scholarly journals Global Transcriptome Analysis of the Responses of a Fluoroquinolone-Resistant Streptococcus pneumoniae Mutant and Its Parent to Ciprofloxacin

2006 ◽  
Vol 50 (1) ◽  
pp. 269-278 ◽  
Author(s):  
Estelle Marrer ◽  
A. Tatsuo Satoh ◽  
Margaret M. Johnson ◽  
Laura J. V. Piddock ◽  
Malcolm G. P. Page

ABSTRACT Streptococcus pneumoniae M22 is a multidrug-resistant mutant selected after exposure of capsulated wild-type S. pneumoniae NCTC 7465 (strain M4) to ciprofloxacin. DNA microarray analysis comparing the gene expression profiles of strain M22 with those of strain M4 showed that strain M22 constitutively expressed 22 genes at levels higher than those observed in strain M4 under all conditions studied. These included the genes encoding the enzymes involved in branched-chain amino acid biosynthesis and two genes (patA and patB) with sequences suggestive of ABC transporter proteins. Expression of the patA and patB genes was induced by ciprofloxacin in both strains, but in strain M4 it only reached the levels observed in strain M22 after long incubation with high concentrations of ciprofloxacin. The altered expression profile observed with strain M22 suggested that the mutation or mutations acquired during resistance selection bring the cell into a state in which the expression of critical genes is preemptively altered to correct for the potential effects of ciprofloxacin on gene expression in the parent strain.

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Christine Kleinert ◽  
Matthieu Blanchet ◽  
François Gagné ◽  
Michel Fournier

The determination of changes in gene expression profiles with xenobiotic dose will allow identifying biomarkers and modes of toxicant action. The harbor seal (Phoca vitulina) 11B7501 B lymphoma cell line was exposed to 1, 10, 100, 1000, 10,000, or 25,000 μg/L 17α-ethinyl estradiol (EE2, the active compound of the contraceptive pill) for 24 h. Following exposure, RNA was extracted and transformed into cDNA. Transcript expression in exposed vs. control lymphocytes was analyzed via RT-qPCR to identify genes with altered expression. Our analysis indicates that gene expression for all but the reference gene varied with dose, suggesting that different doses induce distinct physiological responses. These findings demonstrate that RT-qPCR could be used to identify immunotoxicity and relative dose in harbor seal leukocytes.


2021 ◽  
Author(s):  
Sean Si Qian Ma ◽  
Luyi Ye ◽  
Fan Zhang ◽  
Tiansheng Xu ◽  
Zai-Si Ji ◽  
...  

Abstract Background: Specific gene expression profiles correlate with recurrence of breast cancer in lymph node-negative patients. In contrast, insufficient knowledge is available regarding tumor-specific gene expression in patients with lymph node metastasis before surgery. Furthermore, such patients experience cumulative incidences of relapse greater than 50%. Methods: Sections of formalin-fixed paraffin embedded (FFPE) were prepared from breast tumors of 37 patients who were followed for at least 5 years. FFPE samples of patients with recurrent ductal breast cancer (n = 25) and 12 FFPE samples of such patients without recurrence were subjected to microarray analysis to identify gene expression profiles specifically associated with positive lymph nodes confirmed during surgery that were accompanied by lymphocytic invasion. Immunohistochemistry was employed to determine the estrogen receptor (ER) status of cancer tissues. All patients were administered tamoxifen after surgery, and this treatment continued for more than 5 years, or until cancer recurred. This strategy eliminated interactions between different therapeutics as potential confounding factors that influenced patients' outcomes.Results: Sixteen genes were expressed at significantly higher levels in patients with ER-positive (+) breast cancer with recurrence compared with those without recurrence. Gene Set Enrichment Analysis of The Kyoto Encyclopedia of Genes and Genomes (KEGG) identified 73 genes encoding olfactory receptors included in the “Olfactory transduction” pathway that were enriched in the ER+ recurrence group (FDR P < 0.05). The KEGG “Histidine metabolism” and “Retinol metabolism” pathways were enriched in patients with ER-negative (–) breast cancer with recurrence (FDR P < 0.05). Conclusions: The present study is the first, to our knowledge, to identify 16 genes encoding proteins with diverse functions as well as 73 genes encoding olfactory receptors. These genes may serve as presurgical biomarkers for the recurrence of ER+ breast cancers with lymph node metastasis before surgery. These findings identify potential therapeutic targets for preventing cancer relapse, particularly after lymph nodes metastasis.


2004 ◽  
Vol 14 (5) ◽  
pp. 984-997 ◽  
Author(s):  
J. Q. Cui ◽  
Y. F. Shi ◽  
H. J. Zhou ◽  
J. Q. Li

The purpose of this study is to investigate changes of gene expression profiles in hydatidiform moles (HM) and choriocarcinoma and to explore causes of trophoblastic hyperplasia. Using cDNA microarray, 4096 genes were analyzed in two pairs of the tissues of HM versus normal villi and in two pairs of normal primary culture trophoblasts versus JAR cell line of choriocarcinoma. The expressions of two genes in normal villi and HM, as well as in JAR and JEG-3, were examined with the help of immunohistochemistry, immunoblot, and reverse transcriptase-polymerase chain reaction in order to confirm the findings of cDNA microarray. Twenty-four genes were upregulated and 65 genes were downregulated in all HM. Four hundred thirty-three genes were upregulated and 380 genes were downregulated in JAR. Forty-six genes were upregulated in both HM and choriocarcinoma, whereas 13 genes were downregulated. Genes associated with the inhibition of cell proliferation were significantly downregulated, whereas genes associated with cell proliferation, malignant transformation, metastasis, and drug resistance were upregulated. Thymidine kinase-1 (TK-1) and small subunit ribonucleotide reductase (RRM-2) were overexpressed in HM, JAR, and JEG-3. The expressions of TK-1 and RRM-2 in moles were positively correlated with proliferative index of trophoblasts. Our results suggest that altered expression of genes exist in HM and choriocarcinoma. Trophoblastic hyperplasia may be involved in the overexpression of DNA synthetic enzymes.


2010 ◽  
Vol 45 (6) ◽  
pp. 379-390 ◽  
Author(s):  
Denis Delić ◽  
Nicole Gailus ◽  
Hans-Werner Vohr ◽  
Mohamed Dkhil ◽  
Saleh Al-Quraishy ◽  
...  

Testosterone has been previously shown to induce persistent susceptibility to Plasmodium chabaudi malaria in otherwise resistant female C57BL/6 mice. Here, we investigate as to whether this conversion coincides with permanent changes of hepatic gene expression profiles. Female mice aged 10–12 weeks were treated with testosterone for 3 weeks; then, testosterone treatment was discontinued for 12 weeks before challenging with 106 P. chabaudi-infected erythrocytes. Hepatic gene expression was examined after 12 weeks of testosterone withdrawal and after subsequent infection with P. chabaudi at peak parasitemia, using Affymetrix microarrays with 22 690 probe sets representing 14 000 genes. The expression of 54 genes was found to be permanently changed by testosterone, which remained changed during malaria infection. Most genes were involved in liver metabolism: the female-prevalent genes Cyp2b9, Cyp2b13, Cyp3a41, Cyp3a44, Fmo3, Sult2a2, Sult3a1, and BC014805 were repressed, while the male-prevalent genes Cyp2d9, Cyp7b1, Cyp4a10, Ugt2b1, Ugt2b38, Hsd3b5, and Slco1a1 were upregulated. Genes encoding different nuclear receptors were not persistently changed. Moreover, testosterone induced persistent upregulation of genes involved in hepatocellular carcinoma such as Lama3 and Nox4, whereas genes involved in immune response such as Ifnγ and Igk-C were significantly decreased. Our data provide evidence that testosterone is able to induce specific and robust long-term changes of gene expression profiles in the female mouse liver. In particular, those changes, which presumably indicate masculinized liver metabolism and impaired immune response, may be critical for the testosterone-induced persistent susceptibility of mice to P. chabaudi malaria.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Gui-Hua Yue ◽  
Shao-Yuan Zhuo ◽  
Meng Xia ◽  
Zhuo Zhang ◽  
Yi-Wen Gao ◽  
...  

Objective. Hypertension is one of the most common cardiovascular disorders with high mortality. Here we explored the antihypertension effects of Huanglian Jiedu Decoction (HJD) on thoracic aorta gene expression in spontaneous hypertensive rats.Methods. A rat model of spontaneous hypertension was used. The gene change profile of thoracic aorta after JHD treatment was assessed by GeneChip(GC) analysis using the Agilent Whole Rat Genome Oligo Microarray.Results. Hypertension induced 441 genes upregulated and 417 genes downregulated compared with the normal control group. Treatment of HJD resulted in 76 genes downregulated and 20 genes upregulated. GC data analysis showed that the majority of change genes were involved in immune system process, developmental process, and cell death.Conclusion. Hypertension altered expression of many genes that regulate various biological functions. HJD significantly reduced hypertension and altered the gene expression profiles of SHR rats. These changing genes were involved in many cellular functions such as regulating smooth muscle contraction, Ca(2+) homeostasis, and NO pathway. This study provides the potential novel insights into hypertension and antihypertension effects of HJD.


2005 ◽  
Vol 187 (9) ◽  
pp. 3259-3266 ◽  
Author(s):  
Anyou Wang ◽  
David E. Crowley

ABSTRACT Genome-wide analysis of temporal gene expression profiles in Escherichia coli following exposure to cadmium revealed a shift to anaerobic metabolism and induction of several stress response systems. Disruption in the transcription of genes encoding ribosomal proteins and zinc-binding proteins may partially explain the molecular mechanisms of cadmium toxicity.


2011 ◽  
Vol 30 (10) ◽  
pp. 1701-1709 ◽  
Author(s):  
Kayo Sumida ◽  
Yoshinobu Igarashi ◽  
Naoki Toritsuka ◽  
Tomochika Matsushita ◽  
Kaori Abe-Tomizawa ◽  
...  

Dimethyl sulfoxide (DMSO) is a very common organic solvent used for dissolving lipophilic substances, for example for in vitro cell-based assays. At the same time, DMSO is known to be cytotoxic at high concentrations. Therefore, it is important to define threshold concentrations of DMSO for cells but relevant data at the molecular level are very limited. We have focused on conducting microarray analyses of human and rat hepatocytes treated with more than 100 chemicals in attempts to identify candidate biomarker genes. In the present study, the effects of DMSO on gene expression and cytotoxicity were assessed in human cryopreserved hepatocytes and rat primary cultured hepatocytes. A cytotoxicity test with lactate dehydrogenase (LDH) activity demonstrated DMSO to be noncytotoxic up to a concentration of 2% (v/v) in both cases and there were only few effects on the gene expression profiles up to 0.5% (v/v). The observed differences from controls were considered to be of little toxicological importance, but still need to be taken into account in interpretation of findings when DMSO is used at high concentration.


2020 ◽  
Vol 117 (44) ◽  
pp. 27354-27364 ◽  
Author(s):  
Siddhant U. Jain ◽  
Sima Khazaei ◽  
Dylan M. Marchione ◽  
Stefan M. Lundgren ◽  
Xiaoshi Wang ◽  
...  

A high percentage of pediatric gliomas and bone tumors reportedly harbor missense mutations at glycine 34 in genes encoding histone variant H3.3. We find that these H3.3 G34 mutations directly alter the enhancer chromatin landscape of mesenchymal stem cells by impeding methylation at lysine 36 on histone H3 (H3K36) by SETD2, but not by the NSD1/2 enzymes. The reduction of H3K36 methylation by G34 mutations promotes an aberrant gain of PRC2-mediated H3K27me2/3 and loss of H3K27ac at active enhancers containing SETD2 activity. This altered histone modification profile promotes a unique gene expression profile that supports enhanced tumor development in vivo. Our findings are mirrored in G34W-containing giant cell tumors of bone where patient-derived stromal cells exhibit gene expression profiles associated with early osteoblastic differentiation. Overall, we demonstrate that H3.3 G34 oncohistones selectively promote PRC2 activity by interfering with SETD2-mediated H3K36 methylation. We propose that PRC2-mediated silencing of enhancers involved in cell differentiation represents a potential mechanism by which H3.3 G34 mutations drive these tumors.


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