miR-378-3p Knockdown Recapitulates Many of the Features of Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are clonal neoplasms of the hematopoietic stem cell that result in aberrant differentiation of hematopoietic lineages caused by a wide range of underlying genetic, epigenetic, and other causes. Despite the myriad origins, a recognizable MDS phenotype has been associated with miRNA aberrant expression. A model of aberrant myeloid maturation that mimics MDS was generated using a stable knockdown of miR-378-3p. This model exhibited a transcriptional profile indicating aberrant maturation and function, immunophenotypic and morphologic dysplasia, and aberrant growth that characterizes MDS. Moreover, aberrant signal transduction in response to stimulation specific to the stage of myeloid maturation as indicated by CyTOF mass cytometry was similar to that found in samples from patients with MDS. The aberrant signaling, immunophenotypic changes, cellular growth, and colony formation ability seen in this myeloid model could be reversed with azacytidine, albeit without significant improvement of neutrophil function.

Whistle repertoire and structure reflect ecotype distinction of pantropical spotted dolphins in the Eastern Tropical Pacific.

The pantropical spotted dolphin in the Eastern Tropical Pacific (ETP) is found in two genetically and phenotypically diverged ecotypes, coastal and offshore. These habitats have distinct acoustic characteristics, which can lead to the evolution of distinct acoustic communication. Whistles are sounds widely used by dolphins to mediate species and individual recognition and social interactions. Here, we study the whistle acoustic structure and repertoire diversity of offshore and coastal pantropical spotted dolphins. Our results show that there is significantly more within- and across-group variation in whistle fundamental frequency between ecotypes than between offshore groups and between coastal groups. A Random Forest classification analysis performed with an accuracy of 83.99% and identified duration, peak and minimum frequency as the most informative variables for distinguishing between ecotypes. Overall, coastal spotted dolphins produced significantly shorter whistles that were significantly lower in frequency (peak, minimum and maximum, and start and end) than offshore dolphins. Ecotypes produced whistle repertoires that were similar in diversity, but different in contour composition, with the coastal ecotype producing more upsweep whistles than offshore dolphins. The results of this study suggest that acoustic adaptations to coastal and offshore environments could be important contributors to intraspecific variation of dolphin whistle repertoires.