Guillot, E. | bioRxiv Science

bioRxiv2026

Contrasting biotic and abiotic drivers of Glomeromycotina and Mucoromycotina mycorrhizal associations in a durum wheat field

Mucoromycotina fine root endophyte (M-FRE), although commonly present in cultivated crops, represent a largely overlooked symbiosis, and their diversity and ecological functions under natural field conditions remain poorly understood. The co-occurrence of M-FRE and Glomeromycotina arbuscular mycorrhizal fungi (G-AMF) was assessed in field-grown durum wheat (Triticum turgidum subsp. durum (Desf.) Husn.), testing the effects of combined water and nitrogen limitation on root colonization and fungal community diversity in roots, rhizosphere, and extra-radical hyphae. The M-FRE colonization was reduced under combined water and nitrogen stress but was unaffected by wheat genotype. In contrast, G-AMF colonization varied among genotypes and was insensitive to this combined stress. While G-AMF colonization correlated with root traits, M-FRE abundance was rather determined by soil properties and the applied stress. Remarkably, under stress, M-FRE but not G-AMF colonization correlated with nitrogen and phosphorus uptake in plant shoots. Partial 18S metabarcoding detected 74 G-AMF taxa and 12 M-FRE taxa, some shared across compartments, revealing active growth of M-FRE extra-radical hyphae. Stress had contrasting effects on diversity: G-AMF alpha diversity remained stable, whereas M-FRE diversity declined, with stress driving distinct community structures for both groups. These results indicate that M-FRE and G-AMF are shaped by divergent drivers, highlighting functional differences between these morphologically similar symbioses.

ecology↗

bioRxiv2022

Breakthrough: A First-In-Class Virtual Simulator for Dose Optimization of ACE Inhibitors in Veterinary Cardiology

AO_SCPLOWBSTRACTC_SCPLOWThe human and canine renin-angiotensin-aldosterone-systems (RAAS) play a central role in the pathophysiology of congestive heart failure (CHF), justifying the use of angiotensin converting enzyme inhibitors inhibitors (ACEi) in this indication. Seminal studies in canine CHF had suggested that the pharmacological action of benazepril was relatively independent of doses > 0.25 mg/kg P.O, thereby providing a rationale for the European label dose of 0.25 mg/kg P.O q24h in dogs with cardiovascular diseases. However, most of these earlier studies on benazepril pharmacodynamics relied on measures of ACE activity - a sub-optimal endpoint to characterize the effect of benazepril on the RAAS. Nonlinear mixed-effects (NLME) modeling is an established framework for characterizing the effect of therapeutics on complex biological systems, such as the RAAS cascade. Importantly for therapeutic schedule optimization, one can use such a model to predict the outcomes of various hypothetical dosing schedules via simulation. The objectives of this study were (i) to expand on previous NLME modeling efforts of the dose-exposure-response relationship of benazepril on biomarkers of the RAAS which are relevant to CHF pathophysiology and disease prognosis {angiotensins I, II, III, IV, (1-7)} by using a quantitative systems pharmacology (QSP) modeling approach; and (ii) to develop a software implementation of the model capable of simulating clinical trials in benazepril in dogs bedside dose optimization. This study expands on previous modeling efforts to characterize the changes in RAAS pharmacodynamics in response to benazepril administration and showcase how QSP modeling can be used for efficient dose optimization of ACEis at the bedside. Our results suggest that 0.5 mg/kg PO q12h of benazepril produced the most robust reduction in AngII and upregulation of RAAS alternative pathway biomarkers. This model will eventually be expanded to include relevant clinical endpoints, which will be evaluated in an upcoming prospective trial in canine patients with CHF. AO_SCPLOWUTHORC_SCPLOW SO_SCPLOWUMMARYC_SCPLOWCongestive heart failure (CHF) is a disease of the heart, common to both dogs and humans, where the heart is not healthy enough to pump blood around the body efficiently. Because the blood isnt moving around the body as efficiently, it tends to get congested in various areas of the body and increases strain on the heart. Benazepril is a drug for CHF used in both dogs and humans to reduce congestion and improve the functioning of the cardiovascular system. Although benazepril is effective, theres evidence that suggests the dosing could be improved if the therapeutic was further studied. In this experiment, we tested benazepril at several safe dosages in well-cared for and healthy dogs to collect data on the relationship between dose size, dosing frequency, and effect on the cardiovascular system. Using this data, we built computer models of benazepril to simulate many clinical trials. By studying these simulations, we were able to make several predictions about the optimal dosing schedule of benazepril in dogs. Weve also built a web-app version of the computer model for veterinary researchers to use, modify, and study. This work also provides a platform and roadmap for optimizing benazepril dosages in human CHF.

pharmacology and toxicology↗

bioRxiv2017

Complex genetic patterns in human arise from a simple range-expansion model over continental landmasses

Although it is generally accepted that geography is a major factor shaping human genetic differentiation, it is still disputed how much of this differentiation is a result of a simple process of isolation-by-distance, and if there are factors generating distinct clusters of genetic similarity. We address this question using a geographically explicit simulation framework coupled with an Approximate Bayesian Computation approach. Based on six simple summary statistics only, we estimated the most probable demographic parameters that shaped modern human evolution under an isolation by distance scenario, and found these were the following: an initial population in East Africa spread and grew from 4000 individuals to 5.7 million in about 132 000 years. Subsequent simulations with these estimates followed by cluster analyses produced results nearly identical to those obtained in real data. Thus, a simple diffusion model from East Africa explains a large portion of the genetic diversity patterns observed in modern humans. We argue that a model of isolation by distance along the continental landmasses might be the relevant null model to use when investigating selective effects in humans and probably many other species.

genetics↗