Quantitative biology of single neurons

The building blocks of complex biological systems are single cells. Fundamental insights gained from single-cell analysis promise to provide the framework for understanding normal biological systems development as well as the limits on systems/cellular ability to respond to disease. The interplay of cells to create functional systems is not well understood. Until recently, the study of single cells has concentrated primarily on morphological and physiological characterization. With the application of new highly sensitive molecular and genomic technologies, the quantitative biochemistry of single cells is now accessible.     

Dynamic Assessment of Functional Lipidomic Analysis in Human Urine

The development of enabling mass spectrometry platforms for the quantification of diverse lipid species in human urine is of paramount importance for understanding metabolic homeostasis in normal and pathophysiological conditions. Urine represents a non‐invasive biofluid that can capture distinct differences in an individual's physiological status. However, currently there is a lack of quantitative workflows to engage in high throughput lipidomic analysis. This study describes the development of a MS/MS^ALL shotgun lipidomic workflow and a micro liquid chromatography–high resolution tandem mass spectrometry (LC–MS/MS) workflow for urine structural and mediator lipid analysis, respectively. This workflow was deployed to understand biofluid sample handling and collection, extraction efficiency, and natural human variation over time. Utilization of 0.5 mL of urine for structural lipidomic analysis resulted in reproducible quantification of more than 600 lipid molecular species from over 20 lipid classes. Analysis of 1 mL of urine routinely quantified in excess of 55 mediator lipid metabolites comprised of octadecanoids, eicosanoids, and docosanoids generated by lipoxygenase, cyclooxygenase, and cytochrome P450 activities. In summary, the high‐throughput functional lipidomics workflow described in this study demonstrates an impressive robustness and reproducibility that can be utilized for population health and precision medicine applications.     

Molecular Interactions of Tannic Acid with Proteins Associated with SARS-CoV-2 Infectivity

The overall impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on our society is unprecedented. The identification of small natural ligands that could prevent the entry and/or replication of the coronavirus remains a pertinent approach to fight the coronavirus disease (COVID-19) pandemic. Previously, we showed that the phenolic compounds corilagin and 1,3,6-tri-O-galloyl-β-D-glucose (TGG) inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 target receptor on the cell membrane of the host organism. Building on these promising results, we now assess the effects of these phenolic ligands on two other crucial targets involved in SARS-CoV-2 cell entry and replication, respectively: transmembrane protease serine 2 (TMPRSS2) and 3-chymotrypsin like protease (3CLpro) inhibitors. Since corilagin, TGG, and tannic acid (TA) share many physicochemical and structural properties, we investigate the binding of TA to these targets. In this work, a combination of experimental methods (biochemical inhibition assays, surface plasmon resonance, and quartz crystal microbalance with dissipation monitoring) confirms the potential role of TA in the prevention of SARS-CoV-2 infectivity through the inhibition of extracellular RBD/ACE2 interactions and TMPRSS2 and 3CLpro activity. Moreover, molecular docking prediction followed by dynamic simulation and molecular mechanics Poisson–Boltzmann surface area (MMPBSA) free energy calculation also shows that TA binds to RBD, TMPRSS2, and 3CLpro with higher affinities than TGG and corilagin. Overall, these results suggest that naturally occurring TA is a promising candidate to prevent and inhibit the infectivity of SARS-CoV-2.     

Absorption of silicon from artesian aquifer water and its impact on bone health in postmenopausal women: a 12 week pilot study

Background  

Decreased bone mineral density and osteoporosis in postmenopausal women represents a growing source of physical limitations and financial concerns in our aging population. While appropriate medical treatments such as bisphosphonate drugs and hormone replacement therapy exist, they are associated with serious side effects such as osteonecrosis of the jaw or increased cardiovascular risk. In addition to calcium and vitamin D supplementation, previous studies have demonstrated a beneficial effect of dietary silicon on bone health. This study evaluated the absorption of silicon from bottled artesian aquifer water and its effect on markers of bone metabolism.