Biology subjects

Sousa, L. P.

Publications and source records attributed to Sousa, L. P..

4 recordsLinked to original sources

bioRxiv2026

Sugarcane's drought memory legacy: how past stress shapes future resilience

Plants frequently experience recurrent drought events separated by periods of rehydration. Although drought imposes strong constraints on plant physiology, prior exposure may alter subsequent stress responsiveness through memory-based mechanisms. Here, we investigated whether recurrent drought at distinct developmental stages establishes stress memory in sugarcane and whether this response persists across vegetative propagation. Two genotypes contrasting in drought tolerance and productivity (IACCTC07-8008 and IACSP95-5000, respectively) were grown under greenhouse conditions and subjected to three drought cycles imposed either at tillering or maturation stage. Gas exchange, photochemical performance, leaf water status, primary metabolite profile, and growth traits were assessed across cycles, and vegetative propagules were subsequently evaluated under renewed drought. The first drought cycle imposed strong limitations on carbon assimilation and photochemistry in both genotypes and developmental stages. However, subsequent cycles resulted in attenuated reductions in A and g, improved intrinsic water use efficiency, and partial stabilization of PSII performance, indicating a modified stress-response trajectory. Young plants displayed earlier improvements (from the second cycle), whereas in mature plants this shift was evident mainly during the third cycle. Recurrent drought promoted sustained reorganization of amino acid, carbohydrate, organic acid and polyol metabolism alongside increased root biomass and higher relative water content during later cycles. Importantly, propagules derived from drought-conditioned plants exhibited faster recovery of photosynthetic performance and reduced cumulative physiological impairment under renewed drought, despite showing similar stress sensitivity at maximum water deficit. This persistence of enhanced recovery capacity across vegetative propagation indicates that drought-induced memory was maintained beyond the initially stressed plants. Together, our findings demonstrate that recurrent drought establishes a metabolically imprinted state in clonal sugarcane, integrating physiological adjustment, metabolic reprogramming, and whole-plant acclimation. These results highlight the potential of stress memory as a mechanism supporting resilience in perennial crops exposed to increasingly recurrent drought events.

plant biology↗

bioRxiv2025

P2Y12-P-Selectin Mediated Platelet Activation Drives Dengue-Associated Thrombocytopenia

Dengue virus (DENV) infection frequently causes thrombocytopenia, a hallmark of severe disease. The underlying mechanisms of this condition remain incompletely understood. Using a murine model that mirrors human hematologic and inflammatory responses, we show that DENV impairs megakaryopoiesis, causing necrotic loss of bone marrow megakaryocytes and compensatory thrombopoietin elevation. Megakaryocyte-derived platelets exhibit mitochondrial dysfunction and phosphatidylserine exposure, consistent with apoptosis. Systemically, DENV drives P-selectin- dependent platelet activation and platelet-monocyte aggregates, accompanied by increased plasmatic chemokines (CXCL4, CCL5, CXCL1) and vascular leakage in target organs such as liver and lungs, reflecting heightened thromboinflammation. Pharmacologic blockade of P-selectin or inhibition of P2Y12 with clopidogrel restored platelet counts, rescued megakaryocyte numbers, and reduced systemic inflammation. Collectively, these findings demonstrate for the first time in an in vivo model that DENV-induced thrombocytopenia arises from combined megakaryocyte impairment and platelet hyperactivation and highlight platelet-targeted interventions as potential therapeutic strategies. KEY POINTSO_LIDENV disrupts platelet production and survival via megakaryocyte necrosis and intramedullary platelet apoptosis, driving thrombocytopenia. C_LIO_LIDENV triggers thrombocytopenia via P-selectin platelet activation; blocking it with antibody P-selectin or clopidogrel reduces inflammation. C_LI

immunology↗

bioRxiv2025

Cyclodextrin-Based Delivery of the Annexin A1 Mimetic Peptide Ac2-26 Enhances Anti-Inflammatory Effects and PreventsDengue-Induced Lethality in Combination with AntiviralTherapy

Severe dengue is characterized by systemic inflammation, cytokine storm, vascular leakage, and hemorrhagic manifestations, largely driven by the host immune response to dengue virus (DENV) infection. Despite its burden, no licensed antivirals or host-directed therapies are currently available. Our group has previously identified Annexin A1 (AnxA1) as an endogenous regulator of inflammation in dengue. Treatment with the AnxA1 peptidomimetic, Ac2-26, improved clinical outcomes in murine models of severe dengue by promoting resolution of inflammation without affecting viral control. To explore new delivery strategies, we developed a novel formulation of Ac2-26 complexed with hydroxypropyl-{beta}-cyclodextrin (CDX-Ac2-26). In DENV-2-infected A129 mice, both intraperitoneal and oral CDX-Ac2-26 improved clinical scores and reversed thrombocytopenia. Notably, CDX-Ac2-26 reduced mast cell degranulation, MCPT-1 plasma levels, and CCL2 expression in spleen, with no effect on viral titers, indicating a host-targeted mechanism and overcoming the anti-inflammatory effects of the free peptide. Intraperitoneal administration achieved the same efficacy as oral dosing with only one-third of the dose. Importantly, the combination of CDX-Ac2-26 with the antiviral nucleotide analog sofosbuvir fully prevented disease and mortality in infected mice, highlighting a combinatorial effect between host-directed and antiviral therapies. These findings underscore the therapeutic potential of anti-inflammatory/pro-resolving strategies in severe dengue and support the development of CDX-Ac2-26 as a novel adjunctive treatment. Combining anti-inflammatory and antiviral approaches may enhance efficacy and reduce treatment-associated toxicity, offering a promising path for clinical translation. What is already known on this topic?O_LIPlasma levels of Annexin A1 are inversely correlated with the severity of clinical outcomes in dengue virus infection. C_LIO_LIThe Annexin A1 peptidomimetic Ac2-26 exhibits anti-inflammatory and pro-resolving effects against severe dengue in a murine model. C_LI What does this study add?O_LIThe Ac2-26-cyclodextrin complex enhances the anti-inflammatory effects of the peptide against dengue virus infection, allowing for lower dosing and oral administration. C_LIO_LIThe administration of the CDX-Ac2-26 with a nucleoside analog antiviral exhibits a combinatorial effectt, providing complete protection against the lethal outcome of severe dengue. C_LI What is the clinical significance?O_LICurrent dengue treatment relies on symptomatic management, as no directed anti-inflammatory agents or antivirals are currently available. We have identified a novel host-targeted strategy to resolve the disease. C_LIO_LIOur findings strongly support CDX-Ac2-26 as a promising adjunctive treatment strategy in combination with antiviral therapy for severe dengue, highlighting the potential of combinatorial approaches. C_LI

immunology↗

bioRxiv2021

Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease

Host immune responses contribute to dengues pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise the disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known to counterbalance overexuberant inflammation and mast cell (MC) activation. We hypothesised that inadequate AnxA1 engagement underlies the cytokine storm and vascular pathologies associated with dengue disease. Levels of AnxA1 were examined in the plasma of dengue patients and infected mice. Immunocompetent, IFN/{beta}R-/-, AnxA1-/- and FPR2/ALX-/- mice were infected with Dengue virus (DENV) and treated with the AnxA1 mimetic peptide Ac2-26 for analysis. Additionally, the effect of Ac2-26 on DENV-induced MC degranulation was assessed in vitro and in vivo. We observed that circulating levels of AnxA1 were reduced in dengue patients and DENV-infected mice. While the absence of AnxA1 or its receptor FPR2/ALX aggravated illness in infected mice, treatment with AnxA1 agonistic peptide attenuated disease manifestations. Both clinical outcomes were attributed to modulation of DENV-mediated viral load-independent MC degranulation. We have thereby identified that altered levels of the pro-resolving mediator AnxA1 are of pathological relevance in DENV infection, suggesting FPR2/ALX agonists as a therapeutic target for dengue disease.

microbiology↗