scholarly journals Mammary gene expression profiles during an intramammary challenge reveal potential mechanisms linking negative energy balance with impaired immune response

2010 ◽  
Vol 41 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Kasey M. Moyes ◽  
James K. Drackley ◽  
Dawn E. Morin ◽  
Sandra L. Rodriguez-Zas ◽  
Robin E. Everts ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Energy Balance ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Differentially Expressed ◽  
Positive Energy ◽  
Ad Libitum

Our objective was to compare mammary tissue gene expression profiles during a Streptococcus uberis ( S. uberis) mastitis challenge between lactating cows subjected to dietary-induced negative energy balance (NEB; n = 5) and cows fed ad libitum to maintain positive energy balance (PEB; n = 5) to better understand the mechanisms associated with NEB and risk of mastitis during the transition period. The NEB cows were feed-restricted to 60% of calculated net energy for lactation requirements for 7 days, and cows assigned to PEB were fed the same diet for ad libitum intake. Five days after feed restriction, one rear mammary quarter of each cow was inoculated with 5,000 cfu of S. uberis (O140J). At 20 h postinoculation, S. uberis-infected mammary quarters from all cows were biopsied for RNA extraction. Negative energy balance resulted in 287 differentially expressed genes (DEG; false discovery rate ≤ 0.05), with 86 DEG upregulated and 201 DEG downregulated in NEB vs. PEB. Canonical pathways most affected by NEB were IL-8 signaling (10 genes), glucocorticoid receptor signaling ( 13 ), and NRF2-mediated oxidative stress response ( 10 ). Among the genes differentially expressed by NEB, cell growth and proliferation ( 48 ) and cellular development ( 36 ) were the most enriched functions. Regarding immune response, HLA-A was upregulated due to NEB, whereas the majority of genes involved in immune response were downregulated (e.g., AKT1, IRAK1, MAPK9, and TRAF6). This study provided new avenues for investigation into the mechanisms relating NEB and susceptibility to mastitis in lactating dairy cows.

scholarly journals PSI-1 A systematic review and meta-analysis of GWAS and gene expression results of Holstein cattle under negative energy balance and ketosis

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 265-266
Author(s):  
Riani Ananda Nunes Soares ◽  
Giovana Vargas ◽  
Malane M Muniz ◽  
Maria Amelia Menck Soares ◽  
Angela Canovas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systematic Review ◽  
Energy Balance ◽  
Gene Network ◽  
Meta Analysis ◽  
Significant Snps ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Differentially Expressed ◽  
Metabolic Conditions

Abstract Development of ketosis in high-producing dairy cows contributes to animal health issues and highlights the need for better understanding the genetic basis of metabolic diseases. Thus, the aim of this study was to evaluate the pattern of differential gene expression in liver of cows under negative energy balance (NEB), subclinical, and clinical ketosis through a systematic review and meta-analysis of published gene expression and genome-wide association studies (GWAS) results. After screening of the 118 articles found in the systematic review, 20 articles were included in the analysis. For this, 430 significant SNPs identified by GWAS were investigated to see if they were located within genes reported in gene expression studies. A permutation approach was used to identify the biological pathways associated with the metabolic conditions studied. A gene network was created using the differentially expressed genes harboring significant SNPs and a QTL enrichment analysis was performed to identify potential positional candidate loci. This study revealed 14 genes that are differentially expressed in the liver of cows in different metabolic conditions, which harbor 24 significant polymorphisms in reported GWAS. Three significant metabolic pathways were associated with NEB, subclinical and clinical ketosis. In addition, two important genes, PPARA and ACACA, were identified as differentially expressed in the three metabolic conditions. Gene network analysis revealed co-expression interactions among 34 genes associated with functions involving fatty acid transport and metabolism. The genes FN1 and PTK2 were enriched for QTL previously associated with the trait “ketosis” on chromosome 2 and with the trait “milk iron content” on chromosome 14, respectively. These findings improve the understanding of negative energy balance and ketosis in dairy cows, which could enhance selection for cows less susceptible to ketosis and help with the development of potential biomarkers for early diagnosis and prevention of ketosis.

scholarly journals Modulation of the Immune Response by Deferasirox in Myelodysplastic Syndrome Patients

2021 ◽  
Vol 14 (1) ◽  
pp. 41
Author(s):  
Hana Votavova ◽  
Zuzana Urbanova ◽  
David Kundrat ◽  
Michaela Dostalova Merkerova ◽  
Martin Vostry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Blood Cell ◽  
Myelodysplastic Syndrome ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Adaptive Immune Response ◽  
Gene Expression Profiles ◽  
Iron Chelator ◽  
Multiple Cancer

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34+ cells were assessed by whole-genome microarrays. Initially, differentially expressed genes (DEGs) were determined between patients with normal ferritin levels and those with IO to address the effect of excessive iron on cellular pathways. These DEGs were annotated to Gene Ontology terms associated with cell cycle, apoptosis, adaptive immune response and protein folding and were enriched in cancer-related pathways. The deregulation of multiple cancer pathways in iron-overloaded patients suggests that IO is a cofactor favoring the progression of MDS. The DEGs between patients with IO and those treated with DFX were involved predominantly in biological processes related to the immune response and inflammation. These data indicate DFX modulates the immune response mainly via neutrophil-related genes. Suppression of negative regulators of blood cell differentiation essential for cell maturation and upregulation of heme metabolism observed in DFX-treated patients may contribute to the hematopoietic improvement.

4 Molecularly guided multiplexed digital spatial analysis reveals differential gene expression profiles in the WNT-β-catenin pathway between melanoma and prostate tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A4-A4
Author(s):  
Anushka Dikshit ◽  
Dan Zollinger ◽  
Karen Nguyen ◽  
Jill McKay-Fleisch ◽  
Kit Fuhrman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Single Molecule ◽  
Spatial Information ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Fluorescence Assay ◽  
Differentially Expressed ◽  
Tumor Type ◽  
Prostate Tumors

BackgroundThe canonical WNT-β-catenin signaling pathway is vital for development and tissue homeostasis but becomes strongly tumorigenic when dysregulated. and alter the transcriptional signature of a cell to promote malignant transformation. However, thorough characterization of these transcriptomic signatures has been challenging because traditional methods lack either spatial information, multiplexing, or sensitivity/specificity. To overcome these challenges, we developed a novel workflow combining the single molecule and single cell visualization capabilities of the RNAscope in situ hybridization (ISH) assay with the highly multiplexed spatial profiling capabilities of the GeoMx™ Digital Spatial Profiler (DSP) RNA assays. Using these methods, we sought to spatially profile and compare gene expression signatures of tumor niches with high and low CTNNB1 expression.MethodsAfter screening 120 tumor cores from multiple tumors for CTNNB1 expression by the RNAscope assay, we identified melanoma as the tumor type with the highest CTNNB1 expression while prostate tumors had the lowest expression. Using the RNAscope Multiplex Fluorescence assay we selected regions of high CTNNB1 expression within 3 melanoma tumors as well as regions with low CTNNB1 expression within 3 prostate tumors. These selected regions of interest (ROIs) were then transcriptionally profiled using the GeoMx DSP RNA assay for a set of 78 genes relevant in immuno-oncology. Target genes that were differentially expressed were further visualized and spatially assessed using the RNAscope Multiplex Fluorescence assay to confirm GeoMx DSP data with single cell resolution.ResultsThe GeoMx DSP analysis comparing the melanoma and prostate tumors revealed that they had significantly different gene expression profiles and many of these genes showed concordance with CTNNB1 expression. Furthermore, immunoregulatory targets such as ICOSLG, CTLA4, PDCD1 and ARG1, also demonstrated significant correlation with CTNNB1 expression. On validating selected targets using the RNAscope assay, we could distinctly visualize that they were not only highly expressed in melanoma compared to the prostate tumor, but their expression levels changed proportionally to that of CTNNB1 within the same tumors suggesting that these differentially expressed genes may be regulated by the WNT-β-catenin pathway.ConclusionsIn summary, by combining the RNAscope ISH assay and the GeoMx DSP RNA assay into one joint workflow we transcriptionally profiled regions of high and low CTNNB1 expression within melanoma and prostate tumors and identified genes potentially regulated by the WNT- β-catenin pathway. This novel workflow can be fully automated and is well suited for interrogating the tumor and stroma and their interactions.GeoMx Assays are for RESEARCH ONLY, not for diagnostics.

Physiological and genetic differences between low and high index dairy cows

2001 ◽  
Vol 26 (1) ◽  
pp. 223-236 ◽  
Author(s):  
M. C. Lucy ◽  
B. A. Crooker
Keyword(s):  
Energy Balance ◽  
Dairy Cattle ◽  
Dairy Cows ◽  
Milk Production ◽  
Negative Energy ◽  
High Index ◽  
Negative Energy Balance ◽  
Positive Energy ◽  
Serum Concentrations ◽  
Days Open

AbstractSelection of dairy cattle for increased milk production has decreased some indices of reproductive efficiency. For example, days open are increased by one day for every 100 kg of increased milk yield per lactation. Some of the change in days open can be explained by delayed onset of oestrous cyclicity and lower conception rate to artificial insemination in cows with greater milk production. Despite these negative associations between milk production and reproduction, reproduction in herds of high producing dairy cattle is not necessarily compromised relative to reproduction in herds of low producing dairy cattle. This is because there is a large environmental effect on dairy reproduction. High producing herds generally have better management and better oestrous detection. Therefore, high producing dairy herds may partially overcome the antagonistic relationship between milk production and reproduction. Physiological mechanisms that lead to poorer reproduction in high producing cows are partially defined. Negative energy balance that occurs in high producing dairy cows can be associated with a delay in the initiation of ovarian cycles and the interval to first breeding. Many of the effects of negative energy balance on postpartum reproduction can be explained by decreased serum luteinizing hormone (LH) that is associated with negative energy balance. Serum LH increases as cows move toward positive energy balance and greater LH stimulates growth and ovulation of ovarian follicles. We have initiated studies to address physiological differences in high and low index dairy cows. The reproductive endocrinology of cows from a control line (5,900 kg milk/lactation) and a select line (10,900 kg milk/lactation) of dairy cows at the University of Minnesota was studied over a two-year period. Cows in Year 1 were similar for serum concentrations of LH, follicle stimulating hormone (FSH), and oestradiol (preovulatory period). In both years, serum concentrations of progesterone during luteal phases, however, were decreased in select cows. The Year 2 cows also had a delay in the return to oestrous cyclicity that was associated with reduced LH. The possibility that decreased progesterone causes infertility in dairy cows will require further study. Collectively, these data suggest that changes in blood progesterone concentrations may explain, partially, lower fertility in high index dairy cows.

171 THE EFFECT OF TRICHOSTATIN A ON THE DEVELOPMENT AND THE GLOBAL GENE EXPRESSION PATTERNS IN MOUSE EMBRYOS DEVELOPING IN VITRO

2008 ◽  
Vol 20 (1) ◽  
pp. 165
Author(s):  
X. S. Cui ◽  
X. Y. Li ◽  
T. Kim ◽  
N.-H. Kim
Keyword(s):  
Gene Expression ◽  
Trichostatin A ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Mouse Embryos ◽  
Differentially Expressed ◽  
Gene Expression Patterns ◽  
Cell Stage

Trichostatin A (TSA) is an inhibitor of histone deacetylase and is able to alter gene expression patterns by interfering with the removal of acetyl groups from histones. The aim of this study was to determine the effect of TSA treatment on the development and gene expression patterns of mouse zygotes developing in vitro. The addition of 100 nm TSA to the culture medium did not affect the cleavage of mouse embryos (TSA treatment, 148/150 (99%) v. control, 107/107 (100%)); however, embryos that were treated with TSA arrested at the 2-cell stage (145/148, 98%). We estimated the number of nuclei in control and TSA-treated embryos by propidium iodide staining, taking into account the presence of any cells with two or more nuclei. At 62–63 h post-hCG stimulation, control zygotes had developed to the 4-cell stage and exhibited one nucleus in each blastomere, indicative of normal development. In contrast, we observed tetraploid nuclei in at least one blastomere in 20.8% (11/53) of the embryos that had been treated with TSA. At 28–29 h post-hCG stimulation (metaphase of the 1-cell stage), there was no difference in the mitotic index (as determined by analyzing the microtubule configuration) in the TSA group compared to the control group. At the 2-cell stage, however, we did not observe mitotic spindles and metaphase chromatin in embryos in the TSA treatment group compared to the controls. Interestingly, when embryos were cultured in TSA-free medium from 35 h post-hCG stimulation (S- or early G2-phase of the 2-cell stage) onward, almost all of them (47/50) developed to the blastocyst stage. In contrast, when embryos were cultured in TSA-free medium from 42 h post-hCG stimulation (middle G2-phase of the 2-cell stage) onward, they did not develop to the 4-cell stage. We used Illumina microarray technology to analyze the gene expression profiles in control and TSA-treated late 2-cell-stage embryos. Applied Biosystems Expression System software was used to extract assay signals and assay signal-to-noise ratio values from the microarray images. Our data showed that 897 genes were significantly (P < 0.05; 2-sample t-test) up- or down-regulated by TSA treatment compared to controls. Analysis using the PANTHER classification system (https://panther.appliedbiosystems.com) revealed that the 575 genes that were differentially expressed in the TSA group compared to the control were classified as being associated with putative biological processes or molecular function. Overall, in terms of putative biological processes, more nucleoside, nucleotide, and nucleic acid metabolism, protein metabolism and modification, signal transduction, developmental process, and cell cycle genes were differentially expressed between the TSA and control groups. In terms of putative molecular function, more nucleic acid-binding transcription factor and transferase genes were differentially expressed between the groups. The results collectively suggest that inhibition of histone acetylation in mouse embryos affects gene expression profiles at the time of zygotic genome activation, and this subsequently affects further development.

115 Exosome-mediated microRNA expression profile in follicular fluid of metabolically divergent postpartum cows

2019 ◽  
Vol 31 (1) ◽  
pp. 183
Author(s):  
T. Hailay ◽  
M. Hoelker ◽  
S. Gebremedhn ◽  
F. Rings ◽  
M. M. Saeed-Zidane ◽  
...  
Keyword(s):  
Energy Balance ◽  
Follicular Fluid ◽  
Mirna Expression ◽  
Cell Communication ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Differentially Expressed ◽  
Metabolic Status ◽  
Lactation Period ◽  
Down Regulation

Most high-milking cows enter a state of negative energy balance during the early lactation period. This phenomenon disturbs the metabolic status of the follicular fluid microenvironment, resulting in delayed ovulation. Cell-to-cell communication between the oocyte and the surrounding cells is crucial during folliculogenesis. Exosomes, evolutionarily conserved cargo molecules (30-150nm in diameter) carrying RNA and proteins, are known to be involved in cell-to-cell communication. Here, we aimed to investigate the association between postpartum metabolic status and the expression of exosomal microRNA (miRNA) in follicular fluid of Holstein-Friesian cows. For this, follicular fluid was collected from antral follicles (&gt;8mm in diameter) using ovum pickup procedure from cows (n=30) on a weekly basis between weeks 5 and 10 postpartum. Follicular fluid collected from heifers (n=8) was used as a control. The energy status of each cow was assessed based on the blood metabolite (nonesterified fatty acids and β-hydroxybutyrate) concentration, body weight curve, and overall energy balance determined by dry matter intake. Afterwards, cows were categorized as early negative and late positive (cows show negative energy balance at early weeks and recovered at late weeks postpartum), always negative (cows did not recover until 15 weeks postpartum), and always positive (cows did not enter in to a state of negative energy balance). Following this, exosomes were isolated from pooled samples from each animal category using ultracentrifugation, and their morphology and size was characterised using electron microscopy and nanosight, respectively. Exosomal total RNA enriched with miRNA was isolated using an exosomal RNA isolation kit. Next-generation sequencing of miRNA was performed using Illumina NextSEqn 500 (Illumina Inc., San Diego, CA, USA). MicroRNAs with a fold change ≥2, P-value &lt;0.05, and a false discovery rate of &lt;0.1 were considered differentially expressed. The results showed that a total of 356 known and 156 novel miRNA were identified across samples. Differential expression analysis of miRNA between always-negative cows versus always-positive cows revealed down-regulation of all 6 differentially expressed miRNA, including bta-miR-451, bta-miR-132, and bta-miR-2285. Similarly, down-regulation of 14 miRNA, including bta-miR-20b, bta-miR-363, bta-miR-132, and bta-miR-451, and up-regulation of 3 miRNA was observed in always-negative cows compared to heifers. Furthermore, the target prediction analysis of the down-regulated miRNA have been shown to be involved in regulating different pathways including transforming growth factor-β signalling, cell cycle, hippo signalling, forkhead box O signalling, and endometrial cancer, among others. In conclusion, the results revealed that although negative energy balance in postpartum dairy cows suppressed exosomal miRNA expression in follicular fluid, the opposite was observed in metabolically unstressed cows. This divergence of exosome-mediated miRNA expression in the follicular fluid of metabolically stressed cows could be associated with the reduced fertility of those cows.

Integrated Transcriptomic Analysis of Necrosis-related Gene in Diffuse Gliomas

2019 ◽  
Vol 80 (04) ◽  
pp. 240-249
Author(s):  
Jiajia Wang ◽  
Jie Ma
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Prognostic Index ◽  
Gene Expression Profiles ◽  
Risk Groups ◽  
Low Risk ◽  
Differentially Expressed ◽  
Low Grade

Glioblastoma multiforme (GBM), an aggressive brain tumor, is characterized histologically by the presence of a necrotic center surrounded by so-called pseudopalisading cells. Pseudopalisading necrosis has long been used as a prognostic feature. However, the underlying molecular mechanism regulating the progression of GBMs remains unclear. We hypothesized that the gene expression profiles of individual cancers, specifically necrosis-related genes, would provide objective information that would allow for the creation of a prognostic index. Gene expression profiles of necrotic and nonnecrotic areas were obtained from the Ivy Glioblastoma Atlas Project (IVY GAP) database to explore the differentially expressed genes.A robust signature of seven genes was identified as a predictor for glioblastoma and low-grade glioma (GBM/LGG) in patients from The Cancer Genome Atlas (TCGA) cohort. This set of genes was able to stratify GBM/LGG and GBM patients into high-risk and low-risk groups in the training set as well as the validation set. The TCGA, Repository for Molecular Brain Neoplasia Data (Rembrandt), and GSE16011 databases were then used to validate the expression level of these seven genes in GBMs and LGGs. Finally, the differentially expressed genes (DEGs) in the high-risk and low-risk groups were subjected to gene ontology enrichment, Kyoto Encyclopedia of Genes and Genomes pathway, and gene set enrichment analyses, and they revealed that these DEGs were associated with immune and inflammatory responses. In conclusion, our study identified a novel seven-gene signature that may guide the prognostic prediction and development of therapeutic applications.

scholarly journals Integrated analysis of the aging brain transcriptome and proteome in tauopathy

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Carl Grant Mangleburg ◽  
Timothy Wu ◽  
Hari K. Yalamanchili ◽  
Caiwei Guo ◽  
Yi-Chen Hsieh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Mutant Form ◽  
Brain Gene Expression ◽  
Brain Transcriptome ◽  
Age Dependent

Abstract Background Tau neurofibrillary tangle pathology characterizes Alzheimer’s disease and other neurodegenerative tauopathies. Brain gene expression profiles can reveal mechanisms; however, few studies have systematically examined both the transcriptome and proteome or differentiated Tau- versus age-dependent changes. Methods Paired, longitudinal RNA-sequencing and mass-spectrometry were performed in a Drosophila model of tauopathy, based on pan-neuronal expression of human wildtype Tau (TauWT) or a mutant form causing frontotemporal dementia (TauR406W). Tau-induced, differentially expressed transcripts and proteins were examined cross-sectionally or using linear regression and adjusting for age. Hierarchical clustering was performed to highlight network perturbations, and we examined overlaps with human brain gene expression profiles in tauopathy. Results TauWT induced 1514 and 213 differentially expressed transcripts and proteins, respectively. TauR406W had a substantially greater impact, causing changes in 5494 transcripts and 697 proteins. There was a ~ 70% overlap between age- and Tau-induced changes and our analyses reveal pervasive bi-directional interactions. Strikingly, 42% of Tau-induced transcripts were discordant in the proteome, showing opposite direction of change. Tau-responsive gene expression networks strongly implicate innate immune activation. Cross-species analyses pinpoint human brain gene perturbations specifically triggered by Tau pathology and/or aging, and further differentiate between disease amplifying and protective changes. Conclusions Our results comprise a powerful, cross-species functional genomics resource for tauopathy, revealing Tau-mediated disruption of gene expression, including dynamic, age-dependent interactions between the brain transcriptome and proteome.

scholarly journals Genomewide Expression Profile Analysis of the Candida glabrata Pdr1 Regulon

2010 ◽  
Vol 10 (3) ◽  
pp. 373-383 ◽  
Author(s):  
Kelly E. Caudle ◽  
Katherine S. Barker ◽  
Nathan P. Wiederhold ◽  
Lijing Xu ◽  
Ramin Homayouni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Candida Glabrata ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Resistant Isolate ◽  
Content Type ◽  
Activating Mutations ◽  
Zinc Cluster

ABSTRACTThe ABC transportersCandida glabrataCdr1 (CgCdr1), CgPdh1, and CgSnq2 are known to mediate azole resistance in the pathogenic fungusC. glabrata. Activating mutations inCgPDR1, a zinc cluster transcription factor, result in constitutive upregulation of these ABC transporter genes but to various degrees. We examined the genomewide gene expression profiles of two matched azole-susceptible and -resistantC. glabrataclinical isolate pairs. Of the differentially expressed genes identified in the gene expression profiles for these two matched pairs, there were 28 genes commonly upregulated withCgCDR1in both isolate sets includingYOR1,LCB5,RTA1,POG1,HFD1, and several members of theFLOgene family of flocculation genes. We then sequencedCgPDR1from each susceptible and resistant isolate and found two novel activating mutations that conferred increased resistance when they were expressed in a common background strain in whichCgPDR1had been disrupted. Microarray analysis comparing these reengineered strains to their respective parent strains identified a set of commonly differentially expressed genes, includingCgCDR1,YOR1, andYIM1, as well as genes uniquely regulated by specific mutations. Our results demonstrate that while CgPdr1 activates a broad repertoire of genes, specific activating mutations result in the activation of discrete subsets of this repertoire.

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