bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impacts on terrestrial biodiversity of moving from a 2°C to a 1.5°C target
Authors: Smith Pete , Price Jeff , Molotoks Amy , Warren Rachel , Malhi Yadvinder 
Published: April 2018

We applied a recently developed tool to examine the reduction in climate risk to biodiversity in moving from a 2°C to a 1.5°C target. We then reviewed the recent literature examining the impact of (a) land-based mitigation options and (b) land-based greenhouse gas removal options on biodiversity. We show that holding warming to 1.5°C versus 2°C can significantly reduce the number of species facing a potential loss of 50% of their climatic range. Further, there would be an increase of 5.5–14% of the globe that could potentially act as climatic refugia for plants and animals, an area equivalent to the current global protected area network. Efforts to meet the 1.5°C target through mitigation could largely be consistent with biodiversity protection/enhancement. For impacts of land-based greenhouse gas removal technologies on biodiversity, some (e.g. soil carbon sequestration) could be neutral or positive, others (e.g. bioenergy with carbon capture and storage) are likely to lead to conflicts, while still others (e.g. afforestation/reforestation) are context-specific, when applied at scales necessary for meaningful greenhouse gas removal. Additional effort to meet the 1.5°C target presents some risks, particularly if inappropriately managed, but it also presents opportunities.
This article is part of the theme issue ‘The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.
The legal character and operational relevance of the Paris Agreement's temperature goal
Authors: Rajamani Lavanya , Werksman Jacob 
Published: April 2018

This article assesses the legal character and operational relevance of the Paris Agreement's 1.5°C temperature goal. This article begins with a textual analysis of the 1.5°C goal. It considers whether the goal creates individual or collective obligations for Parties, and whether it is sufficiently specific to enable the tracking of individual or collective performance. Next, it assesses the operational relevance of the 1.5°C temperature goal, by considering the role it will play in the Paris Agreement's institutions and procedures. To the extent that the goal plays a role, and implies global limits on greenhouse gas emissions, this article observes that it could have implications for the sharing of the effort between Parties. Thus, this article considers the relevance of equity and the principle of common but differentiated responsibilities and respective capabilities, in the light of different national circumstances, to understanding how the 1.5°C goal could be reached. In this context, this article explores whether the 1.5°C goal could play a role in the Paris Agreement's ‘ambition cycle’. Finally, this article asks whether there are any legal or political implications, individually or collectively under the Paris Agreement, should the Parties fail to achieve the 1.5°C goal.
This article is part of the theme issue ‘The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels’.
Uncertain impacts on economic growth when stabilizing global temperatures at 1.5°C or 2°C warming
Authors: Pretis Felix , Schwarz Moritz , Tang Kevin , Haustein Karsten , Allen Myles R. 
Published: April 2018

Empirical evidence suggests that variations in climate affect economic growth across countries over time. However, little is known about the relative impacts of climate change on economic outcomes when global mean surface temperature (GMST) is stabilized at 1.5°C or 2°C warming relative to pre-industrial levels. Here we use a new set of climate simulations under 1.5°C and 2°C warming from the ‘Half a degree Additional warming, Prognosis and Projected Impacts' (HAPPI) project to assess changes in economic growth using empirical estimates of climate impacts in a global panel dataset. Panel estimation results that are robust to outliers and breaks suggest that within-year variability of monthly temperatures and precipitation has little effect on economic growth beyond global nonlinear temperature effects. While expected temperature changes under a GMST increase of 1.5°C lead to proportionally higher warming in the Northern Hemisphere, the projected impact on economic growth is larger in the Tropics and Southern Hemisphere. Accounting for econometric estimation and climate uncertainty, the projected impacts on economic growth of 1.5°C warming are close to indistinguishable from current climate conditions, while 2°C warming suggests statistically lower economic growth for a large set of countries (median projected annual growth up to 2% lower). Level projections of gross domestic product (GDP)per capitaexhibit high uncertainties, with median projected global average GDPper capitaapproximately 5% lower at the end of the century under 2°C warming relative to 1.5°C. The correlation between climate-induced reductions inper capitaGDP growth and national income levels is significant at thep < 0.001 level, with lower-income countries experiencing greater losses, which may increase economic inequality between countries and is relevant to discussions of loss and damage under the United Nations Framework Convention on Climate Change.This article is part of the theme issue ‘The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.
Building equity in: strategies for integrating equity into modelling for a 1.5°C world
Authors: Sonja Klinsky , Harald Winkler 
Published: April 2018

Emission pathways consistent with limiting temperature increase to 1.5°C raise pressing questions from an equity perspective. These pathways would limit impacts and benefit vulnerable communities but also present trade-offs that could increase inequality. Meanwhile, rapid mitigation could exacerbate political debates in which equity has played a central role. In this paper, we first develop a set of elements we suggest are essential for evaluating the equity implications of policy actions consistent with 1.5°C. These elements include (i) assess climate impacts, adaptation, loss and damage; (ii) be sensitive to context; (iii) compare costs of mitigation and adaptation policy action; (iv) incorporate human development and poverty; (v) integrate inequality dynamics; and (vi) be clear about normative assumptions and responsive to users. We then assess the ability of current modelling practices to address each element, focusing on global integrated assessment models augmented by national modelling and scenarios. We find current practices face serious limitations across all six dimensions although the severity of these varies. Finally, based on our assessment we identify strategies that may be best suited for enabling us to generate insights into each of the six elements in the context of assessing pathways for a 1.5°C world.This article is part of the theme issue ‘The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.
Can ‘loss and damage’ carry the load?
Authors: Verchick Robert R. M. 
Published: April 2018

Even assuming a heroic rush towards carbon reduction and adaptation, some regions of the world will be hammered hard by climate impacts. Thus, a global consensus now sees the need for a supplemental plan to deal with the kind of harms that cannot be avoided—what Parties call ‘loss and damage’. For a loss-and-damage plan to work, it must be capable of carrying the load, the load being whatever minimal standards that morality and political consensus require. But if residual risk climbs too high, it will fall short of even the most basic expectations. The Paris Agreement calls for holding the rise in global average temperature to ‘well below 2°C above pre-industrial levels’, while working to limit the increase to 1.5°C. How much difference is in that half-degree? From the point of view of residual risk, quite a lot. According to a 2016 study published by the European Geosciences Union, a jump from 1.5°C to 2°C could produce outsize impacts, particularly in tropical latitudes. That difference could mark the line between a plan that is politically and morally defensible and one that is not. At the very least, the difference is enough to inform the design and expectations of any future plan.This article is part of the theme issue ‘The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels’.
Mitigation gambles: uncertainty, urgency and the last gamble possible
Authors: Shue Henry 
Published: April 2018

A rejection by current generations of more ambitious mitigation of carbon emissions inflicts on future generations inherently objectionable risks about which they have no choice. Any gains through savings from less ambitious mitigation, which are relatively minor, would accrue to current generations, and all losses, which are relatively major, would fall on future generations. This mitigation gamble is especially unjustifiable because it imposes a risk of unlimited losses until carbon emissions cease. Ultimate physical collapses remain possible. Much more ominous is prior social collapse from political struggles over conflicting responses to threatened physical collapse. The two most plausible objections to the thesis that less ambitious mitigation is unjustifiable rely, respectively, on the claim that negative emissions will allow a later recovery from a temporary overshoot in emissions and on the claim that ambitious mitigation is incompatible with poverty alleviation that depends on inexpensive fossil fuels. Neither objection stands up. Reliance on negative emissions later instead of ambitious mitigation now permits the passing of tipping points for irreversible change meanwhile, and non-carbon energy is rapidly becoming price competitive in developing countries like India that are committed to poverty alleviation.This article is part of the themed issue ‘The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels’.
The myriad challenges of the Paris Agreement
Authors: Mitchell Dann , Allen Myles R. , Hall Jim W. , Muller Benito , Rajamani Lavanya , Le Quéré Corinne 
Published: April 2018

The much awaited and intensely negotiated Paris Agreement was adopted on 12 December 2015 by the Parties to the United Nations Framework Convention on Climate Change. The agreement set out a more ambitious long-term temperature goal than many had anticipated, implying more stringent emissions reductions that have been under-explored by the research community. By its very nature a multidisciplinary challenge, filling the knowledge gap requires not only climate scientists, but the whole Earth system science community, as well as economists, engineers, lawyers, philosophers, politicians, emergency planners and others to step up. To kick start cross-disciplinary discussions, the University of Oxford's Environmental Change Institute focused its 25th anniversary conference upon meeting the challenges of the Paris Agreement for science and society. This theme issue consists of review papers, opinion pieces and original research from some of the presentations within that meeting, covering a wide range of issues underpinning the Paris Agreement.
This article is part of the theme issue ‘The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.
Deletion of genes encoding PU.1 and Spi-B leads to B cell acute lymphoblastic leukemia associated with driver mutations in Janus Kinases
Authors: Batista Carolina R. , Lim Michelle , Laramée Anne-Sophie , Abu-Sardanah Faisal , Xu Li S. , Hossain Rajon , DeKoter Rodney P. 
Published: April 2018

AbstractPrecursor B-cell acute lymphoblastic leukemia (B-ALL) is associated with recurrent mutations that occur in cancer-initiating cells. There is a need to understand how spontaneous driver mutations influence clonal evolution in leukemia. The ETS-transcription factors PU.1 and Spi-B (encoded bySpi1andSpib) execute a critical role in B cell development and serve as complementary tumour suppressors by opposing the proliferative events mediated by IL-7R signaling. Here, we used a mouse model to conditionally deleteSpi1andSpibgenes in developing B cells. These mice developed B-ALL with a median time to euthanasia of 18 weeks. We performed RNA and whole-exome sequencing (WES) on leukemias isolated from Mb1-CreΔPB mice and identified single-nucleotide variants (SNVs) inJak1,Jak3andIkzf3genes, resulting in amino acid changes and in the gain of early stop-codons. JAK3 mutations resulted in amino acid substitutions located in the pseudo-kinase (R653H, V670A) and in the kinase (T844M) domains. Introduction of these mutations into wild-type pro-B cells conferred survival and proliferation advantages. We conclude that mutations in Janus kinases represent secondary drivers of leukemogenesis in the absence of Spi-B and PU.1 transcription factors. This mouse model represents an useful tool to study clonal evolution and tumour heterogeneity in B-ALL.
Structures of DPAGT1 explain glycosylation disease mechanisms and advance TB antibiotic design
Authors: Dong Yin Yao , Wang Hua , Pike Ashley C.W. , Cochrane Stephen A. , Hamedzadeh Sadra , Wyszyński Filip J. , Bushell Simon R. , Royer Sylvain F. , Widdick David A. , Sajid Andaleeb , Boshoff Helena I. , Lucas Ricardo , Liu Wei-Min , Lee Seung Seo , Machida Takuya , Mehmood Shahid , Belaya Katsiaryna , Liu Wei-Wei , Chu Amy , Shrestha Leela , Mukhopadhyay Shubhashish M.M. , Burgess-Brown Nicola A. , Bibb Mervyn J. , Barry Clifton E. , Robinson Carol V. , Beeson David , Davis Benjamin G. , Carpenter Elisabeth P. 
Published: April 2018

SummaryProtein glycosylation is a widespread post-translational modification. The first committed step to the lipid-linked glycan used for this process is catalysed by dolichyl-phosphate N-acetylglucosamine-phosphotransferase DPAGT1 (GPT/E.C. 2.7.8.15). Missense DPAGT1 variants cause congenital myasthenic syndrome and congenital disorders of glycosylation. In addition, naturally-occurring bactericidal nucleoside analogues such as tunicamycin are toxic to eukaryotes due to DPAGT1 inhibition, preventing their clinical use as antibiotics. However, little is known about the mechanism or the effects of disease-associated mutations in this essential enzyme. Our structures of DPAGT1 with the substrate UDP-GlcNAc and tunicamycin reveal substrate binding modes, suggest a mechanism of catalysis, provide an understanding of how mutations modulate activity (and thus cause disease) and allow design of non-toxic ‘lipid-altered’ tunicamycins. The structure-tuned activity of these analogues against several bacterial targets allowed design of potent antibiotics forMycobacterium tuberculosis, enabling treatmentin vitro,in celluloandin vivothereby providing a promising new class of antimicrobial drug.HighlightsStructures of DPAGT1 with UDP-GlcNAc and tunicamycin reveal mechanisms of catalysisDPAGT1 mutants in patients with glycosylation disorders modulate DPAGT1 activityStructures, kinetics and biosynthesis reveal role of lipid in tunicamycinLipid-altered, tunicamycin analogues give non-toxic antibiotics against TB
Integrative analysis of pharmacogenomics in major cancer cell line databases using CellMinerCDB
Authors: Rajapakse Vinodh N. , Luna Augustin , Yamade Mihoko , Loman Lisa , Varma Sudhir , Sunshine Margot , Iorio Francesco , Sousa Fabricio G. , Elloumi Fathi , Aladjem Mirit I. , Thomas Anish , Sander Chris , Kohn Kurt , Benes Cyril H. , Garnett Mathew , Reinhold William C. , Pommier Yves 
Published: April 2018

AbstractAs precision medicine demands molecular determinants of drug response, CellMinerCDB provides (https://discover.nci.nih.gov/cellminercdb/) a web-based portal for multiple forms of pharmacological, molecular, and genomic analyses, unifying the richest cancer cell line datasets (NCI-60, NCI-SCLC, Sanger/MGH GDSC, and Broad CCLE/CTRP). CellMinerCDB enables genomic and pharmacological data queries for identifying pharmacogenomic determinants, drug signatures, and gene regulatory networks for researchers without requiring specialized bioinformatics support. It leverages overlaps of cell lines and tested drugs to allow assessment of data reproducibility. It builds on the complementarity and strength of each dataset. A panel of 41 drugs evaluated in parallel in the NCI-60 and GDSC is reported, supporting drug reproducibility across databases, repositioning of bisacodyl and acetalax for triple negative breast cancer, and identifying novel drug response determinants and genomic signatures for topoisomerase inhibitors and schweinfurthins in development. CellMinerCDB also allowed the identification ofLIX1Las a novel mesenchymal gene regulating cellular migration and invasiveness.
P. falciparum PfATP4 Multi-Drug Resistance Resistance to KAE609 (Cipargamin) is Present in Africa
Authors: McCulloch James 
Published: April 2018

AbstractThe PfATP4 (PF3D7 1211900) multi-drug resistance mutation G223R is found in Africa by genetically analyzing 2640 worldwide Plasmodium falciparum blood stage isolates (the MalariaGen Pf3k resource). This mutation confers an approximate 8 fold [4] increase in the PfATP4 IC50 of Spiroindolones (KAE609 & KAE678) [14],[16],[4],[10] and Aminopyrazoles (GNF-Pf4492) [4]. It is postulated that the G223R mutation may be a consequence of the drug resistant Southeast Asian Dd2 genotype becoming more dominant in Africa [3]. The presence of this mutation has important policy implications for the eventual general deployment of the Spiroindolone KAE609 (Cipargamin) which is currently undergoing stage 2 clinical trials.
Development of a joint evolutionary model for the genome and the epigenome
Authors: Lu Jia , Cao Xiaoyi , Zhong Sheng 
Published: April 2018

AbstractBackgroundInterspecies epigenome comparisons yielded functional information that cannot be revealed by genome comparison alone, begging for theoretical advances that enable principled analysis approaches. Whereas probabilistic genome evolution models provided theoretical foundation to comparative genomics studies, it remains challenging to extend DNA evolution models to epigenomes.ResultsWe present an effort to develop ab initio evolution models for epigenomes, by explicitly expressing the joint probability of multispecies DNA sequences and histone modifications on homologous genomic regions. This joint probability is modeled as a mixture of four components representing four evolutionary hypotheses, namely dependence and independence of interspecies epigenomic variations to sequence mutations and to sequence insertions and deletions (indels). For model fitting, we implemented a maximum likelihood method by coupling downhill simplex algorithm with dynamic programming. Based on likelihood comparisons, the model can be used to infer whether interspecies epigenomic variations depend on mutation or indels in local genomic sequences. We applied this model to analyze DNase hypersensitive regions and spermatid H3K4me3 ChIP-seq data from human and rhesus macaque. Approximately 5.5% of homologous regions in the genomes exhibited H3K4me3 modification in either species, among which approximately 67% homologous regions exhibited sequence-dependent interspecies H3K4me3 variations. Mutations accounted for less sequence-dependent H3K4me3 variations than indels. Among transposon-mediated indels, ERV1 insertions and L1 insertions were most strongly associated with H3K4me3 gains and losses, respectively.ConclusionThis work initiates a class of probabilistic evolution models that jointly model the genomes and the epigenomes, thus helps to bring evolutionary principles to comparative epigenomic studies.
Rainbow-seq: combining cell lineage tracking with single-cell RNA sequencing in preimplantation embryos
Authors: Biase Fernando , Wu Qiuyang , Calandrelli Riccardo , Rivas-Astroza Marcelo , Zhou Shuigeng , Zhong Sheng 
Published: April 2018

SUMMARYSingle-cell RNA-seq experiments cannot record cell division history and therefore cannot directly connect intercellular differences at a later developmental stage to their progenitor cells. We developed Rainbow-seq to combine cell division lineage tracing with single-cell RNA-seq. With distinct fluorescent protein genes as lineage markers, Rainbow-seq enables each single-cell RNA-seq experiment to simultaneously read single-cell transcriptomes and decode the lineage marker genes. We traced the lineages deriving from each blastomere in two-cell mouse embryos and observed inequivalent contributions to the embryonic and abembryonic poles in 72% of the blastocysts evaluated. Rainbow-seq on four- and eight-cell embryos with lineage tracing triggered at two-cell stage exhibited remarkable transcriptome-wide differences between the two cell lineages at both stages, including genes involved in negative regulation of transcription and signaling. These data provide critical insights on cell fate choices in cleavage embryos. Rainbow-seq bridged a critical gap between cellular division history and single-cell RNA-seq assays.
Fast and simple comparison of semi-structured data, with emphasis on electronic health records
Authors: Robinson Max , Hadlock Jennifer , Yu Jiyang , Khatamian Alireza , Aravkin Aleksandr Y. , Deutsch Eric W. , Price Nathan D. , Huang Sui , Glusman Gustavo 
Published: April 2018

AbstractWe present a locality-sensitive hashing strategy for summarizing semi-structured data (e.g., in JSON or XML formats) into ‘data fingerprints’: highly compressed representations which cannot recreate details in the data, yet simplify and greatly accelerate the comparison and clustering of semi-structured data by preserving similarity relationships. Computation on data fingerprints is fast: in one example involving complex simulated medical records, the average time to encode one record was 0.53 seconds, and the average pairwise comparison time was 3.75 microseconds. Both processes are trivially parallelizable.Applications include detection of duplicates, clustering and classification of semi-structured data, which support larger goals including summarizing large and complex data sets, quality assessment, and data mining. We illustrate use cases with three analyses of electronic health records (EHRs): (1) pairwise comparison of patient records, (2) analysis of cohort structure, and (3) evaluation of methods for generating simulated patient data.