Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems

We describe the preparation, dynamic, assembly characteristics of vase-shaped basket 13− along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1H Nuclear Magnetic Resonance (NMR), 1H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer [12]6−, to be in equilibrium with monomers 1(R)3− (relaxed) and 1(S)3− (squeezed). Through simultaneous line-shape analysis of 1H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1(R)3− includes anticancer drug mitoxantrone (MTO2+) in its pocket to give stable binary complex [MTO⊂1]− (Kd=2.1 μM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well-characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep-cavity baskets

MindKind: A mixed-methods protocol for the feasibility of global digital mental health studies in young people

While an estimated 14-20% of young adults experience mental health conditions worldwide, the best strategies for prevention and management are not fully understood. The ubiquity of smartphone use among young people makes them excellent candidates for collecting data about lived experiences and their relationships to mental health. However, not much is known about the factors affecting young peoples’ willingness to share information about their mental health. OBJECTIVE: We aim to understand the data governance and engagement strategies influencing young peoples’ (aged 16-24) participation in app-based studies of mental health. We hypothesize that willingness to participate in research is influenced by involvement  in how their data is collected, shared, and used. METHODS: Here, we describe the MindKind Study, which employs mixed methods to understand the feasibility of global, smartphone-based studies of youth mental health. A pilot 12-week app-based substudy will query participants’ willingness to engage with remote mental health studies. Participants will be randomized into one of four different data governance models designed to understand their preferences, as well as the acceptability of models that allow them more or less control over how their data are accessed and used. Enrolees will receive one of two different engagement strategies. A companion qualitative study will employ a deliberative democracy approach to examine the preferences, concerns and expectations of young people, with respect to remote mental health research. We also detail our engagement with young people as co-researchers in this study. This pilot study is being conducted in India, South Africa and the United Kingdom. CONCLUSION: This study is expected to generate new insights into the feasibility of, and best practices for, remote smartphone-based studies of mental health in youth and represents an important step toward understanding which approaches could help people better manage their mental health

Gene flow and population structure in the Mexican blind cavefish complex (<it>Astyanax mexicanus</it>)

<p>Abstract</p> <p>Background</p> <p>Cave animals converge evolutionarily on a suite of troglomorphic traits, the best known of which are eyelessness and depigmentation. We studied 11 cave and 10 surface populations of <it>Astyanax mexicanus </it>in order to better understand the evolutionary origins of the cave forms, the basic genetic structuring of both cave and surface populations, and the degree to which present day migration among them affects their genetic divergence.</p> <p>Results</p> <p>To assess the genetic structure within populations and the relationships among them we genotyped individuals at 26 microsatellite loci. We found that surface populations are similar to one another, despite their relatively large geographic separation, whereas the cave populations are better differentiated. The cave populations we studied span the full range of the cave forms in three separate geographic regions and have at least five separate evolutionary origins. Cave populations had lower genetic diversity than surface populations, correlated with their smaller effective population sizes, probably the result of food and space limitations. Some of the cave populations receive migrants from the surface and exchange migrants with one another, especially when geographically close. This admixture results in significant heterozygote deficiencies at numerous loci due to Wahlund effects. Cave populations receiving migrants from the surface contain small numbers of individuals that are intermediate in both phenotype and genotype, affirming at least limited gene flow from the surface.</p> <p>Conclusions</p> <p>Cave populations of this species are derived from two different surface stocks denoted "old" and "new." The old stock colonized caves at least three times independently while the new stock colonized caves at least twice independently. Thus, the similar cave phenotypes found in these caves are the result of repeated convergences. These phenotypic convergences have occurred in spite of gene flow from surface populations suggesting either strong natural or sexual selection for alleles responsible for the cave phenotype in the cave environment.</p