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Mutations affecting spliceosomal proteins are the most common mutations in patients with myelodysplastic syndromes (MDS), but their role in MDS pathogenesis has not been delineated. Here we report that mutations affecting the splicing factor SRSF2 directly impair hematopoietic differentiation in vivo, which is not due to SRSF2 loss of function. By contrast, SRSF2 mutations alter SRSF2's normal sequence-specific RNA binding activity, thereby altering the recognition of specific exonic splicing enhancer motifs to drive recurrent mis-splicing of key hematopoietic regulators. This includes SRSF2 mutation-dependent splicing of EZH2, which triggers nonsense-mediated decay, which, in turn, results in impaired hematopoietic differentiation. These data provide a mechanistic link between a mutant spliceosomal protein, alterations in the splicing of key regulators, and impaired hematopoiesis. ; E.K. is supported by the Worldwide Cancer Research Fund. A.R. was supported by the NIH/NHLBI (U01 HL099993), NIH/NIDDK (K08 DK082783), the J.P. McCarthy Foundation, and the Storb Foundation. S.H. and O.A.-W. are supported by grants from the Edward P. Evans Foundation. S.H. was supported by Yale Comprehensive Cancer Center institutional funds. R.K.B. was supported by the Hartwell Innovation Fund, Damon Runyon Cancer Research Foundation (DFS 04-12), Ellison Medical Foundation (AG-NS-1030-13), NIH/NIDDK (R56 DK103854), NIH/NCI recruitment support (P30 CA015704), and Fred Hutchinson Cancer Research Center institutional funds. J.O.I. was supported by an NIH/NCI training grant (T32 CA009657) and NIH/NIDDK pilot study (P30 DK056465). C.L. is supported by a career development award grant from the Leukemia and Lymphoma Society and an ATIP-Avenir grant from the French government. O.A.-W. is supported by an NIH K08 clinical investigator award (1K08CA160647-01), a Department of Defense Postdoctoral Fellow Award in Bone Marrow Failure Research (W81XWH-12-1-0041), the Josie Robertson Investigator Program, and a Damon Runyon Clinical Investigator Award with support from the Evans Foundation. F.H.-T.A. acknowledges support from the NCCR RNA and Disease funded by the Swiss National Science Foundation and the SNF Sinergia CRSII3_127454. Y.L. and Y.M. were supported by NIH/NIGMS grant R01 GM102869 and Senior Research Fellowship Grant 101908/Z/13/Z (to Y.M.) from the Wellcome Trust. J.D. acknowledges assistance from Dr. Nezih Cereb, HistoGenetics (Ossining, NY). ; This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.ccell.2015.04.006

Meta-Analysis ; This is the final version of the article. Available from the American Diabetes Association via the DOI in this record. ; Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10⁻⁹). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10⁻¹²) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D. ; The major funding for this work comes from Council for Scientific and Industrial Research, Government of India, in the form of the grant "Diabetes mellitus—New drug discovery R&D, molecular mechanisms, and genetic and epidemiological factors" (NWP0032-19). R.T. received a postdoctoral fellowship from the Fogarty International Center and the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health (D43-HD-065249).

As current action remains insufficient to meet the goals of the Paris agreement let alone to stabilize the climate, there is increasing hope that solutions related to demand, services and social aspects of climate change mitigation can close the gap. However, given these topics are not investigated by a single epistemic community, the literature base underpinning the associated research continues to be undefined. Here, we aim to delineate a plausible body of literature capturing a comprehensive spectrum of demand, services and social aspects of climate change mitigation. As method we use a novel double-stacked expert-machine learning research architecture and expert evaluation to develop a typology and map key messages relevant for climate change mitigation within this body of literature. First, relying on the official key words provided to the Intergovernmental Panel on Climate Change by governments (across 17 queries), and on specific investigations of domain experts (27 queries), we identify 121 165 non-unique and 99 065 unique academic publications covering issues relevant for demand-side mitigation. Second, we identify a literature typology with four key clusters: policy, housing, mobility, and food/consumption. Third, we systematically extract key content-based insights finding that the housing literature emphasizes social and collective action, whereas the food/consumption literatures highlight behavioral change, but insights also demonstrate the dynamic relationship between behavioral change and social norms. All clusters point to the possibility of improved public health as a result of demand-side solutions. The centrality of the policy cluster suggests that political actions are what bring the different specific approaches together. Fourth, by mapping the underlying epistemic communities we find that researchers are already highly interconnected, glued together by common interests in sustainability and energy demand. We conclude by outlining avenues for interdisciplinary collaboration, synthetic analysis, community building, and by suggesting next steps for evaluating this body of literature.

As current action remains insufficient to meet the goals of the Paris agreement let alone to stabilize the climate, there is increasing hope that solutions related to demand, services and social aspects of climate change mitigation can close the gap. However, given these topics are not investigated by a single epistemic community, the literature base underpinning the associated research continues to be undefined. Here, we aim to delineate a plausible body of literature capturing a comprehensive spectrum of demand, services and social aspects of climate change mitigation. As method we use a novel double-stacked expert-machine learning research architecture and expert evaluation to develop a typology and map key messages relevant for climate change mitigation within this body of literature. First, relying on the official key words provided to the Intergovernmental Panel on Climate Change by governments (across 17 queries), and on specific investigations of domain experts (27 queries), we identify 121 165 non-unique and 99 065 unique academic publications covering issues relevant for demand-side mitigation. Second, we identify a literature typology with four key clusters: policy, housing, mobility, and food/consumption. Third, we systematically extract key content-based insights finding that the housing literature emphasizes social and collective action, whereas the food/consumption literatures highlight behavioral change, but insights also demonstrate the dynamic relationship between behavioral change and social norms. All clusters point to the possibility of improved public health as a result of demand-side solutions. The centrality of the policy cluster suggests that political actions are what bring the different specific approaches together. Fourth, by mapping the underlying epistemic communities we find that researchers are already highly interconnected, glued together by common interests in sustainability and energy demand. We conclude by outlining avenues for interdisciplinary collaboration, synthetic analysis, community building, and by suggesting next steps for evaluating this body of literature.

As current action remains insufficient to meet the goals of the Paris agreement let alone to stabilize the climate, there is increasing hope that solutions related to demand, services and social aspects of climate change mitigation can close the gap. However, given these topics are not investigated by a single epistemic community, the literature base underpinning the associated research continues to be undefined. Here, we aim to delineate a plausible body of literature capturing a comprehensive spectrum of demand, services and social aspects of climate change mitigation. As method we use a novel double-stacked expert-machine learning research architecture and expert evaluation to develop a typology and map key messages relevant for climate change mitigation within this body of literature. First, relying on the official key words provided to the Intergovernmental Panel on Climate Change by governments (across 17 queries), and on specific investigations of domain experts (27 queries), we identify 121 165 non-unique and 99 065 unique academic publications covering issues relevant for demand-side mitigation. Second, we identify a literature typology with four key clusters: policy, housing, mobility, and food/consumption. Third, we systematically extract key content-based insights finding that the housing literature emphasizes social and collective action, whereas the food/consumption literatures highlight behavioral change, but insights also demonstrate the dynamic relationship between behavioral change and social norms. All clusters point to the possibility of improved public health as a result of demand-side solutions. The centrality of the policy cluster suggests that political actions are what bring the different specific approaches together. Fourth, by mapping the underlying epistemic communities we find that researchers are already highly interconnected, glued together by common interests in sustainability and energy demand. We conclude by outlining avenues for interdisciplinary collaboration, synthetic analysis, community building, and by suggesting next steps for evaluating this body of literature.

The 196 parties to the Convention on Biological Diversity (CBD) will soon agree to a post-2020 global framework for conserving the three elements of biodiversity (genetic, species, and ecosystem diversity) while ensuring sustainable development and benefit sharing. As the most significant global conservation policy mechanism, the new CBD framework has far-reaching consequences- it will guide conservation actions and reporting for each member country until 2050. In previous CBD strategies, as well as other major conservation policy mechanisms, targets and indicators for genetic diversity (variation at the DNA level within species, which facilitates species adaptation and ecosystem function) were undeveloped and focused on species of agricultural relevance. We assert that, to meet global conservation goals, genetic diversity within all species, not just domesticated species and their wild relatives, must be conserved and monitored using appropriate metrics. Building on suggestions in a recent Letter in Science (Laikre et al., 2020) we expand argumentation for three new, pragmatic genetic indicators and modifications to two current indicators for maintaining genetic diversity and adaptive capacity of all species, and provide guidance on their practical use. The indicators are: 1) the number of populations with effective population size above versus below 500, 2) the proportion of populations maintained within species, 3) the number of species and populations in which genetic diversity is monitored using DNA-based methods. We also present and discuss Goals and Action Targets for post-2020 biodiversity conservation which are connected to these indicators and underlying data. These pragmatic indicators and goals have utility beyond the CBD; they should benefit conservation and monitoring of genetic diversity via national and global policy for decades to come. ; Supplementary material: Tables S1 and S2 and Fig. S1 compile estimates of Ne/Nc from several reviews and new data. ; The EU Framework Horizon 2020 through the ...

As current action remains insufficient to meet the goals of the Paris agreement let alone to stabilize the climate, there is increasing hope that solutions related to demand, services and social aspects of climate change mitigation can close the gap. However, given these topics are not investigated by a single epistemic community, the literature base underpinning the associated research continues to be undefined. Here, we aim to delineate a plausible body of literature capturing a comprehensive spectrum of demand, services and social aspects of climate change mitigation. As method we use a novel double-stacked expert—machine learning research architecture and expert evaluation to develop a typology and map key messages relevant for climate change mitigation within this body of literature. First, relying on the official key words provided to the Intergovernmental Panel on Climate Change by governments (across 17 queries), and on specific investigations of domain experts (27 queries), we identify 121 165 non-unique and 99 065 unique academic publications covering issues relevant for demand-side mitigation. Second, we identify a literature typology with four key clusters: policy, housing, mobility, and food/consumption. Third, we systematically extract key content-based insights finding that the housing literature emphasizes social and collective action, whereas the food/consumption literatures highlight behavioral change, but insights also demonstrate the dynamic relationship between behavioral change and social norms. All clusters point to the possibility of improved public health as a result of demand-side solutions. The centrality of the policy cluster suggests that political actions are what bring the different specific approaches together. Fourth, by mapping the underlying epistemic communities we find that researchers are already highly interconnected, glued together by common interests in sustainability and energy demand. We conclude by outlining avenues for interdisciplinary collaboration, synthetic ...

International audience ; As current action remains insufficient to meet the goals of the Paris agreement let alone to stabilize the climate, there is increasing hope that solutions related to demand, services and social aspects of climate change mitigation can close the gap. However, given these topics are not investigated by a single epistemic community, the literature base underpinning the associated research continues to be undefined. Here, we aim to delineate a plausible body of literature capturing a comprehensive spectrum of demand, services and social aspects of climate change mitigation. As method we use a novel double-stacked expert—machine learning research architecture and expert evaluation to develop a typology and map key messages relevant for climate change mitigation within this body of literature. First, relying on the official key words provided to the Intergovernmental Panel on Climate Change by governments (across 17 queries), and on specific investigations of domain experts (27 queries), we identify 121 165 non-unique and 99 065 unique academic publications covering issues relevant for demand-side mitigation. Second, we identify a literature typology with four key clusters: policy, housing, mobility, and food/consumption. Third, we systematically extract key content-based insights finding that the housing literature emphasizes social and collective action, whereas the food/consumption literatures highlight behavioral change, but insights also demonstrate the dynamic relationship between behavioral change and social norms. All clusters point to the possibility of improved public health as a result of demand-side solutions. The centrality of the policy cluster suggests that political actions are what bring the different specific approaches together. Fourth, by mapping the underlying epistemic communities we find that researchers are already highly interconnected, glued together by common interests in sustainability and energy demand. We conclude by outlining avenues for interdisciplinary ...

Abstract As current action remains insufficient to meet the goals of the Paris agreement let alone to stabilize the climate, there is increasing hope that solutions related to demand, services and social aspects of climate change mitigation can close the gap. However, given these topics are not investigated by a single epistemic community, the literature base underpinning the associated research continues to be undefined. Here, we aim to delineate a plausible body of literature capturing a comprehensive spectrum of demand, services and social aspects of climate change mitigation. As method we use a novel double-stacked expert—machine learning research architecture and expert evaluation to develop a typology and map key messages relevant for climate change mitigation within this body of literature. First, relying on the official key words provided to the Intergovernmental Panel on Climate Change by governments (across 17 queries), and on specific investigations of domain experts (27 queries), we identify 121 165 non-unique and 99 065 unique academic publications covering issues relevant for demand-side mitigation. Second, we identify a literature typology with four key clusters: policy, housing, mobility, and food/consumption. Third, we systematically extract key content-based insights finding that the housing literature emphasizes social and collective action, whereas the food/consumption literatures highlight behavioral change, but insights also demonstrate the dynamic relationship between behavioral change and social norms. All clusters point to the possibility of improved public health as a result of demand-side solutions. The centrality of the policy cluster suggests that political actions are what bring the different specific approaches together. Fourth, by mapping the underlying epistemic communities we find that researchers are already highly interconnected, glued together by common interests in sustainability and energy demand. We conclude by outlining avenues for interdisciplinary collaboration, synthetic analysis, community building, and by suggesting next steps for evaluating this body of literature.

International audience ; As current action remains insufficient to meet the goals of the Paris agreement let alone to stabilize the climate, there is increasing hope that solutions related to demand, services and social aspects of climate change mitigation can close the gap. However, given these topics are not investigated by a single epistemic community, the literature base underpinning the associated research continues to be undefined. Here, we aim to delineate a plausible body of literature capturing a comprehensive spectrum of demand, services and social aspects of climate change mitigation. As method we use a novel double-stacked expert—machine learning research architecture and expert evaluation to develop a typology and map key messages relevant for climate change mitigation within this body of literature. First, relying on the official key words provided to the Intergovernmental Panel on Climate Change by governments (across 17 queries), and on specific investigations of domain experts (27 queries), we identify 121 165 non-unique and 99 065 unique academic publications covering issues relevant for demand-side mitigation. Second, we identify a literature typology with four key clusters: policy, housing, mobility, and food/consumption. Third, we systematically extract key content-based insights finding that the housing literature emphasizes social and collective action, whereas the food/consumption literatures highlight behavioral change, but insights also demonstrate the dynamic relationship between behavioral change and social norms. All clusters point to the possibility of improved public health as a result of demand-side solutions. The centrality of the policy cluster suggests that political actions are what bring the different specific approaches together. Fourth, by mapping the underlying epistemic communities we find that researchers are already highly interconnected, glued together by common interests in sustainability and energy demand. We conclude by outlining avenues for interdisciplinary ...

International audience ; As current action remains insufficient to meet the goals of the Paris agreement let alone to stabilize the climate, there is increasing hope that solutions related to demand, services and social aspects of climate change mitigation can close the gap. However, given these topics are not investigated by a single epistemic community, the literature base underpinning the associated research continues to be undefined. Here, we aim to delineate a plausible body of literature capturing a comprehensive spectrum of demand, services and social aspects of climate change mitigation. As method we use a novel double-stacked expert—machine learning research architecture and expert evaluation to develop a typology and map key messages relevant for climate change mitigation within this body of literature. First, relying on the official key words provided to the Intergovernmental Panel on Climate Change by governments (across 17 queries), and on specific investigations of domain experts (27 queries), we identify 121 165 non-unique and 99 065 unique academic publications covering issues relevant for demand-side mitigation. Second, we identify a literature typology with four key clusters: policy, housing, mobility, and food/consumption. Third, we systematically extract key content-based insights finding that the housing literature emphasizes social and collective action, whereas the food/consumption literatures highlight behavioral change, but insights also demonstrate the dynamic relationship between behavioral change and social norms. All clusters point to the possibility of improved public health as a result of demand-side solutions. The centrality of the policy cluster suggests that political actions are what bring the different specific approaches together. Fourth, by mapping the underlying epistemic communities we find that researchers are already highly interconnected, glued together by common interests in sustainability and energy demand. We conclude by outlining avenues for interdisciplinary ...

As current action remains insufficient to meet the goals of the Paris agreement let alone to stabilize the climate, there is increasing hope that solutions related to demand, services and social aspects of climate change mitigation can close the gap. However, given these topics are not investigated by a single epistemic community, the literature base underpinning the associated research continues to be undefined. Here, we aim to delineate a plausible body of literature capturing a comprehensive spectrum of demand, services and social aspects of climate change mitigation. As method we use a novel double-stacked expert—machine learning research architecture and expert evaluation to develop a typology and map key messages relevant for climate change mitigation within this body of literature. First, relying on the official key words provided to the Intergovernmental Panel on Climate Change by governments (across 17 queries), and on specific investigations of domain experts (27 queries), we identify 121 165 non-unique and 99 065 unique academic publications covering issues relevant for demand-side mitigation. Second, we identify a literature typology with four key clusters: policy, housing, mobility, and food/consumption. Third, we systematically extract key content-based insights finding that the housing literature emphasizes social and collective action, whereas the food/consumption literatures highlight behavioral change, but insights also demonstrate the dynamic relationship between behavioral change and social norms. All clusters point to the possibility of improved public health as a result of demand-side solutions. The centrality of the policy cluster suggests that political actions are what bring the different specific approaches together. Fourth, by mapping the underlying epistemic communities we find that researchers are already highly interconnected, glued together by common interests in sustainability and energy demand. We conclude by outlining avenues for interdisciplinary collaboration, synthetic analysis, community building, and by suggesting next steps for evaluating this body of literature.

As far back as the industrial revolution, significant development in technical innovation has succeeded in transforming numerous manual tasks and processes that had been in existence for decades where humans had reached the limits of physical capacity. Artificial Intelligence (AI) offers this same transformative potential for the augmentation and potential replacement of human tasks and activities within a wide range of industrial,intellectual and social applications. The pace of change for this new AI technological age is staggering, with new breakthroughs in algorithmic machine learning and autonomous decision-making, engendering new opportunities for continued innovation. The impact of AI could be significant, with industries ranging from: finance, healthcare, manufacturing, retail, supply chain, logistics and utilities, all potentially disrupted by the onset of AI technologies. The study brings together the collective insight from a number of leading expert contributors to highlight the significant opportunities, realistic assessment of impact, challenges and potential research agenda posed by the rapid emergence of AI within a number of domains: business and management, government, public sector, and science and technology. This research offers significant and timely insight to AI technology and its impact on the future of industry and society in general, whilst recognising the societal and industrial influence on pace and direction of AI development. ; If this is to be REF-eligible it needs a full text file attached, this cannot be the final published pdf but could be the version after review but before publisher formatting applied. RVO 3/10/19 Now more than 3 months post-publication and no file supplied so passing metadata only

As far back as the industrial revolution, great leaps in technical innovation succeeded in transforming numerous manual tasks and processes that had been in existence for decades where humans had reached the limits of physical capacity. Artificial Intelligence (AI) offers this same transformative potential for the augmentation and potential replacement of human tasks and activities within a wide range of industrial, intellectual and social applications. The pace of change for this new AI technological age is staggering, with new breakthroughs in algorithmic machine learning and autonomous decision making engendering new opportunities for continued innovation. The impact of AI is significant, with industries ranging from: finance, retail, healthcare, manufacturing, supply chain and logistics all set to be disrupted by the onset of AI technologies. The study brings together the collective insight from a number of leading expert contributors to highlight the significant opportunities, challenges and potential research agenda posed by the rapid emergence of AI within a number of domains: technological, business and management, science and technology, government and public sector. The research offers significant and timely insight to AI technology and its impact on the future of industry and society in general.