MMP14 Cleavage of VEGFR1 in the Cornea Leads to a VEGF-Trap Antiangiogenic Effect

PURPOSE: To determine the possible antiangiogenic effect of metalloproteinase (MMP) 14 cleavage of vascular endothelial growth factor receptor 1 (VEGFR1) in the cornea. METHODS: Recombinant mouse (rm) VEGFR1 was incubated with various concentrations of recombinant MMP14 to examine proteolysis in vitro. The reaction mixture was analyzed by SDS-PAGE and stained with Coomassie blue. The fragments resulting from rmVEGFR1 cleavage by MMP14 were subjected to Edman degradation, and the amino acid sequences were aligned with rmVEGFR1 sequences. Surface plasmon resonance was used to determine the equilibrium dissociation constant (K(D)) between MMP14 and rmVEGFR1. The K(D) value of rmVEGFR1 and the 59.8-kDa cleavage product binding to VEGF-A(165) was also determined. Cell proliferation assays were performed in the presence of VEGF-A(165) plus the 59.8-kDa VEGFR1 fragment or VEGF-A(165) alone. RESULTS: Matrix metalloproteinase 14 binds and cleaves rmVEGFR1 to produce 59.8-kDa (N-terminal fragment, Ig domains 1–5), 35-kDa (C-terminal fragment containing IgG and His-tag), and 21-kDa (Ig domains 6–7) fragments. The 59.8-kDa fragment showed binding to VEGF-A(165) and inhibited VEGF-induced endothelial cell mitogenesis. CONCLUSIONS: Our findings suggest that VEGFR1 cleavage by MMP14 in the cornea leads to a VEGF-trap effect, reducing the proangiogenic effect of VEGF-A(165), thereby reducing corneal angiogenesis

Avian brains and a new understanding of vertebrate brain evolution.

We believe that names have a powerful influence on the experiments we do and the way in which we think. For this reason, and in the light of new evidence about the function and evolution of the vertebrate brain, an international consortium of neuroscientists has reconsidered the traditional, 100-year-old terminology that is used to describe the avian cerebrum. Our current understanding of the avian brain - in particular the neocortex-like cognitive functions of the avian pallium - requires a new terminology that better reflects these functions and the homologies between avian and mammalian brains

Avian brains and a new understanding of vertebrate brain evolution.

We believe that names have a powerful influence on the experiments we do and the way in which we think. For this reason, and in the light of new evidence about the function and evolution of the vertebrate brain, an international consortium of neuroscientists has reconsidered the traditional, 100-year-old terminology that is used to describe the avian cerebrum. Our current understanding of the avian brain - in particular the neocortex-like cognitive functions of the avian pallium - requires a new terminology that better reflects these functions and the homologies between avian and mammalian brains

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health