Safe but stifled: Assessing the impact of space and place on risk and adaptive response among shelter residents during the COVID-19 pandemic.

The COVID-19 pandemic dramatically changed society's interactions with spaces and places. This is especially true for shelter residents who had greater perceived risks of contracting the virus, largely because of communal living. To understand how shelter residents conceptualized their risk and resilience, we implemented a PhotoVoice project with five artists living in a Miami, FL shelter. Although these residents sometimes perceived the shelter as safe, it was often to the detriment of self-determination. Despite profound restrictions, residents still found ways to adapt to their environment. This article helps shelters and scholars alike better understand the ways that residents conceptualize their lived environments and highlights opportunities to empower residents despite challenging circumstances.

Optimizing the Targeting of Mouse Parvovirus 1 to Murine Melanoma Selects for Recombinant Genomes and Novel Mutations in the Viral Capsid Gene.

Combining virus-enhanced immunogenicity with direct delivery of immunomodulatory molecules would represent a novel treatment modality for melanoma, and would require development of new viral vectors capable of targeting melanoma cells preferentially. Here we explore the use of rodent protoparvoviruses targeting cells of the murine melanoma model B16F10. An uncloned stock of mouse parvovirus 1 (MPV1) showed some efficacy, which was substantially enhanced following serial passage in the target cell. Molecular cloning of the genes of both starter and selected virus pools revealed considerable sequence diversity. Chimera analysis mapped the majority of the improved infectivity to the product of the major coat protein gene, VP2, in which linked blocks of amino acid changes and one or other of two apparently spontaneous mutations were selected. Intragenic chimeras showed that these represented separable components, both contributing to enhanced infection. Comparison of biochemical parameters of infection by clonal viruses indicated that the enhancement due to changes in VP2 operates after the virus has bound to the cell surface and penetrated into the cell. Construction of an in silico homology model for MPV1 allowed placement of these changes within the capsid shell, and revealed aspects of the capsid involved in infection initiation that had not been previously recognized.

Exploring novel strategies for AIDS protozoal pathogens: α-helix mimetics targeting a key allosteric protein-protein interaction in C. hominis TS-DHFR.

The bifunctional enzyme thymidylate synthase-dihydrofolate reductase (TS-DHFR) from the protozoal parasite Cryptosporidium hominis is a potential molecular target for the design of antiparasitic therapies for AIDS-related opportunistic infections. The enzyme exists as a homodimer with each monomer containing a unique swap domain known as a "crossover helix" that binds in a cleft on the adjacent DHFR active site. This crossover helix is absent in species containing monofunctional forms of DHFR such as human. An in-depth understanding of protein-protein interactions between the crossover helix and adjacent DHFR active site that might modulate enzyme integrity or function would allow for insights into rational design of species-specific allosteric inhibitors. Mutational analysis coupled with structural studies and biophysical and kinetic characterization of crossover helix mutants identifies this domain as essential for full enzyme stability and catalytic activity, and pinpoints these effects to distinct faces of the crossover helix important in protein-protein interactions. Moreover, targeting this helical protein interaction with α-helix mimetics of the crossover helix leads to selective inhibition and destabilization of the C. hominis TS-DHFR enzyme, thus validating this region as a new avenue to explore for species-specific inhibitor design.