Publications by authors named "Alan O'Doherty"

Information graphics or infographics combine visual representations of information or data with text. They have been used in health research to disseminate research findings, translate knowledge and address challenges in health communication to lay audiences. There is emerging evidence of the design of infographics with the involvement of patients and the public in health research.

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Pregnancy rates for in vitro produced (IVP) embryos are usually lower than for embryos produced in vivo after ovarian superovulation (MOET). This is potentially due to alterations in their trophectoderm (TE), the outermost layer in physical contact with the maternal endometrium. The main objective was to apply a multi-omics data integration approach to identify both temporally differentially expressed and differentially methylated genes (DEG and DMG), between IVP and MOET embryos, that could impact TE function.

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Sperm contributes genetic and epigenetic information to the embryo to efficiently support development. However, the mechanism underlying such developmental competence remains elusive. Here, we investigated whether all sperm cells have a common epigenetic configuration that primes transcriptional program for embryonic development.

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Bovine tuberculosis is caused by infection with , which can also cause disease in a range of other mammals, including humans. Alveolar macrophages are the key immune effector cells that first encounter and how the macrophage epigenome responds to mycobacterial pathogens is currently not well understood. Here, we have used chromatin immunoprecipitation sequencing (ChIP-seq), RNA-seq and miRNA-seq to examine the effect of infection on the bovine alveolar macrophage (bAM) epigenome.

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DNA methylation is pivotal in orchestrating gene expression patterns in various mammalian biological processes. Perturbation of the bovine alveolar macrophage (bAM) transcriptome, due to Mycobacterium bovis (M. bovis) infection, has been well documented; however, the impact of this intracellular pathogen on the bAM epigenome has not been determined.

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Background: Assisted reproductive technologies (ART) are widely used to treat fertility issues in humans and for the production of embryos in mammalian livestock. The use of these techniques, however, is not without consequence as they are often associated with inauspicious pre- and postnatal outcomes including premature birth, intrauterine growth restriction and increased incidence of epigenetic disorders in human and large offspring syndrome in cattle. Here, global DNA methylation profiles in the trophectoderm and embryonic discs of in vitro produced (IVP), superovulation-derived (SOV) and unstimulated, synchronised control day 17 bovine conceptuses (herein referred to as AI) were interrogated using the EmbryoGENE DNA Methylation Array (EDMA).

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A greater understanding of the key molecules associated with embryo development during human-assisted reproduction is imperative for the development of advanced diagnostics. Previous studies have shown that follicular microRNAs (miRNAs) are reliable markers of the polycystic ovarian syndrome (PCOS). Leveraging the utility of miRNAs in PCOS, the aim of this study was to identify miRNAs in human granulosa cells that may be indicative of blastocyst development.

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Here we interrogated, using three separate but complementary experimental approaches, the impact of vitamin B availability and methotrexate exposure on Daphnia magna, which we hypothesised should have an opposite effect on One carbon metabolism (OCM). OCM is a vital biological process supporting a variety of physiological processes, including DNA methylation. Contrary to mammalian models, this process remains largely unexplored in invertebrates.

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In a recent genome-wide association study, 40 Fleckvieh bulls with exceptionally poor fertility were found to be homozygous for a nonsense mutation in the transmembrane protein 95 (TMEM95) encoding gene. Ejaculates from these individuals exhibited normal sperm concentration, morphology, viability, and motility. However, only 1.

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Monoallelically expressed genes that exert their phenotypic effect in a parent-of-origin specific manner are considered to be subject to genomic imprinting, the most well understood form of epigenetic regulation of gene expression in mammals. The observed differences in allele specific gene expression for imprinted genes are not attributable to differences in DNA sequence information, but to specific chemical modifications of DNA and chromatin proteins. Since the discovery of genomic imprinting some three decades ago, over 100 imprinted mammalian genes have been identified and considerable advances have been made in uncovering the molecular mechanisms regulating imprinted gene expression.

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Background: In mammals, maternal differentially methylated regions (DMRs) acquire DNA methylation during the postnatal growth stage of oogenesis, with paternal DMRs acquiring DNA methylation in the perinatal prospermatagonia. Following fusion of the male and female gametes, it is widely accepted that murine DNA methylation marks at the DMRs of imprinted genes are stable through embryogenesis and early development, until they are reprogrammed in primordial germ cells. However, the DNA methylation dynamics at DMRs of bovine imprinted genes during early stages of development remains largely unknown.

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Sperm undergo some of the most extensive chromatin modifications seen in mammalian biology. During male germline development, paternal DNA methylation marks are erased and established on a global scale through waves of demethylation and de novo methylation. As spermatogenesis progresses, the majority of the histones are removed and replaced by protamines, enabling a tighter packaging of the DNA and transcriptional shutdown.

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Ovarian follicle development in post-partum, high-producing dairy cows, occurs in a compromised endogenous metabolic environment (referred to as negative energy balance, NEB). Key events that occur during oocyte/follicle growth, such as the vital process of genomic imprinting, may be detrimentally affected by this altered ovarian environment. Imprinting is crucial for placental function and regulation of fetal growth, therefore failure to establish and maintain imprints during oocyte growth may contribute to early embryonic loss.

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Background: Oocytes and early embryos contain minute amounts of DNA, RNA and proteins, making the study of early mammalian development highly challenging. The study of the embryo epigenome, in particular the DNA methylome, has been made accessible thanks to the possibility of amplifying specific sequences according to their initial methylation status. This paper describes a novel platform dedicated to the genome-wide study of bovine DNA methylation, including a complete pipeline for data analysis and visualization.

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Chito-oligosaccharide (COS) is a natural bioactive compound, which has been shown to suppress lipid metabolic genes and lipid accumulation in differentiating adipocytes. Leptin has been identified as a key regulator of energy homeostasis and is known to be under epigenetic regulation during adipogenesis. Hence, the first objective of this experiment was to compare leptin gene (LEP) expression and leptin secretion during the different stages of adipogenesis and to investigate the effect of COS on these processes.

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A subset of genes, known as imprinted genes, is present in the mammalian genome. Genomic imprinting governs the monoallelic expression of these genes, depending on whether the gene was inherited from the sperm or the egg. This parent-of-origin specific gene expression is generally dependent on the epigenetic modification, DNA methylation, and the DNA methylation status of CpG dinucleotides residing in loci known as differentially methylated regions (DMRs).

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The DNA methyltransferase 3-like (Dnmt3L) protein is a crucial cofactor in the germ line for the de novo methyltransferase Dnmt3a, which establishes imprints and represses transposable elements. We have previously shown that Dnmt3L transcription is regulated via three different promoters in mice, producing transcripts we term Dnmt3L(s) (stem cell), Dnmt3L(o) (oocyte) and Dnmt3L(at) (adult testis). Here we show that both Dnmt3L(s) and Dnmt3L(o) produce full-length proteins but that the Dnmt3L(at) transcripts are not translated.

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Studies have shown in humans and other species that the major histocompatibility complex class I (MHC-I) region is involved at a number of levels in the establishment and maintenance of pregnancy. The aim of this study was to characterize how a bovine nonclassical MHC-I gene (NC1) is regulated. Initial serial deletion experiments of a 2-kb fragment of the NC1 promoter identified regions with positive regulatory elements in the proximal promoter and evidence for a silencer module(s) further upstream that cooperatively contributed to constitutive NC1 expression.

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CATSPER1 and CATSPER2 are two cation channel-like proteins exclusively expressed in the testis and essential for normal sperm motility and male fertility. Using in silico subtraction and database mining, we identified expressed sequence tags encoding two previously uncharacterized cation channel-like proteins structurally homologous to CATSPER1 and CATSPER2. Similar to CATSPER1 and CATSPER2, these two proteins contain a single-ion transport domain comprised of six transmembrane spanning regions, in which the fourth transmembrane region resembles a voltage sensor and a pore-forming region lies between transmembrane regions 5 and 6.

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DNA (cytosine-5-)-methyltransferase genes are important for normal development in mice and humans. We describe here 11 pseudogenes spread among human, mouse, and rat belonging to this gene family, ranging from 1 pseudogene in humans to 7 in rat, all belonging to the Dnmt3 subfamily. All except 1 rat Dnmt3b pseudogene appear to be transcriptionally silent.

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