Summary
Identification of genomic variants within dogs is important for understanding genetic factors contributing to breed diversity and phenotypic traits. This study aimed to identify sources of ...variation in the Bullmastiff using high‐density signal intensity and whole‐genome sequence data. Close to 3000 copy number variants (CNVs) were identified in Bullmastiff dogs using Canine HD BeadChip data. When CNVs were collated, 82 CNV regions (CNVRs) were detected, 50% in transcribed regions encompassing 432 genes. Fifty of the CNVRs detected have not been reported in other breeds and represent potential breed‐specific variants. A proportion of the CNVR variants with predicted modifying effects on gene pathways may contribute to breed traits. Approximately 5 million putative variants per dog, inclusive of single nucleotide polymorphisms (SNPs), multi‐nucleotide polymorphisms (MNPs) and insertion and deletions (INDELs), were identified from DNA sequence data on a small number of animals. Identification of genetic variants in the Bullmastiff highlights sources of variation in the breed and molecular markers that will assist in future trait and disease investigations in dogs.
Abstract
Natural variability in menstrual cycle length, coupled with rapid changes in endometrial gene expression, makes it difficult to accurately define and compare different stages of the ...endometrial cycle. Here we develop and validate a method for precisely determining endometrial cycle stage based on global gene expression. Our ‘molecular staging model’ reveals significant and remarkably synchronised daily changes in expression for over 3400 endometrial genes throughout the cycle, with the most dramatic changes occurring during the secretory phase. Our study significantly extends existing data on the endometrial transcriptome, and for the first time enables identification of differentially expressed endometrial genes with increasing age and different ethnicities. It also allows reinterpretation of all endometrial RNA-seq and array data that has been published to date. Our molecular staging model will significantly advance understanding of endometrial-related disorders that affect nearly all women at some stage of their lives, such as heavy menstrual bleeding, endometriosis, adenomyosis, and recurrent implantation failure.
Abstract
The etiology and pathogenesis of endometriosis are complex with both genetic and environmental factors contributing to disease risk. Genome-wide association studies (GWAS) have identified ...multiple signals in the estrogen receptor 1 (ESR1) region associated with endometriosis and other reproductive traits and diseases. In addition, candidate gene association studies identified signals in the ESR1 region associated with endometriosis risk suggesting genetic regulation of genes in this region may be important for reproductive health. This study aimed to investigate hormonal and genetic regulation of genes in the ESR1 region in human endometrium. Changes in serum oestradiol and progesterone concentrations and expression of hormone receptors ESR1 and progesterone receptor (PGR) were assessed in endometrial samples from 135 women collected at various stages of the menstrual cycle. Correlation between hormone concentrations, receptor expression and expression of genes in the ESR1 locus was investigated. The effect of endometriosis risk variants on expression of genes in the region was analyzed to identify gene targets. Hormone concentrations and receptor expression varied significantly across the menstrual cycle. Expression of genes in the ESR1 region correlated with progesterone concentration; however, they were more strongly correlated with expression of ESR1 and PGR suggesting coregulation of genes. There was no evidence that endometriosis risk variants directly regulated expression of genes in the region. Limited sample size and cellular heterogeneity in endometrial tissue may impact the ability to detect significant genetic effects on gene expression. Effects of these variants should be validated in a larger dataset and in relevant individual cell types.
Abstract
Endometriotic lesions are composed in part of endometrial-like stromal cells, however, there is a shortage of immortalized human endometrial stromal cultures available for research. As ...genetic factors play a role in endometriosis risk, it is important that genotype is also incorporated into analysis of pathological mechanisms. Human telomerase reverse transcriptase (hTERT) immortalization (using Lenti-hTERT-green fluorescent protein virus) took place following genotype selection; 13 patients homozygous for either the risk or non-risk ‘other’ allele for one or more important endometriosis risk single nucleotide polymorphism on chromosome 1p36.12 (rs3820282, rs56318008, rs55938609, rs12037376, rs7521902 or rs12061255). Short tandem repeat DNA profiling validated that donor tissue matched that of the immortalized cell lines and confirmed that cultures were genetically novel. Expression of morphological markers (vimentin and cytokeratin) and key genes of interest (telomerase, estrogen and progesterone receptors and LINC00339) were examined and functional assays for cell proliferation, steroid hormone and inflammatory responses were performed for 7/13 cultures. All endometrial stromal cell lines maintained their fibroblast-like morphology (vimentin-positive) and homozygous endometriosis-risk genotype following introduction of hTERT. Furthermore, the new stromal cultures demonstrated positive and diverse responses to hormones (proliferation and decidualisation changes) and inflammation (dose-dependent response), while maintaining hormone receptor expression. In conclusion, we successfully developed a range of human endometrial stromal cell lines that carry important endometriosis-risk alleles. The wider implications of this approach go beyond advancing endometriosis research; these cell lines will be valuable tools for multiple endometrial pathologies offering a level of genetic and phenotypic diversity not previously available.
Mass vaccination with the measles-mumps-rubella (MMR) vaccine for children aged 12-15 months was introduced in 1988; schoolgirl vaccination was discontinued in 1996 and replaced by a second dose of ...MMR for preschool children and post-partum vaccination of susceptible women identified through antenatal testing. In the UK, declining uptake rates due to concerns about the MMR vaccine, and increasing numbers of cases in some European countries where rubella surveillance and preconceptional vaccination are inadequate, coupled with poor uptake rates, has started to show in the number of rubella-susceptible patients presenting at antenatal clinics (ANCs). In this study, samples were collected in serum separator tubes at the West Middlesex University Hospital (WMUH) ANC and sent to the laboratory. Rubella status was determined using a third-generation rubella IgG enzyme immunoassay. Any negative results were retested and confirmed using an alternative method. The concentrations were expressed as iu/mL (World Health Organization WHO standard). Over a five-year period, the number of rubella-susceptible patients increased from 4.1% to 6.8% of the total number of specimens tested. The current population susceptibility levels seem to be influenced by a number of factors: the target population, age at vaccination and the level of coverage, and exposure to wild virus.
Historically, the weighing out and manipulation of dangerous chemicals frequently occurred without adequate protection from inhalation or accidental ingestion. The use of gloves, eye protection using ...goggles, masks or visors was scant. From Canary Girls and chimney sweeps to miners, stone cutters and silo fillers, these are classic exemplars of the subtle (and in some cases not so subtle) effects that substances, environments and practices can have on individual health.
The ASTRODEEP Frontier Fields catalogues Di Criscienzo, M.; Merlin, E.; Castellano, M. ...
Astronomy and astrophysics (Berlin),
11/2017, Volume:
607
Journal Article
Peer reviewed
Open access
Aims. We present the multiwavelength photometry of two Frontier Fields massive galaxy clusters, MACS-J0717 and MACS-J1149, and their parallel fields, ranging from Hubble Space Telescope (HST) to ...ground-based K and Spitzer IRAC bands, and the public release of photometric redshifts and rest-frame properties of galaxies found in cluster and parallel pointings. This work was carried out within the ASTRODEEP project and aims to provide a reference for future investigations of extragalactic populations. Methods. To fully exploit the depth of the images and detect faint sources, we used an accurate procedure, which carefully removes the foreground light of bright cluster sources and the intra-cluster light thus enabling detection and measurement of accurate fluxes in crowded cluster regions. This same procedure has been successfully used to derive the photometric catalogue of MACS-J0416 and Abell-2744. Results. The obtained multiband photometry was used to derive photometric redshifts, magnification, and physical properties of sources. In line with the first two FF catalogues released by ASTRODEEP, the photometric redshifts reach ~4% accuracy. Moreover we extend the presently available samples to galaxies intrinsically as faint as H160 ~ 32–34 mag thanks to the magnification factors induced by strong gravitational lensing. Our analysis allows us to probe galaxy masses larger than 107 M⊙ and/or SFR = 0.1–1 M⊙/yr out to redshift z> 6.
The risk of infection associated with occupations can, and does, extend to certain leisure and sports activities. Generally, such pastimes are regarded as important for human health and mental ...wellbeing. However, infections may, rarely, be acquired during leisure activities that include water sports and water-related relaxation, and certain sports.
Laboratory-acquired infections are as old as laboratories themselves. As soon as the culture of microorganisms was introduced, so too was their transfer to laboratory workers. It is only in ...relatively recent history that such infections have been fully understood, and methods of spread and their prevention or avoidance developed. This paper endeavours to provide an overview of the history of laboratory-acquired infection and the steps taken, particularly in the UK, for its prevention.
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