Alternative splicing (AS) may increase the number of proteoforms produced by a gene. Alzheimer’s disease (AD) is a neurodegenerative disease with well-characterized AS proteoforms. In this study, we used a proteogenomics strategy to build a customized protein sequence database and identify orthologous AS proteoforms between humans and mice on publicly available shotgun proteomics (MS/MS) data of the corpus callosum (CC) and olfactory bulb (OB). Identical proteotypic peptides of six orthologous AS proteoforms were found in both species: PKM1 (gene PKM/Pkm), STXBP1a (gene STXBP1/Stxbp1), Isoform 3 (gene HNRNPK/Hnrnpk), LCRMP-1 (gene CRMP1/Crmp1), SP3 (gene CADM1/Cadm1), and PKCβII (gene PRKCB/Prkcb). These AS variants were also detected at the transcript level by publicly available RNA-Seq data and experimentally validated by RT-qPCR. Additionally, PKM1 and STXBP1a were detected at higher abundances in a publicly available MS/MS dataset of the AD mouse model APP/PS1 than its wild type. These data corroborate other reports, which suggest that PKM1 and STXBP1a AS proteoforms might play a role in amyloid-like aggregate formation. To the best of our knowledge, this report is the first to describe PKM1 and STXBP1a overexpression in the OB of an AD mouse model. We hope that our strategy may be of use in future human neurodegenerative studies using mouse models.

Biological control agents (BCA) are an alternative to chemical pesticides and an emerging strategy to safely eliminate plant pathogens. Trichoderma spp. are the most common fungi used as BCAs. They produce spores that are released into the air and can potentially interact with immune system of mammals. We previously showed that Trichoderma affects expression of genes encoding pattern recognition receptors (PRRs) and cytokines in mice. PRRs are involved in the recognition of microorganisms and can lead to pro-tumoral signaling. Here, we evaluated if mice injected with low doses of murine melanoma exhibited increased development of lung tumor when treated with conidia of T. stromaticum. Mice treated with T. stromaticum and inoculated with B16-F10 melanoma cells exhibited significant increase in tumor uptake (p = 0.006) and increased number of visible nodules in the lungs (p = 0.015). We also analyzed mRNA expression levels of genes encoding PRRs in lung of mice exposed to T. stromaticum and demonstrated that mice treated with T. stromaticum conidia exhibited lower expression levels of Clec7a and increased expression of Tlr4 (toll like receptor 4) compared to non-treated controls. The expression levels of Clec7a and Tlr2 were increased in mice treated with T. stromaticum and inoculated with murine melanoma compared to controls only inoculated with melanoma. Our results demonstrate that intranasal exposition to T. stromaticum increases tumor in the B16-F10 model, which may raise concerns regarding the safety of its use in agriculture.