ASC specks as a single-molecule fluid biomarker of inflammation in neurodegenerative diseases.

Immunotherapeutic strategies for Alzheimer's and Parkinson's disease would be facilitated by better measures of inflammation. Here we established an ultra-sensitive single-molecule pull-down immunoassay combined with direct stochastic optical reconstruction microscopy (dSTORM) to measure the number, size and shape of individual extracellular inflammasome ASC specks. We assayed human post-mortem brain, serum and cerebrospinal fluid of patients with Parkinson's and Alzheimer's as well as healthy elderly.

Large-bipolaron liquids in cuprate superconductors.

Uniquely, large-bipolarons' self-trapped holes occupy superoxygens, each comprising four oxygens circumscribed by four coppers in a CuO2 plane, formed as oxygens relax inward and coppers relax outward. Critically, concomitant oxygen-to-copper electron transfer eliminates copper spins. The d-symmetry of superoxygens' ground state molecular orbital tracks the superoxygens' predominant zero-point radial vibrations.

Imaging Protein Aggregates in Parkinson's Disease Serum Using Aptamer-Assisted Single-Molecule Pull-Down.

The formation of soluble α-synuclein (α-syn) and amyloid-β (Aβ) aggregates is associated with the development of Parkinson's disease (PD). Current methods mainly focus on the measurement of the aggregate concentration and are unable to determine their heterogeneous size and shape, which potentially also change during the development of PD due to increased protein aggregation. In this work, we introduce aptamer-assisted single-molecule pull-down (APSiMPull) combined with super-resolution fluorescence imaging of α-syn and Aβ aggregates in human serum from early PD patients and age-matched controls.