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It is becoming increasingly apparent that small molecules can self-assemble into a wide-range of nano-entities in solution that have intriguing properties. The recently introduced NMR aggregation assay is playing an important role in revealing these nano-entities. Here, we employ the NMR aggregation assay to expose the self-aggregation tendencies of dyes in solution. This dilution-based assay demonstrates that some dyes can exist as single-molecule entities whereas others can adopt aggregates of distinct sizes. Interestingly, dyes with highly related chemical structures can adopt largely different sized aggregates - demonstrating the existence of structure-nanoentity relationships (SNR) – which suggests that they can assume and/or be designed to have distinct properties. One property was evaluated where the drug Quetiapine (Seroquel) was added to the dye Congo red which resulted in the absorption of the drug into the dye nano-entity. This showed a direct drug-dye interaction, and it demonstrated that dye aggregates can have influences on drug solution behaviors. The NMR method described in this study provides a practical and valuable tool to monitor dye aggregates and to better understand their associated properties (e.g. toxicity, off-target activity) and potential utility (e.g. drug encapsulation, drug delivery systems). [ABSTRACT FROM AUTHOR]

Phylogenetics has been advanced as a structural framework to infer evolving trends in the regional spread of HIV-1 and guide public health interventions. In Quebec, molecular network analyses tracked HIV transmission dynamics from 2002–2020 using MEGA10-Neighbour-joining, HIV-TRACE, and MicrobeTrace methodologies. Phylogenetics revealed three patterns of viral spread among Men having Sex with Men (MSM, n = 5024) and heterosexuals (HET, n = 1345) harbouring subtype B epidemics as well as B and non-B subtype epidemics (n = 1848) introduced through migration. Notably, half of new subtype B infections amongst MSM and HET segregating as solitary transmissions or small cluster networks (2–5 members) declined by 70% from 2006–2020, concomitant to advances in treatment-as-prevention. Nonetheless, subtype B epidemic control amongst MSM was thwarted by the ongoing genesis and expansion of super-spreader large cluster variants leading to micro-epidemics, averaging 49 members/cluster at the end of 2020. The growth of large clusters was related to forward transmission cascades of untreated early-stage infections, younger at-risk populations, more transmissible/replicative-competent strains, and changing demographics. Subtype B and non-B subtype infections introduced through recent migration now surpass the domestic epidemic amongst MSM. Phylodynamics can assist in predicting and responding to active, recurrent, and newly emergent large cluster networks, as well as the cryptic spread of HIV introduced through migration. [ABSTRACT FROM AUTHOR]