Showing papers by "University of Aberdeen published in 2019"

The UNITE database for molecular identification of fungi: handling dark taxa and parallel taxonomic classifications.

Abstract: Alfred P. Sloan Foundation [G-2015-14062]; Swedish Research Council of Environment, Agricultural Sciences, and Spatial Planning [FORMAS, 215-2011-498]; European Regional Development Fund (Centre of Excellence EcolChange) [TK131]; Estonian Research Council [IUT20-30]. Funding for open access charge: Swedish Research Council of Environment, Agricultural Sciences and Spatial Planning.

Genome-wide association study identifies 30 loci associated with bipolar disorder

Abstract: Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.

The technological and economic prospects for CO2 utilization and removal

Abstract: The capture and use of carbon dioxide to create valuable products might lower the net costs of reducing emissions or removing carbon dioxide from the atmosphere. Here we review ten pathways for the utilization of carbon dioxide. Pathways that involve chemicals, fuels and microalgae might reduce emissions of carbon dioxide but have limited potential for its removal, whereas pathways that involve construction materials can both utilize and remove carbon dioxide. Land-based pathways can increase agricultural output and remove carbon dioxide. Our assessment suggests that each pathway could scale to over 0.5 gigatonnes of carbon dioxide utilization annually. However, barriers to implementation remain substantial and resource constraints prevent the simultaneous deployment of all pathways. Ten pathways for the utilization of carbon dioxide are reviewed, considering their potential scale, economics and barriers to implementation.

Calibration: the Achilles heel of predictive analytics

Abstract: The assessment of calibration performance of risk prediction models based on regression or more flexible machine learning algorithms receives little attention. Herein, we argue that this needs to change immediately because poorly calibrated algorithms can be misleading and potentially harmful for clinical decision-making. We summarize how to avoid poor calibration at algorithm development and how to assess calibration at algorithm validation, emphasizing balance between model complexity and the available sample size. At external validation, calibration curves require sufficiently large samples. Algorithm updating should be considered for appropriate support of clinical practice. Efforts are required to avoid poor calibration when developing prediction models, to evaluate calibration when validating models, and to update models when indicated. The ultimate aim is to optimize the utility of predictive analytics for shared decision-making and patient counseling.

Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Abstract: Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

Twenty-three unsolved problems in hydrology (UPH)–a community perspective

Abstract: This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.

Defining and measuring multimorbidity: a systematic review of systematic reviews.

Abstract: Background Multimorbidity, the coexistence of multiple health conditions, is a growing public health challenge. Research and intervention development are hampered by the lack of consensus regarding defining and measuring multimorbidity. The aim of this systematic review was to pool the findings of systematic reviews examining definitions and measures of multimorbidity. Methods Medline, Embase, PubMed and Cochrane were searched from database inception to February 2017. Two authors independently screened titles, abstracts and full texts and extracted data from the included papers. Disagreements were resolved with a third author. Reviews were quality assessed. Results Of six reviews, two focussed on definitions and four on measures. Multimorbidity was commonly defined as the presence of multiple diseases or conditions, often with a cut-off of two or more. One review developed a holistic definition including biopsychosocial and somatic factors as well as disease. Reviews recommended using measures validated for the outcome of interest. Disease counts are an alternative if no validated measure exists. Conclusions To enable comparison between studies and settings, researchers and practitioners should be explicit about their choice of definition and measure. Using a cut-off of two or more conditions as part of the definition is widely adopted. Measure selection should be based on tools validated for the outcome being considered. Where there is no validated measure, or where multiple outcomes or populations are being considered, disease counts are appropriate.

Advanced materials and technologies for hybrid supercapacitors for energy storage – A review

Abstract: Supercapacitors have become the most significant energy conversion and storage system in recent renewable and sustainable nanotechnology. Due to its large energy capacity and supply with relatively short time and longer lifetime, supercapacitors breakthrough in advance energy applications. This review presents a comparative study of different materials, working principles, analysis, applications, advantages and disadvantages of various technologies available for supercapacitors. The aim of this article is to discuss the possibility of hybrid supercapacitor for the next generation of energy technology. The development of composite materials containing a wide range of active constituents (e.g., graphene, activated carbon, transition metals, metal oxides, perovskites and conducting polymers) by in-situ hybridization and ex-situ recombination is also discussed. This review consecrated largely the contribution of combining all materials (electrode and electrolyte) and their synthesis process and electrochemical performance. Enduringly, the potential issues and the perspectives for future research based on hybrid supercapacitors in energy applications are also presented.

Comparing and contrasting predictive biomarkers for immunotherapy and targeted therapy of NSCLC

Abstract: The era of personalized medicine for advanced-stage non-small-cell lung cancer (NSCLC) began when biomarker-based evidence of molecular pathway and/or oncogene addiction of the tumour became mandatory for the allocation of specific targeted therapies. More recently, the immunotherapy revolution, specifically, the development of immune-checkpoint inhibitors (ICIs), has dramatically altered the NSCLC treatment landscape. Herein, we compare and contrast the clinical development of immunotherapy and oncogene-directed therapy for NSCLC, focusing on the role of predictive biomarkers. Immunotherapy biomarkers are fundamentally different from oncogene biomarkers in that they are continuous rather than categorical (binary), spatially and temporally variable and reliant on multiple complex interactions rather than a single, dominant determinant. The performance of predictive biomarkers for ICIs might be improved by combining different markers to reduce the assumptive risks associated with each one. Novel combinations with chemotherapy and ICIs complicate biomarker discovery but do not decrease the value of the markers identified. Perfectly predictive biomarkers of benefit from immunotherapy are unlikely to be identified, although exclusionary biomarkers of minimal benefit or an unacceptable risk of toxicity might be feasible. The clinical adoption and applicability of such biomarkers might vary depending on line of treatment, the available therapeutic alternatives and health economic considerations. The advent of effective molecularly targeted treatments and immunotherapies for non-small-cell lung cancer (NSCLC) has greatly improved patient outcomes. Whereas most patients selected for treatment with molecularly targeted drugs derive benefits from these agents, benefit from immunotherapy is more difficult to predict. Herein, Camidge and colleagues compare and contrast predictive biomarkers for immunotherapy and targeted therapy of NSCLC to highlight considerations for biomarker development.

A culture of control

Abstract: Lorraine Hawick, Alan Thomson & Jennifer Cleland In this edition, Zeeman et al. report on a study that aimed to evaluate students’ predictions of their academic use of time and to assess the same students’ logged academic time. Students were asked to predict how much time they would spend on nine academic and other predefined activities during a typical weekday. Faculty members were also asked to predict student time use.

New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries

Abstract: Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.

Compendium of 4,941 rumen metagenome-assembled genomes for rumen microbiome biology and enzyme discovery

Abstract: Ruminants provide essential nutrition for billions of people worldwide. The rumen is a specialized stomach that is adapted to the breakdown of plant-derived complex polysaccharides. The genomes of the rumen microbiota encode thousands of enzymes adapted to digestion of the plant matter that dominates the ruminant diet. We assembled 4,941 rumen microbial metagenome-assembled genomes (MAGs) using approximately 6.5 terabases of short- and long-read sequence data from 283 ruminant cattle. We present a genome-resolved metagenomics workflow that enabled assembly of bacterial and archaeal genomes that were at least 80% complete. Of note, we obtained three single-contig, whole-chromosome assemblies of rumen bacteria, two of which represent previously unknown rumen species, assembled from long-read data. Using our rumen genome collection we predicted and annotated a large set of rumen proteins. Our set of rumen MAGs increases the rate of mapping of rumen metagenomic sequencing reads from 15% to 50–70%. These genomic and protein resources will enable a better understanding of the structure and functions of the rumen microbiota. Comprehensive resource of cattle rumen genomes and a database of predicted proteins.

A critical review of the impacts of cover crops on nitrogen leaching, net greenhouse gas balance and crop productivity.

Abstract: Cover crops play an increasingly important role in improving soil quality, reducing agricultural inputs and improving environmental sustainability. The main objectives of this critical global review and systematic analysis were to assess cover crop practices in the context of their impacts on nitrogen leaching, net greenhouse gas balances (NGHGB) and crop productivity. Only studies that investigated the impacts of cover crops and measured one or a combination of nitrogen leaching, soil organic carbon (SOC), nitrous oxide (N2 O), grain yield and nitrogen in grain of primary crop, and had a control treatment were included in the analysis. Long-term studies were uncommon, with most data coming from studies lasting 2-3 years. The literature search resulted in 106 studies carried out at 372 sites and covering different countries, climatic zones and management. Our analysis demonstrates that cover crops significantly (p 0.05) effects on direct N2 O emissions. Cover crops could mitigate the NGHGB by 2.06 ± 2.10 Mg CO2 -eq ha-1 year-1 . One of the potential disadvantages of cover crops identified was the reduction in grain yield of the primary crop by ≈4%, compared to the control treatment. This drawback could be avoided by selecting mixed cover crops with a range of legumes and non-legumes, which increased the yield by ≈13%. These advantages of cover crops justify their widespread adoption. However, management practices in relation to cover crops will need to be adapted to specific soil, management and regional climatic conditions.

Microbial Proteases Applications.

Abstract: The use of chemicals around the globe in different industries has increased tremendously, affecting the health of people. The modern world intends to replace these noxious chemicals with environmental friendly products for the betterment of life on the planet. Establishing enzymatic processes in spite of chemical processes has been a prime objective of scientists. Various enzymes, specifically microbial proteases, are the most essentially used in different corporate sectors, such as textile, detergent, leather, feed, waste, and others. Proteases with respect to physiological and commercial roles hold a pivotal position. As they are performing synthetic and degradative functions, proteases are found ubiquitously, such as in plants, animals, and microbes. Among different producers of proteases, Bacillus sp. are mostly commercially exploited microbes for proteases. Proteases are successfully considered as an alternative to chemicals and an eco-friendly indicator for nature or the surroundings. The evolutionary relationship among acidic, neutral, and alkaline proteases has been analyzed based on their protein sequences, but there remains a lack of information that regulates the diversity in their specificity. Researchers are looking for microbial proteases as they can tolerate harsh conditions, ways to prevent autoproteolytic activity, stability in optimum pH, and substrate specificity. The current review focuses on the comparison among different proteases and the current problems faced during production and application at the industrial level. Deciphering these issues would enable us to promote microbial proteases economically and commercially around the world.

Contribution of the land sector to a 1.5 °C world

Abstract: The Paris Agreement introduced an ambitious goal of limiting warming to 1.5 °C above pre-industrial levels. Here we combine a review of modelled pathways and literature on mitigation strategies, and develop a land-sector roadmap of priority measures and regions that can help to achieve the 1.5 °C temperature goal. Transforming the land sector and deploying measures in agriculture, forestry, wetlands and bioenergy could feasibly and sustainably contribute about 30%, or 15 billion tonnes of carbon dioxide equivalent (GtCO2e) per year, of the global mitigation needed in 2050 to deliver on the 1.5 °C target, but it will require substantially more effort than the 2 °C target. Risks and barriers must be addressed and incentives will be necessary to scale up mitigation while maximizing sustainable development, food security and environmental co-benefits. Transformation of the land sector is required to meet the Paris Agreement goal of limiting warming to 1.5 °C. Here, modelled emission pathways and mitigation strategies are reviewed. A land-sector roadmap of priority measures and key regions is presented.

Development of an ABAQUS plugin tool for periodic RVE homogenisation

Abstract: EasyPBC is an ABAQUS CAE plugin developed to estimate the homogenised effective elastic properties of user created periodic representative volume element (RVE), all within ABAQUS without the need to use third-party software. The plugin automatically applies the concepts of the periodic RVE homogenisation method in the software’s user interface by categorising, creating, and linking sets necessary for achieving deformable periodic boundary surfaces, which can distort and no longer remain plane. Additionally, it allows the user to benefit from finite element analysis data within ABAQUS CAE interface after calculating homogenised properties. In this article, the algorithm of the plugin based on periodic RVE homogenisation method is explained, which could be developed for other commercial FE software packages. Furthermore, examples of its implementation and verification are illustrated.

PD-1/PD-L1 pathway: Basic biology and role in cancer immunotherapy

Abstract: Over the course of past few years, cancer immunotherapy has been accompanied with promising results. However, preliminary investigations with respect to immunotherapy concentrated mostly on targeting the immune checkpoints, nowadays, emerge as the most efficient strategy to raise beneficial antitumor immune responses. Programmed cell death protein 1 (PD-1) plays an important role in subsiding immune responses and promoting self-tolerance through suppressing the activity of T cells and promoting differentiation of regulatory T cells. PD-1 is considered as an immune checkpoint and protects against autoimmune responses through both induction of apoptosis in antigen-specific T cells and inhibiting apoptosis in regulatory T cells. Several clinical trials exerting PD-1 monoclonal antibodies as well as other immune-checkpoint blockades have had prosperous outcomes and opened new horizons in tumor immunotherapy. Nonetheless, a bulk of patients have failed to respond to these newly emerging immune-based approach and the survival rate was not satisfying. Additional strategies, especially combination therapies, has been initiated and been further promising. Attempts to identify novel and well-suited predictive biomarkers are also sensed. In this review, the promotion of cancer immunotherapy targeting PD-1 immunoinhibitory pathway is discussed.

Microplastics and synthetic particles ingested by deep-sea amphipods in six of the deepest marine ecosystems on Earth

Abstract: While there is now an established recognition of microplastic pollution in the oceans, and the detrimental effects this may have on marine animals, the ocean depth at which such contamination is in...

No Surgical Innovation Without Evaluation: Evolution and Further Development of the IDEAL Framework and Recommendations

Abstract: Objective:To update, clarify, and extend IDEAL concepts and recommendations.Background:New surgical procedures, devices, and other complex interventions need robust evaluation for safety, efficacy, and effectiveness. Unlike new medicines, there is no internationally agreed evaluation pathway for gen

Matching policy and science: Rationale for the ‘4 per 1000 - soils for food security and climate’ initiative

Abstract: At the 21st session of the United Nations Framework Convention on Climate Change (UNFCCC, COP21), a voluntary action plan, the ‘4 per 1000 Initiative: Soils for Food Security and Climate’ was proposed under the Agenda for Action. The Initiative underlines the role of soil organic matter (SOM) in addressing the three-fold challenge of food and nutritional security, adaptation to climate change and mitigation of human-induced greenhouse gases (GHGs) emissions. It sets an ambitious aspirational target of a 4 per 1000 (i.e. 0.4%) rate of annual increase in global soil organic carbon (SOC) stocks, with a focus on agricultural lands where farmers would ensure the carbon stewardship of soils, like they manage day-to-day multipurpose production systems in a changing environment. In this paper, the opportunities and challenges for the 4 per 1000 initiative are discussed. We show that the 4 per 1000 target, calculated relative to global top soil SOC stocks, is consistent with literature estimates of the technical potential for SOC sequestration, though the achievable potential is likely to be substantially lower given socio-economic constraints. We calculate that land-based negative emissions from additional SOC sequestration could significantly contribute to reducing the anthropogenic CO2 equivalent emission gap identified from Nationally Determined Contributions pledged by countries to stabilize global warming levels below 2 °C or even 1.5 °C under the Paris agreement on climate. The 4 per 1000 target could be implemented by taking into account differentiated SOC stock baselines, reversing the current trend of huge soil CO2 losses, e.g. from agriculture encroaching peatland soils. We further discuss the potential benefits of SOC stewardship for both degraded and healthy soils along contrasting spatial scales (field, farm, landscape and country) and temporal (year to century) horizons. Last, we present some of the implications relative to non-CO2 GHGs emissions, water and nutrients use as well as co-benefits for crop yields and climate change adaptation. We underline the considerable challenges associated with the non-permanence of SOC stocks and show how the rates of adoption and the duration of improved soil management practices could alter the global impacts of practices under the 4 per 1000 initiative. We conclude that the 4 per 1000 initiative has potential to support multiple sustainable development goals (SDGs) of the 2030 Agenda. It can be regarded as no-regret since increasing SOC in agricultural soils will contribute to food security benefits that will enhance resilience to climate change. However, social, economic and environmental safeguards will be needed to ensure an equitable and sustainable implementation of the 4 per 1000 target.

The association between maternal body mass index and child obesity: A systematic review and meta-analysis

Abstract: Background There is a global obesity crisis, particularly among women and disadvantaged populations. Early-life intervention to prevent childhood obesity is a priority for public health, global health, and clinical practice. Understanding the association between childhood obesity and maternal pre-pregnancy weight status would inform policy and practice by allowing one to estimate the potential for offspring health gain through channelling resources into intervention. This systematic review and meta-analysis aimed to examine the dose–response association between maternal body mass index (BMI) and childhood obesity in the offspring. Methods and findings Searches in MEDLINE, Child Development & Adolescent Studies, CINAHL, Embase, and PsycInfo were carried out in August 2017 and updated in March 2019. Supplementary searches included hand-searching reference lists, performing citation searching, and contacting authors. Two researchers carried out independent screening, data extraction, and quality assessment. Observational studies published in English and reporting associations between continuous and/or categorical maternal and child BMI or z-score were included. Categorical outcomes were child obesity (≥95th percentile, primary outcome), overweight/obesity (≥85th percentile), and overweight (85th to 95th percentile). Linear and nonlinear dose–response meta-analyses were conducted using random effects models. Studies that could not be included in meta-analyses were summarised narratively. Seventy-nine of 41,301 studies identified met the inclusion criteria (n = 59 cohorts). Meta-analyses of child obesity included 20 studies (n = 88,872); child overweight/obesity, 22 studies (n = 181,800); and overweight, 10 studies (n = 53,238). Associations were nonlinear and there were significantly increased odds of child obesity with maternal obesity (odds ratio [OR] 3.64, 95% CI 2.68–4.95) and maternal overweight (OR 1.89, 95% CI 1.62–2.19). Significantly increased odds were observed for child overweight/obesity (OR 2.69, 95% CI 2.10–3.46) and for child overweight (OR 1.80, 95% CI 1.25, 2.59) with maternal obesity. A limitation of this research is that the included studies did not always report the data in a format that enabled inclusion in this complex meta-analysis. Conclusions This research has identified a 264% increase in the odds of child obesity when mothers have obesity before conception. This study provides substantial evidence for the need to develop interventions that commence prior to conception, to support women of childbearing age with weight management in order to halt intergenerational obesity.

A heritable subset of the core rumen microbiome dictates dairy cow productivity and emissions

Abstract: A 1000-cow study across four European countries was undertaken to understand to what extent ruminant microbiomes can be controlled by the host animal and to identify characteristics of the host rumen microbiome axis that determine productivity and methane emissions. A core rumen microbiome, phylogenetically linked and with a preserved hierarchical structure, was identified. A 39-member subset of the core formed hubs in co-occurrence networks linking microbiome structure to host genetics and phenotype (methane emissions, rumen and blood metabolites, and milk production efficiency). These phenotypes can be predicted from the core microbiome using machine learning algorithms. The heritable core microbes, therefore, present primary targets for rumen manipulation toward sustainable and environmentally friendly agriculture.