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Modern humans arrived in Europe more than 45,000 years ago, overlapping at least 5,000 years with Neanderthals 1-4 . Limited genomic data from these early modern humans have shown that at least two genetically distinct groups inhabited Europe, represented by Zlatý kůň, Czechia 3 and Bacho Kiro, Bulgaria 2 . Here we deepen our understanding of early modern humans by analyzing one high-coverage genome and five low-coverage genomes from ~45,000 year-old remains from Ilsenhöhle in Ranis, Germany 4 , and a further high-coverage genome from Zlatý kůň. We show that distant familial relationships link the Ranis and Zlatý kůň individuals and that they were part of the same small, isolated population that represents the deepest known split from the Out-of-Africa lineage. Ranis genomes harbor Neanderthal segments that originate from a single admixture event shared with all non-Africans that we date to ~45,000-49,000 years ago. This implies that ancestors of all non-Africans sequenced to-date resided in a common population at this time, and further suggests that modern human remains older than 50,000 years from outside Africa represent different non-African populations., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Malaria-causing protozoa of the genus Plasmodium have exerted one of the strongest selective pressures on the human genome, and resistance alleles provide biomolecular footprints that outline the historical reach of these species 1 . Nevertheless, debate persists over when and how malaria parasites emerged as human pathogens and spread around the globe 1,2 . To address these questions, we generated high-coverage ancient mitochondrial and nuclear genome-wide data from P. falciparum, P. vivax and P. malariae from 16 countries spanning around 5,500 years of human history. We identified P. vivax and P. falciparum across geographically disparate regions of Eurasia from as early as the fourth and first millennia BCE, respectively; for P. vivax, this evidence pre-dates textual references by several millennia 3 . Genomic analysis supports distinct disease histories for P. falciparum and P. vivax in the Americas: similarities between now-eliminated European and peri-contact South American strains indicate that European colonizers were the source of American P. vivax, whereas the trans-Atlantic slave trade probably introduced P. falciparum into the Americas. Our data underscore the role of cross-cultural contacts in the dissemination of malaria, laying the biomolecular foundation for future palaeo-epidemiological research into the impact of Plasmodium parasites on human history. Finally, our unexpected discovery of P. falciparum in the high-altitude Himalayas provides a rare case study in which individual mobility can be inferred from infection status, adding to our knowledge of cross-cultural connectivity in the region nearly three millennia ago., (© 2024. The Author(s).)

Recent excavations at Ranis (Germany) identified an early dispersal of Homo sapiens into the higher latitudes of Europe by 45,000 years ago. Here we integrate results from zooarchaeology, palaeoproteomics, sediment DNA and stable isotopes to characterize the ecology, subsistence and diet of these early H. sapiens. We assessed all bone remains (n = 1,754) from the 2016-2022 excavations through morphology (n = 1,218) or palaeoproteomics (zooarchaeology by mass spectrometry (n = 536) and species by proteome investigation (n = 212)). Dominant taxa include reindeer, cave bear, woolly rhinoceros and horse, indicating cold climatic conditions. Numerous carnivore modifications, alongside sparse cut-marked and burnt bones, illustrate a predominant use of the site by hibernating cave bears and denning hyaenas, coupled with a fluctuating human presence. Faunal diversity and high carnivore input were further supported by ancient mammalian DNA recovered from 26 sediment samples. Bulk collagen carbon and nitrogen stable isotope data from 52 animal and 10 human remains confirm a cold steppe/tundra setting and indicate a homogenous human diet based on large terrestrial mammals. This lower-density archaeological signature matches other Lincombian-Ranisian-Jerzmanowician sites and is best explained by expedient visits of short duration by small, mobile groups of pioneer H. sapiens., (© 2024. The Author(s).)

The spread of Homo sapiens into new habitats across Eurasia ~45,000 years ago and the concurrent disappearance of Neanderthals represents a critical evolutionary turnover in our species' history. 'Transitional' technocomplexes, such as the Lincombian-Ranisian-Jerzmanowician (LRJ), characterize the European record during this period but their makers and evolutionary significance have long remained unclear. New evidence from Ilsenhöhle in Ranis, Germany, now provides a secure connection of the LRJ to H. sapiens remains dated to ~45,000 years ago, making it one of the earliest forays of our species to central Europe. Using many stable isotope records of climate produced from 16 serially sampled equid teeth spanning ~12,500 years of LRJ and Upper Palaeolithic human occupation at Ranis, we review the ability of early humans to adapt to different climate and habitat conditions. Results show that cold climates prevailed across LRJ occupations, with a temperature decrease culminating in a pronounced cold excursion at ~45,000-43,000 cal BP. Directly dated H. sapiens remains confirm that humans used the site even during this very cold phase. Together with recent evidence from the Initial Upper Palaeolithic, this demonstrates that humans operated in severe cold conditions during many distinct early dispersals into Europe and suggests pronounced adaptability., (© 2024. The Author(s).)

The Middle to Upper Palaeolithic transition in Europe is associated with the regional disappearance of Neanderthals and the spread of Homo sapiens. Late Neanderthals persisted in western Europe several millennia after the occurrence of H. sapiens in eastern Europe 1 . Local hybridization between the two groups occurred 2 , but not on all occasions 3 . Archaeological evidence also indicates the presence of several technocomplexes during this transition, complicating our understanding and the association of behavioural adaptations with specific hominin groups 4 . One such technocomplex for which the makers are unknown is the Lincombian-Ranisian-Jerzmanowician (LRJ), which has been described in northwestern and central Europe 5-8 . Here we present the morphological and proteomic taxonomic identification, mitochondrial DNA analysis and direct radiocarbon dating of human remains directly associated with an LRJ assemblage at the site Ilsenhöhle in Ranis (Germany). These human remains are among the earliest directly dated Upper Palaeolithic H. sapiens remains in Eurasia. We show that early H. sapiens associated with the LRJ were present in central and northwestern Europe long before the extinction of late Neanderthals in southwestern Europe. Our results strengthen the notion of a patchwork of distinct human populations and technocomplexes present in Europe during this transitional period., (© 2024. The Author(s).)

Bimanual movements are fundamental components of everyday actions, yet the underlying mechanisms coordinating adaptation of the two hands remain unclear. Although previous studies highlighted the contextual effect of kinematics of both arms on internal model formation, we do not know how the sensorimotor control system associates the learned memory with the experienced states in bimanual movements. More specifically, can, and if so, how, does the sensorimotor control system combine multiple states from different effectors to create and adapt a motor memory? Here, we tested motor memory formation in two groups with a novel paradigm requiring the encoding of the kinematics of the right hand to produce the appropriate predictive force on the left hand. While one group was provided with training movements in which this association was evident, the other group was trained on conditions in which this association was ambiguous. After adaptation, we tested the encoding of the learned motor memory by measuring the generalization to new movement combinations. While both groups adapted to the novel dynamics, the evident group showed a weighted encoding of the learned motor memory based on movements of the other (right) hand, whereas the ambiguous group exhibited mainly same (left) hand encoding in bimanual trials. Despite these differences, both groups demonstrated partial generalization to unimanual movements of the left hand. Our results show that motor memories can be encoded depending on the motion of other limbs, but that the training conditions strongly shape the encoding of the motor memory formation and determine the generalization to novel contexts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Orschiedt, Franklin. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Until now, it was considered certain that the last reindeer hunters of the Ahrensburgian (tanged point groups) existed exclusively in northwestern Central Europe during the Younger Dryas Cold Period (~ Greenland Stadial 1). The excavations carried out since 2006 on the forecourt (Vorplatz) of the small Blätterhöhle in Hagen on the northern edge of the Sauerland uplands of southern Westphalia (North Rhine-Westphalia, western Germany) have now changed this view. Beneath a surprisingly extensive sequence of Mesolithic find horizons, Pleistocene sediments could be reached whose excavations yielded a Final Palaeolithic lithic ensemble of the Younger Dryas, unusual for the region and beyond. It is characterised by numerous backed lithic projectile points of high variability. Comparisons suggest a typological-technological connection with the Western European Laborian / Late Laborian. Neither in the nearer nor in the wider surroundings has a comparable lithic find ensemble been found so far. In addition, there is a lack of clear evidence for the reindeer in the fauna. Surprisingly, the vast majority of radiocarbon dates of bones and charcoals from the investigated archaeological horizon of the Final Pleistocene proved to be significantly older than expected from their stratigraphic position. This phenomenon has not yet been clarified., Competing Interests: The authors declare that there are no existing competing interests., (Copyright: © 2023 Baales et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: When moving in public space, individuals are challenged with having to master multiple cognitive and motor demands, either simultaneously or in short succession. Empirical evidence suggests that cognitive-motor multi-tasking during walking may impact one or both, cognitive and motor performance. These performance changes may result from unintentional task-interference effects, but also from strategic behavioral changes to cope with the multiple task demands. Strategic changes in human walking behavior have been uncovered in experimental scenarios, in which individuals avoid colliding with other individuals or objects in the environment. However, whether collision avoidance behavior is sensitive to cognitive-motor multi-task demands has remained underexplored, yet. Thus, with this study, we aimed at systematically studying cognitive-motor multi-task effects on collision avoidance during human locomotion., Methods: Ten healthy participants (23.9 ± 4.3 years, 4 female) were walking at their preferred speed from a predefined start to end position under four experimental conditions: walking only (BL), walking while having to avoid a collision with another person (IO), writing a text message on a mobile phone while walking (cognitive-motor dual-task, DT), and writing while walking with collision avoidance demand (multi-task, MT). Parameters quantifying locomotor as well as collision avoidance behavior (path length, walking speed, minimum distance, path and speed adjustment) were assessed using optical motion tracking. In addition, performance in the writing task (errors, writing speed) was examined., Results: Participants' locomotor behavior was significantly affected by experimental conditions, with additive effects of multi-task demands on both path length (BL = DT < IO < MT) and walking speed (BL > IO > DT > MT). Further, participants showed an increased error rate and writing speed in the writing task when walking as compared to when standing still, independent of the presence of an interferer. Importantly, collision avoidance behavior was selectively influenced by cognitive-motor multi-task demands, with an increased minimum distance to the other person in the MT-condition, but no differences in path or speed adjustment., Discussion: Our results suggest significant multi-tasking effects of writing a message on the mobile phone while walking on both locomotor behavior and writing task performance. Collision avoidance behavior seems to be selectively affected by multi-task demands, reflected in an increased minimum passing distance, without overt changes in path or speed adjustments. This may be indicative for a strategic change in collision avoidance behavior towards a more cautious strategy to account for altered attention allocation and less visual feedback when writing while walking., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Real-word evidence from diverse data sources is increasingly important in terms of generating rapid insights to effectively manage patient populations, especially during major public health disruptions such as the ongoing COVID-19 pandemic. Patients with chronic and inflammatory diseases - such as multiple sclerosis (MS) - were reported to experience potentially negative effects due to the use of immunosuppressive drugs in combination with a COVID-19 infection. In this research, we explored the impact of the COVID-19 pandemic on medication use in patients with MS in Germany., Methods: Patient-level pharmacy dispensing data from the Permea platform - covering approximately 44% of all community pharmacy dispensing in Germany - were analysed from 2019 - 2021. Longitudinal use patterns of MS medication and antidepressants and patient demographics were assessed. Daily variation in MS medication use was specifically studied around the dates of the first and second lockdowns in Germany., Results: We included data from 539,400 prescriptions which included at least 1 MS drug. The medication data showed a stable level of monthly prescriptions for MS medication at 2.02 ± 0.03 prescriptions per pharmacy during the study period. Although there was a sharp increase in daily prescriptions before the first lockdown (from an average 660.08 ± 137.59 daily prescriptions in the observed period to a maximum dispensing number of 998 daily prescriptions), the overall number of prescriptions remained at pre-pandemic levels (603 ± 90.31 daily prescriptions in 2019). Similar trends were observed for monthly co-prescribed antidepressant use per pharmacy (0.10 ± 0.01 in 2019-0.11 ± 0.02 in 2020)., Conclusion: Throughout the COVID-19 pandemic, the use of MS medications and co-prescribed antidepressants was stable. These insights from real-world data demonstrate the value of evidence-based insights for managing patient care., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Orschiedt (ORCID# 0000-0002-2813-6343) is employed by the Temedica GmbH and the Technical University of Munich. E. Jacyshyn-Owen, M. Eberl, M. Kahn (ORCID# 0000-0002-9596-6339) and B. Friedrich (ORCID# 0000-0002-2198-9925) are employed by the Temedica GmbH. S. Jansen is employed by the Noventi Health SE. N. Joschko is an employee of Roche Pharma AG and shareholder of F. Hoffmann-La Roche Ltd. S. Schneeweiss (ORCID# 0000-0003-2575-467X) is participating in investigator-initiated grants to the Brigham and Women’s Hospital from Boehringer Ingelheim and UCB unrelated to the topic of this study. He is a consultant to Aetion Inc., a software manufacturer of which he owns equity. His interests were declared, reviewed, and approved by the Brigham and Women’s Hospital in accordance with their institutional compliance policies., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Lactase persistence (LP), the continued expression of lactase into adulthood, is the most strongly selected single gene trait over the last 10,000 years in multiple human populations. It has been posited that the primary allele causing LP among Eurasians, rs4988235-A [1], only rose to appreciable frequencies during the Bronze and Iron Ages [2, 3], long after humans started consuming milk from domesticated animals. This rapid rise has been attributed to an influx of people from the Pontic-Caspian steppe that began around 5,000 years ago [4, 5]. We investigate the spatiotemporal spread of LP through an analysis of 14 warriors from the Tollense Bronze Age battlefield in northern Germany (∼3,200 before present, BP), the oldest large-scale conflict site north of the Alps. Genetic data indicate that these individuals represent a single unstructured Central/Northern European population. We complemented these data with genotypes of 18 individuals from the Bronze Age site Mokrin in Serbia (∼4,100 to ∼3,700 BP) and 37 individuals from Eastern Europe and the Pontic-Caspian Steppe region, predating both Bronze Age sites (∼5,980 to ∼3,980 BP). We infer low LP in all three regions, i.e., in northern Germany and South-eastern and Eastern Europe, suggesting that the surge of rs4988235 in Central and Northern Europe was unlikely caused by Steppe expansions. We estimate a selection coefficient of 0.06 and conclude that the selection was ongoing in various parts of Europe over the last 3,000 years., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Burials of the Late Palaeolithic (14 000-11 600 cal years before present, henceforth BP) are a rare phenomenon in Europe. Several sites possess burials of single and double individuals. As with the preceding Magdalenian, the burial of more than two individuals in the same grave cutting seems to be unusual, but does occur occasionally. The deposition of isolated and disarticulated human remains with or without cut marks seems additionally to belong to the Magdalenian context. In the final Palaeolithic phase (13 000-11 600 cal years BP) there is evidence for cemetery-like clusters of burials, which contrast to the Magdalenian evidence, instead showing some similarities with the succeeding Mesolithic. The earliest Mesolithic burials 11 600-10 500 cal BP) are a very rare phenomenon, covering a short time span between the beginning of the Preboreal and the beginning of the Boreal phase of the early Holocene. Here the evidence includes single inhumations, cemetery-like structures and a number of isolated human remains. Caves and rock shelters were the most common places for inhumations in both the final Palaeolithic and the early Mesolithic. Although the number of sites with a chronological continuity from the LUP to the Early Mesolithic burial is low, several aspects indicate a general continuity in burial patterns over this period. Apart from this continuity, the Mesolithic burials in general seem to represent a new level of diversity in burial practices.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'., (© 2018 The Author(s).)

Ancient DNA studies have established that Neolithic European populations were descended from Anatolian migrants who received a limited amount of admixture from resident hunter-gatherers. Many open questions remain, however, about the spatial and temporal dynamics of population interactions and admixture during the Neolithic period. Here we investigate the population dynamics of Neolithization across Europe using a high-resolution genome-wide ancient DNA dataset with a total of 180 samples, of which 130 are newly reported here, from the Neolithic and Chalcolithic periods of Hungary (6000-2900 bc, n = 100), Germany (5500-3000 bc, n = 42) and Spain (5500-2200 bc, n = 38). We find that genetic diversity was shaped predominantly by local processes, with varied sources and proportions of hunter-gatherer ancestry among the three regions and through time. Admixture between groups with different ancestry profiles was pervasive and resulted in observable population transformation across almost all cultural transitions. Our results shed new light on the ways in which gene flow reshaped European populations throughout the Neolithic period and demonstrate the potential of time-series-based sampling and modelling approaches to elucidate multiple dimensions of historical population interactions.

The Bronze Age site in the Tollense valley, Germany, has yielded thousands of human and animal bones and a number of archaeological artifacts. Several of the human bones exhibit blunt and sharp force lesions, and the assemblage has been interpreted as representing victims of a large scale conflict. One of the earliest finds is a human humerus with an embedded flint arrowhead. Alleged signs of healing initially reported for this humerus based on clinical CT imaging were interpreted as evidence of an antemortem lesion. The present study, using micro-CT imaging, revealed that the arrowhead lesion in the humerus, contrary to the previous interpretation, shows no signs of healing. The structure previously assumed to represent a sclerotic margin around the wound canal was shown to actually represent compacted trabecular debris. Thus, our re-analysis of the specimen led to a re-classification of the arrow wound as a perimortem lesion. The findings of the present study demonstrate the value of micro-CT imaging as a non-destructive method for obtaining information on the nature of bone lesions and healing reactions critical for the reconstruction of interpersonal conflict scenarios in the past., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Debate on the ancestry of Europeans centers on the interplay between Mesolithic foragers and Neolithic farmers. Foragers are generally believed to have disappeared shortly after the arrival of agriculture. To investigate the relation between foragers and farmers, we examined Mesolithic and Neolithic samples from the Blätterhöhle site. Mesolithic mitochondrial DNA sequences were typical of European foragers, whereas the Neolithic sample included additional lineages that are associated with early farmers. However, isotope analyses separate the Neolithic sample into two groups: one with an agriculturalist diet and one with a forager and freshwater fish diet, the latter carrying mitochondrial DNA sequences typical of Mesolithic hunter-gatherers. This indicates that the descendants of Mesolithic people maintained a foraging lifestyle in Central Europe for more than 2000 years after the arrival of farming societies.

We review the hominin fossil record from western Central Europe in light of the recent major revisions of the geochronological context. The mandible from Mauer (Homo heidelbergensis), dated to circa 500,000 years ago, continues to represent the earliest German hominin and may coincide with the occupation of Europe north of the high alpine mountain chains. Only limited new evidence is available for the Middle Pleistocene, mostly in the form of skull fragments, a pattern that may relate to taphonomic processes. These finds and their ages suggest the gradual evolution of a suite of Neandertal features during this period. Despite new finds of classic Neandertals, there is no clear proof for Neandertal burial from Germany. Alternatively, cut marks on a skull fragment from the Neandertal type site suggest special treatment of that individual. New Accelerator Mass Spectrometry (AMS) radiocarbon dates of previous finds leave little reliably dated evidence for anatomically modern humans (AMH) in Europe before 30,000 BP; the remains from Hahnöfersand, Binshof-Speyer, Paderborn-Sande, and Vogelherd are now of Holocene age. Thus, a correlation of AMH with the Aurignacian remains to be proven, and the general idea of a long coexistence of Neandertals and AMH in Europe may be questioned. In western Central Europe, evidence of Gravettian human fossils is also very limited, although a new double grave from lower Austria may be relevant. The only dated burial from the German Upper Paleolithic (from Mittlere Klause) falls into a time period (circa 18,600 BP) represented by only a few occupation sites in western Central Europe. A number of human remains at Magdalenian sites appear to result from variable (secondary) burial practices. In contrast, the Final Paleolithic (circa 12,000-9600 cal. BC) yields an increase of hominin finds, including multiple burials (Bonn-Oberkassel, Neuwied-Irlich), similar to the situation in western and southern Europe.