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22122 research outputs found
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Mars Sample Return Sample Receiving Project Measurement Definition Team Final Report
No full textInternational audienc
Increased rainfall in southern Central America under glacial climate conditions
No full textInternational audienceLate Pleistocene hydroclimate variability in Central America and its associated climate forcings are poorly constrained. The region is influenced by complex ocean-atmosphere-continent interactions, and documented palaeohydrological responses, which vary by site and/or proxy specificity, are far from conclusive. We used δD of n-alkanes from a marine sediment core in the Panama Basin to infer past changes in precipitation over the last 56 kyr. Our results indicate a progressive intensification of precipitation during the last glacial period, culminating in a precipitation maximum during the Last Glacial Maximum (LGM, 23-19 kyr BP), followed by a rapid decline during the Heinrich Event 1 (H1, 18-15 kyr BP) time interval. While the regional pattern of the precipitation anomaly during the LGM is proxy and site dependent, the regional drying during H1 shows a clear north-south signature associated with the southward meridional migration of the Intertropical Convergence Zone 1 (ITCZ). Using iTrace and PMIP4 model simulations, we show that the precipitation changes associated with the ITCZ shift are closely linked to the equatorial SST front induced by changes in the oceanic circulation. We propose that an increase in this latitudinal SST gradient could have locally pushed the ITCZ further north, bringing rainfall to southern Central America during the LGM
Structural Plasticity of Flavin-Dependent Thymidylate Synthase Controlled by the Enzyme Redox State
No full textInternational audience2′-Deoxythymidine-5′-monophosphate, dTMP, is an essential precursor of thymine, one of the four canonical bases of DNA. In almost all living organisms, dTMP is synthesized de novo by a reductive methylation reaction of 2′-deoxyuridine-5′-monophosphate (dUMP) catalyzed by the thymidylate synthase, where the carbon used for the methylation is derived from methylenetetrahydrofolate (CH2THF). Many microbes, including human pathogens, utilize the flavin-dependent thymidylate synthase encoded by the thyX gene to generate dTMP. The mechanism of action relies on the reduced coenzyme FADH−, which acts both as a mediator, facilitating methylene transfer from CH2THF to dUMP, and as a reducing agent. Here, we present for the first-time crystallographic structures of ThyX from Thermotoga maritima in the reduced state alone and in complex with dUMP. ThyX flavin reduction appears to order the active site, favoring a flavin conformation that drastically deviates from that observed in the oxidized enzyme. The structures show that FADH− potentially controls access to the folate site and the conformation of two active site loops, affecting the degree of accessibility of substrate pockets to the solvent. Our results provide the molecular basis for the sequential enzyme mechanism implemented by ThyX during dTMP biosynthesis
Pastoral Knowledge, Spirituality and Adaptation to Climate Change among the Pastoralists of Hulun Buir (China)
No full textInternational audienc
Vertical and temporal niche partitioning in Amazonian butterflies: implications for the evolution of thermal tolerance
No full textInternational audienceClosely related species living in sympatry are often partitioned into divergent ecological niches. Such specialization can be enabled by the evolution of divergent traits enhancing adaptation to different niches. In this study, we investigate the partitioning of closely related butterfly species into different forest strata and daily activity time and test the effects of such spatio‐temporal niches on the evolution of thermal traits. First, using experiments in the field in Amazonia, we precisely characterized the daily activity patterns of nine species of Morpho butterflies, therefore documenting extensive temporal segregation among species and observing significant variations in temperature between their respective niches. Using controlled experiments in the lab, we then tested the thermal tolerance of wild individuals to both hot and cold conditions. The vertical distribution of species (understory versus canopy micro‐habitats) had a significant effect on several thermal traits, even when controlling for the phylogenetic distances between species, suggesting that forest stratification may have shaped thermal adaptation in these tropical butterflies. However, butterfly activity time did not correlate with any thermal traits measured. The extensive temporal segregation observed between these sympatric species might thus stem from ecological interactions observed between species rather than thermal factors
Local translation controls early reactive changes in perisynaptic astrocyte processes at pre-symptomatic stages of Alzheimer’s disease
No full textUnderstanding the progression of cellular dysfunction in preclinical Alzheimer’s disease (AD) is essential for developing new therapeutic strategies. Early alterations in astrocyte perisynaptic functions have been observed in AD [1], yet the molecular underpinnings remain poorly characterized. Here, we hypothesized that local protein synthesis—a critical mechanism for maintaining astrocyte polarity and subcellular compartmentalization [2, 3]—could be impaired at early AD stages. METHODS We studied the effect of oligomeric Aß on mRNA translation by imaging puromycylated-nascent protein chains in primary astrocytes alone or in coculture with neurons. To further characterize effects on astrocyte translation, we extracted by translating ribosome affinity purification (TRAP) [4], ribosome-bound mRNAs from hippocampal astrocytes and perisynaptic astrocyte processes (PAP) in wild type (WT) and APPswe/PS1dE9 (APP) mice at 5.5 months, a pre-symptomatic stage corresponding to the initiation of Aß plaque formation. mRNAs were analyzed by high throughput RNA sequencing and compared between genotypes and astrocyte compartments. Results were further verified by RT-qPCR in purified hippocampal synaptogliosomes as well as gliovascular units, and by fluorescent in situ hybridization (FISH). We addressed the role of the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription 3 (STAT3) pathway - a master regulator of reactive astrocytes [5] - on the early mRNA expression and distribution in astrocytes by astrocyte-specific viral gene transfer of the pathway inhibitor Suppressor Of Cytokine Signaling 3 (SOCS3) in hippocampal astrocytes in WT and APP mice. RESULTS Aß induced global and local translational perturbations in primary astrocytes. 5.5 months APP PAPs showed prominent translational changes compared to whole APP astrocytes and WT. They were related mainly to axon development, neurotransmitter transport, inflammation and endoplasmic reticulum (ER) stress. Some upregulated mRNAs accumulated in APP PAPs from 3 months, but not in astrocyte perivascular processes (PvAP). From this stage, Serpina3n total mRNAs encoding the serine protease inhibitor A3 accumulated in astrocyte soma and PAPs, and this effect was rescued in PAPs upon JAK-STAT3 inhibition. DISCUSSION Our findings show that in APP mice, significant translational changes predominantly occur in PAPs at pre-symptomatic stages of AD. They are sustained, as observed for Serpina3n, by the upregulation and distribution of total mRNAs specifically in PAPs from 3 months. The JAK-STAT3 pathway contribute to the distribution of Serpina3n mRNAs in APP PAPs as early as 3 months. These early local events could be related to soluble Aβ as well as early synaptic dysregulations sensed by PAPs, which may trigger local astrocyte reactivity. Thus, targeting local translation in astrocytes may represent a promising therapeutic strategy to counteract early synaptic alterations in AD. HIGHLIGHTS Soluble Aβ influences the global and local translation in primary astrocytes At 5.5 months, when Aβ plaques start to form, translation is severely and predominantly altered in APP PAPs. Local translation changes in APP PAPs impact mRNAs encoding proteins involved in astrocyte reactivity, synaptic development and functions and ER stress. Upregulation of Serpina3n mRNAs in APP astrocyte soma and processes occurs as early as 3 months. JAK-STAT3 pathway contributes to Serpina3n mRNA upregulation in PAPs as early as 3 months
Gene expression cartography of a developing neuronal structure
No full textThe brain is a complex structure comprising thousands to billions of neurons that belong to thousands to millions of different neuronal types. These neurons often come from different progenitor domains and have very diverse developmental histories, yet they need to find their precise location in the brain and integrate into appropriate circuits. Therefore, describing the neuronal parts list of the brain in the form of single-cell mRNA sequencing atlases, while invaluable, lacks the spatial information that is instrumental to brain structures. While a large number of brain single-cell mRNA sequencing atlases have become available over the last years, spatial transcriptomic studies have lagged behind for a variety of reasons. Here, we use a gene expression cartography algorithm, called Novosparc, to reconstruct the spatial distribution of gene expression and cell type localization in a complex, yet tractable, developing brain structure, the Drosophila optic lobe. We generate a three-dimensional atlas of this structure, which we made available through a dedicated website ( https://larva3dnovosparc.ijm.fr ). This allowed us to identify spatially compartmentalized cell types and spatially patterned genes, to predict hotspots of neuronal cell death and identify the expression of neuronal type-defining transcription factors. Importantly, we identify caveats in such algorithms that could allow for the development of refined versions. Altogether, this work provides an invaluable tool for brain researchers to formulate hypotheses and paves the way for the generation of three-dimensional atlases of more complex brain structures, which will enhance our understanding of how neurons with diverse developmental lineages can integrate to form a functional brain
The Baldwin Effect Reloaded: Intermediate Levels of Phenotypic Plasticity Favor Evolutionary Rescue
No full textInternational audienceAbstract Since the late 1890s and until today, how phenotypic plasticity interacts with genetic adaptation is a debated issue. Proponents of a positive causal role of phenotypic plasticity –James M. Bald-win in the first place– supported the view that, in altered environmental conditions, phenotypic plasticity is a key factor allowing a population to avoid extinction and then genetic evolution to catch up (“Original Baldwin Effect”, thereafter OBE). Opponents, like for instance Ernst Mayr, regularly pointed out that phenotypic plasticity, by masking genetic variation, slows gene-level evolution (“Mayr Effect”, thereafter ME). For decades this opposition remained only verbal and qualitative. To resolve it, we propose here a stochastic model that, following Baldwin’s intuitive take, combines the minimal number of ingredients to account for extinction, selection, mutation and plasticity. We study evolutionary rescue of the population (arrival and invasion of an adaptive genetic mutant) in the altered environment for different values of phenotypic plasticity, here quantified as the probability p that the maladapted genotype develops into the adapted phenotype. Our claim is that OBE can be a genuine evolutionary mechanism, depending on the level of phenotypic plasticity with respect to a threshold value p ⋆ : when p < p ⋆ , increasing p promotes evolutionary rescue by delaying extinction (“Strong” OBE); when p > p ⋆ , plasticity sustains population survival and increasing p has two antagonistic effects: to accelerate adaptation by increasing the supply of adaptive mutants (“Weak” OBE, intermediate values of p ), and to slow down adaptation by decreasing their fitness advantage (ME, high values of p )
