Highly Selective Aptamer-Molecularly Imprinted Polymer Hybrids for Recognition of SARS-CoV-2 Spike Protein Variants.

Virus recognition has been driven to the forefront of molecular recognition research due to the COVID-19 pandemic. Development of highly sensitive recognition elements, both natural and synthetic is critical to facing such a global issue. However, as viruses mutate, it is possible for their recognition to wane through changes in the target substrate, which can lead to detection avoidance and increased false negatives. Likewise, the ability to detect specific variants is of great interest for clinical analysis of all viruses. Here, a hybrid aptamer-molecularly imprinted polymer (aptaMIP), that maintains selective recognition for the spike protein template across various mutations, while improving performance over individual aptamer or MIP components (which themselves demonstrate excellent performance). The aptaMIP exhibits an equilibrium dissociation constant of 1.61 nM toward its template which matches or exceeds published examples of imprinting of the spike protein. The work here demonstrates that "fixing" the aptamer within a polymeric scaffold increases its capability to selectivity recognize its original target and points toward a methodology that will allow variant selective molecular recognition with exceptional affinity.

Type 2 Diabetes and Chronic Conditions Disparities in Medicare Beneficiaries in the State of Michigan.

BACKGROUND: This study aimed to describe the prevalence of type 2 diabetes and combinations of multiple chronic conditions (MCCs) that are leading causes of death (LCD) and confirm that disparities exist between groups based on race and sex. MATERIALS AND METHODS: We conducted a retrospective cohort study using 2012 Medicare claims data from beneficiaries with type 2 diabetes over the age of 65 in the state of Michigan. RESULTS: Female beneficiaries have type 2 diabetes and 1 or more MCCs that are LCD more often than males. Most type 2 diabetes patients have diabetes alone without MCCs, while a large proportion have at least 1 additional chronic condition that is a LCD. One in 3 patients have 3 or more chronic conditions. The most prevalent type 2 diabetes coexisting MCCs are congestive heart failure (CHF), chronic obstructive pulmonary disease and chronic kidney disease. Asian/Pacific Islanders have the highest prevalence of type 2 diabetes without MCCs, and the highest prevalence of diabetes plus CHF. While fewer black beneficiaries have diabetes alone or 1 additional MCC, the prevalence of 3 or more MCCs in blacks generally exceeds the prevalence in other races. In beneficiaries with newly diagnosed type 2 diabetes, chronic obstructive pulmonary disease and CHF are the first new chronic conditions to be diagnosed after an initial type 2 diabetes diagnosis. CONCLUSIONS: Race and sex disparities occur in the prevalence of type 2 diabetes and MCCs that are LCD in Medicare beneficiaries in the state of Michigan.

UNG protects B cells from AID-induced telomere loss.

Activation-induced deaminase (AID) initiates antibody gene diversification by creating G:U mismatches in the immunoglobulin loci. However, AID also deaminates nonimmunoglobulin genes, and failure to faithfully repair these off-target lesions can cause B cell lymphoma. In this study, we identify a mechanism by which processing of G:U produced by AID at the telomeres can eliminate B cells at risk of genomic instability. We show that telomeres are off-target substrates of AID and that B cell proliferation depends on protective repair by uracil-DNA glycosylase (UNG). In contrast, in the absence of UNG activity, deleterious processing by mismatch repair leads to telomere loss and defective cell proliferation. Indeed, we show that UNG deficiency reduces B cell clonal expansion in the germinal center in mice and blocks the proliferation of tumor B cells expressing AID. We propose that AID-induced damage at telomeres acts as a fail-safe mechanism to limit the tumor promoting activity of AID when it overwhelms uracil excision repair.