Natural recovery of corals after severe disturbance.

Ecosystem recovery from human-induced disturbances, whether through natural processes or restoration, is occurring worldwide. Yet, recovery dynamics, and their implications for broader ecosystem management, remain unclear. We explored recovery dynamics using coral reefs as a case study. We tracked the fate of 809 individual coral recruits that settled after a severe bleaching event at Lizard Island, Great Barrier Reef. Recruited Acropora corals, first detected in 2020, grew to coral cover levels that were equivalent to global average coral cover within just 2 years. Furthermore, we found that just 11.5 Acropora recruits per square meter were sufficient to reach this cover within 2 years. However, wave exposure, growth form and colony density had a marked effect on recovery rates. Our results underscore the importance of considering natural recovery in management and restoration and highlight how lessons learnt from reef recovery can inform our understanding of recovery dynamics in high-diversity climate-disturbed ecosystems.

On the Challenges of Identifying Benthic Dominance on Anthropocene Coral Reefs.

The concept of dominance is frequently used to describe changes in rapidly reconfiguring ecosystems, but the definition of dominance can vary widely among studies. Using coral reefs as a model, we use extensive benthic composition data to explore how variability in applying dominance concepts can shape perceptions. We reveal that coral dominance is sensitive to the exclusion of key algal groups and the categorization of other benthic groups, with ramifications for detecting an ecosystem phase shift. For example, ignoring algal turf inflates the dominance of hard and soft corals in the benthic habitats underpinning reef ecosystems. We need a consensus on how dominance concepts are applied so that we can build a more comprehensive understanding of ecosystem shifts across a broad range of aquatic and terrestrial settings. For reefs, we highlight the benefits of comprehensive and inclusive surveys for evaluating and managing the altered ecosystem states that are emerging in the Anthropocene.

B cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke in mice.

Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury. B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery. B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery occlusion (tMCAo), independent of changing immune populations in recipient mice. Testing a direct neurotrophic effect, B cells cocultured with mixed cortical cells protected neurons and maintained dendritic arborization after oxygen-glucose deprivation. Whole-brain volumetric serial two-photon tomography (STPT) and a custom-developed image analysis pipeline visualized and quantified poststroke B cell diapedesis throughout the brain, including remote areas supporting functional recovery. Stroke induced significant bilateral B cell diapedesis into remote brain regions regulating motor and cognitive functions and neurogenesis (e.g., dentate gyrus, hypothalamus, olfactory areas, cerebellum) in the whole-brain datasets. To confirm a mechanistic role for B cells in functional recovery, rituximab was given to human CD20+ (hCD20+) transgenic mice to continuously deplete hCD20+-expressing B cells following tMCAo. These mice experienced delayed motor recovery, impaired spatial memory, and increased anxiety through 8 wk poststroke compared to wild type (WT) littermates also receiving rituximab. B cell depletion reduced stroke-induced hippocampal neurogenesis and cell survival. Thus, B cell diapedesis occurred in areas remote to the infarct that mediated motor and cognitive recovery. Understanding the role of B cells in neuronal health and disease-based plasticity is critical for developing effective immune-based therapies for protection against diseases that involve recruitment of peripheral immune cells into the injured brain.

Collapsing ecosystem functions on an inshore coral reef.

Ecosystem functions underpin productivity and key services to humans, such as food provision. However, as the severity of environmental stressors intensifies, it is becoming increasingly unclear if, and to what extent, critical functions and services can be sustained. This issue is epitomised on coral reefs, an ecosystem at the forefront of environmental transitions. We provide a functional profile of a coral reef ecosystem, linking time-series data to quantified processes. The data reveal a prolonged collapse of ecosystem functions in this previously resilient system. The results suggest that sediment accumulation in algal turfs has led to a decline in resource yields to herbivorous fishes and a decrease in fish-based ecosystem functions, including a collapse of both fish biomass and productivity. Unfortunately, at present, algal turf sediment accumulation is rarely monitored nor managed in coral reef systems. Our examination of functions through time highlights the value of directly assessing functions, their potential vulnerability, and the capacity of algal turf sediments to overwhelm productive high-diversity coral reef ecosystems.

A Pilot Study Identifying Brain-Targeting Adaptive Immunity in Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury.

OBJECTIVES: Extracorporeal membrane oxygenation provides short-term cardiopulmonary life support, but is associated with peripheral innate inflammation, disruptions in cerebral autoregulation, and acquired brain injury. We tested the hypothesis that extracorporeal membrane oxygenation also induces CNS-directed adaptive immune responses which may exacerbate extracorporeal membrane oxygenation-associated brain injury. DESIGN: A single center prospective observational study. SETTING: Pediatric and cardiac ICUs at a single tertiary care, academic center. PATIENTS: Twenty pediatric extracorporeal membrane oxygenation patients (0-14 yr; 13 females, 7 males) and five nonextracorporeal membrane oxygenation Pediatric Logistic Organ Dysfunction score matched patients INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS: Venous blood samples were collected from the extracorporeal membrane oxygenation circuit at day 1 (10-23 hr), day 3, and day 7 of extracorporeal membrane oxygenation. Flow cytometry quantified circulating innate and adaptive immune cells, and CNS-directed autoreactivity was detected using an in vitro recall response assay. Disruption of cerebral autoregulation was determined using continuous bedside near-infrared spectroscopy and acquired brain injury confirmed by MRI. Extracorporeal membrane oxygenation patients with acquired brain injury (n = 9) presented with a 10-fold increase in interleukin-8 over extracorporeal membrane oxygenation patients without brain injury (p < 0.01). Furthermore, brain injury within extracorporeal membrane oxygenation patients potentiated an inflammatory phenotype in adaptive immune cells and selective autoreactivity to brain peptides in circulating B cell and cytotoxic T cell populations. Correlation analysis revealed a significant relationship between adaptive immune responses of extracorporeal membrane oxygenation patients with acquired brain injury and loss of cerebral autoregulation. CONCLUSIONS: We show that pediatric extracorporeal membrane oxygenation patients with acquired brain injury exhibit an induction of pro-inflammatory cell signaling, a robust activation of adaptive immune cells, and CNS-targeting adaptive immune responses. As these patients experience developmental delays for years after extracorporeal membrane oxygenation, it is critical to identify and characterize adaptive immune cell mechanisms that target the developing CNS.

T and B cell subsets differentially correlate with amyloid deposition and neurocognitive function in patients with amnestic mild cognitive impairment after one year of physical activity.

Individuals with amnestic mild cognitive impairment (aMCI) experience cognitive declines in learning and memory greater than expected for normal aging, and are at a high risk of dementia. We previously reported that sedentary aMCI patients exhibited neuroinflammation that correlated with brain amyloid beta (Aß) burden, as determined by 18F-florbetapir positron emission tomography (PET). These aMCI patients enrolled in a one-year randomized control trial (AETMCI, NCT01146717) to test the beneficial effects of 12 months of moderate-to-high intensity aerobic exercise training (AET) or stretching/toning (ST) control intervention on neurocognitive function. A subset of aMCI participants had PET imaging, cognitive testing, and immunophenotyping of cerebrospinal fluid (CSF) and peripheral blood after AET or ST interventions. As adaptive immune responses were similar between AET and ST groups, we combined AET/ST into a general 'physical activity' (PA) group and compared Aß burden, cognitive function, and adaptive immune cell subsets to sedentary lifestyle before intervention. We found that PAinduced immunomodulation of CD4+ and CD8+ T cells in CSF correlated with changes in Aß burden in brain regions associated with executive function. Furthermore, after PA, cognitive scores on tests of memory, processing speed, attention, verbal fluency, and executive function were associated with increased percent representation of circulating naïve B + T cells. We review the literature on aMCI-related cognition and immune changes as they relate to exercise, and highlight how our preliminary data suggest a complex interplay between the adaptive immune system, physical activity, cognition, and Aß burden in aMCI.

Strong Electronic Coupling of Molecular Sites to Graphitic Electrodes via Pyrazine Conjugation.

Glassy carbon electrodes were functionalized with redox-active moieties by condensation of o-phenylenediamine derivatives with o-quinone sites native to graphitic carbon surfaces. Electrochemical and spectroscopic investigations establish that these graphite-conjugated catalysts (GCCs) exhibit strong electronic coupling to the electrode, leading to electron transfer (ET) behavior that diverges fundamentally from that of solution-phase or surface-tethered analogues. We find that (1) ET is not observed between the electrode and a redox-active GCC moiety regardless of applied potential. (2) ET is observed at GCCs only if the interfacial reaction is ion-coupled. (3) Even when ET is observed, the oxidation state of a transition metal GCC site remains unchanged. From these observations, we construct a mechanistic model for GCC sites in which ET behavior is identical to that of catalytically active metal surfaces rather than to that of molecules in solution. These results suggest that GCCs provide a versatile platform for bridging molecular and heterogeneous electrocatalysis.

Adaptive lymphocyte profiles correlate to brain Aß burden in patients with mild cognitive impairment.

BACKGROUND: We previously found that subjects with amnestic mild cognitive impairment exhibit a pro-inflammatory immune profile in the cerebrospinal fluid similar to multiple sclerosis, a central nervous system autoimmune disease. We therefore hypothesized that early neuroinflammation would reflect increases in brain amyloid burden during amnestic mild cognitive impairment. METHODS: Cerebrospinal fluid and blood samples were collected from 24 participants with amnestic mild cognitive impairment (12 men, 12 women; 66 ± 6 years; 0.5 Clinical Dementia Rating) enrolled in the AETMCI study. Analyses of cerebrospinal fluid and blood included immune profiling by multi-parameter flow cytometry, genotyping for apolipoprotein (APO)ε, and quantification of cytokine and immunoglobin levels. Amyloid (A)ß deposition was determined by 18F-florbetapir positron emission tomography. Spearman rank order correlations were performed to assess simple linear correlation for parameters including amyloid imaging, central and peripheral immune cell populations, and protein cytokine levels. RESULTS: Soluble Aß42 in the cerebrospinal fluid declined as Aß deposition increased overall and in the precuneous and posterior cingulate cortices. Lymphocyte profiling revealed a significant decline in T cell populations in the cerebrospinal fluid, specifically CD4+ T cells, as Aß deposition in the posterior cingulate cortex increased. In contrast, increased Aß burden correlated positively with increased memory B cells in the cerebrospinal fluid, which was exacerbated in APOε4 carriers. For peripheral circulating lymphocytes, only B cell populations decreased with Aß deposition in the precuneous cortex, as peripheral T cell populations did not correlate with changes in brain amyloid burden. CONCLUSIONS: Elevations in brain Aß burden associate with a shift from T cells to memory B cells in the cerebrospinal fluid of subjects with amnestic mild cognitive impairment in this exploratory cohort. These data suggest the presence of cellular adaptive immune responses during Aß accumulation, but further study needs to determine whether lymphocyte populations contribute to, or result from, Aß dysregulation during memory decline on a larger cohort collected at multiple centers. TRIAL REGISTRATION: AETMCI NCT01146717.

The disease-ameliorating function of autoregulatory CD8 T cells is mediated by targeting of encephalitogenic CD4 T cells in experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS, and CD8 T cells are the predominant T cell population in MS lesions. Given that transfer of CNS-specific CD8 T cells results in an attenuated clinical demyelinating disease in C57BL/6 mice with immunization-induced experimental autoimmune encephalomyelitis (EAE), we investigated the cellular targets and mechanisms of autoreactive regulatory CD8 T cells. In this study we report that myelin oligodendrocyte glycoprotein peptide (MOG35-55)-induced CD8 T cells could also attenuate adoptively transferred, CD4 T cell-mediated EAE. Whereas CD8(-/-) mice exhibited more severe EAE associated with increased autoreactivity and inflammatory cytokine production by myelin-specific CD4 T cells, this was reversed by adoptive transfer of MOG-specific CD8 T cells. These autoregulatory CD8 T cells required in vivo MHC class Ia (K(b)D(b)) presentation. Interestingly, MOG-specific CD8 T cells could also suppress adoptively induced disease using wild-type MOG35-55-specific CD4 T cells transferred into K(b)D(b-/-) recipient mice, suggesting direct targeting of encephalitogenic CD4 T cells. In vivo trafficking analysis revealed that autoregulatory CD8 T cells are dependent on neuroinflammation for CNS infiltration, and their suppression/cytotoxicity of MOG-specific CD4 T cells is observed both in the periphery and in the CNS. These studies provide important insights into the mechanism of disease suppression mediated by autoreactive CD8 T cells in EAE.

Disease exacerbation of multiple sclerosis is characterized by loss of terminally differentiated autoregulatory CD8+ T cells.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). Although its etiology remains unknown, pathogenic T cells are thought to underlie MS immune pathology. We recently showed that MS patients harbor CNS-specific CD8+ Tregs that are deficient during disease relapse. We now demonstrate that CNS-specific CD8+ Tregs were cytolytic and could eliminate pathogenic CD4+ T cells. These CD8+ Tregs were present primarily in terminally differentiated (CD27-, CD45RO-) subset and their suppression was IFNγ, perforin and granzyme B-dependent. Interestingly, MS patients with acute relapse displayed a significant loss in terminally differentiated CD8+ T cells, with a concurrent loss in expression of perforin and granzyme B. Pre-treatment of exacerbation-derived CD8+ T cells with IL-12 significantly restored suppressive capability of these cells through upregulation of granzyme B. Our studies uncover immune-suppressive mechanisms of CNS-specific CD8+ Tregs, and may contribute to design of novel immune therapies for MS.

IL-21 promotes the production of anti-DNA IgG but is dispensable for kidney damage in lyn-/- mice.

The autoimmune disease systemic lupus erythematosus is characterized by loss of tolerance to nuclear Ags and a heightened inflammatory environment, which together result in end organ damage. Lyn-deficient mice, a model of systemic lupus erythematosus, lack an inhibitor of B-cell and myeloid cell activation. This results in B-cell hyper-responsiveness, plasma cell accumulation, autoantibodies, and glomerulonephritis (GN). IL-21 is associated with autoimmunity in mice and humans and promotes B-cell differentiation and class switching. Here, we explore the role of IL-21 in the autoimmune phenotypes of lyn(-/-) mice. We find that IL-21 mRNA is reduced in the spleens of lyn(-/-) IL-6(-/-) and lyn(-/-) Btk(lo) mice, neither of which produce pathogenic autoantibodies or develop significant GN. While IL-21 is dispensable for plasma cell accumulation and IgM autoantibodies in lyn(-/-) mice, it is required for anti-DNA IgG antibodies and some aspects of T-cell activation. Surprisingly, GN still develops in lyn(-/-) IL-21(-/-) mice. This likely results from the presence of IgG autoantibodies against a limited set of non-DNA Ags. These studies identify a specific role for IL-21 in the class switching of anti-DNA B cells and demonstrate that neither IL-21 nor anti-DNA IgG is required for kidney damage in lyn(-/-) mice.

Repetitive hypoxic preconditioning induces an immunosuppressed B cell phenotype during endogenous protection from stroke.

BACKGROUND: Repetitive hypoxic preconditioning (RHP) creates an anti-inflammatory phenotype that protects from stroke-induced injury for months after a 2-week treatment. The mechanisms underlying long-term tolerance are unknown, though one exposure to hypoxia significantly increased peripheral B cell representation. For this study, we sought to determine if RHP specifically recruited B cells into the protected ischemic hemisphere, and whether RHP could phenotypically alter B cells prior to stroke onset. METHODS: Adult, male SW/ND4 mice received RHP (nine exposures over 2 weeks; 8 to 11 % O2; 2 to 4 hours) or identical exposures to 21 % O2 as control. Two weeks following RHP, a 60-minute transient middle cerebral artery occlusion was induced. Standard techniques quantified CXCL13 mRNA and protein expression. Two days after stroke, leukocytes were isolated from brain tissue (70:30 discontinuous Percoll gradient) and profiled on a BD-FACS Aria flow cytometer. In a separate cohort without stroke, sorted splenic CD19+ B cells were isolated 2 weeks after RHP and analyzed on an Illumina MouseWG-6 V2 Bead Chip. Final gene pathways were determined using Ingenuity Pathway Analysis. Student's t-test or one-way analysis of variance determined significance (P < 0.05). RESULTS: CXCL13, a B cell-specific chemokine, was upregulated in post-stroke cortical vessels of both groups. In the ischemic hemisphere, RHP increased B cell representation by attenuating the diapedesis of monocyte, macrophage, neutrophil and T cells, to quantities indistinguishable from the uninjured, contralateral hemisphere. Pre-stroke splenic B cells isolated from RHP-treated mice had >1,900 genes differentially expressed by microarray analysis. Genes related to B-T cell interactions, including antigen presentation, B cell differentiation and antibody production, were profoundly downregulated. Maturation and activation were arrested in a cohort of B cells from pre-stroke RHP-treated mice while regulatory B cells, a subset implicated in neurovascular protection from stroke, were upregulated. CONCLUSIONS: Collectively, our data characterize an endogenous neuroprotective phenotype that utilizes adaptive immune mechanisms pre-stroke to protect the brain from injury post-stroke. Future studies to validate the role of B cells in minimizing injury and promoting central nervous system recovery, and to determine whether B cells mediate an adaptive immunity to systemic hypoxia that protects from subsequent stroke, are needed.

Quantum of fear: Herbivore grazing rates not affected by reef shark presence.

Grazing by nominally herbivorous fishes is widely recognised as a critical ecosystem function on coral reefs. However, several studies have suggested that herbivory is reduced in the presence of predators, especially sharks. Nevertheless, the effects of shark presence on grazing, under natural settings, remains poorly resolved. Using ∼200 h of video footage, we quantify the extent of direct disturbance by reef sharks on grazing fishes. Contrary to expectations, grazing rate was not significantly suppressed due to sharks, with fishes resuming feeding in as little as 4 s after sharks passed. Based on our observations, we estimate that an average m2 area of reef at our study locations would be subjected to ∼5 s of acute shark disturbance during daylight hours. It appears the short-term impact of reef shark presence has a negligible effect on herbivore grazing rates, with the variable nature of grazing under natural conditions overwhelming any fear effects.

Hot spots of bleaching in massive Porites coral colonies.

Coral bleaching events have become more frequent and severe due to ocean warming. While the large-scale impacts of bleaching events are well-known, there is growing recognition of the importance of small-scale spatial variation in bleaching and survival probability of individual coral colonies. By quantifying bleaching in 108 massive Porites colonies spread across Lizard Island, Great Barrier Reef, during the 2016 bleaching event, we investigated how hydrodynamic exposure levels and colony size contribute to local variability in bleaching prevalence and extent. Our results revealed that exposed locations were the least impacted by bleaching, while lagoonal areas exhibited the highest prevalence of bleaching and colony-level bleaching extents. Such patterns of bleaching could be due to prolonged exposure to warm water in the lagoon. These findings highlight the importance of considering location-specific factors when assessing coral health and emphasize the vulnerability of corals in lagoonal habitats to rapid and/or prolonged elevated temperatures.

Benthic composition changes on coral reefs at global scales.

Globally, ecosystems are being reconfigured by a range of intensifying human-induced stressors. Coral reefs are at the forefront of this environmental transformation, and if we are to secure their key ecosystem functions and services, it is important to understand the likely configuration of future reefs. However, the composition and trajectory of global coral reef benthic communities is currently unclear. Here our global dataset of 24,468 observations spanning 22 years (1997-2018) revealed that particularly marked declines in coral cover occurred in the Western Atlantic and Central Pacific. The data also suggest that high macroalgal cover, widely regarded as the major degraded state on coral reefs, is a phenomenon largely restricted to the Western Atlantic. At a global scale, the raw data suggest decreased average (± standard error of the mean) hard coral cover from 36 ± 1.4% to 19 ± 0.4% (during a period delineated by the first global coral bleaching event (1998) until the end of the most recent event (2017)) was largely associated with increased low-lying algal cover such as algal turfs and crustose coralline algae. Enhanced understanding of reef change, typified by decreased hard coral cover and increased cover of low-lying algal communities, will be key to managing Anthropocene coral reefs.

Spatial and temporal variability in tropical off-reef zooplankton across broad spatial and temporal scales.

Productivity of oligotrophic coral reefs is largely dependent on the constant influx of zooplankton. However, our understanding of how zooplankton communities in tropical reef-associated regions vary over large spatial and temporal scales is limited. Using the Australian continuous plankton recorder dataset, we explored if, and to what extent, the off-reef zooplankton community along the Queensland shelf (including most of the Great Barrier Reef lagoon) varied with latitude, month, and diel time. The zooplankton community was consistently dominated by copepods (∼60%) which, with appendicularians, chaetognaths, non-copepod crustaceans, and thaliaceans, comprised ∼98% of the zooplankton. However, the abundance of these taxonomic groups did not vary predictably across latitude, month, or diel time, with these gradients only explaining 5% of community variation. At the scales sampled herein the composition of zooplankton was highly predictable in terms of broad taxonomic groups but variation in the relative abundance of these groups was not predictable.

Hyperacute immune responses associate with immediate neuropathology and motor dysfunction in large vessel occlusions.

OBJECTIVE: Despite successful endovascular therapy, a proportion of stroke patients exhibit long-term functional decline, regardless of the cortical reperfusion. Our objective was to evaluate the early activation of the adaptive immune response and its impact on neurological recovery in patients with large vessel occlusion (LVO). METHODS: Nineteen (13 females, 6 males) patients with acute LVO were enrolled in a single-arm prospective cohort study. During endovascular therapy (EVT), blood samples were collected from pre and post-occlusion, distal femoral artery, and median cubital vein (controls). Cytokines, chemokines, cellular and functional profiles were evaluated with immediate and follow-up clinical and radiographic parameters, including cognitive performance and functional recovery. RESULTS: In the hyperacute phase (within hours), adaptive immune activation was observed in the post-occlusion intra-arterial environment (post). Ischemic vascular tissue had a significant increase in T-cell-related cytokines, including IFN-γ and MMP-9, while GM-CSF, IL-17, TNF-α, IL-6, MIP-1a, and MIP-1b were decreased. Cellularity analysis revealed an increase in inflammatory IL-17+ and GM-CSF+ helper T-cells, while natural killer (NK), monocytes and B-cells were decreased. A correlation was observed between hypoperfused tissue, infarct volume, inflammatory helper, and cytotoxic T-cells. Moreover, helper and cytotoxic T-cells were also significantly increased in patients with improved motor function at 3 months. INTERPRETATION: We provide evidence of the activation of the inflammatory adaptive immune response during the hyperacute phase and the association of pro-inflammatory cytokines with greater ischemic tissue and worsening recovery after successful reperfusion. Further characterization of these immune pathways is warranted to test selective immunomodulators during the early stages of stroke rehabilitation.