In mammals, TUBBY-like proteins play an important role in maintenance and function of neuronal cells during postdifferentiation and development. We have identified a TUBBY-like protein gene family with 11 members in Arabidopsis, named AtTLP1-11. Although seven of the AtTLP genes are located on chromosome I, no local tandem repeats or gene clusters are identified. Except for AtTLP4, reverse transcription-PCR analysis indicates that all these genes are expressed in various organs in 6-week-old Arabidopsis. AtTLP1, 2, 3, 6, 7, 9, 10, and 11 are expressed ubiquitously in all the organs tested, but the expression of AtTLP5 and 8 shows dramatic organ specificity. These 11 family members share 30% to 80% amino acid similarities across their conserved C-terminal tubby domains. Unlike the highly diverse N-terminal region of animal TUBBY-like proteins, all AtTLP members except AtTLP8 contain a conserved F-box domain (51–57 residues). The interaction between AtTLP9 and ASK1 (Arabidopsis Skp1-like 1) is confirmed via yeast (Saccharomyces cerevisiae) two-hybrid assays. Abscisic acid (ABA)-insensitive phenotypes are observed for two independent AtTLP9 mutant lines, whereas transgenic plants overexpressing AtTLP9 are hypersensitive to ABA. These results suggest that AtTLP9 may participate in the ABA signaling pathway.

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Our study shows for the first time that the NLRP3 inflammasome is hyperactivated in macrophages of both male and female SLE patients. The mechanisms underlying NLRP3 hyperactivation might be different between the sexes. Furthermore, the AIM2 inflammasome might also contribute sex-differentially to SLE pathogenesis and severity.

Objective: Oncogene-driven stress-related DNA damage has been observed in lesions of colon cancer. Furthermore, DNA sensors and nucleases are stimulated during active DNA damage and replication. However, their changes and influences with respect to cancer remain largely unknown. Methods: The gene expression levels of cGAS, IFI16, STING, TBK1, IFNB1, TREX1, SAMHD1, RNASEH2A, RNASEH2B, and RNASEH2C were examined in the paired colorectal cancer and adjacent normal part tissues of 53 patients. Their associations with the clinical stages of cancer were then analyzed. Results: All cytosolic DNA-sensing and nuclease-related genes except cGAS, RNASEH2A, and RNASEH2B showed lower mRNA expressions in the colorectal tumor tissues. Moreover, cGAS upregulation was found to be associated with early-stage colorectal cancers, while higher expressions of RNASEH2B, RNASEH2C, and SAMHD1 correlated with metastasis. RNASEH2C knockdown in a colon cancer cell line impaired cell migration, and analysis of the cancer RNA-seq data from The Cancer Genome Atlas (TCGA) database revealed a negative correlation between RNASEH2C expression and E-cadherin levels. Conclusions: In contrast to DNA-sensing events in viral infections or autoimmunity, cGAS-STING-IFNB signaling is disrupted in colorectal cancer. The expression levels of cGAS, RNASEH2B, RNASEH2C, and SAMHD1 could be prognostic markers of colorectal cancer.

Phenylalanine ammonia-lyase is the first enzyme of general phenylpropanoid pathway. A PAL gene, designated as BoPAL1, was cloned from a Bambusa oldhamii cDNA library. The open reading frame of BoPAL1 was 2,139 bp in size and predicted to encode a 712-amino acid polypeptide. BoPAL1 was the first intronless PAL gene found in angiosperm plant. Several putative cis-acting elements such as P box, GT-1motif, and SOLIPs involved in light responsiveness were found in the 5'-flanking sequence of BoPAL1 which was obtained by TAIL-PCR method. Recombinant BoPAL1 protein expressed in Pichia pastoris was active. The optimum temperature and pH for BoPAL1 activity was 50°C and 9.0, respectively. The molecular mass of recombinant BoPAL1 was estimated as 323 kDa using gel filtration chromatography and the molecular mass of full-length BoPAL was about 80 kDa, indicating that BoPAL1 presents as a homotetramer. The Km and kcat values of BoPAL1 for L-Phe were 1.01 mM and 10.11 s(-1), respectively. The recombinant protein had similar biochemical properties with PALs reported in other plants.

Monocytes/macrophages are important in orchestrating inflammatory responses. However, knowledge of the long noncoding RNA (lncRNA) regulation of monocytic cell differentiation and diseases remains limited. We aimed to elucidate the role of the 17 kb lncRNA noncoding transcript in T cells (NTT) in monocyte functions. Knockdown and chromatin immunoprecipitation (ChIP) assays in THP-1 cells (human monocytic leukemia cell line) revealed that NTT is regulated by the monocyte key transcription factor C/EBPβ and that it binds to the promoter of nearby gene PBOV1 via hnRNP-U. Overexpression of PBOV1 in THP-1 cells resulted in cell cycle G1 arrest, differentiation into macrophages, a marked increase in IL-10 and CXCL10 mRNA levels, and upregulation of the costimulatory molecules. In contrast to the downregulated NTT observed in lipopolysaccharide (LPS)-treated THP-1 cells, the C/EBPβ/NTT/PBOV1 axis was found to be hyperactivated in peripheral blood mononuclear cells (PBMCs) of first-time diagnosed untreated early rheumatoid arthritis (RA) patients, and their gene expression levels decreased markedly after treatment. Higher initial C/EBPβ/NTT/PBOV1 expression levels were associated with a trend of higher disease activity DAS28 scores. In conclusion, our study suggests that the lncRNA NTT is a regulator of inflammation in monocytes, and its activation participates in monocyte/macrophage differentiation and the pathogenesis of RA.

HHP1 (heptahelical protein 1), a protein with a predicted seven transmembrane domain structure homologous to adiponectin receptors (AdipoRs) and membrane progestin receptors (mPRs), has been characterized. Expression of HHP1 was increased in response to abscisic acid (ABA) and salt/osmotic stress as shown by quantitative real-time PCR and HHP1 promoter-controlled GUS activity. The HHP1 T-DNA insertion mutant (hhp1-1) showed a higher sensitivity to ABA and osmotic stress than the wild-type (WT), as revealed by the germination rate and post-germination growth rate. The induced expression of stress-responsive genes (RD29A, RD29B, ADH1, KIN1, COR15A, and COR47) was more sensitive to exogenous ABA and osmotic stress in hhp1-1 than in the WT. The hypersensitivity in the hhp1-1 mutant was reversed in the complementation mutant of HHP1 expressing the HHP1 gene. The data suggest that the mutation of HHP1 renders plants hypersensitive to ABA and osmotic stress and HHP1 might be a negative regulator in ABA and osmotic signalling.

BackgroundPrevious studies on the association of enterobiasis and chronic inflammatory diseases have revealed contradictory results. The interaction of Enterobius vermicularis infection in particular with gut microbiota and induced immune responses has never been thoroughly examined.Methodology/FindingsIn order to answer the question of whether exposure to pinworm and mebendazole can shift the intestinal microbial composition and immune responses, we recruited 109 (30 pinworm-negative, 79 pinworm-infected) first and fourth grade primary school children in Taichung, Taiwan, for a gut microbiome study and an intestinal cytokine and SIgA analysis. In the pinworm-infected individuals, fecal samples were collected again at 2 weeks after administration of 100 mg mebendazole. Gut microbiota diversity increased after Enterobius infection, and it peaked after administration of mebendazole. At the phylum level, pinworm infection and mebendazole deworming were associated with a decreased relative abundance of Fusobacteria and an increased proportion of Actinobacteria. At the genus level, the relative abundance of the probiotic Bifidobacterium increased after enterobiasis and mebendazole treatment. The intestinal SIgA level was found to be lower in the pinworm-infected group, and was elevated in half of the mebendazole-treated group. A higher proportion of pre-treatment Salmonella spp. was associated with a non-increase in SIgA after mebendazole deworming treatment.Conclusions/SignificanceChildhood exposure to pinworm plus mebendazole is associated with increased bacterial diversity, an increased abundance of Actinobacteria including the probiotic Bifidobacterium, and a decreased proportion of Fusobacteria. The gut SIgA level was lower in the pinworm-infected group, and was increased in half of the individuals after mebendazole deworming treatment.