Neutrophil extracellular traps (NETs) evolved as a unique effector mechanism contributing to resistance against infection that can also promote tissue damage in inflammatory conditions. Malaria ...infection can trigger NET release, but the mechanisms and consequences of NET formation in this context remain poorly characterized. Here we show that patients suffering from severe malaria had increased amounts of circulating DNA and increased neutrophil elastase (NE) levels in plasma. We used cultured erythrocytes and isolated human neutrophils to show that Plasmodium-infected red blood cells release macrophage migration inhibitory factor (MIF), which in turn caused NET formation by neutrophils in a mechanism dependent on the C-X-C chemokine receptor type 4 (CXCR4). NET production was dependent on histone citrullination by peptidyl arginine deiminase-4 (PAD4) and independent of reactive oxygen species (ROS), myeloperoxidase (MPO) or NE. In vitro, NETs functioned to restrain parasite dissemination in a mechanism dependent on MPO and NE activities. Finally, C57/B6 mice infected with P. berghei ANKA, a well-established model of cerebral malaria, presented high amounts of circulating DNA, while treatment with DNAse increased parasitemia and accelerated mortality, indicating a role for NETs in resistance against Plasmodium infection.
Strigolactones (SLs) are important ex‐planta signalling molecules in the rhizosphere, promoting the association with beneficial microorganisms, but also affecting plant interactions with harmful ...organisms. They are also plant hormones in‐planta, acting as modulators of plant responses under nutrient‐deficient conditions, mainly phosphate (Pi) starvation. In the present work, we investigate the potential role of SLs as regulators of early Pi starvation signalling in plants. A short‐term pulse of the synthetic SL analogue 2′‐epi‐GR24 promoted SL accumulation and the expression of Pi starvation markers in tomato and wheat under Pi deprivation. 2′‐epi‐GR24 application also increased SL production and the expression of Pi starvation markers under normal Pi conditions, being its effect dependent on the endogenous SL levels. Remarkably, 2′‐epi‐GR24 also impacted the root metabolic profile under these conditions, promoting the levels of metabolites associated to plant responses to Pi limitation, thus partially mimicking the pattern observed under Pi deprivation. The results suggest an endogenous role for SLs as Pi starvation signals. In agreement with this idea, SL‐deficient plants were less sensitive to this stress. Based on the results, we propose that SLs may act as early modulators of plant responses to P starvation.
The current work provides evidences supporting that the phytohormone strigolactones are early modulators of plant responses to low Pi availability and that they impact metabolic profiles in the roots. This knowledge may help to develop new strategies to optimize plant Pi acquisition efficiency and use.
Inorganic phosphorus (Pi) fertilizers are expected to become scarce in the near future; so, breeding for improved Pi acquisition-related root traits would decrease the need for fertilizer ...application. This work aimed to decipher the physiological and molecular mechanisms underlying the differences between two commercial wheat cultivars (Crac and Tukan) with contrasting Pi acquisition efficiencies (PAE). For that, four independent experiments with different growth conditions were conducted. When grown under non-limiting Pi conditions, both cultivars performed similarly. Crac was less affected by Pi starvation than Tukan, presenting higher biomass production, and an enhanced root development, root:shoot ratio, and root efficiency for Pi uptake under this condition. Higher PAE in Crac correlated with enhanced expression of the Pi transporter genes TaPht1;2 and TaPht1;10. Crac also presented a faster and higher modulation of the IPS1-miR399-PHO2 pathway upon Pi starvation. Interestingly, Crac showed increased levels of strigolactones, suggesting a direct relationship between this phytohormone and plant P responses. Based on these findings, we propose that higher PAE of the cultivar Crac is associated with an improved P signalling through a fine-tuning modulation of PHO2 activity, which seems to be regulated by strigolactones. This knowledge will help to develop new strategies for improved plant performance under P stress conditions.
COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular ...mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes and macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently promotes glycolysis. HIF-1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19.
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•Elevated glucose levels regulate viral replication and cytokine production in monocytes•Glycolysis sustains CoV-2-induced monocyte response and viral replication•mtROS/HIF-1α is necessary for CoV-2 replication and monocyte cytokine production•Monocyte-derived cytokines drive T cell dysfunction and epithelial cell death
Diabetic people with uncontrolled blood glucose levels have a greater risk to develop severe COVID-19 disease. Codo et al. show that elevated glucose levels and glycolysis promote SARS-CoV-2 (CoV-2) replication and cytokine production in monocytes through a mitochondrial ROS/hypoxia-inducible factor-1α dependent pathway, resulting in T cell dysfunction and epithelial cell death.
Agroforestry systems (AFSs) have gained recognition as a land use strategy to address food security and climate change. They involve intentionally cultivating trees alongside crops and/or animals. ...AFSs cover approximately 5% of the global forest area and promote sustainable soil conservation, including soil organic carbon (C) sequestration (CSEQ). In some areas of Chile, AFSs are used to preserve the ecological value of native forests. This study evaluates the effects of two AFSs, namely, an agroforest for fodder production (AGROFRST) and Silvopastoral (SPS), within a degraded native forest (Nothofagus obliqua sp.). The evaluation focuses on their impact on CSEQ capacity and soil quality (SQ), using soil quality indexes (SQIs) derived from 30 soil quality indicators (SINDs) related to physical, chemical, and microbiological properties at two depths (0–5 and 5–20 cm). The results for the total depth analyzed (0–20 cm) indicate an average CSEQ of 6.88 and 4.83 Mg C yr−1 and a global SQI of 37.8% and 31.0% for AGROFRST and SPS, respectively. Among the thirteen SINDs that demonstrated significant differences (p < 0.05), five were associated with the considered depths (P+, Ca2+, S, ECEC, and AlSAT), three differed between AGROFRST and SPS (BD, NH4+, NO3−), while SOC, K+, and Mg2+ varied across all conditions (e.g., combinations of systems and depths), and β-GLU and NMIN differed in a single condition. However, almost all 30 SINDs analyzed showed higher values at the 0–5 cm depth, indicating the positive effects of soil organic matter (SOM)/SOC additions. Significant interactions (Pearson’s correlation) revealed that SOC correlated with most SINDs (e.g., N, NH4+, P+, K+, Ca2+, Mg2+, S, ECEC, NMIN). These findings suggest that both AGROFRST and SPS systems have similar capabilities in restoring the ecological value of native Nothofagus forests while providing conditions for productive and complementary use. This sustainable option offers opportunities for cattle production alongside ecological restoration efforts and provides a possible strategy to generate public policies related to the ecosystem services of agroforestry systems.
This study aimed to examine how interactions at both plant genotype and arbuscular mycorrhizal fungus species levels affected the expression of root traits and the subsequent effect on plant ...nutrition and growth. We used two wheat cultivars with contrasting phosphorus (P) acquisition efficiencies (Tukan and Crac) and two arbuscular mycorrhizal (AM) fungi (Rhizophagus intraradices and Claroideoglomus claroideum). Plant growth, as well as morphological and architectural root traits, were highly dependent on the myco-symbiotic partner in the case of the less P-acquisition efficient cultivar Tukan, with mycorrhizal responses ranging from -45 to 54 % with respect to non-mycorrhizal plants. Meanwhile, these responses were between only -7 and 5 % in the P-acquisition efficient cultivar Crac. The AM fungal species produced contrasting mechanisms in the improvement of plant nutrition and root trait responses. Colonization by R. intraradices increased Ca accumulation, regardless of the cultivar, but reduced root growth on Tukan plants. On the other hand, C. claroideum increased P content in both cultivars, with a concomitant increase in root growth and diffusion-based nutrient acquisition by Tukan. Moreover, plants in symbiosis with R. intraradices showed greater organic acid concentration in their rhizosphere compared to C. claroideum-colonized plants, especially Tukan (24 and 35 % more citrate and oxalate, respectively). Our results suggest that the responses in plant-AM fungal interactions related to nutrient dynamics are highly influenced at the fungus level and also by intra-specific variations in root traits at the genotype level, while growth responses related to improved nutrition depend on plant intrinsic acquisition efficiency.
The relationship between phosphorus (P) availability and water restriction was explored in this study, focusing on its impact on phosphorus use efficiency (PUE) and water use efficiency (WUE) in ...various bromegrass (Bromus spp.) genotypes. Under controlled conditions, five bromegrass genotypes, as well as one ryegrass (Lolium perenne) cultivar, were compared by subjecting them to two P levels and two watering regimes. It was determined that combining water and phosphorus limitations led to reduced plant productivity. Initially, the ryegrass outperformed the bromegrass, but this result declined over time, while bromegrass exhibited consistent stability. Notably, under P and water stress, enhanced root development was observed in bromegrass compared to that in ryegrass. Distinct patterns of PUE and WUE allowed for the categorization of bromegrass genotypes into three groups. Genotype 3457 emerged as the most efficient, scoring 20 out of 24, while Pro 94-49 A achieved a score of only 10 out of 24. This study suggests that the drought resilience of bromegrass may be linked to increased root growth during the early vegetative stages, which potentially facilitates improved P acquisition. However, further validation through long-term field experiments is needed. The insights from this study are potentially valuable for use in shaping plant breeding programs by revealing the plant adaptation mechanisms for both P and water absorption.
Reducing phosphate fertilizer inputs while increasing food nutritional quality has been posited as a major challenge to decrease human undernourishment and ensure food security. In this context, ...quinoa has emerged as a promising crop due to its ability to tolerate different stress conditions and grow in marginal soils with low nutrient content, in addition to the exceptional nutritional quality of its grains. However, there is scarce information about the phosphorus acquisition capacity of quinoa roots. This work aimed to provide new insights into P acquisition and functional root traits, such as root biomass, rhizosphere pH, carboxylate exudation, and acid phosphatase activity of thirty quinoa genotypes grown under P limiting conditions (7 mg P kg
). Significant genotypic variation was observed among genotypes, with average P accumulation ranging from 1.2 to 11.8 mg. The shoot biomass production varied more than 14 times among genotypes and was correlated with the P accumulation on shoots (r = 0.91). Despite showing high variability in root traits, only root biomass production highly correlated with P acquisition (r = 0.77), suggesting that root growth/morphology rather than the measured biochemical activity possesses a critical role in the P nutrition of quinoa.
The COVID-19 pandemic was initiated by the rapid spread of a SARS-CoV-2 strain. Though mainly classified as a respiratory disease, SARS-CoV-2 infects multiple tissues throughout the human body, ...leading to a wide range of symptoms in patients. To better understand how SARS-CoV-2 affects the proteome from cells with different ontologies, this work generated an infectome atlas of 9 cell models, including cells from brain, blood, digestive system, and adipocyte tissue. Our data shows that SARS-CoV-2 infection mainly trigger dysregulations on proteins related to cellular structure and energy metabolism. Despite these pivotal processes, heterogeneity of infection was also observed, highlighting many proteins and pathways uniquely dysregulated in one cell type or ontological group. These data have been made searchable online via a tool that will permit future submissions of proteomic data ( https://reisdeoliveira.shinyapps.io/Infectome_App/ ) to enrich and expand this knowledgebase.
The effects of rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve remain uncertain.
In this randomized trial, we compared rivaroxaban (20 mg once daily) with ...dose-adjusted warfarin (target international normalized ratio, 2.0 to 3.0) in patients with atrial fibrillation and a bioprosthetic mitral valve. The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months.
A total of 1005 patients were enrolled at 49 sites in Brazil. A primary-outcome event occurred at a mean of 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (difference calculated as restricted mean survival time, 7.4 days; 95% confidence interval CI, -1.4 to 16.3; P<0.001 for noninferiority). Death from cardiovascular causes or thromboembolic events occurred in 17 patients (3.4%) in the rivaroxaban group and in 26 (5.1%) in the warfarin group (hazard ratio, 0.65; 95% CI, 0.35 to 1.20). The incidence of stroke was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (hazard ratio, 0.25; 95% CI, 0.07 to 0.88). Major bleeding occurred in 7 patients (1.4%) in the rivaroxaban group and in 13 (2.6%) in the warfarin group (hazard ratio, 0.54; 95% CI, 0.21 to 1.35). The frequency of other serious adverse events was similar in the two groups.
In patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months. (Funded by PROADI-SUS and Bayer; RIVER ClinicalTrials.gov number, NCT02303795.).
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