Phialemonium globosum strain:LMS 16-13
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ABSTRACT:
PROVIDER: PRJNA1080882 | ENA |
REPOSITORIES: ENA
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Project description:Chaetomium globosum is a model of conditional pathogens abundant on a wide variety of substrates in soil, water, and atmosphere environments. Homothallic C. globosum produces hairy perithecia bearing meiotic ascospores that are resistant to harsh conditions for dispersal, and asexual reproduction of conidia has never been observed. RNAs were samples from nine distinct morphological stages during the nearly synchronic perithecial development for C. globosum. Unlike the heterothallic Neurospora crassa, the mating type gene mat a-1 showed comparatively lower expression changes but highly coordinate with expression regulation of mat A-1 in C. globosum. Key regulators, including orthologs of N. crassa sub-1, sub-1 dependent gene NCU00309, and asl-1, in the initiation of sexual development in response to light stimuli, showed similar regulation dynamics between C. globosum and N. crassa. Knockout phenotyping directed by the comparative analysis of transcriptomics between C. globosum and its’ closely related Neurospora crassa also suggested some genes that are critical for perithecial development. Among 24 secondary metabolism clusters composed more than 3 genes in C. globosum, 11 showed highly coordinated expression across the perithecial development, and dramatically up-regulation was recorded for all 12 genes in the cochliodones biosynthesis cluster. Up-regulation of chaetoglocin and aureonitol biosynthesis clusters was found to be associated with disturbance in early sexual development and with ascospore maturation. Similar to pathogenic Fusarium graminearum, C. globosum showed coordinately up-regulated expression of homologs of histidine kinases in hyperosmotic response pathways, consist with their ecology adapting to high humidity.
2019-12-29 | GSE131190 | GEO
Project description:Purpose: DDL and LMS are two common subtypes of soft tissue sarcoma, a rare group of diseases for which new treatments are needed. Chemotherapy remains the standard option for advanced disease. Targeting CDK4/6 in DDL and mTOR in LMS is of biologic interest. When combined, the CDK4 inhibitor ribociclib and the mTOR inhibitor everolimus, have shown synergistic growth inhibition in multiple tumor models, suggesting that this combination could be beneficial in patients.Methods: This was a single arm, open label, multi-center phase II study of the combination of ribociclib and everolimus. Patients were enrolled into one of two cohorts: DDL or LMS with intact Rb. The primary endpoint was progression free rate (PFR) at 16 weeks. Secondary endpoints included progression free (PFS) and overall survival, safety and biomarker analyses. Results: In the DDL cohort, 33.3% (95% CI 15.6%-55.3%) of patients were progression free at 16 weeks. Median PFS in this cohort was 15.4 weeks (95% CI, 8-36 weeks) with 2 partial responses. In the LMS cohort the PFR at 16 weeks was 29.2% (95% CI 12.6%-51.1%). Median PFS in this cohort was 15.7 weeks (95% CI 7.7-NA). Most common toxicities included fatigue (66.7%), anorexia (43.8%) and hyperglycemia (43.8%). Concordance between Rb testing methodologies was poor.Conclusions: The combination of ribociclib and everolimus demonstrates activity in DDL with prolonged stable disease (≥16 weeks) meeting the primary endpoint. Notably partial responses were observed. The primary endpoint was not reached in the LMS cohort. The combination was well tolerated with expected side effects.
2023-11-09 | GSE247026 | GEO
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