Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Using 3D Printing To Understand Vertebrate Form and Function

Using 3D Printing To Understand Vertebrate Form and Function

Molecular characterization and genetic diversity of Staphylococcus aureus isolates of dairy production farms in Rio de Janeiro, Brazil

Staphylococcus aureus is an important pathogen involved in subclinical bovine mastitis, causing high economic losses for the dairy industry. The successful persistence of this pathogen in the host occurs due to a series of factors associated with colonization ability and the acquisition of virulence factors. This bacterial species carries genetic heterogeneity, and genetically diverse strains characterize the population. Analysis of the genetic variation is an important tool for epidemiological studies. For this study, S. aureus strains were randomly selected by molecular profiling. All strains were originated from the milk of cows of subclinical mastitis on farms in the State of Rio de Janeiro. Strains of S. aureus were profiled using virulence gene analysis profiles, agr and spa typing, Pulsed Field Gel Electrophoresis (PFGE), and Multilocus Sequence Typing (MLST). 47% (8/17) of the tested strains were positive strains for icaA gene; 82.3% (14/17) for icaD gene; 41% (7/17) for fbnA gene; 47% (8/17) positive for fbnB gene; 94% (16/17) for the hlA gene and 70.5% (12/17) for hlB gene. These virulence results generated 11 different profiles. Most strains (58.8% - 10/17) were classified as type-II by agr system. spa typing identified seven different spa types. PFGE analysis found extensive genetic heterogeneity and no clones were observed. MLST analysis generated five different types of ST/CC. Considering the results observed at the present study, a high genetic variety of S. aureus strains associated of the presence of different virulence factors justified the absence of clonal strains at the properties evaluated. Besides, that, the definition of S. aureus clonal strain as well dynamic population in not fully understood since there are a limited number of studies in S. aureus associated with bovine mastitis

Overlapped Sequence Types (STs) and Serogroups of Avian Pathogenic (APEC) and Human Extra-Intestinal Pathogenic (ExPEC) <i>Escherichia coli</i> Isolated in Brazil

<div><p>Avian pathogenic <i>Escherichia coli</i> (APEC) strains belong to a category that is associated with colibacillosis, a serious illness in the poultry industry worldwide. Additionally, some APEC groups have recently been described as potential zoonotic agents. In this work, we compared APEC strains with extraintestinal pathogenic <i>E. coli</i> (ExPEC) strains isolated from clinical cases of humans with extra-intestinal diseases such as urinary tract infections (UTI) and bacteremia. PCR results showed that genes usually found in the ColV plasmid (<i>tsh</i>, <i>iuc</i>A, <i>iss</i>, and <i>hly</i>F) were associated with APEC strains while <i>fyu</i>A, <i>irp</i>-2, <i>fep</i>C <i>sit</i>D_chrom, <i>fim</i>H, <i>crl</i>, <i>csg</i>A, <i>afa</i>, <i>iha</i>, <i>sat</i>, <i>hly</i>A, <i>hra</i>, <i>cnf</i>1, <i>kps</i>MTII, <i>clpV</i>_Sakai and <i>mal</i>X were associated with human ExPEC. Both categories shared nine serogroups (O2, O6, O7, O8, O11, O19, O25, O73 and O153) and seven sequence types (ST10, ST88, ST93, ST117, ST131, ST155, ST359, ST648 and ST1011). Interestingly, ST95, which is associated with the zoonotic potential of APEC and is spread in avian <i>E. coli</i> of North America and Europe, was not detected among 76 APEC strains. When the strains were clustered based on the presence of virulence genes, most ExPEC strains (71.7%) were contained in one cluster while most APEC strains (63.2%) segregated to another. In general, the strains showed distinct genetic and fingerprint patterns, but avian and human strains of ST359, or ST23 clonal complex (CC), presented more than 70% of similarity by PFGE. The results demonstrate that some “zoonotic-related” STs (ST117, ST131, ST10CC, ST23CC) are present in Brazil. Also, the presence of moderate fingerprint similarities between ST359 <i>E. coli</i> of avian and human origin indicates that strains of this ST are candidates for having zoonotic potential.</p></div

Frequencies of sequence types (STs) among APEC (n = 76) and ExPEC (n = 53) strains isolated in Brazil.

<p>Frequencies of sequence types (STs) among APEC (n = 76) and ExPEC (n = 53) strains isolated in Brazil.</p

Dendrogram showing similarity relationship among APEC (n = 76) and human ExPEC (n = 53).

<p>Similarity was established by the presence of virulence genes, using the Pearson correlation (centered). Isolates were clustered by the complete linkage method. Legends adopt the following pattern: STRAIN ID/CATEGORY (either APEC or human ExPEC)/ECOR/ST (ST COMPLEX – if applicable)/SEROTYPE. Darker spots indicate the presence of the referred genes.</p

Frequencies of 43 virulence genes tested in APEC (n = 76) and ExPEC (n = 53) strains from Brazil.

1<p>Serine protease autotransporter.</p>2<p>Escape from host defenses.</p>3<p>Type VI secretion system.</p