Genome Sequence of the Chestnut Blight Fungus Cryphonectria parasitica EP155: A Fundamental Resource for an Archetypical Invasive Plant Pathogen.

Cryphonectria parasitica is the causal agent of chestnut blight, a fungal disease that almost entirely eliminated mature American chestnut from North America over a 50-year period. Here, we formally report the genome of C. parasitica EP155 using a Sanger shotgun sequencing approach. After finishing and integration with simple-sequence repeat markers, the assembly was 43.8 Mb in 26 scaffolds (L50 = 5; N50 = 4.0Mb). Eight chromosomes are predicted: five scaffolds have two telomeres and six scaffolds have one telomere sequence. In total, 11,609 gene models were predicted, of which 85% show similarities to other proteins. This genome resource has already increased the utility of a fundamental plant pathogen experimental system through new understanding of the fungal vegetative incompatibility system, with significant implications for enhancing mycovirus-based biological control

Genome analysis of the ubiquitous boxwood pathogen Pseudonectria foliicola

Boxwood (Buxus spp.) are broad-leaved, evergreen landscape plants valued for their longevity and ornamental qualities. Volutella leaf and stem blight, caused by the ascomycete fungi Pseudonectria foliicola and P. buxi, is one of the major diseases affecting the health and ornamental qualities of boxwood. Although this disease is less severe than boxwood blight caused by Calonectria pseudonaviculata and C. henricotiae, its widespread occurrence and disfiguring symptoms have caused substantial economic losses to the ornamental industry. In this study, we sequenced the genome of P. foliicola isolate ATCC13545 using Illumina technology and compared it to other publicly available fungal pathogen genomes to better understand the biology of this organism. A de novo assembly estimated the genome size of P. foliicola at 28.7 Mb (425 contigs; N50 = 184,987 bp; avg. coverage 188×), with just 9,272 protein-coding genes. To our knowledge, P. foliicola has the smallest known genome within the Nectriaceae. Consistent with the small size of the genome, the secretome, CAzyme and secondary metabolite profiles of this fungus are reduced relative to two other surveyed Nectriaceae fungal genomes: Dactylonectria macrodidyma JAC15-245 and Fusarium graminearum Ph-1. Interestingly, a large cohort of genes associated with reduced virulence and loss of pathogenicity was identified from the P. foliicola dataset. These data are consistent with the latest observations by plant pathologists that P. buxi and most likely P. foliicola, are opportunistic, latent pathogens that prey upon weak and stressed boxwood plants

Trade unions and the challenge of fostering solidarities in an era of financialisation

This articles re-examines evidence that trade unions in the UK have struggled to renew themselves despite considerable investment of time and effort. It argues that financialisation in the realms of capital accumulation, organisational decision making and everyday life has introduced new barriers to building the solidarities within and between groups of workers that would be necessary to develop a stronger response to the catastrophic effects on labour of financialisation in general, and the financial crisis specifically. The crisis highlighted the weaknesses of trade unions as institutions of economic and industrial democracy, but has also given some opportunities to establish narratives of solidarity in spaces and platforms created within a financialised context

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Incorporation of a Horizontally Transferred Gene into an Operon during Cnidarian Evolution

Genome sequencing has revealed examples of horizontally transferred genes, but we still know little about how such genes are incorporated into their host genomes. We have previously reported the identification of a gene (flp) that appears to have entered the Hydra genome through horizontal transfer. Here we provide additional evidence in support of our original hypothesis that the transfer was from a unicellular organism, and we show that the transfer occurred in an ancestor of two medusozoan cnidarian species. In addition we show that the gene is part of a bicistronic operon in the Hydra genome. These findings identify a new animal phylum in which trans-spliced leader addition has led to the formation of operons, and define the requirements for evolution of an operon in Hydra. The identification of operons in Hydra also provides a tool that can be exploited in the construction of transgenic Hydra strains

Amyloid precursor protein drives down-regulation of mitochondrial oxidative phosphorylation independent of amyloid beta

Amyloid precursor protein (APP) and its extracellular domain, soluble APP alpha (sAPPα) play important physiological and neuroprotective roles. However, rare forms of familial Alzheimer’s disease are associated with mutations in APP that increase toxic amyloidogenic cleavage of APP and produce amyloid beta (Aβ) at the expense of sAPPα and other non-amyloidogenic fragments. Although mitochondrial dysfunction has become an established hallmark of neurotoxicity, the link between Aβ and mitochondrial function is unclear. In this study we investigated the effects of increased levels of neuronal APP or Aβ on mitochondrial metabolism and gene expression, in human SH-SY5Y neuroblastoma cells. Increased non-amyloidogenic processing of APP, but not Aβ, profoundly decreased respiration and enhanced glycolysis, while mitochondrial DNA (mtDNA) transcripts were decreased, without detrimental effects to cell growth. These effects cannot be ascribed to Aβ toxicity, since higher levels of endogenous Aβ in our models do not cause oxidative phosphorylation (OXPHOS) perturbations. Similarly, chemical inhibition of β-secretase decreased mitochondrial respiration, suggesting that non-amyloidogenic processing of APP may be responsible for mitochondrial changes. Our results have two important implications, the need for caution in the interpretation of mitochondrial perturbations in models where APP is overexpressed, and a potential role of sAPPα or other non-amyloid APP fragments as acute modulators of mitochondrial metabolism

Learning at the bottom of the pyramid : Science, measurement, and policy in low-income countries

In this volume, a diverse group of authors discuss and analyse the scientific tensions in understanding learning among poor and marginalized populations in Low- and Middle-income countries (LMICs). Four broad areas are considered: how to define the BoP; how to measure and assess learning outcomes across diverse populations within a country; variations in learning across the life-span; and the implications for international education policy. Each of the 12 chapters is complemented by two commentaries, thus there are a total of 36 contributions. In the social sciences, learning is defined most commonly as a change – such as in knowledge, skills, attitudes, and values – based on experiences of some kind.Thus, schooling is not the same thing as learning. While schooling is usually designed to foster curriculum-based learning in classrooms, research increasingly demonstrates that much of what we presume is learned in school is not, and that a great deal of learning takes place outside of schools. There is a large and diverse empirical research base in the area of human learning. However, much of the available research is limited by constraints of various kinds. Most prominent among these is the limited ability to generalize from findings in one population or context to others. In Chapter 1, Schmelkes considers common elements to human learning, in and out of school, including important cultural variations that are large and often poorly understood. She concludes that much more should be done to improve educational policy and address such contextual issues. A second key priority is to determine what populations are meant by the phrase BoP. How do populations differ in LMICs – both across and within countries? As pointed out by Montoya in Chapter 2, there are at least six prominent dimensions through which populations at the BoP may be described in low-income countries, and each is important for considering the ways that young people can escape from persistent poverty. Building on the first two chapters, Crouch (Chapter 3) lays out a conceptual model, buttressed by data from international assessments, that describes how to flatten the learning pyramid to ensure more equitable learning outcomes for all by focusing on the poorest learners. Overall, these three chapters provide a framework for considering the nature and extent of BoP studies of learning. There are many critiques of the educational assessment enterprise, the beginning of which is sometimes attributed to the French psychometrician Alfred Binet. In order to support the expansion of public schooling in France, Binet famously created assessments through which he could predict which children would have the most difficulty in school. In this section, we consider contemporary approaches to learning assessments, with a specific focus on the socio-cultural determinants of who succeeds and who does not at the BoP. Kanjee, in Chapter 4, takes a broad perspective by reviewing the purposes of international assessment studies, suggesting that assessments have only limited impact on supporting BoP learning achievement. He concludes that assessments can better address the learning needs of poor and marginalized learners by reporting results through formative evaluations that can impact children before learning gaps widen. In Chapter 5, Willms describes a conceptual model for improved learning over the life-course, empirically supported by research in Uruguay among preschool children, and in Canada with young indigenous children. One of his findings is that in order to succeed in school, children need to learn to read with confidence during the primary grades, and use language to think critically, solve problems, and create new knowledge. He concludes that national and international assessments can serve to establish standards, assess the extent of inequalities among various subpopulations, and provide a framework for basic or theoretical research, but that there should be greater focus on changing classroom practice. One way to understand the inner workings of assessments and use them to promote learning at the BoP is provided by Vagh and Sharma (Chapter 6) in their action research project in Allahabad, India. This project sought to develop and evaluate a local language literacy and numeracy programme for children from low socioeconomic backgrounds in government school primary grades, using measurement and assessment to drive programme change. It highlights some of the strengths and challenges of localized assessments. Moreover, it suggests that assessments can be used by teachers to support early reading. Finally, in Chapter 7, Maddox asks a seminal question: To what extent are learning assessments able to identify and include individual and cultural differences, without reproducing relations of disadvantage? These issues are described in terms of test fairness and procedures for anticipating and removing sources of test bias. In a series of ethnographic studies, Maddox advises the reader to pay close attention to how assessments are carried out in situ, and how questions are interpreted by the person tested. Serious problems can and will ensue without such care in local contexts. Another approach to BoP issues is through a life-span perspective. How do measurement tools on learning and learning outcomes vary for young children, students in school, as well as among youth and adults? Three chapters in this section consider such age-related differences. Dowd and Pisani, in Chapter 8, have been deeply involved in the field of assessments of young children before they reach school age. Their chapter reviews the application of the International Development and Early Learning Assessment (IDELA) instrument to explore young children’s skills at the BoP and identify learning gaps in early academic, physical, and social-emotional development. Based on the broad findings from more than 20 LMICs, and closer analysis of particular contexts, the authors make that case that there is much variation in early childhood learning within countries, particularly between urban and rural contexts. They argue that national policies in support of early childhood need to be guided by disaggregated data in order to ensure that children at the BoP receive adequate support. In Chapter 9, Care, Robertson, and Ferido describe how well-designed assessments for school-aged children can provide individualized information that can support school-based learning. These assessments build on the skill levels that children bring to the classroom. Through what they term a ‘learning progression model’, they present data on children in the Philippines who are best able to learn from specifically guided instruction tailored to their particular skill level. They conclude that learning assessments can and should be inclusive of diverse groups within any larger target population. Finally, Oketch (Chapter 10) focuses on youth and adult learning in subSaharan African, pointing out that rapidly changing demographics and economies in the region require significantly greater attention. Further, the population of low-skilled youth is growing dramatically, even though more African children are going to school than ever before. This chapter describes the importance of technical and vocational education and training (TVET) and non-formal education as two known methodologies for directly providing instruction and learning outside of the classroom in support of out-of-school youth and adults. The problem remains, according to Oketch, that there is a paucity of research in this domain, and in particular among populations at the BoP. In Chapters 1–10, authors and commentators present multiple views on scientific definitions, measurement tools, and life-span approaches for understanding learning at the BoP. This final section of the volume considers the kinds of educational policy implications that need to be considered by both national and international decision-makers. Benavot (Chapter 11) raises a key issue in supporting learning at the BoP, notably the need to move beyond easily accessible measures of learning – namely, school-based surveys of a narrow range of learning outcomes at the primary and lower secondary level – and engage with the broader and more comprehensive learning agenda proposed in the SDGs. He points out that many of the UN goals contain diverse elements of learning, and the specific targets for each goal may vary a great deal across diverse populations. Further, he notes that many of the key markers of disadvantage in education (such as socio-economic status, SES) are very difficult to change. He concludes that a serious focus on learning at the BoP will require greater clarity of definitions, and a more deliberate approach to building evidence on how best to improve relevant learning outcomes for the disadvantaged. In Chapter 12, Van Damme provides a global policy perspective supported by the findings of the Organisation for Economic Co-operation and Development (OECD) international learning assessments. He asserts that international educational policies can only be inclusive and sustainable if those at the bottom of the social and educational pyramid benefit from them. To support this perspective, Van Damme presents findings that demonstrate how higher levels of economic growth are driven by more years of education and greater learning achievement within countries. By disaggregating data from the Programme for International Student Assessment (PISA) 2015 assessment, he reminds us that students with very low proficiency tend to drive down national averages (similar to the findings by Crouch in Chapter 3). He concludes that countries need to focus on raising average learning outcomes to desired national standards while at the same time narrowing the distribution of national learning outcomes

Draft genomes of Amanita jacksonii, Ceratocystis albifundus, Fusarium circinatum, Huntiella omanensis, Leptographium procerum, Rutstroemia sydowiana, and Sclerotinia echinophila

The genomes of fungi provide an important resource to resolve issues pertaining to their taxonomy, biology, and evolution. The genomes of Amanita jacksonii, Ceratocystis albifundus, a Fusarium circinatum variant, Huntiella omanensis, Leptographium procerum, Sclerotinia echinophila, and Rutstroemia sydowiana are presented in this genome announcement. These seven genomes are from a number of fungal pathogens and economically important species. The genome sizes range from 27 Mb in the case of Ceratocystis albifundus to 51.9 Mb for Rutstroemia sydowiana. The latter also encodes for a predicted 17 350 genes, more than double that of Ceratocystis albifundus. These genomes will add to the growing body of knowledge of these fungi and provide a value resource to researchers studying these fungi.The US Department of Agriculture (USDA) Agricultural Research Service, grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Royal Ontario Museum to J.M.M.; Graduate Scholarships from the Consejo Nacional de Ciencia y Tecnologia (Mexico) and the University of Toronto to SSR; and a Undergraduate Student Research Award from NSERC to M.S. Financial support was provided by members of the Tree Protection Cooperative Program (TPCP), the Department of Science and Technology (DST)/ National Research Foundation (NRF) Centre of Excellence in Tree Health Biotechnology, and the Genomics Research Institute of the University of Pretoria. This project was supported by multiple grants from the NRF, South Africa, including the grant specific unique reference number (UID) 83924.http://www.imafungus.orgam201

Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma

Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE