The F-BAR protein pacsin2 inhibits asymmetric VE-cadherin internalization from tensile adherens junctions

Vascular homoeostasis, development and disease critically depend on the regulation of endothelial cell-cell junctions. Here we uncover a new role for the F-BAR protein pacsin2 in the control of VE-cadherin-based endothelial adhesion. Pacsin2 concentrates at focal adherens junctions (FAJs) that are experiencing unbalanced actomyosin-based pulling. FAJs move in response to differences in local cytoskeletal geometry and pacsin2 is recruited consistently to the trailing end of fast-moving FAJs via a mechanism that requires an intact F-BAR domain. Photoconversion, photobleaching, immunofluorescence and super-resolution microscopy reveal polarized dynamics, and organization of junctional proteins between the front of FAJs and their trailing ends. Interestingly, pacsin2 recruitment inhibits internalization of the VE-cadherin complex from FAJ trailing ends and is important for endothelial monolayer integrity. Together, these findings reveal a novel junction protective mechanism during polarized trafficking of VE-cadherin, which supports barrier maintenance within dynamic endothelial tissue

Stomatal responses of Eucalyptus species to elevated CO2 concentration and drought stress

Five species of Eucalyptus (E. grandis, E. urophylla, E. camaldulensis, E. torelliana, and E. phaeotrica), among the ten species most commonly used in large scale plantations, were selected for studies on the effects of elevated CO2 concentration [CO2] and drought stress on stomatal responses of 2.5-month old seedlings. The first three species belong to the subgenus Smphyomyrtus, whereas the fourth species belongs to the subgenus Corymbia and E. phaeotrica is from the subgenus Monocalyptus. Seedlings were grown in four pairs of open-top chambers, arranged to have 2 plants of each species in each chamber, with four replications in each of two CO2 concentrations: 350 ± 30 mumol mol-1 and 700 ± 30 mumol mol-1. After 100 days in the chambers, a series of gas exchange measurements were made. Half the plants in each chamber, one plant per species per chamber, were drought-stressed by withholding irrigation, while the remaining plants continued to be watered daily. Drought stress decreased stomatal conductance, photosynthesis and transpiration rates in all the species. The effect of drought stress on stomatal closure was similar in both [CO2]. The positive effects of elevated [CO2] on photosynthesis and water use efficiency were maintained longer during the stress period than under well-watered conditions. The photosynthetic rate of E. phaeotrica was higher even in the fourth day of the drought stress. Drought stress increased photoinhibition of photosynthesis, as measured by chlorophyll fluorescence, which varied among the species, as well as in relation to [CO2]. The results are in agreement with observed differences in stomatal responses between some eucalyptus species of the subgenera Symphyomyrtus and Monocalyptus

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript