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Campos, D.

Publications and source records attributed to Campos, D..

11 recordsLinked to original sources

Social copying drives spatial allocation in gregarious herbivores

Resting patch selection in free-ranging social cattle (Bos taurus) inhabiting steep, rugged, mountain valleys is critical, because the recurrent use of flatter resting patches may reduce energetic costs and enhance fitness prospects. As these patches may constitute a limited resource, understanding their pattern of use dynamics may help explain resting patch selection. We therefore combine empirical data with a theoretical modelling framework to investigate the processes underlying resting patch selection. Using high-resolution GPS tracking data from 144 cows collected over three seasons, we identify several recurrently used resting patches located on significantly gentler slopes than expected in the valley. We then build a simple, memory-free agent-based model, which suggests that the dynamics of resting patch selection arise from social copying and, to a lesser extent, from individual heterogeneity. The model quantitatively reproduces three empirical observables: a slowing (sub-linear) discovery of new sites through time, heterogeneous occupancy across resting patches and similarity in patch use among individuals. These results suggest that collective dynamics in social species can emerge primarily from a simple social mechanism with weaker modulation from inter-individual heterogeneity, such as age, without explicitly incorporating individual memory to reproduce the aggregate patterns.

ecology↗

Dynamic Workforce Modulation and Foraging Efficiency in Eusocial Insect Colonies

Understanding the fitness advantages conferred by eusociality remains a central challenge in behavioral ecology. One promising approach is to identify collective strategies that shift efficiency within social groups. Here, we test the hypothesis that reserve workforces in eusocial insect colonies represent an adaptive mechanism that enhances flexibility and foraging efficiency under fluctuating environmental conditions. We examine how such reserve workers modulate the departure and return rates of foragers and how these time-dependent dynamics shape the colonys overall energetic balance. By integrating an energetic-balance framework with stochastic search simulations inspired by empirical results from Aphaenogaster senilis, we quantify the energetic requirements for colony viability, incorporating energy intake, search costs, and basal metabolic demands. Our results show that as colonies grow, maintaining a positive energy balance requires a disproportionately larger relative workforce. By modulating departure and return rates over time, colonies control the synchrony of their collective search and efficiently activate or suppress their reserve workforce to scale foraging effort as needed. These findings suggest that the "lazy" or weakly engaged workers commonly observed in large colonies function as an essential reserve that stabilizes colony energetics and enhances responsiveness. Together, our results provide a functional explanation for sublinear metabolic scaling in eusocial groups and highlight workforce modulation as a key factor underlying their energetic stability and evolutionary success.

ecology↗

Potent broad-spectrum antiviral activity of the marine natural product Plitidepsin

Viruses pose a critical global health threat, yet therapeutic options remain limited. Finding drugs with broad-spectrum antiviral activity is essential to confront this threat. Here, we investigated whether plitidepsin, a marine-derived anticancer drug targeting the host eukaryotic elongation factor 1A (eEF1A), has such broad-spectrum activity. Using in vitro infection models and complementary assays (MTT, plaque-forming assays, RT-qPCR, Western blot, flow cytometry), we demonstrated that plitidepsin exhibits potent dose-dependent antiviral activity against Mayaro virus (MAYV) and Chikungunya virus (CHIKV). The compound achieved 4-6 log10 reduction in viral titers at nanomolar concentrations across multiple cell lines and viral strains. Plitidepsin protected human dermal fibroblasts from viral cytopathic effects and disrupted both entry and post-entry replication stages by suppressing viral protein expression (E1, nsP1) and RNA synthesis. The compound also demonstrated antiviral activity against other medically important arboviruses, including Una, Punta Toro, Zika, and Oropouche viruses, as well as RNA and DNA viruses such as influenza A virus, vesicular stomatitis virus, and human cytomegalovirus. These findings establish plitidepsin as a potent host-directed antiviral agent with reduced likelihood of resistance development and therapeutic potential against multiple viral families.

microbiology↗

Reg3β removes aged neutrophils after myocardial infarction

AO_SCPLOWBSTRACTC_SCPLOWRecruitment and resolution of immune cell accumulation after myocardial infarction (MI) is critical for effective wound healing and prevention of maladaptive remodeling. Numerous signals are known to recruit neutrophils, critical drivers of inflammation, but knowledge about signals containing and resolving their accumulation is limited. We discovered that Regenerating-islet derived protein 3 beta (REG3{beta}) limits the persistence of neutrophils after MI, thereby promoting resolution of inflammation. REG3{beta} selectively binds to aged and hyperactive neutrophils and induces rapid cell death, enabling clearance via macrophage-mediated efferocytosis. Selective binding of REG3{beta} is achieved by interaction with paucimannosylated proteins that translocate from azurophile granules to the plasma membrane in an activation- and age-dependent manner. Endocytotic uptake and accumulation of REG3{beta} in lysosomes initiates programmed cell death of neutrophils via lyosomal membrane permeabilization and release of cathepsins. Our work establishes REG3{beta} as a local immune checkpoint essential for neutrophil resolution and cardiac repair.

immunology↗

Broad-spectrum antiviral activity of the synthetic rocaglate zotatifin against multiple viruses

Viruses pose a significant threat to global public health, yet therapeutic options are limited. Zotatifin, a synthetic rocaglate, targets eukaryotic initiation factor 4A (eIF4A), thereby inhibiting viral protein synthesis and triggering an interferon response. Whether zotatifin exhibits broad-spectrum antiviral activity is unknown. Here we evaluated zotatifins cytotoxicity using the MTT method and its antiviral activity using plaque-forming assays, Western blot analysis, immunofluorescence, and flow cytometry across multiple cell lines and virus strains. Zotatifin demonstrated better tolerability than rocaglates rocaglamide A and CR-1-31-B. The compound exhibited potent, dose-dependent inhibition of the Mayaro virus, achieving greater than a 4-log reduction in viral titers at a 50 nM dose, regardless of the cell line or virus strain tested. In addition, zotatifin was effective to inhibit multiple arboviruses (Chikungunya, Una, and Zika), influenza A virus, vesicular stomatitis virus, and vaccinia virus. Zotatifin down-regulated viral protein synthesis for all viruses tested and analysis of gene expression using RT-qPCR revealed activation of the type I interferon pathway in zotatifin-treated cells. Taken together, these results suggest that zotatifin exhibits broad-spectrum antiviral activity against five virus families, likely via several molecular mechanisms. This work supports the potential therapeutic use of zotatifin as a pan-antiviral drug in humans.

microbiology↗

Differential susceptibility of human microglia HMC3 cells and brain microvascular endothelial HBEC-5i cells to Mayaro and Una virus infection

Mayaro (MAYV) and Una (UNAV) are emerging alphaviruses circulating in the Americas. Earlier reports have revealed that MAYV infects different human cell lines, including synovial and dermal fibroblasts, chondrocytes, osteoblasts, astrocytes and pericytes, as well as neural progenitor cells. In this study we evaluated the susceptibility of immortalized human microglia HMC3 cells and brain microvascular endothelial HBEC-5i cells to MAYV and UNAV infection. Cytopathic effects, cell viability, viral progeny yields, and the presence of E1 and nsP1 proteins in HMC3 and HBEC-5i cells infected with several MAYV or UNAV strains were assessed using an inverted microscope, MTT assay, plaque-forming assays, and immunofluorescence or Western blot, respectively. Finally, the expression of immune response genes was analyzed using qRT-PCR. MAYV and UNAV demonstrated strong cytopathic effects and significantly reduced cell viability in HMC3 cells. Moreover, the HMC3 cells were efficiently infected regardless of the virus strains tested, and E1 and nsP1 viral proteins were detected. In contrast, only MAYV appeared to infect HBEC-5i cells, and minimal effects on cell morphology or viability were observed. Furthermore, the MAYV titer and viral protein levels were substantially lower in the infected HBEC-5i cells when compared to those of the infected microglia cells. Finally, unlike UNAV, MAYV elicited a strong expression of specific interferon-stimulated genes in microglia cells, along with pro-inflammatory cytokines implicated in the immune response. Collectively, these findings demonstrate that MAYV and UNAV are capable of infecting relevant human brain cells.

microbiology↗

Ghost fragment ions in structure and site-specific glycoproteomics analysis

Mass spectrometry (MS) can unlock crucial insights into the intricate world of glycosylation analysis. Despite its immense potential, the qualitative and quantitative analysis of isobaric glycopeptide structures remains one of the most daunting hurdles in the field of glycoproteomics. The ability to distinguish between these complex glycan structures poses a significant challenge, hindering our ability to accurately measure and understand the role of glycoproteins in biological systems. A few recent publications described the use of collision energy (CE) modulation to improve structural elucidation, especially for qualitative purposes. Different linkages of glycan units usually demonstrate different stabilities under CID/HCD fragmentation conditions. Fragmentation of the glycan moiety produces low molecular weight ions (oxonium ions) that can serve as a structure-specific signature for specific glycan moieties, however, specificity of these fragments has never been examined closely. Here, we investigated fragmentation specificity using synthetic stable isotope-labelled glycopeptide standards. These standards were isotopically labelled at the reducing terminal GlcNAc, which allowed us to resolve fragments produced by oligomannose core moiety and fragments generated from outer antennary structures. Our research identified the potential for false positive structure assignments due to the occurrence of "Ghost" fragments resulting from single glyco unit rearrangement or mannose core fragmentation within the collision cell. To mitigate this issue, we have established a minimal intensity threshold for these fragments to prevent the misidentification of structure-specific fragments in glycoproteomics analysis. Our findings provide a crucial step forward in the quest for more accurate and reliable glycoproteomics measurements. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/541150v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1a5bb21org.highwire.dtl.DTLVardef@1a09b5aorg.highwire.dtl.DTLVardef@137504borg.highwire.dtl.DTLVardef@78831e_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

Hypotrochoidal scaffolds for cartilage regeneration

The main function of articular cartilage is to provide a low friction surface and protect the underlying subchondral bone. The extracellular matrix composition of articular cartilage mainly consists of glycosaminoglycans and collagen type II. Specifically the collagen type II organization has a characteristic organization in three distinct zones; (1) the superficial zone which has collagen fibers oriented parallel to the surface, (2) the intermediate zone where there is no predominant orientation, and (3) the deep zone which shows a high orientation with fibers perpendicular to the underlying bone. Collagen type II fibers in these 3 zones take an arch-like organization that can be mimicked with segments of a hypotrochoidal curve. In this study, a script was developed that allowed the fabrication of scaffolds with a hypotrochoidal design. This design was investigated and compared to a regular 0-90 woodpile design. The results showed that the hypotrochoidal design was successfully fabricated. Micro-CT analyses divided the areas of the scaffold in their distinct zones. In addition, the mechanical analyses revealed that the hypotrochoidal design had a lower component Youngs modulus while the toughness and strain at yield were higher compared to the woodpile design. Fatigue tests showed that the hypotrochoidal design lost more energy per cycle due to the damping effect of the unique microarchitecture. Finite element analyses revealed that the hypotrochoidal design had an improved stress distribution compared to the 0-90 woodpile design due to the lower component stiffness. In addition, data from cell culture under dynamic stimulation demonstrated that the collagen type II deposition was improved in the hypotrochoidal design. Finally, Alcian blue staining revealed that the areas where the stress was higher during the stimulation produced more glycosaminoglycans. Our results highlight a new and simple scaffold design based on hypotrochoidal curves that could be used for cartilage tissue engineering.

bioengineering↗

Honokiol and alfa-Mangostin inhibit Mayaro virus replication by stimulating the type I interferon pathway

Mayaro virus (MAYV) is an emerging arbovirus with increasing circulation across the Americas. In the present study, we evaluated the potential antiviral activity of the following natural compounds against MAYV and other arboviruses: Sanguinarine, (R)-Shikonin, Fisetin, Honokiol, Tanshinone IIA and -Mangostin. Sanguinarine and Shikonin showed significant cytotoxicity, whereas Fisetin, Honokiol, Tanshinone IIA and -Mangostin were well-tolerated in all the cell lines tested. Honokiol and -Mangostin treatment protected Vero-E6 cells against MAYV-induced damage and resulted in a dose-dependent reduction in viral progeny yields for each of the MAYV strains and human cell lines assessed. Also, Honokiol and -Mangostin disrupted MAYV infection at different stages of the virus life cycle. Moreover, these compounds decreased Una, Chikungunya and Zika viral titers and downmodulated the expression of E1 and nsP1 viral proteins from MAYV, Una and Chikungunya. Finally, in Honokiol- and -Mangostin-treated cells, we observed an upregulation in the expression of type I interferon and specific interferon-stimulated genes, including IFN, IFN{beta}, MxA, ISG15, OAS2, MDA-5, TNF and IL-1{beta}, which may promote an antiviral cellular state. Our results indicate that Honokiol and -Mangostin present potential broad-spectrum activity against different arboviruses through a possible modulation of the interferon pathway.

microbiology↗

Targeting Host PIM Protein Kinases Reduces Mayaro Virus Replication

Mayaro virus (MAYV) manipulates cell machinery to successfully replicate. Thus, identifying host proteins implicated in MAYV replication, represents an opportunity to discover potential antiviral targets. PIM kinases are enzymes that regulate essential cell functions and also appear to be critical factors in the replication of certain viruses. In this study we explored the consequences of PIM kinase inhibition in the replication of MAYV and other arboviruses. Cytopathic effects or viral titers in samples from MAYV-, Chikungunya-, Una-or Zika-infected cells treated with PIM kinase inhibitors were evaluated using an inverted microscope or plaque-forming assays. The expression of viral proteins E1 and nsP1 in MAYV-infected cells was assessed using an immunofluorescence confocal microscope or Western blot. Our results revealed that PIM kinase inhibition partially prevented MAYV-induced cell damage and also promoted a decrease in viral titers for MAYV, UNAV and ZIKV. The inhibitory effect of PIM kinase blocking was observed for each of the MAYV strains tested and also occurred as late as 8 hpi. Finally, PIM kinase inhibition suppressed the expression of MAYV E1 and nsP1 proteins. Taken together, these findings suggest that PIM kinases could represent an antiviral target for MAYV and other arboviruses.

microbiology↗

Random searchers cope with cognitive errors and uncertainty better than path planners

There is a widespread belief in ecology that the capacity of animals to orchestrate systematic and planned paths should represent a significant benefit for efficient search and exploration. Within this view, stochasticity observed in real animal trajectories is mostly understood as undesirable noise caused by internal or external effects. Far less is known, however, about the case when cognitive errors and limitations inherent to living systems are explicitly put into play. Here we compare within this context the search efficiency of (i) walkers driven by Bayesian rules generating deterministic paths, (ii) standard random walkers, and (iii) human trajectories obtained from search experiments in a soccer field and on the computer screen. Our results clearly challenge the view that deterministic paths are generally better for exploration than random strategies, as the latter are more resilient to cognitive errors. Instead, we provide numerical and experimental evidence that stochasticity would provide living organisms with a sufficient and cognitively simple exploration solution to the problem of uncertainty.

ecology↗