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Molecular profiling to characterize the effects of environmental exposures is important from the human health and performance as well as the occupational medicine perspective in space exploration. We have developed a novel exosome-based platform that allows profiling of biological processes in the body from a variety of body fluids. The technology is suitable for diagnostic applications as well as studying the pathophysiology of the Space Associated Neuro-Ocular Syndrome in astronauts and monitoring patients with chronically impaired cerebrospinal fluid drainage or elevated intracranial pressure. In this proof-of-concept, we demonstrate that: (a) exosomes from different biofluids contain a specific population of RNA transcripts; (b) urine collection hardware aboard the ISS is compatible with exosome gene expression technology; (c) cDNA libraries from exosomal RNA can be stored in dry form and at room temperature, representing an interesting option for the creation of longitudinal molecular catalogs that can be stored as a repository for retrospective analysis.

Proper functioning of a multi-cellular organism requires well-coordinated intra- and inter-cellular communication among its cells. Mammalian cells have well established modes of inter-cellular communication, which include cell-cell contact via gap junctions, synaptic transmission, and paracrine and endocrine communication through secreted molecules. Extracellular vesicles (EV) serve as a vehicle for transfer of biomolecules between cells. This study aims to establish if EV mediated transfer of encapsulated RNA represents a novel mode of inter-cellular communication. At the outset, we developed and validated a novel and efficient approach of isolation of EVs. Comprehensive characterization of EV RNA derived from several cell types revealed the diversity of small RNA cargo, and suggested non-random and cell type specific sorting of RNA molecules into EVs. Further analysis revealed gene family specific fragmentation patterns of non-coding RNAs detected within EVs. Next, we explored the temporal dynamics, spatial localization, and integrity of EV RNA upon transfer into another cell. We further demonstrated cell state dependent dynamicity of EV RNA cargo, as well as cell type specific molecular responses, when different cells were exposed to the same EV stimuli, underscoring the context dependent interpretation of the complex EV messages. Finally, as a specific example of EV RNA functionality, we reported the possible involvement of a 31 nucleotide processed fragment of RNY5, one of the most abundant and enriched RNA components of cancer cell derived EVs, in selectively inducing cell death in primary cells of diverse developmental origins and identified an eight nucleotide motif crucial for its functionality. The transfer of processed, functional RNY5 fragments through EVs hints at the under-appreciated role of EV RNA in cancer cell microenvironment. Thus, our study supports the hypothesis that EV mediated transfer of RNA represents a novel mode of inter-cellular communication, through which cells may shape the transcriptional landscape of another cell in their microenvironment.

We obtain BPS configurations of the BLG theory and its variant including mass terms for scalars and fermions in addition to a background field with different world-volume and R-symmetries. Three cases are considered, with world-volume symmetries SO(1,1) and SO(2) and preserving different amounts of supersymmetry. In the former case we obtain a singular configuration preserving N=(3,3) supersymmetry and an one-quarter BPS configuration corresponding to intersecting M2-M5-M5-branes. In the latter instance the BPS equations are reduced to those in the self-dual Chern-Simons theory with two complex scalars. In want of an exact solution, we find a topological vortex solution numerically in this case. Other solutions are given by combinations of domain walls.

We study the moduli space of scalars in the BLG theory with and without a constant background four-form field. The classical vacuum moduli space is sixteen-dimensional in the absence of the four-form field. In its presence, however, the moduli space of BPS configurations may be reduced in dimension. We exemplify this with a BPS configuration having \\(SO(1,2)\\) world-volume symmetry and \\(SO(4) \\times SO(4)\\) R-symmetry in the presence of a four-form field, by constructing an explicit solution.