scholarly journals Cardiac physiology and metabolic gene expression during late organogenesis among F. heteroclitus embryo families from crosses between pollution-sensitive and -resistant parents

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Goran Bozinovic ◽  
Zuying Feng ◽  
Damian Shea ◽  
Marjorie F. Oleksiak
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Parental Effects ◽  
Cardiac Physiology ◽  
Heart Rates ◽  
Metabolic Gene ◽  
Metabolic Gene Expression ◽  
Morphological Deformities

Abstract Background The teleost fish Fundulus heteroclitus inhabit estuaries heavily polluted with persistent and bioaccumulative chemicals. While embryos of parents from polluted sites are remarkably resistant to toxic sediment and develop normally, embryos of parents from relatively clean estuaries, when treated with polluted sediment extracts, are developmentally delayed, displaying deformities characteristic of pollution-induced embryotoxicity. To gain insight into parental effects on sensitive and resistant phenotypes during late organogenesis, we established sensitive, resistant, and crossed embryo families using five female and five male parents from relatively clean and predominantly PAH-polluted estuaries each, measured heart rates, and quantified individual embryo expression of 179 metabolic genes. Results Pollution-induced embryotoxicity manifested as morphological deformities, significant developmental delays, and altered cardiac physiology was evident among sensitive embryos resulting from crosses between females and males from relatively clean estuaries. Significantly different heart rates among several geographically unrelated populations of sensitive, resistant, and crossed embryo families during late organogenesis and pre-hatching suggest site-specific adaptive cardiac physiology phenotypes relative to pollution exposure. Metabolic gene expression patterns (32 genes, 17.9%, at p < 0.05; 11 genes, 6.1%, at p < 0.01) among the embryo families indicate maternal pollutant deposition in the eggs and parental effects on gene expression and metabolic alterations. Conclusion Heart rate differences among sensitive, resistant, and crossed embryos is a reliable phenotype for further explorations of adaptive mechanisms. While metabolic gene expression patterns among embryo families are suggestive of parental effects on several differentially expressed genes, a definitive adaptive signature and metabolic cost of resistant phenotypes is unclear and shows unexpected sensitive-resistant crossed embryo expression profiles. Our study highlights physiological and metabolic gene expression differences during a critical embryonic stage among pollution sensitive, resistant, and crossed embryo families, which may contribute to underlying resistance mechanisms observed in natural F. heteroclitus populations living in heavily contaminated estuaries.

scholarly journals 415. Airway Gene-Expression Classifiers for Respiratory Syncytial Virus (RSV) Disease Severity in Infants

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S210-S210
Author(s):  
Mary T Caserta ◽  
Lu Wang ◽  
Chin-Yi Chu ◽  
Christopher Slaunwhite ◽  
Jeanne Holden-Wiltse ◽  
...  
Keyword(s):  
Gene Expression ◽  
Model Selection ◽  
Disease Severity ◽  
Severity Score ◽  
Cross Validation ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Multivariate Linear Regression Analysis ◽  
Linear Predictor

Abstract Background RSV infection is common in infants with a majority of those affected displaying mild clinical symptoms. However, a substantial number develop severe symptoms requiring hospitalization. We currently lack sensitive and specific predictors to identify a majority of those who develop severe disease. Methods High throughput RNA sequencing (RNAseq) of nasal epithelial cells defined airway gene expression patterns in RSV-infected subjects. Using multivariate linear regression analysis with AIC-based model selection, we built a sparse linear predictor of RSV disease severity, the Nasal Gene Severity Score-NGSS1. Using a similar statistical approach, we built an alternate predictor based upon genes displaying stable expression over time (NGSS2). We evaluated predictive performance of both models using leave-one-out cross-validation analyses. Results We defined comprehensive airway gene expression profiles from 106 full-tem previously healthy RSV-infected subjects with a range of RSV disease severity prospectively enrolled in the AsPIRES study. Nasal samples were obtained during acute infection (day 1–10 of illness; 106 samples), and convalescence (day 14–28 of illness; 69 samples). All subjects had a primary infection and were assigned a cumulative clinical illness severity score (GRSS) (Table 1). From the RNA seq data 41 genes were identified as the NGSS1 which is strongly correlated with disease severity (GRSS) in both the naive (ρ=0.935) and cross-validated analysis (ρ of 0.813). As a binary classifier (mild vs. severe), NGSS1 correctly classifies 89.6% of the subjects following cross-validation (Figure 1). Next, we evaluated genes that were stably expressed in both acute illness and convalescence samples in 54 subjects with data from both time points. Repeating the regression based step wise model selection identified 13 genes as NGSS2, which was significantly correlated with GRSS (ρ = 0.741). This model has slightly less, but comparable, prediction accuracy with a cross-validated correlation of 0.741 and cross-validated classification accuracy of 84.0% (Figure 2). Conclusion Airway gene expression patterns, obtained following a minimally-invasive nasal procedure, have potential utility as prognostic biomarkers for severe infant RSV infections. Disclosures All authors: No reported disclosures.

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.

scholarly journals Aortic Gene Expression Profiles Show How ApoA-I Levels Modulate Inflammation, Lysosomal Activity, and Sphingolipid Metabolism in Murine Atherosclerosis

2020 ◽  
Author(s):  
Marco Busnelli ◽  
Stefano Manzini ◽  
Matteo Chiara ◽  
Alice Colombo ◽  
Fabrizio Fontana ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Sphingolipid Metabolism ◽  
Gene Expression Patterns ◽  
Peripheral Tissues ◽  
Lysosomal Activity ◽  
Better Regulation ◽  
Atherosclerosis Development

Objective: HDL (high-density lipoprotein) particles are known to possess several antiatherogenic properties that include the removal of excess cholesterol from peripheral tissues, the maintenance of endothelial integrity, antioxidant, and anti-inflammatory activities. ApoA-I overexpression in apoE-deficient (EKO) mice has been shown to increase HDL levels and to strongly reduce atherosclerosis development. The aim of the study was to investigate gene expression patterns associated with atherosclerosis development in the aorta of EKO mice and how HDL plasma levels relate to gene expression patterns at different stages of atherosclerosis development and with different dietary treatments. Approach and Results: Eight-week-old EKO mice, EKO mice overexpressing human apoA-I, and wild-type mice as controls were fed either normal laboratory or Western diet for 6 or 22 weeks. Cholesterol distribution among lipoproteins was evaluated, and atherosclerosis of the aorta was quantified. High-throughput sequencing technologies were used to analyze the transcriptome of the aorta of the 3 genotypes in each experimental condition. In addition to the well-known activation of inflammation and immune response, the impairment of sphingolipid metabolism, phagosome-lysosome system, and osteoclast differentiation emerged as relevant players in atherosclerosis development. The reduced atherosclerotic burden in the aorta of EKO mice expressing high levels of apoA-I was accompanied by a reduced activation of immune system markers, as well as reduced perturbation of lysosomal activity and a better regulation of the sphingolipid synthesis pathway. Conclusions: ApoA-I modulates atherosclerosis development in the aorta of EKO mice affecting the expression of pathways additional to those associated with inflammation and immune response.

Clinical phenotype and gene expression profile in Crohn's disease

2007 ◽  
Vol 292 (1) ◽  
pp. G298-G304 ◽  
Author(s):  
Claudio Csillag ◽  
Ole Haagen Nielsen ◽  
Rehannah Borup ◽  
Finn Cilius Nielsen ◽  
Jørgen Olsen
Keyword(s):  
Gene Expression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intracellular Transport ◽  
Clinical Phenotype ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Principal Component ◽  
Gene Profiling ◽  
Gene Expression Patterns

The clinical course varies significantly among patients with Crohn's disease (CD). This study investigated whether gene expression profiles generated by DNA microarray technology might predict disease progression. Biopsies from the descending colon were obtained colonoscopically from 40 CD patients. Gene profiling analyses were performed using a Human Genome U133 Plus 2.0 GeneChip Array, and summarization into a single expression measure for each probe set was performed using the robust multiple array procedure. Principal component analysis demonstrated that three components explain two-thirds of the total variation. The most important parameters for the determination of the colonic gene expression patterns were the presence of disease (CD) and presence of inflammation. Superimposition of clinical phenotype data revealed a grouping of the samples from patients with stenosis toward negative values on the axis of the second principal component. The functional annotation analysis suggested that the expression of genes involved in intracellular transport and cytoskeletal organization might influence the development of stenosis. In conclusion, even though most variation in the colonic gene expression patterns is due to presence or absence of CD and inflammation status, the development of stenosis is a parameter that affects colonic gene expression to some extent.

Distinct Gene Expression Patterns Defining Human Osteoblasts' Response to BMP2 Treatment: Is the Therapeutic Success All a Matter of Timing?

2016 ◽  
Vol 57 (3-4) ◽  
pp. 197-210 ◽  
Author(s):  
Sabrina Ehnert ◽  
Romina Haydée Aspera-Werz ◽  
Thomas Freude ◽  
Marie Karolina Reumann ◽  
Björn Gunnar Ochs ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Therapeutic Success ◽  
Human Osteoblasts ◽  
Osteoblast Function ◽  
Repulsive Guidance Molecule

Background: Bone morphogenetic proteins (BMPs) play a key role in bone formation. Local application of BMP2 (Dibotermin alfa) supports bone formation when applied to complex fractures. However, up to 33% of patients do not respond to this therapy. Purpose: Aiming to investigate whether inter-individual responses to BMP2 treatment can be predicted by gene expression patterns, we investigated the effect of BMP2 on primary human osteoblasts and THP-1 cell-derived osteoclasts from 110 donors. Methods: Osteoblasts were obtained by collagenase digestion of spongy bone tissues. Osteoclasts were differentiated from THP-1 cells using the conditioned media of the osteoblasts. Viability was determined by resazurin conversion. As functional characteristics AP and Trap5B activity were measured. Gene expression levels were determined by RT-PCR in 21 of the 110 evaluated donors and visualized by electrophoresis. Results: Based on our data, we could classify three response groups: (i) In 51.8% of all donors, BMP2 treatment induced osteoblast function. These donors strongly expressed the BMP2 inhibitor Noggin (NOG), the alternative BMP2 receptors repulsive guidance molecule B (RGMb) and activin receptor-like kinase 6 (Alk6), as well as the Wnt inhibitor sclerostin (SOST). (ii) In 17.3% of all donors, BMP2 treatment induced viability. In these donors, the initial high SOST expression significantly dropped with BMP2 treatment. (iii) 30.9% of all donors were not directly affected by BMP2 treatment. These donors expressed high levels of the pseudoreceptor BMP and activin membrane-bound inhibitor (BAMBI) and lacked SOST expression. In all donors, SOST expression correlated directly with receptor activator of NF-κB ligand (RANKL) expression, defining the cells' potential to stimulate osteoclastogenesis. Conclusions: Our data identified three donor groups profiting from BMP2 treatment either directly via stimulation of osteoblast function or viability and/or indirectly via inhibition of osteoclastogenesis, depending on their expression of BAMBI, SOST, NOG, and RANKL. On the basis of patients' respective expression profiles, the clinical application of BMP2 as well as its timing might be modified in order to better fit the patients' needs to promote bone formation or to inhibit bone resorption.

Gene expression profiling of cerebellar development with high-throughput functional analysis

2005 ◽  
Vol 22 (1) ◽  
pp. 8-13 ◽  
Author(s):  
Sakae Saito ◽  
Kimi Honma ◽  
Hiroko Kita-Matsuo ◽  
Takahiro Ochiya ◽  
Kikuya Kato
Keyword(s):  
Gene Expression ◽  
Neurite Outgrowth ◽  
High Throughput ◽  
Functional Data ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Principal Component ◽  
Data Matrix ◽  
Cerebellar Development ◽  
Gene Expression Patterns

We measured the expression levels of 450 genes during mouse postnatal cerebellar development by quantitative PCR using RNA purified from layers of the cerebellar cortex. Principal component analysis of the data matrix demonstrated that the first and second components corresponded to general levels of gene expression and gene expression patterns, respectively. We introduced 288 of the 450 genes into PC12 cells using a high-throughput transfection assay based on atelocollagen and determined the ability of each gene to promote neurite outgrowth or cell proliferation. Five genes induced neurite outgrowth, and seven genes enhanced proliferation. Evaluation of the functional data and gene expression patterns showed that none of these genes exhibited elevated expression at maturation, suggesting that genes characteristic of mature neurons are not likely to participate in neuronal development. These results demonstrate that functional data can facilitate interpretation of expression profiles and identification of new molecules that participate in biological processes.

scholarly journals Gene Expression Patterns in Human Liver Cancers

2002 ◽  
Vol 13 (6) ◽  
pp. 1929-1939 ◽  
Author(s):  
Xin Chen ◽  
Siu Tim Cheung ◽  
Samuel So ◽  
Sheung Tat Fan ◽  
Christopher Barry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Gene Expression Patterns ◽  
Genotypic Differences ◽  
P53 Overexpression ◽  
Multiple Tumor ◽  
Liver Cancers ◽  
Genotypic Characteristics

Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Using cDNA microarrays to characterize patterns of gene expression in HCC, we found consistent differences between the expression patterns in HCC compared with those seen in nontumor liver tissues. The expression patterns in HCC were also readily distinguished from those associated with tumors metastatic to liver. The global gene expression patterns intrinsic to each tumor were sufficiently distinctive that multiple tumor nodules from the same patient could usually be recognized and distinguished from all the others in the large sample set on the basis of their gene expression patterns alone. The distinctive gene expression patterns are characteristic of the tumors and not the patient; the expression programs seen in clonally independent tumor nodules in the same patient were no more similar than those in tumors from different patients. Moreover, clonally related tumor masses that showed distinct expression profiles were also distinguished by genotypic differences. Some features of the gene expression patterns were associated with specific phenotypic and genotypic characteristics of the tumors, including growth rate, vascular invasion, and p53 overexpression.

LBH589, a Novel Deacetylase Inhibitor (DACi), Treatment of Patients with Cutaneous T-Cell Lymphoma (CTCL). Skin Gene Expression Profiles in the First 24 Hours Related to Clinical Response Following Therapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2715-2715 ◽  
Author(s):  
Miles Prince ◽  
D.J. George ◽  
R. Johnstone ◽  
C. McCormack ◽  
L. Ellis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Gene Expression Patterns ◽  
Functional Categories ◽  
Patient Response ◽  
Individual Gene ◽  
Tumor Gene Expression ◽  
Tumor Gene

Abstract Background: LBH589 is a novel DACi in Phase I trials. Pre-clinical studies have demonstrated that DACi alter gene expression and other DACi have induced disease regression in CTCL. Indeed, CTCL is an ideal disease to assess variation in tumor gene expression over time following drug administration. In this study we evaluated the safety and activity of LBH589 in CTCL and examined changes in tumor gene expression in the first 24 hours following oral LBH589. Methods: Pts with advanced-stage CTCL, who had progressed following prior systemic therapy were entered into the oral DLT dose level 30 mg M,W,F cohort (n=1), the subsequent MTD dose level 20 mg M,W, F weekly (n=9). LBH589 was continued until disease progression or unacceptable toxicity. Intensive cardiac monitoring was performed. Six pts had 3 mm punch biopsies from CTCL-involved skin lesions at 0, 4, 8 and 24 h after administration, which were subjected to gene expression profiling using Affymetrix U133 plus 2.0 GeneChips with 47,000 probesets. Alteration in gene expression patterns was confirmed by QRT-PCR of selected genes. Individual gene expression analysis is underway, utilizing set enrichment analysis to elucidate the functional categories which correlate with degree of patient response. Results: 10 pts are currently evaluable for response. 2 of the pts attained a complete response (CR), 4 attained a partial response (PR), 1 achieved stable disease (SD) with ongoing improvement, and 2 progressed on treatment (PD). (RR = 6/10; 60%). Microarray data on 5 pts demonstrated distinct gene expression response profiles between pts. Individual gene expression within patient tumors varied over the timepoints in the first 24 hours following treatment. To demonstrate effects of LBH589 as an epigenetic modulator, global changes in gene expression patterns in responding versus progressing patients have been delineated. In addition, functional categories of genes which correlate with degree of patient response have been identified. Conclusions: LBH589 induces CR’s in CTCL pts. Preliminary microarray analysis of tumor samples have identified distinct gene expression profiles.

Predictive gene expression patterns of response to adriamycin and cyclophosphamide (AC) in human breast cancers

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 527-527
Author(s):  
A. Makris ◽  
C. Creighton ◽  
K. C. Osborne ◽  
S. Hilsenbeck ◽  
M. K. Harrison ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Molecular Profile ◽  
Gene Expression Patterns ◽  
Predictive Test ◽  
Qrt Pcr

527 Background: Adriamycin and cyclophosphamide (AC) and docetaxel (D) are widely used in the treatment of breast cancer. We conducted a prospective, randomized, multicenter trial to discover predictive markers of AC and D and hypothesized that gene expression profiles can select appropriate patients who may respond to AC, and that these patterns are different from our published docetaxel (D) profiles Methods: One hundred and twenty patients were randomized to either 4 cycles of AC (60/600 mg/m2) or D (100mg/m2) prior to surgery. Core biopsies from 60 patients were obtained before treatment with neoadjuvant AC. Pathologic responses were assessed after AC. Gene expression patterns were determined using Affymetrix U133A GeneChips. Differential genes for AC response were then validated by QRT-PCR in an independent cohort of 33 patients treated with AC. Results: The median age was 48 yrs (range 30–72), clinical response rates were 57% (34/60), and pathological complete response (pCR) or near pCR (npCR) was observed in 22% (12/60) in AC arm. Differential expression between sensitive and resistant tumors with a low false discovery rate (FDR 5–10%) was obtained. Of these 82 differentially expressed genes, pathways up-regulated in sensitive tumors included TOP2A, metabolism (LYZ), survival (CFLAR, CASP3), cell cycle (MKI67), cytokines and other inflammatory genes. This molecular portrait for AC was not predictive of docetaxel response. By QRT-PCR of 4 genes (LYZ, CFLAR, MKI67 and TOP2A) in the independent tumor set, LYZ was predictive of AC pathologic complete response. Additional genes will be validated in the second cohort. Conclusions: The molecular profile for AC is different from the docetaxel expression profile. This potential predictive test may allow selection of the most appropriate chemotherapy schedule for women with breast cancer. No significant financial relationships to disclose.

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