Zhang, Meng

Objective Raynaud phenomenon (RP) is often the initial clinical manifestation of systemic sclerosis (SSc), but some patients develop other manifestations first. To help elucidate the diversity of SSc presentation in its early stages, we describe the initial clinical manifestations and antinuclear antibody (ANA) profiles of patients in two early SSc cohorts. Methods All patient data in the Genetics vs Environment in Scleroderma Outcomes Study (GENISOS) and Collaborative National Quality and Efficacy Registry (CONQUER) cohorts were reviewed. Both studies enrolled patients within five years of the first non‐RP symptom. Results In GENISOS and CONQUER, respectively, 194 (44.2%) of 439 and 292 (31.1%) of 938 patients had a non‐RP initial symptom, most commonly puffy fingers/hands. Black patients had a non‐RP symptom before RP more commonly than patients in other race and ethnicity categories. Non‐RP first patients were more likely than RP first patients to have diffuse cutaneous involvement and joint contractures at enrollment and had a higher prevalence of RNA polymerase III antibody positivity. Conclusion In two large US cohorts, >30% of patients began to manifest SSc with puffy fingers/hands or other symptoms, without the “warning sign” of RP as their initial symptom. These patients presented with more severe skin and musculoskeletal disease on average, highlighting the importance of early recognition. The most common autoantibody associated with this presentation was RNA polymerase III. These results should be considered in efforts to recognize SSc in its earliest stages. Puffy fingers/hands, even in the absence of RP, should prompt consideration of early SSc and testing for ANA and SSc‐associated autoantibodies, including RNA polymerase III.

Abstract Although structures of vitrified supramolecular complexes have been determined at near-atomic resolution, elucidating in situ molecular structure in living cells remains a major challenge. Here, we apply a novel but simple liquid-cell technique, developed previously for real-time imaging of the dynamics at a liquid-gas interface, to image wet biological samples. With extra scattering from the liquid phase, the transmission electron micrographs show amplitude contrast comparable to that in negatively stained samples. Single-molecule domains are resolved in the protein complex GroEL imaged in buffer solution at room temperature. Moreover, various stages of virus cell entry, which are transient events with very few structural information to date, are also captured. Morphological details are reconstructed using the technique of individual particle electron tomography. These results demonstrate that this approach can be a valuable yet cost-effective technique complementary to other microscopy techniques for addressing important biological questions at the molecular level.