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The origin of funerary practices has important implications for the emergence of so-called modern cognitive capacities and behaviour. We provide new multidisciplinary information on the archaeological context of the La Ferrassie 8 Neandertal skeleton (grand abri of La Ferrassie, Dordogne, France), including geochronological data -14C and OSL-, ZooMS and ancient DNA data, geological and stratigraphic information from the surrounding context, complete taphonomic study of the skeleton and associated remains, spatial information from the 1968–1973 excavations, and new (2014) fieldwork data. Our results show that a pit was dug in a sterile sediment layer and the corpse of a two-year-old child was laid there. A hominin bone from this context, identified through Zooarchaeology by Mass Spectrometry (ZooMS) and associated with Neandertal based on its mitochondrial DNA, yielded a direct 14C age of 41.7–40.8 ka cal BP (95%), younger than the 14C dates of the overlying archaeopaleontological layers and the OSL age of the surrounding sediment. This age makes the bone one of the most recent directly dated Neandertals. It is consistent with the age range for the Châtelperronian in the site and in this region and represents the third association of Neandertal taxa to Initial Upper Palaeolithic lithic technocomplex in Western Europe. A detailed multidisciplinary approach, as presented here, is essential to advance understanding of Neandertal behavior, including funerary practices.

International audience; Studying endocasts has long allowed anthropologists to examine changes in the external topography and the overall size of the brain throughout the evolutionary history of hominins. The nearly complete calvaria of Manot 1 presents an opportunity to gain insights into the external brain morphology, vascular system, and dimensions of the brain of this late Middle Paleolithic hominin. Detailed size and shape analyses of the Manot 1 endocast indicate a modern Homo sapiens anatomy, despite the presence of some primitive features of the calvaria. Traits considered to be derived endocranial features for H. sapiens are present in Manot 1, including an elongated parietal sagittal chord with an elevated superior part of the hemisphere, a widened posterior part of the frontal lobes, a considerable development of the parietal reliefs such as the supramarginal lobules, and a slight posterior projection of the occipital lobes. These findings, together with data presented in previous studies, rule out the possibility of a direct Neanderthal ancestry for the Manot 1 hominin and instead confirm its affiliation with H. sapiens. The Manot 1 calvaria is more similar to that of later Upper Paleolithic H. sapiens than it is to the earlier Levantine populations of Skhul and Qafzeh. The late Middle Paleolithic date of Manot 1 provides an opportunity to analyze the recent developments in human cerebral morphology and organization.

OBJECTIVES We provide the description and comparative analysis of all the human fossil remains found at Axlor during the excavations carried out by J. M. de Barandiaran from 1967 to 1974: a cranial vault fragment and eight teeth, five of which likely belonged to the same individual, although two are currently lost. Our goal is to describe in detail all these human remains and discuss both their taxonomic attribution and their stratigraphic context. MATERIALS AND METHODS We describe external and internal anatomy, and use classic and geometric morphometrics. The teeth from Axlor are compared to Neandertals, Upper Paleolithic, and recent modern humans. RESULTS Three teeth (a left dm2, a left di1, and a right I1) and the parietal fragment show morphological features consistent with a Neandertal classification, and were found in an undisturbed Mousterian context. The remaining three teeth (plus the two lost ones), initially classified as Neandertals, show morphological features and a general size that are more compatible with their classification as modern humans. DISCUSSION The combined anatomical and stratigraphic study suggest that the remains of two different adult Neandertals have been recovered during the old excavations performed by Barandiaran: a left parietal fragment (Level VIII) and a right I1 (Level V). Additionally, two different Neandertal children lost deciduous teeth during the formations of levels V (left di1) and IV (right dm2). In addition, a modern human individual is represented by five remains (two currently lost) from a complex stratigraphic setting. Some of the morphological features of these remains suggest that they may represent one of the scarce examples of Upper Paleolithic modern human remains in the northern Iberian Peninsula, which should be confirmed by direct dating.

International audience; Although Neandertals are the best-known fossil hominins, the tempo and evolutionary processes in their lineage are strongly debated. This is in part due to the scarcity of the fossil record, in particular before the marine isotopic stage (MIS) 5. In 2010, a partial hominin mandible was discovered at the Middle Paleolithic site of Payre (France) in a layer that is dated to the end of MIS 8/beginning of MIS 7, a time period for which very few fossils are known in Europe. The Payre 15 mandible retains the complete symphyseal region and right lateral corpus with heavily worn P4, M1, and M2 in situ. Taphonomic modifications in the form of three notches suggest that this individual was chewed by a carnivore. We provide here the first detailed description of this specimen and a comparative analysis that includes morphological features, linear mandibular dimensions, an elliptic Fourier analysis of the symphysis, and a morphometric analysis of the M1 roots (based on segmented CT scan data). Our comparative sample encompasses European Middle and Upper Pleistocene specimens attributed to Homo heidelbergensis and Homo neanderthalensis, Upper Pleistocene Homo sapiens, and Holocene Homo sapiens. The Payre 15 mandible shows a combination of primitive and Neandertal-like features, with a receding symphyseal profile without any element of the mentum osseum, a posterior location of the mental foramen and lateral prominence. Its mandibular body is tall and thick anteriorly. Payre 15 has mesotaurodont M1 roots and a three-rooted M2. By its dimensions and combination of features, Payre 15 aligns better with Middle Pleistocene European hominins than with MIS 6–3 Neandertals. Noteworthy, it falls well within the range of variation of the Sima de los Huesos sample. Our results underscore that the total pattern of Neandertal-derived morphology was not achieved at the beginning of the MIS 7 and suggest a low level of mandibular diachronic changes for the period MIS 11–7.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death in the world, and curative systemic therapies are lacking. Chimeric antigen receptor (CAR)–expressing T cells induce robust antitumor responses in patients with hematologic malignancies but have limited efficacy in patients with solid tumors, including HCC. IL15 and IL21 promote T-cell expansion, survival, and function and can improve the antitumor properties of T cells. We explored whether transgenic expression of IL15 and/or IL21 enhanced glypican-3-CAR (GPC3-CAR) T cells' antitumor properties against HCC. We previously optimized the costimulation in GPC3-CARs and selected a second-generation GPC3-CAR incorporating a 4-1BB costimulatory endodomain (GBBz) for development. Here, we generated constructs encoding IL15, IL21, or both with GBBz (15.GBBz, 21.GBBz, and 21.15.GBBz, respectively) and examined the ability of transduced T cells to kill, produce effector cytokines, and expand in an antigen-dependent manner. We performed gene-expression and phenotypic analyses of GPC3-CAR T cells and CRISPR-Cas9 knockout of the TCF7 gene. Finally, we measured GPC3-CAR T-cell antitumor activity in murine xenograft models of GPC3+ tumors. The increased proliferation of 21.15.GBBz T cells was at least in part dependent on the upregulation and maintenance of TCF-1 (encoded by TCF7) and associated with a higher percentage of stem cell memory and central memory populations after manufacturing. T cells expressing 21.15.GBBz had superior in vitro and in vivo expansion and persistence, and the most robust antitumor activity in vivo. These results provided preclinical evidence to support the clinical evaluation of 21.15.GPC3-CAR T cells in patients with HCC.

Cranial anatomical features play a prominent part in the definition of extinctHomotaxa and in species identification in fossils. Thus, knowledge of cranial morphology considered within its geochronological framework is essential to the understanding of the evolution, chronology, and dispersal of the genusHomo. The brain is also a valuable object of study for research on human evolution, because of features such as its large size and a high encephalization quotient in someHomospecies, as well as the complexity of human cognition. However, the joint evolution of endo- and ectocranial anatomies is still little studied, and landmarks representing cerebral anatomy rather than inner cranial bone anatomy are still rarely used. This exploratory piece of research examines endo- and ectocranial profiles in samples representing 3Homotaxa:Homo sapiens(fossil and recent specimens),Homo erectus, andHomo neanderthalensis. We used 2D geometric morphometrics to analyze the shape of the endo- and ectocranial vaults, as well as the relationships between selected anatomical features such as the extension of lobes and bones. The shapes of the vaults were computed using both fixed landmarks and sliding semi-landmarks. The fixed landmarks used for the endocranium were chosen in order to represent cerebral anatomy, in that they are defined by the imprints left by brain structures on the inner bone surface of the skull, and not by bony structures such as the inferior side of cranial sutures. Among other results, we have shown or confirmed specific features in the shape of the endocranium inHomo sapiens, as well as a few differences in the patterns of interplay between lobes and bones. These data, and any further results obtained with larger samples, may provide new insights into the development of the endocranial anatomical pattern inHomo sapiensand of its variability.

Although recently the internal structure of the non-supranuchal fossa of Homo sapiens has been described and compared to that observed in the Neandertal suprainiac fossa, until now it has not been examined in any modern human children. In this study, the internal structure of this fossa in the occipital bones of three children (two aged 3‒4 years and one aged 5 years ± 16 months) and one adult individual representing recent Homo sapiens from Australia was analysed and compared to that of the Neandertal suprainiac fossa. In order to analyse the internal composition of the fossae of the examined specimens, initially, high-resolution micro-CT datasets were obtained for their occipital bones; next, 3D topographic maps of the variation in thickness of structural layers of the occipital bones were made and 2D virtual sections in the median region of these fossae were prepared. In the fossa of one immature individual, the thinning of the diploic layer characteristic of a Neandertal suprainiac fossa was firmly diagnosed. The other Neandertal-like trait, concerning the lack of substantial thinning of the external table of the bone in the region of the fossa, was established in two individuals (one child and one adult) due to the observation of an irregular pattern of the thickness of this table in the other specimens, suggesting the presence of an inflammatory process. Our study presents, for the first time, Neandertal-like traits (but not the whole set of features that justifies the autapomorphic status of the Neandertal supraniac fossa) in the internal structure of non-supranuchal fossae of some recent Homo sapiens. We discuss the phylogenetic implications of the results of our analysis and stress the reasons that use of the 3D topographic mapping method is important for the correct diagnosis of Neandertal traits of the internal structure of occipital fossae.

Objectives Bilateral asymmetry of diaphyseal shape and size may be a reflection of relative activity levels and patterns of habitual biomechanical stress in the upper arms of Neandertals and Homo sapiens. The main purpose of our study was to assess the level of directional asymmetry of humeral cross sections in Neandertals, recent Australian aborigines, and medieval farmers. Materials and methods Indices of directional and absolute asymmetry (%DA and %AA) of humeral cross-sectional properties in Neandertals and recent Homo sapiens were calculated. Evenly distributed semilandmarks around the external and internal borders of cortical bone were digitized in the course of computed tomography for analysis of shape differences between sides of the body. Results The medieval farmers were characterized by significant %DA and %AA for polar second moment of area (J), ratio of maximum to minimum second moments of area, and ratio of antero-posterior to medio-lateral bending strength. In Australian aborigines, only J in males shows significant %DA and %AA, while Neandertals exhibit no significant asymmetry of any cross-sectional properties. Differences in cross-sectional shape between sides of the body were established in all three analyzed groups. Discussion High levels of directional asymmetry of cross-sectional shape and properties in medieval farmers may be caused by the performance of more physically demanding tasks using one side of the body from an early age in that population. Various patterns of asymmetry in Neandertals and modern humans may be caused by different habitual behaviors during growth, eco-geographic patterns in body proportions, genetic factors, and differences in ontogeny.

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International audience; The La Ferrassie 1 (LF1) skeleton, discovered over a century ago, is one of the most important Neandertal individuals both for its completeness and due to the role it has played historically in the interpretation of Neandertal anatomy and lifeways. Here we present new skeletal remains from this individual, which include a complete right middle ear ossicular chain (malleus, incus, and stapes), three vertebral fragments, and two costal remains. Additionally, the study of the skeleton has allowed us to identify new pathological lesions, including a congenital variant in the atlas, a greenstick fracture of the left clavicle, and a lesion in a mid-thoracic rib of unknown etiology. In addition, we have quantified the amount of vertebral pathology, which is greater than previously appreciated. We have complemented the paleopathological analysis with a taphonomic analysis to identify any potential perimortem fractures. The taphonomic analysis indicates that no surface alteration is present in the LF1 skeleton and that the breakage pattern is that of bone that has lost collagen, which would be consistent with the intentional burial of this individual proposed by previous researchers. In this study, we used CT and microCT scans in order to discover new skeletal elements to better characterize the pathological lesions and to quantify the fracture orientation of those bones in which the current plaster reconstruction did not allow its direct visualization, which underlines the broad potential of imaging technologies in paleoanthropological research. A century after its discovery, LF1 is still providing new insights into Neandertal anatomy and behavior.

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Among all tumor suppressor microRNAs, reduced let-7 expression occurs most frequently in cancer and typically correlates with poor prognosis. Activation of either LIN28A or LIN28B, two highly related RNA binding proteins (RBPs) and proto-oncogenes, is responsible for the global post-transcriptional downregulation of the let-7 microRNA family observed in many cancers. Specifically, LIN28A binds the terminal loop of precursor let-7 and recruits the Terminal Uridylyl Transferase (TUTase) ZCCHC11 that polyuridylates pre-let-7, thereby blocking microRNA biogenesis and tumor suppressor function. For LIN28B, the precise mechanism responsible for let-7 inhibition remains controversial. Functionally, the decrease in let-7 microRNAs leads to overexpression of their oncogenic targets such as MYC, RAS, HMGA2, BLIMP1, among others. Furthermore, mouse models demonstrate that ectopic LIN28 expression is sufficient to drive and/or accelerate tumorigenesis via a let-7 dependent mechanism. In this review, the LIN28/let-7 pathway is discussed, emphasizing its role in tumorigenesis, cancer stem cell biology, metabolomics, metastasis, and resistance to ionizing radiation and several chemotherapies. Also, emerging evidence will be presented suggesting that molecular targeting of this pathway may provide therapeutic benefit in cancer.

Cervical vertebrae not only protect the spinal cord but also are the insertion and origin points for muscles related to the movement of the head, upper limb, and trunk, among others, and are thus important elements in primate evolution. While previous work has been undertaken on the first two cervical vertebrae, there is a dearth of studies on the subaxial cervical spine in hominines. In this paper, we provide detailed morphological information on two important aspects of the subaxial cervical vertebrae (C3 - C7): mid-sagittal morphology and superior facet orientation. We studied large samples of African apes including modern humans and the most complete fossil hominin subaxial cervical vertebrae using both traditional and geometric morphometrics. There are significant differences between extant hominoids related to the relative length and orientation of the spinous process as well as to the orientation of the articular facets, which are related to size, locomotion, and neck posture. In fact, fossil hominins do not completely conform to any of the extant groups. Our assessment of mid-sagittal morphology and superior articular facet orientation shows that australopiths have more Homo-like upper subaxial cervical vertebrae coupled with more "primitive" lower cervical vertebrae. Based on these results, we hypothesize that those changes, maybe related to postural changes derived from bipedalism, did not affect the entire subaxial cervical spine at once. From a methodological point of view, the combination of traditional and geometric morphometric data provides a more integrative perspective of morphological change and evolution, which is certainly useful in human evolutionary studies.

International audience; We previously described a neurofilament derived cell-penetrating peptide, NFL-TBS.40-63, that specifically enters in glioblastoma cells where it disturbs the microtubule network both in vitro and in vivo. The aim of this study is to test whether this peptide can increase the targeted uptake by glioblastoma cells of lipid nanocapsules filled with Paclitaxel, and thus can increase their anti-proliferation in vitro and in vivo. Here, using the drop tensiometry we show that approximately 60 NFL-TBS.40-63 peptides can bind to one 50 nm lipid nanocapsule. When nanocapsules are filled with a far-red fluorochrome (DiD) and Paclitaxel, the presence of the NFL-TBS.40-63 peptide increases their uptake by glioblastoma cells in culture as evaluated by FACS analysis, and thus reduces their proliferation. Finally, when such nanocapsules were injected in mice bearing a glioma tumour, they are preferentially targeted to the tumour and reduce its progression. These results show that nanocapsules functionalized with the NFL-TBS.40-63 peptide represent a powerful drug-carrier system for glioma targeted treatment.

Indonesia, and particularly Java island, has been the place of the longest occupation by Homo erectus' species. Since the first Homo erectus found by Eugene Dubois in 1891 in the Trinil site, the discoveries of human remains have been regular, allowing the gathering of the most important concentration of Homo erectus in the world spanning more than 1.7 million years. The new fossil specimen discovered near Sendang Klampok in the Sangiran Dome (Central Java, Indonesia), which represents the left infero-posterior part of a skullcap, supplements the more ancient sample from Sangiran dome. The metrical and morphological features observed on this specimen with in particular the length of the parietomastoid suture, the lower position of the temporal lines which relief is blunt and joining those of the mastoidal crest and lateral part of the transverse occipital torus constituting an extensive formation covering the junction of the temporal, parietal and occipital bones, the protruding mastoid process, external occipital crest well expressed and shape of cerebellar lobes are many characters closer to the Ngandong hominins, clearly different from those of Kabuh (Bapang) and Zhoukoudian Lower Cave specimens.

In this study, a new active targeting strategy to favour ferrociphenol (FcdiOH) internalisation into brain tumour cells was developed by the use of lipid nanocapsules (LNCs) coated with a cell-internalising peptide (NFL-TBS.40-63 peptide) that interacts with tubulin-binding sites. In comparison, OX26 murine monoclonal antibodies (OX26-MAb) targeting transferrin receptors were also inserted onto the LNC surface. The incorporation of OX26 or peptide did not influence the in vitro antiproliferative effect of FcdiOH-LNCs on the 9L cells since their IC50 values were found in the same range. In vivo, intracerebral administration of OX26-FcdiOH-LNCs or peptide-FcdiOH-LNCs by convection enhanced delivery did not enhance the animal median survival time in comparison with untreated rats (25 days). Interestingly, intra-carotid treatment with peptide-FcdiOH-LNCs led to an ameliorated survival time of treated rats with the presence of animals surviving until days 35, 40 and 44. Such results were not obtained with OX26-MAbs, demonstrating the benefit of NFL-TBS.40-63 peptide as an active ligand for peripheral drug delivery to the brain tumours.

The occipital bone of Neandertals contains an association of morphological features that is considered characteristic of this fossil human population. One of the possible autapomorphic traits of Neandertals is the presence of a suprainiac fossa, a horizontal oval-shaped depression located on the occipital plane. The question of whether suprainiac depressions observed on Neandertals and in other human samples are homologous has been widely discussed. The present study provides a detailed anatomical description of the fossa and of the underlying internal bone composition for Neandertals of various geographical and chronological origins, and of different developmental stages. The suprainiac fossa is systematically present on Neandertals from the earliest developmental stages as well as at the beginning of the differentiation of the Neandertal lineage. A similar pattern for the structural composition of the bone is found among all analyzed Neandertals (i.e., the suprainiac fossa corresponds to a thinning of the diploic layer with no substantial remodeling nor variation in the external table thickness in this area). On the contrary, the occipital depressions present on a sample of anatomically modern humans from Europe and Africa correspond to a resorptive area of the external cranial surface only. These depressions also differ in shape, disposition, and aspect on the external cranial surface from those fossae on Neandertals. We demonstrate that the depressions described in anatomically modern humans, as well as other hominin species, are not homologous to the suprainiac fossa of Neandertals. Consequently, we confirm the autapomorphic status of the Neandertal suprainiac fossa.

The first evidence of the partial infant Neandertal skeleton La Ferrassie 8 (LF8) was discovered in 1970, although most of the remains were found in 1973 as part of the 1968-1973 work at the site by H. Delporte. This individual and the other Neandertal children from La Ferrassie were published in the early 1980s by J.-L. Heim, and since then LF8 has been regarded as coming from a poorly documented excavation. The recent rediscovery of the box that contained the hominin bones given by Delporte to Heim in the Museum national d'Histoire naturelle (MNHN) collection provided new fossils and helped to locate LF8 in the site: level M2 in square 1. Two visits to the Musee d'Archeologie nationale et Domaine national de Saint-Germain-en-Laye (MAN) yielded additional fossil remains from both the 1970 and 1973 excavations and resulted in the discovery of all of the notes from the excavation of H. Delporte between 1968 and 1973. Here the new fossil remains (47 after performing all possible refits), representing significant portions of the cranium, mandible, and vertebral column together with fragmentary hand and costal remains, are described. Unsurprisingly, the morphology of the bony labyrinth and of a complete stapes from the nearly complete left temporal show clear Neandertal affinities. Additionally, a complete reassessment of the original LF8 collection has resulted in the identification of several errors in the anatomical determination. Despite the significant increase in the anatomical representation of LF8, the skeletal remains are still limited to the head, thorax, pelvis, and four hand phalanges, with some very fragile elements relatively well preserved. Different hypotheses are proposed to explain this anatomical representation, which can be tested during future fieldwork.

Cranial vault thickness (CVT) of Liang Bua 1, the specimen that is proposed to be the holotype of Homo floresiensis, has not yet been described in detail and compared with samples of fossil hominins, anatomically modern humans or microcephalic skulls. In addition, a complete description from a forensic and pathological point of view has not yet been carried out. It is important to evaluate scientifically if features related to CVT bring new information concerning the possible pathological status of LB1, and if it helps to recognize affinities with any hominin species and particularly if the specimen could belong to the species Homo sapiens. Medical examination of the skull based on a micro-CT examination clearly brings to light the presence of a sincipital T (a non-metrical variant of normal anatomy), a scar from an old frontal trauma without any evident functional consequence, and a severe bilateral hyperostosis frontalis interna that may have modified the anterior morphology of the endocranium of LB1. We also show that LB1 displays characteristics, related to the distribution of bone thickness and arrangements of cranial structures, that are plesiomorphic traits for hominins, at least for Homo erectus s.l. relative to Homo neanderthalensis and H. sapiens. All the microcephalic skulls analyzed here share the derived condition of anatomically modern H. sapiens. Cranial vault thickness does not help to clarify the definition of the species H. floresiensis but it also does not support an attribution of LB1 to H. sapiens. We conclude that there is no support for the attribution of LB1 to H. sapiens as there is no evidence of systemic pathology and because it does not have any of the apomorphic traits of our species.

X-ray Computed Tomography (CT) scanning is a powerful imaging process for the digitization, exploration and 3D modeling of objects in the natural sciences. It allows for the observation of the internal structures of any type of sample (mineral, fossil, extant) on a sub-micron scale. The finest structures can be selected and extracted as virtual 3D models, and quantified in a repetitive way. These CT-scanned models have applications for the preventive conservation of rare and fragile specimens. The Museum national d'Histoire naturelle, Paris, France, recently acquired a high-resolution CT scan, a v|tome|x L240-180 from GE Sensing and Inspection Technologies phoenix|x-ray, with unique performance capabilities and applications for the natural science field. Indeed, the two x-ray microfocus and nanofocus sources, coupled with a large-size detector, allow for the imaging of samples with extremely variable sizes and densities. Here we present the new MNHN CT scanning Platform “AST-RX” and some results of several projects developed using it.

International audience; Cell-penetrating peptides (CPPs) can translocate through the plasma membrane and localize in different cell compartments providing a promising delivery system for peptides, proteins, nucleic acids, and other products. Here we describe features of a novel cell-penetrating peptide derived from the intermediate filament protein vimentin, called Vim-TBS.58-81. We show that it enters cells from a glioblastoma line via endocytosis where it distributes throughout the cytoplasm and nucleus. Moreover, when coupled to the pro-apoptogenic peptide P10, it localizes to the nucleus inhibiting cell proliferation. Thus, the Vim-TBS.58-81 peptide represents an effective vector for delivery of peptides and potentially a broad range of cargos to the nucleus.

International audience; Brain shape asymmetries or petalias consist of the extension of one cerebral hemisphere beyond the other. A larger frontal or caudal projection is usually coupled with a larger lateral extent of the more projecting hemisphere relative to the other. The concurrence of these petalial components is characteristic of hominins. Studies aimed at quantifying petalial asymmetries in human and great ape endocasts rely on the definition of the midline of the endocranial surface. Studies of brain material show that, at least in humans, most of the medial surface of the left occipital lobe distorts along the midline and protrudes on to the right side, making it difficult for midline and corresponding left and right reference point identification. In order to accurately quantify and compare brain shape asymmetries in extant hominid species, we propose here a new protocol based on the objective definition of cranial landmarks. We describe and quantify for the first time in three dimensions the positions of frontal and occipital protrusions in large samples of Pan paniscus, Pan troglodytes and Gorilla gorilla. This study confirms the existence of frontal and occipital petalias in African apes. Moreover, the detailed analysis of the 3D structure of these petalias reveals shared features, as well as features that are unique to the different great ape species.; Les asymétries de forme du cerveau, communément appelées petalias, consistent en l’extension d’un des hémisphères cérébraux au delà de l’autre. L’hémisphère se projetant par rapport à l’autre en avant, pour les lobes frontaux, ou en arrière, pour les lobes occipitaux, a souvent aussi une extension latérale plus importante. La coïncidence de ces différentes asymétries serait caractéristique des homininés. Les études antérieures qui ont cherché à quantifier les pétalias cérébraux sur des endocrânes d’hommes actuels ou de grands singes reposent sur l’utilisation du plan sagittal médian de l’endocrâne pour caractériser ces asymétries. Néanmoins, des travaux menés directement sur des cerveaux humains montrent que la majeure partie médiale du lobe occipital gauche traverse ce référentiel central et se propage vers la droite, rendant délicate la détermination même du plan de référence ainsi que la définition des points de référence des côtés gauche et droit. Dans ce contexte, nous proposons ici un protocole inédit basé sur l’utilisation de points crâniens pour déterminer de manière indépendante et non-biaisée un référentiel permettant de quantifier précisément les asymétries cérébrales. Nous décrivons et quantifions ainsi pour la première fois la position tridimensionnelle des projections maximales des lobes frontaux et occipitaux sur de larges échantillons de spécimens sauvages appartenant aux espèces Pan paniscus, Pan troglodytes et Gorilla gorilla. Cette étude démontre la présence d’asymétrie pour les différentes composantes tridimensionnelles des pétalias antéro-postérieurs des lobes frontaux et occipitaux chez ces grands singes, l’existence de caractères partagés, ainsi que de spécificités pour chacun de ces groupes. Les implications fonctionnelles de ces asymétries demeurent délicates à interpréter en raison du peu d’informations disponibles sur le comportement de ces primates dans leur milieu naturel. Par ailleurs, des études ultérieures analyserons les schéma de distribution des pétalias chez les hominidés, en intégrant les homininés fossiles, afin d’interpréter les potentielles variations de taille et de distribution de ces asymétries et leurs éventuelles relations avec la latéralisation manuelle, les capacités de langage et les spécialisations dans les taches cognitives.

Cranial anomalies vary in degree of expression. Although some are nominal i.e. slight in expression, other anomalies are quite striking in appearance. Such is the case in a cranium recovered from the archaeological site of Carthage in Tunisia. Based on observations during ongoing research by the second author, this specimen was seen to exhibit a twinned right external auditory meatus. Possible explanations for the presence of this anomaly are explored. Trauma and perhaps disease can likely be excluded; congenital or epigenetic variation is more of a probable cause. Copyright © 2009 John Wiley & Sons, Ltd.

The temporal bone is used frequently to determine taxonomic affinities as it contains several features that differentiate Neandertals from anatomically modern Homo sapiens. However, only little information is available about temporal bone pneumatization in Neandertals. This study provides descriptions and comparisons of the disposition and the extensiveness of the pneumatization of the temporal bone in large samples of Neandertal specimens of different geological and developmental ages (25 individuals and 33 temporal bones from the sites of Engis,Krapina, La Chapelle aux Saints, La Ferrassie, La Quina, Pech de l'Azé, and Spy).Although temporal bone pneumatization shows some individual variability, a similar pattern of distribution is found in all adult Neandertal individuals from Krapina and Western Europe. Pneumatization is restricted mainly to most parts of the petromastoid areas. We also retrace forthe first time the modalities of growth and development of this pneumatization in Neandertals. Finally, this study provides new information about possible correlations between the extension and position of temporal bone pneumatization and some of the morphological features used to characterize the temporal bone of the Neandertals. These latter features include the relatively low and short temporal squama, the robust zygomatic process with a relatively marked lateral projection, the strong supramastoid crest, the significant thickness of the tympanic part of the temporal bone, and the relatively small mastoid process and large juxtamastoid eminence. Our results suggest that the development of pneumatization in Neandertals is related to available space and to temporal bone morphology. Moreover, it appears that the development of pneumatization does not play an active role in determining the morphology of the apomorphic features of the temporal bone in Neandertals.; Les caractères morphologiques de la surface externe de l'os temporal sont fréquemment utilisés lors des discussions taxinomiques afin d'identifier les spécimens Néandertaliens. A l'opposé, très peu de données sont disponibles au sujet de la pneumatisation de cette région anatomique chez ce groupe fossile. Cette étude propose une analyse comparative de la disposition et de l'extension de la pneumatisation de l'os temporal chez plusieurs échantillons Néandertaliens, comprenant de nombreux spécimens d'âges individuel et chronologique différents.Nous analysons 25 individus, pour un total de 33 os temporaux, provenant des sites d'Engis, Krapina, La Chapelle aux Saints, La Ferrassie, La Quina, Pech de l'Azé et Spy.Les résultats montrent qu'il existe chez les Néandertaliens un modèle adulte de distribution de la pneumatisation de l'os temporal. Cette dernière est très majoritairement localisée dans la région pétro-mastoïdienne. Aucune propagation des cellules pneumatiques n'a été observéedans les parties squameuse et tympanique de l'os temporal, ou en arrière du processus mastoïdien; alors que la pneumatisation est exceptionnelle et très limitée sous la crête supramastoïdienne, à l'apex du processus mastoïdien et à l'intérieur de l'éminence juxtamastoïdienne.

International audience; The external morphological features of the temporal bone are used frequently to determine taxonomic affinities of fossils of the genus Homo.Temporal bone pneumatization has been widely studied in great apes and in early hominids. However, this feature is rarely examined in the later hominids, particularly in Asian Homo erectus. We provide a comparative morphological and quantitative analysis of Asian Homo erectus from the sites of Ngandong, Sambungmacan, and Zhoukoudian, and of Neandertals and anatomically modern Homo sapiens in order to discuss causes and modalities of temporal bone pneumatization during hominid evolution. The evolution of temporal bone pneumatization in the genus Homo is more complex than previously described. Indeed, the Zhoukoudian fossils have a unique pattern of temporal bone pneumatization, whereas Ngandong and Sambungmacan fossils, as well as the Neandertals, more closely resemble the modern human pattern. Moreover, these Chinese fossils are characterized by a wide midvault and a relatively narrow occipital bone. Our results support the point of view that cell development does not play an active role in determining cranial base morphology. Instead, pneumatization is related to available space and to temporal bone morphology, and its development is related to correlated morphology and the relative disposition of the bones and cerebral lobes. Because variation in pneumatization is extensive within the same species, the phyletic implications of pneumatization are limited in the taxa considered here.; Les caractères morphologiques de la surface de l'os temporal sont fréquemment utilisés pour discuter des affinités taxinomiques des représentants fossiles du genre Homo. Par ailleurs, la pneumatisation de cette région du crâne a été largement étudiée chez les primates actuels et chez les Australopithéques, Paranthropes et premiers représentants du genre Homo. Une analyse morphologique et quantitative transversale chez des fossiles asiatiques attribués a` Homo erectus, des Néandertaliens et des Hommes anatomiquement modernes, est effectuée dans le but d'argumenter les causes et modalités de la pneumatisation de l'os temporal chez ces hominidés. L'évolution de cette pneumatisation au sein du genre Homo semble plus complexe que cela n'était proposé. En effet, son extension et sa répartition chez les fossiles de Zhoukoudian sont particulières alors que les fossiles de Ngandong, Sambungmacan et les Néandertaliens se rapprochent du schéma observé chez les Hommes anatomiquement modernes.De plus, ces fossiles chinois présentent certaines spécificités morphologiques des parties basales de la voûte crânienne. Les implications phylétiques des caractéristiques de cette pneumatisation restent néanmoins limitées puisque les variations peuvent être importantes au sein d'une même espèce.Nos résultats suggèrent que le développement des cellules pneumatiques de l'os temporal n'a pas d'implication fonctionnelle et que ce phénomène est lié à l'espace disponible, à la morphologie et à la position relative des lobes cérébraux et des structures osseuses.

National audience; This study presents the preliminary results of an examination of internal clavicular structures using CT scan data analysis. The complex morphology of this bone makes the determination of a reproducible CT slice plane impossible and so any classical analysis of the two-dimensional CT data is ruled out. We propose a new protocol which enables quantification in three dimensions of the variations in volume of the internal morphological structures of the clavicles.These are divided into three distinct groups (porosity, low density structures and high density structures) according to their radiological density. The first results show that the high density structures are represented by a larger volume than the low density structures. Moreover, chimpanzee clavicles are characterized by a relative volume of high density bone structure superior to that of gorillas and humans. For a quarter of chimpanzees, this is characterized by an absence of low density structures at the inflexion point of the acromial curvature. These differences can be interpreted as adaptations to the strainsto which the clavicles are subjected.; Ce travail présente les résultats préliminaires d'une étude sur les structures claviculaires internes, par l'intermédiairedu scanner à rayon X. La morphologie complexe de cet os rend impossible la détermination d'un plan de coupe similaire et reproductible d'un individu à l'autre et interdit ainsi toute analyse classique des données scanographiquesbidimensionnelles. Nous proposons un protocole inédit permettant de quantifier de manière précise et répétitive les variations volumiques en trois dimensions des structures morphologiques internes des clavicules. Celles-ci sont dissociées en trois ensembles distincts (structures osseuses denses, structures osseuses peu denses et porosité) en fonction de leur densité radiologique. Les premiers résultats montrent que les structures osseuses denses sont représentées par un volume plus important que les structures osseuses peu denses. De plus, les clavicules de chimpanzé sont caractérisées par un volume relatif des structures osseuses denses plus important que chez les gorilles et les hommes. Ceci s'exprime, entre autres, chez un quart des chimpanzés, par une absence des structures osseuses peu denses au point d'inflexion de la courbure acromiale. Ces différences peuvent être interprétées comme des adaptations aux contraintes subies par les clavicules.

International audience; Internal cranial structures of the Sambungmacan 1Homo erectus (Java, Indonesia). The Sambungmacan 1 fossil(Java, Indonesia) is assigned to the Homo erectus group. The carbonated matrix contained in this calvaria prevents the analysis of the internal surface. The CT data of the original fossil enables us to observe the conservation and mineralization state and the internal structures. Furthermore, we use the CT data to reconstruct the endocast, which shows that the morphological characterof Sambungmacan 1 is close to the Ngandong hominids.; Le fossile Sambungmacan 1 (Java, Indonésie), attribué aux Homo erectus, est une calotte crânienne pour laquelle la présence d'une matrice carbonatée empêchait tout accès à la surface interne. À partir des données scannographiques du fossile original, nous avons pu observer son état de conservation et de minéralisation ainsi que ses structures internes, et effectuer unereconstitution de l'endocrâne, dont les caractères morphologiques le rapprochent des hominidés de Ngandong.

International audience; We previously reported that a 24 amino acid peptide (NFL-TBS.40-63) corresponding to the tubulin-binding site located on the light neurofilament subunit, selectively enters in glioblastoma cells where it disrupts their microtubule network and inhibits their proliferation. Here, we analyzed the structure-function relationships using an alanine-scanning strategy, in order to identify residues essential for these biological activities. We showed that the majority of modified peptides present a decreased or total loss to penetrate in these cells, or to alter microtubules. Correspondingly, circular dichroism measurements showed that this peptide forms either β-sheet or α-helix structures according to the solvent and that alanine substitution modified or destabilized the structure, in relation with changes in the biological activities. Moreover, substitution of serine residues by phosphoserine or aspartic acid concomitantly decreased the cell penetrating activity and the structure stability. These results indicate the importance of structure for the activities, including selectivity to glioblastoma cells of this peptide, and its regulation by phosphorylation.