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Gatto, M.

Publications and source records attributed to Gatto, M..

10 recordsLinked to original sources

NAD Metabolism Drives CTCF-Cohesin Chromatin Regulation in EBV-Transformed B-Cells

Chromatin architecture regulates gene expression, and it is maintained by architectural proteins such as CTCF and the cohesin complex. In Epstein Barr virus infected cells, viral chromatin organization is stabilized through the interaction between PARP1 and CTCF, ensuring maintenance of latent gene expression. EBV B cells exhibit elevated PARP1 activity, which imposes a substantial metabolic burden due to NAD consumption by PARP1 itself. We demonstrate that efficient EBV infection and B-cell transformation rely on the NAD salvage pathway to sustain PARP1 activity and CTCF and cohesin chromatin folding. Pharmacologic inhibition of the rate-limiting enzyme NAMPT with FK866 phenocopies the chromatin architectural disruption induced by PARP1 and changes in NAD levels affects CTCF/cohesin chromatin architectural remodeling and loop extrusion. Moreover, NAMPT inhibition reduces tumor burden in EBV xenograft models. These findings identify a critical metabolic dependency linking NAD homeostasis to CTCF-cohesin mediated chromatin architecture and reveal a therapeutic vulnerability in EBV-associated malignancies.

microbiology↗

Reactive persistence of riverine metapopulations

Understanding the conditions that favor the persistence of metapopulations inhabiting riverine landscapes (riverscapes) is critical to guiding conservation and restoration efforts aimed at preserving biodiversity and ecological integrity in freshwater environments. In this study, we present a modeling framework to examine the transient persistence of fluvial metapopulations---the temporary occupation of riverscape patches by a metapopulation expected to become extinct in the long run. Our approach is theoretically grounded in the concept of ecological reactivity, which effectively complements asymptotic stability analysis in the study of the short-term response of ecological systems to impulsive perturbations of otherwise stable steady states. Our results suggest that, under ecohydrological conditions conducive to reactive metapopulation extinction equilibria, a metapopulation asymptotically bound to extinction can still colonize parts of the riverscape for significant periods of time. We also find that, in the presence of repeated positive perturbations of the extinction equilibrium, the temporal scales associated with these transient phenomena may allow for reactive pseudo-persistence. This phenomenon involves an arbitrarily long delay in the eventual extinction of the metapopulation, which may occur well below the deterministic extinction threshold. Identifying the ecohydrological drivers of reactivity-driven metapopulation persistence and the riverscape patches that contribute most to transient metapopulation dynamics over different temporal scales may provide valuable suggestions for the spatial prioritization of conservation and restoration efforts.

ecology↗

Shifting ecological niches of Prunus species under climate change

Climate change is strongly impacting agriculture, reducing crop production and shifting the geographic distribution of suitable areas for crop cultivation. To safeguard future global yield and feed a growing world population, the migration of crop production areas to new suitable sites represents a way to adapt to a changing climate. Here, we aim to identify the ecological niche of Prunus species, namely peach, plum, almond, apricot and sweet cherry, and examine their expected future shifts under climate change. For each Prunus species, we selected from the literature processed-based phenological models for dormancy break, blooming and fruit ripening, whose fulfillment determines whether an area is suitable for crop cultivation. Historically, the ecological niche of Prunus species spans mid-low European latitudes, while higher latitudes fail satisfying the forcing requirements for blooming and fruit ripening. In future, this constraint is expected to become less restrictive with a northwards expansion of the suitable areas. However, this will be contrasted by a contraction of the niche at low latitudes due to dormancy break failures. While bridging established mechanistic knowledge on the climatic effects of plant phenological traits with citizen science observations, our work brings new insights into how fruit crops will respond to global warming.

ecology↗

Phenological and epidemiological impacts of climate change on peach production

Agricultural food security is threatened by climate change impacts, which can distress crop growth and favor the spread of infectious diseases. Here, we examined the synergism of the two potentially most disruptive causes of future yield failure in peach production: the effects of global climate change on fruit growth and on the spread of fungal diseases. Coupling a phenological and epidemiological model across the French continental territory, we provided projections of yield losses for four peach cultivars (early, mid-early, mid-late, and late) in the XXI century under different climate change scenarios. Global warming is expected to impair fruit phenology with blooming failure events in the south-western part of the country. This will be less extreme under the more moderate emission scenario, even though sporadic blooming failures will still occur. In contrast, future warmer and drier conditions will decrease brown rot-induced yield loss in the historical locations devoted to peach cultivation. To adapt to these changes, the benefits of shifting peach production sites to new suitable areas are evaluated. Thanks to this strategy, the peach national yield could still be fulfilled even under the most extreme climate change scenario. Comprehensive mathematical frameworks, that concomitantly consider the climatic effects on the plant hosts and on their pathogens, are required to provide reliable future predictions of crop yields and to inform control and adaptation strategies to guarantee food security under global warming.

ecology↗

Helminth ecological requirements shape the impact of climate change on the hazard of infection

Outbreaks and spread of infectious diseases are often associated with seasonality and changes caused by global warming. Free-living stages of soil-transmitted helminths are highly susceptible to environmental drivers, however, how multiple climatic variables affect helminth species, and the long-term consequences of these interactions, is poorly understood. We used experiments on nine trichostrongylid species to develop a temperature- and humidity-dependent model of infection hazard, which was then implemented at the European scale under climate change scenarios. Intestinal and stomach helminths exhibited contrasting climatic responses, with the former group strongly affected by temperature while the latter primarily impacted by humidity. These differences generated seasonal changes in the timing and intensity of the infection hazard and spatial heterogeneities within and between the two groups. A future range expansion of both groups toward northern latitudes is expected to create new opportunities for the co-circulation of the studied helminth species.

ecology↗

Modeling the contribution of antibodies to the within-host dynamics of single and dual helminth infections in a natural system

Within-host models of infection can provide important insights into the processes that affect parasite spread and persistence in host populations. However, modeling is often limited by the availability of empirical data, a problem commonly encountered in natural systems. Here, we used six years of immune-infection observations of two gastrointestinal helminths (Trichostrongylus retortaeformis and Graphidium strigosum) from a population of European rabbits (Oryctolagus cuniculus) to develop an age-dependent, within-host mathematical model that explicitly included species-specific and cross-reacting antibody (IgA and IgG) responses to each helminth in hosts with single or dual infections. Different models of single infection were formally compared to test alternative mechanisms of parasite regulation. The two models that best described single infections of each helminth species were then coupled through antibody cross-immunity to examine how the presence of one species could alter the host immune response to, and the within-host dynamics of, the other species. For both single infections, model selection suggested that either IgA or IgG responses could equally explain the observed parasite intensities at different host age. However, the strength of this response drastically changed between the two helminths, being stronger against T. retortaeformis than against G. strigosum and causing contrasting age-intensity profiles. When the two helminths coinfect the same host, we found a decrease of the species-specific immune response to both species together with an asymmetric cross-immune response driven by IgG. Changes in the level and affinity of antibodies from single to dual infections contributed to the significant increase of both helminth abundances. By combining mathematical modeling with immuno-infection data, our work provides a model framework for disentangling some of the complexities generated by host-parasite and parasite-parasite interactions from natural systems. Our approach thus offers a tractable general tool to examine immune-infection relationships within hosts. Author summaryThe host immune response often plays a critical role in regulating parasite dynamics and transmission. We developed a mathematical model to evaluate whether and how the observed variation in host antibody responses could explain the relative differences in the abundance of two parasite species in hosts with single and dual infections from a natural rabbit population. Our results indicated that either IgA or IgG could describe the contrasting trends of the two parasites in rabbits with single infections. Specifically, antibodies appeared to control T. retortaeformis, while the effect was less clear for G. strigosum. For dual infections, we found a weaker specific antibody response against both helminths and an asymmetric cross-immunity, which could explain the significantly greater intensities observed for T. retortaeformis and, secondly, for G. strigosum. Our within-host mathematical framework provides a plausible mechanism for the mediated role of antibodies in hosts with single and dual parasite infections, and how the strength of these infection-immune interactions changes with host age. This model framework offers a way forward to our understanding of the within-host processes that generate individual variation in infection and is relatively flexible to be applied to other natural systems.

immunology↗

A climate-driven compartmental model for fungal diseases in fruit orchards: The impacts of climate change on a brown rot-peach system

As a well-known driving force of diseases in crops, climate change is likely to impact future crop yields. In the present work, we account for climate-related influences on the key parameters of a SIR-type epidemiological model for fungal diseases in stone fruit aimed at simulating different observed epidemic patterns, and, eventually, evaluating the possible impacts of climate change on the disease-induced yield loss. Brown rot disease in peach orchards is used here as a study system. We contrasted simulation results with epidemiological measures collected from an experimental orchard in Avignon (southern France) in two consecutive years, characterized by dissimilar brown rot outbreaks. The capacity of our climate-driven model to adequately reproduce the observed disease patterns suggests temperature and precipitation as key drivers of brown rot epidemics. Overall, the model predicts a potential decrease of brown rot severity under warmer and drier climatic conditions. To comprehensively understand the effect of future climate change on peach yield, alterations of crop phenology must also be accounted for. We thus build a model that considers the synergism between the two factors: vulnerability to the pathogen and varying phenology. Using plausible climate change scenarios, we find that the peach yield in the considered Mediterranean region will be considerably impaired: although brown rot-related yield losses are expected to decrease in warmer and drier climatic conditions, climate change will hinder fruit blooming and consequently the yield because milder winters will impede the achievement of dormancy. By deepening our understanding of climatic impacts on crop fungal infections, the present study may serve as a useful tool to plan and implement suitable adaptation strategies for peach cultivation.

plant biology↗

The Enemy of my Enemy is my Friend: Immune-Mediated Facilitation Contributes to Fitness of Co-Infecting Helminths

Our conceptual understanding of immune-mediated interactions between parasites is rooted in the theory of community ecology. One of the limitations of this approach is that most of the theory and empirical evidence has focused on resource or immune-mediated parasite competition and yet, there is ample evidence of positive interactions between species that could be generated by immune-mediated facilitation. Here, we develop an immuno-epidemiological framework and apply it to longitudinal infection data of two gastrointestinal helminths that infect a population of free-living rabbits to investigate, through model testing, the mechanisms of immune-mediated facilitation in dual infections. Simulations show that weakened, species-specific IgA antibody responses and unequal, albeit low, IgA cross-reactions explain higher parasite intensities in dual compared to single infections, for both helminths. Simulations also show that rabbits with dual infections shed more free-living stages that survive fort longer in the environment, implying greater onward transmission than hosts with single infections. These findings support the hypothesis that the two helminths interact through immune-mediated facilitation which contributes to greater fitness and the long-term co-circulation of both species in the host population.

ecology↗

Shifts in the thermal niche of fruit trees under climate change: the case of peach cultivation inFrance.

Climate influences plant phenological traits, thus playing a key role in defining the geographical range of crops. Foreseeing the impact of climate change on fruit trees is essential to inform policy decisions to guide the adaptation to new climatic conditions. To this end, we propose and use a phenological process-based model to assess the impacts of climate change upon the phenology, the suitability and the distribution of economically important cultivars of peach (Prunus persica), across the entire continental France. The model combines temperature dependent sub-models of dormancy, blooming, fruit survival and ripening, using chilling units, forcing units, frost occurrence and growing degree days, respectively. We find that climate change will have divergent impacts upon peach production. On the one hand, blooming will occur earlier, warmer temperatures will decrease spring frost occurrence and fruit ripening will be easily achieved before the start of fall. On the other hand, milder winters will impede the plant buds from breaking endodormancy, with consequent abnormal patterns of fruit development or even blooming failure. This latter impact will dramatically shift the geographic range of sites where peach production will be profitable. This shift will mainly be from the south of France (Languedoc-Roussillon, Rhone-Alpes and Provence-Alpes-Cote dAzur), to northwestern areas where the winter chilling requirement will still be fulfilled. Our study provides novel insights for understanding and forecasting climate change impacts on peach phenology and it is the first framework that maps the ecological thermal niche of peach at national level.

plant biology↗

Prawn aquaculture as a method for schistosomiasis control and poverty alleviation: a win-win approach to address a critical infectious disease of poverty

Recent evidence suggests crustacean snail predators may aid schistosomiasis control programs by targeting the environmental component of the parasites life cycle through predation of the snail species that serve as intermediate hosts of the parasite. We evaluate costs, benefits, and potential synergies between schistosomiasis control and aquaculture of giant prawns using an integrated bio-economic-epidemiologic model. We identified combinations of stocking density and aquaculture cycle length that maximize profit and offer disease control benefits for sustainable schistosomiasis control. We consider two prawn species in sub-Saharan Africa: the endemic, non-domesticated Macrobrachium vollenhovenii, and the non-native, domesticated Macrobrachium rosenbergii. We find that, at profit-optimal densities, both M. rosenbergii and M. vollenhovenii can complement conventional control approaches (mass drug treatment of people) and lead to sustainable schistosomiasis control. We conclude that integrated aquaculture strategies can be a win-win strategy in terms of health and sustainable development in schistosomiasis endemic regions of the world.

epidemiology↗