BACKGROUNDPediatric SARS-CoV-2 infection can be complicated by a dangerous hyperinflammatory condition termed multisystem inflammatory syndrome in children (MIS-C). The clinical and immunologic ...spectrum of MIS-C and its relationship to other inflammatory conditions of childhood have not been studied in detail.METHODSWe retrospectively studied confirmed cases of MIS-C at our institution from March to June 2020. The clinical characteristics, laboratory studies, and treatment response were collected. Data were compared with historic cohorts of Kawasaki disease (KD) and macrophage activation syndrome (MAS).RESULTSTwenty-eight patients fulfilled the case definition of MIS-C. Median age at presentation was 9 years (range: 1 month to 17 years); 50% of patients had preexisting conditions. All patients had laboratory confirmation of SARS-CoV-2 infection. Seventeen patients (61%) required intensive care, including 7 patients (25%) who required inotrope support. Seven patients (25%) met criteria for complete or incomplete KD, and coronary abnormalities were found in 6 cases. Lymphopenia, thrombocytopenia, and elevation in inflammatory markers, D-dimer, B-type natriuretic peptide, IL-6, and IL-10 levels were common but not ubiquitous. Cytopenias distinguished MIS-C from KD and the degree of hyperferritinemia and pattern of cytokine production differed between MIS-C and MAS. Immunomodulatory therapy given to patients with MIS-C included intravenous immune globulin (IVIG) (71%), corticosteroids (61%), and anakinra (18%). Clinical and laboratory improvement were observed in all cases, including 6 cases that did not require immunomodulatory therapy. No mortality was recorded in this cohort.CONCLUSIONMIS-C encompasses a broad phenotypic spectrum with clinical and laboratory features distinct from KD and MAS.FUNDINGThis work was supported by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute of Allergy and Infectious Diseases; Rheumatology Research Foundation Investigator Awards and Medical Education Award; Boston Children's Hospital Faculty Career Development Awards; the McCance Family Foundation; and the Samara Jan Turkel Center.
T cell receptor (TCR) cross-reactivity between major histocompatibility complex II (MHCII)-binding self and foreign peptides could influence the naive CD4+ T cell repertoire and autoimmunity. We ...found that nonamer peptides that bind to the same MHCII molecule only need to share five amino acids to cross-react on the same TCR. This property was biologically relevant because systemic expression of a self peptide reduced the size of a naive cell population specific for a related foreign peptide by deletion of cells with cross-reactive TCRs. Reciprocally, an incompletely deleted naive T cell population specific for a tissue-restricted self peptide could be triggered by related microbial peptides to cause autoimmunity. Thus, TCR cross-reactivity between similar self and foreign peptides can reduce the size of certain foreign peptide-specific T cell populations and might allow T cell populations specific for tissue-restricted self peptides to cause autoimmunity after infection.
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•MHCII-bound nonamer peptides need to only share five residues to bind the same TCR•A self peptide can cause deletion of T cells specific for a similar foreign peptide•Naive T cell populations can be small because of clonal deletion by self peptides•A foreign peptide can cause autoimmunity to a similar ignored self peptide
Immune responses to some antigens are stronger than others. The findings of Nelson and colleagues indicate that a T cell response can be weak because the eliciting foreign peptide resembles a self peptide to which the host is tolerant.
A naive CD4+ T cell population specific for a microbial peptide:major histocompatibility complex II ligand (p:MHCII) typically consists of about 100 cells, each with a different T cell receptor ...(TCR). Following infection, this population produces a consistent ratio of effector cells that activate microbicidal functions of macrophages or help B cells make antibodies. We studied the mechanism that underlies this division of labor by tracking the progeny of single naive T cells. Different naive cells produced distinct ratios of macrophage and B cell helpers but yielded the characteristic ratio when averaged together. The effector cell pattern produced by a given naive cell correlated with the TCR-p:MHCII dwell time or the amount of p:MHCII. Thus, the consistent production of effector cell subsets by a polyclonal population of naive cells results from averaging the diverse behaviors of individual clones, which are instructed in part by the strength of TCR signaling.
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•Individual naive CD4+ T cells have unique effector differentiation potentials•The diverse progeny of clones average to produce a consistent effector cell pattern•TCR signal amount helps dictate cell-mediated versus humoral immunity•Small CD4+ T cell repertoires produce different types of immunity between animals
Single naive T cells generate distinct ratios of macrophage and B cell helpers, based in part on the strength of signals through their unique TCRs.
Natural and anthropogenic disturbances have led to rapid declines in the amount and quality of available habitat in many ecosystems. Many studies have focused on how habitat loss has affected the ...composition and configuration of habitats, but there have been fewer studies that investigate how this loss affects ecosystem function. We investigated how a large‐scale seagrass die‐off altered the distribution of energetic resources of three seagrass‐associated consumers with varied resource use patterns. Using long‐term benthic habitat monitoring data and resource use data from Bayesian stable isotope mixing models, we generated energetic resource landscapes (E‐scapes) annually between 2007 and 2019. E‐scapes link the resources being used by a consumer to the habitats that produce those resources to calculate a habitat resource index as a measurement of energetic quality of the landscape. Overall, our results revealed that following the die‐off there was a reduction in trophic function across all species in areas affected by the die‐off event, but the response was species‐specific and dependent on resource use and recovery patterns. This study highlights how habitat loss can lead to changes in ecosystem function. Incorporating changes in ecosystem function into models of habitat loss could improve understanding of how species will respond to future change.
Natural and anthropogenic disturbances, especially related to human land use change, have led to rapid declines in the amount and quality of available habitat in many ecosystems, but not much is known about how these changes alter ecosystem function. Using long‐term habitat monitoring and resource use data, we investigated how a widespread seagrass die‐off altered trophic function. We found that large‐scale habitat loss led to ecosystem‐scale loss of trophic function, but the response was species‐specific and dependent on resource use and habitat recovery patterns.
In this study we investigated the removal of viruses with similar size and shape but with different external surface capsid proteins by a bench-scale membrane bioreactor (MBR). The goal was to ...determine which virus removal mechanisms (retention by clean backwashed membrane, retention by cake layer, attachment to biomass, and inactivation) were most impacted by differences in the virus surface properties. Seven bench-scale MBR experiments were performed using mixed liquor wastewater sludge that was seeded with three lab-cultured bacteriophages with icosahedral capsids of ∼30 nm diameter (MS2, phiX174, and fr). The operating conditions were designed to simulate those at a reference, full-scale MBR facility. The virus removal mechanism most affected by virus type was attachment to biomass (removals of 0.2 log for MS2, 1.2 log for phiX174, and 3 log for fr). These differences in removal could not be explained by electrostatic interactions, as the three viruses had similar net negative charge when suspended in MBR permeate. Removals by the clean backwashed membrane (less than 1 log) and cake layer (∼0.6 log) were similar for the three viruses. A comparison between the clean membrane removals seen at the bench-scale using a virgin membrane (∼1 log), and the full-scale using 10-year old membranes (∼2–3 logs) suggests that irreversible fouling, accumulated on the membrane over years of operation that cannot be removed by cleaning, also contributes towards virus removal. This study enhances the current mechanistic understanding of virus removal in MBRs and will contribute to more reliable treatment for water reuse applications.
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•We examined virus removal mechanisms most impacted by virus surface properties.•We used wastewater and three viruses with different surface properties.•The virus removal mechanism most affected by virus type was attachment to biomass.•Removals by clean membrane and cake layer were similar for three viruses studied.•Long-term operation increases virus removal through clean membrane mechanism.
Atopic disorders, including atopic dermatitis, food and environmental allergies, and asthma, are increasingly prevalent diseases. Atopic disorders are often associated with eosinophilia, driven by T ...helper type 2 (Th2) immune responses, and triggered by disrupted barrier function leading to abnormal immune priming in a susceptible host. Immune deficiencies, in contrast, occur with a significantly lower incidence, but are associated with greater morbidity and mortality. A subset of atopic disorders with eosinophilia and elevated IgE are associated with monogenic inborn errors of immunity (IEI). In this review, we discuss current knowledge of IEI that are associated with atopy and the lessons these immunologic disorders provide regarding the fundamental mechanisms that regulate type 2 immunity in humans. We also discuss further mechanistic insights provided by animal models.
Fisheries rely on threatened salt marshes Baker, Ronald; Taylor, Matthew D; Able, Kenneth W ...
Science (American Association for the Advancement of Science),
11/2020, Letnik:
370, Številka:
6517
Journal Article
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•Study uses niche metrics as a tool to quantify food web recovery after restoration.•Food web hypervolumes generated with stable isotope values from restoration projects.•Food webs ...take longer to recover when restoring biogenic habitats.•Variation in resource use changes following restoration.•This approach can be a powerful tool to quantify restoration success.
The primary goal of habitat restoration is to recover the ecological structure, function, and services of natural ecosystems lost due to disturbance. Post-restoration success typically focuses on the return of a desired habitat type, consumer species composition, or abundance relative to a reference site. However, how energy flow responds to habitat restoration has not been widely studied, and there is a need to develop a better understanding of how energy flows through a restored vs reference ecosystem following restoration. We tested recently developed niche metrics as a tool to assess the degree of recovery of ecosystem energy flow and evaluate the success of habitat restoration. Using published stable isotope values from six systems, one to three years post-restoration, we used Bayesian mixing models to quantify resource use by consumers to generate food web hypervolumes for restored and reference habitats in each ecosystem and to quantify similarity in resource use between restored and reference systems. Our analysis showed that there were differences in restoration success at each restoration project between the restored and reference food webs, but two general patterns emerged in the early stages following restoration. Restoration efforts that restore biogenic habitats display lower levels of recovery of food web function than those that only restore abiotic habitat structural. Restoration increases the variability in basal resource use of consumers in food webs that rely heavily on one basal resource, while in food webs that relied on multiple basal resources consumers decrease variability in basal resource use. Our results demonstrate that hypervolume analysis is a powerful tool that can be used to quantify energy flow, the recovery of food web function, and measure restoration success.
Studies of repertoires of mouse monoclonal CD4(+) T cells have revealed several mechanisms of self-tolerance; however, which mechanisms operate in normal repertoires is unclear. Here we studied ...polyclonal CD4(+) T cells specific for green fluorescent protein expressed in various organs, which allowed us to determine the effects of specific expression patterns on the same epitope-specific T cells. Peptides presented uniformly by thymic antigen-presenting cells were tolerated by clonal deletion, whereas peptides excluded from the thymus were ignored. Peptides with limited thymic expression induced partial clonal deletion and impaired effector T cell potential but enhanced regulatory T cell potential. These mechanisms were also active for T cell populations specific for endogenously expressed self antigens. Thus, the immunotolerance of polyclonal CD4(+) T cells was maintained by distinct mechanisms, according to self-peptide expression patterns.
Energetic resources and habitat distribution are inherently linked. Energetic resource availability is a major driver of the distribution of consumers, but estimating how much specific habitats ...contribute to the energetic resource needs of a consumer can be problematic.
We present a new approach that combines remote sensing information and stable isotope ecology to produce maps of energetic resources (E‐scapes). E‐scapes project species‐specific resource use information onto the landscape to classify areas based on energetic importance.
Using our E‐scapes, we investigated the relationship between energetic resource distribution and white shrimp distribution and how the scale used to generate the E‐scape mediated this relationship.
E‐scapes successfully predicted the size, abundance, biomass, and total energy of a consumer in salt marsh habitats in coastal Louisiana, USA at scales relevant to the movement of the consumer.
Our E‐scape maps can be used alone or in combination with existing models to improve habitat management and restoration practices and have potential to be used to test fundamental movement theory.
E‐scapes combine remote sensing and stable isotope analysis to map the consumer‐specific distribution of energetic resources across the landscape
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