Principal components analysis of sources of variability in retinal ganglion cell responses

An approach to the functional organization of retinal ganglion cell processing in terms of corelation matrices (Levine and Shefner, 1975; 1977a, b; Shefner and Levine, 1979) is extended by applying Principal Components Analysis. This analysis reduces each correlation matrix to a few components which are implicit in the data. The component loadings describe properties of the system in terms of loadings (correlations) of time bins on the underlying components. Each component is identified by the experimental conditions associated with the highest loadings. Mixed conditions are quantitatively interpreted as weighted contributions from the various identified components. This has led to new interpretations of existing data. Several properties of ganglion cell inputs are analyzed in this manner, including ON and OFF processes, center and surround mechanisms, rod and cone inputs, and spatially distinct areas within the receptive field center. Although the details vary, generally one of the components is highly associated with ON processes and the other with OFF and/or MAINTAINED processes. Several advantages may be realized through the use of Principal Components Analysis: (1) all of the data contribute to the analysis, (2) the number and relative importance of contributing processes may be assessed, (3) the relative contribution of underlying processes to mixed responses may be assessed, and (4) the most parsimonious representation of the data is obtained.     

Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies

The recently reported “UK variant” (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result of several changes, including the N501Y mutation. We present a 2.9-Å resolution cryo-electron microscopy (cryo-EM) structure of the complex between the ACE2 receptor and N501Y spike protein ectodomains that shows Y501 inserted into a cavity at the binding interface near Y41 of ACE2. This additional interaction provides a structural explanation for the increased ACE2 affinity of the N501Y mutant, and likely contributes to its increased infectivity. However, this mutation does not result in large structural changes, enabling important neutralization epitopes to be retained in the spike receptor binding domain. We confirmed this through biophysical assays and by determining cryo-EM structures of spike protein ectodomains bound to 2 representative potent neutralizing antibody fragments.