Biology subjects

Sousa, D.

Publications and source records attributed to Sousa, D..

5 recordsLinked to original sources

bioRxiv2025

The paradoxical impact of drought on West Nile virus risk: insights from long-term ecological data

Mosquito-borne diseases are deeply embedded within ecological communities, with environmental changes - particularly climate change - shaping their dynamics. Increasingly intesense droughts across the globe have profound implications for the transmission of these diseases, as drought conditions can alter mosquito breeding habitats, host-seeking behaviors, and mosquito-host contact rates. To quantify the effect of drought on disease transmission, we use West Nile virus (WNV) as a model system and leverage a robust mosquito and virus dataset consisting of over 500,000 trap nights collected from 2010-2023, spanning a historic drought period followed by atmospheric rivers. We pair this surveillance dataset with a novel modeling approach that incorporates monthly changes in bird host community competence, along with drought conditions, to estimate the effect of drought severity on WNV risk using panel regression models. Our results show that while drought decreases mosquito abundances, it paradoxically increases WNV infection rates. This counterintuitive pattern likely stems from reduced water availability, which concentrates mosquitos and pathogen-amplifying bird hosts around limited water sources, thereby increasing disease transmission risk. However, the magnitude of the effect depends critically on mosquito species, suggesting species-specific behavioral traits are key to understanding the effect of drought on mosquito-borne disease risk across real landscapes.

ecology↗

bioRxiv2022

Scalable early detection of grapevine virus infection with airborne imaging spectroscopy

Viral diseases, including Grapevine Leafroll-associated Virus Complex 3 (GLRaV-3), cause $3 billion in damages and losses to the United States wine and grape industry annually. GLRaV-3 has a well-studied, year-long latent period in which vines are infectious but do not yet display visible symptoms, making it an ideal model pathosystem to evaluate the scalability of symptomatic and asymptomatic imaging spectroscopy-based disease detection. Plant disease causes physiological and chemical changes to occur locally and systemically throughout a plant, which imaging spectroscopy can detect both directly and indirectly. Reliable and scalable disease detection during the latent period would greatly reduce management costs, as current detection methods are entirely ground-based, labor-intensive, and expensive. Here, we use data collected in September 2020 by the NASA Airborne Visible/Infrared Imaging Spectrometer Next Generation (AVIRIS-NG) to detect GLRaV-3 in Cabernet Sauvignon grapevines in Lodi, CA. During September 2020 and 2021, industry collaborators scouted 317 acres of Vitis vinifera winegrapes for visible disease symptoms, and collected a subset for confirmation molecular testing at a commercial facility. Grapevines identified as visibly diseased in 2021 were assumed to have been latently infected (asymptomatic) during the September 2020 AVIRIS-NG data collection. We combined random forest with synthetic minority oversampling technique (SMOTE) to train multiple spectral models able to distinguish between non-infected (NI) and GLRaV-3-infected grapevines. We observed clear spectral differences that allowed for differentiation between NI and GLRaV-3 infected vines both pre- and post-symptomatically at 1m through 5m resolution. Our two best performing models had 87% accuracy (0.73 Kappa) distinguishing between NI and asymptomatic (aSy), and 85% accuracy (0.71 Kappa) distinguishing between NI and (aSy + symptomatic [Sy]) respectively. We hypothesize these spectral differences are linked to changes in overall plant physiology induced by disease, as visible foliar symptoms were restricted to the lower canopy. HighlightsO_LIAirborne imaging spectroscopy allows for scalable early-detection models of grapevine leafroll-associated virus complex 3 (GLRaV-3). C_LIO_LIRandom Forest based models trained with scouting ground data and imaging spectroscopy are accurate up to 5 meter but perform best at 3 meter spatial resolution. C_LIO_LIGLRaV-3 detection via imaging spectroscopy will not replace existing field scouting strategies or molecular testing but supplement by allowing for more strategic resource deployment to improve the overall financial, environmental, and societal sustainability of winegrape production. C_LI

pathology↗

bioRxiv2022

Generation and Maturation of Human iPSC-derived Cardiac Organoids in Long Term Culture

Cardiovascular diseases remain the leading cause of death worldwide; hence there is an increasing focus on developing physiologically relevant in vitro cardiovascular tissue models suitable for studying personalized medicine and pre-clinical tests. Despite recent advances, models that reproduce both tissue complexity and maturation are still limited. We have established a scaffold-free protocol to generate multicellular, beating and self-organized human cardiac organoids (hCO) in vitro from hiPSCs that can be cultured for long term. This is achieved by differentiation of hiPSC in 2D monolayer culture towards cardiovascular lineage, followed by further aggregation on low-attachment culture dishes in 3D. The generated human cardiac organoids (hCOs) containing multiple cell types that physiologically compose the heart, gradually self-organize and beat without external stimuli for more than 50 days. We have shown that 3D hCOs display improved cardiac specification, survival and maturation as compared to standard monolayer cardiac differentiation. We also confirmed the functionality of hCOs by their response to cardioactive drugs in long term culture. Furthermore, we demonstrated that hCOs can be used to study chemotherapy-induced cardiotoxicity. This study could help to develop more physiologically-relevant cardiac tissue models, and represent a powerful platform for future translational research in cardiovascular biology.

cell biology↗

bioRxiv2018

Osteoclasts control sensory neurons axonal growth through epidermal growth factor receptor signaling

The patterning of peripheral innervation is accomplished through the tissue expression, in specific space and timeframe, of attractive or repulsive axonal guidance cues. At the bone microenvironment, neurotrophic factors such as nerve growth factor, brain-derived neurotrophic factor, vascular endothelial growth factor, netrin-1 and others were described to regulate the nerve ingrowth towards the bone compartment, by acting directly on receptors expressed at the nerve terminals. Interestingly, besides the gradient of soluble factors, neurons were described to be responsive to extracellular vesicles (EV) derived from myelinating cells and mesenchymal stem cells. Here we provide evidence on a new mechanism by which peripheral innervation can be coordinated. We show that sensory nerves outgrowth and electric signal propagation are dependent on the EV secreted by osteoclasts, the bone resorbing cells. Furthermore, we demonstrate that the axonal sprouting is achieved through the activation of epidermal-growth factor receptor (EGFR) family signaling pathway. We proved that the EV-depleted osteoclast secretome leads to a significant decrease of neurons firing rate and axonal sprouting, concomitant with a decrease of EGFR/ErbB2 activation levels. Excitingly, the proteomic analysis of the osteoclast-derived EV cargo shows a high correlation with synaptic components reinforcing the role on sensory neurons/osteoclast crosstalk. Our findings that osteoclast-derived EV hold effect in axonal outgrowth, contributing actively to the dynamics of the sensory neurons sprouting and electrophysiology, is a step toward unraveling target mechanisms to control electrical signal propagation and nerve fibers sprouting and consequently open new avenues for the development of innovative therapies to control bone pain. Significance StatementSensory nerve fibers sprouting in bone pathologies is highly associated with pain. Thus, understanding the mechanisms behind sensory nerves ingrowth, sprouting and electrical activity, within the bone compartment, is essential for improving the strategies to overcome pain in bone disorders. We provide a new mechanism on the sensory nerves sprouting, indicating that the effect is dependent on the extracellular vesicles (EV) released by osteoclasts, through the epidermal growth factor receptor family targeting, by integrin independent pathways. We show different electrophysiology patterns being triggered in the presence of osteoclasts secretome and the abolishment of sensory neurons firing rate in EV-depleted conditions. Overall, our results elucidate novel mechanisms on the peripheral nerves sprouting, essential for pursuing new targets for bone pain therapies.

cell biology↗

bioRxiv2016

Mechanism of ribosome rescue by ArfA and RF2

ArfA rescues ribosomes stalled on truncated mRNAs by recruiting the release factor RF2, which normally binds stop codons to catalyze peptide release. We report two 3.2-[A] resolution cryo-EM structures - determined from a single sample - of the 70S ribosome with ArfA*RF2 in the A site. In both states, the ArfA C-terminus occupies the mRNA tunnel downstream of the A site. One state contains a compact inactive RF2 conformation, hitherto unobserved in 70S termination complexes. Ordering of the ArfA N-terminus in the second state rearranges RF2 into an extended conformation that docks the catalytic GGQ motif into the peptidyl-transferase center. Our work thus reveals the structural dynamics of ribosome rescue. The structures demonstrate how ArfA \"senses\" the vacant mRNA tunnel and activates RF2 to mediate peptide release without a stop codon, allowing stalled ribosomes to be recycled.

biochemistry↗