Sweeneyhirsch4096

The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor and is a major determinant of host range and a dominant target of neutralizing antibodies. Here, we experimentally measure how all amino acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD's surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity-enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.

To determine the proportion of indexed ophthalmology journals with article processing charges (APCs) and potential factors associated with APCs.

Cross-sectional study.

Web of Science-indexed Ophthalmology journals in 2019.

Indexed ophthalmology journal web sites were reviewed to obtain information on APCs, impact factor (IF), publication mode, publisher type, journal affiliation, waiver discount, and continent of origin. For data unavailable on the web site, the journal was contacted. Journal publication mode was categorized into subscription, fully open access, and hybrid (open access and subscription combined). Linear regression analysis was used to evaluate the association between APCs and the above variables.

Proportion of ophthalmology journals with APCs.

59 indexed ophthalmology journals were identified; 3 (5.1%) subscription only, 10 (16.9%) open access, and 46 (78.0%) hybrid. Overall 52/59 (88.1%) journals had APCs; 10 of 59 journals (16.9%) required APCs for publication (7 fully open access and 3 hybrid journals), whereas 42/59 (71.2%, all hybrid journals) had optional APCs for open access. The 7/59 journals (11.9%) without APCs included 100% (3/3) of the subscription-only journals, 30% (3/10) of the open access, and 2% (1/46) of the hybrid journals. The mean cost for journals with APCs was US$2854 ± 708.9 (range US$490-5000). Higher IF, publication mode, and commercial publishers were associated with higher APCs.

16.9% of indexed ophthalmology journals in 2019 required APCs, and additional 71.2% hybrid journals had APCs for the option of open access. Independent predictors of APCs were IF and publication mode.

16.9% of indexed ophthalmology journals in 2019 required APCs, and additional 71.2% hybrid journals had APCs for the option of open access. Independent predictors of APCs were IF and publication mode.In vertebrates, epithelial permeability is regulated by the tight junction (TJ) formed by specialized adhesive membrane proteins, adaptor proteins, and the actin cytoskeleton. Despite the TJ's critical physiological role, a molecular-level understanding of how TJ assembly sets the permeability of epithelial tissue is lacking. Here, we identify a 28-amino-acid sequence in the TJ adaptor protein ZO-1, which is responsible for actin binding, and show that this interaction is essential for TJ permeability. In contrast to the strong interactions at the adherens junction, we find that the affinity between ZO-1 and actin is surprisingly weak, and we propose a model based on kinetic trapping to explain how affinity could affect TJ assembly. Finally, by tuning the affinity of ZO-1 to actin, we demonstrate that epithelial monolayers can be engineered with a spectrum of permeabilities, which points to a promising target for treating transport disorders and improving drug delivery.Human pluripotent stem cell (hPSC)-derived intestinal organoids (HIOs) lack some cellular populations found in the native organ, including vasculature. Using single-cell RNA sequencing (scRNA-seq), we have identified a population of endothelial cells (ECs) present early in HIO differentiation that declines over time in culture. Here, we developed a method to expand and maintain this endogenous population of ECs within HIOs (vHIOs). MIRA-1 cost Given that ECs possess organ-specific gene expression, morphology, and function, we used bulk RNA-seq and scRNA-seq to interrogate the developing human intestine, lung, and kidney in order to identify organ-enriched EC gene signatures. By comparing these gene signatures and validated markers to HIO ECs, we find that HIO ECs grown in vitro share the highest similarity with native intestinal ECs relative to kidney and lung. Together, these data demonstrate that HIOs can co-differentiate a native EC population that is properly patterned with an intestine-specific EC transcriptional signature in vitro.Damage to the intestinal stem cell niche can result from mechanical stress, infections, chronic inflammation or cytotoxic therapies. Progenitor cells can compensate for insults to the stem cell population through dedifferentiation. The microenvironment modulates this regenerative response by influencing the activity of signaling pathways, including Wnt, Notch, and YAP/TAZ. For instance, mesenchymal cells and immune cells become more abundant after damage and secrete signaling molecules that promote the regenerative process. Furthermore, regeneration is influenced by the nutritional state, microbiome, and extracellular matrix. Here, we review how all these components cooperate to restore epithelial homeostasis in the intestine after injury.The mechanisms that govern cell interactions during organ formation are not fully understood. In this issue of Developmental Cell, Miao et al. demonstrate a channel-independent role for gap junction proteins in the establishment of contacts between three cell types that build up the micropyle during oocyte development in Drosophila.In this issue of Developmental Cell, Xie et al. show that in cystic fibrosis, airway gland mucus gels form under conditions of high acidity and protein concentration. This causes them to be unusually stiff. This abnormal rheology cannot be corrected by changing pH or calcium levels in the bathing medium.