Subarctic climate for the earliest Homo sapiens in Europe

Acknowledgments The re-excavation of Bacho Kiro Cave was jointly conducted by the National Institute of Archaeology with Museum, Bulgarian Academy of Sciences, Sofia and the Department of Human Evolution at the MPI-EVA. We would like to thank the National Museum of Natural History (Sofia), the Archaeology Department at the New Bulgarian University (Sofia), the Regional Museum of History in Gabrovo, and the History Museum in Dryanovo for assistance on this project and the opportunity to study the Bacho Kiro Cave faunal material. We would like to thank M. Trost, S. Hesse, M. Kaniecki, and P. Dittmann (MPI-EVA) for technical assistance during stable isotope sample preparation. S. Steinbrenner is thanked for technical assistance with TC/EA-IRMS maintenance. Thanks are also due to H. Temming and U. Schwarz (MPI-EVA) for the production of microCT scans and replicas of the sample materials. We would also like to acknowledge the assistance of to D. Veres with taking OSL samples. Last but not least we would like to thank the handling editor, S. Ortman, as well as three anonymous reviewers for their thoughtful comments that greatly improved this manuscript. Funding: The field work was financed by the Max Planck Society. The stable isotope work was funded by the Max Planck Society as part of S.P.’s doctoral project. S.P. was supported by the Max Planck Society and the University of Aberdeen. K.B. was supported by a Philip Leverhulme Prize from The Leverhulme Trust (PLP-2019-284). N.B.’s work was supported as part of a grant by the German Research Foundation (“PALÄODIET” Project 378496604). V.A. was supported by a grant from the Foundation for Science and Technology, Portugal (IF/01157/2015/CP1308/CT0002). Author contributions: The study was devised by S.P., K.B., S.P.M., J.-J.H., and T.T. Archaeological excavation was undertaken by N.S. and T.T. in collaboration with Z.R. and S.P.M. who all contributed contextual information. V.A. collected sedimentological data at the site and untertook micromorphological investigations that provided information on site formation for this study. Zooarchaeological and paleontological analyses were performed by G.M.S. and R.S. OSL dating was carried out by T.L. Radiocarbon dating and recalibration of radiocarbon dates were conducted by H.F. MC-ICPMS analysis was conducted by N.B. and S.P. Sampling, sample processing for oxygen and strontium stable isotope analysis, and TC/EA-IRMS analysis were carried out by S.P. Code and data analyses were written and conducted by S.P. N.-H.T. consulted on statistical analysis and coding. S.P. wrote the paper with input from all authors. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.Peer reviewedPublisher PD

Initial Upper Palaeolithic humans in Europe had recent Neanderthal ancestry

Modern humans appeared in Europe by at least 45,000 years ago1–5, but the extent of their interactions with Neanderthals, who disappeared by about 40,000 years ago6, and their relationship to the broader expansion of modern humans outside Africa are poorly understood. Here we present genome-wide data from three individuals dated to between 45,930 and 42,580 years ago from Bacho Kiro Cave, Bulgaria1,2. They are the earliest Late Pleistocene modern humans known to have been recovered in Europe so far, and were found in association with an Initial Upper Palaeolithic artefact assemblage. Unlike two previously studied individuals of similar ages from Romania7 and Siberia8 who did not contribute detectably to later populations, these individuals are more closely related to present-day and ancient populations in East Asia and the Americas than to later west Eurasian populations. This indicates that they belonged to a modern human migration into Europe that was not previously known from the genetic record, and provides evidence that there was at least some continuity between the earliest modern humans in Europe and later people in Eurasia. Moreover, we find that all three individuals had Neanderthal ancestors a few generations back in their family history, confirming that the first European modern humans mixed with Neanderthals and suggesting that such mixing could have been common

Identifying the unidentified fauna enhances insights into hominin subsistence strategies during the Middle to Upper Palaeolithic transition

Understanding Palaeolithic hominin subsistence strategies requires the comprehensive taxonomic identification of faunal remains. The high fragmentation of Late Pleistocene faunal assemblages often prevents proper taxonomic identification based on bone morphology. It has been assumed that the morphologically unidentifiable component of the faunal assemblage would reflect the taxonomic abundances of the morphologically identified portion. In this study, we analyse three faunal datasets covering the Middle to Upper Palaeolithic transition (MUPT) at Bacho Kiro Cave (Bulgaria) and Les Cottés and La Ferrassie (France) with the application of collagen type I peptide mass fingerprinting (ZooMS). Our results emphasise that the fragmented component of Palaeolithic bone assemblages can differ significantly from the morphologically identifiable component. We obtain contrasting identification rates between taxa resulting in an overrepresentation of morphologically identified reindeer (Rangifer tarandus) and an underrepresentation of aurochs/bison (Bos/Bison) and horse/European ass (Equus) at Les Cottés and La Ferrassie. Together with an increase in the relative diversity of the faunal composition, these results have implications for the interpretation of subsistence strategies during a period of possible interaction between Neanderthals and Homo sapiens in Europe. Furthermore, shifts in faunal community composition and in carnivore activity suggest a change in the interaction between humans and carnivores across the MUPT and indicate a possible difference in site use between Neanderthals and Homo sapiens. The combined use of traditional and biomolecular methods allows (zoo)archaeologists to tackle some of the methodological limits commonly faced during the morphological assessment of Palaeolithic bone assemblages

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Clinical Evaluation of CAD/CAM Indirect Zirconia Restorations of Severely Destroyed Vital Teeth in the Posterior Area – Early Clinical Results

Background: Dental applications of CAD/CAM concept have been available for almost 30 years. They have allowed dentists to work with novel materials with better properties. One of these materials is zirconia ceramic

Morphological Study Of Border Area Of Pulp-Capping Materials And Er:YAG Laser Prepared Hard Dental Surface

Introduction: Vital pulp therapy involves biologically based therapeutic activities aimed at restoring health and preserving the vitality of cariously or traumatically damaged pulp. Adaptation of pulp-capping materials to the prepared tooth surface may be the key to the success of biological tooth treatment

Modulating the RNA processing and decay by the exosome: Altering Rrp44/Dis3 activity and end-product

In eukaryotes, the exosome plays a central role in RNA maturation, turnover, and quality control. In Saccharomyces cerevisiae, the core exosome is composed of nine catalytically inactive subunits constituting a ring structure and the active nuclease Rrp44, also known as Dis3. Rrp44 is a member of the ribonuclease II superfamily of exoribonucleases which include RNase R, Dis3L1 and Dis3L2. In this work we have functionally characterized three residues located in the highly conserved RNB catalytic domain of Rrp44: Y595, Q892 and G895. To address their precise role in Rrp44 activity, we have constructed Rrp44 mutants and compared their activity to the wild-type Rrp44. When we mutated residue Q892 and tested its activity in vitro , the enzyme became slightly more active. We also showed that when we mutated Y595, the final degradation product of Rrp44 changed from 4 to 5 nucleotides. This result confirms that this residue is responsible for the stacking of the RNA substrate in the catalytic cavity, as was predicted from the structure of Rrp44. Furthermore, we also show that a strain with a mutation in this residue has a growth defect and affects RNA processing and degradation. These results lead us to hypothesize that this residue has an important biological role. Molecular dynamics modeling of these Rrp44 mutants and the wild-type enzyme showed changes that extended beyond the mutated residues and helped to explain these results. © 2013 Reis et al.FCT, Portugal (PEst-OE/EQB/LA0004/2011); European Commission (FP7-KBBE-2011-1-289326, FP7 HEALTH-F3-2009-223431, FP7 HEALTH-2011-278603); National Institutes of Health (R01GM099790); Welch foundation (AU-177); the Spanish Ministerio de Ciencia e Innovación (SAF2007-61926, IPT2011-0964-900000, SAF2011-13156-E); Fundación Ramón Areces; Centro de Computación Científica CCC-UAM; European Social FundPeer Reviewe