Biology subjects

Descombes, P.

Publications and source records attributed to Descombes, P..

6 recordsLinked to original sources

bioRxiv2023

Rank-based deep learning from citizen-science data to model plant communities

In the age of big data, scientific progress is fundamentally limited by our capacity to extract critical information. We show that recasting multispecies distribution modeling as a ranking problem allows analyzing ubiquitous citizen-science observations with unprecedented efficiency. Based on 6.7M observations, we jointly modeled the distributions of 2477 plant species and species aggregates across Switzerland, using deep neural networks (DNNs). Compared to commonly-used approaches, multispecies DNNs predicted species distributions and especially community composition more accurately. Moreover, their setup allowed investigating understudied aspects of ecology: including seasonal variations of observation probability explicitly allowed approximating flowering phenology, especially for small, herbaceous species; reweighting predictions to mirror cover-abundance allowed mapping potentially canopy-dominant tree species nationwide; and projecting DNNs into the future allowed assessing how distributions, phenology, and dominance may change. Given their skill and their versatility, multispecies DNNs can refine our understanding of the distribution of plants and well-sampled taxa in general.

ecology↗

bioRxiv2023

Leaf metabolic traits reveal hidden dimensions of plant form and function

The plant metabolome encompasses the biochemical mechanisms through which evolutionary and ecological processes shape plant form and function1,2. However, while the metabolome should thus be an important component of plant life-history variation3, we know little about how it varies across the plant kingdom. Here, we use the plant functional trait concept4 - a powerful framework for describing plant form and function5-7 - to interpret leaf metabolome variation among 457 tropical and 339 temperate plant species. Distilling metabolite chemistry into five discriminant metabolic functional traits reveals that plants vary along two major axes of leaf metabolic specialization - a leaf chemical defense spectrum and an expression of leaf longevity. These axes are qualitatively consistent for tropical and temperate species, with many trait combinations being viable. However, axes of leaf metabolic specialization vary orthogonally to life-history strategies described by widely used functional traits5-7, while being at least equally important to them. Our findings question classical trait6 and plant defense8 theory that predicts relationships between the leaf chemical phenotype, plant productivity, and pace of life. Moreover, we show that metabolic functional traits describe unique dimensions of plant life-history variation that are complementary to, and independent from, those captured by existing plant functional traits.

ecology↗

bioRxiv2022

Strategies for sampling pseudo-absences for species distribution models in complex mountainous terrain

O_LIPredictions from species distribution models (SDMs) that rely on presence-only data are strongly influenced by how pseudo-absences are derived. However, which strategies to generate pseudo-absences give rise to faithful SDMs in complex mountainous terrain, and whether species-specific or generic strategies perform better remain open questions. C_LIO_LIHere, across 500 plant species, we investigated comprehensively how predictions of SDMs at a 93 m spatial resolution are influenced by pseudo-absence strategies, using the complex topography of the Swiss mountains as a model system. We used five generic (random, equal-stratified, proportional-stratified, target, density) and three species-specific (target specific, density specific and geographic specific) approaches to derive pseudo-absence data. We conducted performance tests for each of our eight strategies in combination with (a) spatial bias, generated within our occurrence dataset on sites with highest sampling density, to investigate how this common bias problem influences the performance of pseudo-absence sampling strategies, and (b) a new approach to reduce model extrapolation in environmental space by including background data from all environmental conditions of the study area. SDMs were evaluated against an independent and well-sampled dataset of true presences and absences. C_LIO_LIThe random, the density (generic), and the geographic specific (species-specific) strategies consistently performed best, even in cases of strong spatial sampling bias in the occurrence data. Including a background of environmentally stratified pseudo-absences improved predictions of species distributions towards environmental extremes, and significantly reduced spatial extrapolations of model predictions in environmental space. C_LIO_LIOur results indicate that both generic and species-specific pseudo-absence strategies allow estimating robust SDMs and we provide clear recommendations which strategies to choose in complex terrain and when presence data are prone to high sampling bias. In datasets with strong sampling bias, most pseudo-absence strategies produce extrapolation problems and we additionally recommend environmentally stratified pseudo-absences in these cases. Overall, in species rich datasets the use of complex and computationally demanding, species-specific pseudo-absence strategies may not always be justified compared to simpler generic approaches. C_LI

ecology↗

bioRxiv2021

Compound- and fiber type-selective requirement of AMPKγ3 for insulin-independent glucose uptake in skeletal muscle

Objective: The metabolic master-switch AMP-activated protein kinase (AMPK) mediates insulin-independent glucose uptake in muscle and regulates the metabolic activity of brown and beige adipose tissue (BAT). The regulatory AMPK{gamma}3 isoform is uniquely expressed in skeletal muscle and also potentially in BAT. Here, we investigated the role that AMPK{gamma}3 plays in mediating skeletal muscle glucose uptake and whole-body glucose clearance in response to small-molecule activators that act on AMPK via distinct mechanisms. We also assessed if {gamma}3 plays a role in adipose thermogenesis and browning. Methods: Global AMPK{gamma}3 knockout (KO) mice were generated. A systematic whole-body, tissue and molecular phenotyping linked to glucose homeostasis was performed in {gamma}3 KO and wild type (WT) mice. Glucose uptake in glycolytic and oxidative skeletal muscle ex vivo, as well as blood glucose clearance in response to small molecule AMPK activators that target nucleotide-binding domain of {gamma} subunit (AICAR) and allosteric drug and metabolite (ADaM) site located at the interface of the and {beta} subunit (991, MK-8722) were assessed. Oxygen consumption, thermography, and molecular phenotyping with a {beta}3-adrenergic receptor agonist (CL-316,243) treatment were performed to assess BAT thermogenesis, characteristics and function. Results: Genetic ablation of {gamma}3 did not affect body weight, body composition, physical activity, and parameters associated with glucose homeostasis under chow or high fat diet. {gamma}3 deficiency had no effect on fiber-type composition, mitochondrial content and components, or insulin-stimulated glucose uptake in skeletal muscle. Glycolytic muscles in {gamma}3 KO mice showed a partial loss of AMPK2 activity, which was associated with reduced levels of AMPK2 and {beta}2 subunit isoforms. Notably, {gamma}3 deficiency resulted in a selective loss of AICAR-, but not MK-8722-induced blood glucose-lowering in vivo and glucose uptake specifically in glycolytic muscle ex vivo. We detected {gamma}3 in BAT and found that it preferentially interacts with 2 and {beta}2. We observed no differences in oxygen consumption, thermogenesis, morphology of BAT and inguinal white adipose tissue (iWAT), or markers of BAT activity between WT and {gamma}3 KO mice. Conclusions: These results demonstrate that {gamma}3 plays a key role in mediating AICAR- but not ADaM site binding drug-stimulated blood glucose clearance and glucose uptake specifically in glycolytic skeletal muscle. We also showed that {gamma}3 is dispensable for thermogenesis and browning of iWAT.

physiology↗

bioRxiv2020

In-vivo Transcriptomic Profiling of Systemic Aging using Cell Encapsulation

Sustained exposure to a young systemic environment rejuvenates aged organisms and promotes cellular function. However, due to the intrinsic complexity of tissues it remains challenging to pinpoint niche-independent effects of circulating factors on specific cell populations. Here we describe a method for the encapsulation of human and mouse skeletal muscle progenitors in diffusible polyethersulfone hollow fiber capsules that can be used to profile systemic aging in vivo independent of heterogeneous short-range tissue interactions. We observed that circulating long-range signaling factors in the old systemic environment lead to an activation of Myc and E2F transcription factors, induce senescence and suppress myogenic differentiation. Importantly, in vitro profiling using young and old serum in 2D culture does not capture all pathways deregulated in encapsulated cells in aged mice. Thus, in vivo transcriptomic profiling using cell encapsulation allows for the characterization of effector pathways of systemic aging with unparalleled accuracy.

bioengineering↗

bioRxiv2018

AMPK promotes induction of a tumor suppressor FLCN through activation of TFEB independently of mTOR

AMP-activated protein kinase (AMPK) is a central energy sensor and master regulator of energy homeostasis. AMPK not only elicits acute metabolic responses, but also promotes metabolic reprogramming and adaptions in the long-term through regulation of specific transcription factors/co-activators. We performed a whole-genome transcriptome profiling in wild-type and AMPK-deficient mouse embryonic fibroblasts (MEF) and mouse primary hepatocytes that had been treated with two distinct classes of small-molecule AMPK activators, namely 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) or 991. This led to the identification of distinct compound-dependent gene expression signatures and to the discovery of several AMPK-regulated genes, including folliculin (Flcn), a gene encoding for a tumor suppressor and nutrient sensor. Gene set enrichment and pathway analyses identified the lysosomal pathway and the associated transcription factor EB (TFEB) as key transcriptional mediator responsible for AMPK-dependent gene expression changes. AMPK-induced Flcn expression was abolished in TFEB/TFE3 double knockout MEF and the promoter activity of Flcn was profoundly reduced when its putative TFEB-binding site was mutated. Mechanistically, we have found that AMPK promotes the dephosphorylation and nuclear localization of TFEB independently of mTOR activity.\n\nCollectively, we identified the AMPK-TFEB-FLCN axis as a potential key regulator for cellular and metabolic homeostasis. Moreover, data from zebrafish with physiologically and pharmacologically activated AMPK confirmed the AMPK-TFEB-FLCN cascade in vivo.

molecular biology↗