L’homme-lion d’Hohlenstein – Stadel

The fragments of the figurine called “lion-man” were found in 1939 in the cave of Hohlenstein-Stadel, in southwestern Germany. Joachim Hahn was the first to assemble the figure in 1969; the statuette was then restored between 1987 and 1988 in the workshops of the regional museum of Württemberg in Stuttgart. New excavations, conducted by the State Office for Cultural Heritage of Baden-Württemberg (Esslingen, Germany), were held in the same cave between 2009 and 2013. Then, hundreds of small fragments were found; some of them clearly belonged to the lion-man. Following these excavations, a second restoration was undertaken in the workshops of the State office of Cultural Heritage in 2012 and 2013. The Lion-Man, the tallest of the figures from the last Ice Age, got a new appearance. After the refitting of the fragments, a large part of the figurine has been completed.     

Biogeographic relationships of African carnivoran faunas, 7–1.2 Ma

This study analyses the carnivore component of African fossil faunas from three time slices: 7–5 Ma, 4–3 Ma, and 2.5–1.2 Ma, using cluster analysis and principal coordinate analysis (PCO) of presence/absence data on genera. The faunas mostly cluster by time slice, with the exception of Laetoli (Tanzania) and Ahl al Oughlam (Morocco), which differ from all other faunas. The separation during the Late Miocene of a Chado–Libyan bioprovince from the remainder of Africa is supported. No such distinctions are present in the other time slices. Taxonomic distance is not generally correlated with geographic distance, though if Langebaanweg is removed from the 7–5 Ma time slice, the correlation at that time is significant. Comparison of these paleontological results with phylogeographic studies of modern species leads to some general comments on the analytic power of the fossil record with regard to interregional migrations.     

LEVELNET to visualize,explore, and compare protein–protein interaction networks

Physical interactions between proteins are central to all biological processes. Yet, the current knowledge of who interacts with whom in the cell and in what manner relies on partial, noisy, and highly heterogeneous data. Thus, there is a need for methods comprehensively describing and organizing such data. LEVELNET is a versatile and interactive tool for visualizing, exploring, and comparing protein–protein interaction (PPI) networks inferred from different types of evidence. LEVELNET helps to break down the complexity of PPI networks by representing them as multi-layered graphs and by facilitating the direct comparison of their subnetworks toward biological interpretation. It focuses primarily on the protein chains whose 3D structures are available in the Protein Data Bank. We showcase some potential applications, such as investigating the structural evidence supporting PPIs associated to specific biological processes, assessing the co-localization of interaction partners, comparing the PPI networks obtained through computational experiments versus homology transfer, and creating PPI benchmarks with desired properties.     

When did Cuon reach Java? – Reinvestigation of canid fossils from Homo erectus faunas

The presence of the genus Cuon during the Pleistocene of Java is attested by the endemic species C. sangiranensis and C. crassidens, sometimes classified as C. alpinus, a species that is also part of the Holocene fauna and has persisted until today. The current study revises the fossil canid material from the Sangiran Dome, previously assigned variously to C. sangiranensis, C. crassidens, C. alpinus, C. javanicus, and C. trinilensis. It aims to reinvestigate the arrival of Cuon in Java, in particular in relation to the late early Pleistocene endemic canid of Java: the Cuon-sized Xenocyon trinilensis, which had evolved in situ on Java from the large X. merriami, and which could be a potential competitor to early Cuon in case of contemporaneity. We found that a mandible fragment from Pandejan (holotype of C. crassidens) shows a morphology typical for C. alpinus. However, a maxilla and a mandible from the Bapang Formation at Sangiran, including the holotype of C. sangiranensis, is here assigned to the early dhole species C. priscus. Our results indicate that Cuon was already present in Java during the early middle Pleistocene and probably arrived as part of the immigration events during the Kedung Brubus faunal stage. Since X. trinilensis and Cuon are both hypercarnivorous medium-sized dogs, similar ecological niches are expected for both species. Thus, X. trinilensis probably was outcompeted and replaced by C. priscus. In turn, the latter species was replaced by the extant species, C. alpinus, during the Nangdong faunal stage, likely as part of the next immigration phase, which then disappeared during the tropical rainforest fauna of the Punung faunal stage and re-entered at the onset of the Holocene.     

Nadaouiyeh – A Homo erectus in Acheulean context

The Middle East is apparently the most important passage for the dispersal of early hominins. Numerous archeological sites prove the existence of hominin populations in this region, but despite these rich cultural remains, hominin fossils are very rare. In 1996, a hominin left parietal was found in an Acheulean context. In addition, the faunal remains indicate a steppe environment. What does this single cranial fragment tell us? Based on new publications and in particular on recent finds, the value of isolated elements is discussed.     

The Iron Gates Mesolithic – a brief review of recent developments

The Iron Gates section of the Lower Danube valley along the border between Romania and Serbia has an unparalleled record of Mesolithic and Early Neolithic settlement spanning the period from ca. 12,700 to 5600 cal BC. Over 50 cave and open-air sites were identified during archaeological surveys in advance of dam construction in the 1960s and 1980s, and follow-up rescue excavations revealed numerous burials and architectural remains and produced rich inventories of faunal material and portable artifacts including artworks and ornaments of bone, shell and stone. Most sites are no longer accessible, submerged beneath the reservoirs created by the Iron Gates I and II dams. Since 1990, new excavations have been conducted at Aria Babi and Vlasac in Serbia, and Schela Cladovei in Romania, while detailed studies of the finds from both new and old excavations have been undertaken by researchers based in Romania, Serbia and the UK fueled by developments in archaeological science. In this paper, we review the main advances in knowledge of the Mesolithic and the transition to farming in the Iron Gates over the past 25 years, and especially the period since 2005. The paper is divided into sections dealing with chronology, mortuary practices, isotopic studies of subsistence and mobility patterns, and the nature and timing of the transition from Mesolithic to Neolithic in the Iron Gates region. The review concludes with a forward look at research in progress.     

8-Br-cADPR, a TRPM2 ion channel antagonist,inhibits renal ischemia–reperfusion injury

The transient receptor potential melastatin-2 (TRPM2) channel belongs to the transient receptor potential channel superfamily and is a cation channel permeable to Na⁺ and Ca ²⁺. The TRPM2 ion channel is expressed in the kidney and can be activated by various molecules such as hydrogen peroxide, calcium, and cyclic adenosine diphosphate (ADP)-ribose (cADPR) that are produced during acute kidney injury. In this study, we investigated the role of 8-bromo-cyclic ADP-ribose (8-Br-cADPR; a cADPR antagonist) in renal ischemia–reperfusion injury using biochemical and histopathological parameters. CD38, cADPR, tumor necrosis factor-α, interleukin-1β, and myeloperoxidase (inflammatory markers), urea and creatinine, hydrogen peroxide (oxidant), and catalase (antioxidant enzyme) levels that increase with ischemia–reperfusion injury decreased in the groups treated with 8-Br-cADPR. In addition, renin levels were elevated in the groups treated with 8-Br-cADPR. Histopathological examination revealed that 8-Br-cADPR reduced renal damage and the expression of caspase-3 and TRPM2. Our results suggest that the inhibition of TRPM2 ion channel may be a new treatment modality for ischemic acute kidney injury.     

Dwellings and workspaces at Strandvägen, 5600–5000 cal. BC

This paper describes identified workspaces and the manufacture of slotted bone points at the Late Mesolithic settlement Strandvägen in Motala, in eastern central Sweden. Several dwellings were documented, Dwelling 1 being typically round-oval in shape 9 × 5.5 meters, with a floor area covering 49.5 m². Radiocarbon dates fall between approximately 5600-5200 cal BC. A combined archaeological record, with lithics and bone artefacts as well as analyses of the osteological assemblage has shown that slotted bone tools with mounted lithic inserts have been produced adjacent of the dwelling. The spatial distribution of bone flakes, microblades, processed resin and slotted artefacts testify to a clearly and delimited craft area near the shoreline of the river Motala Ström. Analyses of the finds, e.g. birch bark resin and prepared bone preforms by direct percussion, also help in reconstructing the stages of manufacturing composite projectile points in this part of Eurasia.     

Les occupations gravettiennes de la Grotte Santa Maria di Agnano (Pouilles,Italie) – Zone SMA-Esterno : typo-technologie lithique et archéozoologie

The Gravettian in Apulia constitutes a singular cultural entity in the context of the prehistoric chrono-cultures of Upper Paleolithic in Italy. This situation can particularly be observed in the Gravettian sequence of the Paglicci cave on Mount Gargano, the lithic series of which show an original development. In the very heart of Apulia, until recently, no field for comparison could be found for the time sequence of the Paglicci cave. But the recent discovery of Gravettian occupation in the stratigraphic sequence of the SMA-external area of Santa Maria di Agnano makes it possible to revisit the status of the Paglicci cave, but also to clarify the specific characters of the Gravettian in Apulia. The lithic industry of SU 9-6 of SMA-Esterno is characterized by the presence of many burins on retouched truncation associated with straight backed points, Gravette or Vachons type. This association reminds us of the assemblage of Paglicci layer 21, attributed to Middle Gravettian. C14 datings for both sites match. Finally, at the base of the Gravettian SMA sequence, SU 11 provided large dihedral burins matching those found Paglicci layers 23-22 attributed to ancient Gravettian. The preliminary zooarchaeological study was carried out on a sample of 2007 remains of large mammals. In total, 816 taxinomic and anatomic remains (NRDt) could be identified, i.e. a 40.7% determination rate. The faunic spectrum consists of 10 taxons, among which 4 species of carnivores (leopard, wolf, fox, badger), 5 ungulates (horse, aurochs, ibex, deer and wild boar) and 1 leporid (hare). Ungulates prevail, as far as remains (98.7% of NRDt) or the minimum number of individuals (82.4% of NMI total) are concerned. Taphonomic analyses indicate that bones were not subject to deep post-depositional modifications. Consequences of weathering are visible on 17% of the cortical surfaces. Non-anthropic biological modifications are scarce: 13% of the material were impacted by roots and 0.7% show the results of carnivorous activity. The hare may be the only species, among herbivores, that was accumulated by a carnivore. The analysis of bone fractures and the traces left by the edge of a lithic tool reveal that the bone material was essentially accumulated and modified by human groups. Hunting is clearly aimed at both Horses (Equus caballus) and Aurochs (Bos primigenius), with occasional Red Deer (Cervus elaphus), Wild Boar (Sus s. scrofa) and Ibex (Capra ibex). The individuals represented are mainly sub-adults and mature adults. The human groups living on the site probably got their meat resources from the plain bordering the Adriatic shore and the vast, more or less flat, plateau overlooking the site. According to the skeleton representations in which the stylopod and zeugopod prevailed, after an initial treatment at the slaughter site, the Gravettians carried the most nutritious parts to the camp. The study of human activities indicates extensive processing of carcasses for their meat and extraction of marrow from long bones. Finally, specific research for fat from the cancellous tissue of the epiphyses of both long and short bones is proposed.     

Neumark-Nord 2 – A multiphase Middle Palaeolithic open-air site in the Geisel Valley (Central Germany)

The lake basin Neumark-Nord 2 (NN 2) is located in the Geisel Valley in Saxony-Anhalt (Germany). It was scientifically investigated between 2003 and 2008. The sediment sequence, which is about 10 to 11 m thick, consists of limnic deposits, mostly silts mixed with clays and sands. Sedimentological as well as palynological, malacological and palaeomagnetic investigations, supported by absolute datings, date the entire sequence into the Eemian and Early Weichselian. Within the deposits several archaeological find horizons were discovered. Neumark-Nord 2/2 (NN 2/2) at the beginning of the Eemian and Neumark-Nord 2/0 (NN 2/0) with an early Weichselian were the most important archaeological horizons. Both find horizons represent former lake shore sites, where numerous crushed animal bones and other faunal debris were found, which can be regarded as remains of hunted game. With regard to the rich lithic material, both find horizons differ remarkably. In NN2/2, a simple artefact spectrum with a certain Levallois component and a dominance of denticulated, notched and laterally retouched specimens. In NN 2/0, on the other hand, bifacial tools such as backed knives and sometimes finely retouched scrapers are dominant, while the Levallois component fades completely into the background. Thus, NN 2 is one of the few open-air sites in archaeological landscape of Central German where several middle Palaeolithic find horizons occur in superposition.     

Moulin Quignon 1863–1864 : détours inédits et bilan historiographique

The historical file of Moulin Quignon (Abbeville, France), around the human jaw unearthed in this site, is a form of black hole that swallowed a prehistoric archaeological site and Lower Palaeolithic collection. This article, based on a corpus of unpublished archives, illuminates the matter in a different light. It focuses on archaeological and epistemological issues, the roles of the different actors, interaction games and solidarity in a global scientific community previously welded by the recognition in 1859 of the paradigm of high antiquity of Man.     

Mechanisms of mechanosensing — mechanosensitive channels,function and re-engineering

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SYNE1-QK1 SNPs,G × G and G × E interactions on the risk of hyperlipidaemia

This study aimed to assess the relationship of 3 spectrin repeat containing nuclear envelope protein 1 (SYNE1) and 4 KH domain containing RNA binding (QK1) single nucleotide polymorphisms (SNPs), their haplotypes, gene-gene (G × G), gene-environment (G × E) interactions and hypercholesterolaemia (HCH) and hypertriglyceridaemia (HTG) in the Chinese Maonan minority. The genetic make-up of the SYNE1-QK1 SNPs in 1932 unrelated subjects (normal, 641; HCH, 649; and HTG, 642) was obtained by next-generation sequencing technologies. The genotypic frequencies of following SNPs were suggestively distinctive between the control and HCH groups (rs2623963, rs7745725, rs9459317, rs16897566), or between the control and HTG groups (rs2623963, rs1358317, rs7745725, rs1923608, rs16897566 SNPs; P < .05, respectively). Multiple-locus linkage disequilibrium analysis indicated that the identified SNPs were not inherited independently. Several haplotypes and gene-gene interaction haplotypes among the detected SNPs may be related with an increased morbidity of HCH (C-G-A, C-G-G and C-G-G-T-C-A-T) and HTG (C-G-G, G-T-G-C, C-G-G-G-T-G-C and C-G-G-T-C-A-T), whereas others may be related with an decreased risk of HCH (G-A-A, G-C-A-T, C-A-A-T-C-A-T and G-A-A-G-C-A-T) and HTG (G-A-A, G-C-A-T, C-A-A-T-C-A-T and G-A-A-G-C-A-T). The association evaluation based on haplotypes and gene-gene interactions could improve the power of detecting the risk of dyslipidaemia than anyone of SNP alone. There was significant three-locus model involving SNP-SNP, haplotype-haplotype/environment and G × G interactions (P < .05-0.001) that were detected by GMDR in HCH and HTG groups. Different interactions between genetic and environmental factors would produce different redundancy or synergy effects on the morbidity of HCH and/or HTG.     

trans-Cyclooctene — a stable,voracious dienophile for bioorthogonal labeling

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Genotype × region and genotype × production level interactions in Holstein cows

The identification of the presence of genotype by environment interaction effects on important traits in Holstein cattle allows for the use of international genetic evaluations and a more efficient design of regional genetic evaluation programmes. The aim of this study was to determine the genotype × environment interaction effects in Chilean Holstein dairy cattle through the analysis of records corresponding to calvings between 1998 and 2015. Herds were classified in the central and southern regions of Chile based on herd location as well as by high and low levels of production environments based on the fat plus protein yield averages per herd within each region. The central region has a Mediterranean climate and a confined production system while the southern region has a humid temperate climate and a production system based on grazing with supplementation. Traits studied were milk yield (MY), fat yield (FY), protein yield (PY), fat content (FC) and protein content (PC) by lactation, age at first calving (AFC) and calving interval (CI). Several four-trait mixed animal models were applied to environmental category data as different traits, which included herd-year-calving season (herd-year-birth season for AFC) and lactation number as fixed effects, and animal additive genetic, sire-herd, permanent environment and residual effects as random effects. Genetic correlations (r_g) for MY, FY, FC, PC and CI were found to decrease as differences between environmental categories increased. The r_g between the most extreme environmental categories considered in this study for AFC (0.26) was the only one found statistically lower than 0.60. Genetic correlation values statistically lower than 0.80 (P < 0.05) were observed for AFC, CI, MY, FY and PY between some environmental categories. If separate genetic evaluations are adopted as practical criteria when the value of r_g is lower than 0.60, the consequence of improving a multi-trait economic breeding objective in this population is likely to be small unless extreme environmental categories are considered. However, a moderate decrease in selection response and re-ranking of selection candidates is expected for AFC, CI and yield traits when selection is performed in different environmental conditions. Genotype × environment interaction effects involving production systems in a Mediterranean climate and confinement vs. Temperate Oceanic climate and grazing with supplementation, and between two fat plus protein yield level categories within each environment, were at most moderate for the studied traits.     

Novel screening methods — biosensors

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Le radiopharmaceutique : situation et perspectives depuis la 8e Conférence internationale de l’ACOMEN (Bordeaux, 11–12–13 mai 2005)

Since previous ACOMEN's conference in 2005 on radiopharmaceuticals, many improvements have been encountered: active research has allowed the development of numerous new tracers of interest, with a large part dedicated for PET; clinical applications of radiopharmaceuticals have resulted in patients care improvement, both for management and survival; therapeutic applications are now fully recognized, as internal targeted radiotherapy could be considered as efficient in several cancer diseases; and regulation, despite remaining difficulties, will certainly become more favourable for radiopharmaceuticals. Thus we could make sure that radiopharmaceuticals use will be even more established in the next years.     

In-vivo dosimetry for field sizes down to 6 × 6 mm2 in shaped beam radiosurgery with microMOSFET

The aim of this study is to evaluate microMOSFET as in-vivo dosimeter in 6 MV shaped-beam radiosurgery for field sizes down to 6 × 6 mm². A homemade build-up cap was developed and its use with microMOSFET was evaluated down to 6 × 6 mm². The study with the homemade build-up cap was performed considering its influence on field size over-cover occurring at surface, achievement of the overall process of electronic equilibrium, dose deposition along beam axis and dose attenuation. An optimized calibration method has been validated using MOSFET in shaped-beam radiosurgery for field sizes from 98 × 98 down to 18 × 18 mm². The method was detailed in a previous study and validated in irregular field shapes series measurements performed on a head phantom. The optimized calibration method was applied to microMOSFET equipped with homemade build-up cap down to 6 × 6 mm². Using the same irregular field shapes, dose measurements were performed on head phantom. MicroMOSFET results were compared to previous MOSFET ones. Additional irregular field shapes down to 8.8 × 8.8 mm² were studied with microMOSFET. Isocenter dose attenuation due to the homemade build-up cap over the microMOSFET was near 2% irrespective of field size. Our results suggested that microMOSFET equipped with homemade build-up cap is suitable for in-vivo dosimetry in shaped-beam radiosurgery for field sizes down to 6 × 6 mm² and therefore that the required build-up cap dimensions to perform entrance in-vivo dosimetry in small-fields have to ensure only partial charge particle equilibrium.     

Metabolomics – an overview. From basic principles to potential biomarkers (part 2)

The metabolome, which represents the complete set of molecules (metabolites) of a biological sample (cell, tissue, organ, organism), is the final downstream product of the metabolic cell process that involves the genome and exogenous sources. The metabolome is characterized by a large number of small molecules with a huge diversity of chemical structures and abundances. Exploring the metabolome requires complementary analytical platforms to reach its extensive coverage. The metabolome is continually evolving, reflecting the continuous flux of metabolic and signaling pathways. Metabolomic research aims to study the biochemical processes by detecting and quantifying metabolites to obtain a metabolic picture able to give a functional readout of the physiological state. Recent advances in mass spectrometry (one of the mostly used technologies for metabolomics studies) have given the opportunity to determine the spatial distribution of metabolites in tissues. In a two-part article, we describe the usual metabolomics technologies, workflows and strategies leading to the implementation of new clinical biomarkers. In this second part, we first develop the steps of a metabolomic analysis from sample collection to biomarker validation. Then with two examples, autism spectrum disorders and Alzheimer's disease, we illustrate the contributions of metabolomics to clinical practice. Finally, we discuss the complementarity of in vivo (positron emission tomography) and in vitro (metabolomics) molecular explorations for biomarker research.