ABSTRACT
One of ecology's grand challenges is developing general rules to explain and predict highly complex systems. Understanding and predicting ecological processes from species' traits has been ...considered a ‘Holy Grail’ in ecology. Plant functional traits are increasingly being used to develop mechanistic models that can predict how ecological communities will respond to abiotic and biotic perturbations and how species will affect ecosystem function and services in a rapidly changing world; however, significant challenges remain. In this review, we highlight recent work and outstanding questions in three areas: (i) selecting relevant traits; (ii) describing intraspecific trait variation and incorporating this variation into models; and (iii) scaling trait data to community‐ and ecosystem‐level processes. Over the past decade, there have been significant advances in the characterization of plant strategies based on traits and trait relationships, and the integration of traits into multivariate indices and models of community and ecosystem function. However, the utility of trait‐based approaches in ecology will benefit from efforts that demonstrate how these traits and indices influence organismal, community, and ecosystem processes across vegetation types, which may be achieved through meta‐analysis and enhancement of trait databases. Additionally, intraspecific trait variation and species interactions need to be incorporated into predictive models using tools such as Bayesian hierarchical modelling. Finally, existing models linking traits to community and ecosystem processes need to be empirically tested for their applicability to be realized.
The UK's Research Excellence Framework (REF) is a performance-based research funding system that was introduced in 2014. REF is a process of expert review in universities which assesses the quality ...and reach of research across higher education. It highlights areas of excellence, benchmarks the quality of previously funded research and provides accountability for ongoing public investment in research. In addition to assessing the quality of research outputs and the environment in which research is undertaken, the REF became the first exercise to evaluate the impact of research outside of academia.
This article specifically addresses the impact component of the REF, explaining what is understood by the term ‘impact’ and considering how impact is gaining significance within the REF framework as a measure of research excellence. It also reflects on the complexities of measuring impact and ongoing resistance from academics to the impact agenda, which they believe threatens academic freedom and appears only to value research that generates specific outcomes. In order to address these and other issues arising from the first-ever assessment of impact in REF 2014, institutions were consulted on the proposed guidance for the REF 2021 submission.
The final REF 2021 guidance has sought to provide clearer detail on interpretations of impact and its underpinning research in order to reassure researchers that their academic freedom will not come under threat. However, this process still fails to capture other impactful research being undertaken across institutions, which falls outside of the strict REF criteria.
Most human monoclonal antibodies (mAbs) neutralizing SARS-CoV-2 recognize the spike (S) protein receptor-binding domain and block virus interactions with the cellular receptor angiotensin-converting ...enzyme 2. We describe a panel of human mAbs binding to diverse epitopes on the N-terminal domain (NTD) of S protein from SARS-CoV-2 convalescent donors and found a minority of these possessed neutralizing activity. Two mAbs (COV2-2676 and COV2-2489) inhibited infection of authentic SARS-CoV-2 and recombinant VSV/SARS-CoV-2 viruses. We mapped their binding epitopes by alanine-scanning mutagenesis and selection of functional SARS-CoV-2 S neutralization escape variants. Mechanistic studies showed that these antibodies neutralize in part by inhibiting a post-attachment step in the infection cycle. COV2-2676 and COV2-2489 offered protection either as prophylaxis or therapy, and Fc effector functions were required for optimal protection. Thus, natural infection induces a subset of potent NTD-specific mAbs that leverage neutralizing and Fc-mediated activities to protect against SARS-CoV-2 infection using multiple functional attributes.
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•Natural SARS-2 infection induces a subset of potent N-terminal domain-specific mAbs•N-terminal domain reactive human monoclonal antibodies can neutralize live virus•COV2-2676 and COV2-2489 offer protection in a hACE2-transgenic mouse model•COV2-2676 and COV2-2489 Fc-effector functions are essential for optimal protection
Suryadevara et al. find human neutralizing antibodies to the spike protein N-terminal domain that arise from natural infection with SARS-CoV-2. These antibodies inhibit post-attachment steps of the viral cycle and initiate protective immune responses via the antibody Fc domain.
The ongoing pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major threat to global health
and the medical ...countermeasures available so far are limited
. Moreover, we currently lack a thorough understanding of the mechanisms of humoral immunity to SARS-CoV-2
. Here we analyse a large panel of human monoclonal antibodies that target the spike (S) glycoprotein
, and identify several that exhibit potent neutralizing activity and fully block the receptor-binding domain of the S protein (S
) from interacting with human angiotensin-converting enzyme 2 (ACE2). Using competition-binding, structural and functional studies, we show that the monoclonal antibodies can be clustered into classes that recognize distinct epitopes on the S
, as well as distinct conformational states of the S trimer. Two potently neutralizing monoclonal antibodies, COV2-2196 and COV2-2130, which recognize non-overlapping sites, bound simultaneously to the S protein and neutralized wild-type SARS-CoV-2 virus in a synergistic manner. In two mouse models of SARS-CoV-2 infection, passive transfer of COV2-2196, COV2-2130 or a combination of both of these antibodies protected mice from weight loss and reduced the viral burden and levels of inflammation in the lungs. In addition, passive transfer of either of two of the most potent ACE2-blocking monoclonal antibodies (COV2-2196 or COV2-2381) as monotherapy protected rhesus macaques from SARS-CoV-2 infection. These results identify protective epitopes on the S
and provide a structure-based framework for rational vaccine design and the selection of robust immunotherapeutic agents.
Ecosystem services such as protection from storms and erosion, tourism benefits, and climate adaptation and mitigation have been increasingly recognized as important considerations for environmental ...policymaking. Recent research has shown that coastal ecosystems such as seagrasses, salt marshes, and mangroves provide climate mitigation services because they are particularly effective at sequestering and storing carbon dioxide, referred to as “coastal blue carbon”. Unfortunately, degradation of blue carbon ecosystems due to anthropogenic impacts contributes to anthropogenic carbon emissions from land use impacts and prevents these ecosystems from continuing to sequester and store carbon. Given the impressive carbon sequestration and storage in coastal ecosystems, many countries with blue carbon resources are beginning to implement blue carbon restoration projects using carbon financing mechanisms. This study analyzed four case studies of projects in Kenya, India, Vietnam, and Madagascar, evaluating the individual carbon financing mechanisms, the project outcomes, and the policy implications of each. Strengths and challenges of implementing blue carbon projects are discussed and considerations that all projects should address are examined in order to develop long-term sustainable climate mitigation or adaptation policies. This analysis can help to inform future project design considerations as well as policy opportunities.
•Coastal wetlands store a lot of “blue carbon,” mostly in soils.•Coastal wetland restoration is becoming an important climate mitigation option.•Successful projects involve local stakeholders & consider alternative livelihoods.•Funding has come from voluntary carbon markets or other non-carbon finance.•Only one case study included soil carbon in their carbon credits (India).
SARS-CoV-2 has caused the global COVID-19 pandemic. Although passively delivered neutralizing antibodies against SARS-CoV-2 show promise in clinical trials, their mechanism of action in vivo is ...incompletely understood. Here, we define correlates of protection of neutralizing human monoclonal antibodies (mAbs) in SARS-CoV-2-infected animals. Whereas Fc effector functions are dispensable when representative neutralizing mAbs are administered as prophylaxis, they are required for optimal protection as therapy. When given after infection, intact mAbs reduce SARS-CoV-2 burden and lung disease in mice and hamsters better than loss-of-function Fc variant mAbs. Fc engagement of neutralizing antibodies mitigates inflammation and improves respiratory mechanics, and transcriptional profiling suggests these phenotypes are associated with diminished innate immune signaling and preserved tissue repair. Immune cell depletions establish that neutralizing mAbs require monocytes and CD8+ T cells for optimal clinical and virological benefit. Thus, potently neutralizing mAbs utilize Fc effector functions during therapy to mitigate lung infection and disease.
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•Neutralizing mAbs do not require Fc effector functions when given as prophylaxis•MAbs against SARS-CoV-2 require Fc effector functions for therapeutic protection•Fc engagement of mAbs decreases viral burden and mitigates lung inflammation•CD8+ T cells and monocytes are necessary for optimal Fc-dependent mAb protection
Neutralizing human monoclonal antibodies (mAbs) against SARS-CoV-2 require Fc effector functions for optimal protection during post-exposure therapy, with intact mAbs reducing SARS-CoV-2 burden and lung disease in rodent models better than LALA-PG loss-of-function Fc variant mAbs and requiring monocytes and CD8+ T cells for optimal clinical and virological benefit.
Whooping cough caused by Bordetella pertussis is a re-emerging infectious disease despite the introduction of safer acellular pertussis vaccines (Pa). One explanation for this is that Pa are less ...protective than the more reactogenic whole cell pertussis vaccines (Pw) that they replaced. Although Pa induce potent antibody responses, and protection has been found to be associated with high concentrations of circulating IgG against vaccine antigens, it has not been firmly established that host protection induced with this vaccine is mediated solely by humoral immunity. The aim of this study was to examine the relative contribution of Th1 and Th17 cells in host immunity to infection with B. pertussis and in immunity induced by immunization with Pw and Pa and to use this information to help rationally design a more effective Pa. Our findings demonstrate that Th1 and Th17 both function in protective immunity induced by infection with B. pertussis or immunization with Pw. In contrast, a current licensed Pa, administered with alum as the adjuvant, induced Th2 and Th17 cells, but weak Th1 responses. We found that IL-1 signalling played a central role in protective immunity induced with alum-adsorbed Pa and this was associated with the induction of Th17 cells. Pa generated strong antibody and Th2 responses, but was fully protective in IL-4-defective mice, suggesting that Th2 cells were dispensable. In contrast, Pa failed to confer protective immunity in IL-17A-defective mice. Bacterial clearance mediated by Pa-induced Th17 cells was associated with cell recruitment to the lungs after challenge. Finally, protective immunity induced by an experimental Pa could be enhanced by substituting alum with a TLR agonist that induces Th1 cells. Our findings demonstrate that alum promotes protective immunity through IL-1β-induced IL-17A production, but also reveal that optimum protection against B. pertussis requires induction of Th1, but not Th2 cells.
Although normothermic machine perfusion of donor livers may allow assessment of graft viability prior to transplantation, there are currently no data on what would be a good parameter of graft ...viability. To determine whether bile production is a suitable biomarker that can be used to discriminate viable from non-viable livers we have studied functional performance as well as biochemical and histological evidence of hepatobiliary injury during ex vivo normothermic machine perfusion of human donor livers. After a median duration of cold storage of 6.5 h, twelve extended criteria human donor livers that were declined for transplantation were ex vivo perfused for 6 h at 37 °C with an oxygenated solution based on red blood cells and plasma, using pressure controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion. During perfusion, two patterns of bile flow were identified: (1) steadily increasing bile production, resulting in a cumulative output of ≥ 30 g after 6 h (high bile output group), and (2) a cumulative bile production <20 g in 6 h (low bile output group). Concentrations of transaminases and potassium in the perfusion fluid were significantly higher in the low bile output group, compared to the high bile output group. Biliary concentrations of bilirubin and bicarbonate were respectively 4 times and 2 times higher in the high bile output group. Livers in the low bile output group displayed more signs of hepatic necrosis and venous congestion, compared to the high bile output group. In conclusion, bile production could be an easily assessable biomarker of hepatic viability during ex vivo machine perfusion of human donor livers. It could potentially be used to identify extended criteria livers that are suitable for transplantation. These ex vivo findings need to be confirmed in a transplant experiment or a clinical trial.
Gynaecology cancers, including ovarian (OC), endometrial (EC), and cervical (CC), are prevalent with high mortality. Sarcopenia is found in 38.7% of cancer patients, adversely affecting prognosis. ...Computed tomography (CT) is performed routinely in oncology, yet CT assessments of sarcopenia are not commonly used to measure prognosis. This systematic review and meta-analysis aimed to evaluate the prognostic potential of pre-treatment sarcopenia assessments on overall survival (OS) and progression free survival (PFS) in gynaecology cancer.
Four electronic databases were systematically searched from 2000 to May 2020 in English: Ovid Medline, EMBASE, Web of Science, and CINAHL plus. Titles and abstracts were screened, eligible full-texts were reviewed, and data from included studies was extracted. Meta-analyses were conducted on homogenous survival data, heterogenous data were narratively reported.
The initial search yielded 767 results; 27 studies were included in the systematic review (n = 4286), all published between 2015 and 2020. Meta-analysis of unadjusted results revealed a negative effect of pre-treatment sarcopenia on OS in OC (HR: 1.40, 1.20-1.64, p < 0.0001) (n = 10), EC (HR: 1.42, 0.97-2.10, p = 0.07) (n = 4) and CC (HR: 1.10, 0.93-1.31, p = 0.28) (n = 5), and a negative effect on PFS in OC (HR: 1.28, 1.11-1.46, p = 0.0005) (n = 8), EC (HR: 1.51, 1.03-2.20, p = 0.03) (n = 2) and CC (HR: 1.14, 0.85-1.53, p = 0.37) (n = 2). Longitudinal analysis indicated negative effects of muscle loss on survival. Overall, there was a high risk of bias.
Pre-treatment sarcopenia negatively affected survival in gynaecology cancers. Incorporating such assessments into cancer management may be beneficial. Heterogeneity in sarcopenia assessments makes data interpretation challenging. Further research in prospective studies is required.
Part 1 of this review synthesizes recent research on status and climate vulnerability of freshwater and saltwater wetlands, and their contribution to addressing climate change (carbon cycle, ...adaptation, resilience). Peatlands and vegetated coastal wetlands are among the most carbon rich sinks on the planet sequestering approximately as much carbon as do global forest ecosystems. Estimates of the consequences of rising temperature on current wetland carbon storage and future carbon sequestration potential are summarized. We also demonstrate the need to prevent drying of wetlands and thawing of permafrost by disturbances and rising temperatures to protect wetland carbon stores and climate adaptation/resiliency ecosystem services. Preventing further wetland loss is found to be important in limiting future emissions to meet climate goals, but is seldom considered. In Part 2, the paper explores the policy and management realm from international to national, subnational and local levels to identify strategies and policies reflecting an integrated understanding of both wetland and climate change science. Specific recommendations are made to capture synergies between wetlands and carbon cycle management, adaptation and resiliency to further enable researchers, policy makers and practitioners to protect wetland carbon and climate adaptation/resiliency ecosystem services.
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