Characterizing the supra- and subsolidus processes that generated the Current PGE-Cu-Ni deposit, Thunder Bay North Intrusive Complex, Canada: insights from trace elements and multiple S isotopes of sulfides.

Unlabelled: The Current deposit is hosted by serpentinized peridotite that intruded rocks of the Quetico Subprovince in the Midcontinent Rift, and is subdivided into three morphologically distinct regions - the shallow and thin Current-Bridge Zone in the northwest, the deep and thick 437-Southeast Anomaly (SEA) Zone in the southeast, and the thick Beaver-Cloud Zone in the middle. The magma parental to the Current deposit became saturated in sulfide as a result of the addition of external S from at least two sources - a deep source characterized by high ΔS (< 3‰) values, and a shallow source, potentially the Archean metasedimentary country rocks, characterized by low ΔS (< 0.3‰).

From (Tool)Bench to Bedside: The Potential of Necroptosis Inhibitors.

Necroptosis is a regulated caspase-independent form of necrotic cell death that results in an inflammatory phenotype. This process contributes profoundly to the pathophysiology of numerous neurodegenerative, cardiovascular, infectious, malignant, and inflammatory diseases. Receptor-interacting protein kinase 1 (RIPK1), RIPK3, and the mixed lineage kinase domain-like protein (MLKL) pseudokinase have been identified as the key components of necroptosis signaling and are the most promising targets for therapeutic intervention.

Development of NanoLuc-targeting protein degraders and a universal reporter system to benchmark tag-targeted degradation platforms.

Modulation of protein abundance using tag-Targeted Protein Degrader (tTPD) systems targeting FKBP12 (dTAGs) or HaloTag7 (HaloPROTACs) are powerful approaches for preclinical target validation. Interchanging tags and tag-targeting degraders is important to achieve efficient substrate degradation, yet limited degrader/tag pairs are available and side-by-side comparisons have not been performed. To expand the tTPD repertoire we developed catalytic NanoLuc-targeting PROTACs (NanoTACs) to hijack the CRL4 complex and degrade NanoLuc tagged substrates, enabling rapid luminescence-based degradation screening.

Transitioning to telegenetics in the COVID-19 era: Patient satisfaction with remote genetic counseling in adult neurology.

The COVID-19 pandemic rapidly changed genetic counseling services across the United States. At the University of Pennsylvania (UPenn), a large academic hospital in an urban setting, nearly all genetic counseling (GC) visits for adult-onset disorders within the Department of Neurology were conducted via secure videoconferencing (telegenetics) or telephone between March and December 2020. Although telemedicine services have been steadily emerging, many clinical programs, including the neurogenetics program at UPenn, had not built infrastructure or widely utilized these services prior to the pandemic.

Temporal trends and yield of clinical diagnostic genetic testing in adult neurology.

While genetics evaluation is increasingly utilized in adult neurology patients, its usage and efficacy are not well characterized. Here, we report our experience with 1461 consecutive patients evaluated in an adult neurogenetics clinic at a large academic medical center between January 2015 and March 2020. Of the 1461 patients evaluated, 1215 patients were referred for the purposes of identifying a genetic diagnosis for an undiagnosed condition, 90.