Copy number variation mapping and genomic variation of autochthonous and commercial turkey populations

This study aims at investigating genomic diversity of several turkey populations using Copy Number Variants (CNVs). A total of 115 individuals from six Italian breeds (Colle Euganei, Bronzato Comune Italiano, Parma e Piacenza, Brianzolo, Nero d\u2019Italia, and Ermellinato di Rovigo), seven Narragansett, 38 commercial hybrids, and 30 Mexican turkeys, were genotyped with the Affymetrix 600K single nucleotide polymorphism (SNP) turkey array. The CNV calling was performed with the Hidden Markov Model of PennCNV software and with the Copy Number Analysis Module of SVS 8.4 by Golden Helix\uae. CNV were summarized into CNV regions (CNVRs) at population level using BEDTools. Variability among populations has been addressed by hierarchical clustering (pvclust R package) and by principal component analysis (PCA). A total of 2,987 CNVs were identified covering 4.65% of the autosomes of the Turkey_5.0/melGal5 assembly. The CNVRs identified in at least two individuals were 362\u2014189 gains, 116 losses, and 57 complexes. Among these regions the 51% contain annotated genes. This study is the first CNV mapping of turkey population using 600K chip. CNVs clustered the individuals according to population and their geographical origin. CNVs are known to be indicators also of adaptation, as some researches in different species are suggesting

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

Copy number variants reveal genomic diversity in a Mexican Creole cattle population

Mexican Creole Cattle (MCC) derived from cattle of the Iberian Peninsula, mainly from Andaluc\ueda and Extremadura, and were introduced in central America the 16th century. Copy Number Variants (CNVs) are structural variants contributing to the genetic diversity among populations and related to variation in phenotypic expression. More than half of the identified CNVs regions in human and livestock include protein-coding genes involved in essential function, as cellular functionality, metabolic pathways and disease susceptibility. The aim of this study is to investigate the CNVs genomic variation in the MCC population. A total of 48 unrelated individuals (5 males and 43 females) were genotyped with the BovineHD Genotyping BeadChip Illumina, containing 7,77,962 polymorphic SNPs. A total of 2170 CNVs were detected in 40 individuals, summarized into 733 CNV regions, covering 32.1 Mb of the bovine autosome genome. Functional analysis of the CNVRs identified 131 genes mainly involved in immune response and inflammation, and 923 overlapping QTL classified in six difference QTL-term categories. Cluster and PCA analyses showed a samples distribution in concordance with the geographical origins of the sub-populations, highlighting both a sharing genetic background together with a diversification of populations as a response to adaptation to different and adverse environments

Design and Construction of the Full-Length Prototype of the 11-T Dipole Magnet for the High Luminosity LHC Project at CERN

The luminosity upgrade of the Large Hadron Collider (LHC) at CERN requires the installation of additional collimators in the dispersion suppressor regions of the accelerator. The upgrade foresees the installation of one additional collimator on either side of interaction point 7 (IP7) at the location of the existing main dipoles (MBs) that will be replaced by shorter and more powerful dipoles, and of one additional collimator on either side of IP2 at the location of existing empty cryostats. This paper describes the design and the construction status of the full-length prototype of the 11-T dipole magnet, which is needed for IP7. This magnet features a two-in-one structure, like the LHC MB, impregnated coils made of Nb 3 Sn conductor, an inner bore of 60 mm, and a magnetic length of about 5.3 m. Two 11-T magnets are needed to replace a 15-m long MB. A by-pass cryostat placed in between the two magnets allows creating a room temperature space for the additional collimators. The magnet is designed to provide the same integrated field as the MB at nominal field. However, due to the difference in transfer function at lower field, a correction by means of a trim current has been considered. A full-length prototype is currently under construction at CERN with the goal of developing the manufacturing and inspection procedures prior to launch the series production. For this, new tooling has been developed and optimized during the fabrication of fully representative practice coils. This paper describes the design of the magnet, the main manufacturing steps, and corresponding quality indicators, which will be used to monitor the series production. Finally, the production and installation schedule will be presented

Design, assembly, and test of the CERN 2-m long 11 T dipole in single coil configuration

The upgrade of the LHC collimation system includes additional collimators in the LHC lattice. The longitudinal space for the collimators can be obtained by replacing some LHC main dipoles with shorter but stronger dipoles compatible with the LHC lattice and the existing powering circuits, cryogenics, and beam vacuum. A joint development programme aiming at building a 5.5 m long two-in-one aperture Nb3Sn dipole prototype suitable for installation in the LHC is being conducted by FNAL and CERN. As part of the first phase of the programme, 1 m and 2 m long single aperture models are being built and tested. Later on, the collared coils from these models will be assembled and tested in a two-in-one aperture configuration in both laboratories. A 2 m long practice model made of a single coil wound with Nb3Sn cable, MBHSM101, was developed and constructed at CERN. It has been completed, and tested at both 4.3 K and 1.9 K. This practice model features collared coils based on removable pole concept, S2-glass cable insulation braided over a mica layer, and coil end spacers made of sintered stainless steel with springy legs. The paper describes the main features of this practice model, the main manufacturing steps and the results of the cold tests

Interdiffusion in the Mg-Al System and Intrinsic Diffusion in beta-Mg2Al3

Solid-to-solid diffusion couples were assembled and annealed to examine the diffusion between pure Mg (99.96 pct) and Al (99.999 pct). Diffusion anneals were carried out at 573 K, 623 K and 673 K (300 A degrees C, 350 A degrees C and 400 A degrees C) for 720, 360, and 240 hours, respectively. Optical and scanning electron microscopes were used to identify the formation of the intermetallic phases, gamma-Mg17Al12, and beta-Mg2Al3, as well as the absence of the epsilon-Mg23Al30 in the diffusion couples. The thicknesses of the gamma-Mg17Al12 and beta-Mg2Al3 phases were measured and the parabolic growth constants were calculated to determine the activation energies for growth. Concentration profiles were determined with electron microprobe analysis using pure elemental standards. Composition-dependent interdiffusion coefficients in Mg-solid solution, gamma-Mg17Al12, beta-Mg2Al3, and Al-solid solutions were calculated based on the Boltzmann-Matano analysis. Integrated and average effective interdiffusion coefficients for each phase were also calculated, and the magnitude was the highest for the beta-Mg2Al3 phase, followed by gamma-Mg17Al12, Al-solid solution, and Mg-solid solution. Intrinsic diffusion coefficients based on Huemann\u27s analysis (e.g., marker plane) were determined for the similar to Mg-62 at. pct Al in the beta-Mg2Al3 phase. Activation energies and the pre-exponential factors for the interdiffusion and intrinsic diffusion coefficients were calculated for the temperature range examined. The beta-Mg2Al3 phase was found to have the lowest activation energies for growth and interdiffusion among all four phases studied. At the marker location in the beta-Mg2Al3 phase, the intrinsic diffusion of Al was found to be faster than that of Mg. Extrapolations of the impurity diffusion coefficients in the terminal solid solutions were made and compared with the available self-diffusion and impurity diffusion data from the literature. Thermodynamic factor, tracer diffusion coefficients, and atomic mobilities at the marker plane composition were approximated using the available literature values of Mg activity in the beta-Mg2Al3 phase

Regulated expression of glutamyl-tRNA synthetase is directed by a mobile genetic element in the cyanobacterium Tolypothrix sp. PCC 7601

International audienceThe genome of Tolypothrix sp. PCC 7601 carries two copies of a novel insertion sequence, ISTosp1. One of the two copies is located upstream of the gene encoding glutamyl-tRNA synthetase, an enzyme playing a key role in protein and pigment synthesis. The tnpA gene of the IS element and gltX were co-transcribed and their expression was transiently upregulated upon retrieval of the ammonium source irrespective of whether nitrate or no nitrogen source were available. The second copy is also transcribed and shows a similar regulatory pattern. Structural elements of the promoter (-10 and -35 sequences) directing the expression of the tnpA-gltX operon have been localized within the IS. Regulatory sequences involving the NtcA transcription factor in the control of tnpA-gltX expression were found both within and in sequences upstream of the insertion element. The expression of gltX in a closely related cyanobacterium, Nostoc sp. PCC 7120, which lacks the insertion upstream of gltX, decreased upon ammonium retrieval, a regulatory pattern that markedly differs from that observed in Tolypothrix sp. PCC 7601. ISTosp1 constitutes a good example of how cells can make use of a transposable element to evolve an original regulatory mechanism