Long genetic and social isolation in Neanderthals before their extinction.

Neanderthal genomes have been recovered from sites across Eurasia, painting an increasingly complex picture of their populations' structure that mostly indicates that late European Neanderthals belonged to a single metapopulation with no significant evidence of population structure. Here, we report the discovery of a late Neanderthal individual, nicknamed "Thorin," from Grotte Mandrin in Mediterranean France, and his genome. These dentognathic fossils, including a rare example of distomolars, are associated with a rich archeological record of Neanderthal final technological traditions in this region ∼50-42 thousand years ago. Thorin's genome reveals a relatively early divergence of ∼105 ka with other late Neanderthals. Thorin belonged to a population with a small group size that showed no genetic introgression with other known late European Neanderthals, revealing some 50 ka of genetic isolation of his lineage despite them living in neighboring regions. These results have important implications for resolving competing hypotheses about causes of the disappearance of the Neanderthals.

Loss of ninein interferes with osteoclast formation and causes premature ossification.

Ninein is a centrosome protein that has been implicated in microtubule anchorage and centrosome cohesion. Mutations in the human NINEIN gene have been linked to Seckel syndrome and to a rare form of skeletal dysplasia. However, the role of ninein in skeletal development remains unknown. Here, we describe a ninein knockout mouse with advanced endochondral ossification during embryonic development. Although the long bones maintain a regular size, the absence of ninein delays the formation of the bone marrow cavity in the prenatal tibia. Likewise, intramembranous ossification in the skull is more developed, leading to a premature closure of the interfrontal suture. We demonstrate that ninein is strongly expressed in osteoclasts of control mice, and that its absence reduces the fusion of precursor cells into syncytial osteoclasts, whereas the number of osteoblasts remains unaffected. As a consequence, ninein-deficient osteoclasts have a reduced capacity to resorb bone. At the cellular level, the absence of ninein interferes with centrosomal microtubule organization, reduces centrosome cohesion, and provokes the loss of centrosome clustering in multinucleated mature osteoclasts. We propose that centrosomal ninein is important for osteoclast fusion, to enable a functional balance between bone-forming osteoblasts and bone-resorbing osteoclasts during skeletal development.

Toward Smart Biomimetic Apatite-Based Bone Scaffolds with Spatially Controlled Ion Substitutions.

Biomimetic apatites exhibit a high reactivity allowing ion substitutions to modulate their in vivo response. We developed a novel approach combining several bioactive ions in a spatially controlled way in view of subsequent releases to address the sequence of events occurring after implantation, including potential microorganisms' colonization. Innovative micron-sized core-shell particles were designed with an external shell enriched with an antibacterial ion and an internal core substituted with a pro-angiogenic or osteogenic ion. After developing the proof of concept, two ions were particularly considered, Ag+ in the outer shell and Cu2+ in the inner core. In vitro evaluations confirmed the cytocompatibility through Ag-/Cu-substituting and the antibacterial properties provided by Ag+. Then, these multifunctional "smart" particles were embedded in a polymeric matrix by freeze-casting to prepare 3D porous scaffolds for bone engineering. This approach envisions the development of a new generation of scaffolds with tailored sequential properties for optimal bone regeneration.

Safe-by-Design Antibacterial Peroxide-Substituted Biomimetic Apatites: Proof of Concept in Tropical Dentistry.

Bone infections are a key health challenge with dramatic consequences for affected patients. In dentistry, periodontitis is a medically compromised condition for efficient dental care and bone grafting, the success of which depends on whether the surgical site is infected or not. Present treatments involve antibiotics associated with massive bacterial resistance effects, urging for the development of alternative antibacterial strategies. In this work, we established a safe-by-design bone substitute approach by combining bone-like apatite to peroxide ions close to natural in vivo oxygenated species aimed at fighting pathogens. In parallel, bone-like apatites doped with Ag+ or co-doped Ag+/peroxide were also prepared for comparative purposes. The compounds were thoroughly characterized by chemical titrations, FTIR, XRD, SEM, and EDX analyses. All doped apatites demonstrated significant antibacterial properties toward four major pathogenic bacteria involved in periodontitis and bone infection, namely Porphyromonas gingivalis (P. gingivalis), Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Fusobacterium nucleatum (F. nucleatum), and S. aureus. By way of complementary tests to assess protein adsorption, osteoblast cell adhesion, viability and IC50 values, the samples were also shown to be highly biocompatible. In particular, peroxidated apatite was the safest material tested, with the lowest IC50 value toward osteoblast cells. We then demonstrated the possibility to associate such doped apatites with two biocompatible polymers, namely gelatin and poly(lactic-co-glycolic) acid PLGA, to prepare, respectively, composite 2D membranes and 3D scaffolds. The spatial distribution of the apatite particles and polymers was scrutinized by SEM and µCT analyses, and their relevance to the field of bone regeneration was underlined. Such bio-inspired antibacterial apatite compounds, whether pure or associated with (bio)polymers are thus promising candidates in dentistry and orthopedics while providing an alternative to antibiotherapy.

Low-energy electron beam sterilization of solid alginate and chitosan, and their polyelectrolyte complexes.

Polysaccharidic scaffolds hold great hope in regenerative medicine, however their sterilization still remains challenging since conventional methods are deleterious. Recently, electron beams (EB) have raised interest as emerging sterilization techniques. In this context, the aim of this work was to study the impact of EB irradiations on polysaccharidic macroporous scaffolds. The effects of continuous and pulsed low energy EB were examined on polysaccharidic or on polyelectrolyte complexes (PEC) scaffolds by SEC-MALLS, FTIR and EPR. Then the scaffolds' physicochemical properties: swelling, architecture and compressive modulus were investigated. Finally, sterility and in vitro biocompatibility of irradiated scaffolds were evaluated to validate the effectiveness of our approach. Continuous beam irradiations appear less deleterious on alginate and chitosan chains, but the use of a pulsed beam limits the time of irradiation and better preserve the architecture of PEC scaffolds. This work paves the way for low energy EB tailor-made sterilization of sensitive porous scaffolds.

A general Lewis acidic etching route for preparing MXenes with enhanced electrochemical performance in non-aqueous electrolyte.

Two-dimensional carbides and nitrides of transition metals, known as MXenes, are a fast-growing family of materials that have attracted attention as energy storage materials. MXenes are mainly prepared from Al-containing MAX phases (where A = Al) by Al dissolution in F-containing solution; most other MAX phases have not been explored. Here a redox-controlled A-site etching of MAX phases in Lewis acidic melts is proposed and validated by the synthesis of various MXenes from unconventional MAX-phase precursors with A elements Si, Zn and Ga. A negative electrode of Ti3C2 MXene material obtained through this molten salt synthesis method delivers a Li+ storage capacity of up to 738 C g-1 (205 mAh g-1) with high charge-discharge rate and a pseudocapacitive-like electrochemical signature in 1 M LiPF6 carbonate-based electrolyte. MXenes prepared via this molten salt synthesis route may prove suitable for use as high-rate negative-electrode materials for electrochemical energy storage applications.

Alginate-chitosan PEC scaffolds: A useful tool for soft tissues cell therapy.

In this study we evaluate macroporous scaffolds made of alginate-chitosan polyelectrolyte complexes (PEC) as tools to optimize the results of soft tissues cell therapy. Cell therapy using mesenchymal stem cells (MSC) has become attractive for tissue repair and regeneration in a number of acute and chronic injuries. Unfortunately their low retention and/or survival after injection limit their beneficial effects. A biomaterial-assisted implantation, providing cells a three-dimensional (3D) microenvironment is a promising strategy. To this purpose, we designed a family of PEC scaffolds, and studied if they could meet the requirement of such application. Xray tomography showed that all PEC scaffolds present an interconnected macroporosity, and both rheology and tensile measurements reveal optimized mechanical properties (higher storage moduli and Young moduli) compared to alginate reference scaffolds. In vitro assays demonstrated their ability to allow MSC retention (higher than 90%), long-term viability and FGF2 secretion. Then, we used a skeletal muscle implantation model to assess the biological response to scaffolds graft, and showed that they support in vivo vascular formation within the implant-derived tissue. The combination of alginate/chitosan PEC scaffolds architecture and angiogenic potential make them appear as interesting tools to optimize MSC therapy results in soft tissues.

A geometric morphometric approach to the study of variation of shovel-shaped incisors.

OBJECTIVES: The scoring and analysis of dental nonmetric traits are predominantly accomplished by using the Arizona State University Dental Anthropology System (ASUDAS), a standard protocol based on strict definitions and three-dimensional dental plaques. However, visual scoring, even when controlled by strict definitions of features, visual reference, and the experience of the observer, includes an unavoidable part of subjectivity. In this methodological contribution, we propose a new quantitative geometric morphometric approach to quickly and efficiently assess the variation of shoveling in modern human maxillary central incisors (UI1). MATERIALS AND METHODS: We analyzed 87 modern human UI1s by means of virtual imaging and the ASU-UI1 dental plaque grades using geometric morphometrics by placing semilandmarks on the labial crown aspect. The modern human sample was composed of individuals from Europe, Africa, and Asia and included representatives of all seven grades defined by the ASUDAS method. RESULTS: Our results highlighted some limitations in the use of the current UI1 ASUDAS plaque, indicating that it did not necessarily represent an objective gradient of expression of a nonmetric tooth feature. Rating of shoveling tended to be more prone to intra- and interobserver bias for the highest grades. In addition, our analyses suggest that the observers were strongly influenced by the depth of the lingual crown aspect when assessing the shoveling. DISCUSSION: In this context, our results provide a reliable and reproducible framework reinforced by statistical results supporting the fact that open scale numerical measurements can complement the ASUDAS method.

Bi2(C2O4)3·7H2O and Bi(C2O4)OH Oxalates Thermal Decomposition Revisited. Formation of Nanoparticles with a Lower Melting Point than Bulk Bismuth.

Two bismuth oxalates, namely, Bi2(C2O4)3·7H2O and Bi(C2O4)OH, were studied in terms of synthesis, structural characterization, particle morphology, and thermal behavior under several atmospheres. The oxalate powders were produced by chemical precipitation from bismuth nitrate and oxalic acid solutions under controlled pH, then characterized by X-ray diffraction (XRD), temperature-dependent XRD, IR spectroscopy, scanning electron microscopy, and thermogravimetric differential thermal analyses. New results on the thermal decomposition of bismuth oxalates under inert or reducing atmospheres are provided. On heating in nitrogen, both studied compounds decompose into small bismuth particles. Thermal properties of the metallic products were investigated. The Bi(C2O4)OH decomposition leads to a Bi-Bi2O3 metal-oxide composite product in which bismuth is confined in a nanometric size, due to surface oxidation. The melting point of such bismuth particles is strongly related to their crystallite size. The nanometric bismuth melting has thus been evidenced ∼40 °C lower than for bulk bismuth. These results should contribute to the development of the oxalate precursor route for low-temperature soldering applications.

Intra-individual metameric variation expressed at the enamel-dentine junction of lower post-canine dentition of South African fossil hominins and modern humans.

OBJECTIVES: The aim of this study is to compare the degree and patterning of inter- and intra-individual metameric variation in South African australopiths, early Homo and modern humans. Metameric variation likely reflects developmental and taxonomical issues, and could also be used to infer ecological and functional adaptations. However, its patterning along the early hominin postcanine dentition, particularly among South African fossil hominins, remains unexplored. MATERIALS AND METHODS: Using microfocus X-ray computed tomography (µXCT) and geometric morphometric tools, we studied the enamel-dentine junction (EDJ) morphology and we investigated the intra- and inter-individual EDJ metameric variation among eight australopiths and two early Homo specimens from South Africa, as well as 32 modern humans. RESULTS: Along post-canine dentition, shape changes between metameres represented by relative positions and height of dentine horns, outlines of the EDJ occlusal table are reported in modern and fossil taxa. Comparisons of EDJ mean shapes and multivariate analyses reveal substantial variation in the direction and magnitude of metameric shape changes among taxa, but some common trends can be found. In modern humans, both the direction and magnitude of metameric shape change show increased variability in M2 -M3 compared to M1 -M2 . Fossil specimens are clustered together showing similar magnitudes of shape change. Along M2 -M3 , the lengths of their metameric vectors are not as variable as those of modern humans, but they display considerable variability in the direction of shape change. CONCLUSION: The distalward increase of metameric variation along the modern human molar row is consistent with the odontogenetic models of molar row structure (inhibitory cascade model). Though much remains to be tested, the variable trends and magnitudes in metamerism in fossil hominins reported here, together with differences in the scale of shape change between modern humans and fossil hominins may provide valuable information regarding functional morphology and developmental processes in fossil species.

Elaboration and evaluation of alginate foam scaffolds for soft tissue engineering.

Controlling microarchitecture in polymer scaffolds is a priority in material design for soft tissue applications. This paper reports for the first time the elaboration of alginate foam-based scaffolds for mesenchymal stem cell (MSC) delivery and a comparative study of various surfactants on the final device performance. The use of surfactants permitted to obtain highly interconnected porous scaffolds with tunable pore size on surface and in cross-section. Their mechanical properties in compression appeared to be adapted to soft tissue engineering. Scaffold structures could sustain MSC proliferation over 14 days. Paracrine activity of scaffold-seeded MSCs varied with the scaffold structure and growth factors release was globally improved in comparison with control alginate scaffolds. Our results provide evidence that exploiting different surfactant types for alginate foam preparation could be an original method to obtain biocompatible scaffolds with tunable architecture for soft tissue engineering.

Morphoarchitectural variation in South African fossil cercopithecoid endocasts.

Despite the abundance of well-preserved crania and natural endocasts in the South African Plio-Pleistocene cercopithecoid record, which provide direct information relevant to the evolution of their endocranial characteristics, few studies have attempted to characterize patterns of external brain morphology in this highly successful primate Superfamily. The availability of non-destructive penetrating radiation imaging systems, together with recently developed computer-based analytical tools, allow for high resolution virtual imaging and modeling of the endocranial casts and thus disclose new perspectives in comparative paleoneurology. Here, we use X-ray microtomographic-based 3D virtual imaging and quantitative analyses to investigate the endocranial organization of 14 cercopithecoid specimens from the South African sites of Makapansgat, Sterkfontein, Swartkrans, and Taung. We present the first detailed comparative description of the external neuroanatomies that characterize these Plio-Pleistocene primates. Along with reconstruction of endocranial volumes, we combine a semi-automatic technique for extracting the neocortical sulcal pattern together with a landmark-free surface deformation method to investigate topographic differences in morphostructural organization. Besides providing and comparing for the first time endocranial volume estimates of extinct Plio-Pleistocene South African cercopithecoid taxa, we report additional information regarding the variation in the sulcal pattern of Theropithecus oswaldi subspecies, and notably of the central sulcus, and the neuroanatomical condition of the colobine taxon Cercopithecoides williamsi, suggested to be similar for some aspects to the papionin pattern, and discuss potential phylogenetic and taxonomic implications. Further research in virtual paleoneurology, applied to specimens from a wider geographic area, is needed to clarify the polarity, intensity, and timing of cortical surface evolution in cercopithecoid lineages.

Upper third molar internal structural organization and semicircular canal morphology in Plio-Pleistocene South African cercopithecoids.

Despite the abundance of cercopithecoids in the fossil record, especially in South Africa, and the recent development of morphometric approaches, uncertainties regarding the taxonomic identification of isolated cranio-dental specimens remain. Because cercopithecoids, nearly always found in stratigraphic association with hominin remains in Plio-Pleistocene deposits, are considered as sensitive ecological and chronological biomarkers, a significant effort should be made to clarify their palaeobiodiversity by assessing additional reliable morphological diagnostic criteria. Here we test the relevance of both molar crown internal structure and bony labyrinth morphology for discrimination of fossil cercopithecoid species. We use microtomographic-based 3D virtual imaging and quantitative analyses to investigate tooth endostructural organization and inner ear shape in 29 craniodental specimens from the South African sites of Kromdraai, Makapansgat, Sterkfontein and Swartkrans and provide the first detailed description of the internal structural condition characterizing this Plio-Pleistocene primate assemblage. Our preliminary results show that enamel-dentine junction morphology could be informative for discriminating highly autapomorphic taxa such as Theropithecus, while semicircular canal shape is tentatively proposed as an efficient criterion for diagnosing Dinopithecus ingens. Further research in virtual paleoprimatology may contribute to the identification of unassigned isolated fossil remains and shed new light on the internal craniodental morphology of extinct primate taxa.

Further morphological evidence on South African earliest Homo lower postcanine dentition: Enamel thickness and enamel dentine junction.

The appearance of the earliest members of the genus Homo in South Africa represents a key event in human evolution. Although enamel thickness and enamel dentine junction (EDJ) morphology preserve important information about hominin systematics and dietary adaptation, these features have not been sufficiently studied with regard to early Homo. We used micro-CT to compare enamel thickness and EDJ morphology among the mandibular postcanine dentitions of South African early hominins (N = 30) and extant Homo sapiens (N = 26), with special reference to early members of the genus Homo. We found that South African early Homo shows a similar enamel thickness distribution pattern to modern humans, although three-dimensional average and relative enamel thicknesses do not distinguish australopiths, early Homo, and modern humans particularly well. Based on enamel thickness distributions, our study suggests that a dietary shift occurred between australopiths and the origin of the Homo lineage. We also observed that South African early Homo postcanine EDJ combined primitive traits seen in australopith molars with derived features observed in modern human premolars. Our results confirm that some dental morphological patterns in later Homo actually occurred early in the Homo lineage, and highlight the taxonomic value of premolar EDJ morphology in hominin species.

Understanding the Fragmentation Pattern of Marine Plastic Debris.

The global estimation of microplastic afloat in the ocean is only approximately 1% of annual global plastic inputs. This reflects fundamental knowledge gaps in the transformation, fragmentation, and fates of microplastics in the ocean. In order to better understand microplastic fragmentation we proceeded to a thorough physicochemical characterization of samples collected from the North Artlantic subtropical gyre during the sea campaign Expedition seventh Continent in May 2014. The results were confronted with a mathematical approach. The introduction of mass distribution in opposition to the size distribution commonly proposed in this area clarify the fragmentation pattern. The mathematical analysis of the mass distribution points out a lack of debris with mass lighter than 1 mg. Characterization by means of microscopy, microtomography, and infrared microscopy gives a better understanding of the behavior of microplastic at sea. Flat pieces of debris (2 to 5 mm in length) typically have one face that is more photodegraded (due to exposure to the sun) and the other with more biofilm, suggesting that they float in a preferred orientation. Smaller debris, with a cubic shape (below 2 mm), seems to roll at sea. All faces are evenly photodegraded and they are less colonized. The breakpoint in the mathematical model and the experimental observation around 2 mm leads to the conclusion that there is a discontinuity in the rate of fragmentation: we hypothesized that the smaller microplastics, the cubic ones mostly, are fragmented much faster than the parallelepipeds.