Epigenetic loss of RNA‑methyltransferase NSUN5 in glioma targets ribosomes to drive stress adaptive translational program

Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence of aberrant RNA modification landscapes in the so-called epitranscriptome. Here, we report that human glioma cells undergo DNA methylation-associated epigenetic silencing of NSUN5, a candidate RNA methyltransferase for 5-methylcytosine. In this setting, NSUN5 exhibits tumor-suppressor characteristics in vivo glioma models. We also found that NSUN5 loss generates an unmethylated status at the C3782 position of 28S rRNA that drives an overall depletion of protein synthesis, and leads to the emergence of an adaptive translational program for survival under conditions of cellular stress. Interestingly, NSUN5 epigenetic inactivation also renders these gliomas sensitive to bioactivatable substrates of the stress-related enzyme NQO1. Most importantly, NSUN5 epigenetic inactivation is a hallmark of glioma patients with long-term survival for this otherwise devastating disease

Morphological diversity, evolution and biogeography of early Pleistocene rabbits (genus Oryctolagus)

Abstract The early Pleistocene is the key period for understanding the evolutionary history and palaeobiogeography of rabbits (genus Oryctolagus). In western Europe, many species were endemic, making them a reliable indicator of the evolution of the terrestrial ecosystems in which many species have evolved. However, the morphological variability of rabbit species is still poorly understood and their phylogeny remains a subject of debate. Through both qualitative (morphological description) and quantitative (linear measurements and two-dimensional geometric morphometrics) approaches, we address here the morphometric diversity of the third lower premolar (p3), a tooth commonly used to distinguish leporid species, in order to assess intra- and inter-regional morphological variations in several early Pleistocene rabbit populations. Our results suggest that the different approaches are complementary and allow, on different levels, a full characterization of the p3 variability of early Pleistocene rabbits and to imply relations between populations. The size and shape variations of this tooth reflect the taxonomic and phylogenetic signals of the different species but were probably also significantly impacted by geographical position and local climatic conditions. In view of the great morphometric variability highlighted in this work, we suggest a careful reconsideration of certain dental criteria previously considered ‘diagnostic’ in the characterization of these species. However, the overall results allowed us to discuss the phylogeny of the genus Oryctolagus and to hypothesize the ecological requirements and different phases of the dispersal of taxa in western Europe, probably associated with global climate changes

Influence of captivity and selection on limb long bone cross-sectional morphology of reindeer

Abstract The emergence of pastoralism and animal husbandry has been a critical point in the history of human evolution. Beyond profound behavioural changes in domesticated animals compared to wild ones, characterising the morphological changes associated with domestication process remains challenging. Because reindeer (Rangifer tarandus) can be considered to still be in the early phases of the domestication process, the study of modern populations provides a unique opportunity to examine the impact of captivity and selective breeding on skeletal changes. In this work, we investigated the morphological changes in long limb bone cross-sections using 137 wild and domestic reindeer individuals bred in free-range, in captivity or used for racing and pulling. The shape and shaft cortical thickness of the six long limb bones (i.e., humerus, radioulna, metacarpal, femur, tibia and metatarsal) were measured using a 2D-geometric morphometrics approach taking into account subspecies, sex, body mass and lifestyle differences. These bones are important to understanding functional morphological changes because they can provide information on feeding and locomotor behaviours, as well as on body propulsion and weight bearing. Apart from the effects of taxonomy, etho-ecology and sex, we have found that captivity and selection induced important variations in the size and body mass of modern reindeer. Our results also showed that patterns of variation in cortical bone thickness of long limb bone cross-sections were strongly impacted by body mass and human-imposed restrictions in roaming. This demonstrates that bone cross-sections can provide information on changes in locomotor, reproductive and feeding behaviours induced by the domestication process. These results are valuable not only for (paleo) biologists studying the impact of captivity and selection in ungulates but also for archaeologists exploring the origins of domestication and early herding strategies

Reconstructing past migratory behaviour of reindeer (Rangifer tarandus):insights from geometric morphometric analysis of proximal phalanx morphology from extant caribou populations

Abstract Reindeer mobility patterns vary widely in modern ecosystems, notably between more open or more wooded environments. This renders the reconstruction of past reindeer mobility patterns challenging, while being at the same time key if archaeologists want to better understand the role that reindeer herds played in the subsistence and territorial organisation of Prehistoric hunter-gatherer societies. Studying the morphology associated with different habitats and mobility patterns can be a useful method for understanding past reindeer behaviour. To access paleoecological information, the relationship between locomotor anatomy and substrate type can be explored in modern animals and transposed to the past, as previous studies have proven that an animal’s environment affects bone morphology. In this study, 3D Geometric Morphometrics are used to explore the impact of extant reindeer habitat type and mobility pattern on phalanx morphology. Results obtained reflects on the potential archaeological application of such an approach for paleoecological reconstructions. Size and shape of phalanx vary significantly, yet complex to interpret in light of interplaying factors such as subspecies, sexual dimorphism and the influence of migration costs, snow cover and substrate type. If direct application to the archaeological record remains preliminary, this first study permits to highlight promising avenues for future research

Who Killed the Small Mammals of Ittenheim (Northeastern France)?:an integrative approach and new taphonomic data for investigating bone assemblages accumulated by small carnivores

Abstract Small carnivores are susceptible to regularly accumulating small- to medium-sized mammal remains in both natural and archaeological sites. However, compared to nocturnal birds of prey, these accumulations are still poorly documented and are generally based on a limited number of samples, including those of relatively small size. Here, we present an analysis of European hamster remains from a rescue excavation at Ittenheim (Bas-Rhin, Grand-Est, France), which were recovered from an infilled burrow, three meters below the current surface. The remains are well preserved and exhibit large proportions of tooth marks. Comparisons with a new and existing reference collection combined with an analysis of all recovered faunal remains suggest the accumulation reflects the action of young red foxes. This is supported by the fact that, although these young individuals leave teeth mark, they do not necessarily consume all parts of medium-sized prey species, including the European hamster. Conversely, the remains of smaller rodents, such as microtine, show distinct patterns of digestion and tooth marks. Carnivore bone accumulations from scats are generally poorly preserved; however, our results demonstrate prey size plays a major role, both qualitatively and quantitatively, in skeletal representation, bone preservation, and bone surface modifications. The present paper underlines the need for more diversified taphonomic reference collections based on an integrative approach designed to evaluate multi-taxa accumulations

Impact of selection and domestication on hindlimb bones of modern reindeer populations:archaeological implications for early reindeer management by Sámi in Fennoscandia

Abstract For centuries, reindeer herding has been an integral part of the subsistence and culture among the Sámi of northern Fennoscandia. Despite the importance of this husbandry in their history, the timing and details of early reindeer domestication are still highly debated. Indeed, identifying domesticated individuals in the archaeological record remains complicated because reindeer are still considered to be in the early phases of the domestication process. In this work, we propose solutions for identifying domestic individuals using 3D geometric morphometrics on isolated elements from the long bones of the hindlimb in modern reindeer populations. These bones are important for understanding both the mobility of reindeer and the effect of load carrying or draught. A good level of distinction between the size and shape variables of these bones was found among subspecies, sex and lifestyles. This demonstrates that the long bones of the hindlimb can provide information on changes in locomotor behaviour induced by the domestication process, such as control and reduction of reindeer mobility by humans. This also demonstrates that analysis in geometric morphometrics is useful for exploring the use of draught reindeer in early Sámi reindeer herding and the implications for understanding reindeer domestication and early reindeer herding strategies

Earliest archaeological evidence for domesticated reindeer economy among the Sámi of Northeastern Fennoscandia AD 1300 onwards

Abstract The domestication of the reindeer among the Sámi of Northern Fennoscandia is a pressing question for the archaeology of the area and has wider relevance to animal domestication studies globally. Despite considerable research activity, many details of reindeer domestication and early reindeer management remain unclear. This paper explores the use of draught reindeer in early Sámi reindeer herding and the implications for understanding reindeer domestication and early reindeer herding strategies. Faunal assemblages from three Sámi dwelling sites in Northeastern Fennoscandia (AD 1300–1800) were subjected to radiocarbon dating and analysis of palaeopathological lesions, entheseal changes and osteometric measurements. The results suggest that working reindeer were present in the archaeological assemblages from AD 1300 onwards. This is the earliest direct evidence of draught reindeer use by the Sámi. It predates the earliest unequivocal historical sources on draught reindeer use, and confirms the hypothesis that draught reindeer were important in early reindeer herding. Our results show that that small-scale reindeer herding was integrated into the subsistence strategy of the Sámi of Northeastern Fennoscandia earlier than previously suggested. Furthermore, the results imply that training and working together with reindeer were ways of constructing the domestication relationship between the Sámi and reindeer

Identifying early stages of reindeer domestication in the archaeological record:a 3D morphological investigation on forelimb bones of modern populations from Fennoscandia

Abstract Reindeer herding probably developed during the Late Iron Age onwards and is still an important part of the subsistence and culture of many peoples in northern Eurasia. However, despite the importance of this husbandry in the history of these Arctic people, the period and place of the origin as well as the spread of domestic reindeer is still highly debated. Besides the existence of different breeding methods in these territories, identifying domesticated individuals in the archaeological record is complicated because reindeers are considered to still be in the early phases of the domestication process. Indeed, the traditional morphological markers used in zooarchaeology to decipher the domestication syndrome are hardly perceptible in these early stages. In this work, we propose solutions for identifying domestic reindeer bones using 3D geometric morphometrics on isolated elements from the long bones of the forelimb (i.e. humerus, radio-ulna and metacarpal). These bones are important to understand both the feeding behaviour and the mobility of reindeer, and the potential effect of load-carrying or draught in the case of domestic reindeer. We analysed 123 modern specimens from Fennoscandia, including the two interbreeding subspecies currently present in these territories: mountain reindeer (Rangifer tarandus tarandus) and forest reindeer (R.t. fennicus); and where the sex and the lifestyle were known (i.e. free-ranging, racing or draught and captive individuals). A good level of discrimination between the size and shape variables of the bones of the forelimb was found among both subspecies and sexes. Moreover, individuals bred in captivity had smaller bone elements and a thinner and more slender morphology than free-ranging individuals. This demonstrates that the long bones of the forelimb can provide information on changes in feeding and locomotor behaviour prompted by the domestication process, like control and/or reduction of mobility and food of individual reindeer by humans. This also demonstrates that analysis in 3D geometric morphometrics is useful in detecting reindeer incipient domestication markers. Our results can be used by archaeologists to trace the early stages of domestication from fossil reindeer remains, and aid in reconstructing the socio-economic changes of past Arctic populations over time

Investigating the domestication and early management of reindeer (Rangifer tarandus) in the Sámi archaeological context from teeth geometric morphometrics

Abstract For centuries, reindeer herding has been an integral part of the subsistence, lifeways, economy and cosmology of the Sámi of northern Fennoscandia. Despite its importance, the timing and details of early reindeer domestication are still highly debated. Identifying domesticated individuals in the archaeological record remains complicated due to the presence of two interbreeding subspecies in Fennoscandia and a mixed socio-economic organisation by Sámi populations, which was mainly a combination of wild reindeer hunting and small-scale reindeer herding. This study proposes methodological improvement for identifying domestic individuals using 2D landmark and sliding semi-landmark based geometric morphometrics on the isolated lower molars of 389 modern specimens, and 90 teeth from four archaeological sites in Finnish Lapland. Our results indicate that despite the significant impact of wear on overall tooth morphology, our protocol is very useful for identifying subspecies (classification accuracy of the two species is between 78 and 91% depending on the wear class) and understanding the morphological changes induced by the domestication process. We suggest that the morphological variation observable among modern populations has been impacted by recent changes in herding strategies in northern Fennoscandia, and that the archaeological domesticated reindeer populations were relatively different, probably due to selection by the Sámi. This study also highlights the importance of using other direct evidence or contextual archaeological data to better trace the early evidence of a domesticated reindeer economy in northern Fennoscandia, and aid in reconstructing the socio-economic changes in Sámi populations over time

La faune de la fin du Pléistocène moyen de la décharge d’Aubais (Gard, France)

Résumé Il y a une vingtaine d’années, des dents de mammouths ont été retrouvées dans les déblais de la décharge de la commune d’Aubais (Gard, Sud-Est de la France). Des opérations de fouille de sauvetage, de tri et de tamisage ont par la suite été menées et ont permis d’identifier la présence de 19 taxons de vertébrés continentaux. Les carnivores dominent (n=10), suivis par les herbivores (n=5), les oiseaux (n=1) et les léporidés (n=2) dont les restes sont les plus abondants. Aucun reste de micromammifères n’a en revanche été retrouvé. Les observations sédimentologiques croisées aux données géologiques locales permettent d’affirmer l’homogénéité de la faune piégée dans une ancienne doline creusée dans des niveaux burdigaliens. Les restes osseux étaient à l’origine en bon état de conservation mais ont été fragmentés lors de leur extraction par des engins de terrassement (fracturation et griffures d’engins). Le type d’extraction du sédiment à l’origine de ces déblais n’a pas permis de procéder à une étude taphonomique. Les différentes études fauniques permettent de positionner chronologiquement le gisement au cours du stade isotopique 6. Aucune trace d’activités humaines et carnivores n’a été détectée et la faune de la décharge d’Aubais permet de mieux comprendre l’environnement dans lequel évoluaient les groupes humains de la région à fin du Pléistocène moyen.Abstract Twenty years ago, mammoth teeth were discovered in Aubais landfill (Gard, Southeastern France). Salvage excavations were subsequently conducted and the sediment has been sifted and screened. Therefore, 19 continental vertebrate species have been identified. Carnivores species are dominant (n=10) followed by the herbivorous (n=5), birds (n=1) and leporids (n=2) which are the most abundant. In contrast, no micromammal remains were found. The analysis of the sediments and the local geological data permit to indicate that this fauna is homogeneous and has been trapped in an oldest sinkhole opened in the Burdigalian. The faunal remains were well preserved initially but they were fragmented during their extraction by earth-moving machine (breakage, scratches). Consequently, it was not possible to study the taphonomical processes. The paleontological study allows us to chronologically relate the deposit to the marine isotopic stage 6. Although no indication of human activities has been detected, the Aubais fauna provides a better understanding of the local environment of human groups during the late Middle Pleistocene