Genomic analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea

This is the final version of the article. Available from the publisher via the DOI in this record.Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38-39 Mb genomes include 11,860-14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared to <1% of B. cinerea. The arsenal of genes associated with necrotrophic processes is similar between the species, including genes involved in plant cell wall degradation and oxalic acid production. Analysis of secondary metabolism gene clusters revealed an expansion in number and diversity of B. cinerea-specific secondary metabolites relative to S. sclerotiorum. The potential diversity in secondary metabolism might be involved in adaptation to specific ecological niches. Comparative genome analysis revealed the basis of differing sexual mating compatibility systems between S. sclerotiorum and B. cinerea. The organization of the mating-type loci differs, and their structures provide evidence for the evolution of heterothallism from homothallism. These data shed light on the evolutionary and mechanistic bases of the genetically complex traits of necrotrophic pathogenicity and sexual mating. This resource should facilitate the functional studies designed to better understand what makes these fungi such successful and persistent pathogens of agronomic crops.The Sclerotinia sclerotiorum genome project was supported by the USDA Cooperative State Research, Education and Extension Service (USDA-NRI 2004). Sclerotinia sclerotiorum ESTs were funded by a grant to JA Rollins from USDA specific cooperative agreement 58-5442-4-281. The genome sequence of Botrytis cinerea strain T4 was funded by Genoscope, CEA, France. M Viaud was funded by the “Projet INRA Jeune-Equipe”. PM Coutinho and B Henrissat were funded by the ANR to project E-Tricel (grant ANR-07-BIOE-006). The CAZy database is funded in part by GIS-IBiSA. DM Soanes and NJ Talbot were partly funded by the UK Biotechnology and Biological Sciences Research Council. KM Plummer was partially funded by the New Zealand Bio-Protection Research Centre, http://bioprotection.org.nz/. BJ Howlett and A Sexton were partially funded by the Australian Grains Research and Development Corporation, www.grdc.com.au. L Kohn was partially funded by NSERC Discovery Grant (Natural Sciences and Engineering Research Council of Canada) - Grant number 458078. M Dickman was supported by the NSF grant MCB-092391 and BARD grant US-4041-07C. O Yarden was supported by BARD grant US-4041-07C. EG Danchin obtained financial support from the European Commission (STREP FungWall grant, contract: LSHB - CT- 2004 - 511952). A Botrytis Genome Workshop (Kaiserslautern, Germany) was supported by a grant from the German Science Foundation (DFG; HA1486) to M Hahn

Association of ultra-rare coding variants with genetic generalized epilepsy: A case\u2013control whole exome sequencing study

Objective: We aimed to identify genes associated with genetic generalized epilepsy (GGE) by combining large cohorts enriched with individuals with a positive family history. Secondarily, we set out to compare the association of genes independently with familial and sporadic GGE. Methods: We performed a case\u2013control whole exome sequencing study in unrelated individuals of European descent diagnosed with GGE (previously recruited and sequenced through multiple international collaborations) and ancestry-matched controls. The association of ultra-rare variants (URVs; in 18&nbsp;834 protein-coding genes) with epilepsy was examined in 1928 individuals with GGE (vs. 8578 controls), then separately in 945 individuals with familial GGE (vs. 8626 controls), and finally in 1005 individuals with sporadic GGE (vs. 8621 controls). We additionally examined the association of URVs with familial and sporadic GGE in two gene sets important for inhibitory signaling (19&nbsp;genes encoding \u3b3-aminobutyric acid type A [GABAA] receptors, 113&nbsp;genes representing the GABAergic pathway). Results: GABRG2 was associated with GGE (p&nbsp;=&nbsp;1.8&nbsp; 7&nbsp;10 125), approaching study-wide significance in familial GGE (p&nbsp;=&nbsp;3.0&nbsp; 7&nbsp;10 126), whereas no gene approached a significant association with sporadic GGE. Deleterious URVs in the most intolerant subgenic regions in genes encoding GABAA receptors were associated with familial GGE (odds ratio [OR]&nbsp;=&nbsp;3.9, 95% confidence interval [CI]&nbsp;=&nbsp;1.9\u20137.8, false discovery rate [FDR]-adjusted p&nbsp;=.0024), whereas their association with sporadic GGE had marginally lower odds (OR&nbsp;=&nbsp;3.1, 95% CI&nbsp;=&nbsp;1.3\u20136.7, FDR-adjusted p&nbsp;=.022). URVs in GABAergic pathway genes were associated with familial GGE (OR&nbsp;=&nbsp;1.8, 95% CI&nbsp;=&nbsp;1.3\u20132.5, FDR-adjusted p&nbsp;=.0024) but not with sporadic GGE (OR&nbsp;=&nbsp;1.3, 95% CI&nbsp;=.9\u20131.9, FDR-adjusted p&nbsp;=.19). Significance: URVs in GABRG2 are likely an important risk factor for familial GGE. The association of gene sets of GABAergic signaling with familial GGE is more prominent than with sporadic GGE

Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data

The classic epileptic encephalopathies, including infantile spasms (IS) and Lennox–Gastaut syndrome (LGS), are severe seizure disorders that usually arise sporadically. De novo variants in genes mainly encoding ion channel and synaptic proteins have been found to account for over 15% of patients with IS or LGS. The contribution of autosomal recessive genetic variation, however, is less well understood. We implemented a rare variant transmission disequilibrium test (TDT) to search for autosomal recessive epileptic encephalopathy genes in a cohort of 320 outbred patient–parent trios that were generally prescreened for rare metabolic disorders. In the current sample, our rare variant transmission disequilibrium test did not identify individual genes with significantly distorted transmission over expectation after correcting for the multiple tests. While the rare variant transmission disequilibrium test did not find evidence of a role for individual autosomal recessive genes, our current sample is insufficiently powered to assess the overall role of autosomal recessive genotypes in an outbred epileptic encephalopathy population

Does the Letter Matter (and for Everyone)? Quasi-Experimental Evidence on the Effects of Home Invitation on Mammography Uptake

We exploit regional variation in the availability of breast cancer screening policies and variations in age eligibility criteria across European regions to estimate the causal effect of home invitation on mammography uptake. We link administrative public data about regional breast cancer screening policies from various sources to individual Survey of Health Ageing and Retirement in Europe (SHARE) data. We find that home invitation increases mammography uptakes by almost 20 percentage points. At the same time, we find that home invitation reduces education-related inequalities but increases gradient in the use related to cognitive functions. In addition, significant effects on mammography use are found only when at least 50 per cent of the population is reached by the home invitation. Our results suggest that an exogenous informational shock affects preventive decisions especially among less informed individuals but the effectiveness of invitation is strongly reduced for women who are less able to process information.In diesem Papier nutzen wir regionale Unterschiede im Zugang zu Brustkrebs-Screening-Programmen sowie regionale Unterschiede in den altersspezifischen Teilnahmebedingungen, um den kausalen Effekt von schriftlichen Einladungen auf die Teilnahme an Mammographie-Screening-Programmen zu untersuchen. Hierzu werden administrative regionale Daten zu Brustkrebs-Screening-Programmen herangezogen und mit Individualdaten des Survey of Health Ageing and Retirement (SHARE) verknüpft. Wir finden heraus, dass die Einladung zum Screening die Teilnahme am Screening um fast 20 Prozentpunkte erhöht. Gleichzeitig reduziert die Einladung zum Screening bildungsbezogene Ungleichheiten in der Inanspruchnahme, jedoch erhöht sie kognitiv bezogene Ungleichheiten. Signifikante Effekte auf die Mammographieteilnahme werden nur gefunden, wenn mindestens 50 Prozent der Bevölkerung eine Einladung erhält. Unsere Ergebnisse lassen schlussfolgern, dass ein durch die schriftliche Einladung ausgelöster exogener Informationsschock einen starken Einfluss auf Präventionsentscheidungen hat. Diese Schlussfolgerung gilt insbesondere für weniger informierte Personen. Demgegenüber ist die Einladung zum Screening nicht so effektiv, wenn die Frauen weniger in der Lage sind Informationen zu verarbeiten

Determinantes individuales y sociales del estado de salud subjetivo y bienestar de la población de la tercera edad de Portugal

This article aims to identify the main determinants of self-rated health and well-being in the elderly Portuguese population, using a set of dimensions including demographic and socioeconomic indicators, characteristics of interpersonal networks and social activities, health, sexual activity, representations of aging, and feeling of happiness. Taking socioeconomic, behavioral, and attitudinal predictors into account to analyze the explanatory value of the interrelated dimensions and weights for each factor, the author argues that social capital, activities associated with active aging, and greater optimism towards aging can contribute greatly to better self-rated health and wellbeing among the elderly, partially offsetting the effect of socioeconomic factors and illness associated with age.Neste artigo pretende-se identificar os principais determinantes da autoavaliação do estado de saúde e do bem-estar da população sênior, tendo em conta um conjunto de dimensões que reúnem indicadores demográficos e socioeconômicos, características das redes interpessoais e atividades sociais praticadas, de saúde, atividade sexual, de representações sobre o envelhecimento e sentimento de felicidade. A equação em simultâneo de preditores socioeconômicos e de caráter comportamental e atitudinal dessas várias vertentes, com o intuito de analisar o valor explicativo de cada uma das dimensões inter-relacionadas e o peso de cada um dos fatores, permite concluir que o social capital, a prática de atividades associadas ao envelhecimento ativo e um maior otimismo em relação ao envelhecimento podem contribuir em grande medida para uma melhor autoavaliação do estado de saúde e do bemestar dos mais velhos, compensando, em parte, o efeito de fatores socioeconômicos e de doença associados à idade

X-ray Diffraction Results from Mars Science Laboratory: Mineralogy of Rocknest at Gale Crater

The Mars Science Laboratory rover Curiosity scooped samples of soil from the Rocknest aeolian bedform in Gale crater. Analysis of the soil with the Chemistry and Mineralogy (CheMin) x-ray diffraction (XRD) instrument revealed plagioclase (~An57), forsteritic olivine (~Fo62), augite, and pigeonite, with minor K-feldspar, magnetite, quartz, anhydrite, hematite, and ilmenite. The minor phases are present at, or near, detection limits. The soil also contains 27 ± 14 weight percent x-ray amorphous material, likely containing multiple Fe^(3+)- and volatile-bearing phases, including possibly a substance resembling hisingerite. The crystalline component is similar to the normative mineralogy of certain basaltic rocks from Gusev crater on Mars and of martian basaltic meteorites. The amorphous component is similar to that found on Earth in places such as soils on the Mauna Kea volcano, Hawaii

Mineralogy of a Mudstone at Yellowknife Bay, Gale Crater, Mars

Sedimentary rocks at Yellowknife Bay (Gale Crater) on Mars include mudstone sampled by the Curiosity rover. The samples, John Klein and Cumberland, contain detrital basaltic minerals, Ca-sulfates, Fe oxide/hydroxides, Fe-sulfides, amorphous material, and trioctahedral smectites. The John Klein smectite has basal spacing of ~10 Å indicating little interlayer hydration. The Cumberland smectite has basal spacing at ~13.2 Å as well as ~10 Å. The ~13.2 Å spacing suggests a partially chloritized interlayer or interlayer Mg or Ca facilitating H_2O retention. Basaltic minerals in the mudstone are similar to those in nearby eolian deposits. However, the mudstone has far less Fe-forsterite, possibly lost with formation of smectite plus magnetite. Late Noachian/Early Hesperian or younger age indicates that clay mineral formation on Mars extended beyond Noachian time