Biology subjects

Salvador, J.

Publications and source records attributed to Salvador, J..

5 recordsLinked to original sources

bioRxiv2026

MaRNAV-1 infection of Plasmodium vivax is associated with increased parasite transmission and host inflammatory responses

MaRNAV-1 is an RNA virus recently identified in Plasmodium vivax-infected samples, but definitive evidence that it infects the parasite and influences malaria pathogenesis remains unknown. Here, we demonstrate that MaRNAV-1 is an intracellular virus that is present in P. vivax at various stages of its life cycle, including blood, sporozoite, and liver stages. Viral prevalence varied geographically between Cambodian and Ethiopian parasites. MaRNAV-1 presence and load were positively associated with parasite transmission potential, as reflected by increased gametocyte abundance and higher oocyst prevalence and intensity in membrane feeding assays. MaRNAV-1 loads were higher in symptomatic compared to asymptomatic infections, and higher MaRNAV-1 loads were associated with elevated body temperature, independently of parasitemia. MaRNAV-1 infection elicits an antibody response and is associated with dendritic cell activation, a shift from Th2 to a Th1-driven immune response, and an increased frequency of double-negative B cells. Accordingly, MaRNAV-1-infected patients had higher concentrations of circulating cytokines, such as IFN-{gamma}, CXCL10, IL-1RA, and IL-6, independently of parasitemia. Together, these findings demonstrate that MaRNAV-1 is a genuine parasite-infecting virus associated with increased parasite transmission potential and with modulation of clinical outcomes in, and host immune response to, P. vivax infections. Our study broadens the conventional view of host-pathogen interactions in malaria by revealing complex virus-parasite-host relationships.

microbiology↗

bioRxiv2024

Spatiotemporal dynamics of primary and motile cilia throughout lung development

Cilia are specialized structures found on a variety of mammalian cells, with variable roles in the transduction of mechanical and biological signals (by primary cilia, PC), as well as the generation of fluid flow (by motile cilia). Their critical role in the establishment of a left-right axis in early development is well described, as is the innate immune function of multiciliated upper airway epithelium. By contrast, the dynamics of ciliary status during organogenesis and postnatal development is largely unknown. In this study, we define the progression of ciliary status within the endothelium, epithelium, and mesenchyme of the lung. Remarkably, we find that endothelial cells (ECs) lack PC at all stages of development, except in low numbers in the most proximal portions of the pulmonary arteries. In the lung epithelium, a proximodistal ciliary gradient is established over time, as the uniformly mono-ciliated epithelium transitions into proximal, multiciliated cells, and the distal alveolar epithelium loses its cilia. Mesenchymal cells, interestingly, are uniformly ciliated in early development, but with restriction to PDGFR+ fibroblasts in the adult alveoli. This dynamic process in multiple cellular populations both challenges prior assertions that PC are found on all cells, and highlights a need to understand their spatiotemporal functions. HighlightsO_LIPrimary cilia are found broadly throughout early embryonic tissues. C_LIO_LIPrimary cilia are observed in both epithelial and mesenchymal cells in the early lung. C_LIO_LIPulmonary endothelial cells largely do not possess primary cilia during embryonic development. C_LIO_LIDifferential multiciliation and loss of epithelial cilia in a proximal-distal axis. C_LIO_LIMaintenance of cilia in adult pulmonary PDGFR+ fibroblasts. C_LI

developmental biology↗

bioRxiv2024

The moon's influence on the activity of tropical forest mammals

Changes in lunar illumination alter the balance of risks and opportunities for animals at night, influencing activity patterns and species interactions. Our knowledge about behavioral responses to moonlight is incomplete, yet it can serve to assess and predict how species respond to environmental changes such as light pollution or loss of canopy cover. As a baseline, we wish to examine if and how wildlife responds to the lunar cycle in some of the darkest places inhabited by terrestrial mammals: the floors of tropical forests. We quantified the prevalence and direction of activity responses to the moon in tropical forest mammal communities. Using custom Bayesian multinomial logistic regression models, we analyzed long-term camera trapping data on 88 mammal species from 17 protected forests on three continents. We also tested the hypothesis that nocturnal species are more prone to avoiding moonlight, as well as quantified diel activity shifts in response to moonlight. We found that, apparent avoidance of moonlight (lunar phobia, 16% of species) is more common than apparent attraction (lunar philia, 3% of species). The three species exhibiting lunar philia followed diurnal or diurnal-crepuscular activity patterns. Lunar phobia, detected in 14 species, is more pronounced with higher degree of nocturnality, and is disproportionately common among rodents. Strongly lunar phobic species were less active during moonlit nights, which in most cases also decreases their total daily activity. Our findings indicate that moonlight influences animal behavior even beneath the forest canopy. This suggests that such impacts may be exacerbated in degraded and fragmented forests. Additionally, the effect of artificial light on wild communities is becoming increasingly apparent. Our study offers empirical data from protected tropical forests as a baseline for comparison with more disturbed areas, together with a robust approach for detecting activity shifts in response to environmental change. Open Research statement: The data and code for performing the analyses described in this article are available at https://github.com/richbi/TropicalMoon.

ecology↗

bioRxiv2021

Transcriptional evaluation of the ductus arteriosus at the single-cell level uncovers a requirement for vimentin for complete closure

OBJECTIVEFailure to close the ductus arteriosus immediately post-birth, patent ductus arteriosus (PDA), accounts for up to 10% of all congenital heart defects. Despite significant advances in PDA management options, including pharmacological treatment targeting the prostaglandin pathway, a proportion of patients fail to respond and must undergo surgical intervention. Thus, further refinement of the cellular and molecular mechanisms that govern vascular remodeling of this vessel is required. APPROACH AND RESULTSAs anticipated, single-cell RNA sequencing on the ductus arteriosus in mouse embryos at E18.5, P0.5, and P5, revealed broad transcriptional alterations in the endothelial, smooth muscle, and fibroblast cell compartments. Making use of these data sets, vimentin emerged as an interesting candidate for further investigation. Subsequent studies demonstrated that, in fact, mice with genetic deletion of vimentin fail to complete vascular remodeling of the ductus arteriosus, as per presence of a functional lumen. CONCLUSIONSThrough single-cell RNA-sequencing and by tracking closure of the ductus arteriosus postnatally in mice, we uncovered the unexpected contribution of vimentin in driving complete closure of the ductus arteriosus potentially through regulation of the Notch signaling pathway. HIGHLIGHTSO_LISingle-cell RNA-sequencing on the ductus arteriosus at E18.5, P0.5, and P5 reveals how the ductus arteriosus undergoes drastic transcriptional changes at the single-cell level. C_LIO_LIEndothelial cells increase levels of Vimentin, Notch1 and Jag1 transcripts soon after birth (P0.5), concurrent with ductus arteriosus closure. C_LIO_LILoss of vimentin, the major intermediate filament protein of endothelial cells, prevents proper permanent closure of the ductus arteriosus. C_LI

developmental biology↗

bioRxiv2018

Schlafen 11 Restricts Flavivirus Replication

Schlafen 11 (Slfn11) is a ubiquitously expressed interferon stimulating gene (ISG) that controls synthesis of proteins by regulating tRNA abundance. Likely through this mechanism, Slfn11 has previously been shown to impair human immunodeficiency virus 1 (HIV-1) infection and the expression of codon-biased open reading frames. Because replication of positive-sense single-stranded RNA [(+)ssRNA viruses] requires the immediate translation of the incoming viral genome whereas negative sense, single stranded [(-)ssRNA] viruses carry at infection an RNA replicase that makes multiple translation competent copies of the incoming viral genome, we reasoned that (+)ssRNA viruses will be more sensitive to the effect of Slfn11 on protein synthesis than (-)ssRNA viruses. To evaluate this hypothesis, we tested the effects of Slfn11 on the replication of a panel of ssRNA viruses in the human glioblastoma cell line A172, which naturally expresses Slfn11. Depletion of Slfn11 in this cell line significantly increased the replication of (+)ssRNA viruses from the Flavivirus family, including West Nile (WNV), dengue (DENV), and Zika virus (ZIKV) but had no significant effect on the replication of the (-)ssRNA viruses vesicular stomatitis (VSV, Rhabdoviridae family) and Rift Valley fever (RVFV, Phenuiviridae family). Despite that WNV titers in Slfn11-deficient cells were almost 100-fold higher than in cells expressing this protein; they produced approximately two-fold less viral particles, as determined by PCR-based quantification of virion-associated WNV RNA in the cell culture supernatant. These data indicated that Slfn11 impairs WNV fitness but does not affect other steps of the viral life cycle including entry, viral RNA replication and translation, and budding. Similarly to the proposed anti-HIV-1 mechanism of Slfn11, this protein prevented WNV-induced down-regulation of a subset of tRNAs implicated in the translation of 19% of the viral polyprotein. Importantly, we provided evidence suggesting that the broad anti-viral activity of Slfn11 requires other cellular proteins, since overexpression of Slfn11 in cells that naturally lack the expression of this protein, did not impair WNV or HIV-1 infection. In summary, this study demonstrates that Slfn11 restricts flaviviruses replication by impairing viral fitness.\n\nAUTHOR SUMMARYThe host targets mechanisms that viruses have evolved to optimize replication. We provide evidence that the cellular protein Schlafen 11 (Slf11) impairs replication of flaviviruses, including West Nile (WNV), dengue (DENV), and Zika virus (ZIKV). However, replication of single-stranded, negative RNA viruses was not affected. Specifically, Slf11 decreases the fitness of WNV potentially by preventing virus-induced modifications of the host tRNA repertoire that could lead to enhanced viral protein folding. Furthermore, we demonstrated that Slf11 is not the limiting factor of this novel broad anti-viral pathway.

microbiology↗