen III Oxidase Homolog in Soybean.

[This corrects the article DOI: 10.3389/fpls.2020.00557.].

Genetic Mapping of a Light-Dependent Lesion Mimic Mutant Reveals the Function of Coproporphyrinogen III Oxidase Homolog in Soybean.

Lesion mimic mutants provide ideal genetic materials for elucidating the molecular mechanism of cell death and disease resistance. Here, we isolated a Glycine max lesion mimic mutant 2-1 (Gmlmm2-1), which displayed a light-dependent cell death phenotype. Map-based cloning revealed that GmLMM2 encods a coproporphyrinogen III oxidase and participates in tetrapyrrole biosynthesis. Knockout of GmLMM2 led to necrotic spots on developing leaves of CRISPR/Cas9 induced mutants. The GmLMM2 defect decreased the chlorophyll content by disrupting tetrapyrrole biosynthesis and enhanced resistance to Phytophthora sojae. These results suggested that GmLMM2 gene played an important role in the biosynthesis of tetrapyrrole and light-dependent defense in soybeans.

Electrical sensing of DNA-hybridization using two-port network based on suspended carbon nanotube membrane.

An approach was presented for electrical sensing of deoxyribonucleic acid (DNA)-hybridization in solution using a two-port network based on single-walled suspended carbon nanotube (SWCNT) membrane. A single stranded probe DNA (5'-NH2-(CH2)6-CGC CGA TTG GAC AAA ACT TAA A-3') was immobilized on the SWCNT membrane. A solution with the complementary single stranded DNA (D'FITC: 5'-FITC-T TTA AGT TTT GTC CAA TCG GCG-3') in various concentrations was then dropped on the membrane. The two-port network composed of the suspended SWCNT membrane and its underneath gate were characterized by coupling with a vector network analyzer. The resonance frequency of transmission coefficient S21 was observed to be around 10 MHz. The resonance frequency shifts with DNA-hybridization, and the sensing limit was approximately 50 nM. The advantages of this approach include low-noise frequency output, solution based real time detection and capable of on-chip integration, etc.