Antigen expression determines adenoviral vaccine potency independent of IFN and STING signaling

Recombinant adenoviral vectors (rAds) are lead vaccine candidates for protection against a variety of pathogens, including Ebola, HIV, tuberculosis, and malaria, due to their ability to potently induce T cell immunity in humans. However, the ability to induce protective cellular immunity varies among rAds. Here, we assessed the mechanisms that control the potency of CD8 T cell responses in murine models following vaccination with human-, chimpanzee-, and simian-derived rAds encoding SIV-Gag antigen (Ag). After rAd vaccination, we quantified Ag expression and performed expression profiling of innate immune response genes in the draining lymph node. Human-derived rAd5 and chimpanzee-derived chAd3 were the most potent rAds and induced high and persistent Ag expression with low innate gene activation, while less potent rAds induced less Ag expression and robustly induced innate immunity genes that were primarily associated with IFN signaling. Abrogation of type I IFN or stimulator of IFN genes (STING) signaling increased Ag expression and accelerated CD8 T cell response kinetics but did not alter memory responses or protection. These findings reveal that the magnitude of rAd-induced memory CD8 T cell immune responses correlates with Ag expression but is independent of IFN and STING and provide criteria for optimizing protective CD8 T cell immunity with rAd vaccines.     

Contribution of abdominal muscle strength to various activities of daily living of stroke patients with mild paralysis

[Purpose] The trunk muscles frequently become weak after stroke, thus impacting overall activities of daily living. However, activities of daily living items closely related with trunk strength remain unclear. This study aimed to clarify the influence of trunk muscle weakness on activities of daily living items. [Subjects] The subjects were 24 stroke patients who fulfilled the following inclusion criteria: first stroke and the absence of severe paralysis, marked cognitive function deterioration, unilateral spatial neglect or apathy. [Methods] According to abdominal strength, the 24 patients were divided into a nonweakness group and a weakness group. For the assessment, we used the stroke impairment assessment set, the Berg balance scale, a simple test for evaluating hand function, grip strength, and functional independence measure scale scores and the results were compared between the groups. [Results] The Berg balance scale score and scores for dressing, toilet use, transfer to bed, and walk items of the functional independence measure were significantly lower in the weakness group than in the nonweakness group. [Conclusion] Our results suggest that weakness of the abdominal muscles adversely impacts the balance of patients with mild stroke as well as their ability to dress, use a toilet, transfer, and walk. Trunk training, including abdominal muscle exercises, can effectively improve the performance of these activities of daily living items.Key words: Stroke, Activities of daily living, Abdominal muscles     

Quantitative analysis of β1,6GlcNAc-branched N-glycans on β4 integrin in cutaneous squamous cell carcinoma

α6β4 integrin plays pivotal roles in cancer progression in several types of cancers. Our previous study using N-glycan-manipulated cell lines demonstrated that defects in N-glycans or decreased β1,6GlcNAc-branched N-glycans on β4 integrin suppress β4 integrin-mediated cancer cell adhesion, migration, invasion, and tumorigenesis. Furthermore, immunohistochemical analysis has shown that colocalization of β1,6GlcNAc-branched N-glycans with β4 integrin was observed in cutaneous squamous cell carcinoma (SCC) tissue. However, until now there has been no direct evidence that β1,6GlcNAc-branched N-glycans are upregulated on β4 integrin in cutaneous SCC. In the present study, we performed an ELISA analysis of β1,6GlcNAc-branched N-glycans on β4 integrins as well as β4 integrins in cell lysates from human normal skin and cutaneous SCC tissues. The SCC samples showed a 4.9- to 7.4-fold increase in the ratio of β1,6GlcNAc-branched N-glycans to β4 integrin compared with normal skin samples. These findings suggest that the addition of β1,6GlcNAc-branched N-glycans onto β4 integrin was markedly elevated in cutaneous SCC tissue compared to normal skin tissue. The value of β1,6GlcNAc-branched N-glycans on β4 integrin may be useful as a diagnostic marker associated with cutaneous SCC tumor progression.     

Disseminated Cunninghamella bertholletiae infection with septic pulmonary embolism after allogeneic bone marrow transplantation

Mucormycosis in immunocompromised patients is often reported. We report a patient who developed non‐thrombotic pulmonary embolism due to Cunninghamella bertholletiae after allogeneic stem cell transplantation.