The origins and spread of domestic horses from the Western Eurasian steppes

Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region.Domestication of horses fundamentally transformed long-range mobility and warfare(1). However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling(2-4) at Botai, Central Asia around 3500 bc(3). Other longstanding candidate regions for horse domestication, such as Iberia(5) and Anatolia(6), have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association(7) between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc(8,9) driving the spread of Indo-European languages(10). This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture(11,12).Descriptive and Comparative Linguistic

The origins and spread of domestic horses from the Western Eurasian steppes

Domestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 bc. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture

Efficacy and safety of pegylated full-length recombinant factor VIII with extended half-life for perioperative haemostasis in haemophilia A patients

Introduction: BAX 855 is a pegylated full-length recombinant factor VIII (rFVIII) with an extended half-life, built on a licensed rFVIII (ADVATE (R)). BAX 855 demonstrated efficacy and safety in prophylaxis and the treatment of bleeding episodes in previously treated patients (PTPs) with severe haemophilia A. Aim: This phase 3 surgery study evaluates the haemostatic efficacy and safety of BAX 855 for perioperative haemostasis in PTPs with severe haemophilia A undergoing surgery. Methods: Elective procedures were prospectively classified as major or minor. The dose and frequency of BAX 855 administered perioperatively were to be guided by each patient's pharmacokinetic profile for major procedures or BAX 855 incremental recovery for minor procedures. Haemostatic efficacy was evaluated using a predefined scale. Blood loss was compared to the expected average and maximum blood loss predicted preoperatively. Results: A total of 15 male patients (aged 19-52 years) underwent 15 procedures (11 major and four minor). The overall intra-and perioperative haemostatic efficacy of BAX 855 was 'excellent' in all 15 subjects (100%). Postoperatively, evaluated at postoperative Day 1, all treatments were 'excellent' except for one minor (dental) procedure which was rated 'good'. No related adverse events, allergic reactions, thrombotic events, nor signs of immunogenicity in terms of induction of binding antibodies to FVIII, PEG or PEG-VIII, or FVIII inhibitors were observed. Conclusion: These results demonstrate that BAX 855 is safe and haemostatically effective in patients with severe haemophilia A undergoing surgery

Minimally Manipulated Bone Marrow-Derived Cells Can Be Used for Tissue Engineering In Situ and Simultaneous Formation of Personalized Tissue Models

Red bone marrow and autologous bone tissue (bone fragments and bone chips) of the donor were harvested intraoperatively during autoplasty of talus bone defect. Titanium chips were obtained by grinding a fragment of a microporous titanium-coated hip arthroplasty (Zimmer). Bone marrow mononuclear cells were isolated in the operating room, and bone and titanium fragments were incubated with a suspension of mononuclear cells. The quality of revitalization was assessed by fluorescence microscopy and histological examination after culturing of adherent cells on the bone and titanium fragments. During culturing on bone chips, bone marrow mononuclear fraction cells demonstrated significantly higher metabolic activity than bone marrow cells (p=0.04). Mononuclear fraction cells were also capable of stable colonization of titanium fragments with the formation of composite tissue model. © 2022, Springer Science+Business Media, LLC, part of Springer Nature

A clinical trial of a whole-virus H5N1 vaccine derived from cell culture

10.1056/NEJMoa073121New England Journal of Medicine358242573-258

Safety and immunogenicity of two different doses of a Vero cell-derived, whole virus clade 2 H5N1 (A/Indonesia/05/2005) influenza vaccine

10.1016/j.vaccine.2011.10.088Vaccine302329-335VACC

A cell culture (Vero)-derived H5N1 whole-virus vaccine induces cross-reactive memory responses

10.1086/605608Journal of Infectious Diseases20071113-1118JIDI