A physical map of the chicken genome

Strategies for assembling large, complex genomes have evolved to include a combination of whole-genome shotgun sequencing and hierarchal map-assisted sequencing. Whole-genome maps of all types can aid genome assemblies, generally starting with low-resolution cytogenetic maps and ending with the highest resolution of sequence. Fingerprint clone maps are based upon complete restriction enzyme digests of clones representative of the target genome, and ultimately comprise a near-contiguous path of clones across the genome. Such clone-based maps are used to validate sequence assembly order, supply long-range linking information for assembled sequences, anchor sequences to the genetic map and provide templates for closing gaps. Fingerprint maps are also a critical resource for subsequent functional genomic studies, because they provide a redundant and ordered sampling of the genome with clones. In an accompanying paper we describe the draft genome sequence of the chicken, Gallus gallus, the first species sequenced that is both a model organism and a global food source. Here we present a clone-based physical map of the chicken genome at 20-fold coverage, containing 260 contigs of overlapping clones. This map represents approximately 91% of the chicken genome and enables identification of chicken clones aligned to positions in other sequenced genomes

Altered promoter usage characterizes monoallelic transcription arising with ERBB2 amplification in human breast cancers

Analysis of a collection of human breast cancers (n = 150), enriched in ERBB2-positive cases (n = 57) and involving tumor genotyping relative to population-matched blood genotyping (n = 749) for a common ERBB2 single nucleotide polymorphism Ala(G)1170Pro(C), revealed that ERBB2 amplification in breast cancer is invariably monoallelic. Analysis of paired breast cancer and blood samples from informative (G1170C heterozygotic) ERBB2-positive (n = 12) and ERBB2-negative (n = 17) cases not only confirmed monoallelic amplification and ERBB2 transcriptional overexpression but also revealed that most low ERBB2 expressing breast cancers (12/17) exhibit unbalanced allelic transcription, showing 3-fold to nearly 5,000-fold preferential expression from one of two inherited alleles. To explore cis-acting transcriptional mechanisms potentially selected during ERBB2 amplification, levels of four different ERBB2 transcript variants (5.2, 4.7, 2.1, and 1.4 kb) were correlated with total (4.6 kb) ERBB2 mRNA levels in ERBB2-positive (n = 14) versus ERBB2-negative (n = 43) primary breast cancers. Relative expression of only the 2.1 kb extracellular domain-encoding splice variant and a 4.7 kb mRNA variant that uses an alternative start site were significantly increased in association with ERBB2-positivity, implicating altered promoter usage and selective transcript regulation within the ERBB2 amplicon. Altogether, these findings provide new mechanistic insights into the development of ERBB2-positive breast cancer and strong rationale for delineating candidate cis-acting regulatory elements that may link allele-specific ERBB2 transcription in premalignant breast epithelia with subsequent development of breast cancers bearing monoallelic ERBB2 amplicons

Contribution of Bordetella Filamentous Hemagglutinin and Adenylate Cyclase Toxin to Suppression and Evasion of Interleukin-17-Mediated Inflammation

Bordetella pertussis and Bordetella bronchiseptica establish respiratory infections with notorious efficiency. Our previous studies showed that the fhaB genes of B. pertussis and B. bronchiseptica, which encode filamentous hemagglutinin (FHA), are functionally interchangeable and provided evidence that FHA-deficient B. bronchiseptica induces more inflammation in the lungs of mice than wild-type B. bronchiseptica. We show here that the robust inflammatory response to FHA-deficient B. bronchiseptica is characterized by the early and sustained influx of interleukin-17 (IL-17)-positive neutrophils and macrophages and, at 72 h postinoculation, IL-17-positive CD4(+) T cells, suggesting that FHA allows the bacteria to suppress the development of an IL-17-mediated inflammatory response. We also show that the cyaA genes of B. pertussis and B. bronchiseptica, which encode adenylate cyclase toxin (ACT), are functionally interchangeable and that ACT, specifically its catalytic activity, is required for B. bronchiseptica to resist phagocytic clearance but is neither required for nor inhibitory of the induction of inflammation if bacteria are present in numbers sufficient to persist during the first 3 days postinoculation. Incubation of bone marrow-derived macrophages with a ΔcyaA strain caused decreased production of IL-1β and increased production of tumor necrosis factor alpha (TNF-α) and IL-12, while incubation with a ΔcyaA ΔfhaB strain caused increased production of IL-23. These data suggest that FHA and ACT both contribute to suppress the recruitment of neutrophils and the development of an IL-17-mediated immune response. To our knowledge, this is the first demonstration of a microbial pathogen suppressing IL-17-mediated inflammation in vivo as a strategy to evade innate immunity

SPHERE+: Imaging young Jupiters down to the snowline

SPHERE (Beuzit et al,. 2019) has now been in operation at the VLT for more than 5 years, demonstrating a high level of performance. SPHERE has produced outstanding results using a variety of operating modes, primarily in the field of direct imaging of exoplanetary systems, focusing on exoplanets as point sources and circumstellar disks as extended objects. The achievements obtained thus far with SPHERE (~200 refereed publications) in different areas (exoplanets, disks, solar system, stellar physics...) have motivated a large consortium to propose an even more ambitious set of science cases, and its corresponding technical implementation in the form of an upgrade. The SPHERE+ project capitalizes on the expertise and lessons learned from SPHERE to push high contrast imaging performance to its limits on the VLT 8m-telescope. The scientific program of SPHERE+ described in this document will open a new and compelling scientific window for the upcoming decade in strong synergy with ground-based facilities (VLT/I, ELT, ALMA, and SKA) and space missions (Gaia, JWST, PLATO and WFIRST). While SPHERE has sampled the outer parts of planetary systems beyond a few tens of AU, SPHERE+ will dig into the inner regions around stars to reveal and characterize by mean of spectroscopy the giant planet population down to the snow line. Building on SPHERE's scientific heritage and resounding success, SPHERE+ will be a dedicated survey instrument which will strengthen the leadership of ESO and the European community in the very competitive field of direct imaging of exoplanetary systems. With enhanced capabilities, it will enable an even broader diversity of science cases including the study of the solar system, the birth and death of stars and the exploration of the inner regions of active galactic nuclei

SPHERE+: Imaging young Jupiters down to the snowline

White paper submitted to ESO on Feb. 20th, 2020SPHERE (Beuzit et al,. 2019) has now been in operation at the VLT for more than 5 years, demonstrating a high level of performance. SPHERE has produced outstanding results using a variety of operating modes, primarily in the field of direct imaging of exoplanetary systems, focusing on exoplanets as point sources and circumstellar disks as extended objects. The achievements obtained thus far with SPHERE (~200 refereed publications) in different areas (exoplanets, disks, solar system, stellar physics...) have motivated a large consortium to propose an even more ambitious set of science cases, and its corresponding technical implementation in the form of an upgrade. The SPHERE+ project capitalizes on the expertise and lessons learned from SPHERE to push high contrast imaging performance to its limits on the VLT 8m-telescope. The scientific program of SPHERE+ described in this document will open a new and compelling scientific window for the upcoming decade in strong synergy with ground-based facilities (VLT/I, ELT, ALMA, and SKA) and space missions (Gaia, JWST, PLATO and WFIRST). While SPHERE has sampled the outer parts of planetary systems beyond a few tens of AU, SPHERE+ will dig into the inner regions around stars to reveal and characterize by mean of spectroscopy the giant planet population down to the snow line. Building on SPHERE's scientific heritage and resounding success, SPHERE+ will be a dedicated survey instrument which will strengthen the leadership of ESO and the European community in the very competitive field of direct imaging of exoplanetary systems. With enhanced capabilities, it will enable an even broader diversity of science cases including the study of the solar system, the birth and death of stars and the exploration of the inner regions of active galactic nuclei

SPHERE+: Imaging young Jupiters down to the snowline

SPHERE (Beuzit et al,. 2019) has now been in operation at the VLT for more than 5 years, demonstrating a high level of performance. SPHERE has produced outstanding results using a variety of operating modes, primarily in the field of direct imaging of exoplanetary systems, focusing on exoplanets as point sources and circumstellar disks as extended objects. The achievements obtained thus far with SPHERE (~200 refereed publications) in different areas (exoplanets, disks, solar system, stellar physics...) have motivated a large consortium to propose an even more ambitious set of science cases, and its corresponding technical implementation in the form of an upgrade. The SPHERE+ project capitalizes on the expertise and lessons learned from SPHERE to push high contrast imaging performance to its limits on the VLT 8m-telescope. The scientific program of SPHERE+ described in this document will open a new and compelling scientific window for the upcoming decade in strong synergy with ground-based facilities (VLT/I, ELT, ALMA, and SKA) and space missions (Gaia, JWST, PLATO and WFIRST). While SPHERE has sampled the outer parts of planetary systems beyond a few tens of AU, SPHERE+ will dig into the inner regions around stars to reveal and characterize by mean of spectroscopy the giant planet population down to the snow line. Building on SPHERE's scientific heritage and resounding success, SPHERE+ will be a dedicated survey instrument which will strengthen the leadership of ESO and the European community in the very competitive field of direct imaging of exoplanetary systems. With enhanced capabilities, it will enable an even broader diversity of science cases including the study of the solar system, the birth and death of stars and the exploration of the inner regions of active galactic nuclei

SPHERE+: Imaging young Jupiters down to the snowline

White paper submitted to ESO on Feb. 20th, 2020SPHERE (Beuzit et al,. 2019) has now been in operation at the VLT for more than 5 years, demonstrating a high level of performance. SPHERE has produced outstanding results using a variety of operating modes, primarily in the field of direct imaging of exoplanetary systems, focusing on exoplanets as point sources and circumstellar disks as extended objects. The achievements obtained thus far with SPHERE (\raisebox-0.5ex~200 refereed publications) in different areas (exoplanets, disks, solar system, stellar physics...) have motivated a large consortium to propose an even more ambitious set of science cases, and its corresponding technical implementation in the form of an upgrade. The SPHERE+ project capitalizes on the expertise and lessons learned from SPHERE to push high contrast imaging performance to its limits on the VLT 8m-telescope. The scientific program of SPHERE+ described in this document will open a new and compelling scientific window for the upcoming decade in strong synergy with ground-based facilities (VLT/I, ELT, ALMA, and SKA) and space missions (Gaia, JWST, PLATO and WFIRST). While SPHERE has sampled the outer parts of planetary systems beyond a few tens of AU, SPHERE+ will dig into the inner regions around stars to reveal and characterize by mean of spectroscopy the giant planet population down to the snow line. Building on SPHERE's scientific heritage and resounding success, SPHERE+ will be a dedicated survey instrument which will strengthen the leadership of ESO and the European community in the very competitive field of direct imaging of exoplanetary systems. With enhanced capabilities, it will enable an even broader diversity of science cases including the study of the solar system, the birth and death of stars and the exploration of the inner regions of active galactic nuclei