Lipidic folding pathway of α-Synuclein via a toxic oligomer.

Aggregation intermediates play a pivotal role in the assembly of amyloid fibrils, which are central to the pathogenesis of neurodegenerative diseases. The structures of filamentous intermediates and mature fibrils are now efficiently determined by single-particle cryo-electron microscopy. By contrast, smaller pre-fibrillar α-Synuclein (αS) oligomers, crucial for initiating amyloidogenesis, remain largely uncharacterized.

Differences in Trends in Cancer Incidence Rates Among People with HIV during 2001-2019 By Race and Ethnicity and By Risk Group in the United States.

Background: Cancer risk among people with HIV (PWH) has declined over time as a result of antiretroviral therapy, but it is unclear whether all racial/ethnic groups and transmission risk groups have experienced equal declines.

Methods: We used data on PWH aged ≥20 years old from the HIV/AIDS Cancer Match Study during 2001-2019. We used Poisson regression to assess time trends in incidence rates for each cancer site by racial/ethnicity and risk group, adjusting for age, registry, and sex.

Elemental mapping in single-particle reconstructions by reconstructed electron energy-loss analysis.

For macromolecular structures determined by cryogenic electron microscopy, no technique currently exists for mapping elements to defined locations, leading to errors in the assignment of metals and other ions, cofactors, substrates, inhibitors and lipids that play essential roles in activity and regulation. Elemental mapping in the electron microscope is well established for dose-tolerant samples but is challenging for biological samples, especially in a cryo-preserved state. Here we combine electron energy-loss spectroscopy with single-particle image processing to allow elemental mapping in cryo-preserved macromolecular complexes.