Targeted Lipidomics To Measure Phospholipids and Sphingomyelins in Plasma: A Pilot Study To Understand the Impact of Race/Ethnicity in Alzheimer's Disease.

The number of people suffering from Alzheimer's disease (AD) is increasing rapidly every year. One aspect of AD that is often overlooked is the disproportionate incidence of AD among African American/Black populations. With the recent development of novel assays for lipidomics analysis in recent times, there has been a drastic increase in the number of studies focusing on changes of lipids in AD. However, very few of these studies have focused on or even included samples from African American/Black individuals samples. In this study, we aimed to determine if the lipidome in AD is universal across non-Hispanic White and African American/Black individuals. To accomplish this, a targeted mass spectrometry lipidomics analysis was performed on plasma samples (N = 113) obtained from cognitively normal (CN, N = 54) and AD (N = 59) individuals from African American/Black (N = 56) and non-Hispanic White (N = 57) backgrounds. Five lipids (PS 18:0_18:0, PS 18:0_20:0, PC 16:0_22:6, PC 18:0_22:6, and PS 18:1_22:6) were altered between AD and CN sample groups (p value < 0.05). Upon racial stratification, there were notable differences in lipids that were unique to African American/Black or non-Hispanic White individuals. PS 20:0_20:1 was reduced in AD in samples from non-Hispanic White but not African American/Black adults. We also tested whether race/ethnicity significantly modified the association between lipids and AD status by including a race × diagnosis interaction term in a linear regression model. PS 20:0_20:1 showed a significant interaction (p = 0.004). The discovery of lipid changes in AD in this study suggests that identifying relevant lipid biomarkers for diagnosis will require diversity in sample cohorts.

Solvent Composition Can Have a Measurable Influence on the Ion Mobility-Derived Collision Cross Section of Small Molecules.

Ion mobility (IM) is an important analytical technique for increasing identification coverage of metabolites in untargeted studies, especially when integrated into traditional liquid chromatography-mass spectrometry workflows. While there has been extensive work surrounding best practices to obtain and standardize collision cross section (CCS) measurements necessary for comparing across different IM techniques and laboratories, there has been little investigation into experimental factors beyond the mobility separation region that could potentially influence CCS measurements. The first-principles derived CCS of 15 chemical standards were evaluated across 27 aqueous:organic solvent compositions using a high-precision drift tube instrument. A small but measurable dependency of the CCS on the solvent composition was observed, with the larger analytes from this study (m/z > 400) exhibiting a characteristic increase in CCS at the intermediate (40-60%) solvent compositions. Parallels to the behavior of solvent viscosity and protonation site tautomers (protomers) were noted, although the origin of these solvent-dependent CCS trends is as yet unclear. Taken together, these findings document a solvent dependency on CCS, which, while minor (<0.5%), identifies an important need for reporting the solvent system when utilizing CCS in comparative ion mobility studies.

Coagulase-Negative Staphylococcal Strain Prevents Staphylococcus aureus Colonization and Skin Infection by Blocking Quorum Sensing.

Coagulase-negative staphylococci (CoNS) and Staphylococcus aureus are part of the natural flora of humans and other mammals. We found that spent media from the CoNS species Staphylococcus caprae can inhibit agr-mediated quorum sensing by all classes of S. aureus. A biochemical assessment of the inhibitory activity suggested that the S. caprae autoinducing peptide (AIP) was responsible, and mass spectrometric analysis identified the S. caprae AIP as an eight-residue peptide (YSTCSYYF). Using a murine model of intradermal MRSA infection, the therapeutic efficacy of synthetic S. caprae AIP was evident by a dramatic reduction in both dermonecrotic injury and cutaneous bacterial burden relative to controls. Competition experiments between S. caprae and MRSA demonstrated a significant reduction in MRSA burden using murine models of both skin colonization and intradermal infection. Our findings indicate that important interactions occur between commensals that can impact disease outcomes and potentially shape the composition of the natural flora.