In Silico Investigations of Calcium Phosphate Mineralization in Extracellular Vesicles

Calcification in bone, cartilage, and cardiovascular tissues involves the release of specialized extracellular vesicles (EVs) that promote mineral nucleation. The small size of the EVs, however, makes molecular level studies difficult, and consequently uncertainty exists on the role and function of these structures in directing mineralization. The lack of mechanistic understanding associated with the initiators of ectopic mineral deposition has severely hindered the development of potential therapeutic options. Here, we used multiscale molecular dynamics simulations to investigate the calcification within the EVs. Results show that Ca2+–HPO42– and phosphatidylserine complexes facilitate the early nucleation. Use of coarse-grained simulations allows investigations of Ca2+–PO43– nucleation and crystallization in the EVs. Systematic variation in the ion-to-water ratio shows that the crystallization and growth strongly depend on the enrichment of the ions and dehydration inside the EVs. Our investigations provide insights into the role of EVs on calcium phosphate mineral nucleation and growth in both physiological and pathological mineralization

In Silico Investigations of Calcium Phosphate Mineralization in Extracellular Vesicles

Calcification in bone, cartilage, and cardiovascular tissues involves the release of specialized extracellular vesicles (EVs) that promote mineral nucleation. The small size of the EVs, however, makes molecular level studies difficult, and consequently uncertainty exists on the role and function of these structures in directing mineralization. The lack of mechanistic understanding associated with the initiators of ectopic mineral deposition has severely hindered the development of potential therapeutic options. Here, we used multiscale molecular dynamics simulations to investigate the calcification within the EVs. Results show that Ca²⁺–HPO₄^2– and phosphatidylserine complexes facilitate the early nucleation. Use of coarse-grained simulations allows investigations of Ca²⁺–PO₄^3– nucleation and crystallization in the EVs. Systematic variation in the ion-to-water ratio shows that the crystallization and growth strongly depend on the enrichment of the ions and dehydration inside the EVs. Our investigations provide insights into the role of EVs on calcium phosphate mineral nucleation and growth in both physiological and pathological mineralization

In Silico Investigations of Calcium Phosphate Mineralization in Extracellular Vesicles

Calcification in bone, cartilage, and cardiovascular tissues involves the release of specialized extracellular vesicles (EVs) that promote mineral nucleation. The small size of the EVs, however, makes molecular level studies difficult, and consequently uncertainty exists on the role and function of these structures in directing mineralization. The lack of mechanistic understanding associated with the initiators of ectopic mineral deposition has severely hindered the development of potential therapeutic options. Here, we used multiscale molecular dynamics simulations to investigate the calcification within the EVs. Results show that Ca2+–HPO42– and phosphatidylserine complexes facilitate the early nucleation. Use of coarse-grained simulations allows investigations of Ca2+–PO43– nucleation and crystallization in the EVs. Systematic variation in the ion-to-water ratio shows that the crystallization and growth strongly depend on the enrichment of the ions and dehydration inside the EVs. Our investigations provide insights into the role of EVs on calcium phosphate mineral nucleation and growth in both physiological and pathological mineralization

Lipid II Binding and Transmembrane Properties of Various Antimicrobial Lanthipeptides

There has been an alarming rise in antibacterial resistant infections in recent years due to the widespread use of antibiotics, and there is a dire need for the development of new antibiotics utilizing novel modes of action. Lantibiotics are promising candidates to engage in the fight against resistant strains of bacteria due to their unique modes of action, including interference with cell wall synthesis by binding to lipid II and creating pores in bacterial membranes. In this study, we use atomic-scale molecular dynamics computational studies to compare both the lipid II binding ability and the membrane interactions of five lanthipeptides that are commonly used in antimicrobial research: nisin, Mutacin 1140 (MU1140), gallidermin, NVB302, and NAI107. Among the five peptides investigated, nisin is found to be the most efficient at forming water channels through a membrane, whereas gallidermin and MU1140 are found to be better at binding the lipid II molecules. Nisin’s effectiveness in facilitating water transport across the membrane is due to the creation of several different water trajectories along with no significant water delay points along the paths. The shorter peptide deoxyactagardine B (NVB302) was found to not form a water channel. These detailed observations provide insights into the dual mechanisms of the action of lantibiotic peptides and can facilitate the design and development of novel lanthipeptides by strategic placement of different residues

Additional file 2 of Medulloblastoma cerebrospinal fluid reveals metabolites and lipids indicative of hypoxia and cancer-specific RNAs

Additional file 2.: Lipid profile of MB and normal CSF samples

Additional file 4 of Medulloblastoma cerebrospinal fluid reveals metabolites and lipids indicative of hypoxia and cancer-specific RNAs

Additional file 4.: Supplementary tables and figures

Additional file 3 of Medulloblastoma cerebrospinal fluid reveals metabolites and lipids indicative of hypoxia and cancer-specific RNAs

Additional file 3: The list of qPCR primers

Additional file 1 of Medulloblastoma cerebrospinal fluid reveals metabolites and lipids indicative of hypoxia and cancer-specific RNAs

Additional file 1: The genomic coordination of MB upregulated circRNAs