Interleukin-17 (IL-17) and Rho-kinase (ROCK) play an important role in regulating the expression of inflammatory mediators, immune cell recruitment, hyper-responsiveness, tissue remodeling, and ...oxidative stress. Modulation of IL-17 and ROCK proteins may represent a promising approach for the treatment of this disease.
To study the effects of an anti-IL17 neutralizing antibody and ROCK inhibitor treatments, separately and in combination, in a murine model of chronic allergy-induced lung inflammation.
Sixty-four BALBc mice, were divided into eight groups (
= 8): SAL (saline-instilled); OVA (exposed-ovalbumin); SAL-RHOi (saline and ROCK inhibitor), OVA-RHOi (exposed-ovalbumin and ROCK inhibitor); SAL-anti-IL17 (saline and anti-IL17); OVA-anti-IL17 (exposed-ovalbumin and anti-IL17); SAL-RHOi-anti-IL17 (saline, ROCK inhibitor and anti-IL17); and OVA-RHOi-anti-IL17 (exposed-ovalbumin, anti-IL17, and ROCK inhibitor). A 28-day protocol of albumin treatment was used for sensitization and induction of pulmonary inflammation. The anti-IL17A neutralizing antibody (7.5 μg per treatment) was administered by intraperitoneal injection and ROCK inhibitor (Y-27632) intranasally (10 mg/kg), 1 h prior to each ovalbumin challenge (days 22, 24, 26, and 28).
Treatment with the anti-IL17 neutralizing antibody and ROCK inhibitor attenuated the percentage of maximal increase of respiratory system resistance and respiratory system elastance after challenge with methacholine and the inflammatory response markers evaluated (CD4
, CD8
, ROCK1, ROCK2, IL-4, IL-5, IL-6, IL-10 IL-13, IL-17, TNF-α, TGF-β, NF-κB, dendritic cells, iNOS, MMP-9, MMP-12, TIMP-1, FOXP3, isoprostane, biglycan, decorin, fibronectin, collagen fibers content and gene expression of IL-17, VAChT, and arginase) compared to the OVA group (
< 0.05). Treatment with anti-IL17 and the ROCK inhibitor together resulted in potentiation in decreasing the percentage of resistance increase after challenge with methacholine, decreased the number of IL-5 positive cells in the airway, and reduced, IL-5, TGF-β, FOXP3, ROCK1 and ROCK2 positive cells in the alveolar septa compared to the OVA-RHOi and OVA-anti-IL17 groups (
< 0.05).
Anti-IL17 treatment alone or in conjunction with the ROCK inhibitor, modulates airway responsiveness, inflammation, tissue remodeling, and oxidative stress in mice with chronic allergic lung inflammation.
Background and aims:
Expansion and morphological dysregulation of the bronchial vascular network occurs in asthmatic airways. Interleukin (IL) -17 and Rho-kinase (ROCK) are known to act in ...inflammation control and remodeling. Modulation of Rho-kinase proteins and IL-17 may be a promising approach for the treatment of asthma through the control of angiogenesis. Our objective was to analyze the effects of treatment with anti-IL17 and/or Rho-kinase inhibitor on vascular changes in mice with chronic allergic pulmonary inflammation.
Methods:
Sixty-four BALB/c mice, with pulmonary inflammation induced by ovalbumin were treated with anti-IL17A (7.5/µg per dose, intraperitoneal) and/or Rho-kinase inhibitor (Y-27632-10 mg/kg, intranasal), 1 h before each ovalbumin challenge (22, 24, 26, and 28/days). Control animals were made to inhale saline. At the end of the protocol, lungs were removed, and morphometric analysis was performed to quantify vascular inflammatory, remodeling, and oxidative stress responses.
Results:
Anti-IL17 or Rho-kinase inhibitor reduced the number of CD4+, CD8+, dendritic cells, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, Rho-kinase 1 and 2, transforming growth factor (TGF-β), vascular endothelial growth factor (VEGF), nuclear factor (NF)-KappaB, iNOS, metalloproteinase (MMP)-9, MMP-12, metalloproteinase inhibitor-1 (TIMP-1), FOXP-3, signal transducer and activator of transcription 1 (STAT1) and phospho-STAT1-positive cells, and actin, endothelin-1, isoprostane, biglycan, decorin, fibronectin and the collagen fibers volume fraction compared with the ovalbumin group (p < 0.05). The combination treatment, when compared with anti-IL17, resulted in potentiation of decrease in the number of IL1β- and dendritic cells-positive cells. When we compared the OVA-RHO inhibitor-anti-IL17 with OVA-RHO inhibitor we found a reduction in the number of CD8+ and IL-17, TGF-β, and phospho-STAT1-positive cells and endothelin-1 in the vessels (p < 0.05). There was an attenuation in the number of ROCK 2-positive cells in the group with the combined treatment when compared with anti-IL17 or Rho-kinase inhibitor-treated groups (p < 0.05).
Conclusion:
We observed no difference in angiogenesis after treatment with Rho-kinase inhibitor and anti-IL17. Although the treatments did not show differences in angiogenesis, they showed differences in the markers involved in the angiogenesis process contributing to inflammation control and vascular remodeling.
The reviews of this paper are available via the supplemental material section.
The prediction of vegetation responses to climate requires a knowledge of how climate-sensitive plant traits mediate not only the responses of individual plants, but also shifts in the species and ...functional compositions of whole communities. The emission of isoprene gas – a trait shared by one-third of tree species – is known to protect leaf biochemistry under climatic stress. Here, we test the hypothesis that isoprene emission shapes tree species compositions in tropical forests by enhancing the tolerance of emitting trees to heat and drought.
Using forest inventory data, we estimated the proportional abundance of isoprene-emitting trees (pIE) at 103 lowland tropical sites. We also quantified the temporal composition shifts in three tropical forests – two natural and one artificial – subjected to either anomalous warming or drought.
Across the landscape, pIE increased with site mean annual temperature, but decreased with dry season length. Through time, pIE strongly increased under high temperatures, and moderately increased following drought.
Our analysis shows that isoprene emission is a key plant trait determining species responses to climate. For species adapted to seasonal dry periods, isoprene emission may tradeoff with alternative strategies, such as leaf deciduousness. Community selection for isoprene-emitting species is a potential mechanism for enhanced forest resilience to climatic change.
Amazon forests are being degraded by myriad anthropogenic disturbances, altering ecosystem and climate function. We analyzed the effects of a range of land‐use and climate‐change disturbances on ...fine‐scale canopy structure using a large database of profiling canopy lidar collected from disturbed and mature Amazon forest plots. At most of the disturbed sites, surveys were conducted 10–30 years after disturbance, with many exhibiting signs of recovery. Structural impacts differed in magnitude more than in character among disturbance types, producing a gradient of impacts. Structural changes were highly coordinated in a manner consistent across disturbance types, indicating commonalities in regeneration pathways. At the most severely affected site – burned igapó (seasonally flooded forest) – no signs of canopy regeneration were observed, indicating a sustained alteration of microclimates and consequently greater vulnerability to transitioning to a more open‐canopy, savanna‐like state. Notably, disturbances rarely shifted forests beyond the natural background of structural variation within mature plots, highlighting the similarities between anthropogenic and natural disturbance regimes, and indicating a degree of resilience among Amazon forests. Studying diverse disturbance types within an integrated analytical framework builds capacity to predict the risk of degradation‐driven forest transitions.
Despite the superior performance in modeling complex patterns to address challenging problems, the black-box nature of Deep Learning (DL) methods impose limitations to their application in real-world ...critical domains. The lack of a smooth manner for enabling human reasoning about the black-box decisions hinder any preventive action to unexpected events, in which may lead to catastrophic consequences. To tackle the unclearness from black-box models, interpretability became a fundamental requirement in DL-based systems, leveraging trust and knowledge by providing ways to understand the model's behavior. Although a current hot topic, further advances are still needed to overcome the existing limitations of the current interpretability methods in unsupervised DL-based models for Anomaly Detection (AD). Autoencoders (AE) are the core of unsupervised DL-based for AD applications, achieving best-in-class performance. However, due to their hybrid aspect to obtain the results (by requiring additional calculations out of network), only agnostic interpretable methods can be applied to AE-based AD. These agnostic methods are computationally expensive to process a large number of parameters. In this paper, we present the RXP (Residual eXPlainer), a new interpretability method to deal with the limitations for AE-based AD in large-scale systems. It stands out for its implementation simplicity, low computational cost and deterministic behavior, in which explanations are obtained through the deviation analysis of reconstructed input features. In an experiment using data from a real heavy-haul railway line, the proposed method achieved superior performance compared to SHAP, demonstrating its potential to support decision making in large scale critical systems.
Windthrows change forest structure and species composition in central Amazon forests. However, the effects of widespread tree mortality associated with wind disturbances on soil properties have not ...yet been described in this vast region. We investigated short-term effects (7 years after disturbance) of widespread tree mortality caused by a squall line event from mid-January of 2005 on soil carbon stocks and concentrations in a central Amazon terra firme forest. The soil carbon stock (averaged over a 0–30 cm depth profile) in disturbed plots (61.4 ± 8.2 Mg ha−1, mean ±95 % confidence interval) was marginally higher (p = 0.09) than that from undisturbed plots (47.7 ± 13.6 Mg ha−1). The soil organic carbon concentration in disturbed plots (2.0 ± 0.17 %) was significantly higher (p < 0.001) than that from undisturbed plots (1.36 ± 0.24 %). Moreover, soil carbon stocks were positively correlated with soil clay content (r2 = 0.332, r = 0.575 and p = 0.019) and with tree mortality intensity (r2 = 0.257, r = 0.506 and p = 0.045). Our results indicate that large inputs of plant litter associated with large windthrow events cause a short-term increase in soil carbon content, and the degree of increase is related to soil clay content and tree mortality intensity. The higher carbon content and potentially higher nutrient availability in soils from areas recovering from windthrows may favor forest regrowth and increase vegetation resilience.
Tropical ecosystems are undergoing unprecedented rates of degradation from deforestation, fire, and drought disturbances. The collective effects of these disturbances threaten to shift large portions ...of tropical ecosystems such as Amazon forests into savanna‐like structure via tree loss, functional changes, and the emergence of fire (savannization). Changes from forest states to a more open savanna‐like structure can affect local microclimates, surface energy fluxes, and biosphere–atmosphere interactions. A predominant type of ecosystem state change is the loss of tree cover and structural complexity in disturbed forest. Although important advances have been made contrasting energy fluxes between historically distinct old‐growth forest and savanna systems, the emergence of secondary forests and savanna‐like ecosystems necessitates a reframing to consider gradients of tree structure that span forest to savanna‐like states at multiple scales. In this Innovative Viewpoint, we draw from the literature on forest–grassland continua to develop a framework to assess the consequences of tropical forest degradation on surface energy fluxes and canopy structure. We illustrate this framework for forest sites with contrasting canopy structure that ranges from simple, open, and savanna‐like to complex and closed, representative of tropical wet forest, within two climatically distinct regions in the Amazon. Using a recently developed rapid field assessment approach, we quantify differences in cover, leaf area vertical profiles, surface roughness, albedo, and energy balance partitioning between adjacent sites and compare canopy structure with adjacent old‐growth forest; more structurally simple forests displayed lower net radiation. To address forest–atmosphere feedback, we also consider the effects of canopy structure change on susceptibility to additional future disturbance. We illustrate a converse transition—recovery in structure following disturbance—measuring forest canopy structure 10 yr after the imposition of a 5‐yr drought in the ground‐breaking Seca Floresta experiment. Our approach strategically enables rapid characterization of surface properties relevant to vegetation models following degradation, and advances links between surface properties and canopy structure variables, increasingly available from remote sensing. Concluding, we hypothesize that understanding surface energy balance and microclimate change across degraded tropical forest states not only reveals critical atmospheric forcing, but also critical local‐scale feedbacks from forest sensitivity to additional climate‐linked disturbance.
Amazon forests are fire-sensitive ecosystems and consequently fires affect forest structure and composition. For instance, the legacy of past fire regimes may persist through some species and traits ...that are found due to past fires. In this study, we tested for relationships between functional traits that are classically presented as the main components of plant ecological strategies and environmental filters related to climate and historical fires among permanent mature forest plots across the range of local and regional environmental gradients that occur in Amazonia. We used percentage surface soil pyrogenic carbon (PyC), a recalcitrant form of carbon that can persist for millennia in soils, as a novel indicator of historical fire in old-growth forests. Five out of the nine functional traits evaluated across all 378 species were correlated with some environmental variables. Although there is more PyC in Amazonian soils than previously reported, the percentage soil PyC indicated no detectable legacy effect of past fires on contemporary functional composition. More species with dry diaspores were found in drier and hotter environments. We also found higher wood density in trees from higher temperature sites. If Amazon forest past burnings were local and without distinguishable attributes of a widespread fire regime, then impacts on biodiversity would have been small and heterogeneous. Alternatively, sufficient time may have passed since the last fire to allow for species replacement. Regardless, as we failed to detect any impact of past fire on present forest functional composition, if our plots are representative then it suggests that mature Amazon forests lack a compositional legacy of past fire.
Aim
Water availability is the major driver of tropical forest structure and dynamics. Most research has focused on the impacts of climatic water availability, whereas remarkably little is known about ...the influence of water table depth and excess soil water on forest processes. Nevertheless, given that plants take up water from the soil, the impacts of climatic water supply on plants are likely to be modulated by soil water conditions.
Location
Lowland Amazonian forests.
Time period
1971–2019.
Methods
We used 344 long‐term inventory plots distributed across Amazonia to analyse the effects of long‐term climatic and edaphic water supply on forest functioning. We modelled forest structure and dynamics as a function of climatic, soil‐water and edaphic properties.
Results
Water supplied by both precipitation and groundwater affects forest structure and dynamics, but in different ways. Forests with a shallow water table (depth <5 m) had 18% less above‐ground woody productivity and 23% less biomass stock than forests with a deep water table. Forests in drier climates (maximum cumulative water deficit < −160 mm) had 21% less productivity and 24% less biomass than those in wetter climates. Productivity was affected by the interaction between climatic water deficit and water table depth. On average, in drier climates the forests with a shallow water table had lower productivity than those with a deep water table, with this difference decreasing within wet climates, where lower productivity was confined to a very shallow water table.
Main conclusions
We show that the two extremes of water availability (excess and deficit) both reduce productivity in Amazon upland (terra‐firme) forests. Biomass and productivity across Amazonia respond not simply to regional climate, but rather to its interaction with water table conditions, exhibiting high local differentiation. Our study disentangles the relative contribution of those factors, helping to improve understanding of the functioning of tropical ecosystems and how they are likely to respond to climate change.
Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main ...tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors.
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