Biology subjects

Santini, L.

Publications and source records attributed to Santini, L..

5 recordsLinked to original sources

bioRxiv2020

NMD is required for timely cell fate transitions by fine-tuning gene expression and controlling translation

Cell fate transitions depend on balanced rewiring of transcription and translation programmes to mediate ordered developmental progression. Here we identify a feedback loop between nonsense-mediated mRNA decay (NMD) and translation initiation. We show that NMD controls the translation initiation factor Eif4a2 and its premature termination codon encoding isoform (Eif4a2PTC). NMD deficiency leads to translation of a specific truncated Eif4a2 protein, which elicits increased translation rates and is causative for significant delays in mouse embryonic stem cell (ESC) differentiation. Our results show identical mRNA targets for Smg5, Smg6 and Smg7, but illustrate a clear hierarchy between KOs in amplitude of target deregulation and differentiation phenotype (Smg5 > Smg6 > Smg7). This hierarchy highlights heterodimer independent functions for Smg5 and Smg7. Together, our findings expose an intricate link between mRNA stability and translation initiation control, that must be maintained for normal dynamics of cell state transitions.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cell biology↗

bioRxiv2020

Assessing the reliability of species distribution projections in climate change research

AimForecasting changes in species distribution under future scenarios is one of the most prolific areas of application for species distribution models (SDMs). However, no consensus yet exists on the reliability of such models for drawing conclusions on species distribution response to changing climate. In this study we provide an overview of common modelling practices in the field and assess model predictions reliability using a virtual species approach. LocationGlobal MethodsWe first provide an overview of common modelling practices in the field by reviewing the papers published in the last 5 years. Then, we use a virtual species approach and three commonly applied SDM algorithms (GLM, MaxEnt and Random Forest) to assess the estimated (cross-validated) and actual predictive performance of models parameterized with different modelling settings and violations of modelling assumptions. ResultsOur literature review shows that most papers that model species distribution under climate change rely on single models (65%) and small samples (< 50 presence points, 62%), use presence-only data (85%), and binarize models output to estimate range shift, contraction or expansion (74%). Our virtual species approach reveals that the estimated predictive performance tends to be over-optimistic compared to the real predictive performance. Further, the binarization of predicted probabilities of presence reduces models predictive ability considerably. Sample size is one of the main predictors of real accuracy, but has little influence on estimated accuracy. Finally, the inclusion of irrelevant predictors and the violation of modelling assumptions increases estimated accuracy but decreases real accuracy of model projections, leading to biased estimates of range contraction and expansion. Main conclusionsOur study calls for extreme caution in the application and interpretation of SDMs in the context of biodiversity conservation and climate change research, especially when modelling a large number of species where species-specific model settings become impracticable.

ecology↗

bioRxiv2020

The island rule explains consistent patterns of body size evolution across terrestrial vertebrates

Island faunas can be characterized by gigantism in small animals and dwarfism in large animals, but the extent to which this so-called island rule provides a general explanation for evolutionary trajectories on islands remains contentious. Here we use a phylogenetic meta-analysis to assess patterns and drivers of body size evolution across a global sample of paired island-mainland populations of terrestrial vertebrates. We show that island rule effects are widespread in mammals, birds and reptiles, but less evident in amphibians, which mostly tend towards gigantism. We also found that the magnitude of insular dwarfism and gigantism is mediated by climate as well as island size and isolation, with more pronounced effects in smaller, more remote islands for mammals and reptiles. We conclude that the island rule is pervasive across vertebrates, but that the implications for body size evolution are nuanced and depend on an array of context-dependent ecological pressures and environmental conditions.

ecology↗

bioRxiv2020

Cooperative molecular networks drive a mammalian cell state transition

In the mammalian embryo, epiblast cells must exit their naive state and acquire formative pluripotency. This cell state transition is recapitulated by mouse embryonic stem cells (ESCs), which undergo pluripotency progression in defined conditions in vitro. However, our understanding of the molecular cascades and gene-networks involved in the exit from naive pluripotency remains fragmented. Here we employed a combination of genetic screens in haploid ESCs, CRISPR/Cas9 gene disruption, large-scale transcriptomics and computational systems-biology to delineate the regulatory circuits governing naive state exit. Transcriptome profiles for 73 knockout ESC lines predominantly manifest delays on the trajectory from naive to formative epiblast. We find that gene networks operative in ESCs are active during transition from pre- to post-implantation epiblast in utero. We identified 374 naive-associated genes tightly connected to epiblast state and largely conserved in human ESCs and primate embryos. Integrated analysis of mutant transcriptomes revealed funneling of multiple gene activities into discrete regulatory modules. Finally, we delineate how intersections with signaling pathways direct this pivotal mammalian cell state transition.

systems biology↗

bioRxiv2020

Weak support for the abundant niche-centre hypothesis in North American birds

Species abundance is expected to decrease from the centre towards the edge of their ecological niches (abundant niche-centre hypothesis). Recently, Osorio-Olvera et al. (2020) reported strong support for the abundant niche-centre relationship in North American birds. We demonstrate here that methodological decisions strongly affected perceived support. Avoiding these issues casts doubt on conclusions by Osorio-Olvera et al. and the putative support for the abundant nichecentre hypothesis in North American birds.

ecology↗