A new method to determine the tropopause

The tropopause has a complex structure and some interference information may exist in high-resolution global positioning system (GPS)/low earth-orbiting (LEO) radio occultation (RO) data. The position of the tropopause cannot be accurately determined using traditional cold point tropopause (CPT) and lapse rate tropopause (LRT) algorithms. In this paper, an integrative algorithm is developed to determinate tropopause parameters. The algorithm is applied to GPS/COSMIC RO data to obtain a global distribution of the height and temperature of the tropopause. This algorithm improves the utilization rate of GPS/LEO RO data by 30% compared with that from the traditional CPT method. The rationality and reliability of GPS/LEO RO data in probing the Earth’s atmosphere are verified by our study of the tropopause using COSMIC data

Nitrate reductase is required for sclerotial development and virulence of Sclerotinia sclerotiorum

Sclerotinia sclerotiorum, the causal agent of Sclerotinia stem rot (SSR) on more than 450 plant species, is a notorious fungal pathogen. Nitrate reductase (NR) is required for nitrate assimilation that mediates the reduction of nitrate to nitrite and is the major enzymatic source for NO production in fungi. To explore the possible effects of nitrate reductase SsNR on the development, stress response, and virulence of S. sclerotiorum, RNA interference (RNAi) of SsNR was performed. The results showed that SsNR-silenced mutants showed abnormity in mycelia growth, sclerotia formation, infection cushion formation, reduced virulence on rapeseed and soybean with decreased oxalic acid production. Furthermore SsNR-silenced mutants are more sensitive to abiotic stresses such as Congo Red, SDS, H2O2, and NaCl. Importantly, the expression levels of pathogenicity-related genes SsGgt1, SsSac1, and SsSmk3 are down-regulated in SsNR-silenced mutants, while SsCyp is up-regulated. In summary, phenotypic changes in the gene silenced mutants indicate that SsNR plays important roles in the mycelia growth, sclerotia development, stress response and fungal virulence of S. sclerotiorum

A Novel Gammapartitivirus That Causes Changes in Fungal Development and Multi-Stress Tolerance to Important Medicinal Fungus Cordyceps chanhua

Cicada flower, scientifically named Cordyceps chanhua, is an important and well-known Chinese cordycipitoid medicinal mushroom. Although most mycoviruses seem to induce latent infections, some mycoviruses cause host effects. However, the effects of mycovirus on the fungal development and stress tolerance of C. chanhua remain unknown. In this study, we report a novel mycovirus designated Cordyceps chanhua partitivirus 1 (CchPV1) from C. chanhua isolate RCEF5997. The CchPV1 genome comprises dsRNA 1 and dsRNA 2, 1784 and 1563 bp in length, respectively. Phylogenetic analysis using the aa sequences of RdRp revealed that CchPV1 grouped with members of the genus Gammapartitivirus in the family Partitiviridae. We further co-cultivated on PDA donor strain RCEF5997 and recipient C. chanhua strain RCEF5833 (Vf) for 7 days, and we successfully obtained an isogenic line of strain RCEF5833 with CchPV1 (Vi) through single-spore isolation, along with ISSR marker and dsRNA extraction. The biological comparison revealed that CchPV1 infection slows the growth rate of the host, but increases the conidiation and formation of fruiting bodies of the host. Furthermore, the assessment of fungal tolerance demonstrated that CchPV1 weakens the multi-stress tolerance of the host. Thus, CchPV1 infection cause changes in fungal development and multi-stress tolerance of the host C. chanhua. The findings of this study elucidate the effects of gammapartitivirus on host entomogenous fungi and provide a novel strategy for producing high-quality fruiting bodies of C. chanhua

The Histone Mark H3K36me3 Regulates Human DNA Mismatch Repair through Its Interaction with MutSα

SummaryDNA mismatch repair (MMR) ensures replication fidelity by correcting mismatches generated during DNA replication. Although human MMR has been reconstituted in vitro, how MMR occurs in vivo is unknown. Here, we show that an epigenetic histone mark, H3K36me3, is required in vivo to recruit the mismatch recognition protein hMutSα (hMSH2-hMSH6) onto chromatin through direct interactions with the hMSH6 PWWP domain. The abundance of H3K36me3 in G1 and early S phases ensures that hMutSα is enriched on chromatin before mispairs are introduced during DNA replication. Cells lacking the H3K36 trimethyltransferase SETD2 display microsatellite instability (MSI) and an elevated spontaneous mutation frequency, characteristic of MMR-deficient cells. This work reveals that a histone mark regulates MMR in human cells and explains the long-standing puzzle of MSI-positive cancer cells that lack detectable mutations in known MMR genes

A novel partitivirus orchestrates conidiation, stress response, pathogenicity, and secondary metabolism of the entomopathogenic fungus Metarhizium majus.

Mycoviruses are widely present in all major groups of fungi but those in entomopathogenic Metarhizium spp. remain understudied. In this investigation, a novel double-stranded (ds) RNA virus is isolated from Metarhizium majus and named Metarhizium majus partitivirus 1 (MmPV1). The complete genome sequence of MmPV1 comprises two monocistronic dsRNA segments (dsRNA 1 and dsRNA 2), which encode an RNA-dependent RNA polymerase (RdRp) and a capsid protein (CP), respectively. MmPV1 is classified as a new member of the genus Gammapartitivirus in the family Partitiviridae based on phylogenetic analysis. As compared to an MmPV1-free strain, two isogenic MmPV1-infected single-spore isolates were compromised in terms of conidiation, and tolerance to heat shock and UV-B irradiation, while these phenotypes were accompanied by transcriptional suppression of multiple genes involved in conidiation, heat shock response and DNA damage repair. MmPV1 attenuated fungal virulence since infection resulted in reduced conidiation, hydrophobicity, adhesion, and cuticular penetration. Additionally, secondary metabolites were significantly altered by MmPV1 infection, including reduced production of triterpenoids, and metarhizins A and B, and increased production of nitrogen and phosphorus compounds. However, expression of individual MmPV1 proteins in M. majus had no impact on the host phenotype, suggesting insubstantive links between defective phenotypes and a single viral protein. These findings indicate that MmPV1 infection decreases M. majus fitness to its environment and its insect-pathogenic lifestyle and environment through the orchestration of the host conidiation, stress tolerance, pathogenicity, and secondary metabolism

Pharmacological activation of GPX4 ameliorates doxorubicin-induced cardiomyopathy

Due to the cardiotoxicity of doxorubicin (DOX), its clinical application is limited. Lipid peroxidation caused by excessive ferrous iron is believed to be a key molecular mechanism of DOX-induced cardiomyopathy (DIC). Dexrazoxane (DXZ), an iron chelator, is the only drug approved by the FDA for reducing DIC, but it has many side effects and cannot be used as a preventive drug in clinical practice. Single-nucleus RNA sequencing (snRNA-seq) analysis identified myocardial and epithelial cells that are susceptible to DOX-induced ferroptosis. The glutathione peroxidase 4 (GPX4) activator selenomethione (SeMet) significantly reduced polyunsaturated fatty acids (PUFAs) and oxidized lipid levels in vitro. Consistently, SeMet significantly decreased DOX-induced lipid peroxidation in H9C2 cells and mortality in C57BL/6 mice compared to DXZ, ferrostatin-1, and normal saline. SeMet can effectively reduce serum markers of cardiac injury in C57BL/6 mice and breast cancer patients. Depletion of the GPX4 gene in C57BL/6 mice resulted in an increase in polyunsaturated fatty acid (PUFA) levels and eliminated the protective effect of SeMet against DIC. Notably, SeMet exerted antitumor effects on breast cancer models with DOX while providing cardiac protection for the same animal without detectable toxicities. These findings suggest that pharmacological activation of GPX4 is a valuable and promising strategy for preventing the cardiotoxicity of doxorubicin