Immune checkpoint therapy targeting the PD-1/PD-L1 axis is a potentially novel development in anticancer therapy and has been applied to clinical medicine. However, there are still some problems, including a relatively low response rate, innate mechanisms of resistance against immune checkpoint blockades, and the absence of reliable biomarkers to predict responsiveness. In this study of in vitro and in vivo models, we demonstrate that PD-L1–vInt4, a splicing variant of PD-L1, plays a role as a decoy in anti–PD-L1 antibody treatment. First, we showed that PD-L1–vInt4 was detectable in clinical samples and that it was possible to visualize the secreting variants with IHC. By overexpressing the PD-L1–secreted splicing variant on MC38 cells, we observed that an immune-suppressing effect was not induced by their secretion alone. We then demonstrated that PD-L1–vInt4 secretion resisted anti–PD-L1 antibody treatment, compared with WT PD-L1, which was explicable by the PD-L1–vInt4’s decoying of the anti–PD-L1 antibody. The decoying function of PD-L1 splicing variants may be one of the reasons for cancers being resistant to anti–PD-L1 therapy. Measuring serum PD-L1 levels might be helpful in deciding the therapeutic strategy.

The pathogen causing Fusarium wilt in banana is reported to be Fusarium oxysporum f. sp. cubense (FOC). In 2019, wilt symptoms in banana plants (cultivar: Cavendish) in the Philippines were detected, i.e., the yellowing of the leaves and discoloration of the pseudostem and vascular tissue. The fungus isolated from the vascular tissue was found to be pathogenic to Cavendish bananas and was identified as a new species, F. mindanaoense, belonging to the F. fujikuroi species complex (FFSC); species classification was assessed using molecular phylogenetic analyses based on the tef1, tub2, cmdA, rpb1, and rpb2 genes and morphological analyses. A reciprocal blast search using genomic data revealed that this fungus exclusively included the Secreted in Xylem 6 (SIX6) gene among the SIX homologs related to pathogenicity; it exhibited a highly conserved amino acid sequence compared with that of species in the FFSC, but not with that of FOC. This was the first report of Fusarium wilt in Cavendish bananas caused by a species of the genus Fusarium other than those in the F. oxysporum species complex.

The innate immune system ofDrosophilais activated by ingestion of microorganisms.D. melanogasterbreeds on fruits fermented bySaccharomyces cerevisiae, whereasD. virilisbreeds on slime flux and decaying bark of tree housing a variety of bacteria, yeasts, and molds. In this study, it is shown thatD. virilishas a higher resistance to oral infection of a species of filamentous fungi belonging to the genusPenicilliumcompared toD. melanogaster. In response to the fungal infection, a transcriptome profile of immune-related genes was considerably different betweenD. melanogasterandD. virilis: the genes encoding antifungal peptides, Drosomycin and Metchnikowin, were highly expressed inD. melanogasterwhereas, the genes encoding Diptericin and Defensin were highly expressed inD. virilis. On the other hand, the immune-induced molecule (IM) genes showed contrary expression patterns between the two species: they were induced by the fungal infection inD. melanogasterbut tended to be suppressed inD. virilis. Our transcriptome analysis also showed newly predicted immune-related genes inD. virilis. These results suggest that the innate immune system has been extensively differentiated during the evolution of theseDrosophilaspecies.

Recent advances in high-throughput sequencing technologies have significantly enhanced the accuracy of phylogenetic inference, enabling comprehensive genome-wide analyses. Fusarium fungi, which include numerous agriculturally and medically important species, are typically classified at the species complex (SC) level. Clarifying the evolutionary relationships and distinctiveness of these SCs is therefore essential for accurate identification and understanding of their biology. Recent large-scale phylogenetic studies based on genomic data have provided a more resolved understanding of the evolutionary relationships among Fusarium SCs, supporting the view that most represent evolutionarily coherent and stable lineages. However, the phylogenetic position of Fusarium commune has not been explicitly examined, despite incongruence between phylogenies inferred from nucleotide and amino acid sequence data. This study aimed to clarify the phylogenetic placement of F. commune at the SC level by re-examining its position using a genome dataset independent of those employed in previous studies. Our results are largely consistent with previously reported genome-scale phylogenetic analyses of the genus Fusarium and support the stability of most SCs. However, F. commune was not clearly included in any of the currently recognized SCs and instead formed an independent lineage. These findings provide insights into the evolutionary history of Fusarium SCs and contribute to a better understanding of the taxonomic position of F. commune.

In this paper, we consider the pricing problem of the premium of a whole life insurance by using a model where (I) the health condition of each insured person is described by a two-state Markov chain, and (II) the insured may surrender the insurance according as her/his health condition and the premium. This is a toy model of the authors' general framework called “thermodynamical approach to insurance”.