Genome Sequence of the Model Mushroom Schizophyllum Commune

Much remains to be learned about the biology of mushroom-forming fungi, which are an important source of food, secondary metabolites and industrial enzymes. The wood-degrading fungus Schizophyllum commune is both a genetically tractable model for studying mushroom development and a likely source of enzymes capable of efficient degradation of lignocellulosic biomass. Comparative analyses of its 38.5-megabase genome, which encodes 13,210 predicted genes, reveal the species\u27s unique wood-degrading machinery. One-third of the 471 genes predicted to encode transcription factors are differentially expressed during sexual development of S. commune. Whereas inactivation of one of these, fst4, prevented mushroom formation, inactivation of another, fst3, resulted in more, albeit smaller, mushrooms than in the wild-type fungus. Antisense transcripts may also have a role in the formation of fruiting bodies. Better insight into the mechanisms underlying mushroom formation should affect commercial production of mushrooms and their industrial use for producing enzymes and pharmaceuticals

Associations between human leukocyte antigen class I variants and the Mycobacterium tuberculosis subtypes causing disease

BACKGROUND. The development of active tuberculosis disease has been shown to be multifactorial. Interactions between host and bacterial genotype may influence disease outcome, with some studies indicating the adaptation of M. tuberculosis strains to specific human populations. Here we investigate the role of the human leukocyte antigen (HLA) class I genes in this biological process. METHODS. Three hundred patients with tuberculosis from South Africa were typed for their HLA class I alleles by direct sequencing. Mycobacterium tuberculosis genotype classification was done by IS6110 restriction fragment length polymorphism genotyping and spoligotyping. RESULTS. We showed that Beijing strain occurred more frequently in individuals with multiple disease episodes (P < .001) with the HLA-B27 allele lowering the odds of having an additional episode (odds ratio, 0.21; P = .006). Associations were also identified for specific HLA types and disease caused by the Beijing, LAM, LCC, and Quebec strains. HLA types were also associated with disease caused by strains from the Euro-American or East Asian lineages, and the frequencies of these alleles in their sympatric human populations identified potential coevolutionary events between host and pathogen. CONCLUSIONS. This is the first report of the association of human HLA types and M. tuberculosis strain genotype, highlighting that both host and pathogen genetics need to be taken into consideration when studying tuberculosis disease development.Web of Scienc

Deep Inelastic Scattering of Polarized Electrons by Polarized 3^3He and the Study of the Neutron Spin Structure

The neutron longitudinal and transverse asymmetries $A^n_1$ and $A^n_2$ have been extracted from deep inelastic scattering of polarized electrons by a polarized $^3$He target at incident energies of 19.42, 22.66 and 25.51 GeV. The measurement allows for the determination of the neutron spin structure functions $g^n_1 (x,Q^2)$ and $g^n_2(x,Q^2)$ over the range $0.03 < x < 0.6$ at an average $Q^2$ of 2 (GeV$/c)^2$. The data are used for the evaluation of the Ellis-Jaffe and Bjorken sum rules. The neutron spin structure function $g^n_1 (x,Q^2)$ is small and negative within the range of our measurement, yielding an integral ${\int_{0.03}^{0.6} g_1^n(x) dx}= -0.028 \pm 0.006 (stat) \pm 0.006 (syst)$. Assuming Regge behavior at low $x$, we extract $\Gamma_1^n=\int^1_0 g^n_1(x)dx = -0.031 \pm 0.006 (stat)\pm 0.009 (syst)$. Combined with previous proton integral results from SLAC experiment E143, we find $\Gamma_1^p - evaluated using$\alpha_s = 0.32\pm 0.05$

Steric sea level variability (1993-2010) in an ensemble of ocean reanalyses and objective analyses

Quantifying the effect of the seawater density changes on sea level variability is of crucial importance for climate change studies, as the sea level cumulative rise can be regarded as both an important climate change indicator and a possible danger for human activities in coastal areas. In this work, as part of the Ocean Reanalysis Intercomparison Project, the global and regional steric sea level changes are estimated and compared from an ensemble of 16 ocean reanalyses and 4 objective analyses. These estimates are initially compared with a satellite-derived (altimetry minus gravimetry) dataset for a short period (2003–2010). The ensemble mean exhibits a significant high correlation at both global and regional scale, and the ensemble of ocean reanalyses outperforms that of objective analyses, in particular in the Southern Ocean. The reanalysis ensemble mean thus represents a valuable tool for further analyses, although large uncertainties remain for the inter-annual trends. Within the extended intercomparison period that spans the altimetry era (1993–2010), we find that the ensemble of reanalyses and objective analyses are in good agreement, and both detect a trend of the global steric sea level of 1.0 and 1.1 ± 0.05 mm/year, respectively. However, the spread among the products of the halosteric component trend exceeds the mean trend itself, questioning the reliability of its estimate. This is related to the scarcity of salinity observations before the Argo era. Furthermore, the impact of deep ocean layers is non-negligible on the steric sea level variability (22 and 12 % for the layers below 700 and 1500 m of depth, respectively), although the small deep ocean trends are not significant with respect to the products spread

Large-scale genome sequencing of mycorrhizal fungi provides insights into the early evolution of symbiotic traits

Mycorrhizal fungi are mutualists that play crucial roles in nutrient acquisition in terrestrial ecosystems. Mycorrhizal symbioses arose repeatedly across multiple lineages of Mucoromycotina, Ascomycota, and Basidiomycota. Considerable variation exists in the capacity of mycorrhizal fungi to acquire carbon from soil organic matter. Here, we present a combined analysis of 135 fungal genomes from 73 saprotrophic, endophytic and pathogenic species, and 62 mycorrhizal species, including 29 new mycorrhizal genomes. This study samples ecologically dominant fungal guilds for which there were previously no symbiotic genomes available, including ectomycorrhizal Russulales, Thelephorales and Cantharellales. Our analyses show that transitions from saprotrophy to symbiosis involve (1) widespread losses of degrading enzymes acting on lignin and cellulose, (2) co-option of genes present in saprotrophic ancestors to fulfill new symbiotic functions, (3) diversification of novel, lineage-specific symbiosis-induced genes, (4) proliferation of transposable elements and (5) divergent genetic innovations underlying the convergent origins of the ectomycorrhizal guild. Mycorrhizal symbioses have evolved repeatedly in diverse fungal lineages. A large phylogenomic analysis sheds light on genomic changes associated with transitions from saprotrophy to symbiosis, including divergent genetic innovations underlying the convergent origins of the ectomycorrhizal guild.Peer reviewe

How Immunocontraception Can Contribute to Elephant Management in Small, Enclosed Reserves: Munyawana Population as a Case Study

Immunocontraception has been widely used as a management tool to reduce population growth in captive as well as wild populations of various fauna. We model the use of an individual-based rotational immunocontraception plan on a wild elephant, Loxodonta africana, population and quantify the social and reproductive advantages of this method of implementation using adaptive management. The use of immunocontraception on an individual, rotational basis stretches the inter-calving interval for each individual female elephant to a management-determined interval, preventing exposing females to unlimited long-term immunocontraception use (which may have as yet undocumented negative effects). Such rotational immunocontraception can effectively lower population growth rates, age the population, and alter the age structure. Furthermore, such structured intervention can simulate natural process such as predation or episodic catastrophic events (e.g., drought), which regulates calf recruitment within an abnormally structured population. A rotational immunocontraception plan is a feasible and useful elephant population management tool, especially in a small, enclosed conservation area. Such approaches should be considered for other long-lived, social species in enclosed areas where the long-term consequences of consistent contraception may be unknown

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

The Paleozoic Origin of Enzymatic Lignin Decomposition Reconstructed from 31 Fungal Genomes

Wood is a major pool of organic carbon that is highly resistant to decay, owing largely to the presence of lignin. The only organisms capable of substantial lignin decay are white rot fungi in the Agaricomycetes, which also contains non–lignin-degrading brown rot and ectomycorrhizal species. Comparative analyses of 31 fungal genomes (12 generated for this study) suggest that lignin-degrading peroxidases expanded in the lineage leading to the ancestor of the Agaricomycetes, which is reconstructed as a white rot species, and then contracted in parallel lineages leading to brown rot and mycorrhizal species. Molecular clock analyses suggest that the origin of lignin degradation might have coincided with the sharp decrease in the rate of organic carbon burial around the end of the Carboniferous period

Role of neutrophils in the regulation of IL-17A inflammatory response during pulmonary infection by mycobacteria

La pandémie de tuberculose (TB) causée par Mycobactérium tuberculosis (Mtb) n’est pas contrôlée par le vaccin vivant BCG. Mtb induit la formation de granulomes qui évoluent vers une réaction inflammatoire exacerbée détruisant le poumon lors de la TB active. Les rôles des polynucléaires neutrophiles (PNN) et de la cytokine inflammatoire IL-17A dans cette évolution sont à clarifier. Nous montrons, chez la souris, que les PNN sont recrutés dans le poumon en deux vagues après infection par Mtb ou BCG. La deuxième vague dépend du récepteur IL-17RA exprimé par les cellules non-hématopoïétiques. Les chimiokines CXCL-1 et 5 attirant les PNN semblent impliquées. Dans le poumon, ces PNN produisent la cytokine immunosuppressive IL-10 qui diminue la production d’IL-17A. Les cellules dendritiques infectées, présentes dans le granulome, sécrètent aussi CXCL-1. Elles attirent les PNN qui produisent de l’IL-10 bloquant la production d’IL-17A mais pas d’IFN-γ. En effet, seuls les lymphocytes CD4+ Th17 expriment le récepteur à l’IL-10. Nos travaux apportent un éclairage nouveau sur les PNN régulateurs dans le contrôle de inflammation due à l’IL-17A lors de la TB.Tuberculosis (TB) pandemic, caused by Mycobacterium tuberculosis (Mtb), is not controlled by the live vaccine BCG. Mtb induces granuloma formation developing to exacerbated inflammation that destroys the lung during active TB. Roles played by polymorphonuclear neutrophils (PMN) and inflammatory cytokine IL-17A remain ill defined. We show, in the mouse model, that PMN reach the lung in two waves following lung infection with BCG or Mtb. Only the second wave depends on receptor IL-17A expression by non hematopoietic cells. PMN chemoattractants CXCL-1 and 5 seem involved in this late recruitment. In the lung PMN produce immunosuppressive IL-10 that dampens IL-17A production. Mycobacteria infected dendritic cells, present inside granuloma, also secrete CXCL-1. Neutrophils attracted towards infected dendritic cells secrete IL-10 that inhibits IL-17A but not IFN-g production. Indeed, CD4+ Th17 and not Th1 express the IL-10 receptor. Our data shed new light on regulatory PMN in IL-17A-driven lung inflammation during TB