PROTHIOCONAZOLE TOLERANT \u3ci\u3eCRYPTOCOCCUS FLAVESCENS\u3c/i\u3e STRAINS FOR BIOLOGICAL CONTROL OF FUSARIUM HEAD BLIGHT

Strains of Cryptococcus flavescens which are superior antagonists of F. graminearum for suppression and control of FHB in cereals, particularly in wheat and barley, are described. The strains are prothioconazole tolerant variants of previously described C. flavescens OH 182.9 (NRRL Y-30216). Moreover, these prothioconazole tolerant variants exhibit significantly increased efficacy against F. graminearum in comparison to the parent strain OH 182.9

Carbon-to-Nitrogen Ratio and Carbon Loading of Production Media Influence Freeze-Drying Survival and Biocontrol Efficacy of \u3ci\u3eCryptococcus nodaensis\u3c/i\u3e OH 182.9

Fusarium head blight (FHB), caused by Gibberella zeae, is a devastating disease of wheat worldwide. Cryptococcus nodaensis OH 182.9 is an effective biocontrol agent for this disease. Development of a dried product of OH 182.9 would have potential advantages of ease of handling, favorable economics, and acceptance by end users. Isolate OH 182.9 was grown for 48 and 72 h in semi-defined complete liquid (SDCL) medium with carbon-to-nitrogen (C/N) ratios of 6.5:1, 9:1, 11:1, 15:1, and 30:1, and in SDCL C/N 30:1 media with varied carbon loadings of 7, 14, 21, and 28 g/liter. Total biomass production and cell survival at 15 days after freeze-drying were evaluated. Biomass production of OH 182.9 (CFU per milliliter) was not different for all cultivation time by medium C/N or carbon loading combinations. In general, cells harvested at 48 h survived freeze-drying better than those harvested at 72 h. Survival of freeze-dried cells was greatest for cells grown for 48 h in C/N 30:1 medium. Cells produced in C/N 6.5:1 medium generally exhibited the poorest survival. For the C/N 30:1 media, cells from 7 g/liter carbon loading medium harvested after 48 h had the best survival after freezedrying. The difference in freeze-dried cell populations between superior and inferior treatments was typically 1 to 2 log units at 15 days after freeze-drying. The biomass of OH 182.9 produced in SDCL with varied C/N ratios and in SDCL C/N 30:1 media with differing carbon loadings was tested for biocontrol efficacy against FHB in greenhouse studies. The biomass harvested from SDCL C/N 9:1, 11:1, and 15:1 media after 48 h significantly reduced symptoms of FHB. None of the treatments with cells harvested at 72 h consistently reduced FHB severity (P ≤ 0.05). Cells grown in SDCL C/N 30:1 media with 7 and 14 g/liter carbon loading significantly reduced FHB disease severity. Cells harvested from SDCL C/N 9:1, 11:1, and 30:1 with 14 g/liter carbon increased the 100-kernel weight compared with the disease control. The potential of improving OH 182.9 product quality via management of the nutritional environment of the production medium is demonstrated in this study

Carbon-to-Nitrogen Ratio and Carbon Loading of Production Media Influence Freeze-Drying Survival and Biocontrol Efficacy of \u3ci\u3eCryptococcus nodaensis\u3c/i\u3e OH 182.9

Fusarium head blight (FHB), caused by Gibberella zeae, is a devastating disease of wheat worldwide. Cryptococcus nodaensis OH 182.9 is an effective biocontrol agent for this disease. Development of a dried product of OH 182.9 would have potential advantages of ease of handling, favorable economics, and acceptance by end users. Isolate OH 182.9 was grown for 48 and 72 h in semi-defined complete liquid (SDCL) medium with carbon-to-nitrogen (C/N) ratios of 6.5:1, 9:1, 11:1, 15:1, and 30:1, and in SDCL C/N 30:1 media with varied carbon loadings of 7, 14, 21, and 28 g/liter. Total biomass production and cell survival at 15 days after freeze-drying were evaluated. Biomass production of OH 182.9 (CFU per milliliter) was not different for all cultivation time by medium C/N or carbon loading combinations. In general, cells harvested at 48 h survived freeze-drying better than those harvested at 72 h. Survival of freeze-dried cells was greatest for cells grown for 48 h in C/N 30:1 medium. Cells produced in C/N 6.5:1 medium generally exhibited the poorest survival. For the C/N 30:1 media, cells from 7 g/liter carbon loading medium harvested after 48 h had the best survival after freezedrying. The difference in freeze-dried cell populations between superior and inferior treatments was typically 1 to 2 log units at 15 days after freeze-drying. The biomass of OH 182.9 produced in SDCL with varied C/N ratios and in SDCL C/N 30:1 media with differing carbon loadings was tested for biocontrol efficacy against FHB in greenhouse studies. The biomass harvested from SDCL C/N 9:1, 11:1, and 15:1 media after 48 h significantly reduced symptoms of FHB. None of the treatments with cells harvested at 72 h consistently reduced FHB severity (P ≤ 0.05). Cells grown in SDCL C/N 30:1 media with 7 and 14 g/liter carbon loading significantly reduced FHB disease severity. Cells harvested from SDCL C/N 9:1, 11:1, and 30:1 with 14 g/liter carbon increased the 100-kernel weight compared with the disease control. The potential of improving OH 182.9 product quality via management of the nutritional environment of the production medium is demonstrated in this study

CHOLINE-UTILIZING MICROBLAL STRAINS FOR BIOLOGICALLY CONTROLLING FUSARIUM HEAD BLIGHT

Three choline utilizing strains of microorganisms isolated from the anthers of wheat, Aureobasidium pullulans strainAS 55.2, Arthrobacter species strain OH 221.3, and Pseudomonas species strain AS 64.4, are superior antagonists of F. graminearum. These microorganisms are effective for suppression and control of FHB in cereals, particularly in wheat and barley

Titin-truncating variants affect heart function in disease cohorts and the general population

Titin-truncating variants (TTNtv) commonly cause dilated cardiomyopathy (DCM). TTNtv are also encountered in ~1% of the general population, where they may be silent, perhaps reflecting allelic factors. To better understand TTNtv, we integrated TTN allelic series, cardiac imaging and genomic data in humans and studied rat models with disparate TTNtv. In patients with DCM, TTNtv throughout titin were significantly associated with DCM. Ribosomal profiling in rat showed the translational footprint of premature stop codons in Ttn, TTNtv-position-independent nonsense-mediated degradation of the mutant allele and a signature of perturbed cardiac metabolism. Heart physiology in rats with TTNtv was unremarkable at baseline but became impaired during cardiac stress. In healthy humans, machine-learning-based analysis of high-resolution cardiac imaging showed TTNtv to be associated with eccentric cardiac remodeling. These data show that TTNtv have molecular and physiological effects on the heart across species, with a continuum of expressivity in health and disease

Ubiquitin ligase STUB1 destabilizes IFNγ-receptor complex to suppress tumor IFNγ signaling

The cytokine IFNγ differentially impacts on tumors upon immune checkpoint blockade (ICB). Despite our understanding of downstream signaling events, less is known about regulation of its receptor (IFNγ-R1). With an unbiased genome-wide CRISPR/Cas9 screen for critical regulators of IFNγ-R1 cell surface abundance, we identify STUB1 as an E3 ubiquitin ligase for IFNγ-R1 in complex with its signal-relaying kinase JAK1. STUB1 mediates ubiquitination-dependent proteasomal degradation of IFNγ-R1/JAK1 complex through IFNγ-R1K285 and JAK1K249. Conversely, STUB1 inactivation amplifies IFNγ signaling, sensitizing tumor cells to cytotoxic T cells in vitro. This is corroborated by an anticorrelation between STUB1 expression and IFNγ response in ICB-treated patients. Consistent with the context-dependent effects of IFNγ in vivo, anti-PD-1 response is increased in heterogenous tumors comprising both wildtype and STUB1-deficient cells, but not full STUB1 knockout tumors. These results uncover STUB1 as a critical regulator of IFNγ-R1, and highlight the context-dependency of STUB1-regulated IFNγ signaling for ICB outcome

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

PROTHIOCONAZOLE TOLERANT \u3ci\u3eCRYPTOCOCCUS FLAVESCENS\u3c/i\u3e STRAINS FOR BIOLOGICAL CONTROL OF FUSARIUM HEAD BLIGHT

Strains of Cryptococcus flavescens which are superior antagonists of F. graminearum for suppression and control of FHB in cereals, particularly in wheat and barley, are described. The strains are prothioconazole tolerant variants of previously described C. flavescens OH 182.9 (NRRL Y-30216). Moreover, these prothioconazole tolerant variants exhibit significantly increased efficacy against F. graminearum in comparison to the parent strain OH 182.9

\u3ci\u3eBACILLUS\u3c/i\u3e SPECIES FOR REDUCING \u3ci\u3eFUSARIUM\u3c/i\u3e HEAD BLIGHT IN CEREALS

Microbial antagonists that will suppress Fusarium head blight (head scab) in cereals, particularly in wheat and barley have been identified. Two superior antagonists include NRRL B-30210 and NRRL B-30211