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  1. Abstract Background

    Filamentous fungi are prolific producers of bioactive molecules and enzymes with important applications in industry. Yet, the vast majority of fungal species remain undiscovered or uncharacterized. Here we focus our attention to a wild fungal isolate that we identified asAnthostomella pinea. The fungus belongs to a complex polyphyletic genus in the family ofXylariaceae, which is known to comprise endophytic and pathogenic fungi that produce a plethora of interesting secondary metabolites. Despite that,Anthostomellais largely understudied and only two species have been fully sequenced and characterized at a genomic level.

    Results

    In this work, we used long-read sequencing to obtain the complete 53.7 Mb genome sequence including the full mitochondrial DNA. We performed extensive structural and functional annotation of coding sequences, including genes encoding enzymes with potential applications in biotechnology. Among others, we found that the genome ofA. pineaencodes 91 biosynthetic gene clusters, more than 600 CAZymes, and 164 P450s. Furthermore, untargeted metabolomics and molecular networking analysis of the cultivation extracts revealed a rich secondary metabolism, and in particular an abundance of sesquiterpenoids and sesquiterpene lactones. We also identified the polyketide antibiotic xanthoepocin, to which we attribute the anti–Gram-positive effect of the extracts that we observed in antibacterial plate assays.

    Conclusions

    Taken together, our results provide a first glimpse into the potential ofAnthstomella pineato provide new bioactive molecules and biocatalysts and will facilitate future research into these valuable metabolites.

     
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  2. Abstract Background The function of DNA methyltransferase genes of insects is a puzzle, because an association between gene expression and methylation is not universal for insects. If the genes normally involved in cytosine methylation are not influencing gene expression, what might be their role? We previously demonstrated that gametogenesis of Oncopeltus fasciatus is interrupted at meiosis following knockdown of DNA methyltransferase 1 ( Dnmt1 ) and this is unrelated to changes in levels of cytosine methylation. Here, using transcriptomics, we tested the hypothesis that Dmnt1 is a part of the meiotic gene pathway. Testes, which almost exclusively contain gametes at varying stages of development, were sampled at 7 days and 14 days following knockdown of Dmnt1 using RNAi. Results Using microscopy, we found actively dividing spermatocysts were reduced at both timepoints. However, as with other studies, we saw Dnmt1 knockdown resulted in condensed nuclei after mitosis–meiosis transition, and then cellular arrest. We found limited support for a functional role for Dnmt1 in our predicted cell cycle and meiotic pathways. An examination of a priori Gene Ontology terms showed no enrichment for meiosis. We then used the full data set to reveal further candidate pathways influenced by Dnmt1 for further hypotheses. Very few genes were differentially expressed at 7 days, but nearly half of all transcribed genes were differentially expressed at 14 days. We found no strong candidate pathways for how Dnmt1 knockdown was achieving its effect through Gene Ontology term overrepresentation analysis. Conclusions We, therefore, suggest that Dmnt1 plays a role in chromosome dynamics based on our observations of condensed nuclei and cellular arrest with no specific molecular pathways disrupted. 
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    Free, publicly-accessible full text available December 1, 2024
  3. Abstract

    The observation ofγrays from the decay of44Ti in the remnants of core-collapse supernovae (CCSNe) provides crucial information regarding the nucleosynthesis occurring in these events, as44Ti production is sensitive to CCSNe conditions. The final abundance of44Ti is also sensitive to specific nuclear input parameters, one of which is the57Ni(p,γ)58Cu reaction rate. A precise rate for57Ni(p,γ)58Cu is thus critical if44Ti production is to be an effective probe into CCSNe. To experimentally constrain the57Ni(p,γ)58Cu rate, the structure properties of58Cu were measured via the58Ni(3He,t)58Cu*(γ) reaction using GODDESS (GRETINA ORRUBA Dual Detectors for Experimental Structure Studies) at Argonne National Laboratory’s ATLAS facility. Details of the experiment, ongoing analysis, and plans are presented.

     
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    Free, publicly-accessible full text available September 1, 2024
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  6. Free, publicly-accessible full text available May 1, 2024
  7. Background: Neoadjuvant chemotherapy (NACT) is an increasingly used approach for treatment of breast cancer. The pathological complete response (pCR) is considered a good predictor of disease-specific survival. This study investigated whether circulating exosomal microRNAs could predict pCR in breast cancer patients treated with NACT. Method: Plasma samples of 20 breast cancer patients treated with NACT were collected prior to and after the first cycle. RNA sequencing was used to determine microRNA profiling. The Cancer Genome Atlas (TCGA) was used to explore the expression patterns and survivability of the candidate miRNAs, and their potential targets based on the expression levels and copy number variation (CNV) data. Results: Three miRNAs before that NACT (miR-30b, miR-328 and miR-423) predicted pCR in all of the analyzed samples. Upregulation of miR-127 correlated with pCR in triple-negative breast cancer (TNBC). After the first NACT dose, pCR was predicted by exo-miR-141, while miR-34a, exo-miR182, and exo-miR-183 predicted non-pCR. A significant correlation between the candidate miRNAs and the overall survival, subtype, and metastasis in breast cancer, suggesting their potential role as predictive biomarkers of pCR. Conclusions: If the miRNAs identified in this study are validated in a large cohort of patients, they might serve as predictive non-invasive liquid biopsy biomarkers for monitoring pCR to NACT in breast cancer. 
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