Background: The metabolism of tryptophan to kynurenines (KYN) by indoleamine-2,3-dioxygenase or tryptophan-2,3-dioxygenase is a key pathway of constitutive and adaptive tumor immune resistance. The immunosuppressive effects of KYN in the tumor microenvironment are predominantly mediated by the aryl hydrocarbon receptor (AhR), a cytosolic transcription factor that broadly suppresses immune cell function. Inhibition of AhR thus offers an antitumor therapy opportunity via restoration of immune system functions.
View Article and Find Full Text PDFAnalysis of convalescent plasma derived from individuals has shown that IgG3 has the most important role in binding to SARS-CoV-2 antigens; however, this has not yet been confirmed in large studies, and the link between binding and neutralization has not been confirmed. By analyzing plasma pools consisting of 247-567 individual convalescent donors, we demonstrated the binding of IgG3 and IgM to Spike-1 protein and the receptor-binding domain correlates strongly with viral neutralization in vitro. Furthermore, despite accounting for only approximately 12% of total immunoglobulin mass, collectively IgG3 and IgM account for approximately 80% of the total neutralization.
View Article and Find Full Text PDFDespite the burgeoning field of coronavirus disease-19 (COVID-19) research, the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibodies remains unclear. This study validated two high-throughput immunological methods for use as surrogate live virus neutralisation assays and employed them to examine the half-life of SARS-CoV-2 neutralising antibodies in convalescent plasma donations made by 42 repeat donors between April and September 2020. SARS-CoV-2 neutralising antibody titres decreased over time but typically remained above the methods' diagnostic cut-offs.
View Article and Find Full Text PDFSerious mandibular diseases such as tumor or osteonecrosis often require segmental or marginal mandibulectomy, the latter with improved outcome thanks to preserved mandibular continuity. Nevertheless, gradual osteolytic and/or osteosclerotic skeletal changes frequently indicate repetitive resections. Based on the fundamental adaptivity of bone to mechanical loads, the question arose whether resection-related anatomical alterations trigger relevant pathological skeletal adaptations.
View Article and Find Full Text PDFIncreasing evidence suggests that both attachment representations and autobiographical memories are moderately stable over time. Evidence examining the stability of attachment-related memories is scarce, although these memories of early caregiving are thought to underpin attachment representations. Connecting research on stability of autobiographical memories with research on attachment representation, the present study investigated the stability of attachment-related autobiographical memories, which were provided by 151 emerging adults in repeated Adult Attachment Interviews conducted seven years apart.
View Article and Find Full Text PDF