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PubMed2006

Gene expression profiles in fathead minnow exposed to 2,4-DNT: correlation with toxicity in mammals.

Toxicogenomics, the genome-wide analysis of gene expression to study the effect of toxicants, has great potential for use in environmental toxicology. Applied to standard test organisms, it has possible applications in aquatic toxicology as a sensitive monitoring tool to detect the presence of contaminants while providing information on the mechanisms of action of these pollutants. We describe the use of a complementary DNA (cDNA) microarray of the fathead minnow (Pimephales promelas) a standard sentinel organism in aquatic toxicology, to better understand the mechanisms of toxicity of 2,4-dinitrotoluene (2,4-DNT) which is released in the environment through military and industrial use. We have constructed a fathead minnow microarray containing 5000 randomly picked anonymous cDNAs from a whole fish cDNA library. Expression profiles were analyzed in fish exposed to 2,4-DNT for 10 days at three concentrations (11, 22, and 44 microM, respectively) below the measured median lethal concentration (58 microM). Sequence analysis of cDNAs corresponding to differentially expressed genes affected by exposure revealed that lipid metabolism and oxygen transport genes were prominently affected in a dose-specific manner. We measured liver lipids and demonstrate that lipid metabolism is indeed perturbed following exposure. These observations correlate well with available toxicological data on 2,4-DNT. We present possible modes of action of 2,4-DNT toxicity and suggest that fathead minnow cDNA microarrays can be useful to identify mechanisms of toxicity in fish and as a predictive tool for toxicity in mammals.

Animals↗

PubMed2000

Aged human muscle demonstrates an altered gene expression profile consistent with an impaired response to exercise.

The gene expression profile of skeletal muscle from healthy older (62-75 years old) compared with younger (20-34 years old) men demonstrated elevated expression of genes typical of a stress or damage response, and decreased expression of a gene encoding a DNA repair/cell cycle checkpoint protein. Although the expression of these genes was relatively unaffected by a single bout of resistance exercise in older men, acute exercise altered gene expression in younger men such that post-exercise gene expression in younger men was similar to baseline gene expression in older men. The lack of response of muscle from older subjects to resistance exercise was also apparent in the expression of the inflammatory response gene IL-1beta, which did not differ between the age groups at baseline, but increased within 24 h of the exercise bout only in younger subjects. Other genes with potentially important roles in the adaptation of muscle to exercise, specifically in the processes of angiogenesis and cell proliferation, showed a similar response to exercise in older compared with younger subjects. Only one gene encoding the multifunctional, early growth response transcription factor EGR-1, showed an opposite pattern of expression in response to exercise, acutely decreasing in younger and increasing in older subjects. These results may provide a molecular basis for the inherent variability in the response of muscle from older as compared with younger individuals to resistance training.

Adult↗

PubMed2005

[Analysis on tumor related gene expression profiles in benzene poisoning using cDNA microarray].

OBJECTIVE: To detect target genes for further study by way of analyzing the gene expression profiles of benzene poisoning by using cDNA microarray. METHODS: Peripheral mononuclear cells were isolated from seven patients with benzene poisoning of different degrees, and sevene age-and sex-matched normal subjects. Total RNA was extracted and purified, followed by revese transcription to cDNAs with concomitant incorporation of fluorescent dCTP (Cy3 or Cy5). The cDNAs were used as probes in microarray of 2780 cloned cDNA. Fluorescent signals were scanned to detect genes differentially expressed in patients and normal subjects. RESULTS: Among 7 pieces of cDNA microarray of 2780 tumour related genes, the expression of 16 genes, such as GRO1, TGFBR3, LYN ctc was upregulated, whereas the expression of 28 genes, such as FOSB, DJ-1, MCT-1 etc was down-regulated. CONCLUSION: Abnormal expression of tumour related genes of patients exposed to benzene suggests that they may be the key genes, which play important role in benzene-induced leucocythemia. cDNA microarray technique is useful to indicate the expression mode of benzene poisoning tumour related genes, and to find rapidly and effectively new research object and the way of gene therapy.

Benzene↗

PubMed2004

Gene expression profiles of bovine trophoblastic cell line (BT-1) analyzed by a custom cDNA microarray.

Gene expression of bovine trophoblast cell line (BT-1) was analyzed with a custom utero-placenta complementary DNA microarray. Expression comparison with in vivo tissues of trophoblast derivation was performed to investigate characteristics of the expression in BT-1. BT-1 is a cell line established without feeder cells using trophoblast cells that are separated from bovine blastocysts. The bovine in vivo tissues of the trophoblast derivation were collected on day 17 through 56 of gestation. Of 1,773 genes, 933 exhibited an expression difference exceeding two-fold between BT-1 and in vivo tissues. These genes were analyzed by the k-means clustering method and were distributed into six clusters. Some genes, such as placental lactogen, interferon-tau and pregnancy-associated glycoproteins, all known as trophoblast-specific genes, were detected in BT-1 as well as in vivo tissues throughout the experiment period. These trophoblast-specific genes and octamer-binding transcription factor-4, known as a marker for undifferentiation of cells in mice, were detected by RT-PCR in both BT-1 and in vivo trophoblast tissues. The overall gene expression profile in BT-1 suggests that this cell line contains trophoblast-specific characteristics and is similar to trophoblast cells around the implantation period.

Animals↗

PubMed2006

Genomewide expression profiling in the zebrafish embryo identifies target genes regulated by Hedgehog signaling during vertebrate development.

Hedgehog proteins play critical roles in organizing the embryonic development of animals, largely through modulation of target gene expression. Little is currently known, however, about the kinds and numbers of genes whose expression is controlled, directly or indirectly, by Hedgehog activity. Using techniques to globally repress or activate Hedgehog signaling in zebrafish embryos followed by microarray-based expression profiling, we have discovered a cohort of genes whose expression responds significantly to loss or gain of Hedgehog function. We have confirmed the Hedgehog responsiveness of a representative set of these genes with whole-mount in situ hybridization as well as real time PCR. In addition, we show that the consensus Gli-binding motif is enriched within the putative regulatory elements of a sizeable proportion of genes that showed positive regulation in our assay, indicating that their expression is directly induced by Hedgehog. Finally, we provide evidence that the Hedgehog-dependent spatially restricted transcription of one such gene, nkx2.9, is indeed mediated by Gli1 through a single Gli recognition site located within an evolutionarily conserved enhancer fragment. Taken together, this study represents the first comprehensive survey of target genes regulated by the Hedgehog pathway during vertebrate development. Our data also demonstrate for the first time the functionality of the Gli-binding motif in the control of Hedgehog signaling-induced gene expression in the zebrafish embryo.

Animals↗

PubMed2026

Spore type-specific gene expression profiles underlying development and leaf infection processes of Colletotrichum graminicola.

Colletotrichum graminicola causes significant losses of the staple crop maize worldwide. The fungus produces two distinct asexual spore types, oval and falcate conidia, which show unique processes in development and plant interaction. Based on genome resequencing of our laboratory strain (CgM2/M1.001), we investigated the gene expression profiles of oval and falcate conidia during development and early leaf infection using RNA-seq. Our results reveal specific gene expression profiles between the two spore types, indicating fundamental differences in their developmental programs that reflect different modes of infection. We identified expression patterns discriminating both conidia types from mycelium and spore type-specific ones for genes encoding transcription factors, conserved fungal developmental genes, transporters, genes of secondary metabolite clusters, and pathogenicity-related functions, including effectors and carbohydrate-active enzymes (CAZymes). Our study shows that despite the identical genomic basis, oval and falcate conidia show unique transcriptomes across vegetative development and early plant interaction. Taking together, these results provide new insights into the molecular mechanisms determining the biology of C. graminicola and its interaction with the plant host.

Colletotrichum graminicola↗

PubMed2004

Effect of TERT and ATM on gene expression profiles in human fibroblasts.

Telomeres protect chromosomes from degradation, end-to-end fusion, and illegitimate recombination. Loss of telomeres may lead to cell death or senescence or may cause genomic instability, leading to tumor formation. Expression of human telomerase reverse transcriptase (TERT) in human fibroblast cells elongates their telomeres and extends their lifespan. Ataxia telangiectasia mutated (ATM) deficiency in A-T human fibroblasts results in accelerated telomere shortening, abnormal cell-cycle response to DNA damage, and early senescence. Gene expression profiling was performed by serial analysis of gene expression (SAGE) on BJ normal human skin fibroblasts, A-T cells, and BJ and A-T cells transduced with TERT cDNA and expressing telomerase activity. In the four SAGE libraries, 36,921 unique SAGE tags were detected. Pairwise comparisons between the libraries showed differential expression levels of 1%-8% of the tags. Transcripts affected by both TERT and ATM were identified according to expression patterns, making them good candidates for further studies of pathways affected by both TERT and ATM. These include MT2A, P4HB, LGALS1, CFL1, LDHA, S100A10, EIF3S8, RANBP9, and SEC63. These genes are involved in apoptosis or processes related to cell growth, and most have been found to be deregulated in cancer. Our results have provided further insight into the roles of TERT and ATM by identifying genes likely to be involved in their function. Supplementary material for this article can be found on the Genes, Chromosomes and Cancer website at http://www.interscience.wiley.com/jpages/1045-2257/suppmat/index.html.

Ataxia Telangiectasia↗

PubMed2002

Use of cDNA arrays to generate differential expression profiles for inflammatory genes in human gestational membranes delivered at term and preterm.

Inflammatory processes are implicated in preterm labour (PTL). To identify potential novel markers for PTL, we have used commercial cDNA arrays to generate profiles of differential expression of inflammation-associated genes in gestational membranes with term and PTL. RNA for cDNA probe synthesis was isolated from reflected human amnion and choriodecidua membranes delivered following Caesarean section at term before the onset of labour (TNL, n = 4), spontaneous labour at term (TSL, n = 4), and PTL with and without chorioamnionitis (PTL(+INF) and PTL(-INF) respectively, n = 4 each). Profiles were displayed relative to TNL and statistical comparisons of TSL versus TNL and PTL(+INF) versus PTL(-INF) were performed. Elevated expression of chemokines macrophage inflammatory protein 1beta(MIP-1beta) and pulmonary and activation-regulated chemokine (PARC) was observed in PTL(+INF) compared to PTL(-INF) amnion and choriodecidua respectively (P = 0.03). Likewise, the cytokines oncostatin-M and pre-B cell enhancing factor (PBEF) were more highly expressed in PTL(+INF) compared with PTL(-INF) and in TSL compared with TNL respectively (P = 0.03). Conversely, inhibin A, tissue inhibitors of matrix metalloproteinase (TIMP)-3 and TIMP-4 were all significantly elevated in PTL(-INF) compared with PTL(+INF) (P = 0.03). Furthermore, differential expression patterns of classes of genes, grouped according to function (e.g. chemokines), were noted. The cDNA array approach holds promise for identification of new candidate markers or combinations thereof for prediction or diagnosis of PTL, as well as for increasing our understanding of the particular aetiologies involved.

Cytokines↗

PubMedDate not supplied

mRNA expression profile of matrix metalloproteinases and their tissue inhibitors in malignant and non-malignant prostatic tissue.

BACKGROUND: Increased expression of matrix metalloproteinases (MMPs) was found in various carcinomas. The aim of this study was to present a comprehensive mRNA expression profile of MMPs in benign and malignant prostatic tissue. MATERIALS AND METHODS: mRNA expression patterns of MMP-1, -2, -7, -9, -11, -14 and their tissue inhibitors (TIMPs) -1, -2 and -3 were studied in cancerous and non-cancerous parts of 17 prostates removed by radical prostatectomy. Competitive reverse transcritpion PCR was used for quantification of MMP and TIMP mRNA. RESULTS: Both decreased (MMP-2, MMP-11, MMP-14) and a tendency to increased (MMP-9) MMP values in cancerous compared to the non-cancerous samples were observed. Significantly reduced TIMP-2 and TIMP-3 values were remarkable. Relatively strong associations were found among the three TIMPs while only a significant correlation between MMPs was observed between MMP-2 and MMP-7. There were no significant correlations between MMPs and tumor grade and stage and serum prostate-specific antigen. Receiver operation characteristic analyses proved that MMP and TIMP mRNA and their ratios have an insufficient capability to differentiate between cancerous and non-cancerous tissue. The ratios of MMP-9 to all three TIMPs and the ratio of MMP-14 to TIMP-3 were significantly increased. CONCLUSION: These increased ratios support the view of an imbalance between MMP-9 activity and its inhibitory counterparts in cancerous tissue as an important step in the development of prostate carcinoma and implicate the rationale of using synthetic inhibitors of MMPs as potential therapeutic tools.

Adenocarcinoma↗

PubMed2000

A pulmonary rat gene array for screening altered expression profiles in air pollutant-induced lung injury.

Pulmonary tissue injury and repair processes involve complex and coordinated cellular events such as necrosis, inflammation, cell growth/differentiation, apoptosis, and remodeling of extracellular matrix. These processes are regulated by expression of multiple mediator genes. Commercially available microarray blots and slides allow screening of hundreds to thousands of genes in a given tissue or cell preparation. However, often these blots do not contain cDNAs of one's interest and are difficult to interpret. In order to analyze the tissue expression profile of a large number of genes involved in pulmonary injury and pathology, we developed a rat gene array filter using array technology. This array consisted of 27 genes representing inflammatory and anti-inflammatory cytokines, growth factors, adhesion molecules, stress proteins, transcription factors and antioxidant enzymes; 3 negative controls, and 2 blank spots. Using rat gene-specific polymerase chain reaction (PCR) primer pairs, cDNAs for these genes were amplified and cloned into a TA vector. Plasmids with recombinant cDNA inserts were purified and blotted onto a nylon membrane. Lung total RNA was isolated at 3 or 24 h following intratracheal (IT) exposure of male Sprague Dawley rats to either saline (control), residual oil fly ash (ROFA; 3.3 mg/kg) or metals found in one instillate of ROFA: nickel (NiSO(4); 1. 3 micromol/kg) or vanadium (VSO(4); 2.2 micromol/kg). (32)P-Labeled cDNA was generated from RNA samples in a reverse transcriptase reaction and subsequently hybridized to array blots. Densitometric scans of array blots revealed a twofold induction of interleukin (IL)-6 and TIMP-1 at 24 h post ROFA or Ni exposure. The pulmonary expressions of cellular fibronectin (cFn-EIIIA), ICAM-1, IL-1beta, and iNOS genes were also increased 24 h post ROFA-, V-, or Ni-exposure. Consistent hybridization of beta-actin in all array blots and absence of hybridization signals in negative controls indicated gene specific hybridization. ROFA or metal-induced increase in the expression of IL-6 observed in array blot was validated by Northern blot hybridization. Developing a pulmonary rat gene array may provide a tool for screening the expression profile of tissue specific markers following exposure to toxic air contaminants.

Air Pollutants↗

PubMed2002

Gene expression profiles of bladder cancers: evidence for a striking effect of in vitro cell models on gene patterns.

In order to assess the effect of in vitro models on the expression of key genes known to be implicated in the development or progression of cancer, we quantified by real-time quantitative PCR the expression of 28 key genes in three bladder cancer tissue specimens and in their derived cell lines, studied either as one-dimensional single cell suspensions, two-dimensional monolayers or three-dimensional spheroids. Global analysis of gene expression profiles showed that in vitro models had a dramatic impact upon gene expression. Remarkably, quantitative differences in gene expression of 2-63-fold were observed in 24 out of 28 genes among the cell models. In addition, we observed that the in vitro model which most closely mimicked in vivo mRNA phenotype varied with both the gene and the patient. These results provide evidence that mRNA expression databases based on cancer cell lines, which are studied to provide a rationale for selection of therapy on the basis of molecular characteristics of a patient's tumour, must be carefully interpreted.

Clone Cells↗

PubMed2006

Cytokine expression profile over time in severely burned pediatric patients.

A severe burn leads to hypermetabolism and catabolism resulting in compromised function and structure of essential organs. The massive release of cytokines is implicated in this hypermetabolic response. The aim of the present study was to compare cytokine expression profiles from severely burned children without signs of infections or inhalation injury (n = 19) to the cytokine profiles from normal, noninfected, nonburned children (n = 14). The Bio-Plex suspension array system was used to measure the concentration of 17 cytokines. The expression of proinflammatory and anti-inflammatory cytokines was maximal during the first week after thermal injury. Significant increases were measured for 15 mediators during the first week after thermal injury: interleukin (IL) 1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 p70, IL-13, IL-17, interferon gamma, monocyte chemoattractant protein 1, macrophage inflammatory protein 1beta, and granulocyte colony-stimulating factor (P < 0.05). Granulocyte-macrophage colony-stimulating factor was significantly increased during the second week after burn (P < 0.05). Within 5 weeks, the serum concentrations of most cytokines decreased, approaching normal levels. When compared with the cytokine levels measured in normal children, a total of 16 cytokines were significantly altered (P < 0.05). After severe burn, a specific cytokine expression profile is observed in patients without complications such as inhalation injury or sepsis. The cytokine concentrations decrease during 5 weeks after burn but remain elevated over nonburned values. Furthermore, the elevation in most serum cytokine levels during the first week after burn may indicate a potential window of opportunity for therapeutic intervention.

Adolescent↗

PubMed2002

Quantitative assessment of the use of modified nucleoside triphosphates in expression profiling: differential effects on signal intensities and impacts on expression ratios.

BACKGROUND: The power of DNA microarrays derives from their ability to monitor the expression levels of many genes in parallel. One of the limitations of such powerful analytical tools is the inability to detect certain transcripts in the target sample because of artifacts caused by background noise or poor hybridization kinetics. The use of base-modified analogs of nucleoside triphosphates has been shown to increase complementary duplex stability in other applications, and here we attempted to enhance microarray hybridization signal across a wide range of sequences and expression levels by incorporating these nucleotides into labeled cRNA targets. RESULTS: RNA samples containing 2-aminoadenosine showed increases in signal intensity for a majority of the sequences. These results were similar, and additive, to those seen with an increase in the hybridization time. In contrast, 5-methyluridine and 5-methylcytidine decreased signal intensities. Hybridization specificity, as assessed by mismatch controls, was dependent on both target sequence and extent of substitution with the modified nucleotide. Concurrent incorporation of modified and unmodified ATP in a 1:1 ratio resulted in significantly greater numbers of above-threshold ratio calls across tissues, while preserving ratio integrity and reproducibility. CONCLUSIONS: Incorporation of 2-aminoadenosine triphosphate into cRNA targets is a promising method for increasing signal detection in microarrays. Furthermore, this approach can be optimized to minimize impact on yield of amplified material and to increase the number of expression changes that can be detected.

Adenosine↗

PubMed2004

Orthologous gene-expression profiling in multi-species models: search for candidate genes.

Microarray-driven gene-expression profiles are generally produced and analyzed for a single specific experimental model. We have assessed an analytical approach that simultaneously evaluates multi-species experimental models within a particular biological condition using orthologous genes as linkers for the various Affymetrix microarray platforms on multi-species models of ventilator-associated lung injury. The results suggest that this approach may be a useful tool in the evaluation of biological processes of interest and selection of process-related candidate genes.

Animals↗

PubMed2006

Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling.

Rejection diagnosis by endomyocardial biopsy (EMB) is invasive, expensive and variable. We investigated gene expression profiling of peripheral blood mononuclear cells (PBMC) to discriminate ISHLT grade 0 rejection (quiescence) from moderate/severe rejection (ISHLT > or = 3A). Patients were followed prospectively with blood sampling at post-transplant visits. Biopsies were graded by ISHLT criteria locally and by three independent pathologists blinded to clinical data. Known alloimmune pathways and leukocyte microarrays identified 252 candidate genes for which real-time PCR assays were developed. An 11 gene real-time PCR test was derived from a training set (n = 145 samples, 107 patients) using linear discriminant analysis (LDA), converted into a score (0-40), and validated prospectively in an independent set (n = 63 samples, 63 patients). The test distinguished biopsy-defined moderate/severe rejection from quiescence (p = 0.0018) in the validation set, and had agreement of 84% (95% CI 66% C94%) with grade ISHLT > or = 3A rejection. Patients >1 year post-transplant with scores below 30 (approximately 68% of the study population) are very unlikely to have grade > or = 3A rejection (NPV = 99.6%). Gene expression testing can detect absence of moderate/severe rejection, thus avoiding biopsy in certain clinical settings. Additional clinical experience is needed to establish the role of molecular testing for clinical event prediction and immunosuppression management.

Adolescent↗

PubMed2005

Gene expression profiles in hypoxic preconditioning using cDNA microarray analysis: altered expression of an angiogenic factor, carcinoembryonic antigen-related cell adhesion molecule 1.

Hypoxic preconditioning has been shown to exhibit cardioprotective effects on myocardium from ischemic or reperfusion injury. The specific regulated gene involved in the hypoxia-induced cardioprotective effects is profiled in this study. Young male Wistar rats and ICR mice were exposed to sea level (as normal control) or simulated high altitude for 15 h/day for 2, 4, or 8 weeks, or for 4 weeks at high altitude after 2 weeks at sea level. The left ventricles of the animals were isolated for mRNA isolation and cDNA microarray analysis. Our data demonstrated that hypoxic preconditioning significantly ameliorated cardiac ischemic injury by minimizing the infarct size. After cluster analysis of expression profiles after different courses of hypoxic preconditioning (0, 2, 4, and 8 weeks), 386 genes showed an ascending pattern, whereas 301 genes showed a descending pattern. The ascending genes include several angiogenic factors: FGF receptor 4, vascular endothelial growth factor (vEGF), and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1). The microvessel density was also significantly increased in hypoxic hearts. Using Western blotting and immunohistochemical analysis, the protein expression level and localization of CEACAM-1 were observed in hypoxic myocardium. The results also indicated that CEACAM-1 was upregulated as with other hypoxic angiogenic factors, heme oxygenase 1 (HO-1) and hypoxia inducible factor-1alpha (HIF-1alpha), in in vitro cultured cardiomyocytes (H9c2) after hypoxia treatment and in vivo hypoxic preconditioning. Furthermore, incubation with recombinant vEGF could also increase the expression level of CEACAM-1 in H9c2 cells. These results demonstrated that hypoxic preconditioning resulted in transcriptional changes, and some of these genes have been correlated with angiogenesis. The HIF-1/vEGF/CEACAM-1 pathway might be important for hypoxia-induced angiogenesis in the heart during hypoxic preconditioning.

Animals↗

PubMed2003

[Preliminary study on gene expression profile of endometrial adenocarcinoma].

OBJECTIVE: To determine candidate genes of endometrial adenocarcinoma. METHODS: To compare the gene expression profile in 2 endometrial adenocarcinoma tissues and 2 normal endometria by HGEC-40s GeneChip probe including 4096 genes array. Expression differences between normal and malignant tissue groups were measured by GenePixPro3.0 software. RESULTS: 350 genes with a ratio below 0.5 and above 2.0 showed discrimination between normal and malignant groups. Thirty three genes with ratio above 3 were up-regulated, forty-four genes with ratio below 0.3 were down-regulated. CONCLUSION: The overexpression of oncogenes with their disturbed or constitutively activated signal transduction cascades alone or in combination with the mutation-induced silencing of tumor suppressor genes is associated with malignant transformation.

Adenocarcinoma↗

PubMed2007

Global gene expression profiling of Bacillus subtilis in response to ammonium and tryptophan starvation as revealed by transcriptome and proteome analysis.

The global gene expression profile of Bacillus subtilis in response to ammonium and tryptophan starvation was analyzed using transcriptomics and proteomics which gained novel insights into these starvation responses. The results demonstrate that both starvation conditions induce specific, overlapping and general starvation responses. The TnrA regulon, the glutamine synthetase (glnA) as well as the sigma(L)-dependent bkd and roc operons were most strongly and specifically induced after ammonium starvation. These are involved in the uptake and utilization of ammonium and alternative nitrogen sources such as amino acids, gamma-aminobutyrate, nitrate/nitrite, uric acid/urea and oligopeptides. In addition, several carbon catabolite-controlled genes (e.g. acsA, citB), the alpha-acetolactate synthase/-decarboxylase alsSD operon and several aminotransferase genes were specifically induced after ammonium starvation. The induction of sigma(F)- and sigma(E)-dependent sporulation proteins at later time points in ammonium-starved cells was accompanied by an increased sporulation frequency. The specific response to tryptophan starvation includes the TRAP-regulated tryptophan biosynthesis genes, some RelA-dependent genes (e.g. adeC, ald) as well as spo0E. Furthermore, we recognized overlapping responses between ammonium and tryptophan starvation (e.g. dat, maeN) as well as the common induction of the CodY and sigma(H) general starvation regulons and the RelA-dependent stringent response. Many genes encoding proteins of so far unknown functions could be assigned to specifically or commonly induced genes.

Ammonium Sulfate↗