Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species

Drivers of genetic diversity in secondary metabolic gene clusters within a fungal speciesFilamentous fungi produce a diverse array of secondary metabolites (SMs) critical for defense, virulence, and communication. The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes, an atypical arrangement for metabolic pathways in other eukaryotes. Comparative studies of filamentous fungal species have shown that SM gene clusters are often either highly divergent or uniquely present in one or a handful of species, hampering efforts to determine the genetic basis and evolutionary drivers of SM gene cluster divergence. Here, we examined SM variation in 66 cosmopolitan strains of a single species, the opportunistic human pathogen Aspergillus fumigatus. Investigation of genome-wide within-species variation revealed 5 general types of variation in SM gene clusters: nonfunctional gene polymorphisms; gene gain and loss polymorphisms; whole cluster gain and loss polymorphisms; allelic polymorphisms, in which different alleles corresponded to distinct, nonhomologous clusters; and location polymorphisms, in which a cluster was found to differ in its genomic location across strains. These polymorphisms affect the function of representative A. fumigatus SM gene clusters, such as those involved in the production of gliotoxin, fumigaclavine, and helvolic acid as well as the function of clusters with undefined products. In addition to enabling the identification of polymorphisms, the detection of which requires extensive genome-wide synteny conservation (e.g., mobile gene clusters and nonhomologous cluster alleles), our approach also implicated multiple underlying genetic drivers, including point mutations, recombination, and genomic deletion and insertion events as well as horizontal gene transfer from distant fungi. Finally, most of the variants that we uncover within A. fumigatus have been previously hypothesized to contribute to SM gene cluster diversity across entire fungal classes and phyla. We suggest that the drivers of genetic diversity operating within a fungal species shown here are sufficient to explain SM cluster macroevolutionary patterns.National Science Foundation (grant number DEB-1442113). Received by AR. U.S. National Library of Medicine training grant (grant number 2T15LM007450). Received by ALL. Conselho Nacional de Desenvolvimento Cientı´fico e 573 Tecnológico. Northern Portugal Regional Operational Programme (grant number NORTE-01- 0145-FEDER-000013). Received by FR. Fundação de Amparo à Pesquisa do 572 Estado de São Paulo. Received by GHG. National Institutes of Health (grant number R01 AI065728-01). Received by NPK. National Science Foundation (grant number IOS-1401682). Received by JHW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Maternal smoking during pregnancy and offspring overweight : is there a dose–response relationship? An individual patient data meta-analysis

We want to thank the funders of the individual studies: the UK Medical Research Council and the Wellcome Trust (Grant ref: 102215/2/13/2) and the University of Bristol, the Danish National Research Foundation, Pharmacy Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation, and the Health Foundation, the US NICHD (contracts no. 1-HD-4-2803 and no. 1-HD-1-3127, R01 HD HD034568), the NHMRC, the CNPq (Portuguese acronym for the National Research Council—grant 523474/96-2) and FAPESP (Portuguese acronym for the São Paulo State Research Council—grant 00/0908-7). We would like to thank the participating families of all studies for the use of data. For the ASPAC study, we want to thank the midwives for their help in recruiting families, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. This work was supported by the Deutschen Forschungsgesellschaft (German Research Foundation, DFG) [KR 1926/9-1, KU1443/4-1]. Dr. Gilman’s contribution was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.Peer reviewedPostprin

The 'neutron deficit' in the JET tokamak

The measured D-D neutron rate of neutral beam heated JET baseline and hybrid H-modes in deuterium is found to be between approximately 50% and 100% of the neutron rate expected from the TRANSP code, depending on the plasma parameters. A number of candidate explanations for the shortfall, such as fuel dilution, errors in beam penetration and effectively available beam power have been excluded. As the neutron rate in JET is dominated by beam-plasma interactions, the 'neutron deficit' may be caused by a yet unidentified form of fast particle redistribution. Modelling, which assumes fast particle transport to be responsible for the deficit, indicates that such redistribution would have to happen at time scales faster than both the slowing down time and the energy confinement time. Sawteeth and edge localised modes are found to make no significant contribution to the deficit. There is also no obvious correlation with magnetohydrodynamic activity measured using magnetic probes at the tokamak vessel walls. Modelling of fast particle orbits in the 3D fields of neoclassical tearing modes shows that realistically sized islands can only contribute a few percent to the deficit. In view of these results it appears unlikely that the neutron deficit results from a single physical process in the plasma

The 'neutron deficit' in the JET tokamak

The measured D-D neutron rate of neutral beam heated JET baseline and hybrid H-modes in deuterium is found to be between approximately 50% and 100% of the neutron rate expected from the TRANSP code, depending on the plasma parameters. A number of candidate explanations for the shortfall, such as fuel dilution, errors in beam penetration and effectively available beam power have been excluded. As the neutron rate in JET is dominated by beam-plasma interactions, the 'neutron deficit' may be caused by a yet unidentified form of fast particle redistribution. Modelling, which assumes fast particle transport to be responsible for the deficit, indicates that such redistribution would have to happen at time scales faster than both the slowing down time and the energy confinement time. Sawteeth and edge localised modes are found to make no significant contribution to the deficit. There is also no obvious correlation with magnetohydrodynamic activity measured using magnetic probes at the tokamak vessel walls. Modelling of fast particle orbits in the 3D fields of neoclassical tearing modes shows that realistically sized islands can only contribute a few percent to the deficit. In view of these results it appears unlikely that the neutron deficit results from a single physical process in the plasma

Fractalopolis : a fractal concept for the sustainable development of metropolitean areas

International audienceThe debate about how to manage sustainable development on the scaleof metropolitan areas is still ongoing. Many scholars blame urban sprawl with itsconcomitant pollution and energy consumption for exacerbating traffic congestionand harming the natural environment. The present chapter develops a nuanced viewof suburbanization focusing on social demand and environmental issues. It wouldbe pointless to simply dismiss suburbanization.We show how the scaling propertiesof fractal geometry can help in designing development scenarios that optimize thespatial organization of metropolitan areas. The fractal concept meets the needs ofresidents while addressing various environmental issues

Bandgap Engineering of Quantum Semiconductor Microstructures

International audienc