Publications by authors named "Michael P Mullen"

Article Synopsis
  • Mycobacterium tuberculosis and Mycobacterium bovis are closely related pathogens that both cause tuberculosis but in humans and cattle, respectively, with similar disease mechanisms.
  • A multi-omics approach was used to analyze the immune response in different macrophage types after infection, allowing for a deeper understanding of how these pathogens interact with their hosts.
  • The study identified 32 genes linked to disease resistance, highlighting important pathways involved in the immune response, particularly the NF-κB signaling pathway, which plays a crucial role in the formation of granulomas in response to infection.
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  • Bovine tuberculosis (bTB), caused by Mycobacterium bovis, significantly affects cattle production, and researchers studied the immune response of alveolar macrophages during infection to identify key genes involved in fighting the disease.
  • Using RNA-seq data from infected bovine macrophages, the study applied different computational methods to create six gene sets, uncovering specific genes linked to bTB infection over 24 and 48 hours post-infection.
  • By integrating gene expression data with genome-wide association studies (GWAS), the researchers successfully identified numerous SNPs associated with bTB susceptibility across several cattle breeds, highlighting the effectiveness of their computational approaches.
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We performed a retrospective study of coronavirus disease 2019 (COVID-19) in people with human immunodeficiency virus (PWH). PWH with COVID-19 demonstrated severe lymphopenia and decreased CD4+ T cell counts. Levels of inflammatory markers, including C-reactive protein, fibrinogen, D-dimer, interleukin 6, interleukin 8, and tumor necrosis factor α were commonly elevated.

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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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  • The Galway sheep is the only native Irish breed and is currently at-risk, prompting a study into its genetic history and microevolution.
  • Comparative genomic analyses indicate that British Leicester sheep likely contributed to the Galway breed's formation, and the Galway sheep show moderate genetic diversity despite their decline.
  • The study found unique genetic signatures in the Galway breed, suggesting potential candidate genes related to production and health traits, which could inform conservation efforts.
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Interleukin 8 is a proinflammatory chemokine involved in neutrophil recruitment and activation in response to infection and also in the resolution of inflammation. Our previous studies identified a number of genetic polymorphisms in the bovine IL8 promoter region which segregate into two haplotypes, with balanced frequencies in the Holstein-Friesian (HF). We subsequently showed that these haplotypes confer divergent IL8 activity both in vitro in mammary epithelial cells and in vivo in response to LPS.

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Background: Bevacizumab improves progression free survival (PFS) and overall survival (OS) in metastatic colorectal cancer patients however currently there are no biomarkers that predict response to this treatment. The aim of this study was to assess if differential protein expression can differentiate patients who respond to chemotherapy and bevacizumab, and to assess if select proteins correlate with patient survival.

Methods: Pre-treatment serum from patients with metastatic colorectal cancer (mCRC) treated with chemotherapy and bevacizumab were divided into responders and nonresponders based on their progression free survival (PFS).

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Soluble factors from CD8(+) T cells and cervicovaginal mucosa of women are recognized as important in controlling human immunodeficiency virus type 1 (HIV-1) infection and transmission. Previously, we have shown the strong anti-HIV-1 activity of prothymosin α (ProTα) derived from CD8(+) T cells. ProTα is a small acidic protein with wide cell distribution, to which several functions have been ascribed, depending on its intracellular or extracellular localization.

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The Finnish Landrace (Finnsheep) is a well known high-prolificacy sheep breed and has been used in many countries as a source of genetic material to increase fecundity of local breeds. Analyses to date have indicated that mutations with a large effect on ovulation rate are not responsible for the exceptional prolificacy of Finnsheep. The objectives of this study were to ascertain if: 1) any of 12 known mutations with large effects on ovulation rate in sheep, or 2) any other DNA sequence variants within the candidate genes GDF9 and BMP15 are implicated in the high prolificacy of the Finnish Landrace breed; using material from lines developed by divergent selection on ovulation rate.

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Background: In both beef and dairy cattle, the majority of early embryo loss occurs within the first 14 days following insemination. During this time-period, embryos are completely dependent on their maternal uterine environment for development, growth and ultimately survival, therefore an optimum uterine environment is critical to their survival. The objective of this study was to investigate whether differences in endometrial gene expression during the mid-luteal phase of the estrous cycle exist between crossbred beef heifers ranked as either high (HF) or low fertility (LF) (following four rounds of artificial insemination (AI)) using the Affymetrix® 23 K Bovine Gene Chip.

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Background: There is an international epidemic of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men. Sustained virologic response (SVR) rates with pegylated interferon and ribavirin treatment are higher in these men during acute HCV than during chronic HCV, but treatment is still lengthy and SVR rates are suboptimal.

Methods: We performed a pilot study of combination therapy with telaprevir, pegylated interferon, and ribavirin in acute genotype 1 HCV infection in HIV-infected men.

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Dietary lipids are transported via lymph to the liver and transformed to lipoproteins which bind to members of the low density lipoprotein receptor family (LDL-RFMs). Certain LDL-RFMs, e.g.

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Article Synopsis
  • The study investigates the influence of progesterone (P4) levels and cycle stage on amino acids and glucose in the uterine histotroph during early pregnancy in dairy heifers.
  • Heifers were divided into low, control, and high P4 groups, and uterine flushings were analyzed on Day 7 and Day 13 after estrus.
  • The results showed that Day 13 had higher recoverable amino acids than Day 7, with low P4 heifers showing significantly lower levels of certain amino acids compared to control and high P4 groups, indicating that P4 levels impact nutrient availability for early embryonic development.
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This paper concerns the likely origin of three mutations with large effects on ovulation rate identified in the Belclare and Cambridge sheep breeds; two in the BMP15 gene (FecX(G) and FecX(B)) and the third (FecG(H)) in GDF9. All three mutations segregate in Belclare sheep while one, FecX(B), has not been found in the Cambridge. Both Belclare and Cambridge breeds are relatively recently developed composites that have common ancestry through the use of genetic material from the Finnish Landrace and Lleyn breeds.

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Systemic progesterone affects the timing and duration of uterine endometrial gene and protein expression and has significant effects on conceptus development. The objective of the present study was to examine how changes in progesterone concentrations during the early luteal phase affect retinol-binding protein (RBP4) mRNA and protein concentrations in the uterus. Endometrial tissue and uterine flushings were recovered on Days 7 and 13 of the oestrous cycle in heifers with high, normal and low progesterone concentrations.

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Early embryo loss is a key factor affecting fertility in dairy and beef herds. Prior to implantation, the bovine embryo spends around 16 days free-floating in the uterine environment and is dependent on the composition of uterine fluid for normal growth and development. However, there is a lack of information regarding the protein composition of the bovine uterus and how it relates to plasma.

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Article Synopsis
  • Uterine secretions called histotroph are super important for helping early embryos grow before they attach to the uterus, providing all the necessary nutrients.
  • Researchers studied the proteins in the uterus of high fertility cattle at two key times, finding 300 proteins on Day 7 and 510 on Day 13, with some proteins changing in amount between these days.
  • Their findings help us understand the role of specific proteins in early pregnancy, including how the uterus prepares for the embryo and supports its growth and health.
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Background: The regulation of adult stem cell migration through human hematopoietic tissue involves the chemokine CXCL12 (SDF-1) and its receptor CXCR4 (CD184). In addition, human leukocyte elastase (HLE) plays a key role. When HLE is located on the cell surface (HLE(CS)), it acts not as a proteinase, but as a receptor for α(1)proteinase inhibitor (α(1)PI, α(1)antitrypsin, SerpinA1).

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Insulin-like growth factor 1 (IGF-1) has been shown to be associated with fertility, growth, and development in cattle. The aim of this study was to (1) identify novel single nucleotide polymorphisms (SNPs) in the bovine IGF-1 gene and alongside previously identified SNPs (2) determine their association with traits of economic importance in Holstein-Friesian dairy cattle. Nine novel SNPs were identified across a panel of 22 beef and dairy cattle by sequence analysis of the 5' promoter, intronic, and 3' regulatory regions, encompassing ~5 kb of IGF-1.

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Background: The central role of the somatotrophic axis in animal post-natal growth, development and fertility is well established. Therefore, the identification of genetic variants affecting quantitative traits within this axis is an attractive goal. However, large sample numbers are a pre-requisite for the identification of genetic variants underlying complex traits and although technologies are improving rapidly, high-throughput sequencing of large numbers of complete individual genomes remains prohibitively expensive.

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Background: Genes which are epigenetically regulated via genomic imprinting can be potential targets for artificial selection during animal breeding. Indeed, imprinted loci have been shown to underlie some important quantitative traits in domestic mammals, most notably muscle mass and fat deposition. In this candidate gene study, we have identified novel associations between six validated single nucleotide polymorphisms (SNPs) spanning a 97.

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Background: Studies in mice and humans have shown that imprinted genes, whereby expression from one of the two parentally inherited alleles is attenuated or completely silenced, have a major effect on mammalian growth, metabolism and physiology. More recently, investigations in livestock species indicate that genes subject to this type of epigenetic regulation contribute to, or are associated with, several performance traits, most notably muscle mass and fat deposition. In the present study, a candidate gene approach was adopted to assess 17 validated single nucleotide polymorphisms (SNPs) and their association with a range of performance traits in 848 progeny-tested Irish Holstein-Friesian artificial insemination sires.

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The imprinted insulin-like growth factor 2 gene (IGF2) encodes a fetal mitogenic hormone protein (IGF-II) and has previously been shown to be associated with performance in dairy cattle. In this study we assessed genotype-phenotype associations between four single nucleotide polymorphisms (SNPs) located within the bovine IGF2 locus on chromosome 29 and a range of performance traits related to milk production, animal growth and body size, fertility and progeny survival in 848 progeny-tested Irish Holstein-Friesian sires. Two of the four SNPs (rs42196909 and IGF2.

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Previous studies show that DNA sequence variation within the mammalian DLK1-DIO3 imprinted domain influences production traits in domestic livestock, most notably the ovine callipyge phenotype. We assessed genotype-phenotype associations between 7 single nucleotide polymorphisms (SNPs) within the orthologous bovine DLK1-DIO3 domain and performance traits in 848 progeny-tested Holstein-Friesian dairy sires. One SNP (MEG3_01) located proximal to the maternally expressed 3 (MEG3/Gtl2) gene was associated with milk yield, subcutaneous fat levels, and progeny carcass conformation (P ≤ 0.

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