Ancient pigs reveal a near-complete genomic turnover following their introduction to Europe

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

An Improved ångström-type model for estimating solar radiation over the tibetan plateau

© 2017 by the authors. For estimating the annual mean of daily solar irradiation in plateau mountainous regions, observed data from 15 radiation stations were used to validate different empirical estimation methods over the Tibetan Plateau. Calibration indicates that sunshine-based site-dependent models perform better than temperature-based ones. Then, the highly rated sunshine-based Ångström model and temperature-based Bristow model were selected for regional application. The geographical models perform much better than the average models, but still not ideally. To achieve better performance, the Ångström-type model was improved using altitude and water vapor pressure as the leading factors. The improved model can accurately predict the coefficients at all the stations, and performs the best among all models with an average Nash-Sutcliffe Efficiency value of 0.856. Spatial distribution of the annual mean of daily solar irradiation was then estimated with the improved model. It is indicated that there is an increasing trend of radiation from east to west, with a great center of the annual mean of daily solar irradiation on southwest Tibetan Plateau ranging from 20 to 24 MJm2. The improved model should be further validated against observations before its applications in other plateau mountainous regions

A retrospective analysis of clinical outcome of patients with chemo-refractory metastatic breast cancer treated in a single institution phase I unit

BACKGROUND AND METHODS: Novel approaches to treat chemo-refractory metastatic breast cancer (MBC) are currently under investigation. This retrospective series reviews the outcome of 70 MBC patients who have participated in 30 phase I trials at the Royal Marsden Hospital from 2002 to 2009. RESULTS: The median treatment lines before phase I trial entry for MBC was 5 (range: 1-12 lines). The overall response rate was 11.4% (95% CI: 4.0-18.9%) and the clinical benefit rate at 4 months was 20% (95% CI: 10.6-29.3). The median time to progression was 7.0 weeks (95% CI: 6.4-7.5) and median overall survival was 8.7 months (95% CI: 7.6-9.8) from start of first phase I treatment. No patients discontinued trial because of treatment-related toxicities. Abnormal lactate dehydrogenase, serum albumin <35 mg per 100 ml, >or=5 previous treatment lines, liver metastases and Eastern Cooperative Group performance status >or=2 at study entry were significantly associated with poor overall survival in multivariate analysis. CONCLUSION: This retrospective analysis provides evidence that patients with MBC tolerate phase I clinical trials and a significant proportion of patients with chemo-refractory disease, particularly those with triple-negative or Her2-positive breast cancer, may benefit from treatment

Divergent consensuses on Arctic amplification influence on midlatitude severe winter weather

The article of record as published may be found at https://doi.org/10.1038/s41558-019-0662-yWe thank R. Blackport, C. Deser, L. Sun, J. Screen and D. Smith for discussions and suggested revisions to the manuscript. We also thank J. Screen and L. Sun for model data. A. Amin helped to create Fig. 2. US CLIVAR logistically and financially supported the Arctic-Midlatitude Working Group and Arctic Change and its Influence on Mid-Latitude Climate and Weather workshop that resulted in this article. J.C. is supported by the US National Science Foundation grants AGS-1657748 and PLR-1504361, 1901352. M.W. acknowledges funding by the Deutsche Forschungsgemeinschaft project no. 268020496– TRR 172, within the Transregional Collaborative Research Center “Arctic Amplification: Climate Relevant Atmospheric and Surface Processes, and Feedback Mechanisms (AC)3 ”. T.V. was supported by the Academy of Finland grant 317999. J.O. was supported by the NOAA Arctic Research Program. J.F. was supported by the Woods Hole Research Center. S.W. and H.G. are supported by the US DOE Award Number DE-SC0016605. J.Y. was supported by the Korea Meteorological Administration Research and Development Program under grant KMI2018-01015 and National Research Foundation grant NRF_2017R1A2B4007480. D.H. is supported by the Helmholtz Association of German Research Centers (grant FKZ HRSF-0036, project POLEX). The authors acknowledge the World Climate Research Programme’s Working Group on Coupled Modelling, which is responsible for CMIP, and thank the climate modelling groups (listed in Supplementary Table 1) for producing and making available their model output. For CMIP, the US Department of Energy’s PCMDI provides coordinating support and led development of software infrastructure in partnership with the Global Organization for Earth System Science Portals.The Arctic has warmed more than twice as fast as the global average since the late twentieth century, a phenomenon known as Arctic amplification (AA). Recently, there have been considerable advances in understanding the physical contributions to AA, and progress has been made in understanding the mechanisms that link it to midlatitude weather variability. Observational studies overwhelmingly support that AA is contributing to winter continental cooling. Although some model experiments sup port the observational evidence, most modelling results show little connection between AA and severe midlatitude weather or suggest the export of excess heating from the Arctic to lower latitudes. Divergent conclusions between model and observational studies, and even intramodel studies, continue to obfuscate a clear understanding of how AA is influencing midlatitude weather

Increased copy number at 3p14 in breast cancer

INTRODUCTION: The present study was conducted to investigate if chromosome band 3p14 is of any pathogenic significance in the malignant process of breast cancer. Genetic studies have implicated a tumour suppressor gene on chromosome arm 3p and we have proposed LRIG1 at 3p14 as a candidate tumour suppressor. The LRIG1 gene encodes an integral membrane protein that counteracts signalling by receptor tyrosine kinases belonging to the ERBB family. LRIG1 mRNA and protein are expressed in many tissues, including breast tissue. METHODS: In the present report we analysed the LRIG1 gene by fluorescence in situ hybridisation (FISH), LRIG1 mRNA by quantitative RT-PCR, and LRIG1 protein by western blot analysis. Two tumour series were analysed; one series consisted of 19 tumour samples collected between 1987 and 1995 and the other series consisted of 9 tumour samples with corresponding non-neoplastic breast tissues collected consecutively. RESULTS: The LRIG1 gene showed increased copy number in 11 out of 28 tumours (39%) and only one tumour showed a deletion at this locus. Increased LRIG1 copy number was associated with increased levels of LRIG1 mRNA (two of three tumours) and protein (four of four tumours) in the tumours compared to matched non-neoplastic breast tissue, as assessed by RT-PCR and western blot analysis. CONCLUSION: The molecular function of LRIG1 as a negative regulator of ERBB receptors questions the biological significance of increased LRIG1 copy number in breast cancer. We propose that a common, but hitherto unrecognised, breast cancer linked gene is located within an amplicon containing the LRIG1 locus at 3p14.3

The severity of Puumala hantavirus induced nephropathia epidemica can be better evaluated using plasma interleukin-6 than C-reactive protein determinations

<p>Abstract</p> <p>Background</p> <p>Nephropathia epidemica (NE) is a Scandinavian type of hemorrhagic fever with renal syndrome caused by Puumala hantavirus. The clinical course of the disease varies greatly in severity. The aim of the present study was to evaluate whether plasma C-reactive protein (CRP) and interleukin (IL)-6 levels associate with the severity of NE.</p> <p>Methods</p> <p>A prospectively collected cohort of 118 consecutive hospital-treated patients with acute serologically confirmed NE was examined. Plasma IL-6, CRP, and creatinine, as well as blood cell count and daily urinary protein excretion were measured on three consecutive days after admission. Plasma IL-6 and CRP levels higher than the median were considered high.</p> <p>Results</p> <p>We found that high IL-6 associated with most variables reflecting the severity of the disease. When compared to patients with low IL-6, patients with high IL-6 had higher maximum blood leukocyte count (11.9 <it>vs </it>9.0 × 10⁹/l, <it>P </it>= 0.001) and urinary protein excretion (2.51 <it>vs </it>1.68 g/day, <it>P </it>= 0.017), as well as a lower minimum blood platelet count (55 <it>vs </it>80 × 10⁹/l, <it>P </it>< 0.001), hematocrit (0.34 <it>vs </it>0.38, <it>P </it>= 0.001), and urinary output (1040 <it>vs </it>2180 ml/day, <it>P </it>< 0.001). They also stayed longer in hospital than patients with low IL-6 (8 <it>vs </it>6 days, <it>P </it>< 0.001). In contrast, high CRP did not associate with severe disease.</p> <p>Conclusions</p> <p>High plasma IL-6 concentrations associate with a clinically severe acute Puumala hantavirus infection, whereas high plasma CRP as such does not reflect the severity of the disease.</p

Using ancient DNA to study the origins and dispersal of ancestral Polynesian chickens across the Pacific

The human colonization of Remote Oceania remains one of the great feats of exploration in history, proceeding east from Asia across the vast expanse of the Pacific Ocean. Human commensal and domesticated species were widely transported as part of this diaspora, possibly as far as South America. We sequenced mitochondrial control region DNA from 122 modern and 22 ancient chicken specimens from Polynesia and Island Southeast Asia and used these together with Bayesian modeling methods to examine the human dispersal of chickens across this area. We show that specific techniques are essential to remove contaminating modern DNA from experiments, which appear to have impacted previous studies of Pacific chickens. In contrast to previous reports, we find that all ancient specimens and a high proportion of the modern chickens possess a group of unique, closely-related, haplotypes found only in the Pacific. This group of haplotypes appears to represent the authentic founding mitochondrial DNA chicken lineages transported across the Pacific, and allows the early dispersal of chickens across Micronesia and Polynesia to be modeled. Importantly, chickens carrying this genetic signature persist on several Pacific islands at high frequencies, suggesting that the original Polynesian chicken lineages may still survive. No early South American chicken samples have been detected with the diagnostic Polynesian mtDNA haplotypes, arguing against reports that chickens provide evidence of Polynesian contact with pre-European South America. Two modern specimens from the Philippines carry haplotypes similar to the ancient Pacific samples, providing clues about a potential homeland for the Polynesian chicken.Vicki A. Thomson, Ophélie Lebrasseur, Jeremy J. Austin, Terry Hunt, David Burney, Tim Denham, Nicolas J. Rawlence, Jamie R. Wood, Jaime Gongora, Linus Girdland Flink, Anna Linderholm, Keith Dobney, Greger Larson, Alan Cooper

Pervasive Growth Reduction in Norway Spruce Forests following Wind Disturbance

Background: In recent decades the frequency and severity of natural disturbances by e.g., strong winds and insect outbreaks has increased considerably in many forest ecosystems around the world. Future climate change is expected to further intensify disturbance regimes, which makes addressing disturbances in ecosystem management a top priority. As a prerequisite a broader understanding of disturbance impacts and ecosystem responses is needed. With regard to the effects of strong winds – the most detrimental disturbance agent in Europe – monitoring and management has focused on structural damage, i.e., tree mortality from uprooting and stem breakage. Effects on the functioning of trees surviving the storm (e.g., their productivity and allocation) have been rarely accounted for to date. Methodology/Principal Findings: Here we show that growth reduction was significant and pervasive in a 6.79?million hectare forest landscape in southern Sweden following the storm Gudrun (January 2005). Wind-related growth reduction in Norway spruce (Picea abies (L.) Karst.) forests surviving the storm exceeded 10 % in the worst hit regions, and was closely related to maximum gust wind speed (R 2 = 0.849) and structural wind damage (R 2 = 0.782). At the landscape scale, windrelated growth reduction amounted to 3.0 million m 3 in the three years following Gudrun. It thus exceeds secondary damage from bark beetles after Gudrun as well as the long-term average storm damage from uprooting and stem breakage in Sweden

A 2000 Year Saharan Dust Event Proxy Record from an Ice Core in the European Alps

Dust events originating from the Saharan desert have far reaching environmental impacts but the causal mechanism of magnitude and occurrence of Saharan dust events (SDEs) during the pre‐instrumental era requires further research, particularly as a potential analog for future climate. Using an ultra‐high resolution glacio‐chemical record from the 2013 Colle Gnifetti (CG) ice core drilled in the Swiss‐Italian Alps we reconstructed a 2000 year‐long summer Saharan dust record. We analyzed both modern (1780‐2006) and pre‐modern Common Era (C.E.) major and trace element records to determine air mass source regions to the Colle Gnifetti glacier and assess similarities to modern and reconstructed climate trends in the Northern Hemisphere. This new pSDE (proxy SDE) reconstruction, produced using measurements from a novel, continuous ultra‐high‐resolution (120‐μm) ice core analysis method (laser ablation‐inductively coupled plasma‐mass spectrometer or LA‐ICP‐MS) is comprised of 316,000 data points per element covering the period 1 to 1820 C.E. We found that the CG ice core captures an anomalous increase in Saharan dust transport during the onset of the Medieval Climate Anomaly (870‐1000 C.E.) and records other prominent shorter events (C.E., 140‐170, 370‐450, 1320‐1370, and 1910‐2000), offering a framework for new insights into the implications of Saharan dust variability

Arctic change and possible influence on mid-latitude climate and weather: a US CLIVAR White Paper

The Arctic has warmed more than twice as fast as the global average since the mid 20th century, a phenomenon known as Arctic amplification (AA). These profound changes to the Arctic system have coincided with a period of ostensibly more frequent events of extreme weather across the Northern Hemisphere (NH) mid-latitudes, including extreme heat and rainfall events and recent severe winters. Though winter temperatures have generally warmed since 1960 over mid-to-high latitudes, the acceleration in the rate of warming at high-latitudes, relative to the rest of the NH, started approximately in 1990. Trends since 1990 show cooling over the NH continents, especially in Northern Eurasia. The possible link between Arctic change and mid-latitude climate and weather has spurred a rush of new observational and modeling studies. A number of workshops held during 2013-2014 have helped frame the problem and have called for continuing and enhancing efforts for improving our understanding of Arctic-mid-latitude linkages and its attribution to the occurrence of extreme climate and weather events. Although these workshops have outlined some of the major challenges and provided broad recommendations, further efforts are needed to synthesize the diversified research results to identify where community consensus and gaps exist. Building upon findings and recommendations of the previous workshops, the US CLIVAR Working Group on Arctic Change and Possible Influence on Mid-latitude Climate and Weather convened an international workshop at Georgetown University in Washington, DC, on February 1-3, 2017. Experts in the fields of atmosphere, ocean, and cryosphere sciences assembled to assess the rapidly evolving state of understanding, identify consensus on knowledge and gaps in research, and develop specific actions to accelerate progress within the research community. With more than 100 participants, the workshop was the largest and most comprehensive gathering of climate scientists to address the topic to date. In this white paper, we synthesize and discuss outcomes from this workshop and activities involving many of the working group members