scholarly journals Beyond Field Effect: Analysis of Shrunken Centroids in Normal Esophageal Epithelia Detects Concomitant Esophageal Adenocarcinoma

2007 ◽  
Vol 1 ◽  
pp. BBI.S311 ◽  
Author(s):  
Florin M. Selaru ◽  
Suna Wang ◽  
Jing Yin ◽  
Karsten Schulmann ◽  
Yan Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Barrett’S Esophagus ◽  
Esophageal Adenocarcinoma ◽  
Barrett's Esophagus ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Differentially Expressed ◽  
Gene Expression Patterns ◽  
Neoplastic Progression ◽  
Esophageal Epithelium

Background and Aims Because of the extremely low neoplastic progression rate in Barrett's esophagus, it is difficult to diagnose patients with concomitant adenocarcinoma early in their disease course. If biomarkers existed in normal squamous esophageal epithelium to identify patients with concomitant esophageal adenocarcinoma, potential applications would be far-reaching. The aim of the current study was to identify global gene expression patterns in normal esophageal epithelium capable of revealing simultaneous esophageal adenocarcinoma, even located remotely in the esophagus. Methods Tissues comprised normal esophageal epithelia from 9 patients with esophageal adenocarcinoma, 8 patients lacking esophageal adenocarcinoma or Barrett's, and 6 patients with Barrett's esophagus alone. cDNA microarrays were performed, and pattern recognition in each of these subgroups was achieved using shrunken nearest centroid predictors. Results Our method accurately discriminated normal esophageal epithelia of 8/8 patients without esophageal adenocarcinoma or Barrett's esophagus and of 6/6 patients with Barrett's esophagus alone from normal esophageal epithelia of 9/9 patients with Barrett's esophagus and concomitant esophageal adenocarcinoma. Moreover, we identified genes differentially expressed between the above subgroups. Thus, based on their corresponding normal esophageal epithelia alone, our method accurately diagnosed patients who had concomitant esophageal adenocarcinoma. Conclusions These global gene expression patterns, along with individual genes culled from them, represent potential biomarkers for the early diagnosis of esophageal adenocarcinoma from normal esophageal epithelia. Genes discovered in normal esophagus that are differentially expressed in patients with vs. without esophageal adenocarcinoma merit further pursuit in molecular genetic, functional, and therapeutic interventional studies.

80 GLOBAL GENE EXPRESSION PATTERNS OF FRESH AND VITRIFIED IN VITRO-PRODUCED BOVINE BLASTOCYSTS

2013 ◽  
Vol 25 (1) ◽  
pp. 187
Author(s):  
M. J. Sudano ◽  
E. S. Caixeta ◽  
D. M. Paschoal ◽  
T. S. Rascado ◽  
L. F. Crocomo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Expression Patterns ◽  
Rna Extraction ◽  
Global Gene Expression ◽  
Differentially Expressed ◽  
Microarray Data Analysis ◽  
Gene Expression Patterns ◽  
Mrna Levels

Over the past decades, there have been great advances in in vitro production (IVP) systems with improved culture methods and new knowledge regarding embryo genetics, physiology, ultrastructure, and morphology. Nevertheless, a major obstacle for dissemination of this technology is the great sensitivity of IVP embryos to cryopreservation. The objective was to study the global gene-expression patterns of fresh and vitrified IVP bovine embryos. Oocytes (N = 1290) were matured and fertilized in vitro (Day 0). Presumptive zygotes were cultured in SOFaa with 0.5% BSA and 2.5% of FCS. Cleavage and blastocyst production was evaluated after 3 and 7 days under standard culture conditions (at 38.5°C in atmosphere of 5% O2, 5% CO2, and 90% N2). On Day 7, half of the blastocysts were vitrified (n = 94), warmed (Sudano et al. 2011 Theriogenology 75, 1211–1220), and returned for 24 h of additional culture (re-expansion and hatching; hatched was evaluated 12 and 24 h after warming, respectively) when their RNA was extracted (vitrified group). The remaining embryos returned to culture until Day 8 when their RNA was extracted (fresh group). Total RNA extraction of a single blastocyst was performed using the PicoPure Kit (Applied Biosystems®, Foster City, CA, USA). The RNA samples were DNAse treated (Qiagen®, Valencia, CA, USA), and mRNA was amplified (RiboAmp Kit®). The aRNA output was evaluated with a NanoDrop (Thermo®, Wilmington, DE, USA) and Bioanalyzer (Agilent®, Santa Clara, CA, USA). Biotin-labelled and fragmented cRNA were obtained with the 3′IVT Kit (Affymetrix®, Santa Clara, CA, USA) to perform hybridization (N = 6–7, respectively, for vitrified and fresh groups) using the GeneChip Bovine Array (Affymetrix®). Microarray data analysis was performed with the FlexArray 1.6.1.1. Genes with a fold change of at least 2 and a probability of P ≤ 0.05 were considered differentially expressed. Real-time PCR was used to validate microarray results (N = 11–15, respectively, for vitrified and fresh groups). As a control, a pool of 200 blastocysts was submitted or not to mRNA amplification followed by the reverse transcription and qPCR of 17 genes. For statistical analyses, PROC GLIMMIX, PROC LOGISTIC, and PROC CORR were used. Cleavage and blastocyst production rates were 86.8 ± 1.0 and 32.5 ± 1.9%, respectively. Re-expansion and hatching/hatched rates were 69.3 and 19.3%, respectively. Messenger RNA abundance of amplified and nonamplified RNA had a high correlation (r = 0.89, P < 0.01). The microarray analysis indicated 383 differentially expressed genes (P ≤ 0.05) between fresh and vitrified blastocysts. Genes involved in apoptosis (PRDX2), heat shock (HSPA5), maternal recognition of pregnancy (IFNT2 and PAG2), and cell differentiation and placenta formation (KRT18) were downregulated in vitrified embryos. According to qPCR analysis, mRNA abundance of IFNT2, PRDX2, and KRT18 was downregulated, whereas HSPA5 mRNA levels were upregulated in vitrified blastocysts. Messenger RNA abundance of PAG2 was not different (P = 0.46) between fresh and vitrified embryos. In conclusion, vitrification alters the expression profile of the genes IFNT2, PRDX2, KRT18, and HSPA5 that can be related with embryo postcryopreservation survival capacity. FAPESP and LNBio-CNPEM are acknowledged.

scholarly journals Toxoplasma infection alters dopamine-sensitive behaviors and host gene expression patterns associated with neuropsychiatric disease

2021 ◽  
Author(s):  
Graham L. Cromar ◽  
Jonathan Epp ◽  
Ana Popovic ◽  
Yusing Gu ◽  
Violet Ha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Expression Patterns ◽  
Neurocognitive Disorders ◽  
Differentially Expressed ◽  
Gene Expression Patterns ◽  
Low Grade ◽  
Cocaine Exposure ◽  
Multiple Testing Correction ◽  
The Impact

ABSTRACTToxoplasma gondii is a single celled parasite thought to infect 1 in 3 worldwide. During chronic infection, T. gondii can migrate to the brain where it promotes low-grade neuroinflammation with the capacity to induce changes in brain morphology and behavior. Consequently, infection with T. gondii has been linked with a number of neurocognitive disorders including schizophrenia (SZ), dementia, and Parkinson’s disease. Beyond neuroinflammation, infection with T. gondii can modulate the production of neurotransmitters, such as dopamine. To further dissect these pathways and examine the impact of altered dopaminergic sensitivity in T. gondii-infected mice on both behavior and gene expression, we developed a novel mouse model, based on stimulant-induced (cocaine) hyperactivity. Employing this model, we found that infection with T. gondii did not alter fear behavior but did impact motor activity and neuropsychiatric-related behaviurs. While both behaviors may help reduce predator avoidance, consistent with previous studies, the latter finding is reminiscent of neurocognitive disorders. Applying RNASeq to two relevant brain regions, striatum and hippocampus, we identified a broad upregulation of immune responses. However, we also noted significant associations with more meaningful neurologically relevant terms were masked due to the sheer number of terms incorporated in multiple testing correction. We therefore performed a more focused analysis using a curated set of neurologically relevant terms revealing significant associations across multiple pathways. We also found that T. gondii and cocaine treatments impacted the expression of similar functional pathways in the hippocampus and striatum although, as indicated by the low overlap among differentially expressed genes, largely via different proteins. Furthermore, while most differentially expressed genes reacted to a single condition and were mostly upregulated, we identified gene expression patterns indicating unexpected interactions between T. gondii infection and cocaine exposure. These include sets of genes which responded to cocaine exposure but not upon cocaine exposure in the context of T. gondii infection, suggestive of a neuroprotective effect advantageous to parasite persistence. Given its ability to uncover such complex relationships, we propose this novel model offers a new perspective to dissect the molecular pathways by which T. gondii infection contributes to neuropsychiatric disorders such as schizophrenia.

scholarly journals Alterations in global gene expression patterns resulting from 10 days of endurance training in humans

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Nigel Keith Stepto ◽  
Timothy John Burton ◽  
Therese Griersmith ◽  
David Powell ◽  
Benedict James Canny
Keyword(s):  
Gene Expression ◽  
Endurance Training ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Gene Expression Patterns

scholarly journals Identification of miRNAs and genes for predicting Barrett’s esophagus progressing to esophageal adenocarcinoma using miRNA-mRNA integrated analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260353
Author(s):  
Chengjiao Yao ◽  
Yilin Li ◽  
Lihong Luo ◽  
Qin Xiong ◽  
Xiaowu Zhong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Barrett’S Esophagus ◽  
Esophageal Adenocarcinoma ◽  
Barrett's Esophagus ◽  
Trp Channels ◽  
Functional Enrichment ◽  
Integrated Analysis ◽  
Epstein Barr Virus Infection ◽  
Tissue Samples ◽  
Microarray Datasets

Barrett’s esophagus (BE) is defined as any metaplastic columnar epithelium in the distal esophagus, which predisposes to esophageal adenocarcinoma (EAC). Yet, the mechanism through which BE develops to EAC still remain unclear. Moreover, the miRNA-mRNA regulatory network in distinguishing BE from EAC still remains poorly understood. To identify differentially expressed miRNAs (DEMs) and genes (DEGs) between EAC and BE from tissue samples, gene expression microarray datasets GSE13898, GSE26886, GSE1420 and miRNA microarray datasets GSE16456, GSE20099 were downloaded from Gene Expression Omnibus (GEO) database. GEO2R was used to screen the DEMs and DEGs. Pathway and functional enrichment analysis were performed by DAVID database. The protein–protein interaction (PPI) network was constructed by STRING and been visualized by Cytoscape software. Finnal, survival analysis was performed basing TCGA database. A total of 21 DEMs were identified. The enriched functions and pathways analysis inclued Epstein-Barr virus infection, herpesvirus infection and TRP channels. GART, TNFSF11, GTSE1, NEK2, ICAM1, PSMD12, CTNNB1, CDH1, PSEN1, IL1B, CTNND1, JAG1, CDH17, ITCH, CALM1 and ITGA6 were considered as the hub-genes. Hsa-miR-143 and hsa-miR-133b were the highest connectivity target gene. JAG1 was predicted as the largest number of target miRNAs. The expression of hsa-miR-181d, hsa-miR-185, hsa-miR-15b, hsa-miR-214 and hsa-miR-496 was significantly different between normal tissue and EAC. CDH1, GART, GTSE1, NEK2 and hsa-miR-496, hsa-miR-214, hsa-miR-15b were found to be correlated with survival.

scholarly journals Global gene expression patterns in response to white patch syndrome: Disentangling symbiont loss from the thermal stress response in reef-building coral

2019 ◽  
Author(s):  
Carly D. Kenkel ◽  
Veronique J.L. Mocellin ◽  
Line K. Bay
Keyword(s):  
Gene Expression ◽  
Abiotic Stress ◽  
Thermal Stress ◽  
Stress Response ◽  
Meta Analysis ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Host Protein ◽  
Gene Expression Patterns ◽  
White Patch

AbstractThe mechanisms resulting in the breakdown of the coral symbiosis once the process of bleaching has been initiated remain unclear. Distinguishing symbiont loss from the abiotic stress response may shed light on the cellular and molecular pathways involved in each process. This study examined physiological changes and global gene expression patterns associated with white patch syndrome (WPS) in P. lobata, which manifests in localized bleaching independent of thermal stress. In addition, a meta-analysis of global gene expression studies in other corals and anemones was used to contrast differential regulation as a result of abiotic stress from expression patterns correlated with symbiotic state. Symbiont density, chlorophyll a content, holobiont productivity, instant calcification rate, and total host protein content were uniformly reduced in WPS relative to healthy tissue. While expression patterns associated with WPS were secondary to fixed effects of source colony, specific functional enrichments suggest that the viral infection putatively giving rise to this condition affects symbiont rather than host cells. The meta-analysis revealed that expression patterns in WPS-affected tissues were significantly correlated with prior studies examining short-term thermal stress responses. This correlation was independent of symbiotic state, as the strongest correlations were found between WPS adults and both symbiotic adult and aposymbiotic coral larvae experiencing thermal stress, suggesting that the majority of expression changes reflect a non-specific stress response. Across studies, the magnitude and direction of expression change among particular functional enrichments suggests unique responses to stressor duration, and highlights unique responses to bleaching in an anemone model which engages in a non-obligate symbiosis.

scholarly journals Expression of placental regulatory genes is associated with fetal growth

2017 ◽  
Vol 45 (7) ◽  
Author(s):  
Maya A. Deyssenroth ◽  
Qian Li ◽  
Marina Lacasaña ◽  
Yoko Nomura ◽  
Carmen Marsit ◽  
...  
Keyword(s):  
Gene Expression ◽  
Birth Weight ◽  
Fetal Growth ◽  
Gestational Age ◽  
Expression Patterns ◽  
Regulatory Genes ◽  
Differentially Expressed ◽  
Gene Expression Patterns ◽  
Metabolic Functions

AbstractThe placenta is the principal organ regulating respiratory, nutritional, endocrine and metabolic functions on behalf of the developing fetus. Changes in gene expression patterns of placenta-specific genes may influence fetal growth. We profiled the expression of 17 genes related to placenta functioning in term placentas (n=677) to identify genes differentially expressed across birth weight categories [small (SGA), appropriate (AGA) and large (LGA) for gestational age].

Global gene expression analysis in nonfailing and failing myocardium pre- and postpulsatile and nonpulsatile ventricular assist device support

2010 ◽  
Vol 42 (3) ◽  
pp. 397-405 ◽  
Author(s):  
Patrick Schwientek ◽  
Peter Ellinghaus ◽  
Sonja Steppan ◽  
Donatella D'Urso ◽  
Michael Seewald ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Genome ◽  
Expression Patterns ◽  
Rna Isolation ◽  
Global Gene Expression ◽  
Ventricular Assist Devices ◽  
Reverse Remodeling ◽  
Gene Expression Patterns ◽  
Ventricular Assist ◽  
Genome Array

Mechanical unloading by ventricular assist devices (VAD) leads to significant gene expression changes often summarized as reverse remodeling. However, little is known on individual transcriptome changes during VAD support and its relationship to nonfailing hearts (NF). In addition no data are available for the transcriptome regulation during nonpulsatile VAD support. Therefore we analyzed the gene expression patterns of 30 paired samples from VAD-supported (including 8 nonpulsatile VADs) and 8 nonfailing control hearts (NF) using the first total human genome array available. Transmural myocardial samples were collected for RNA isolation. RNA was isolated by commercial methods and processed according to chip-manufacturer recommendations. cRNA were hybridized on Affymetrix HG-U133 Plus 2.0 arrays, providing coverage of the whole human genome Array. Data were analyzed using Microarray Analysis Suite 5.0 (Affymetrix) and clustered by Expressionist software (Genedata). We found 352 transcripts were differentially regulated between samples from VAD implantation and NF, whereas 510 were significantly regulated between VAD transplantation and NF (paired t-test P < 0.001, fold change ≥1.6). Remarkably, only a minor fraction of 111 transcripts was regulated in heart failure (HF) and during VAD support. Unsupervised hierarchical clustering of paired VAD and NF samples revealed separation of HF and NF samples; however, individual differentiation of VAD implantation and VAD transplantation was not accomplished. Clustering of pulsatile and nonpulsatile VAD did not lead to robust separation of gene expression patterns. During VAD support myocardial gene expression changes do not indicate reversal of the HF phenotype but reveal a distinct HF-related pattern. Transcriptome analysis of pulsatile and nonpulsatile VAD-supported hearts did not provide evidence for a pump mode-specific transcriptome pattern.

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.

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