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Fossil ribcages of Homo sapiens provide new insights into modern human evolution
No full textInternational audienceAbstract Recent research on the Nariokotome Boy’s ribcage suggests the slender thorax of modern H. sapiens is a derived condition. However, since digital ribcage reconstructions of fossil H. sapiens are not available yet, it is unknown whether these individuals would have had a primitive or derived thorax. To address this issue, we first reconstructed the ribcages of Nazlet Khater 2, Ohalo II H2, Dolní Věstonice 13, and Ötzi. We used geometric morphometrics to compare them to 59 recent H. sapiens and three other Homo fossils (Nariokotome Boy, Kebara 2, Shanidar 3). Fossil H. sapiens ribcages exhibit the typical globular proportions of recent humans. Additionally, size and shape seem to be climate-dependent: smaller, cylindrical ribcages in warmer and more temperate climates (Nazlet Khater 2, Ohalo II H2) contrasted with larger, broader ribcages in colder climates (Dolní Věstonice 13). The ribcage of Ötzi presented mixed features, something that could have been beneficial for seasonal alpine transhumance. This suggests H. sapiens ribcage morphology encompasses both slender and stockier forms, highlighting that human anatomical variation might be more complex and context-dependent than previously thought
First geometric morphometric study of the four Arago mandibles: implications for Middle Pleistocene hominin evolution
No full textInternational audienceThe Caune de l'Arago (Pyrénées-Orientales, France) has been the focus of archaeologic work for over 60 years. From 1964, a large excavation inside the cave was opened which would ultimately lead to the discovery of 152 human remains to date. The Arago hominin fossils represent a minimum of 32 individuals, and have been dated between ~560 ka and ~360 ka, making them the oldest hominin remains in France, and the cave, one of the most important sites for the study of European Middle Pleistocene hominin evolution. Among the hominin fossils, six mandibles were found, of which four are in a very good state of preservation. Arago 2, 13, 89 and 119/130 were discovered in layers G and F of the cave which have been dated to ~450 ka. The mandibles, along with the other hominin remains, have recently been thoroughly described in a monograph. The present study aims at complementing this work by studying the four mandibles using up to date geometric morphometric approaches. We collected 251 landmarks and semi-landmarks from the whole morphology of 67 mandibular specimens (i.e., 32 Homo sapiens, 14 Homo neanderthalensis, 6 Homo erectus s.l., 11 Middle Pleistocene individuals and the four Arago mandibles). Missing landmarks were estimated by mirroring and Thin-Plate Spline (TPS) interpolation. The right and left hemi-mandibles landmarks configurations were then aligned using general Procrustes analysis (GPA) and the rest of the study was led on the mean right and left shape of the specimens (i.e. 131 landmarks per specimen). The database was separated into two different matrices, one comprising the full mandibular shape and one focusing on the morphology of the mandibular corpus (i.e. 80 landmarks), which were analysed separately using PCA, to explore the morphological variation within our sample, and Multinomial Component Logistic Regression (MLR) models to estimate the morphological affinities of the specimen of our study group.Our main results indicate that the Arago specimens form a coherent group in terms of mandibular shape variability and show little variation in the morphospaces. They show the strongest shape affinities with other European Middle Pleistocene specimens, such as Mauer and Montmaurin along with one individual from the Sima de los Huesos comparative sample. The shape of the Arago mandibles, and contrary to most of the Sima de los Huesos sample, is on average quite distinct from the Homo neanderthalensis sample analysed in the present study. The Arago mandibular sample appears to be representing a fossil population that was distinct from Homo neanderthalensis and that could be named Homo heidelbergensis given the strong phenetic affinity that they share with the Mauer mandible, holotype of the species. We further discuss the evolutionary significance of the Arago sample and of Homo heidelbergensis with regard to the phenetic affinities between Arago and other important Middle Pleistocene specimens, including specimens fromthe Sima de los Huesos, Tighenif (African Middle Pleistocene hominins) and Xiahe (possible Denisovan specimen from Late Middle Pleistocene Tibet)
Numerical-spatial cognition
No full textInternational audienceFrom an embodied perspective of cognition, sensorimotor mechanisms play a crucial role in abstract processing, such as the understanding of Arabic numerals. For instance, spatial cognition can influence number processing. These spatial-numerical associations (SNAs) have been thoroughly investigated since the pioneering spatial-numerical association of response codes (SNARC) effect, which demonstrates faster left/right responses to small/large numbers, respectively. While there has been no systematic assessment of SNAs on other planes in threedimensional space in the literature, recent primary evidence has revealed that SNAs along the transverse and sagittal planes are mutually exclusive with respect to the required spatial reference frames used by the participant. Specifically, under egocentric spatial reference frames, SNAs have been observed only along the sagittal plane, whereas under allocentric reference frames, the reverse pattern has been observed, with SNAs present exclusively along the transverse plane of the body. Given this empirical evidence, we have hypothesized that the subject's ability to switch spatial reference frames to match that of another person could significantly influence the occurrence of SNAs according to the processed plane. Therefore, this study has two aims. The first is to replicate previous seminal findings. The second is to investigate how referential frame switching (RFS) training can affect this organization. While the results of the two experiments reveal a general replication, more importantly, we find that RFS training enables the development of new situated cognition strategies from egocentric perspectives and the generalization of transverse SNAs to other spatial planes from allocentric perspectives.</div
A General Synthesis Approach to Double‐Guanidinium Stapled Peptides and Foldamers
No full textInternational audienceAbstract In the broader context of peptide macrocyclization, methods enabling the formation of specific crosslinks between orthogonally protected, amino‐functionalized side chains (e.g., Lys–Lys crosslinks) are of potential interest for expanding molecular diversity and stabilizing peptide secondary structures. We recently introduced a solid‐phase synthesis approach for the rapid generation of guanidinium stapled helical peptides and have shown their utility for inhibition of protein–protein interactions. Whereas our previous work concentrated on the formation of mono‐guanidinium crosslinks, we show here that we can expand this approach to prepare bis‐guanidinium stapled peptides and foldamers on‐resin. The methodology similarly uses two orthogonally protected amino‐functionalized side chains and features the use of a diamino connector. The two guanidinium groups are introduced sequentially, the first one intermolecularly and the second intramolecularly. The method is compatible with the i , i + 4 and i , i + 7 cyclization schemes and tolerates a diversity of diamino linkers. We applied the strategy to the synthesis of macrocyclic inhibitors of hDM2 and hDMX and identified several high affinity binders for the two proteins
Bringing memory to Boolean networks: a unifying framework
No full textInternational audienceBoolean networks are extensively applied as models of complex dynamical systems, aiming at capturing essential features related to causality and synchronicity of the state changes of components along time. Dynamics of Boolean networks result from the application of their Boolean map according to a so-called update mode, specifying the possible transitions between network configurations. In this paper, we explore update modes that possess a memory on past configurations, and provide a generic framework to define them. We show that recently introduced modes such as the most permissive and interval modes can be naturally expressed in this framework, and we propose novel update modes, the history-based, trapping, and subcube-based modes. Building on the unified definitions, we provide a comprehensive comparison of memory-based update modes, resulting in their hierarchy by simulation and weak simulation. Finally, we highlight consequences of introducing memory on the notions of trajectory and attractor
Retinal Microvascular Correlates of Cerebral Small Vessel Disease in Older Age
No full textInternational audienceBackground and objectives: Cerebral small vessel disease (cSVD), characterized by pathologic changes in the structure and function of small brain vessels, is detectable on brain MRI in the absence of clinical symptoms. However, imaging cerebral small vessels themselves in vivo remains costly and challenging. There is growing interest in investigating whether retinal microvascular imaging features could be proxies for changes in the brain microvasculature. Using a multipronged approach, we explored the relation of retinal microvascular characteristics with MRI markers of cSVD (MRI-cSVD).Methods: First, we explored this relationship in older community persons from the population-based 3C-Dijon cohort. MRI-cSVD was assessed on a 1.5-Tesla MRI at baseline, comprising white matter hyperintensity volume (WMHV), lacunes, and a composite extreme cSVD phenotype (WMHV extreme distributions and presence/absence of lacunes). At 10-year follow-up, participants underwent measurements of retinal microvascular features on fundus using the Singapore "I" Vessel Assessment software. To support 3C-Dijon findings, we conducted a comprehensive literature review up to July 2024 from PubMed/EMBASE and used 2-sample Mendelian randomization (MR) leveraging large-scale genome-wide association studies, to assess causality and directionality.Results: In 670 3C-Dijon participants (median age 70.7, 65.7% women), multivariable analyses (adjusted for age, sex, axial length, and cardiovascular risk factors) showed a significant association of lower arteriolar fractal dimension (FDa) with extreme cSVD (odds ratio [OR] 1.68, 95% CI 1.20-2.34) after multiple testing correction (p < 0.0042), and at p < 0.05, associations of lower FDa and smaller arteriolar caliber with larger WMHV (β = 0.0534 [95% CI 0.0075-0.0569] and 0.0519 [95% CI 0.0045-0.0993]), and of greater venular tortuosity (TORTv) with lacunes (OR 1.45, 95% CI 1.05-2.00). Lower FDa was also associated with poorer executive function. The systematic review of the literature identified 12 studies (N = 7,796) that showed mostly consistent direction of effects for FDa (5/6 studies), TORTv (4/6), and arteriolar caliber (10/11), although statistical significance was observed in 5 individual studies only. Two-sample MR based on large genome-wide association studies (N = 5,292-52,798) showed evidence for a potentially causal association of greater TORTv with extreme cSVD and larger WMHV (p = 0.0017 and 0.049), with no evidence for reverse causation.Discussion: We provide multimodal evidence that geometric characteristics of the retinal microvasculature are associated with increased burden of MRI-cSVD and possibly worse executive function
Reproducible Boolean model analyses and simulations with the CoLoMoTo software suite: a tutorial
No full textInternational audienceThis tutorial provides stepwise instructions to install over 20 tools, written in multiple languages. Their integration in the CoLoMoTo software suite makes them accessible with a single popular language (Python), thereby enabling reproducible and sophisticated dynamical analyses of logical models of complex cellular networks. The tutorial specifically focuses on the analysis of a previously published model of the regulatory network controlling mammalian cell proliferation. It includes chunks of Python code to reproduce several of the results and figures published in the original article, and further extends these results with the help of selected tools included in the CoLoMoTo suite. The tutorial covers the visualization of the network with the tool GINsim, an attractor analysis with bioLQM, the computation of synchronous attractors with BNS, the extraction of modules from the full model, stochastic simulations of the wild-type model and of selected perturbations with MaBoSS and finally the delineation of compressed probabilistic state transition graphs. The integration of all these analyses in an executable Jupyter Notebook greatly eases their reproducibility, as well as the inclusion of further extensions. The notebook provided along with this tutorial further constitutes a template, which can be enriched with other ColoMoTo tools, to develop comprehensive dynamical analyses of various biological network models
A unified framework for hydromechanical signaling can explain transmission of local and long-distance signals in plants
No full textInternational audienceLocal wounding in plants triggers signals that travel locally within the wounded leaf or systemically through the vasculature to distant leaves. Our understanding of the mechanisms of initiation and propagation of this ubiquitous class of signals remains incomplete. Here, we develop a unifying framework based on poroelastic dynamics to study two coupled biophysical processes—propagation of pressure changes and transmission of chemical elicitors via mass flows driven by these pressure changes—as potential mechanisms for the initiation and propagation of wound-induced signals. We show that rapid pressure changes in the xylem can transmit mechanical information across the plant, while their coupling with neighboring nonvascular tissue drives swelling and mass flow that can transport chemical elicitors to distant leaves. We confront predictions from our model with measurements of signaling dynamics in several species to show that i) the poroelastic model can capture the observed dynamics of purely mechanical changes (swelling of distant leaves) induced by wounding; ii) advection and diffusion of hypothetical elicitors with mass flows induced by poroelastic relaxations can explain distant cellular responses observed with gene-encoded reporters of cytosolic calcium concentration and electrical signals; and iii) poroelastic diffusion of pressure changes around local wounds in nonvascular tissue matches the observed cytosolic calcium signals and represents an alternative hypothesis relative to molecular diffusion of chemical elicitors. This framework provides a valuable foundation for assessing mechanisms of signal transmission and for designing future experiments to elucidate factors involved in signal initiation, propagation, and target elicitation
An Active Flux method for the Euler equations based on the exact acoustic evolution operator
No full textA new Active Flux method for the multi-dimensional Euler equations is based on an additive operator splitting into acoustics and advection. The acoustic operator is solved in a locally linearized manner by using the exact evolution operator. The nonlinear advection operator is solved at third order accuracy using a new approximate evolution operator. To simplify the splitting, the new method uses primitive variables for the point values and for the reconstruction. In order to handle discontinuous solutions, a blended bound preserving limiting is used, that combines a priori and a posteriori approaches. The resulting method is able to resolve multi-dimensional Riemann problems as well as low Mach number flow, and has a large domain of stability
A generalized Active Flux method of arbitrarily high order in two dimensions
No full textInternational audienceThe Active Flux method can be seen as an extended finite volume method. The degrees of freedom of this method are cell averages, as in finite volume methods, and in addition shared point values at the cell interfaces, giving rise to a globally continuous reconstruction. Its classical version was introduced as a one-stage fully discrete, third-order method. Recently, a semi-discrete version of the Active Flux method was presented with various extensions to arbitrarily high order in one space dimension. In this paper we extend the semi-discrete Active Flux method on two-dimensional Cartesian grids to arbitrarily high order, by including moments as additional degrees of freedom (hybrid finite element--finite volume method). The stability of this method is studied for linear advection. For a fully discrete version, using an explicit Runge-Kutta method, a CFL restriction is derived. We end by presenting numerical examples for hyperbolic conservation laws