Phenotypic and transcriptomic characterization of canine myeloid-derived suppressor cells

Myeloid-derived suppressor cells (MDSCs) are key players in immune evasion, tumor progression and metastasis. MDSCs accumulate under various pathological states and fall into two functionally and phenotypically distinct subsets that have been identified in humans and mice: polymorphonuclear (PMN)-MDSCs and monocytic (M)-MDSCs. As dogs are an excellent model for human tumor development and progression, we set out to identify PMN-MDSCs and M-MDSCs in clinical canine oncology patients. Canine hypodense MHC class II-CD5-CD21-CD11b+ cells can be subdivided into polymorphonuclear (CADO48A+CD14-) and monocytic (CADO48A-CD14+) MDSC subsets. The transcriptomic signatures of PMN-MDSCs and M-MDSCs are distinct, and moreover reveal a statistically significant similarity between canine and previously published human PMN-MDSC gene expression patterns. As in humans, peripheral blood frequencies of canine PMN-MDSCs and M-MDSCs are significantly higher in dogs with cancer compared to healthy control dogs (PMN-MDSCs: p < 0.001; M-MDSCs: p < 0.01). By leveraging the power of evolution, we also identified additional conserved genes in PMN-MDSCs of multiple species that may play a role in MDSC function. Our findings therefore validate the dog as a model for studying MDSCs in the context of cancer

Headphones or Speakers? An Exploratory Study of Their Effects on Spontaneous Body Movement to Rhythmic Music

Previous studies have shown that music may lead to spontaneous body movement, even when people try to stand still. But are spontaneous movement responses to music similar if the stimuli are presented using headphones or speakers? This article presents results from an exploratory study in which 35 participants listened to rhythmic stimuli while standing in a neutral position. The six different stimuli were 45 s each and ranged from a simple pulse to excerpts from electronic dance music (EDM). Each participant listened to all the stimuli using both headphones and speakers. An optical motion capture system was used to calculate their quantity of motion, and a set of questionnaires collected data about music preferences, listening habits, and the experimental sessions. The results show that the participants on average moved more when listening through headphones. The headphones condition was also reported as being more tiresome by the participants. Correlations between participants’ demographics, listening habits, and self-reported body motion were observed in both listening conditions. We conclude that the playback method impacts the level of body motion observed when people are listening to music. This should be taken into account when designing embodied music cognition studies

Targeted inversion and reversion of the blood coagulation factor 8 gene in human iPS cells using TALENs

Hemophilia A, one of the most common genetic bleeding disorders, is caused by various mutations in the blood coagulation factor VIII (F8) gene. Among the genotypes that result in hemophilia A, two different types of chromosomal inversions that involve a portion of the F8 gene are most frequent, accounting for almost half of all severe hemophilia A cases. In this study, we used a transcription activator-like effector nuclease (TALEN) pair to invert a 140-kbp chromosomal segment that spans the portion of the F8 gene in human induced pluripotent stem cells (iPSCs) to create a hemophilia A model cell line. In addition, we reverted the inverted segment back to its normal orientation in the hemophilia model iPSCs using the same TALEN pair. Importantly, we detected the F8 mRNA in cells derived from the reverted iPSCs lines, but not in those derived from the clones with the inverted segment. Thus, we showed that TALENs can be used both for creating disease models associated with chromosomal rearrangements in iPSCs and for correcting genetic defects caused by chromosomal inversions. This strategy provides an iPSC-based novel therapeutic option for the treatment of hemophilia A and other genetic diseases caused by chromosomal inversions