Primary Sequences of Protein-Like Copolymers: Levy Flight Type Long Range Correlations

We consider the statistical properties of primary sequences of two-letter HP copolymers (H for hydrophobic and P for polar) designed to have water soluble globular conformations with H monomers shielded from water inside the shell of P monomers. We show, both by computer simulations and by exact analytical calculation, that for large globules and flexible polymers such sequences exhibit long-range correlations which can be described by Levy-flight statistics.Comment: 4 pages, including 2 figures; several references added, some formulations improve

Analysis of 3800-year-old Yersinia pestis genomes suggests Bronze Age origin for bubonic plague

该论文通过对青铜器时代的两个鼠疫杆菌分离株进行测序，深入剖析了鼠疫杆菌的历史。德国、俄罗斯、中国和瑞士等多国研究员共同参与了研究。这篇论文的第一作者是德国马克斯-普朗克研究所的考古遗传学专家Maria Spyrou。她和同事从俄罗斯墓穴中埋葬的九名古代人的牙齿样本入手，发现有两人感染鼠疫杆菌。之后，他们从这些个体中分离出距今约3800年的病原菌。在这项新研究中，研究人员利用液相捕获和Illumina鸟枪法测序技术，对青铜器时代的一名男子（RT5）的鼠疫杆菌和人类宿主序列进行测序，其中鼠疫杆菌基因组的平均覆盖度达到32倍。同时，他们还对另一名感染个体（RT6）的分离株进行测序，平均覆盖度为1.9倍。系统发育分析表明，RT5和RT6分离株是共同谱系的一部分，这个谱系的祖先是史上三次瘟疫大流行的罪魁祸首。除了众所周知的中世纪欧洲瘟疫大流行，鼠疫杆菌还曾造成公元6世纪的查士丁尼瘟疫和19世纪的中国大规模鼠疫。 马克斯-普朗克人类历史科学研究所的古病理学专家Kirsten Bos表示，这些结果表明“具有传播潜力的瘟疫存在的时间比我们想象得更久。”Bos是这篇论文的通讯作者之一。【Abstract】The origin of Yersinia pestis and the early stages of its evolution are fundamental subjects of investigation given its high virulence and mortality that resulted from past pandemics. Although the earliest evidence of Y. pestis infections in humans has been identified in Late Neolithic/Bronze Age Eurasia (LNBA 5000–3500y BP), these strains lack key genetic components required for flea adaptation, thus making their mode of transmission and disease presentation in humans unclear. Here, we reconstruct ancient Y. pestis genomes from individuals associated with the Late Bronze Age period (~3800 BP) in the Samara region of modern-day Russia. We show clear distinctions between our new strains and the LNBA lineage, and suggest that the full ability for flea-mediated transmission causing bubonic plague evolved more than 1000 years earlier than previously suggested. Finally, we propose that several Y. pestis lineages were established during the Bronze Age, some of which persist to the present day.We thank Cosimo Posth, Marcel Keller, Michal Feldman and Wolfgang Haak for useful insights to the manuscript, as well as Alexander Immel and Stephen Clayton for computational support. In addition, we are thankful to Guido Brandt, Antje Wissgott and Cäcilia Freund for laboratory support. M.A.S., A.H., K.I.B. and J.K. were supported by the ERC starting grant APGREID, and by the Max Planck Society. C.C.W. was supported by the Max Planck Society and the Nanqiang Outstanding Young Talents Program of Xiamen University. D.K. was supported by a Marie Heim-Vögtlin grant from the Swiss National Science Foundation

Massive migration from the steppe is a source for Indo-European languages in Europe

We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost four hundred thousand polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of western and far eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, ~8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary, and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a ~24,000 year old Siberian6 . By ~6,000-5,000 years ago, a resurgence of hunter-gatherer ancestry had occurred throughout much of Europe, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but from a population of Near Eastern ancestry. Western and Eastern Europe came into contact ~4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced ~3/4 of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least ~3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for the theory of a steppe origin of at least some of the Indo-European languages of Europe

The type Ia supernova SNLS-03D3bb from a super-Chandrasekhar-mass white dwarf star

The acceleration of the expansion of the universe, and the need for Dark Energy, were inferred from the observations of Type Ia supernovae (SNe Ia). There is consensus that SNe Ia are thermonuclear explosions that destroy carbon-oxygen white dwarf stars that accrete matter from a companion star, although the nature of this companion remains uncertain. SNe Ia are thought to be reliable distance indicators because they have a standard amount of fuel and a uniform trigger -- they are predicted to explode when the mass of the white dwarf nears the Chandrasekhar mass -- 1.4 solar masses. Here we show that the high redshift supernova SNLS-03D3bb has an exceptionally high luminosity and low kinetic energy that both imply a super-Chandrasekhar mass progenitor. Super-Chandrasekhar mass SNe Ia should preferentially occur in a young stellar population, so this may provide an explanation for the observed trend that overluminous SNe Ia only occur in young environments. Since this supernova does not obey the relations that allow them to be calibrated as standard candles, and since no counterparts have been found at low redshift, future cosmology studies will have to consider contamination from such events.Comment: 9 pages, 4 figures. To appear in Nature Sept. 21. Accompanying News & Views in same issue. Supplementary information available at www.nature.com/natur

Theoretical Light Curves of Type II-P SNe and Applications to Cosmology

Based on an extensive grid of stellar models between 13 and 25 Mo and a wide range of metallicities, we have studied the light curves of core collapse supernovae, their application to cosmology and evolutionary effects with redshift. The direct link between the hydro and radiation transport allows to calculate monochromatic light curves. With decreasing metallicity Z and increasing mass, progenitors tend to explode as compact Blue Supergiants and produce sub-luminous supernovae that are about 1.5 mag dimmer compared to "normal" SNe II with Red Supergiant progenitors (RSGs). Progenitors with small masses tend to explode as RSGs even at low Z. The consequences are obvious for probing the chemical evolution, namely, a strong bias when using the statistics of core collapse supernovae to probe the history of star formation. Our study is limited in scope with respect to the explosion energies and the production of radioactive Ni. Within the class of "extreme SNe II-P" supernovae, the light curves are rather insensitive with respect to the progenitor mass and explosion energy compared to analytic models which are based on parameterized stellar structures. We expect a wider range of brightness due to variations in Ni56 because radioactive energy is a main source of luminosity. However, the overall insensitivity of LCs may allow their use as quasi-standard candles for distance determination.Comment: 14 pages, 16 figures, accepted for publication in MNRA

Ancient Plasmodium genomes shed light on the history of human malaria

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 species1. Nevertheless, debate persists over when and how malaria parasites emerged as human pathogens and spread around the globe1,2. 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 millennia3. 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.This project was funded by the National Science Foundation, grants BCS-2141896 and BCS-1528698; the European Research Council (ERC) under the European Union’s Horizon 2020 programme, grants 851511-MICROSCOPE (to S. Schiffels), 771234-PALEoRIDER (to W.H.) and starting grant 805268-CoDisEASe (to K.I.B.); and the ERC starting grant Waves ERC758967 (supporting K. Nägele and S.C.). We thank the Max Planck-Harvard Research Center for the Archaeoscience of the Ancient Mediterranean for supporting M. Michel, E. Skourtanioti, A.M., R.A.B., L.C.B., G.U.N., N.S., V.V.-M., M. McCormick, P.W.S., C.W. and J.K.; the Kone Foundation for supporting E.K.G. and A.S.; and the Faculty of Medicine and the Faculty of Biological and Environmental Sciences at the University of Helsinki for grants to E.K.G. A.S. thanks the Magnus Ehrnrooth Foundation, the Sigrid Jusélius Foundation, the Finnish Cultural Foundation, the Academy of Finland, the Life and Health Medical Foundation and the Finnish Society of Sciences and Letters. M.C.B. acknowledges funding from: research project PID2020-116196GB-I00 funded by MCIN/AEI/10.13039/501100011033; the Spanish Ministry of Culture; the Chiang Ching Kuo Foundation; Fundación Palarq; the EU FP7 Marie Curie Zukunftskolleg Incoming Fellowship Programme, University of Konstanz (grant 291784); STAR2-Santander Universidades and Ministry of Education, Culture and Sports; and CEI 2015 project Cantabria Campus Internacional. M.E. received support from the Czech Academy of Sciences award Praemium Academiae and project RVO 67985912 of the Institute of Archaeology of the Czech Academy of Sciences, Prague. This work has been funded within project PID2020-115956GB-I00 ‘Origen y conformación del Bronce Valenciano’, granted by the Ministry of Science and Innovation of the Government of Spain, and grants from the Canadian Institutes for Health Research (MZI187236), Research Nova Scotia (RNS 2023-2565) and The Center for Health Research in Developing Countries. D.K. is the Canada research chair in translational vaccinology and inflammation. R.L.K. acknowledges support from a 2019 University of Otago research grant (Human health and adaptation along Silk Roads, a bioarchaeological investigation of a medieval Uzbek cemetery). P.O. thanks the Jane and Aatos Erkko Foundation, the Finnish Cultural Foundation and the Academy of Finland. S. Peltola received support from the Emil Aaltonen Foundation and the Ella and Georg Ehrnrooth Foundation. D.C.S.-G. thanks the Generalitat Valenciana (CIDEGENT/2019/061). E.W.K. acknowledges support from the DEEPDEAD project, HERA-UP, CRP (15.055) and the Horizon 2020 programme (grant 649307). M. Spyrou thanks the Elite program for postdocs of the Baden-Württemberg Stiftung. Open access funding provided by Max Planck Society

Binary systems and their nuclear explosions

Peer ReviewedPreprin

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Genome-wide patterns of selection in 230 ancient Eurasians

Ancient DNA makes it possible to directly witness natural selection by analyzing samples from populations before, during and after adaptation events. Here we report the first scan for selection using ancient DNA, capitalizing on the largest genome-wide dataset yet assembled: 230 West Eurasians dating to between 6500 and 1000 BCE, including 163 with newly reported data. The new samples include the first genome-wide data from the Anatolian Neolithic culture whose genetic material we extracted from the DNA-rich petrous bone and who we show were members of the population that was the source of Europe’s first farmers. We also report a complete transect of the steppe region in Samara between 5500 and 1200 BCE that allows us to recognize admixture from at least two external sources into steppe populations during this period. We detect selection at loci associated with diet, pigmentation and immunity, and two independent episodes of selection on height