Biology subjects

Cortez, M.

Publications and source records attributed to Cortez, M..

11 recordsLinked to original sources

bioRxiv2026

Alternative Host Traits and Transient Dynamics of Focal Host Infection Prevalence

Environmental changes driven by climate change and anthropogenic activity are altering the composition of host communities in host-pathogen systems through the loss or introduction of host species, which can impact disease levels in other host species. Although previous work has identified that host species that strongly or weakly spread disease are expected to increase or decrease disease levels in other hosts, respectively, it remains unclear how disease levels change in the transient period of host community composition changes. In this study, we analyze an ordinary differential equation model representing two hosts that share an environmentally-transmitted pathogen to identify how the disease and non-disease traits of a lost host impact disease levels in the remaining host. By simulating our model using parameter sets spanning a broad area of parameter space, we find that short- and long-term changes in focal host disease levels occur in the same direction when the two hosts have dissimilar abilities to spread disease, but that focal host disease levels can change nonmonotonically when hosts have similar abilities to spread disease and the lost host is a sufficiently strong competitor. Additionally, using both local and global sensitivity analysis, we identify that the lost host's birth rate, interspecific competitive ability, pathogen shedding rate, and pathogen uptake rate must be measured precisely when predicting the change in focal host disease levels, while precise measurement of the lost host's infection capacity, recovery rate, and disease mortality rate is only critical in some circumstances.

ecology↗

bioRxiv2026

Direct and indirect effects: estimating the contributions along individual pathways during transient dynamics

All species in a community directly and indirectly affect each other, often through many causal pathways. The effects along each pathway can vary in magnitude as densities fluctuate during transient dynamics. Quantifying the changes in these pathway-specific effects is important for understanding the drivers of population-level dynamics. I present two computational methods that decomposes the total effect of one species on another into contributions along individual pathways during transient dynamics. These methods yield insight into which processes and species interactions are the primary drivers of transient population-level dynamics and how the effects of individual pathways scale with the number of intermediary species, time length, and interspecific interaction strength. I apply the method to two parameterized models, answering questions about the magnitudes of top-down effects in an intraguild predation system and the mechanisms driving disease reduction in a host-parasite system, and how the answers change through time.

ecology↗

bioRxiv2025

A Conserved Domain of Cfap298 Governs Left-Right Symmetry Breaking in Vertebrates

Cfap298 is a highly conserved gene required for ciliary motility and dynein arm assembly. It plays a known role in Left-Right (LR) patterning in zebrafish and is linked to human ciliopathies. Here we describe a new Cfap298 mutant allele, Cfap298{Delta}3aa, which selectively interferes with LR axis establishment in mice. Mutant embryos display a range of laterality defects including situs solitus, situs inversus, and situs ambiguous, as indicated by abnormal heart, lung, and stomach positioning. At embryonic day 8.5, mutant embryos display abnormal Nodal, Pitx2, and Lefty1 expression patterns in the lateral plate mesoderm and midline, consistent with an early disruption in LR symmetry breaking. In mice, LR asymmetry is established by leftward fluid flow in the node, generated by planar-polarized cilia. Although cfap298 mutations are reported to affect cell polarity, we did not observe changes in cilia position, length, or planar cell polarity protein localization within the node, suggesting that Cfap298{Delta}3aafunctions at the level of cilia motility. Consistently, motile cilia lining the trachea of Cfap298{Delta}3aa mutants fail to beat. Expression of the Cfap298{Delta}3aa variant in zebrafish fails to rescue the LR defects of cfap298 (kurly) loss-of-function mutants. These results confirm that Cfap298 functions in LR axis formation in mammals and uncover a novel region of CFAP298 protein with a conserved and essential role in cilia motility. Summary StatementA novel Cfap298 mutation disrupts left-right patterning in mice by impairing ciliary motility, revealing a conserved protein region essential for this function across species.

developmental biology↗

bioRxiv2023

The protein map of the protozoan parasite Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum during growth phase transition and temperature stress

Leishmania parasites cause a spectrum of diseases termed leishmaniasis, which manifests in two main clinical forms, cutaneous and visceral leishmaniasis. Leishmania promastigotes transit from proliferative exponential to quiescent stationary phases inside the insect vector, a relevant step that recapitulates early molecular events of metacyclogenesis. During the insect blood meal of the mammalian hosts, the released parasites interact initially with the skin, an event marked by temperature changes. Deep knowledge on the molecular events activated during Leishmania-host interactions in each step is crucial to develop better therapies and to understand the pathogenesis. In this study, the proteomes of Leishmania (Leishmania) amazonensis (La), Leishmania (Viannia) braziliensis (Lb), and Leishmania (Leishmania) infantum (syn L. L. chagasi) (Lc) were analyzed using quantitative proteomics to uncover the proteome modulation in three different conditions related to growth phases and temperature shifts: 1) exponential phase (Exp); 2) stationary phase (Sta25) and; 3) stationary phase subjected to heat stress (Sta34). Functional validations were performed using orthogonal techniques, focusing on -tubulin, gp63 and heat shock proteins (HSPs). Species-specific and condition-specific modulation highlights the plasticity of the Leishmania proteome, showing that pathways related to metabolism and cytoskeleton are significantly modulated from exponential to stationary growth phases, while protein folding, unfolded protein binding, signaling and microtubule-based movement were differentially altered during temperature shifts. This study provides an in-depth proteome analysis of three Leishmania spp., and contributes compelling evidence of the molecular alterations of these parasites in conditions mimicking the interaction of the parasites with the insect vector and vertebrate hosts.

microbiology↗

bioRxiv2023

Leishmaniinae: evolutionary inferences based on protein expression profiles (PhyloQuant) congruent with phylogenetic relationships among Leishmania, Endotrypanum, Porcisia, Zelonia, Crithidia, and Leptomonas

Evolutionary relationships among parasites of the subfamily Leishmaniinae, which comprises pathogen agents of leishmaniasis, were inferred based on differential protein expression profiles from mass spectrometry-based quantitative data using the PhyloQuant method. Evolutionary distances following identification and quantification of protein and peptide abundances using Proteome Discoverer (PD) and MaxQuant (MQ) softwares were estimated for 11 species from 6 Leishmaniinae genera. Results clustered all dixenous species of the genus Leishmania, subgenera L. (Leishmania), L. (Viannia) and L. (Mundinia), sister to the dixenous species of genera Endotrypanum and Porcisia. Positioned basal to the assemblage formed by all these parasites were the species of genera Zelonia, Crithidia and Leptomonas, so far described as monoxenous of insects although eventually reported from humans. Inferences based on protein expression profiles were congruent with currently established phylogeny using DNA sequences. Our results reinforce PhyloQuant as a valuable approach to infer evolutionary relationships consistent with genera, subgenera, and species-specific biological characteristics, able to resolve within Leishmaniinae, which is comprised of very tightly related trypanosomatids that are just beginning to be phylogenetically unravelled. In additional to evolutionary history, mapping of species-specific protein expression is paramount to understand differences in infection processes, disease presentations, tissue tropisms, potential to jump from insects to vertebrates including humans, and potential targets for species-specific diagnostic and drug development.

evolutionary biology↗

bioRxiv2023

The characteristics of inducible defenses influence predator-prey dynamics

Empirical and theoretical studies suggest inducible and evolving defenses have different effects on predator-prey dynamics. However, theory for inducible defenses does not account for differences in response stimuli, reversibility, and within-generation versus transgenerational responses. We use predator-prey models to explore how these characteristics influence the effects of inducible defenses on stability and predator-prey oscillations. We find that while inducible defenses are typically stabilizing, defenses responding to any stimuli (predator density, conspecific and predator densities, predation rates, or the fitness gradient) can be destabilizing. Also, while induced defenses typically shorten predator-prey phase lags, defenses that respond to prey densities or the fitness gradient can increase the lags. Our theory helps explain why inducible defenses are less likely to be destabilizing and increase phase lags than evolving defenses: inducible defenses typically have negative feedbacks of the trait on its own dynamics whereas evolving defenses under disruptive selection can have positive feedbacks.

ecology↗

bioRxiv2022

Exploring how ecological and epidemiological processes shape multi-host disease dynamics using global sensitivity analysis

We use global sensitivity analysis (specifically, Partial Rank Correlation Coefficients) to explore the roles of ecological and epidemiological processes in shaping the temporal dynamics of a parameterized SIR-type model of two host species and an environmentally transmitted pathogen. We compute the sensitivities of disease prevalence in each host species to model parameters. Sensitivity rankings and subsequent biological interpretations are calculated and contrasted for cases were the pathogen is introduced into a disease-free community and where a second host species is introduced into an endemic single-host community. In some cases the magnitudes and dynamics of the sensitivities can be predicted only by knowing the host species characteristics (i.e., their competitive abilities and disease competence) whereas in other cases they can be predicted by factors independent of the species characteristics (specifically, intraspecific versus interspecific processes or the species roles of invader versus resident). For example, when a pathogen is initially introduced into a disease-free community, disease prevalence in both hosts is more sensitive to the burst size of the first host than the second host. In comparison, disease prevalence in each host is more sensitive to its own infection rate than the infection rate of the other host species. In total, this study illustrates that global sensitivity analysis can provide useful insight into how ecological and epidemiological processes shape disease dynamics and how those effects vary across time and system conditions. Our results show that sensitivity analysis can provide quantification and direction when exploring biological hypotheses.

ecology↗

bioRxiv2022

Comparing the effects of host species richness on different metrics of disease

Changes in host species richness can alter infection risk and disease levels in communities. I review theoretical predictions for direct and environmental transmission pathogens about the effects of host additions (or removals) on three common disease metrics: the pathogen community reproduction number ([R]0) and the proportion (i.e., infection prevalence) and density of infected individuals in a focal host. To help explain why predictions differ between studies and between metrics, I analyze an SIR-type model of an environmentally transmitted pathogen and multiple host species that compete for resources. I use local sensitivity analysis to explore and compare how variation in an added hosts ability to transmit a pathogen, its density, and the pathogen transmission mechanism affect each disease metric. I find that if an added host species is a weak interspecific competitor, then each metric typically increases or decreases, respectively, when the added host has a high or low ability to transmit the pathogen. However, if the added host species is a strong interspecific competitor, then the response of each metric can be strengthened, weakened, or reversed depending on how the competitive effects of the added host propagate through the community and alter the densities of all host species in the community. The three metrics often respond in the same direction, but the metrics can respond in different directions for three reasons: (1) strong density-mediated feedbacks driven by high disease-induced mortality; (2) host additions or removals cause large changes in focal host density via competition or disease-induced mortality; and (3) the metrics use different quantities to define a hosts ability to transmit disease: the quantities for infection prevalence and infected density depend on the instantaneous production rates of infectious propagules whereas the quantities for [R]0 depend on lifetime production of infectious propagules. This study provides a framework that unifies prior theoretical studies and identifies rules governing the context-dependent relationships between host species richness and the three metrics of disease.

ecology↗

bioRxiv2020

Toward a unified dilution effect theory: How competence, competition, and the transmission mechanism influence disease-diversity relationships

Biodiversity in communities is changing globally, including the gain and loss of host species in host-pathogen communities. Increased host diversity can cause infection prevalence in a focal host to increase (amplification) or decrease (dilution). However, it is unclear what general rules govern the context dependent effects, in part because theories for pathogens with different transmission modes have developed largely independently. Using a two-host model, we explore how the pathogen transmission mode and characteristics of a second host (disease competence and competitive ability) influence disease prevalence in a focal host. Our work shows how the theories for pathogens with environmental transmission, density-dependent direct transmission, and frequency-dependent direct transmission can be unified. Our work also identifies general rules about how host and pathogen characteristics affect amplification/dilution. For example, higher competence hosts promote amplification, unless they are strong interspecific competitors; strong interspecific competitors promote dilution, unless they are large sources of new infections; and dilution occurs under frequency-dependent direct transmission more than density-dependent direct transmission, unless interspecific host competition is sufficiently strong. Our work helps explain how the characteristics of the pathogen and a second host affect disease prevalence in a focal host.

ecology↗

bioRxiv2019

Matching the forecast horizon with the relevant ecologicalprocesses

Most phenomenological, statistical models used to generate ecological forecasts take either a time-series approach, based on long-term data from one location, or a space-for-time approach, based on data describing spatial patterns across environmental gradients. Here we consider how the forecast horizon determines whether more accurate predictions come from the time-series approach, the space-for-time approach, or a combination of the two. We use two simulated case studies to show that forecasts for short and long forecast horizons need to focus on different ecological processes, which are reflected in different kinds of data. In the short-term, dynamics reflect initial conditions and fast processes such as birth and death, and the time-series approach makes the best predictions. In the long-term, dynamics reflect the additional influence of slower processes such as evolutionary and ecological selection, colonization and extinction, which the space-for-time approach can effectively capture. At intermediate time-scales, a weighted average of the two approaches shows promise. However, making this weighted model operational will require new research to predict the rate at which slow processes begin to influence dynamics.

ecology↗

bioRxiv2018

Destabilizing evolutionary and eco-evolutionary feedbacks drive eco-evo cycles in empirical systems

We develop a method to identify how ecological, evolutionary, and eco-evolutionary feedbacks influence system stability. We apply our method to nine empirically-parameterized eco-evolutionary models of exploiter-victim systems from the literature and identify which particular feedbacks cause some systems to converge to a steady state or to exhibit sustained oscillations. We find that ecological feedbacks involving the interactions between all species and evolutionary and eco-evolutionary feedbacks involving only the interactions between exploiter species (predators or pathogens) are typically stabilizing. In contrast, evolutionary and eco-evolutionary feedbacks involving the interactions between victim species (prey or hosts) are destabilizing more often than not. We also find that while eco-evolutionary feedbacks rarely altered system stability from what would be predicted from just ecological and evolutionary feedbacks, eco-evolutionary feedbacks have the potential to alter system stability at faster or slower speeds of evolution. As the number of empirical studies demonstrating eco-evolutionary feedbacks increases, we can continue to apply these methods to determine whether the patterns we observe are common in other empirical communities.

ecology↗