SEARCH · PubMed Health

Results for “Tissue Array Analysis”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,153 records · Page 64Linked to original sources

PubMed2006

Gene expression changes and molecular pathways mediating activity-dependent plasticity in visual cortex.

Two key models for examining activity-dependent development of primary visual cortex (V1) involve either reduction of activity in both eyes via dark-rearing (DR) or imbalance of activity between the two eyes via monocular deprivation (MD). Combining DNA microarray analysis with computational approaches, RT-PCR, immunohistochemistry and physiological imaging, we find that DR leads to (i) upregulation of genes subserving synaptic transmission and electrical activity, consistent with a coordinated response of cortical neurons to reduction of visual drive, and (ii) downregulation of parvalbumin expression, implicating parvalbumin-expressing interneurons as underlying the delay in cortical maturation after DR. MD partially activates homeostatic mechanisms but differentially upregulates molecular pathways related to growth factors and neuronal degeneration, consistent with reorganization of connections after MD. Expression of a binding protein of insulin-like growth factor-1 (IGF1) is highly upregulated after MD, and exogenous application of IGF1 prevents the physiological effects of MD on ocular dominance plasticity examined in vivo.

Animals↗

PubMed2005

Prostate cancer and the genomic revolution: Advances using microarray analyses.

The emerging technology of microarray analysis allows the establishment of molecular portraits of prostate cancer and the discovery of novel genes involved in the carcinogenesis process. Many novel genes have already been identified using this technique, and functional analyses of these genes are currently being tested. The combination of microarray analysis with other recently developed high-throughput techniques, such as proteomics, tissue arrays, and gene promoter-methylation, especially using tissue microdissection methods, will provide us with more comprehensive insights into how prostate cancer develops and responds to gene-targeted therapies. Animal models of prostate cancer are being characterized by high throughput techniques to better define the similarities and differences between those models and the human disease, and to determine whether particular models may be useful for specific targeted therapies in pre-clinical studies. Although profiling of mRNA expression provides important information of gene expression, the development of proteomic technologies will allow for an even more precise global insight into cellular signaling and structural alterations during prostate carcinogenesis. Not only will the "omic" revolution change basic science, but it will lead to a new era of molecular medicine.

Animals↗

PubMed2006

Characterization of KIAA0513, a novel signaling molecule that interacts with modulators of neuroplasticity, apoptosis, and the cytoskeleton.

KIAA0513 was previously identified as upregulated in the dorsolateral prefrontal cortex of subjects with schizophrenia by microarray analysis. In the present study, the differential expression in the schizophrenic subjects was confirmed by quantitative RT-PCR. The limited homology to proteins of known function and lack of functional domains in the encoded protein have made it difficult to predict a function for KIAA0513. We used in situ hybridization, RNA blots, western blots, and immunocytochemistry to examine KIAA0513 expression in normal brain and peripheral tissues. The gene is ubiquitously expressed but is enriched in the brain, particularly in the cerebellum. Finally, interacting proteins were identified using a yeast two-hybrid screen to functionally characterize the protein. KIAA0513 interacts with KIBRA, HAX-1, and INTS4, which also interact with proteins involved in neuroplasticity, apoptosis, and cytoskeletal regulation. Therefore, KIAA0513 is likely to be involved in signaling pathways related to these processes.

Animals↗

PubMed2006

Spinal cord transcriptional profile analysis reveals protein trafficking and RNA processing as prominent processes regulated by tactile allodynia.

Since partial peripheral injury does not necessarily lead to the development of neuropathic pain it is possible that a set of genes is directly regulated by the development of neuropathic pain independent of the genes regulated by nerve injury. This study identifies the genes expressed within the spinal cord that are uniquely regulated by tactile allodynia in rats. Using subtractive methods, genes regulated by allodynia were differentiated from those of nerve injury. Gene ontology analysis identified that allodynic genes are involved in a variety of processes including myelination, actin cytoskeleton reorganization, dephosphorylation, phosphorylation, response to stress, as well as protein trafficking and RNA processing. The processes of protein trafficking and RNA processing were found to be as statistically significant as other processes that have been associated with neuropathic pain development such as response to stress, phosphorylation, and cell migration. Trafficking and transcription are linked and undergo activity dependent regulation which results in both rapid and gradual synaptic changes (plasticity). The data presented here greatly expand the list of genes regulated by the development of tactile allodynia and reveal protein trafficking and RNA processing as prominent biological processes that may be involved in synaptic plasticity changes within the spinal cord in response to allodynia.

Animals↗

PubMed2001

NPAS2: an analog of clock operative in the mammalian forebrain.

Neuronal PAS domain protein 2 (NPAS2) is a transcription factor expressed primarily in the mammalian forebrain. NPAS2 is highly related in primary amino acid sequence to Clock, a transcription factor expressed in the suprachiasmatic nucleus that heterodimerizes with BMAL1 and regulates circadian rhythm. To investigate the biological role of NPAS2, we prepared a neuroblastoma cell line capable of conditional induction of the NPAS2:BMAL1 heterodimer and identified putative target genes by representational difference analysis, DNA microarrays, and Northern blotting. Coinduction of NPAS2 and BMAL1 activated transcription of the endogenous Per1, Per2, and Cry1 genes, which encode negatively activating components of the circadian regulatory apparatus, and repressed transcription of the endogenous BMAL1 gene. Analysis of the frontal cortex of wild-type mice kept in a 24-hour light-dark cycle revealed that Per1, Per2, and Cry1 mRNA levels were elevated during darkness and reduced during light, whereas BMAL1 mRNA displayed the opposite pattern. In situ hybridization assays of mice kept in constant darkness revealed that Per2 mRNA abundance did not oscillate as a function of the circadian cycle in NPAS2-deficient mice. Thus, NPAS2 likely functions as part of a molecular clock operative in the mammalian forebrain.

ARNTL Transcription Factors↗

PubMed2003

Classification of clear-cell sarcoma as a subtype of melanoma by genomic profiling.

PURPOSE: To develop a genome-based classification scheme for clear-cell sarcoma (CCS), also known as melanoma of soft parts (MSP), which would have implications for diagnosis and treatment. This tumor displays characteristic features of soft tissue sarcoma (STS), including deep soft tissue primary location and a characteristic translocation, t(12;22)(q13;q12), involving EWS and ATF1 genes. CCS/MSP also has typical melanoma features, including immunoreactivity for S100 and HMB45, pigmentation, MITF-M expression, and a propensity for regional lymph node metastases. MATERIALS AND METHODS: RNA samples from 21 cell lines and 60 pathologically confirmed cases of STS, melanoma, and CCS/MSP were examined using the U95A GeneChip (Affymetrix, Santa Clara, CA). Hierarchical cluster analysis, principal component analysis, and support vector machine (SVM) analysis exploited genomic correlations within the data to classify CCS/MSP. RESULTS: Unsupervised analyses demonstrated a clear distinction between STS and melanoma and, furthermore, showed that CCS/MSP cluster with the melanomas as a distinct group. A supervised SVM learning approach further validated this finding and provided a user-independent approach to diagnosis. Genes of interest that discriminate CCS/MSP included those encoding melanocyte differentiation antigens, MITF, SOX10, ERBB3, and FGFR1. CONCLUSION: Gene expression profiles support the classification of CCS/MSP as a distinct genomic subtype of melanoma. Analysis of these gene profiles using the SVM may be an important diagnostic tool. Genomic analysis identified potential targets for the development of therapeutic strategies in the treatment of this disease.

Algorithms↗

PubMed2001

Chronic cocaine-mediated changes in non-human primate nucleus accumbens gene expression.

Chronic cocaine use elicits changes in the pattern of gene expression within reinforcement-related, dopaminergic regions. cDNA hybridization arrays were used to illuminate cocaine-regulated genes in the nucleus accumbens (NAcc) of non-human primates (Macaca fascicularis; cynomolgus macaque), treated daily with escalating doses of cocaine over one year. Changes seen in mRNA levels by hybridization array analysis were confirmed at the level of protein (via specific immunoblots). Significantly up-regulated genes included: protein kinase A alpha catalytic subunit (PKA(calpha)); cell adhesion tyrosine kinase beta (PYK2); mitogen activated protein kinase kinase 1 (MEK1); and beta-catenin. While some of these changes exist in previously described cocaine-responsive models, others are novel to any model of cocaine use. All of these adaptive responses coexist within a signaling scheme that could account for known inductions of genes(e.g. fos and jun proteins, and cyclic AMP response element binding protein) previously shown to be relevant to cocaine's behavioral actions. The complete data set from this experiment has been posted to the newly created Drug and Alcohol Abuse Array Data Consortium (http://www.arraydata.org) for mining by the general research community.

Animals↗

PubMedDate not supplied

A single administration of the peptide NAP induces long-term protective changes against the consequences of head injury: gene Atlas array analysis.

The femtomolar-acting eight-amino-acid peptide (NAP), derived from activity-dependent neuroprotective protein (ADNP), provides long-term protection against the deleterious effects of closed head injury (CHI) in mice. Fifteen minutes after injury, mice were divided into two groups, control and NAP-treated and a single subcutaneous injection of NAP or vehicle was administered. A third group served as sham-treated (not subjected to head trauma). Each mouse was assessed for its clinical function, using neurological severity score, at various time intervals following CHI, up to 30-45 d. Total cerebral cortex RNA was prepared from the site of injury of CHI mice, and from parallel regions in peptide-treated and sham brains. RNA was then reversed transcribed to yield radioactive cDNA preparations that were hybridized to Atlas array membranes containing 1200 cDNAs spots. Comparison of sham-treated individual mice showed differential expression levels of at least 15 mRNA species. Furthermore, results indicated that one of the genes that did not change among individuals but specifically increased after CHI and decreased after NAP treatment was the cell surface glycoprotein Mac-1 (CD11B antigen). Thus, Mac-1 is suggested as a marker for the long-term outcome of head injury and as a potential target for NAP protective actions.

Animals↗

PubMed2005

Drug dependence, synaptic plasticity, and tissue plasminogen activator.

The mesocorticolimbic dopaminergic system plays an important role in the reinforcing effects of drugs of abuse, and the activity-dependent synaptic plasticity of the system is involved in drug dependence. A DNA microarray screening revealed that the expression levels of tissue plasminogen activator (tPA) mRNA in the nucleus accumbens of morphine- or methamphetamine-dependent rats were significantly increased compared with those in control animals. Since tPA plays a role in synaptic plasticity, we hypothesized that tPA may contribute to the development of drug dependence. Single and repeated morphine treatment as well as repeated methamphetamine treatment induced tPA mRNA expression in the nucleus accumbens, which was associated with an increase in the enzyme activity. Conditioned place preference induced by morphine was markedly reduced in mice with a targeted deletion of the tPA gene (tPA-/- mice), being accompanied by a loss of morphine-induced dopamine release. Similarly, methamphetamine-induced conditioned place preference and locomotor sensitization were reduced in tPA-/- mice. The defects of morphine-induced hyperlocomotion as well as methamphetamine-induced locomotor sensitization in tPA-/- mice were reversed by microinjection of exogenous tPA or plasmin into the nucleus accumbens. These results support our hypothesis that tPA plays a role in long-lasting neuronal changes related to drug dependence.

Animals↗

PubMed2001

ArrayExplorer, a program in Visual Basic for robust and accurate filter cDNA array analysis.

Determining the dynamics in the global regulation of gene expression holds the promise of bringing a better understanding of the processes that govern physiological cell growth regulation and its disruption during the development of disease. The advent for cDNA arrays has created the possibility for the parallel analysis of expression of thousands of genes in a given cell population, simultaneously. The level of expression of a given set of genes within the studied tissue corresponds to the intensity of a labeled cDNA probe synthesized from the studied tissue RNA and bound specifically to the cDNAs of the genes spotted on the array. The accurate extraction of gene expression intensity values is essential for further data analysis and the interpretation of the obtained results. Here, we describe a new array image-processing software developed in Microsoft Visual Basic, the ArrayExplorer, which provides a user-friendly, multiple-window interface and a number of automatic and manual features that facilitate a reliable, robust, and accurate extraction of gene intensity values from filter-array images.

Biotechnology↗

PubMed2004

Msx2 and necdin combined activities are required for smooth muscle differentiation in mesoangioblast stem cells.

Little is known about the molecular mechanism underlying specification and differentiation of smooth muscle (SM), and this is, at least in part, because of the few cellular systems available to study the acquisition of a SM phenotype in vitro. Mesoangioblasts are vessel-derived stem cells that can be induced to differentiate into different cell types of the mesoderm, including SM. We performed a DNA microarray analysis of a mesoangioblast clone that spontaneously expresses an immature SM phenotype and compared it with a sister clone mainly composed of undifferentiated progenitor cells. This study allowed us to define a gene expression profile for "stem" cells versus smooth muscle cells (SMCs) in the absence of differentiation inducers such as transforming growth factor beta. Two transcription factors, msx2 and necdin, are expressed at least 100 times more in SMCs than in stem cells, are coexpressed in all SMCs and tissues, are induced by transforming growth factor beta, and, when coexpressed, induce a number of SM markers in mesoangioblast, fibroblast, and endothelial cell lines. Conversely, their downregulation through RNA interference results in a decreased expression of SM markers. These data support the hypothesis that Msx2 and necdin act as master genes regulating SM differentiation in at least a subset of SMCs.

Animals↗

PubMed2002

Altered expression of novel genes in the cerebral cortex following experimental brain injury.

Damage to the cerebral cortex results in neurological impairments such as motor, attention, memory and executive dysfunctions. To examine the molecular mechanisms contributing to these deficits, mRNA expression was profiled using high-density cDNA microarray hybridization after experimental cortical impact injury in mice. The mRNA levels at 2 h, 6 h, 24 h, 3 days and 14 days after injury were compared with those of control animals. This revealed 86 annotated genes and 24 expression sequence tags (ESTs) as being differentially expressed with a 1.5-fold or greater change. Quantitative real-time PCR analysis was used to independently verify these results for selected genes. Seven functional classes of genes were found to be altered following injury, including transcription factors, signal transduction genes and inflammatory proteins. While a few of these genes have been previously reported to be differentially regulated following injury, the most of the genes have not been previously implicated in traumatic brain injury (TBI) pathophysiology. For example, consistent with previous reports, the transcription factor c-jun and the neurotrophic factor bdnf mRNA levels were altered as a result of TBI. Among the novel genes, the mRNA levels for the high mobility group protein 1 (hmg-1), the regulator of G-protein signaling 2 (rgs-2), the transforming growth factor beta inducible early growth response (tieg), the inhibitor of DNA binding 3 (id3), and the heterogeneous nuclear ribonucleoprotein H (hnrnp h) were changed following injury. The functional significance of these genes in neurite outgrowth, neuronal regeneration, and plasticity following injury are discussed.

Animals↗

PubMed2002

A regression-based method to identify differentially expressed genes in microarray time course studies and its application in an inducible Huntington's disease transgenic model.

Time-course studies with microarray technologies provide enormous potential for exploring underlying mechanisms of biological phenomena in many areas of biomedical research, but the large amount of gene expression data generated by such studies also presents great challenges to data analysis. Here we introduce a regression-based statistical modeling approach that identifies differentially expressed genes in microarray time-course studies. To illustrate this method, we applied it to data generated from an inducible Huntington's disease transgenic model. The regression method accounts for the induction process, incorporates relevant experimental information, and includes parameters that specifically address the research interest: the temporal differences in gene expression profiles between the mutant and control mice over the time course, in addition to heterogeneities that commonly exist in microarray data. Least-squares and estimating equation techniques were used to estimate parameters and variances, and inferences were made based on efficient and robust Z-statistics under a set of well-defined assumptions. A permutation test was also used to estimate the number of false-positives, providing an alternative measurement of statistical significance useful for investigators to make decisions on follow-up studies.

Animals↗

PubMed2006

Transcriptome analysis reveals the population of dendritic RNAs and their redistribution by neural activity.

Subcellular localization of RNA is an efficient way to localize proteins to a specific region of a cell. The dendritic localization of RNAs underlies the establishment and maintenance of the synaptic functions of neuronal cells. A requirement for dendritic RNA localization and subsequent local translation has been demonstrated in several forms of experience-dependent synaptic plasticity. In spite of several attempts to identify these RNAs, the population of RNA species present in dendrites as a whole has not been well described. Here we show the results of microarray analyses with RNAs isolated from heavy portion of polysome (HP) fraction where RNA granules are enriched in and synaptosome fraction, prepared from the rat brain. These analyses revealed the complex nature of the dendritic RNA population, which included RNAs that were not expected to be in the dendrites. Neural activity caused by an electroconvulsive shock triggered a redistribution of the population of dendritic transcriptome towards the area of overlap between the HP and the synaptosome, which is assumed to be neck of spine. This redistribution may accompany some changes in the translatability of those transcriptome, which suggests complex mechanisms of local translation in response to synaptic inputs.

Animals↗

PubMed2005

Neuregulin-regulated gene expression in mammary carcinoma cells.

Recent studies have suggested that autocrine production of Neuregulin (NRG), a growth factor that activates members of the Epidermal Growth Factor Receptor/ErbB family of proto-oncogenes, is sufficient for breast tumor initiation and progression. To elucidate the molecular mechanisms regulating these events, we undertook a global analysis of genes regulated by NRG in luminal mammary epithelial cell lines. Gene expression profiling of estrogen receptor-positive T47D cells exposed to NRG-1 revealed both previously identified and novel targets of NRG activation. Profiling of other estrogen receptor-positive breast cancer cell lines, MCF7 and SUM44, yielded a group of twenty-one genes whose transcripts are upregulated by NRG in all three lines tested. The NRG targets are FBJ murine osteosarcoma viral oncogene homolog B, Early growth response 1, v-jun avian sarcoma virus 17 oncogene homolog, Activating transcription factor 3, Homo sapiens cDNA FLJ31636 fis, Jun B proto-oncogene, Forkhead box C1, Platelet/endothelial cell adhesion molecule 1, NADPH-dependent retinol dehydrogenase/reductase, Dual specificity phosphatase 5, NGF inducible protein TIS21, Connective tissue growth factor, Jun D proto-oncogene, Serum response factor, Cullin 1, v-myc avian myelocytomatosis viral oncogene, Transient receptor potential channel 1, Low density lipoprotein receptor, Transforming growth factor beta 1, Nucleoporin 88 kDa, and Pleckstrin homology-like domain A1. Since NRG activation of these cells induces resistance to anti-hormonal therapy, the identified genes may provide clues to molecular events regulating mammary tumor progression and hormone independence.

Breast Neoplasms↗

PubMed2001

Identification of differentially expressed genes in the denervated rat hippocampus by cDNA arrays.

To elucidate the molecular mechanism underlying the physiological responses to injury in the central nervous system, gene expression profiles in rodent hippocampus following perforant path transection were investigated using cDNA array hybridization. Of the 8000 arrayed clones, 47 exhibited differential expression by >3-fold difference in the denervated hippocampus from control, with 15 up-regulated and 22 down-regulated. They can be functionally assigned into several classes, among which the most prominent are those coding proteins involved in macromolecules synthesis and processing. Northern blot analysis verified the validation of the aforementioned array data. These results throw some new light on the physiological responses of the hippocampus to entorhinal deafferentation at molecular level.

Acetylcholinesterase↗

PubMed2001

EEG1, a putative transporter expressed during epithelial organogenesis: comparison with embryonic transporter expression during nephrogenesis.

A screen for genes differentially regulated in a model of kidney development identified the novel gene embryonic epithelia gene 1 (EEG1). EEG1 exists as two transcripts of 2.4 and 3.5 kb that are most highly expressed at embryonic day 7 and later in the fetal liver, lung, placenta, and kidney. The EEG1 gene is composed of 14 exons spanning a 20-kb region at human chromosome 11p12 and the syntenic region of mouse chromosome 2. Six EEG1 exons have previously been assigned to a longer isoform of eosinophil major basic protein termed proteoglycan 2. Another gene distantly related to EEG1, POV1/PB39, is located 88 kb upstream from the EEG1 gene on chromosome 11. Temporal expression of 65 members of the solute carrier (SLC)-class of transport proteins was followed during kidney development using DNA arrays. POV-1 and EEG1, like glucose transporters, displayed very early maximal gene expression. In contrast, other SLC genes, such as organic anion and cation transporters, amino acid permeases, and nucleoside transporters, had maximal expression later in development. Thus, although the bulk of transporters are expressed late in kidney development, a fraction are expressed near the onset of nephrogenesis. The data raise the possibility that EEG1 and POV1 may define a new family of transport proteins involved in the transport of nutrients or metabolites in rapidly growing and/or developing tissues.

Amino Acid Transport System y+L↗

PubMed2005

Prediction of preadipocyte differentiation by gene expression reveals role of insulin receptor substrates and necdin.

The insulin/IGF-1 (insulin-like growth factor 1) signalling pathway promotes adipocyte differentiation via complex signalling networks. Here, using microarray analysis of brown preadipocytes that are derived from wild-type and insulin receptor substrate (Irs) knockout animals that exhibit progressively impaired differentiation, we define 374 genes/expressed-sequence tags whose expression in preadipocytes correlates with the ultimate ability of the cells to differentiate. Many of these genes, including preadipocyte factor-1 (Pref-1) and multiple members of the Wnt signalling pathway, are related to early adipogenic events. Necdin is also markedly increased in Irs knockout cells that cannot differentiate, and knockdown of necdin restores brown adipogenesis with downregulation of Pref-1 and Wnt10a expression. Insulin receptor substrate proteins regulate a necdin-E2F4 interaction that represses peroxisome-proliferator-activated receptor gamma (PPARgamma) transcription via a cyclic AMP response element binding protein (CREB)-dependent pathway. Together these define a key signalling network that is involved in brown preadipocyte determination.

Adipocytes↗