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Here we present stable carbon, nitrogen and sulfur isotope ratios of collagen extracted from Rangifer, Equus and Bison bone (n = 128) from different stratigraphic levels at the chronologically well-constrained Middle and Upper Palaeolithic site of Les Cottés, France. Samples were taken from five phases of site use (US08, US06, US04 [upper and lower], and US02; ~ 45.8-35.3 ka cal BP) to explore the dietary and spatial palaeoecology of these ungulate species during MIS 3, and the contemporary climate. Temporal trends in δ 15 N values of all species broadly align with other climatic indicators at the site and the lowest values in US04 correspond to the Heinrich 4 cooling event, reflecting changes in the composition of soil/plant nitrogen at this time. Rangifer collagen is 13 C-enriched compared to the other species throughout, consistent with lichen consumption. However, this isotopic niche partitioning between Rangifer and Equus/Bison is most extensive during US04, indicating plasticity in reindeer feeding behaviour, and potentially overall increased lichen biomass during this cooler/more arid phase. Rangifer δ 34 S values are consistently lower than Equus and Bison, which could be indicative of their more extensive spatial ranges incorporating greater inland areas. Equus and Bison demonstrate a significant decrease in δ 34 S values through time, which may be linked to contemporary climatic decline., (© 2023. Springer Nature Limited.)

Evidence of mobiliary art and body augmentation are associated with the cultural innovations introduced by Homo sapiens at the beginning of the Upper Paleolithic. Here, we report the discovery of the oldest known human-modified punctate ornament, a decorated ivory pendant from the Paleolithic layers at Stajnia Cave in Poland. We describe the features of this unique piece, as well as the stratigraphic context and the details of its chronometric dating. The Stajnia Cave plate is a personal 'jewellery' object that was created 41,500 calendar years ago (directly radiocarbon dated). It is the oldest known of its kind in Eurasia and it establishes a new starting date for a tradition directly connected to the spread of modern Homo sapiens in Europe., (© 2021. The Author(s).)

The Upper Palaeolithic in Europe was a time of extensive climatic changes that impacted on the survival and distribution of human populations. During the Late Glacial Maximum (LGM), southern European peninsulas were refugia for flora, fauna, and human groups. One of these refugia, the Cantabrian region (northern Atlantic Spain), was intensively occupied throughout the Upper Palaeolithic. Characterising how climatic events were expressed in local environments is crucial to understand human and animal survival. La Riera Cave (Asturias) has a rich geo-cultural sequence dating between 20.5kyr BP to 6.5kyr BP and represents an ideal location in which to explore this. Stable isotope analysis of red deer and ibex is used alongside other environmental and climatic proxies to reconstruct Late Upper Palaeolithic conditions. Results show that during the LGM, ibex adapted their niche to survive, and became a major prey species for humans. The diverse environmental opportunities offered in the high-relief and coastal environs of La Riera may help to explain the high human population levels in the Cantabrian Region throughout the Late Upper Palaeolithic. Despite fluctuating conditions, herbivores and humans had the flexibility and resilience to adapt, demonstrating the importance of southern European refugia for the survival of different species.

Environmental change has been proposed as a factor that contributed to the extinction of the Neanderthals in Europe during MIS3. Currently, the different local environmental conditions experienced at the time when Anatomically Modern Humans (AMH) met Neanderthals are not well known. In the Western Pyrenees, particularly, in the eastern end of the Cantabrian coast of the Iberian Peninsula, extensive evidence of Neanderthal and subsequent AMH activity exists, making it an ideal area in which to explore the palaeoenvironments experienced and resources exploited by both human species during the Middle to Upper Palaeolithic transition. Red deer and horse were analysed using bone collagen stable isotope analysis to reconstruct environmental conditions across the transition. A shift in the ecological niche of horses after the Mousterian demonstrates a change in environment, towards more open vegetation, linked to wider climatic change. In the Mousterian, Aurignacian and Gravettian, high inter-individual nitrogen ranges were observed in both herbivores. This could indicate that these individuals were procured from areas isotopically different in nitrogen. Differences in sulphur values between sites suggest some variability in the hunting locations exploited, reflecting the human use of different parts of the landscape. An alternative and complementary explanation proposed is that there were climatic fluctuations within the time of formation of these archaeological levels, as observed in pollen, marine and ice cores.

Most drugs are developed through iterative rounds of chemical synthesis and biochemical testing to optimize the affinity of a particular compound for a protein target of therapeutic interest. This process is challenging because candidate molecules must be selected from a chemical space of more than 10 60 drug-like possibilities 1 , and a single reaction used to synthesize each molecule has more than 10 7 plausible permutations of catalysts, ligands, additives and other parameters 2 . The merger of a method for high-throughput chemical synthesis with a biochemical assay would facilitate the exploration of this enormous search space and streamline the hunt for new drugs and chemical probes. Miniaturized high-throughput chemical synthesis 3-7 has enabled rapid evaluation of reaction space, but so far the merger of such syntheses with bioassays has been achieved with only low-density reaction arrays, which analyse only a handful of analogues prepared under a single reaction condition 8-13 . High-density chemical synthesis approaches that have been coupled to bioassays, including on-bead 14 , on-surface 15 , on-DNA 16 and mass-encoding technologies 17 , greatly reduce material requirements, but they require the covalent linkage of substrates to a potentially reactive support, must be performed under high dilution and must operate in a mixture format. These reaction attributes limit the application of transition-metal catalysts, which are easily poisoned by the many functional groups present in a complex mixture, and of transformations for which the kinetics require a high concentration of reactant. Here we couple high-throughput nanomole-scale synthesis with a label-free affinity-selection mass spectrometry bioassay. Each reaction is performed at a 0.1-molar concentration in a discrete well to enable transition-metal catalysis while consuming less than 0.05 milligrams of substrate per reaction. The affinity-selection mass spectrometry bioassay is then used to rank the affinity of the reaction products to target proteins, removing the need for time-intensive reaction purification. This method enables the primary synthesis and testing steps that are critical to the invention of protein inhibitors to be performed rapidly and with minimal consumption of starting materials.

Here we report Sr and Zn isotope ratios of teeth of medieval to early modern Breton people a population whose diet is known from historical, archeological and collagen isotope data. Most of the population, buried in the Dominican convent of Rennes, France, consists of parliamentary nobles, wealthy commoners and ecclesiastics, who had a diet rich in animal products. Our aim is to assess how the Zn isotope ratios of their teeth compare to those of other French historical populations previously studied, which were characterized by cereal-based diets, and those of modern French individuals, who daily eat animal products. We describe a clear offset (∼0.35‰) between local and non-local human individuals in Zn isotope ratios. The δ 66 Zn tooth values of local individuals overlap that of modern French people, and are lower than those of local carnivores. Non-local δ 66 Zn values are similar to those of historical individuals analyzed previously. We conclude the lower Zn isotope ratios of local humans relative to the associated fauna can be explained by the consumption of carnivorous fish and pork, in agreement with historical, zooarchaeological and collagen (C, N, S) isotope data. Zn isotopes could therefore be a tracer of fish and/or substantial meat consumption in ancient populations.

Lake Ontario once supported a large complex of Atlantic Salmon (Salmo salar) populations that became extinct prior to scientific study. Since the 1860s, research efforts to conserve and reintroduce a sustainable population of Atlantic Salmon have focused on determining whether Lake Ontario's original salmon populations had migrated to the Atlantic Ocean as part of their lifecycle (anadromy), stayed in the lake year-round (potamodromy), or both. We used stable carbon, nitrogen, and sulfur isotope analyses of archaeological bones and historical museum-archived salmon scales to show that the original salmon populations from Lake Ontario completed their entire lifecycle without migrating to the Atlantic Ocean. With a time depth of more than 500 years, our findings provide a unique baseline with significant potential for informing modern restocking and conservation efforts.

A geostatistical model to predict human skeletal oxygen isotope values (δ 18 O p ) in Britain is presented here based on a new dataset of Chalcolithic and Early Bronze Age human teeth. The spatial statistics which underpin this model allow the identification of individuals interpreted as 'non-local' to the areas where they were buried (spatial outliers). A marked variation in δ 18 O p is observed in several areas, including the Stonehenge region, the Peak District, and the Yorkshire Wolds, suggesting a high degree of human mobility. These areas, rich in funerary and ceremonial monuments, may have formed focal points for people, some of whom would have travelled long distances, ultimately being buried there. The dataset and model represent a baseline for future archaeological studies, avoiding the complex conversions from skeletal to water δ 18 O values-a process known to be problematic.

Modern humans arrived in Europe ~45,000 years ago, but little is known about their genetic composition before the start of farming ~8,500 years ago. Here we analyse genome-wide data from 51 Eurasians from ~45,000-7,000 years ago. Over this time, the proportion of Neanderthal DNA decreased from 3-6% to around 2%, consistent with natural selection against Neanderthal variants in modern humans. Whereas there is no evidence of the earliest modern humans in Europe contributing to the genetic composition of present-day Europeans, all individuals between ~37,000 and ~14,000 years ago descended from a single founder population which forms part of the ancestry of present-day Europeans. An ~35,000-year-old individual from northwest Europe represents an early branch of this founder population which was then displaced across a broad region, before reappearing in southwest Europe at the height of the last Ice Age ~19,000 years ago. During the major warming period after ~14,000 years ago, a genetic component related to present-day Near Easterners became widespread in Europe. These results document how population turnover and migration have been recurring themes of European prehistory.

The mausoleum complex of the First Emperor of China, Qin Shi Huang (259-210 BC), is one of the most famous and important archaeological sites in China, yet questions remain as to how it was constructed and by whom. Here we present isotopic results of individuals from the Liyi (n = 146) and Shanren sites (n = 14), both associated with the mausoleum complex. Those buried at Liyi represent the local workers/inhabitants of the Qin population, and the δ(13)C (-8.7 ± 1.5%) and δ(15)N (10.3 ± 0.7%) values indicate that they consumed predominately millet and/or domestic animals fed millet. In contrast, the Shanren individuals were prisoners forced to construct the mausoleum (found buried haphazardly in a mass grave and some in iron leg shackles), and their δ(13)C (-15.4 ± 2.9%) and δ(15)N (8.0 ± 0.6%) results indicate a more mixed C3/C4 diet, with possibly less domestic animals and more wild game protein consumed. This pattern of decreased millet consumption is also characteristic of archaeological sites from southern China, and possible evidence the Shanren prisoners originated from this region (possibly the ancient Chu state located in modern day Hubei Province and parts of Hunan and Anhui Provinces). Further, this finding is in agreement with historical sources and is supported by previous ancient DNA evidence that the mausoleum workers had diverse origins, with many genetically related to southern Chinese groups.

In order to explore the possibilities of using zinc (Zn) stable isotope ratios as dietary indicators, we report here on the measurements of the ratio of stable isotopes of zinc ((66)Zn/(64)Zn, expressed here as δ(66)Zn) in bioapatite (bone and dental enamel) of animals from a modern food web in the Koobi Fora region of the Turkana Basin in Kenya. We demonstrate that δ(66)Zn values in both bone and enamel allow a clear distinction between carnivores and herbivores from this food web. Differences were also observed between browsers and grazers as well as between carnivores that consumed bone (i.e. hyenas) compared to those that largely consume flesh (i.e. lions). We conclude that Zn isotope ratio measurements of bone and teeth are a new and promising dietary indicator.

Cetacean mass strandings occur regularly worldwide, yet the compounded effects of natural and anthropogenic factors often complicate our understanding of these phenomena. Evidence of past stranding episodes may, thus, be essential to establish the potential influence of climate change. Investigations on bones from the site of Grotta dell'Uzzo in North West Sicily (Italy) show that the rapid climate change around 8,200 years ago coincided with increased strandings in the Mediterranean Sea. Stable isotope analyses on collagen from a large sample of remains recovered at this cave indicate that Mesolithic hunter-gatherers relied little on marine resources. A human and a red fox dating to the 8.2-kyr-BP climatic event, however, acquired at least one third of their protein from cetaceans. Numerous carcasses should have been available annually, for at least a decade, to obtain these proportions of meat. Our findings imply that climate-driven environmental changes, caused by global warming, may represent a serious threat to cetaceans in the near future.

We present the high-quality genome sequence of a ∼45,000-year-old modern human male from Siberia. This individual derives from a population that lived before-or simultaneously with-the separation of the populations in western and eastern Eurasia and carries a similar amount of Neanderthal ancestry as present-day Eurasians. However, the genomic segments of Neanderthal ancestry are substantially longer than those observed in present-day individuals, indicating that Neanderthal gene flow into the ancestors of this individual occurred 7,000-13,000 years before he lived. We estimate an autosomal mutation rate of 0.4 × 10(-9) to 0.6 × 10(-9) per site per year, a Y chromosomal mutation rate of 0.7 × 10(-9) to 0.9 × 10(-9) per site per year based on the additional substitutions that have occurred in present-day non-Africans compared to this genome, and a mitochondrial mutation rate of 1.8 × 10(-8) to 3.2 × 10(-8) per site per year based on the age of the bone.

Ranging and residence patterns among early hominins have been indirectly inferred from morphology, stone-tool sourcing, referential models and phylogenetic models. However, the highly uncertain nature of such reconstructions limits our understanding of early hominin ecology, biology, social structure and evolution. We investigated landscape use in Australopithecus africanus and Paranthropus robustus from the Sterkfontein and Swartkrans cave sites in South Africa using strontium isotope analysis, a method that can help to identify the geological substrate on which an animal lived during tooth mineralization. Here we show that a higher proportion of small hominins than large hominins had non-local strontium isotope compositions. Given the relatively high levels of sexual dimorphism in early hominins, the smaller teeth are likely to represent female individuals, thus indicating that females were more likely than males to disperse from their natal groups. This is similar to the dispersal pattern found in chimpanzees, bonobos and many human groups, but dissimilar from that of most gorillas and other primates. The small proportion of demonstrably non-local large hominin individuals could indicate that male australopiths had relatively small home ranges, or that they preferred dolomitic landscapes.

Morphological traits typical of Neanderthals began to appear in European hominids at least 400,000 years ago and about 150,000 years ago in western Asia. After their initial appearance, such traits increased in frequency and the extent to which they are expressed until they disappeared shortly after 30,000 years ago. However, because most fossil hominid remains are fragmentary, it can be difficult or impossible to determine unambiguously whether a fossil is of Neanderthal origin. This limits the ability to determine when and where Neanderthals lived. To determine how far to the east Neanderthals ranged, we determined mitochondrial DNA (mtDNA) sequences from hominid remains found in Uzbekistan and in the Altai region of southern Siberia. Here we show that the DNA sequences from these fossils fall within the European Neanderthal mtDNA variation. Thus, the geographic range of Neanderthals is likely to have extended at least 2,000 km further to the east than commonly assumed.

Knowledge of our ancestor's diets is becoming increasingly important in evolutionary medicine, as researchers have argued that we have evolved to specific type of 'Palaeolithic' diet, and many modern nutritional disorders relate to the mismatch between the diet to which we have evolved, and the relatively newer agricultural-based 'Neolithic' diets. However, what is the archaeological evidence for pre-agricultural diets and how have they changed over the four million years of hominid evolution? This paper briefly introduces the three lines of evidence we have for Palaeolithic and Neolithic diets; morphological changes, archaeological material evidence, and direct measurement of diet from bone chemistry. The morphological changes, increasing gracilization of the mandible and increasing brain size have been interpreted (based on analogies with living primates) as the move from plants to higher-quality, more digestible, animal meat, although this is debated. The archaeological evidence is especially weak, as many organic materials, especially plants, do not survive well, and are therefore invisible in the archaeological record. Artefacts, such as stone tools which are likely to be used for hunting and animal bones with evidence of human processing and butchering do indicate that hunting did occur at many times in the past, but it is impossible to judge the frequency. Direct evidence from bone chemistry, such as the measurement of the stable isotopes of carbon and nitrogen, do provide direct evidence of past diet, and limited studies on five Neanderthals from three sites, as well as a number of modern Palaeolithic and Mesolithic humans indicates the importance of animal protein in diets. There is a significant change in the archaeological record associated with the introduction of agriculture worldwide, and an associated general decline in health in some areas. However, there is an rapid increase in population associated with domestication of plants, so although in some regions individual health suffers after the Neolithic revolution, as a species humans have greatly expanded their population worldwide.