Genetics of tibia bone properties of crossbred commercial laying hens in different housing systems

Osteoporosis and bone fractures are a severe problem for the welfare of laying hens, with genetics and environment, such as housing system, each making substantial contributions to bone strength. In this work, we performed genetic analyses of bone strength, bone mineral density, and bone composition, as well as body weight, in 860 commercial crossbred laying hens from 2 different companies, kept in either furnished cages or floor pens. We compared bone traits between housing systems and crossbreds and performed a genome-wide association study of bone properties and body weight. As expected, the 2 housing systems produced a large difference in bone strength, with layers housed in floor pens having stronger bones. These differences were accompanied by differences in bone geometry, mineralization, and chemical composition. Genome scans either combining or independently analyzing the 2 housing systems revealed no genome-wide significant loci for bone breaking strength. We detected 3 loci for body weight that were shared between the housing systems on chromosomes 4, 6, and 27 (either genome-wide significant or suggestive) and these coincide with associations for bone length. In summary, we found substantial differences in bone strength, content, and composition between hens kept in floor pens and furnished cages that could be attributed to greater physical activity in pen housing. We found little evidence for large-effect loci for bone strength in commercial crossbred hens, consistent with a highly polygenic architecture for bone strength in the production environment. The lack of consistent genetic associations between housing systems in combination with the differences in bone phenotypes could be due to gene-by-environment interactions with housing system or a lack of power to detect shared associations for bone strength

The role of OCT-A in retinal disease management

Optical coherence tomography angiography (OCT-A) is a non-invasive, non-dye-based imaging modality that has the potential to enhance our understanding of retinal diseases. While this rapidly advancing imaging modality offers great potential, there is a need for community-wide understanding of the range of technologies and methods for interpreting the images, as well as a need to enhance understanding of images from disease-free eyes for reference when screening for retinal diseases. Importantly, clinical trials have been designed without OCT-A-based endpoints; therefore, caution is required when making treatment decisions based on OCT-A imaging alone. With this in mind, a full understanding of the advantages and limitations of OCT-A will be vital for effective development of the technique within the field of ophthalmology. On behalf of the Vision Academy Steering Committee (sponsored by Bayer), this publication summarizes the views of the authors on the current use of OCT-A imaging and explores its potential for future applications in research and clinical practice

No evidence that selection for egg production persistency causes loss of bone quality in laying hens

Background The physiological adaptations that have evolved for egg laying make hens susceptible to bone fractures and keel bone damage. In modern laying hen breeds, longer periods of egg laying could result in a greater risk of poor bone quality, and selection for increased egg production has frequently been stated to be a cause. However, the existing literature does not support this hypothesis. To test the hypothesis that egg production is associated with quality, breaking strength and density of bone, genetic correlations between these traits were estimated in White Leghorn and Rhode Island Red breeds. Genetic correlations of cortical and medullary bone material chemical properties with bone quality were also estimated, in order to identify methods to improve bone quality with appropriately targeted measurement of key traits. Results Estimates of heritability for bone quality traits were moderate (0.19-0.59) for both White Leghorn and Rhode Island Red breeds, except for the keel bone trait, which had a heritability estimate equal to zero. There was no evidence for genetic or phenotypic relationships between post-peak egg production and bone quality. In the White Leghorn breed, the estimate of the genetic correlation between pre-peak production/age at first egg and bone quality was significant and negative (- 0.7 to - 0.4). Estimates of heritability of thermogravimetric measurements of tibial medullary bone mineralisation were significant (0.18-0.41), as were estimates of their genetic correlations with tibia breaking strength and density (0.6-0.9). Conclusions The low genetic correlation of post-peak egg production with bone quality suggests that selection for increased persistency of egg production may not adversely affect bone quality. Onset of puberty and mineralisation of the medullary bone, which is a specialised adaptation for egg laying, were identified as important factors associated with the quality of the skeleton later during egg production. These are traits for which genetic, as well as environmental and management factors can positively impact the overall quality of the skeleton of laying hens

Genetics of tibia bone properties of crossbred commercial laying hens in different housing systems

Osteoporosis and bone fractures are a severe problem for the welfare of laying hens, with genetics and environment, such as housing system, each making substantial contributions to bone strength. In this work, we performed genetic analyses of bone strength, bone mineral density, and bone composition, as well as body weight, in 860 commercial crossbred laying hens from 2 different companies, kept in either furnished cages or floor pens. We compared bone traits between housing systems and crossbreds and performed a genome-wide association study of bone properties and body weight. As expected, the 2 housing systems produced a large difference in bone strength, with layers housed in floor pens having stronger bones. These differences were accompanied by differences in bone geometry, mineralization, and chemical composition. Genome scans either combining or independently analyzing the 2 housing systems revealed no genome-wide significant loci for bone breaking strength. We detected 3 loci for body weight that were shared between the housing systems on chromosomes 4, 6, and 27 (either genome-wide significant or suggestive) and these coincide with associations for bone length. In summary, we found substantial differences in bone strength, content, and composition between hens kept in floor pens and furnished cages that could be attributed to greater physical activity in pen housing. We found little evidence for large-effect loci for bone strength in commercial crossbred hens, consistent with a highly polygenic architecture for bone strength in the production environment. The lack of consistent genetic associations between housing systems in combination with the differences in bone phenotypes could be due to gene-by-environment interactions with housing system or a lack of power to detect shared associations for bone strength

An eQTL in the cystathionine beta synthase gene is linked to osteoporosis in laying hens

Background Skeletal damage is a challenge for laying hens because the physiological adaptations required for egg laying make them susceptible to osteoporosis. Previously, we showed that genetic factors explain 40% of the variation in end of lay bone quality and we detected a quantitative trait locus (QTL) of large effect on chicken chromosome 1. The aim of this study was to combine data from the commercial founder White Leghorn population and the F2 mapping population to fine-map this QTL and understand its function in terms of gene expression and physiology. Results Several single nucleotide polymorphisms on chromosome 1 between 104 and 110 Mb (galGal6) had highly significant associations with tibial breaking strength. The alternative genotypes of markers of large effect that flanked the region had tibial breaking strengths of 200.4 vs. 218.1 Newton (P < 0.002) and, in a subsequent founder generation, the higher breaking strength genotype was again associated with higher breaking strength. In a subsequent generation, cortical bone density and volume were increased in individuals with the better bone genotype but with significantly reduced medullary bone quality. The effects on cortical bone density were confirmed in a further generation and was accompanied by increased mineral maturity of the cortical bone as measured by infrared spectrometry and there was evidence of better collagen cross-linking in the cortical bone. Comparing the transcriptome of the tibia from individuals with good or poor bone quality genotypes indicated four differentially-expressed genes at the locus, one gene, cystathionine beta synthase (CBS), having a nine-fold higher expression in the genotype for low bone quality. The mechanism was cis-acting and although there was an amino-acid difference in the CBS protein between the genotypes, there was no difference in the activity of the enzyme. Plasma homocysteine concentration, the substrate of CBS, was higher in the poor bone quality genotype. Conclusions Validated markers that predict bone strength have been defined for selective breeding and a gene was identified that may suggest alternative ways to improve bone health in addition to genetic selection. The identification of how genetic variants affect different aspects of bone turnover shows potential for translational medicine

Latin American chronic urticaria registry (CUR) contribution to the understanding and knowledge of the disease in the region

Chronic urticaria (CU) has a widespread spectrum on causal or exacerbating factors, clinical manifestations, therapeutic response and quality of life affectation. Registries are useful tools in several real-life diagnosis and management approach. We aimed to evaluate the characteristics of CU patients living in Latin America through an original cross-sectional registry with data entered by regional allergologists. Results: Three hundred patients were included, being 72% female, with median age of 36 years (1\u201385) and 20 months of CU median evolution time. The cause of CU was reported as unknown in 72% of them. Thirty-nine percent of suspected cases presented positive serology for Mycoplasma, positive autologous serum skin test (ASST) was reported in 47%, and occasional presence of thyroid or antinuclear autoantibodies and parasites. The impact of pruritus in their quality of life was moderate to severe in 60% of patients, with almost 3 out of four patients having partial or lack of urticaria control with anti-histamines. Conclusions: Our registry provides retrospective data on the real-life assistance of a large number of patients from the region. Continuous search for associated conditions and better treatment possibilities are needed, in order to control the significant impact on quality of life and the length of disease

Fitting the Gamma-Ray Spectrum from Dark Matter with DMFIT: GLAST and the Galactic Center Region

We study the potential of GLAST to unveil particle dark matter properties with gamma-ray observations of the Galactic center region. We present full GLAST simulations including all gamma-ray sources known to date in a region of 4 degrees around the Galactic center, in addition to the diffuse gamma-ray background and to the dark matter signal. We introduce DMFIT, a tool that allows one to fit gamma-ray emission from pair-annihilation of generic particle dark matter models and to extract information on the mass, normalization and annihilation branching ratios into Standard Model final states. We assess the impact and systematic effects of background modeling and theoretical priors on the reconstruction of dark matter particle properties. Our detailed simulations demonstrate that for some well motivated supersymmetric dark matter setups with one year of GLAST data it will be possible not only to significantly detect a dark matter signal over background, but also to estimate the dark matter mass and its dominant pair-annihilation mode.Comment: 37 pages, 16 figures, submitted to JCA

Bright ligand-activatable fluorescent protein for high-quality multicolor live-cell super-resolution microscopy

We introduce UnaG as a green-to-dark photoswitching fluorescent protein capable of high-quality super-resolution imaging with photon numbers equivalent to the brightest photoswitchable red protein. UnaG only fluoresces upon binding of a fluorogenic metabolite, bilirubin, enabling UV-free reversible photoswitching with easily controllable kinetics and low background under Epi illumination. The on- and off-switching rates are controlled by the concentration of the ligand and the excitation light intensity, respectively, where the dissolved oxygen also promotes the off-switching. The photo-oxidation reaction mechanism of bilirubin in UnaG suggests that the lack of ligand-protein covalent bond allows the oxidized ligand to detach from the protein, emptying the binding cavity for rebinding to a fresh ligand molecule. We demonstrate super-resolution single-molecule localization imaging of various subcellular structures genetically encoded with UnaG, which enables facile labeling and simultaneous multicolor imaging of live cells. UnaG has the promise of becoming a default protein for high-performance super-resolution imaging. Photoconvertible proteins occupy two color channels thereby limiting multicolour localisation microscopy applications. Here the authors present UnaG, a new green-to-dark photoswitching fluorescent protein for super-resolution imaging, whose activation is based on a noncovalent binding with bilirubin