Overcoming undesirable resilience in the global food system

The current configuration of our global food system is undermining many of the UN Sustainable Development Goals (UN SDGs), leading to calls for major food system reform and transformation. Concurrently, other science-policy and business initiatives call for a food system more resilient to economic and environmental shocks, for example by improving the economic resilience of current supply chains. Prioritisation of short-term security to a subset of vested interests, however, can undermine the resilience of longer-term beneficial outcomes for society. Here we advocate a more inclusive and farsighted approach focussing on the resilience of positive outcomes for the whole of society, i.e., capturing the aim to promote resilient delivery of multiple UN SDGs. A significant challenge is to prioritise suites of interventions that can effectively transform the global food system to deliver these goals. Here, we use a transdisciplinary lens to identify ‘lock-in’ mechanisms that span four key areas— knowledge-based, economic/regulatory, sociocultural and biophysical constraints –which will help avoid ineffective siloed solutions to food system reform. Furthermore, we show how emergent system dynamics need to be considered using a more holistic approach. We highlight the importance of well-coordinated actions on multiple leverage points during windows of opportunity for food system transformation

Maternal microchimerism in cord blood and risk of childhood-onset type 1 diabetes

Background Maternal microchimerism (MMc), the transmission of small quantities of maternal cells to the fetus, is relatively common and persistent. MMc has been detected with increased frequency in the circulation and pancreas of type 1 diabetes (T1D) patients. We investigated for the first time whether MMc levels at birth predict future T1D risk. We also tested whether cord blood MMc predicted MMc in samples taken at T1D diagnosis. Methods Participants in the Norwegian Mother and Child Cohort study were human leukocyte antigen (HLA) class II typed to determine non‐inherited, non‐shared maternal alleles (NIMA). Droplet digital (dd) polymerase chain reaction (PCR) assays specific for common HLA class II NIMA (HLADQB1*03:01, *04:02, and *06:02/03) were developed and validated. MMc was estimated as maternal DNA quantity in the fetal circulation, by NIMA specific ddPCR, measured in cord blood DNA from 71 children who later developed T1D and 126 controls within the cohort. Results We found detectable quantities of MMc in 34/71 future T1D cases (48%) and 53/126 controls (42%) (adjusted odds ratio [aOR] 1.27, 95% confidence interval (CI) 0.68‐2.36), and no significant difference in ranks of MMc quantities between cases and controls (Mann‐Whitney P = .46). There was a possible association in the NIMA HLA‐DQB1*03:01 subgroup with later T1D (aOR 3.89, 95%CI 1.05‐14.4). MMc in cord blood was not significantly associated with MMc at T1D diagnosis. Conclusions Our findings did not support the hypothesis that the degree of MMc in cord blood predict T1D risk. The potential subgroup association with T1D risk should be replicated in a larger cohort

Merlin controls the repair capacity of Schwann cells after injury by regulating Hippo/YAP activity

Loss of the Merlin tumor suppressor and activation of the Hippo signaling pathway play major roles in the control of cell proliferation and tumorigenesis. We have identified completely novel roles for Merlin and the Hippo pathway effector Yes-associated protein (YAP) in the control of Schwann cell (SC) plasticity and peripheral nerve repair after injury. Injury to the peripheral nervous system (PNS) causes a dramatic shift in SC molecular phenotype and the generation of repair-competent SCs, which direct functional repair. We find that loss of Merlin in these cells causes a catastrophic failure of axonal regeneration and remyelination in the PNS. This effect is mediated by activation of YAP expression in Merlin-null SCs, and loss of YAP restores axonal regrowth and functional repair. This work identifies new mechanisms that control the regenerative potential of SCs and gives new insight into understanding the correct control of functional nerve repair in the PNS

Development and evaluation of low-volume tests to detect and characterize antibodies to SARS-CoV-2

Low-volume antibody assays can be used to track SARS-CoV-2 infection rates in settings where active testing for virus is limited and remote sampling is optimal. We developed 12 ELISAs detecting total or antibody isotypes to SARS-CoV-2 nucleocapsid, spike protein or its receptor binding domain (RBD), 3 anti-RBD isotype specific luciferase immunoprecipitation system (LIPS) assays and a novel Spike-RBD bridging LIPS total-antibody assay. We utilized pre-pandemic (n=984) and confirmed/suspected recent COVID-19 sera taken pre-vaccination rollout in 2020 (n=269). Assays measuring total antibody discriminated best between pre-pandemic and COVID-19 sera and were selected for diagnostic evaluation. In the blind evaluation, two of these assays (Spike Pan ELISA and Spike-RBD Bridging LIPS assay) demonstrated >97% specificity and >92% sensitivity for samples from COVID-19 patients taken >21 days post symptom onset or PCR test. These assays offered better sensitivity for the detection of COVID-19 cases than a commercial assay which requires 100-fold larger serum volumes. This study demonstrates that low-volume in-house antibody assays can provide good diagnostic performance, and highlights the importance of using well-characterized samples and controls for all stages of assay development and evaluation. These cost-effective assays may be particularly useful for seroprevalence studies in low and middle-income countries

SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml−1). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies