Genomic insights into glume pubescence in durum wheat: GWAS and haplotype analysis implicates TdELD1-1A as a candidate gene.

Glume pubescence is an important morphological trait for the characterization of wheat cultivars. It shows tolerance to biotic and abiotic stresses to some extent. Hg1 (formerly named Hg) locus on chromosome 1AS controls glume pubescence in wheat. Its genetic analysis, fine-mapping and candidate gene analysis have been widely studied recently, however, the cloning of Hg1 has not yet been reported. Here, we conducted a GWAS between a dense panel of 171,103 SNPs and glume pubescence (Gp) in a durum wheat population of 145 lines, and further analyzed the candidate genes of Hg1 combined with the gene expression, functional annotation, and haplotype analysis. As a results, TRITD0Uv1G104670 (TdELD1-1A), encoding glycosyltransferase-like ELD1/KOBITO 1, was detected as the most promising candidate gene of Hg1 for glume pubescence in durum wheat. Our findings not only contribute to a deeper understanding of its cloning and functional validation but also underscore the significance of accurate genome sequences and annotations. Additionally, our study highlights the relevance of unanchored sequences in chrUn and the application of bioinformatics analysis for gene discovery in durum wheat.

Association of blood eosinophilia and vitamin D insufficiency in young infants with cow milk allergy.

BACKGROUND AND OBJECTIVES: Cow milk allergy is the most common food allergic disease in young infants and vitamin D has a critical role in regulating intestinal inflammation. METHODS AND STUDY DESIGN: To determine roles of vitamin D in cow milk allergy, fifty-six young infants with cow milk allergy were enrolled. The serum 25-hydroxyvitamin D (25OHD), total and specific IgE, circulating regulatory T lymphocytes, and blood eosino-phil counts were determined. RESULTS: The serum 25OHD in cow milk allergy and age-matched infants were sim-ilar (68.3±38.9 nmol/L versus 72.9±33.1 nmol/L, p>0.05), 71% Cow milk allergy infants (40/56) had serum 25OHD lower than 75 nmol/L compared to 66% (37/56) in the controls. The cow milk allergy infants with 25OHD lower than 75 nmol/L had persistent blood eosinophilia and delayed resolution of symptoms after cow milk elimination compared to those with 25OHD above 75 nmol/L (odd ratio 3.7, 95% CI 1.1-12.6, p<0.05). The serum 25OHD inversely correlated with blood eosinophil counts after cow milk elimination (r=-0.37, p<0.01). Cow milk allergy infants with 25OHD lower than 50 nmol/L (vitamin D deficiency, n = 22) were in general at younger age (1.6±0.6 months) compared to infants with insufficient (50-75 nmol/L) or normal (>=75 nmol/L) group (4.3±1.2 and 4.6±0.9 months, respectively, p<0.001). CONCLUSIONS: Low serum vitamin D associates with persistent blood eosinophilia and symptoms in young cow milk allergy infants.

Enhancement of adenovirus infection and adenoviral vector-mediated gene delivery by bromodomain inhibitor JQ1.

Adenovirus-based vectors are among the most commonly used platforms for gene delivery and gene therapy studies. One of the obstacles for potential application is dose-related toxicity. We show here that adenovirus infection and Ad-mediated gene delivery can be enhanced by inhibitors of bromodomain and extra-terminal (BET) family proteins. We showed that JQ1, but not its inactive enantiomer (-)-JQ1, dose-dependently promoted Ad infection and Ad-mediated gene delivery in both epithelial and lymphocyte cells. Given orally, JQ1 also enhanced transgene expression in a murine tumor model. Inhibitors of histone deacetylases (HDACi) are among the commonly reported small molecule compounds which enhance Ad-mediated gene delivery. We found that JQ1 treatment did not cause histone acetylation nor expression of Ad attachment receptor CAR. Instead, JQ1 treatment induced an increase in BRD4 association with CDK9, a subunit of P-TEFb of transcription elongation. Concurrently, we showed that CDK9 inhibition blocked Ad infection and JQ1 enhancement on the infection. The study exemplifies the potentials of BET inhibitors like JQ1 in oncolytic virotherapy.

Suppression of IRG-1 Reduces Inflammatory Cell Infiltration and Lung Injury in Respiratory Syncytial Virus Infection by Reducing Production of Reactive Oxygen Species.

UNLABELLED: Respiratory syncytial virus (RSV) infection is a common cause of lower respiratory tract illness in infants and children. RSV is a negative-sense, single-strand RNA (ssRNA) virus that mainly infects airway epithelial cells. Accumulating evidence indicates that reactive oxygen species (ROS) production is a major factor for pulmonary inflammation and tissue damage of RSV disease. We investigated immune-responsive gene-1 (IRG1) expression during RSV infection, since IRG1 has been shown to mediate innate immune response to intracellular bacterial pathogens by modulating ROS and itaconic acid production. We found that RSV infection induced IRG1 expression in human A549 cells and in the lung tissues of RSV-infected mice. RSV infection or IRG1 overexpression promoted ROS production. Accordingly, knockdown of IRG1 induction blocked RSV-induced ROS production and proinflammatory cytokine gene expression. Finally, we showed that suppression of IRG1 induction reduced immune cell infiltration and prevented lung injury in RSV-infected mice. These results therefore link IRG1 induction to ROS production and immune lung injury after RSV infection. IMPORTANCE: RSV infection is among the most common causes of childhood diseases. Recent studies identify ROS production as a factor contributing to RSV disease. We investigated the cause of ROS production and identified IRG1 as a critical factor linking ROS production to immune lung injury after RSV infection. We found that IRG1 was induced in A549 alveolar epithelial cells and in mouse lungs after RSV infection. Importantly, suppression of IRG1 induction reduced inflammatory cell infiltration and lung injury in mice. This study links IRG1 induction to oxidative damage and RSV disease. It also uncovers a potential therapeutic target in reducing RSV-caused lung injury.

A novel benzenediamine derivative FC98 reduces insulin resistance in high fat diet-induced obese mice by suppression of metaflammation.

Chronic low-grade metabolic inflammation (metaflammation) is a hallmark of metabolic diseases. The aim of this study was to determine the effectiveness of a newly identified benzenediamine derivative (FC98, PubChem CID: 14989837) against metaflammation and insulin resistance using a high fat diet-induced obesity (DIO) murine model. LPS and free fatty acids (FFAs)-induced gene expression and signaling was determined in cell culture systems. Inflammasome activation was determined by measuring IL-1ß release with ELISA. The in vivo activity was assayed in C57BL/6J mice fed with a high fat diet (HFD) by measuring body weight gains, glucose tolerance and insulin sensitivity. The effect was also evaluated by H&E and IHC staining, by measuring gene expression and cytokine production, and by analysis of F4/80(+)CD11b(+) macrophage infiltration. FC98 exhibited anti-inflammatory activity against LPS- and FFAs-induced IL-1ß, IL-6, and TNF-α gene expression and JNK and p38 activation. The IC50 for FC98 to inhibit NO production was determined at 6.8µM. FC98 also dose-dependently inhibited IL-1ß secretion. In DIO mice, FC98 at 10 and 20mg/kg significantly improved metabolic parameters, including body weight, fat mass, glucose disposal and insulin sensitivity. The reduction in adipocyte area, F4/80(+)CD11b(+) macrophage infiltration, proinflammatory gene expression, along with JNK activation, was also significant in those groups. Additionally, FC98-treated animals had increased AKT phosphorylation in response to insulin stimulation. FC98 inhibits metaflammation and ameliorates insulin resistance mainly by inhibiting signaling pathways of proinflammatory response in DIO animals. This study highlights the significance of targeting metaflammation for obesity-attributive metabolic syndrome.