Two Cdc2 Kinase Genes with Distinct Functions in Vegetative and Infectious Hyphae in Fusarium graminearum.

Eukaryotic cell cycle involves a number of protein kinases important for the onset and progression through mitosis, most of which are well characterized in the budding and fission yeasts and conserved in other fungi. However, unlike the model yeast and filamentous fungi that have a single Cdc2 essential for cell cycle progression, the wheat scab fungus Fusarium graminearum contains two CDC2 orthologs. The cdc2A and cdc2B mutants had no obvious defects in growth rate and conidiation but deletion of both of them is lethal, indicating that these two CDC2 orthologs have redundant functions during vegetative growth and asexual reproduction. However, whereas the cdc2B mutant was normal, the cdc2A mutant was significantly reduced in virulence and rarely produced ascospores. Although deletion of CDC2A had no obvious effect on the formation of penetration branches or hyphopodia, the cdc2A mutant was limited in the differentiation and growth of infectious growth in wheat tissues. Therefore, CDC2A plays stage-specific roles in cell cycle regulation during infectious growth and sexual reproduction. Both CDC2A and CDC2B are constitutively expressed but only CDC2A was up-regulated during plant infection and ascosporogenesis. Localization of Cdc2A- GFP to the nucleus but not Cdc2B-GFP was observed in vegetative hyphae, ascospores, and infectious hyphae. Complementation assays with chimeric fusion constructs showed that both the N- and C-terminal regions of Cdc2A are important for its functions in pathogenesis and ascosporogenesis but only the N-terminal region is important for its subcellular localization. Among the Sordariomycetes, only three Fusarium species closely related to F. graminearum have two CDC2 genes. Furthermore, F. graminearum uniquely has two Aurora kinase genes and one additional putative cyclin gene, and its orthologs of CAK1 and other four essential mitotic kinases in the budding yeast are dispensable for viability. Overall, our data indicate that cell cycle regulation is different between vegetative and infectious hyphae in F. graminearum and Cdc2A, possibly by interacting with a stage-specific cyclin, plays a more important role than Cdc2B during ascosporogenesis and plant infection.

Functional analysis of the kinome of the wheat scab fungus Fusarium graminearum.

As in other eukaryotes, protein kinases play major regulatory roles in filamentous fungi. Although the genomes of many plant pathogenic fungi have been sequenced, systematic characterization of their kinomes has not been reported. The wheat scab fungus Fusarium graminearum has 116 protein kinases (PK) genes. Although twenty of them appeared to be essential, we generated deletion mutants for the other 96 PK genes, including 12 orthologs of essential genes in yeast. All of the PK mutants were assayed for changes in 17 phenotypes, including growth, conidiation, pathogenesis, stress responses, and sexual reproduction. Overall, deletion of 64 PK genes resulted in at least one of the phenotypes examined, including three mutants blocked in conidiation and five mutants with increased tolerance to hyperosmotic stress. In total, 42 PK mutants were significantly reduced in virulence or non-pathogenic, including mutants deleted of key components of the cAMP signaling and three MAPK pathways. A number of these PK genes, including Fg03146 and Fg04770 that are unique to filamentous fungi, are dispensable for hyphal growth and likely encode novel fungal virulence factors. Ascospores play a critical role in the initiation of wheat scab. Twenty-six PK mutants were blocked in perithecia formation or aborted in ascosporogenesis. Additional 19 mutants were defective in ascospore release or morphology. Interestingly, F. graminearum contains two aurora kinase genes with distinct functions, which has not been reported in fungi. In addition, we used the interlog approach to predict the PK-PK and PK-protein interaction networks of F. graminearum. Several predicted interactions were verified with yeast two-hybrid or co-immunoprecipitation assays. To our knowledge, this is the first functional characterization of the kinome in plant pathogenic fungi. Protein kinase genes important for various aspects of growth, developmental, and infection processes in F. graminearum were identified in this study.

Systemic immune-inflammation index is associated with coronary heart disease: a cross-sectional study of NHANES 2009-2018.

Background: Inflammation has been linked to the development of coronary heart disease (CHD). The systemic immune inflammation index (SII) is a useful biomarker of systemic inflammation. Our study aimed to explore the correlation between SII and CHD. Methods: We conducted a multivariate logistic regression analysis, smoothing curve fitting, and segmented model comparison on 15,905 participants with a CHD prevalence of 3.31% and a mean age of 46.97 years. Results: Adjusting for gender, age, and race, we found a negative association between SII and CHD [odds ratio (OR) 0.66; 95% confidence interval (CI) 0.48, 0.90]. There was an inverse trend where increasing SII was associated with decreasing odds of CHD (p for trend = 0.0017). After further adjustment, the association was strengthened, with a similar trend (p for trend = 0.0639). Smoothing curve fitting demonstrated a gender-specific association between SII and CHD. Conclusions: Our findings suggest that higher SII values may be associated with a higher incidence of CHD, which varies by gender. SII may be a cost-effective and convenient method to detect CHD. Further studies are needed to confirm the causality of these findings in a larger prospective cohort.

Negative Association between Serum Vitamin D Levels and Depression in a Young Adult US Population: A Cross-Sectional Study of NHANES 2007-2018.

BACKGROUND: Vitamin D has been suggested to play a role in the development of depression, but the nature of the relationship between the two is still not fully understood. Although some studies have shown an association between vitamin D deficiency and depression, others have yielded inconsistent or inconclusive results. As a result, further research is needed to better understand the relationship between vitamin D and depression. OBJECTIVES: This study aims to assess the association between serum vitamin D and the risk of depressive symptoms in individuals aged 20 years and older in the United States. METHODS: We selected 7562 participants from the 2007-2018 US National Health and Nutrition Examination Survey (NHANES). Participants' serum vitamin D levels were determined from laboratory data, and those with a Patient Health Questionnaire-9 (PHQ-9) score of ≥ 10 were considered to have depressive symptoms. Associations between vitamin D and depressive symptoms were investigated using multiple logistic regression, subgroup analysis, and smoothed curve fitting. RESULTS: In our study, 11.17% of the participants had depression. Multiple regression stratified analysis showed a significant inverse association between serum vitamin D and depression in the 29-39 years age group after full adjustment (OR = 0.54, 95% CI: 0.31-0.95, p = 0.0316). This result was supported by subgroup analysis and smoothed curve fitting. CONCLUSIONS: The association between serum vitamin D and depressive status in US adults varied across populations. Among those aged 29-39 years, vitamin D supplementation tended to show a lower rate of depression.

The MAT locus genes play different roles in sexual reproduction and pathogenesis in Fusarium graminearum.

Sexual reproduction plays a critical role in the infection cycle of Fusarium graminearum because ascospores are the primary inoculum. As a homothallic ascomycete, F. graminearum contains both the MAT1-1 and MAT1-2-1 loci in the genome. To better understand their functions and regulations in sexual reproduction and pathogenesis, in this study we assayed the expression, interactions, and mutant phenotypes of individual MAT locus genes. Whereas the expression of MAT1-1-1 and MAT12-1 rapidly increased after perithecial induction and began to decline after 1 day post-perithecial induction (dpi), the expression of MAT1-1-2 and MAT1-1-3 peaked at 4 dpi. MAT1-1-2 and MAT1-1-3 had a similar expression profile and likely are controlled by a bidirectional promoter. Although none of the MAT locus genes were essential for perithecium formation, all of them were required for ascosporogenesis in self-crosses. In outcrosses, the mat11-1-2 and mat11-1-3 mutants were fertile but the mat1-1-1 and mat1-2-1 mutants displayed male- and female-specific defects, respectively. The mat1-2-1 mutant was reduced in FgSO expression and hyphal fusion. Mat1-1-2 interacted with all other MAT locus transcription factors, suggesting that they may form a protein complex during sexual reproduction. Mat1-1-1 also interacted with FgMcm1, which may play a role in controlling cell identity and sexual development. Interestingly, the mat1-1-1 and mat1-2-1 mutants were reduced in virulence in corn stalk rot assays although none of the MAT locus genes was important for wheat infection. The MAT1-1-1 and MAT1-2-1 genes may play a host-specific role in colonization of corn stalks.