The masses of particles in a bovine milk extracellular vesicle (EV) preparation enriched for exosomes were directly determined for the first time by charge detection mass spectrometry (CDMS). In CDMS, both the mass-to-charge ratio (m/z) and z are determined simultaneously for individual particles, enabling mass determinations for particles that are far beyond the mass limit (∼1.0 MDa) of conventional mass spectrometry (MS). Particle masses and charges span a wide range from m ∼ 2 to ∼90 MDa and z ∼ 50 to ∼1300 e (elementary charges) and are highly dependent upon the conditions used to extract and isolate the EVs. EV particles span a continuum of masses, reflecting the highly heterogeneous nature of these samples. However, evidence for unique populations of particles is obtained from correlation of the charges and masses. An analysis that uses a two-dimensional Gaussian model, provides evidence for six families of particles, four of which having masses in the range expected for exosomes. Complementary proteomics measurements and electron microscopy (EM) imaging are used to further characterize the EVs and confirm that these samples have been enriched in exosomes. The ability to characterize such extremely heterogeneous mixtures of large particles with rapid, sensitive, and high-resolution MS techniques is critical to ongoing analytical efforts to separate and purify exosomes and exosome subpopulations. Direct measurement of each particle’s mass and charge is a new means of characterizing the physical and chemical properties of exosomes and other EVs.

Approximately 50-70% of the variation in cannabis use and use disorders can be attributed to heritable factors. For cannabis use, the remaining variance can be parsed in to familial and person-specific environmental factors while for use disorders, only the latter contribute. While numerous candidate gene studies have identified the role of common variation influencing liability to cannabis involvement, replication has been elusive. To date, no genomewide association study has been sufficiently powered to identify significant loci. Despite this, studies adopting polygenic techniques and integrating genetic variation with neural phenotypes and measures of environmental risk, such as childhood adversity, are providing promising new leads. It is likely that the small effect sizes associated with variants related to cannabis involvement will only be robustly identified in substantially larger samples. Results of such large-scale efforts will provide valuable single variant targets for translational research in neurogenetic, pharmacogenetic and non-human animal models as well as polygenic risk indices that can be used to explore a host of other genetic hypotheses related to cannabis use and misuse.

The frequent comorbidity of psychiatric and physical health conditions may be partially attributable to early life stress-related changes in inflammatory signaling and behavior (e.g., borderline personality pathology, health behaviors) that reciprocally maintain and enhance their effects on overall health. Using data from older adults (N=1,630) who participated in the ongoing longitudinal St Louis Personality and Aging Network (SPAN) study, we examined associations between childhood physical abuse, borderline personality pathology, inflammation markers (i.e., interleukin-6 [IL-6], C-reactive protein [CRP]), health behaviors, and physical health. Morning fasting serum IL-6 and CRP were assayed from a subset of participants (n=791). Borderline pathology factor scores were computed using interviews as well as self- and informant-reports across the course of the study. Physical health, health behaviors, and additional covariates (e.g., medication use) were also assessed. IL-6 was associated with higher BPD symptomatology, greater exposure to childhood physical abuse, worse physical health, and lower preventative health behaviors (all p values < 10-11). Similar findings for CRP emerged, though the association with childhood physical abuse was not robust to covariate inclusion. An integrated model suggests an indirect pathway between exposure to childhood physical abuse, greater BPD symptomology, reduced preventative health behaviors, elevated IL-6, and worse health outcomes (-0.07, p < .001).These findings suggest that physical abuse during childhood may be predictive of later poor physical health through behavioral (i.e., borderline pathology, reduced preventative health behaviors), and biological (i.e., inflammatory) pathways.

No abstract