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Biology subjects

Nguyen, P. L.

Publications and source records attributed to Nguyen, P. L..

8 recordsLinked to original sources

Inferring fluctuating interaction probabilities in ecological networks across environmental change

Knowledge of species interactions unlocks our understanding of how ecological communities respond to climate change or habitat loss, explaining their resilience and robustness. Such knowledge requires inferring the presence, sign, and per capita strength of species interactions, as well as species intrinsic growth rates. While various studies have attempted to infer these parameters in isolation, none have successfully inferred them simultaneously. Here, we solve this grand challenge using an integrative approach combining ecological mechanistic models and statistical inference to simultaneously infer these parameters across time, capturing environmental variation and seasonality. We validate our approach on synthetic data in constant and changing environments, highlighting its ability to detect high-probability weak interactions - the key contribution of our method, and proving our ability to detect environmental changes. Applied to empirical data, it recovers the expectations from biological knowledge and unveils network rewiring. Our approach takes one step further to bridge the gap between mechanistic models and empirical ecology. It advances the understanding of ecological networks and their dynamics, thereby helping to validate existing hypotheses, spark new theories, and help guide ecological management and conservation.

ecology↗

Copper deficiency disrupts OXPHOS and mitochondrial dynamics through MTCH2-dependent copper trafficking in skeletal muscle

Copper is an essential trace element for mitochondrial respiration and cellular metabolism, yet its physiological role in skeletal muscle remains incompletely understood. Here, we show that skeletal muscle-specific deletion of the high-affinity copper importer Ctr1 (SMKO) in mice causes local copper deficiency, resulting in exercise intolerance, systemic metabolic dysfunction, and hallmarks of mitochondrial myopathy such as ragged-red fibers, lactic acidosis, and aberrant mitochondrial morphology. Mechanistically, copper starvation disrupted the electron transport chain proteome and drove pathological mitochondrial hyperfusion. We identified mitochondrial carrier homolog 2 (MTCH2), an outer mitochondrial membrane protein, as a copper-binding regulator that coordinates mitochondrial copper distribution and morphology. Restoring copper levels via a copper ionophore or AAV-mediated Ctr1 re-expression rescued mitochondrial function and alleviated myopathic features in SMKO. These findings uncover the functional coupling of CTR1 and MTCH2 as a critical mechanistic link between copper homeostasis and mitochondrial remodeling required for skeletal muscle function.

molecular biology↗

Immune Spatial Organization Predicts Metastasis Risk in Aggressive Localized Prostate Cancer

Risk stratification in localized prostate cancer (PCa) remains imprecise. Computational pathology has emerged as an attractive option for improving risk stratification, but current approaches either lack interpretability or focus solely on tumor morphology. Here, we identify, validate, and provide interpretability for an immune microenvironment-derived computational pathology biomarker for high-grade PCa. Using digitized hematoxylin and eosin-stained (H&E) slides from two independent cohorts of patients treated with radical prostatectomy (n=490), we found that spatial clustering of immune clusters, but not immune cell abundance, was independently associated with reduced risk of distant metastasis for high-grade disease but not low-grade. Joint analysis of H&E images and RNA sequencing (n=326) revealed that in high-grade disease, high-cluster samples were enriched in CD8+ T cells, activated memory CD4+ T cells, and Tregs, as well as clonal T cell populations, overall suggestive of an underlying T cell-mediated antitumor response. No such enrichment was found in low-grade tumors. These findings establish immune spatial architecture as a novel, interpretable computational pathology biomarker and provide insight into the immune landscape of high-grade PCa.

bioinformatics↗

Inferring intrinsic population growth rates and per capita interactions from ecological time-series

Knowledge about the per capita interactions between organisms and their intrinsic growth rates, and how these vary over environmental gradients, allows understanding and predicting species coexistence and community dynamics. Estimating these crucial ecological parameters requires tedious experimental work, with isolation of organisms from their natural context. Here, we provide a novel approach for inferring these key parameters from time-series data by using weighted multivariate regression on the per capita growth rates of populations. Beyond the validation of our approach on synthetic data, we reveal from experimental data an expected allocative trade-off between grazing resistance and rapid growth in algae. Application of observational data suggests facilitation between cyanobacteria and chrysophyte, indicating a possible explanation for cyanobacteria bloom. Our approach offers a way forward for inferring per capita interactions and intrinsic growth rates directly from natural communities, providing realism, mechanistic understanding of eco-evolutionary dynamics, and key parameters to develop predictive models.

ecology↗

On multiple infections by parasites with complex life cycles

Host manipulation is a common strategy of parasites with complex life cycles. It directly affects predator-prey dynamics in trophically transmitted parasites. Theoretical studies suggest that predation-enhancing manipulation of-ten decimates the prey population, making parasites prone to extinction. Host manipulation, however, can also reduce predation due to conflicting interests when multiple parasites infect a host, which is often neglected in theoretical studies. Misaligned interests of coinfecting parasites can occur due to limited carrying capacity or parasitoid developmental stage. Including this realistic complexity in a mathematical model, the results depart from previous studies substantially. We show that coinfecting multi-trophic parasites can preserve the predator-prey system and themselves through manipulation and reproduction parameters. Our study highlights the necessity of and provides the means for incorporating the reality of multiple parasites and their multi-trophic life cycles into the theory of parasite ecology.

ecology↗

Implications of drift and rapid evolution on negative niche construction

O_LIOrganisms throughout their lives constantly modify their surrounding environment; such activities are often termed niche construction. An important property of niche construction is that its consequences can persist for a long period of time and several subsequent generations can be affected. This phenomenon is described as a time lag in niche construction, or ecological inheritance. C_LIO_LIStudies have suggested that time lag in niche construction can help avoiding the tragedy of the commons. In other words, it can lead to evolution of contribution to a common good, which is associated with positive niche construction, or to the limitation of a common bad, which is associated with negative niche construction. C_LIO_LIIn this article, we will study the evolutionary consequences of incorporating time lags in a negative niche construction process: waste production. We consider a population that extrudes waste into its environment as it consumes resources to grow and reproduce. Higher consumption rates can lead to higher waste production. Individuals that adopt this selfish strategy are expected to be selected as toxic effects are equally shared among all individuals. C_LIO_LIWe show that indeed this tragedy of the commons persists in many cases and selfish strategies evolve in general. When evolution is rapid and intragenerational time lag is incorporated, however, selfish strategies are no longer favoured and strategies resulting in less waste production can be selected. Importantly, heavy pollution results in smaller population sizes, so that drift becomes more important than natural selection and limits the evolution of higher waste production. C_LI

evolutionary biology↗

Assembly of functionally antagonistic visual circuits for controlling pupil dynamics

HighlightsO_LITbx20 plays a role in the development of non-image-forming pathways.\nC_LIO_LILoss of Tbx20-expressing RGCs alters specific aspects of the pupil reflex arc.\nC_LIO_LIPreviously unknown role for a specific subset of Tbx20-expressing RGCs in modulating pupil size.\nC_LI\n\neTOCDhande et al. identify a novel genetic program that marks and is required for the development of non-image-forming parallel visual pathways. Moreover, chemogenetic activation of a specific retina-to-OPN pathway reveals a novel circuit element controlling pupil size. These findings provide new insight into the mechanisms that establish defining features of functionally specialized sensory pathways.\n\nSummaryThe functional attributes of parallel sensory circuits are determined by the properties of the individual cell types that comprise them, and their connectivity. The mechanisms controlling the specification and establishment of parallel sensory pathways remain unclear. Here we report the non-uniform distribution of retinal ganglion cells (RGCs) expressing the transcription factor Tbx20 in mice. Owing to their layout within the retina, Tbx20-RGCs are positioned to preferentially encode light information from dorsal visual space. We discovered that Tbx20 expression is mostly restricted to three RGC-types: M1 intrinsically photosensitive RGCs (ipRGCs), M2 ipRGCs and diving RGCs. The axonal projections of Tbx20-RGCs innervate non-image-forming brain centers including the suprachiasmatic nucleus, the medial division of the posterior pretectal nucleus, and the olivary pretectal nucleus (OPN), a principal station in the neural pathway for generating the pupillary light reflex (PLR). Conditional deletion of Tbx20 resulted in reduced Tbx20-RGC axonal innervation of these targets and revealed a key role of these neurons in driving specific phases of the PLR. Furthermore, chemogenetic activation uncovered a novel role for a specific subset of Tbx20-RGCs in controlling pupil dilation. These data offer a new understanding of the genetic and molecular mechanisms that establish specific, behaviorally-relevant visual circuits.

neuroscience↗

Can malaria parasites manipulate the odour-mediated host preference of their mosquito vectors?

Malaria parasites can manipulate mosquito feeding behaviours such as motivation and avidity to feed on vertebrate hosts in ways that increase parasite transmission. However, in natural conditions, not all vertebrate blood-sources are suitable hosts for the parasite. Whether malaria parasites can manipulate mosquito host choice in ways that enhance parasite transmission toward suitable hosts and/or reduce mosquito attraction to unsuitable hosts (i.e. specific manipulation) is unknown. To address this question, we experimentally infected three species of mosquito vectors (Anopheles coluzzii, Anopheles gambiae, and Anopheles arabiensis) with wild isolates of the human malaria parasite Plasmodium falciparum, and examined the effects of immature (oocyst) and mature (sporozoite) infections on mosquito behavioural responses (activation rate and odour choice) to combinations of calf odour, human odour and outdoor air using a dual-port olfactometer. Regardless of parasite developmental stage and mosquito species, P. falciparum infection did not alter mosquito activation rate or their choice for human odours. The overall expression pattern of host choice of all three mosquito species was consistent with a high degree of anthropophily, with both infected and uninfected individuals showing higher attraction toward human odour over calf odour, human odour over outdoor air, and outdoor air over calf odour. Our results suggests that, in this system, the parasite may not be able to manipulate the early long-range behavioural steps involved in the mosquito host-feeding process, including initiation of host-seeking and host orientation. Future studies examining mosquito host-feeding behaviours at a shorter range (i.e. the \"at-host\" foraging activities) are required to test whether malaria parasites can modify their mosquito host choice to enhance transmission toward suitable hosts and/or reduce biting on unsuitable hosts.

evolutionary biology↗