Gall-forming arthropods are highly specialized herbivores that, in combination with their hosts, produce extended phenotypes with unique morphologies [1]. Many are economically important, and others have improved our understanding of ecology and adaptive radiation [2]. However, the mechanisms that these arthropods use to induce plant galls are poorly understood. We sequenced the genome of the Hessian fly (Mayetiola destructor; Diptera: Cecidomyiidae), a plant parasitic gall midge and a pest of wheat (Triticum spp.), with the aim of identifying genic modifications that contribute to its plant-parasitic lifestyle. Among several adaptive modifications, we discovered an expansive reservoir of potential effector proteins. Nearly 5% of the 20,163 predicted gene models matched putative effector gene transcripts present in the M. destructor larval salivary gland. Another 466 putative effectors were discovered among the genes that have no sequence similarities in other organisms. The largest known arthropod gene family (family SSGP-71) was also discovered within the effector reservoir. SSGP-71 proteins lack sequence homologies to other proteins, but their structures resemble both ubiquitin E3 ligases in plants and E3-ligase-mimicking effectors in plant pathogenic bacteria. SSGP-71 proteins and wheat Skp proteins interact in vivo. Mutations in different SSGP-71 genes avoid the effector-triggered immunity that is directed by the wheat resistance genes H6 and H9. Results point to effectors as the agents responsible for arthropod-induced plant gall formation.

Study Objectives: To explore the regional brain activities in patients with chronic primary insomnia (PCPIs) and their sex differences. Methods: Forty-two PCPIs (27 females, 15 males) and 42 good sleepers (GSs; 24 females, 18 males) were recruited. Six PCPIs (3 males, 3 females) were scanned twice by MRI to examine the test-retest reliability. Amplitude of low frequency fluctuation (ALFF) method was used to assess the local brain features. The mean signal values of the different ALFF areas were analyzed with a receiver operating characteristic (ROC) curve. Simple linear regression analysis was performed to investigate the relationships between clinical features and different brain areas. Results: Both female and male PCPIs showed higher ALFF in the temporal lobe and occipital lobe, especially in female PCPIs. Female PCPIs had lower ALFF in the bilateral cerebellum posterior lobe, left dorsolateral prefrontal cortex, and bilateral limbic lobe; however, male PCPIs showed lower ALFF in the left occipital gyrus. The mean signal value of the cerebellum in female PCPIs showed negative correlations with negative emotions. Compared with male PCPIs, female PCPIs showed higher ALFF in the bilateral middle temporal gyrus and lower ALFF in the left limbic lobe. The different areas showed high testretest stability (Clusters of contiguous volumes ≥ 1080 mm 3 with an intraclass correlation coefficient ≥ 0.80) and high degree of sensitivity and specificity. Conclusions: Female PCPIs showed more regional brain differences with higher and lower ALFF responses than male PCPIs. However, they shared analogous excessive hyperarousal mechanism and wide variations in aberrant brain areas. I NTRO DUCTI O NPatients with chronic primary insomnia (PCPIs), who underwent the subjective experience of chronically disturbed sleep, sleep loss, non-refreshing sleep, and heightened arousal in bed with impaired quality of life, showed a decreased ability to disengage from external information processing at sleep onset.1-3 Occasional episodes of insomnia symptoms are reported in half of all adults, while chronic insomnia is prevalent in 10-15% of the adult population. 4 In spite of a recent increase in neuroimaging research into PCPIs, it has not gleaned a consistent conclusion about its neuropathology after reviewing the neuroimaging studies of primary insomnia, especially with regard to the structural studies of brain alterations. 5 The results of structural studies are either contradictory or required replication. Altena et al. found that PCPIs had a smaller volume of reduced gray matter in the precuneus and left orbitofrontal cortex which strongly correlated with the subjective severity of insomnia, but increased gray matter volume was not found. 6 Joo et al. demonstrated significantly reduced gray matter concentrations in the dorsolateral prefrontal and pericentral cortices, superior temporal gyrus, and cerebellum, and decreased gray matter volumes in the medial frontal lobe and middle temporal lobe in PCPIs compared with good sleepers (GSs), ...

Reactive oxygen species (ROS) play a major role in plant defense against pathogens, but evidence for their role in defense against insects is still preliminary and inconsistent. In this study, we examined the potential role of ROS in defense of wheat (Triticum aestivum) and rice (Oryza sativa) against Hessian fly (Mayetiola destructor) larvae. Rapid and prolonged accumulation of hydrogen peroxide (H 2 O 2 ) was detected in wheat plants at the attack site during incompatible interactions. Increased accumulation of both H 2 O 2 and superoxide was detected in rice plants during nonhost interactions with the larvae. No increase in accumulation of either H 2 O 2 or superoxide was observed in wheat plants during compatible interactions. A global analysis revealed changes in the abundances of 250 wheat transcripts and 320 rice transcripts encoding proteins potentially involved in ROS homeostasis. A large number of transcripts encoded class III peroxidases that increased in abundance during both incompatible and nonhost interactions, whereas the levels of these transcripts decreased in susceptible wheat during compatible interactions. The higher levels of class III peroxidase transcripts were associated with elevated enzymatic activity of peroxidases at the attack site in plants during incompatible and nonhost interactions. Overall, our data indicate that class III peroxidases may play a role in ROS generation in resistant wheat and nonhost rice plants during response to Hessian fly attacks.

Wheat and its relatives possess a number of resistance (R) genes specific for the Hessian fly (HF) [Mayetiola destructor (Say)]. HF populations overcome R gene resistance by evolving virulence. Virulent HF larvae manipulate the plant to produce a nutritionally enhanced feeding tissue and, probably, also suppress plant defense responses. Using two wheat R genes, H9 and H13, and three HF strains (biotypes) differing in virulence for H9 and H13, we conducted a genome-wide transcriptional analysis of gene expression during compatible interactions with virulent larvae and incompatible interactions with avirulent larvae. During both types of interactions, a large number of genes (>1,000) showed alterations in gene expression. Analysis of genes with known functions revealed that major targets for differential regulation were genes that encoded defense proteins or enzymes involved in the phenylpropanoid, cell wall, and lipid metabolism pathways. A combination of the enhancement of antibiosis defense, the evasion of nutrient metabolism induction, and the fortification and expansion of the cell wall are likely the collective mechanism for host-plant resistance observed during incompatible interactions. To overcome this resistance, virulent larvae appeared to suppress antibiosis defense while inducing nutrient metabolism, weakening cell wall, and inhibiting plant growth.

Background: CTLA-4 is a well-studied immune checkpoint protein that negatively regulates T cell-mediated immune responses. However, the expression of CTLA-4 in glioma and the effects of CTLA-4 on prognosis in patients with glioma have not yet been examined. Methods: We investigated the protein level of CTLA-4 in human glioma samples, extracted genetic and clinical data from 1024 glioma patients to characterize CTLA-4 expression and its relationship with immune functions in gliomas. R language was used for statistical analysis. Results: Higher CTLA-4 expression was found in patients with higher grade, isocitrate dehydrogenase (IDH)-wildtype, and mesenchymal-molecular subtype gliomas than in patients with lower grade, IDH-mutant, and other molecular subtype gliomas. Further analysis showed that there was a strong positive correlation between CTLA-4 and the specific marker gene expression of immune cells, including CD8 + T cells, regulatory T cells, and macrophages in both databases, suggesting that higher CTLA-4 expression in the glioma microenvironment induced greater immune cell infiltration compared with that in gliomas with lower CTLA-4 expression. We further explored the associations between CTLA-4 and other immune-related molecules. Pearson correlation analysis showed that CTLA-4 was associated with PD-1, CD40, ICOS, CXCR3, CXCR6, CXCL12 and TIGIT. Patients with glioma with lower CTLA-4 expression exhibited significantly longer overall survival. Thus, these findings suggested that increased CTLA-4 expression conferred a worse outcome in glioma. Conclusions: In summary, our findings revealed the expression patterns and clinical characteristics of CTLA-4 in glioma and may be helpful for expanding our understanding of antitumor immunotherapy in gliomas.

In recent years, reports indicated that PCV3 may be involved in porcine dermatitis and nephropathy syndrome (PDNS)-like disease similar to that linked to PCV2.A total of 2,125 porcine samples from 910 cases were collected during 2016-2018 and tested for presence of PCV3 and PCV2 by real-time PCR assays. Results showed high prevalence of PCV3 and PCV2: 28.4% samples from 41.2% cases were PCV3 positive and 16.4% samples from 16.7% cases were PCV2 positive. The overall coinfection rate was 5.4% and 8.4% at the sample and case level, respectively. Temporal analysis indicated that PCV3 positive case rate increased from 31.6% in 2016, 40.9% in 2017, to 55.6% in 2018. Although its prevalence was lower, PCV2-positive case rate in 2018 (28.8%) doubled that in 2017 (14.4%). The coinfection case rate also increased from 3.4% in 2016, 8.0% in 2017 to 16.1% in 2018. The high positive rate of PCV3 (56.9%) and PCV2 (33.8%) in oral fluids, PCV3 in foetuses (57.1%) and PCV2 in tonsils (54.8%) implied viral transmission route and tissue tropism. In phylogenetic analysis, two small PCV3 clusters (1 and 2) were separated but others were clustered with low bootstrapping values indicating overall low genetic diversity. Genotypes, PCV2a-h, were confirmed by analysing 2,944 strains, with a new genotype proposed as PCV2i. In this study, 61 PCV3 unique whole genomes were sequenced; 12 belonged to a separate cluster that were characterized by five consistent amino acid changes in the capsid protein (24V, 27K, 56D, 98R and 168K) and may be associated with potential differences in immunogenicity. Among the 43 unique PCV2 whole genomes sequenced, 31 belonged to PCV2d, 7 to PCV2a and 5 to PCV2b. Thus, our study demonstrates that PCV2d is the predominant genotype and PCV3 is widely circulating in the Midwest of the USA. K E Y W O R D Sgenetic diversity, genotype, PCV2, PCV3, prevalence | 1285 WANG et Al.

Damage by the Russian wheat aphid (RWA), Diuraphis noxia, significantly reduces wheat and barley yields worldwide. In compatible interactions, virulent RWA populations flourish and susceptible plants suffer extensive leaf chlorophyll loss. In incompatible interactions, RWA reproduction and population growth are significantly reduced and RWA-related chlorophyll loss in resistant plants is minor. The objectives of this study were to develop an understanding of the molecular and phytochemical bases of RWA resistance in plants containing the Dnx resistance gene. Microarray, real-time polymerase chain reaction, and phytohormone assays were conducted to identify transcriptome components unique to RWA-infested Dnx plants and susceptible (Dn0) plants, and to identify and characterize putative genes involved in Dnx plant defense responses. We found that RWA-infested Dnx plants upregulated > 180 genes related to reactive oxygen species, signaling, pathogen defense, and arthropod allelochemical and physical defense. The expression of several of these genes in RWA-infested Dnx plants increased significantly from 6- to 24-h post infestation (hpi), but their expression in Dn0 plants, when present, was delayed until 48- to 96 hpi. Concentrations of 16- and 18-carbon fatty acids, trans-methyl-12-oxophytodienoic acid, and abscisic acid were significantly greater in Dnx foliage than in Dn0 foliage after RWA infestation, suggesting that Dnx RWA defense and resistance genes may be regulated via the oxylipin pathway. These findings provide a foundation for the elucidation of the molecular basis for compatible- and incompatible plant-aphid interactions.

BackgroundInosine 5′-monophosphate dehydrogenase type II (IMPDH2) was originally identified as an oncogene in several human cancers. However, the clinical significance and biological role of IMPDH2 remain poorly understood in colorectal cancer (CRC).MethodsQuantitative real-time polymerase chain reaction (qPCR), western blotting analysis, the Cancer Genome Atlas (TCGA) data mining and immunohistochemistry were employed to examine IMPDH2 expression in CRC cell lines and tissues. A series of in-vivo and in-vitro assays were performed to demonstrate the function of IMPDH2 and its possible mechanisms in CRC.ResultsIMPDH2 was upregulated in CRC cells and tissues at both mRNA and protein level. High IMPDH2 expression was closely associated with T stage, lymph node state, distant metastasis, lymphovascular invasion and clinical stage, and significantly correlated with poor survival of CRC patients. Further study revealed that overexpression of IMPDH2 significantly promoted the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of CRC cells in vitro and accelerated xenograft tumour growth in nude mice. On the contrary, knockdown of IMPDH2 achieved the opposite effect. Gene set enrichment analysis (GSEA) showed that the gene set related to cell cycle was linked to upregulation of IMPDH2 expression. Our study verified that overexpressing IMPDH2 could promote G1/S phase cell cycle transition through activation of PI3K/AKT/mTOR and PI3K/AKT/FOXO1 pathways and facilitate cell invasion, migration and EMT by regulating PI3K/AKT/mTOR pathway.ConclusionsThese results suggest that IMPDH2 plays an important role in the development and progression of human CRC and may serve as a novel prognostic biomarker and therapeutic target for CRC.