Hirsutella minnesotensis [Ophiocordycipitaceae (Hypocreales, Ascomycota)] is a dominant endoparasitic fungus by using conidia that adhere to and penetrate the secondary stage juveniles of soybean cyst nematode. Its genome was de novo sequenced and compared with five entomopathogenic fungi in the Hypocreales and three nematode-trapping fungi in the Orbiliales (Ascomycota). The genome of H. minnesotensis is 51.4 Mb and encodes 12,702 genes enriched with transposable elements up to 32%. Phylogenomic analysis revealed that H. minnesotensis was diverged from entomopathogenic fungi in Hypocreales. Genome of H. minnesotensis is similar to those of entomopathogenic fungi to have fewer genes encoding lectins for adhesion and glycoside hydrolases for cellulose degradation, but is different from those of nematode-trapping fungi to possess more genes for protein degradation, signal transduction, and secondary metabolism. Those results indicate that H. minnesotensis has evolved different mechanism for nematode endoparasitism compared with nematode-trapping fungi. Transcriptomics analyses for the time-scale parasitism revealed the upregulations of lectins, secreted proteases and the genes for biosynthesis of secondary metabolites that could be putatively involved in host surface adhesion, cuticle degradation, and host manipulation. Genome and transcriptome analyses provided comprehensive understanding of the evolution and lifestyle of nematode endoparasitism.
Aims The H 2 FPEF score is a convenient risk stratification tool for diagnosing heart failure with preserved ejection fraction (HFpEF). This study examined the value of the H 2 FPEF score for predicting all-cause mortality and rehospitalization in HFpEF patients. Methods and results This was a retrospective cohort study of patients diagnosed with HFpEF by echocardiography at a single tertiary centre between 1 January 2015 and 30 April 2018. According to the H 2 FPEF score, the subjects were divided into low (0-1 points), intermediate (2-5 points), and high (6-9 points) score groups. The primary outcomes were all-cause mortality and rehospitalization. A total of 476 patients (mean age: 70.5 ± 8.4 years, 60.7% female) were included. Of these, 47 (9.9%), 262 (55.0%), and 167 (35.1%) were classified into the low, intermediate, and high score groups, respectively. Over a mean follow-up of 27.5 months, 63 patients (13.2%) died, and 311 patients (65.3%) were rehospitalized. The mortality rates were 3 (6.4%), 29 (11.1%), and 31 (18.6%), and the number of patients with rehospitalization was 28 (59.6%), 159 (60.7%), and 124 (74.3%) for the low, intermediate, and high score groups, respectively. Multivariate Cox regression identified H 2 FPEF score as an independent predictor of all-cause mortality (hazard ratio [HR]: 1.46, 95% CI: 1.23-1.73, P < 0.0001) and rehospitalization (HR: 1.15, 95% CI: 1.08-1.22, P < 0.0001). Receiver operating characteristic (ROC) analysis demonstrated the H 2 FPEF score can effectively predict all-cause mortality (AUC 0.67, 95% CI: 0.60-0.73, P < 0.0001) and rehospitalization (AUC 0.59, 95% CI: 0.54-0.65, P = 0.001) after adjusting for age and NYHA class. With a cutoff value of 5.5, the sensitivity and specificity were 68.3% and 55.4% for all-cause mortality and 50.5% and 66.7% for rehospitalization. Conclusions The H 2 FPEF score can be used to predict prognosis in HFpEF patients. Higher scores are associated with higher all-cause mortality and rehospitalization.
The transcription factor SKN7 is a highly conserved protein among fungi and was initially recognized as a response regulator that protects cells from oxidative stress and maintains cell wall integrity in yeast. Orthologs of SKN7 are extensively present in biocontrol agents of plant pathogens, but they had not been functionally characterized. Here, we identified and characterized the transcription factor SKN7 in the nematode endoparasitic fungus Hirsutella minnesotensis. Null mutant lacking HIM-SKN7 (HIM_03620), which was generated by a gene disruption strategy, demonstrated reduced conidiation, increased sensitivity to high temperature, hydrogen peroxide, mannitol and ethanol, and reduced fungal resistance to farnesol. However, over-expression mutant showed increased conidial production, thermotolerance and resistance to farnesol, suggesting that HIM-SKN7 regulates antiapoptotic-like cell death in H. minnesotensis. Moreover, the results showed that in null mutant, H. minnesotensis had decreased endoparasitic ability as compared to wild type and over-expression strain. During the infection process, the relative expression of the HIM-SKN7 gene was significantly induced in the wild type and over-expression strain. The results of the present study advance our understanding of the functions of the SKN7 gene in biocontrol agents, in particular, nematode endoparasitic fungi.
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