| PMC Ids | Title | Abstract | Authors | Journal | Publication Date | Product Version |
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| pmc1858692 | Expression profiling of genes regulated by TGF-beta: Differential regulation in normal and tumour cells | TGF-beta is one of the key cytokines implicated in various disease processes including cancer. TGF-beta inhibits growth and promotes apoptosis in normal epithelial cells and in contrast, acts as a pro-tumour cytokine by promoting tumour angiogenesis, immune-escape and metastasis. It is not clear if various actions of TGF-beta on normal and tumour cells are due to differential gene regulations. Hence we studied the regulation of gene expression by TGF-beta in normal and cancer cells.ResultsUsing human 19 K cDNA microarrays, we show that 1757 genes are exclusively regulated by TGF-beta in A549 cells in contrast to 733 genes exclusively regulated in HPL1D cells. In addition, 267 genes are commonly regulated in both the cell-lines. Semi-quantitative and real-time qRT-PCR analysis of some genes agrees with the microarray data. In order to identify the signalling pathways that influence TGF-beta mediated gene regulation, we used specific inhibitors of p38 MAP kinase, ERK kinase, JNK kinase and integrin signalling pathways. The data suggest that regulation of majority of the selected genes is dependent on at least one of these pathways and this dependence is cell-type specific. Interestingly, an integrin pathway inhibitor, RGD peptide, significantly affected TGF-beta regulation of Thrombospondin 1 in A549 cells.ConclusionThese data suggest major differences with respect to TGF-beta mediated gene regulation in normal and transformed cells and significant role of non-canonical TGF-beta pathways in the regulation of many genes by TGF-beta. | [ PrathibhaRanganathan, AnimeshAgrawal, RaghuBhushan, Aravinda KChavalmane, Ravi Kiran ReddyKalathur, TakashiTakahashi, PaturuKondaiah] | BMC Genomics | 2007-4-11 | 3.1 |
| pmc1448672 | Differentiation of Escherichia coli Pathotypes by Oligonucleotide Spotted Array† | To accurately determine the pathotypes of Escherichia coli strains, a comprehensive assessment of each strain that targets multiple genes is required. A new approach to the identification and characterization of E. coli pathotypes was developed by constructing gene-specific probes (70-mers) for not only the virulence genes associated with each E. coli pathotype but also the O157-, CFT073-, and K-12-specific and common genes of each pathotype. Analysis of oligonucleotide probes with reference and clinical isolates of E. coli pathotypes indicated that the array could differentiate the pathotypes on the basis of their virulence and specific gene patterns. Probes targeting common genes of E. coli were present in all the reference and clinical strains. Salmonella enterica subsp. enterica-specific genes and Salmonella core genes were used as negative controls. The entire E. coli pathotype showed reactivity to only 4 of the 81 Salmonella-specific gene probes. Characterization of the genetic and virulence profiles of a single strain by using probes for virulence factors and specific and common genes in the spotted array is an ideal diagnostic tool for determination of E. coli pathotypes and could also have a significant impact on the epidemiological analysis of E. coli infections. | [ Raghavan U. M.Palaniappan, YuZhang, DavidChiu, AlfonsoTorres, ChobiDebRoy, Thomas S.Whittam, Yung-FuChang] | Journal of Clinical Microbiology | | |
| pmc3147800 | LMO7 Mediates Cell-Specific Activation of the Rho-Myocardin-Related Transcription Factor-Serum Response Factor Pathway and Plays an Important Role in Breast Cancer Cell Migration ▿ | Serum response factor (SRF) is a ubiquitously expressed transcription factor that regulates cell-specific functions such as muscle development and breast cancer metastasis. The myocardin-related transcription factors (MRTFs), which are transcriptional coactivators mediating cell-specific functions of SRF, are also ubiquitously expressed. How MRTFs and SRF drive cell-specific transcription is still not fully understood. Here we show that LIM domain only 7 (LMO7) is a cell-specific regulator of MRTFs and plays an important role in breast cancer cell migration. LMO7 activates MRTFs by relieving actin-mediated inhibition in a manner that requires, and is synergistic with, Rho GTPase. Whereas Rho is required for LMO7 to activate full-length MRTFs that have three RPEL actin-binding motifs, the disruption of individual actin-RPEL interactions is sufficient to eliminate the Rho dependency and to allow the strong Rho-independent function of LMO7. Mechanistically, we show that LMO7 colocalizes with F-actin and reduces the G-actin/F-actin ratio via a Rho-independent mechanism. The knockdown of LMO7 in HeLa and MDA-MB-231 cells compromises both basal and Rho-stimulated MRTF activities and impairs the migration of MDA-MB-231 breast cancer cells. We also show that LMO7 is upregulated in the stroma of invasive breast carcinoma in a manner that correlates with the increased expression of SRF target genes that regulate muscle and actin cytoskeleton functions. Together, this study reveals a novel cell-specific mechanism regulating Rho-MRTF-SRF signaling and breast cancer cell migration and identifies a role for actin-RPEL interactions in integrating Rho and cell-specific signals to achieve both the synergistic and Rho-dependent activation of MRTFs. | [ QiandeHu, ChunGuo, YaliLi, Bruce J.Aronow, JinsongZhang] | Molecular and Cellular Biology | | |
| pmc3012028 | Differential gene expression and clonal selection during cellular transformation induced by adhesion deprivation | Anchorage independent growth is an important hallmark of oncogenic transformation. Previous studies have shown that when adhesion dependent fibroblasts were prevented from adhering to a substrate they underwent anoikis. In the present study we have demonstrated how anoikis resistant cells gain the transformation related properties with sequential selection of genes. We have proposed this process as a model system for selection of transformed cells from normal cells.ResultsThis report demonstrates that some fibroblasts can survive during late stages of anoikis, at which time they exhibit transformation-associated properties such as in vitro colony formation in soft agar and in vivo subcutaneous tumour formation in nude mice. Cytogenetic characterisation of these cells revealed that they contained a t (2; 2) derivative chromosome and they have a selective survival advantage in non adherent conditions. Gene expression profile indicated that these cells over expressed genes related to hypoxia, glycolysis and tumor suppression/metastasis which could be helpful in their retaining a transformed phenotype.ConclusionOur results reveal some new links between anoikis and cell transformation and they provide a reproducible model system which can potentially be useful to study multistage cancer and to identify new targets for drug development. | [ RajeswariJinka, RenuKapoor, SivapriyaPavuluri, Avinash TRaj, Mahesh JKumar, LakshmiRao, GopalPande] | BMC Cell Biology | 2010-12-2 | |
| pmc2409015 | The Absence of ALTERNATIVE OXIDASE1a in Arabidopsis Results in Acute Sensitivity to Combined Light and Drought Stress[W][OA] | Treatment of Arabidopsis (Arabidopsis thaliana) alternative oxidase1a (aox1a) mutant plants with moderate light under drought conditions resulted in a phenotypic difference compared with ecotype Columbia (Col-0), as evidenced by a 10-fold increase in the accumulation of anthocyanins in leaves, alterations in photosynthetic efficiency, and increased superoxide radical and reduced root growth at the early stages of seedling growth. Analysis of metabolite profiles revealed significant changes upon treatment in aox1a plants typical of combined stress treatments, and these were less pronounced or absent in Col-0 plants. These changes were accompanied by alteration in the abundance of a variety of transcripts during the stress treatment, providing a molecular fingerprint for the stress-induced phenotype of aox1a plants. Transcripts encoding proteins involved in the synthesis of anthocyanins, transcription factors, chloroplastic and mitochondrial components, cell wall synthesis, and sucrose and starch metabolism changed, indicating that effects were not confined to mitochondria, where the AOX1a protein is located. Microarray and quantitative reverse transcription-polymerase chain reaction analysis revealed that transcripts typically induced upon stress treatment or involved in antioxidant defense systems, especially chloroplast-located antioxidant defense components, had altered basal levels in untreated aox1a plants, suggesting a significant change in the basal equilibrium of signaling pathways that regulate these components. Taken together, these results indicate that aox1a plants have a greatly altered stress response even when mitochondria or the mitochondrial electron transport chain are not the primary target of the stress and that AOX1a plays a broad role in determining the normal redox balance in the cell. | [ EstelleGiraud, Lois H.M.Ho, RachelClifton, AdamCarroll, GonzaloEstavillo, Yew-FoonTan, Katharine A.Howell, AnetaIvanova, Barry J.Pogson, A. HarveyMillar, JamesWhelan] | Plant Physiology | | |
| pmc2802026 | Consensus miRNA expression profiles derived from interplatform normalization of microarray data | Eukaryotic gene expression is controlled at the post-transcriptional level by small noncoding RNAs called microRNAs (miRNA). miRNAs play important roles during early development and participate in gene regulatory circuits in the cell. Different high-throughput expression analysis methods including microarrays, bead-based detection, and small RNA cloning have been applied to quantitatively detect miRNAs in various tissues, cell types, and biological conditions. High-throughput expression data was collected from public repositories and processed to create a database of miRNA expression profiles. Several commonly used normalization methods were compared to identify suitable methods for cross-platform comparison of high-throughput miRNA expression data. The database provides interlaboratory and interplatform validated reference expression levels for miRNAs. The normalized expression profiles were validated by querying for well-established features of miRNA expression. Firstly, expression profiles of several tissue-specific miRNAs showed good agreement between the database and previously reported profiles. We have also identified a set of miRNAs that are constitutively expressed across mammalian tissues. Secondly, we used the database to compare the expression patterns of miRNAs belonging to the let-7 family, where the divergence in expression patterns implies that they may have diversified functionally. Lastly, we compared expression profiles of intronic and clustered miRNAs. Expression profiles of intronic miRNAs and clustered miRNAs showed either very good, or in certain cases, very poor correlation with the host gene. Interplatform comparison of miRNA expression profiles thus provides a resource of consensus expression profiles that can be used in the future for studying miRNA function and regulation. | [ RhishikeshBargaje, ManojHariharan, VinodScaria, BeenaPillai] | RNA | | |
| pmc2766089 | Microarray for molecular typing of Salmonella enterica serovars | We describe the development of a spotted array for the delineation of the most common 14 disease causing Salmonella serovars in the United States. Our array consists of 414 70mers targeting core genes of S. enterica, subspecies I specific genes, fimbrial genes, pathogenicity islands, Gifsy elements and other variable genes. Using this array we were able to identify a unique gene presence/absence profile for each of the targeted serovar which was used as the serovar differentiating criteria. Based on this profile, we developed a Matlab programme that compares the profile of an unknown sample to all 14 reference serovar profiles and give out the closest serovar match. Since we have included probes targeting most of the virulence genes and variable genes in Salmonella, in addition to using for serovar detection this array could also be used for studying the virulence gene content and also for evaluating the genetic relation between different isolates of Salmonella. | [ JoyScaria, Raghavan U.M.Palaniappan, DavidChiu, Julie AnnPhan, LalitPonnala, PatrickMcDonough, YrjoGrohn, SteffenPorwollik, MichaelMcClelland, Chien-ShunChiou, ChishihChu, Yung-FuChang] | Molecular and cellular probes | 2008-5-1 | |
| pmc1434774 | Low degree metabolites explain essential reactions and enhance modularity in biological networks | Recently there has been a lot of interest in identifying modules at the level of genetic and metabolic networks of organisms, as well as in identifying single genes and reactions that are essential for the organism. A goal of computational and systems biology is to go beyond identification towards an explanation of specific modules and essential genes and reactions in terms of specific structural or evolutionary constraints.ResultsIn the metabolic networks of Escherichia coli, Saccharomyces cerevisiae and Staphylococcus aureus, we identified metabolites with a low degree of connectivity, particularly those that are produced and/or consumed in just a single reaction. Using flux balance analysis (FBA) we also determined reactions essential for growth in these metabolic networks. We find that most reactions identified as essential in these networks turn out to be those involving the production or consumption of low degree metabolites. Applying graph theoretic methods to these metabolic networks, we identified connected clusters of these low degree metabolites. The genes involved in several operons in E. coli are correctly predicted as those of enzymes catalyzing the reactions of these clusters. Furthermore, we find that larger sized clusters are over-represented in the real network and are analogous to a 'network motif. Using FBA for the above mentioned three organisms we independently identified clusters of reactions whose fluxes are perfectly correlated. We find that the composition of the latter 'functional clusters' is also largely explained in terms of clusters of low degree metabolites in each of these organisms.ConclusionOur findings mean that most metabolic reactions that are essential can be tagged by one or more low degree metabolites. Those reactions are essential because they are the only ways of producing or consuming their respective tagged metabolites. Furthermore, reactions whose fluxes are strongly correlated can be thought of as 'glued together' by these low degree metabolites. The methods developed here could be used in predicting essential reactions and metabolic modules in other organisms from the list of metabolic reactions. | [ AreejitSamal, ShaliniSingh, VarunGiri, SandeepKrishna, NandulaRaghuram, SanjayJain] | BMC Bioinformatics | 2006-3-8 | |
| pmc3070566 | Genome-Wide Expression Analysis of Middle Eastern Colorectal Cancer Reveals FOXM1 as a Novel Target for Cancer Therapy | To identify genes potentially playing an important role in the progression of colorectal carcinoma (CRC), we screened global gene expression using cDNA expression array on 41 CRC tissue samples and 25 noncancerous colorectal tissue samples. Among the up-regulated genes, forkhead box M1 (FOXM1) has been shown to play a critical role in pathogenesis of various malignancies. Using immunohistochemistry on 448 Saudi CRC samples in tissue microarray format, FoxM1 protein overexpression was seen in 66% of CRC tissues and was significantly associated with poorly differentiated and highly proliferative tumors (P = 0.0200 and 0.0018, respectively). FoxM1 expression was also significantly associated with MMP-9 protein expression (P = 0.0002). In vitro data using CRC cell lines showed that inhibition of FoxM1 by thiostrepton resulted in inhibition of proliferation and induction of apoptosis in a dose-dependent manner. Overexpression of FoxM1 potentiated cell proliferation, cell transformation, and migration/invasion of CRC cells via up-regulation of FoxM1 target genes MMP2 and MMP9 and protected these cells from thiostrepton-mediated antiproliferative effects. Finally, in vivo, overexpression of FoxM1 promoted growth of CRC-cell line xenograft tumors in nude mice. Altogether, our data indicate that FoxM1 signaling contributes to aggressiveness in a subset of CRC and that the FOXM1 gene may serve as a useful molecular biomarker and potential therapeutic target. | [ ShahabUddin, MaqboolAhmed, AzharHussain, JehadAbubaker, NasserAl-Sanea, AlaaAbdulJabbar, Luai H.Ashari, SamarAlhomoud, FouadAl-Dayel, ZeenathJehan, PrashantBavi, Abdul K.Siraj, Khawla S.Al-Kuraya] | The American Journal of Pathology | | |
| pmc2633829 | Mapping Metabolic and Transcript Temporal Switches during Germination in Rice Highlights Specific Transcription Factors and the Role of RNA Instability in the Germination Process1[W][OA] | Transcriptome and metabolite profiling of rice (Oryza sativa) embryo tissue during a detailed time course formed a foundation for examining transcriptional and posttranscriptional processes during germination. One hour after imbibition (HAI), independent of changes in transcript levels, rapid changes in metabolism occurred, including increases in hexose phosphates, tricarboxylic acid cycle intermediates, and γ-aminobutyric acid. Later changes in the metabolome, including those involved in carbohydrate, amino acid, and cell wall metabolism, appeared to be driven by increases in transcript levels, given that the large group (over 6,000 transcripts) observed to increase from 12 HAI were enriched in metabolic functional categories. Analysis of transcripts encoding proteins located in the organelles of primary metabolism revealed that for the mitochondrial gene set, a greater proportion of transcripts peaked early, at 1 or 3 HAI, compared with the plastid set, and notably, many of these transcripts encoded proteins involved in transport functions. One group of over 2,000 transcripts displayed a unique expression pattern beginning with low levels in dry seeds, followed by a peak in expression levels at 1 or 3 HAI, before markedly declining at later time points. This group was enriched in transcription factors and signal transduction components. A subset of these transiently expressed transcription factors were further interrogated across publicly available rice array data, indicating that some were only expressed during the germination process. Analysis of the 1-kb upstream regions of transcripts displaying similar changes in abundance identified a variety of common sequence motifs, potential binding sites for transcription factors. Additionally, newly synthesized transcripts peaking at 3 HAI displayed a significant enrichment of sequence elements in the 3′ untranslated region that have been previously associated with RNA instability. Overall, these analyses reveal that during rice germination, an immediate change in some metabolite levels is followed by a two-step, large-scale rearrangement of the transcriptome that is mediated by RNA synthesis and degradation and is accompanied by later changes in metabolite levels. | [ Katharine A.Howell, ReenaNarsai, AdamCarroll, AnetaIvanova, MarcLohse, BjörnUsadel, A. HarveyMillar, JamesWhelan] | Plant Physiology | | |
| pmc2719799 | Global Brain Gene Expression Analysis Links Glutamatergic and GABAergic Alterations to Suicide and Major Depression | Most studies investigating the neurobiology of depression and suicide have focused on the serotonergic system. While it seems clear that serotonergic alterations play a role in the pathogenesis of these major public health problems, dysfunction in additional neurotransmitter systems and other molecular alterations may also be implicated. Microarray expression studies are excellent screening tools to generate hypotheses about additional molecular processes that may be at play. In this study we investigated brain regions that are known to be implicated in the neurobiology of suicide and major depression are likely to represent valid global molecular alterations.Methodology/Principal FindingsWe performed gene expression analysis using the HG-U133AB chipset in 17 cortical and subcortical brain regions from suicides with and without major depression and controls. Total mRNA for microarray analysis was obtained from 663 brain samples isolated from 39 male subjects, including 26 suicide cases and 13 controls diagnosed by means of psychological autopsies. Independent brain samples from 34 subjects and animal studies were used to control for the potential confounding effects of comorbidity with alcohol. Using a Gene Ontology analysis as our starting point, we identified molecular pathways that may be involved in depression and suicide, and performed follow-up analyses on these possible targets. Methodology included gene expression measures from microarrays, Gene Score Resampling for global ontological profiling, and semi-quantitative RT-PCR. We observed the highest number of suicide specific alterations in prefrontal cortical areas and hippocampus. Our results revealed alterations of synaptic neurotransmission and intracellular signaling. Among these, Glutamatergic (GLU) and GABAergic related genes were globally altered. Semi-quantitative RT-PCR results investigating expression of GLU and GABA receptor subunit genes were consistent with microarray data.Conclusions/SignificanceThe observed results represent the first overview of global expression changes in brains of suicide victims with and without major depression and suggest a global brain alteration of GLU and GABA receptor subunit genes in these conditions. | [ AdolfoSequeira, FirozaMamdani, CarlErnst, Marquis P.Vawter, William E.Bunney, VeroniqueLebel, SoniaRehal, TimKlempan, AlainGratton, ChawkiBenkelfat, Guy A.Rouleau, NaguibMechawar, GustavoTurecki] | PLoS ONE | 2009-8-11 | |
| pmc2736006 | Defining Core Metabolic and Transcriptomic Responses to Oxygen Availability in Rice Embryos and Young Seedlings1[W][OA] | Analysis reveals that there is limited overlap in the sets of transcripts that show significant changes in abundance during anaerobiosis in different plant species. This may be due to the fact that a combination of primary effects, changes due to the presence or absence of oxygen, and secondary effects, responses to primary changes or tissue and developmental responses, are measured together and not differentiated from each other. In order to dissect out these responses, the effect of the presence or absence of oxygen was investigated using three different experimental designs using rice (Oryza sativa) as a model system. A total of 110 metabolites and 9,596 transcripts were found to change significantly in response to oxygen availability in at least one experiment. However, only one-quarter of these showed complementary responses to oxygen in all three experiments, allowing the core response to oxygen availability to be defined. A total of 10 metabolites and 1,136 genes could be defined as aerobic responders (up-regulated in the presence of oxygen and down-regulated in its absence), and 13 metabolites and 730 genes could be defined as anaerobic responders (up-regulated in the absence of oxygen and down-regulated in its presence). Defining core sets of transcripts that were sensitive to oxygen provided insights into alterations in metabolism, specifically carbohydrate and lipid metabolism and the putative regulatory mechanisms that allow rice to grow under anaerobic conditions. Transcript abundance of a specific set of transcription factors was sensitive to oxygen availability during all of the different experiments conducted, putatively identifying primary regulators of gene expression under anaerobic conditions. Combined with the possibility of selective transcript degradation, these transcriptional processes are involved in the core response of rice to anaerobiosis. | [ ReenaNarsai, Katharine A.Howell, AdamCarroll, AnetaIvanova, A. HarveyMillar, JamesWhelan] | Plant Physiology | | |
| pmc2716371 | Identification of novel candidate target genes, including EPHB3, MASP1 and SST at 3q26.2–q29 in squamous cell carcinoma of the lung | The underlying genetic alterations for squamous cell carcinoma (SCC) and adenocarcinoma (AC) carcinogenesis are largely unknown.MethodsHigh-resolution array- CGH was performed to identify the differences in the patterns of genomic imbalances between SCC and AC of non-small cell lung cancer (NSCLC).ResultsOn a genome-wide profile, SCCs showed higher frequency of gains than ACs (p = 0.067). More specifically, statistically significant differences were observed across the histologic subtypes for gains at 2q14.2, 3q26.2–q29, 12p13.2–p13.33, and 19p13.3, as well as losses at 3p26.2–p26.3, 16p13.11, and 17p11.2 in SCC, and gains at 7q22.1 and losses at 15q22.2–q25.2 occurred in AC (P < 0.05). The most striking difference between SCC and AC was gains at the 3q26.2–q29, occurring in 86% (19/22) of SCCs, but in only 21% (3/14) of ACs. Many significant genes at the 3q26.2–q29 regions previously linked to a specific histology, such as EVI1,MDS1, PIK3CA and TP73L, were observed in SCC (P < 0.05). In addition, we identified the following possible target genes (> 30% of patients) at 3q26.2–q29: LOC389174 (3q26.2),KCNMB3 (3q26.32),EPHB3 (3q27.1), MASP1 and SST (3q27.3), LPP and FGF12 (3q28), and OPA1,KIAA022,LOC220729, LOC440996,LOC440997, and LOC440998 (3q29), all of which were significantly targeted in SCC (P < 0.05). Among these same genes, high-level amplifications were detected for the gene, EPHB3, at 3q27.1, and MASP1 and SST, at 3q27.3 (18, 18, and 14%, respectively). Quantitative real time PCR demonstrated array CGH detected potential candidate genes that were over expressed in SCCs.ConclusionUsing whole-genome array CGH, we have successfully identified significant differences and unique information of chromosomal signatures prevalent between the SCC and AC subtypes of NSCLC. The newly identified candidate target genes may prove to be highly attractive candidate molecular markers for the classification of NSCLC histologic subtypes, and could potentially contribute to the pathogenesis of the squamous cell carcinoma of the lung. | [ Ji UnKang, Sun HoeKoo, Kye ChulKwon, Jong WooPark, Jin ManKim] | BMC Cancer | 2009-7-16 | 3.3 |
| pmc2492625 | Identification of Regulatory Pathways Controlling Gene Expression of Stress-Responsive Mitochondrial Proteins in Arabidopsis1[W][OA] | In this study we analyzed transcript abundance and promoters of genes encoding mitochondrial proteins to identify signaling pathways that regulate stress-induced gene expression. We used Arabidopsis (Arabidopsis thaliana) alternative oxidase AOX1a, external NADP H-dehydrogenase NDB2, and two additional highly stress-responsive genes, At2g21640 and BCS1. As a starting point, the promoter region of AOX1a was analyzed and functional analysis identified 10 cis-acting regulatory elements (CAREs), which played a role in response to treatment with H2O2, rotenone, or both. Six of these elements were also functional in the NDB2 promoter. The promoter region of At2g21640, previously defined as a hallmark of oxidative stress, shared two functional CAREs with AOX1a and was responsive to treatment with H2O2 but not rotenone. Microarray analysis further supported that signaling pathways induced by H2O2 and rotenone are not identical. The promoter of BCS1 was not responsive to H2O2 or rotenone, but highly responsive to salicylic acid (SA), whereas the promoters of AOX1a and NDB2 were unresponsive to SA. Analysis of transcript abundance of these genes in a variety of defense signaling mutants confirmed that BCS1 expression is regulated in a different manner compared to AOX1a, NDB2, and At2g21640. These mutants also revealed a pathway associated with programmed cell death that regulated AOX1a in a manner distinct from the other genes. Thus, at least three distinctive pathways regulate mitochondrial stress response at a transcriptional level, an SA-dependent pathway represented by BCS1, a second pathway that represents a convergence point for signals generated by H2O2 and rotenone on multiple CAREs, some of which are shared between responsive genes, and a third pathway that acts via EDS1 and PAD4 regulating only AOX1a. Furthermore, posttranscriptional regulation accounts for changes in transcript abundance by SA treatment for some genes. | [ Lois H.M.Ho, EstelleGiraud, VindyaUggalla, RyanLister, RachelClifton, AngelaGlen, DaveThirkettle-Watts, OlivierVan Aken, JamesWhelan] | Plant Physiology | | |
| pmc2585517 | Inhibiting AP-1 activity alters cocaine induced gene expression and potentiates sensitization | We have expressed A-FOS, an inhibitor of AP-1 DNA binding, in adult mouse striatal neurons. We observe normal behavior including locomotion and exploratory activities. Following a single injection of cocaine, locomotion increased similarly in both the A-FOS expressing and littermate controls. However, following repeated injections of cocaine, the A-FOS expressing mice showed increased locomotion relative to littermate controls, an increase that persisted following a week of withdrawal and subsequent cocaine administration. These results indicate that AP-1 suppresses this behavioral responses to cocaine. We analyzed mRNA from the striatum before and 4 and 24 hours after a single cocaine injection in both A-FOS and control striata using Affymetrix microarrays (430 2.0 Array) to identify genes mis-regulated by A-FOS that may mediate the increased locomotor sensitization to cocaine. A-FOS expression did not change gene expression in the basal state or 4 hours following cocaine treatment relative to controls. However, 24 hours after an acute cocaine treatment, 84 genes were identified that were differentially expressed between the A-FOS and control mice. 56 gene are down regulated while 28 genes are up regulated including previously identified candidates for addiction including BDNF and Per1. Using a random sample of identified genes, quantitative PCR was used to verify the microarray studies. The chromosomal location of these 84 genes was compared to human genome scans of addiction to identify potential genes in humans that are involved in addiction. | [ Ronald F.Paletzki, Max V.Myakishev, OksanaPolesskaya, AndrasOrosz, Steven E.Hyman, CharlesVinson] | Neuroscience | 2008-2-7 | |
| pmc2063513 | Gene Expression in Human Hippocampus from Cocaine Abusers Identifies Genes which Regulate Extracellular Matrix Remodeling | The chronic effects of cocaine abuse on brain structure and function are blamed for the inability of most addicts to remain abstinent. Part of the difficulty in preventing relapse is the persisting memory of the intense euphoria or cocaine “rush”. Most abused drugs and alcohol induce neuroplastic changes in brain pathways subserving emotion and cognition. Such changes may account for the consolidation and structural reconfiguration of synaptic connections with exposure to cocaine. Adaptive hippocampal plasticity could be related to specific patterns of gene expression with chronic cocaine abuse. Here, we compare gene expression profiles in the human hippocampus from cocaine addicts and age-matched drug-free control subjects. Cocaine abusers had 151 gene transcripts upregulated, while 91 gene transcripts were downregulated. Topping the list of cocaine-regulated transcripts was RECK in the human hippocampus (FC = 2.0; p<0.05). RECK is a membrane-anchored MMP inhibitor that is implicated in the coordinated regulation of extracellular matrix integrity and angiogenesis. In keeping with elevated RECK expression, active MMP9 protein levels were decreased in the hippocampus from cocaine abusers. Pathway analysis identified other genes regulated by cocaine that code for proteins involved in the remodeling of the cytomatrix and synaptic connections and the inhibition of blood vessel proliferation (PCDH8, LAMB1, ITGB6, CTGF and EphB4). The observed microarray phenotype in the human hippocampus identified RECK and other region-specific genes that may promote long-lasting structural changes with repeated cocaine abuse. Extracellular matrix remodeling in the hippocampus may be a persisting effect of chronic abuse that contributes to the compulsive and relapsing nature of cocaine addiction. | [ Deborah C.Mash, Jarlathffrench-Mullen, NikhilAdi, YujingQin, AndrewBuck, JohnPablo] | PLoS ONE | 2007-11-14 | |
| pmc2174890 | Genome-Wide Analysis of mRNA Decay Rates and Their Determinants in Arabidopsis thaliana[W] | To gain a global view of mRNA decay in Arabidopsis thaliana, suspension cell cultures were treated with a transcriptional inhibitor, and microarrays were used to measure transcript abundance over time. The deduced mRNA half-lives varied widely, from minutes to >24 h. Three features of the transcript displayed a correlation with decay rates: (1) genes possessing at least one intron produce mRNA transcripts significantly more stable than those of intronless genes, and this was not related to overall length, sequence composition, or number of introns; (2) various sequence elements in the 3′ untranslated region are enriched among short- and long-lived transcripts, and their multiple occurrence suggests combinatorial control of transcript decay; and (3) transcripts that are microRNA targets generally have short half-lives. The decay rate of transcripts correlated with subcellular localization and function of the encoded proteins. Analysis of transcript decay rates for genes encoding orthologous proteins between Arabidopsis, yeast, and humans indicated that yeast and humans had a higher percentage of transcripts with shorter half-lives and that the relative stability of transcripts from genes encoding proteins involved in cell cycle, transcription, translation, and energy metabolism is conserved. Comparison of decay rates with changes in transcript abundance under a variety of abiotic stresses reveal that a set of transcription factors are downregulated with similar kinetics to decay rates, suggesting that inhibition of their transcription is an important early response to abiotic stress. | [ ReenaNarsai, Katharine A.Howell, A. HarveyMillar, NicholasO'Toole, IanSmall, JamesWhelan] | The Plant Cell | | |
| pmc3246320 | Evidence for a SAL1-PAP Chloroplast Retrograde Pathway That Functions in Drought and High Light Signaling in Arabidopsis[C][W][OA] | This work describes a chloroplast-to-nucleus retrograde signaling pathway involving SAL1, a chloroplast and mitochondrial enzyme that degrades the phosphonucleotide 3′-phosphoadenosine 5′-phosphate (PAP). In the absence of SAL1 or in response to drought and high light, PAP accumulates and can move between the chloroplast and the nucleus, where it inhibits exoribonucleases, thereby inducing stress-responsive genes. | [ Gonzalo M.Estavillo, Peter A.Crisp, WannaratPornsiriwong, MarkusWirtz, DerekCollinge, ChrisCarrie, EstelleGiraud, JamesWhelan, PascaleDavid, HélèneJavot, CharlesBrearley, RüdigerHell, ElenaMarin, Barry J.Pogson] | The Plant Cell | 2011-11-29 | |
| pmc3252162 | In-Depth Temporal Transcriptome Profiling Reveals a Crucial Developmental Switch with Roles for RNA Processing and Organelle Metabolism That Are Essential for Germination in Arabidopsis1[W][OA] | Germination represents a rapid transition from dormancy to a high level of metabolic activity. In-depth transcriptomic profiling at 10 time points in Arabidopsis (Arabidopsis thaliana), including fresh seed, ripened seed, during stratification, germination, and postgermination per se, revealed specific temporal expression patterns that to our knowledge have not previously been identified. Over 10,000 transcripts were differentially expressed during cold stratification, with subequal numbers up-regulated as down-regulated, revealing an active period in preparing seeds for germination, where transcription and RNA degradation both play important roles in regulating the molecular sequence of events. A previously unidentified transient expression pattern was observed for a group of genes, whereby a significant rise in expression was observed at the end of stratification and significantly lower expression was observed 6 h later. These genes were further defined as germination specific, as they were most highly expressed at this time in germination, in comparison with all developmental tissues in the AtGenExpress data set. Functional analysis of these genes using genetic inactivation revealed that they displayed a significant enrichment for embryo-defective or -arrested phenotype. This group was enriched in genes encoding mitochondrial and nuclear RNA-processing proteins, including more than 45% of all pentatricopeptide domain-containing proteins expressed during germination. The presence of mitochondrial DNA replication factors and RNA-processing functions in this germination-specific subset represents the earliest events in organelle biogenesis, preceding any changes associated with energy metabolism. Green fluorescent protein analysis also confirmed organellar localization for 65 proteins, largely showing germination-specific expression. These results suggest that mitochondrial biogenesis involves a two-step process to produce energetically active organelles: an initial phase at the end of stratification involving mitochondrial DNA synthesis and RNA processing, and a later phase for building the better-known energetic functions. This also suggests that signals with a mitochondrial origin and retrograde signals may be crucial for successful germination. | [ ReenaNarsai, Simon R.Law, ChrisCarrie, LinXu, JamesWhelan] | Plant Physiology | 2011-9-9 | |
| pmc3161910 | Podbat: A Novel Genomic Tool Reveals Swr1-Independent H2A.Z Incorporation at Gene Coding Sequences through Epigenetic Meta-Analysis | Epigenetic regulation consists of a multitude of different modifications that determine active and inactive states of chromatin. Conditions such as cell differentiation or exposure to environmental stress require concerted changes in gene expression. To interpret epigenomics data, a spectrum of different interconnected datasets is needed, ranging from the genome sequence and positions of histones, together with their modifications and variants, to the transcriptional output of genomic regions. Here we present a tool, Podbat (Positioning database and analysis tool), that incorporates data from various sources and allows detailed dissection of the entire range of chromatin modifications simultaneously. Podbat can be used to analyze, visualize, store and share epigenomics data. Among other functions, Podbat allows data-driven determination of genome regions of differential protein occupancy or RNA expression using Hidden Markov Models. Comparisons between datasets are facilitated to enable the study of the comprehensive chromatin modification system simultaneously, irrespective of data-generating technique. Any organism with a sequenced genome can be accommodated. We exemplify the power of Podbat by reanalyzing all to-date published genome-wide data for the histone variant H2A.Z in fission yeast together with other histone marks and also phenotypic response data from several sources. This meta-analysis led to the unexpected finding of H2A.Z incorporation in the coding regions of genes encoding proteins involved in the regulation of meiosis and genotoxic stress responses. This incorporation was partly independent of the H2A.Z-incorporating remodeller Swr1. We verified an Swr1-independent role for H2A.Z following genotoxic stress in vivo. Podbat is open source software freely downloadable from www.podbat.org, distributed under the GNU LGPL license. User manuals, test data and instructions are available at the website, as well as a repository for third party–developed plug-in modules. Podbat requires Java version 1.6 or higher. | [ LaiaSadeghi, CarolinaBonilla, AnnelieStrålfors, KarlEkwall, J. PeterSvensson] | PLoS Computational Biology | 2011-8-25 | |
| pmc3163772 | Ulnar dimelia variant: a case report | We report a case of ulnar dimelia, commonly called mirror hand, in a 2-month-old female child who had restriction of elbow flexion and forearm rotation. There was no facial or other internal organ malformation. Radiographs revealed seven triphalangeal digits with double ulnae (one following the other) and absent radius. To the best of the authors’ knowledge, this is the first report of this mirror hand deformity in which fingers are symmetrical while duplicated ulnae are not. | [ JavedJameel, Abdul QayyumKhan, SohailAhmad, MazharAbbas] | Journal of Orthopaedics and Traumatology : Official Journal of the Italian Society of Orthopaedics and Traumatology | 2011-7-19 | |
| pmc3127811 | Network Clustering Revealed the Systemic Alterations of Mitochondrial Protein Expression | The mitochondrial protein repertoire varies depending on the cellular state. Protein component modifications caused by mitochondrial DNA (mtDNA) depletion are related to a wide range of human diseases; however, little is known about how nuclear-encoded mitochondrial proteins (mt proteome) changes under such dysfunctional states. In this study, we investigated the systemic alterations of mtDNA-depleted (ρ0) mitochondria by using network analysis of gene expression data. By modularizing the quantified proteomics data into protein functional networks, systemic properties of mitochondrial dysfunction were analyzed. We discovered that up-regulated and down-regulated proteins were organized into two predominant subnetworks that exhibited distinct biological processes. The down-regulated network modules are involved in typical mitochondrial functions, while up-regulated proteins are responsible for mtDNA repair and regulation of mt protein expression and transport. Furthermore, comparisons of proteome and transcriptome data revealed that ρ0 cells attempted to compensate for mtDNA depletion by modulating the coordinated expression/transport of mt proteins. Our results demonstrate that mt protein composition changed to remodel the functional organization of mitochondrial protein networks in response to dysfunctional cellular states. Human mt protein functional networks provide a framework for understanding how cells respond to mitochondrial dysfunctions. | [ JouhyunJeon, Jae HoonJeong, Je-HyunBaek, Hyun-JungKoo, Wook-HaPark, Jae-SeongYang, Myeong-HeeYu, SangukKim, Youngmi KimPak] | PLoS Computational Biology | 2011-6-30 | 4.3 |
| pmc3112449 | A study of toxicity and differential gene expression in murine liver following exposure to anti-malarial drugs: amodiaquine and sulphadoxine-pyrimethamine | Amodiaquine (AQ) along with sulphadoxine-pyrimethamine (SP) offers effective and cheaper treatment against chloroquine-resistant falciparum malaria in many parts of sub-Saharan Africa. Considering the previous history of hepatitis, agranulocytosis and neutrocytopenia associated with AQ monotherapy, it becomes imperative to study the toxicity of co-administration of AQ and SP. In this study, toxicity and resulting global differential gene expression was analyzed following exposure to these drugs in experimental Swiss mice.MethodsThe conventional markers of toxicity in serum, oxidative stress parameters in tissue homogenates, histology of liver and alterations in global transcriptomic expression were evaluated to study the toxic effects of AQ and SP in isolation and in combination.ResultsThe combination therapy of AQ and SP results in more pronounced hepatotoxicity as revealed by elevated level of serum ALT, AST with respect to their individual drug exposure regimen. Furthermore, alterations in the activity of major antioxidant enzymes (glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase), indicating the development of oxidative stress, was more significant in AQ+SP combination therapy. cDNA microarray results too showed considerably more perturbed gene expression following combination therapy of AQ and SP as compared to their individual drug treatment. Moreover, a set of genes were identified whose expression pattern can be further investigated for identifying a good biomarker for potential anti-malarial hepatotoxicity.ConclusionThese observations clearly indicate AQ+SP combination therapy is hepatotoxic in experimental Swiss mice. Microarray results provide a considerable number of potential biomarkers of anti-malarial drug toxicity. These findings hence will be useful for future drug toxicity studies, albeit implications of this study in clinical conditions need to be monitored with cautions. | [ Shrawan KumarMishra, PrabhatSingh, Srikanta KumarRath] | Malaria Journal | 2011-5-2 | |
| pmc3057973 | Genes and Gene Ontologies Common to Airflow Obstruction and Emphysema in the Lungs of Patients with COPD | Chronic obstructive pulmonary disease (COPD) is a major public health problem with increasing prevalence worldwide. The primary aim of this study was to identify genes and gene ontologies associated with COPD severity. Gene expression profiling was performed on total RNA extracted from lung tissue of 18 former smokers with COPD. Class comparison analysis on mild (n = 9, FEV1 80–110% predicted) and moderate (n = 9, FEV1 50–60% predicted) COPD patients identified 46 differentially expressed genes (p<0.01), of which 14 genes were technically confirmed by quantitative real-time-PCR. Biological replication in an independent test set of 58 lung samples confirmed the altered expression of ten genes with increasing COPD severity, with eight of these genes (NNMT, THBS1, HLA-DPB1, IGHD, ETS2, ELF1, PTGDS and CYRBD1) being differentially expressed by greater than 1.8 fold between mild and moderate COPD, identifying these as candidate determinants of COPD severity. These genes belonged to ontologies potentially implicated in COPD including angiogenesis, cell migration, proliferation and apoptosis. Our secondary aim was to identify gene ontologies common to airway obstruction, indicated by impaired FEV1 and KCO. Using gene ontology enrichment analysis we have identified relevant biological and molecular processes including regulation of cell-matrix adhesion, leukocyte activation, cell and substrate adhesion, cell adhesion, angiogenesis, cell activation that are enriched among genes involved in airflow obstruction. Exploring the functional significance of these genes and their gene ontologies will provide clues to molecular changes involved in severity of COPD, which could be developed as targets for therapy or biomarkers for early diagnosis. | [ Santiyagu M.Savarimuthu Francis, Jill E.Larsen, Sandra J.Pavey, Edwina E.Duhig, Belinda E.Clarke, Rayleen V.Bowman, Nick K.Hayward, Kwun M.Fong, Ian A.Yang] | PLoS ONE | 2011-3-15 | 4.3 |
| pmc3095337 | Common and distinct organ and stress responsive transcriptomic patterns in Oryza sativa and Arabidopsis thaliana | Arabidopsis thaliana is clearly established as the model plant species. Given the ever-growing demand for food, there is a need to translate the knowledge learned in Arabidopsis to agronomically important species, such as rice (Oryza sativa). To gain a comparative insight into the similarities and differences into how organs are built and how plants respond to stress, the transcriptomes of Arabidopsis and rice were compared at the level of gene orthology and functional categorisation.ResultsOrgan specific transcripts in rice and Arabidopsis display less overlap in terms of gene orthology compared to the orthology observed between both genomes. Although greater overlap in terms of functional classification was observed between root specific transcripts in rice and Arabidopsis, this did not extend to flower, leaf or seed specific transcripts. In contrast, the overall abiotic stress response transcriptome displayed a significantly greater overlap in terms of gene orthology compared to the orthology observed between both genomes. However, ~50% or less of these orthologues responded in a similar manner in both species. In fact, under cold and heat treatments as many or more orthologous genes responded in an opposite manner or were unchanged in one species compared to the other. Examples of transcripts that responded oppositely include several genes encoding proteins involved in stress and redox responses and non-symbiotic hemoglobins that play central roles in stress signalling pathways. The differences observed in the abiotic transcriptomes were mirrored in the presence of cis-acting regulatory elements in the promoter regions of stress responsive genes and the transcription factors that potentially bind these regulatory elements. Thus, both the abiotic transcriptome and its regulation differ between rice and Arabidopsis.ConclusionsThese results reveal significant divergence between Arabidopsis and rice, in terms of the abiotic stress response and its regulation. Both plants are shown to employ unique combinations of genes to achieve growth and stress responses. Comparison of these networks provides a more rational approach to translational studies that is based on the response observed in these two diverse plant models. | [ ReenaNarsai, IanCastleden, JamesWhelan] | BMC Plant Biology | 2010-11-24 | 4.3 |
| pmc2975236 | Conserved and Novel Functions for Arabidopsis thaliana MIA40 in Assembly of Proteins in Mitochondria and Peroxisomes | The disulfide relay system of the mitochondrial intermembrane space has been extensively characterized in Saccharomyces cerevisiae. It contains two essential components, Mia40 and Erv1. The genome of Arabidopsis thaliana contains a single gene for each of these components. Although insertional inactivation of Erv1 leads to a lethal phenotype, inactivation of Mia40 results in no detectable deleterious phenotype. A. thaliana Mia40 is targeted to and accumulates in mitochondria and peroxisomes. Inactivation of Mia40 results in an alteration of several proteins in mitochondria, an absence of copper/zinc superoxide dismutase (CSD1), the chaperone for superoxide dismutase (Ccs1) that inserts copper into CSD1, and a decrease in capacity and amount of complex I. In peroxisomes the absence of Mia40 leads to an absence of CSD3 and a decrease in abnormal inflorescence meristem 1 (Aim1), a β-oxidation pathway enzyme. Inactivation of Mia40 leads to an alteration of the transcriptome of A. thaliana, with genes encoding peroxisomal proteins, redox functions, and biotic stress significantly changing in abundance. Thus, the mechanistic operation of the mitochondrial disulfide relay system is different in A. thaliana compared with other systems, and Mia40 has taken on new roles in peroxisomes and mitochondria. | [ ChrisCarrie, EstelleGiraud, OwenDuncan, LinXu, YanWang, ShaobaiHuang, RachelClifton, MonikaMurcha, AleksandraFilipovska, OliverRackham, AliceVrielink, JamesWhelan] | The Journal of Biological Chemistry | 2010-9-9 | |
| pmc2872972 | Identification of Stage-Specific Gene Modulation during Early Thymocyte Development by Whole-Genome Profiling Analysis after Aryl Hydrocarbon Receptor Activation | The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix transcription factor, implicated as an important modulator of the immune system and of early thymocyte development. We have shown previously that AHR activation by the environmental contaminant and potent AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to a significant decline in the percentage of S-phase cells in the CD3−CD4−CD8− triple-negative stage (TN) 3 and TN4 T-cell committed thymocytes 9 to 12 h after exposure. In the more immature TN1- or TN2-stage cells, no effect on cell cycle was observed. To identify early molecular targets, which could provide insight into how the AHR acts as a modulator of thymocyte development and cell cycle regulation, we performed gene-profiling experiments using RNA isolated from four intrathymic progenitor populations in which the AHR was activated for 6 or 12 h. This microarray analysis of AHR activation identified 108 distinct gene probes that were significantly modulated in the TN1–4 thymocyte progenitor stages. Although most of the genes identified have specific AHR recognition sequences, only seven genes were altered exclusively in the two T-cell committed stages of early thymocyte development (TN3 and TN4) in which the decline of S-phase cells is seen. Moreover, all seven of these genes were reduced in expression, and five of the seven are associated with cell cycle regulatory processes. These seven genes are novel targets for modulation by the TCDD-activated AHR and may be involved in the observed cell-cycle arrest and suppression of early thymocyte development. | [ Michael D.Laiosa, Jeffrey H.Mills, Zhi-WeiLai, Kameshwar P.Singh, Frank A.Middleton, Thomas A.Gasiewicz, Allen E.Silverstone] | Molecular Pharmacology | | |
| pmc2923530 | Defining reference genes in Oryza sativa using organ, development, biotic and abiotic transcriptome datasets | Reference genes are widely used to normalise transcript abundance data determined by quantitative RT-PCR and microarrays. However, the approaches taken to define reference genes can be variable. Although Oryza sativa (rice) is a widely used model plant and important crop specie, there has been no comprehensive analysis carried out to define superior reference genes.ResultsAnalysis of 136 Affymetrix transcriptome datasets comprising of 373 genome microarrays from studies in rice that encompass tissue, developmental, abiotic, biotic and hormonal transcriptome datasets identified 151 genes whose expression was considered relatively stable under all conditions. A sub-set of 12 of these genes were validated by quantitative RT-PCR and were seen to be stable under a number of conditions. All except one gene that has been previously proposed as a stably expressed gene for rice, were observed to change significantly under some treatment.ConclusionA new set of reference genes that are stable across tissue, development, stress and hormonal treatments have been identified in rice. This provides a superior set of reference genes for future studies in rice. It confirms the approach of mining large scale datasets as a robust method to define reference genes, but cautions against using gene orthology or counterparts of reference genes in other plant species as a means of defining reference genes. | [ ReenaNarsai, AnetaIvanova, SophiaNg, JamesWhelan] | BMC Plant Biology | 2010-3-31 | 4.3 |
| pmc2872431 | Karrikins enhance light responses during germination and seedling development in Arabidopsis thaliana | Karrikins are a class of seed germination stimulants identified in smoke from wildfires. Microarray analysis of imbibed Arabidopsis thaliana seeds was performed to identify transcriptional responses to KAR1 before germination. A small set of genes that are regulated by KAR1, even when germination is prevented by the absence of gibberellin biosynthesis or light, were identified. Light-induced genes, putative HY5-binding targets, and ABRE-like promoter motifs were overrepresented among KAR1-up-regulated genes. KAR1 transiently induced the light signal transduction transcription factor genes HY5 and HYH. Germination of afterripened Arabidopsis seed was triggered at lower fluences of red light when treated with KAR1. Light-dependent cotyledon expansion and inhibition of hypocotyl elongation were enhanced in the presence of germination-active karrikins. HY5 is important for the Arabidopsis hypocotyl elongation, but not seed germination, response to karrikins. These results reveal a role for karrikins in priming light responses in the emerging seedling, and suggest that the influence of karrikins on postfire ecology may not be limited to germination recruitment. | [ David C.Nelson, Gavin R.Flematti, Julie-AnneRiseborough, Emilio L.Ghisalberti, Kingsley W.Dixon, Steven M.Smith] | Proceedings of the National Academy of Sciences of the United States of America | 2010-3-29 | |
| pmc2816217 | Gene Expression Profiling and Network Analysis Reveals Lipid and Steroid Metabolism to Be the Most Favored by TNFα in HepG2 Cells | The proinflammatory cytokine, TNFα, is a crucial mediator of the pathogenesis of several diseases, more so in cases involving the liver wherein it is critical in maintaining liver homeostasis since it is a major determiner of hepatocyte life and death. Gene expression profiling serves as an appropriate strategy to unravel the underlying signatures to envisage such varied responses and considering this, gene transcription profiling was examined in control and TNFα treated HepG2 cells.Methods and FindingsMicroarray experiments between control and TNFα treated HepG2 cells indicated that TNFα could significantly alter the expression profiling of 140 genes; among those up-regulated, several GO (Gene Ontology) terms related to lipid and fat metabolism were significantly (p<0.01) overrepresented indicating a global preference of fat metabolism within the hepatocyte and those within the down-regulated dataset included genes involved in several aspects of the immune response like immunoglobulin receptor activity and IgE binding thereby indicating a compromise in the immune defense mechanism(s). Conserved transcription factor binding sites were identified in identically clustered genes within a common GO term and SREBP-1 and FOXJ2 depicted increased occupation of their respective binding elements in the presence of TNFα. The interacting network of “lipid metabolism, small molecule biochemistry” was derived to be significantly overrepresented that correlated well with the top canonical pathway of “biosynthesis of steroids”.ConclusionsTNFα alters the transcriptome profiling within HepG2 cells with an interesting catalog of genes being affected and those involved in lipid and steroid metabolism to be the most favored. This study represents a composite analysis of the effects of TNFα in HepG2 cells that encompasses the altered transcriptome profiling, the functional analysis of the up- and down- regulated genes and the identification of conserved transcription factor binding sites. These could possibly determine TNFα mediated alterations mainly the phenotypes of hepatic steatosis and fatty liver associated with several hepatic pathological states. | [ Amit K.Pandey, NehaMunjal, MalabikaDatta] | PLoS ONE | 2010-2-4 | |
| pmc2815050 | Development of a microarray for identification of pathogenic Clostridium species | In recent years, Clostridium species have rapidly reemerged as human and animal pathogens. The detection and identification of pathogenic Clostridium species is therefore critical for clinical diagnosis and antimicrobial therapy. Traditional diagnostic techniques for clostridia are laborious, time-consuming and may adversely affect the therapeutic outcome. In this study, we developed an oligonucleotide diagnostic microarray for pathogenic Clostridium species. The microarray specificity was tested against 65 Clostridium isolates. The applicability of this microarray in a clinical setting was assessed with the use of mock stool samples. The microarray was successful in discriminating at least four species with the limit of detection as low as 104 CFU/ml. In addition, the pattern of virulence and antibiotic resistance genes of tested strains were determined through the microarrays. This approach demonstrates the high-throughput detection and identification of Clostridium species and provides advantages over traditional methods. Microarray-based techniques are promising applications for clinical diagnosis and epidemiological investigations. | [ TavanJanvilisri, JoyScaria, RobinGleed, SusanFubini, Michelle M.Bonkosky, Yrjö T.Gröhn, Yung-FuChang] | Diagnostic microbiology and infectious disease | 2009-10-30 | |
| pmc2754622 | Remodeled Respiration in ndufs4 with Low Phosphorylation Efficiency Suppresses Arabidopsis Germination and Growth and Alters Control of Metabolism at Night1[W][OA] | Respiratory oxidative phosphorylation is a cornerstone of cellular metabolism in aerobic multicellular organisms. The efficiency of this process is generally assumed to be maximized, but the presence of dynamically regulated nonphosphorylating bypasses implies that plants can alter phosphorylation efficiency and can benefit from lowered energy generation during respiration under certain conditions. We characterized an Arabidopsis (Arabidopsis thaliana) mutant, ndufs4 (for NADH dehydrogenase [ubiquinone] fragment S subunit 4), lacking complex I of the respiratory chain, which has constitutively lowered phosphorylation efficiency. Through analysis of the changes to mitochondrial function as well as whole cell transcripts and metabolites, we provide insights into how cellular metabolism flexibly adapts to reduced phosphorylation efficiency and why this state may benefit the plant by providing moderate stress tolerance. We show that removal of the single protein subunit NDUFS4 prevents assembly of complex I and removes its function from mitochondria without pleiotropic effects on other respiratory components. However, the lack of complex I promotes broad changes in the nuclear transcriptome governing growth and photosynthetic function. We observed increases in organic acid and amino acid pools in the mutant, especially at night, concomitant with alteration of the adenylate content. While germination is delayed, this can be rescued by application of gibberellic acid, and root growth assays of seedlings show enhanced tolerance to cold, mild salt, and osmotic stress. We discuss these observations in the light of recent data on the knockout of nonphosphorylating respiratory bypass enzymes that show opposite changes in metabolites and stress sensitivity. Our data suggest that the absence of complex I alters the adenylate control of cellular metabolism. | [ Etienne H.Meyer, TiagoTomaz, Adam J.Carroll, GonzaloEstavillo, EtienneDelannoy, Sandra K.Tanz, Ian D.Small, Barry J.Pogson, A. HarveyMillar] | Plant Physiology | | |
| pmc2755012 | Comparative analyses of genotype dependent expressed sequence tags and stress-responsive transcriptome of chickpea wilt illustrate predicted and unexpected genes and novel regulators of plant immunity | The ultimate phenome of any organism is modulated by regulated transcription of many genes. Characterization of genetic makeup is thus crucial for understanding the molecular basis of phenotypic diversity, evolution and response to intra- and extra-cellular stimuli. Chickpea is the world's third most important food legume grown in over 40 countries representing all the continents. Despite its importance in plant evolution, role in human nutrition and stress adaptation, very little ESTs and differential transcriptome data is available, let alone genotype-specific gene signatures. Present study focuses on Fusarium wilt responsive gene expression in chickpea.ResultsWe report 6272 gene sequences of immune-response pathway that would provide genotype-dependent spatial information on the presence and relative abundance of each gene. The sequence assembly led to the identification of a CaUnigene set of 2013 transcripts comprising of 973 contigs and 1040 singletons, two-third of which represent new chickpea genes hitherto undiscovered. We identified 209 gene families and 262 genotype-specific SNPs. Further, several novel transcription regulators were identified indicating their possible role in immune response. The transcriptomic analysis revealed 649 non-cannonical genes besides many unexpected candidates with known biochemical functions, which have never been associated with pathostress-responsive transcriptome.ConclusionOur study establishes a comprehensive catalogue of the immune-responsive root transcriptome with insight into their identity and function. The development, detailed analysis of CaEST datasets and global gene expression by microarray provide new insight into the commonality and diversity of organ-specific immune-responsive transcript signatures and their regulated expression shaping the species specificity at genotype level. This is the first report on differential transcriptome of an unsequenced genome during vascular wilt. | [ NasheemanAshraf, DeepaliGhai, PranjanBarman, SwarajBasu, NagarajuGangisetty, Mihir KMandal, NiranjanChakraborty, AsisDatta, SubhraChakraborty] | BMC Genomics | 2009-9-5 | |
| pmc2746189 | Expression profiling identifies genes involved in emphysema severity | Chronic obstructive pulmonary disease (COPD) is a major public health problem. The aim of this study was to identify genes involved in emphysema severity in COPD patients.Gene expression profiling was performed on total RNA extracted from non-tumor lung tissue from 30 smokers with emphysema. Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes. Genes were then selected for technical validation by quantitative reverse transcriptase-PCR (qRT-PCR) if also represented on microarray platforms used in previously published emphysema studies. Genes technically validated advanced to tests of biological replication by qRT-PCR using an independent test set of 62 lung samples.Class comparison identified 98 differentially expressed genes (p < 0.01). Fifty-one of those genes had been previously evaluated in differentiation between normal and severe emphysema lung. qRT-PCR confirmed the direction of change in expression in 29 of the 51 genes and 11 of those validated, remaining significant at p < 0.05. Biological replication in an independent cohort confirmed the altered expression of eight genes, with seven genes differentially expressed by greater than 1.3 fold, identifying these as candidate determinants of emphysema severity.Gene expression profiling of lung from emphysema patients identified seven candidate genes associated with emphysema severity including COL6A3, SERPINF1, ZNHIT6, NEDD4, CDKN2A, NRN1 and GSTM3. | [ Santiyagu M SavarimuthuFrancis, Jill ELarsen, Sandra JPavey, Rayleen VBowman, Nicholas KHayward, Kwun MFong, Ian AYang] | Respiratory Research | 2009-9-2 | 4.3 |
| pmc2735995 | Physiological and Transcriptome Analysis of Iron and Phosphorus Interaction in Rice Seedlings1[C][W] | The antagonistic interaction between iron (Fe) and phosphorus (P) has been noted in the area of plant nutrition. To understand the physiology and molecular mechanisms of this interaction, we studied the growth performance, nutrient concentration, and gene expression profiles of root and shoot segments derived from 10-d-old rice (Oryza sativa) seedlings under four different nutrient conditions: (1) full strength of Fe and P (+Fe+P); (2) full strength of P and no Fe (−Fe+P); (3) full strength of Fe and no P (+Fe−P); and (4) without both Fe and P (−Fe−P). While removal of Fe in the growth medium resulted in very low shoot and root Fe concentrations, the chlorotic symptoms and retarded seedling growth were only observed on seedlings grown in the presence of P. Microarray data showed that in roots, 7,628 transcripts were significantly changed in abundance in the absence of Fe alone. Interestingly, many of these changes were reversed if P was also absent (−Fe−P), with only approximately 15% overlapping with –Fe alone (–Fe+P). Analysis of the soluble Fe concentration in rice seedling shoots showed that P deficiency resulted in significantly increased Fe availability within the plants. The soluble Fe concentration under –Fe–P conditions was similar to that under +Fe+P conditions. These results provide evidence that the presence of P can affect Fe availability and in turn can influence the regulation of Fe-responsive genes. | [ LuqingZheng, FangliangHuang, ReenaNarsai, JiaojiaoWu, EstelleGiraud, FeiHe, LongjunCheng, FangWang, PingWu, JamesWhelan, HuixiaShou] | Plant Physiology | | |
| pmc2694273 | Identification of a Novel Uromodulin-Like Gene Related to Predator-Induced Bulgy Morph in Anuran Tadpoles by Functional Microarray Analysis | Tadpoles of the anuran species Rana pirica can undergo predator-specific morphological responses. Exposure to a predation threat by larvae of the salamander Hynobius retardatus results in formation of a bulgy body (bulgy morph) with a higher tail. The tadpoles revert to a normal phenotype upon removal of the larval salamander threat. Although predator-induced phenotypic plasticity is of major interest to evolutionary ecologists, the molecular and physiological mechanisms that control this response have yet to be elucidated. In a previous study, we identified various genes that are expressed in the skin of the bulgy morph. However, it proved difficult to determine which of these were key genes in the control of gene expression associated with the bulgy phenotype. Here, we show that a novel gene plays an important role in the phenotypic plasticity producing the bulgy morph. A functional microarray analysis using facial tissue samples of control and bulgy morph tadpoles identified candidate functional genes for predator-specific morphological responses. A larger functional microarray was prepared than in the previous study and used to analyze mRNAs extracted from facial and brain tissues of tadpoles from induction-reversion experiments. We found that a novel uromodulin-like gene, which we name here pirica, was up-regulated and that keratin genes were down-regulated as the period of exposure to larval salamanders increased. Pirica consists of a 1296 bp open reading frame, which is putatively translated into a protein of 432 amino acids. The protein contains a zona pellucida domain similar to that of proteins that function to control water permeability. We found that the gene was expressed in the superficial epidermis of the tadpole skin. | [ TsukasaMori, HirokoKawachi, ChiharuImai, ManabuSugiyama, YouichiKurata, OsamuKishida, KinyaNishimura] | PLoS ONE | 2009-6-16 | 4.3 |
| pmc2766699 | Microarray Analysis of Differentially Expressed Genes in the Brains of Tubby Mice | The tubby mouse is characterized by progressive retinal and cochlear degeneration and late-onset obesity. These phenotypes are caused by a loss-of-function mutation in the tub gene and are shared with several human syndromes, suggesting the importance of tubby protein in central nervous system (CNS) functioning. Although evidence suggests that tubby may act as a transcription factor mediating G-protein coupled receptor (GPCR) signaling, any downstream gene regulated by tubby has yet to be identified. To explore potential target genes of tubby with region-specific transcription patterns in the brain, we performed a microarray analysis using the cerebral cortex and hypothalamus of tubby mice. We also validated the changes of gene expression level observed with the microarray analysis using real-time RT-PCR. We found that expression of erythroid differentiation factor 1 (Erdr1) and caspase 1 (Casp1) increased, while p21-activated kinase 1 (Pak1) and cholecystokinin 2 receptor (Cck2r) expression decreased in the cerebral cortex of tubby mice. In the hypothalamic region, Casp 1 was up-regulated and µ-crystallin (CRYM) was down-regulated. Based on the reported functions of the differentially expressed genes, these individual or grouped genes may account for the phenotype of tubby mice. We discussed how altered expression of genes in tubby mice might be understood as the underlying mechanism behind tubby phenotypes. | [ Jeong HoLee, Chul HoonKim, Dong GooKim, Young SooAhn] | The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology | 2009-4-30 | |
| pmc2698405 | Microarray Identification of Clostridium difficile Core Components and Divergent Regions Associated with Host Origin▿ † | Clostridium difficile is a gram-positive, spore-forming enteric anaerobe which can infect humans and a wide variety of animal species. Recently, the incidence and severity of human C. difficile infection has markedly increased. In this study, we evaluated the genomic content of 73 C. difficile strains isolated from humans, horses, cattle, and pigs by comparative genomic hybridization with microarrays containing coding sequences from C. difficile strains 630 and QCD-32g58. The sequenced genome of C. difficile strain 630 was used as a reference to define a candidate core genome of C. difficile and to explore correlations between host origins and genetic diversity. Approximately 16% of the genes in strain 630 were highly conserved among all strains, representing the core complement of functional genes defining C. difficile. Absent or divergent genes in the tested strains were distributed across the entire C. difficile 630 genome and across all the predicted functional categories. Interestingly, certain genes were conserved among strains from a specific host species, but divergent in isolates with other host origins. This information provides insight into the genomic changes which might contribute to host adaptation. Due to a high degree of divergence among C. difficile strains, a core gene list from this study offers the first step toward the construction of diagnostic arrays for C. difficile. | [ TavanJanvilisri, JoyScaria, Angela D.Thompson, AinsleyNicholson, Brandi M.Limbago, Luis G.Arroyo, J. GlennSonger, Yrjö T.Gröhn, Yung-FuChang] | Journal of Bacteriology | 2009-4-17 | |
| pmc2633852 | Experimental Analysis of the Rice Mitochondrial Proteome, Its Biogenesis, and Heterogeneity1[W][OA] | Mitochondria in rice (Oryza sativa) are vital in expanding our understanding of the cellular response to reoxygenation of tissues after anaerobiosis, the crossroads of carbon and nitrogen metabolism, and the role of respiratory energy generation in cytoplasmic male sterility. We have combined density gradient and surface charge purification techniques with proteomics to provide an in-depth proteome of rice shoot mitochondria covering both soluble and integral membrane proteins. Quantitative comparisons of mitochondria purified by density gradients and after further surface charge purification have been used to ensure that the proteins identified copurify with mitochondria and to remove contaminants from the analysis. This rigorous approach to defining a subcellular proteome has yielded 322 nonredundant rice proteins and highlighted contaminants in previously reported rice mitochondrial proteomes. Comparative analysis with the Arabidopsis (Arabidopsis thaliana) mitochondrial proteome reveals conservation of a broad range of known and unknown function proteins in plant mitochondria, with only approximately 20% not having a clear homolog in the Arabidopsis mitochondrial proteome. As in Arabidopsis, only approximately 60% of the rice mitochondrial proteome is predictable using current organelle-targeting prediction tools. Use of the rice protein data set to explore rice transcript data provided insights into rice mitochondrial biogenesis during seed germination, leaf development, and heterogeneity in the expression of nucleus-encoded mitochondrial components in different rice tissues. Highlights include the identification of components involved in thiamine synthesis, evidence for coexpressed and unregulated expression of specific components of protein complexes, a selective anther-enhanced subclass of the decarboxylating segment of the tricarboxylic acid cycle, the differential expression of DNA and RNA replication components, and enhanced expression of specific metabolic components in photosynthetic tissues. | [ ShaobaiHuang, Nicolas L.Taylor, ReenaNarsai, HolgerEubel, JamesWhelan, A. HarveyMillar] | Plant Physiology | | |
| pmc2653327 | Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells | AIM: To determine the cytological and molecular effects of peroxisome proliferation-activated receptor (PPAR)-γ and PPAR-γ agonists on stomach cancer cells.METHODS: To determine the proliferation-suppressive effects of troglitazone and ciglitazone, SNU-216 and SNU-668 stomach cancer cells were plated in media containing 40 μmol/L troglitazone and ciglitazone at a density of 1 × 104 cells/well. After 3, 5 and 7 d, the cells were counted with a hemocytometer. To assess the appearance of PPAR-γ, a reverse-transcription polymerase chain reaction analysis was performed. On day 7, Western blotting was used to determine the effects of troglitazone and ciglitazone on the expression of p21 and phosphorylated-ERK (pERK) genes. Flow cytometry analysis was used to determine which portion of the cell cycle was delayed when troglitazone was used to suppress cell proliferation. In order to clarify the mechanism underlying the activity of troglitazone, microarray analysis was conducted.RESULTS: PPAR-γ was manifested in both SNU-216 and SNU-668 cells. Ciglitazone and troglitazone suppressed cell growth, and troglitazone was a stronger suppressor of stomach cancer cells than ciglitazone, an inducer of cell cycle arrest in the G1 phase. SNU-668 cells were also determined to be more sensitive to ciglitazone and troglitazone than SNU-216 cells. When troglitazone and ciglitazone were administered to stomach cancer cells, levels of p21 expression were increased, but ERK phosphorylation levels were reduced. When GW9662, an antagonist of PPAR-γ, was applied in conjunction with ciglitazone and troglitazone, the cell growth suppression effect was unaffected. The gene transcription program revealed a variety of alterations as the consequence of troglitazone treatment, and multiple troglitazone-associated pathways were detected. The genes whose expression was increased by troglitazone treatment were associated with cell development, differentiation, signal transmission between cells, and cell adhesion, and were also associated with reductions in cell proliferation, the cell cycle, nuclear metabolism, and phosphorylation.CONCLUSION: Troglitazone and ciglitazone suppress the proliferation of stomach cancer cells via a PPAR-γ-independent pathway. | [ Chan WooCheon, Dae HwanKim, Dong HeonKim, Yong HoonCho, Jae HunKim] | World Journal of Gastroenterology : WJG | 2009-1-21 | |
| pmc2646357 | Periodic Gene Expression Patterns during the Highly Synchronized Cell Nucleus and Organelle Division Cycles in the Unicellular Red Alga Cyanidioschyzon merolae | Previous cell cycle studies have been based on cell-nuclear proliferation only. Eukaryotic cells, however, have double membranes-bound organelles, such as the cell nucleus, mitochondrion, plastids and single-membrane-bound organelles such as ER, the Golgi body, vacuoles (lysosomes) and microbodies. Organelle proliferations, which are very important for cell functions, are poorly understood. To clarify this, we performed a microarray analysis during the cell cycle of Cyanidioschyzon merolae. C. merolae cells contain a minimum set of organelles that divide synchronously. The nuclear, mitochondrial and plastid genomes were completely sequenced. The results showed that, of 158 genes induced during the S or G2-M phase, 93 were known and contained genes related to mitochondrial division, ftsZ1-1, ftsz1-2 and mda1, and plastid division, ftsZ2-1, ftsZ2-2 and cmdnm2. Moreover, three genes, involved in vesicle trafficking between the single-membrane organelles such as vps29 and the Rab family protein, were identified and might be related to partitioning of single-membrane-bound organelles. In other genes, 46 were hypothetical and 19 were hypothetical conserved. The possibility of finding novel organelle division genes from hypothetical and hypothetical conserved genes in the S and G2-M expression groups is discussed. | [ TakayukiFujiwara, OsamiMisumi, KousukeTashiro, YamatoYoshida, KeijiNishida, FumiYagisawa, SousukeImamura, MasakiYoshida, ToshiyukiMori, KanTanaka, HarukoKuroiwa, TsuneyoshiKuroiwa] | DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes | 2009-1-14 | |
| pmc2648095 | Regulation of Carotenoid Composition and Shoot Branching in Arabidopsis by a Chromatin Modifying Histone Methyltransferase, SDG8[W] | Carotenoid pigments are critical for plant survival, and carotenoid composition is tuned to the developmental stage, tissue, and to environmental stimuli. We report the cloning of the CAROTENOID CHLOROPLAST REGULATORY1 (CCR1) gene. The ccr1 mutant has increased shoot branching and altered carotenoid composition, namely, reduced lutein in leaves and accumulation of cis-carotenes in dark-grown seedlings. The CCR1 gene was previously isolated as EARLY FLOWERING IN SHORT DAYS and encodes a histone methyltransferase (SET DOMAIN GROUP 8) that methylates histone H3 on Lys 4 and/or 36 (H3K4 and H3K36). ccr1 plants show reduced trimethyl-H3K4 and increased dimethyl-H3K4 surrounding the CAROTENOID ISOMERASE (CRTISO) translation start site, which correlates with low levels of CRTISO mRNA. Microarrays of ccr1 revealed the downregulation of 85 genes, including CRTISO and genes associated with signaling and development, and upregulation of just 28 genes. The reduction in CRTISO transcript abundance explains the altered carotenoid profile. The changes in shoot branching are additive with more axillary branching mutants, but the altered carotenoid profile may partially affect shoot branching, potentially by perturbed biosynthesis of the carotenoid substrates of strigolactones. These results are consistent with SDG8 regulating shoot meristem activity and carotenoid biosynthesis by modifying the chromatin surrounding key genes, including CRTISO. Thus, the level of lutein, the most abundant carotenoid in higher plants that is critical for photosynthesis and photoprotection, appears to be regulated by a chromatin modifying enzyme in Arabidopsis thaliana. | [ Christopher I.Cazzonelli, Abby J.Cuttriss, Susan B.Cossetto, WilliamPye, PeterCrisp, JimWhelan, E. JeanFinnegan, ColinTurnbull, Barry J.Pogson] | The Plant Cell | | |
| pmc2577250 | Complex I Dysfunction Redirects Cellular and Mitochondrial Metabolism in Arabidopsis1[W][OA] | Mitochondrial complex I is a major avenue for reduced NAD oxidation linked to oxidative phosphorylation in plants. However, the plant enzyme has structural and functional features that set it apart from its counterparts in other organisms, raising questions about the physiological significance of this complex in plants. We have developed an experimental model in which rotenone, a classic complex I inhibitor, has been applied to Arabidopsis (Arabidopsis thaliana) cell suspension cultures in order to dissect early metabolic adjustments involved in cell acclimation to mitochondrial dysfunction. Rotenone induced a transitory decrease in cellular respiration (0–4 h after treatment). Cell respiration then progressively recovered and reached a steady state at 10 to 12 h after treatment. Complex I inhibition by rotenone did not induce obvious oxidative stress or cell death but affected longer term cell growth. Integrated analyses of gene expression, the mitochondrial proteome, and changes in primary metabolism indicated that rotenone treatment caused changes in mitochondrial function via alterations in specific components. A physical disengagement of glycolytic activities associated with the mitochondrial outer membrane was observed, and the tricarboxylic acid cycle was altered. Amino acid and organic acid pools were also modified by rotenone treatment, with a marked early decrease of 2-oxoglutarate, aspartate, and glutamine pools. These data demonstrate that, in Arabidopsis cells, complex I inhibition by rotenone induces significant remodeling of metabolic pathways involving the mitochondria and other compartments and point to early metabolic changes in response to mitochondrial dysfunction. | [ MarieGarmier, Adam J.Carroll, EtienneDelannoy, CorinneVallet, David A.Day, Ian D.Small, A. HarveyMillar] | Plant Physiology | | |
| pmc2592866 | Proteomic and Transcriptomic Analysis of Aspergillus fumigatus on Exposure to Amphotericin B▿ † | Amphotericin B (AMB) is the most widely used polyene antifungal drug for the treatment of systemic fungal infections, including invasive aspergillosis. It has been our aim to understand the molecular targets of AMB in Aspergillus fumigatus by genomic and proteomic approaches. In transcriptomic analysis, a total of 295 genes were found to be differentially expressed (165 upregulated and 130 downregulated), including many involving the ergosterol pathway, cell stress proteins, cell wall proteins, transport proteins, and hypothetical proteins. Proteomic profiles of A. fumigatus alone or A. fumigatus treated with AMB showed differential expression levels for 85 proteins (76 upregulated and 9 downregulated). Forty-eight of them were identified with high confidence and belonged to the above-mentioned categories. Differential expression levels for Rho-GDP dissociation inhibitor (Rho-GDI), secretory-pathway GDI, clathrin, Sec 31 (a subunit of the exocyst complex), and RAB GTPase Ypt51 in response to an antifungal drug are reported here for the first time and may represent a specific response of A. fumigatus to AMB. The expression of some of these genes was validated by real-time reverse transcription-PCR. The AMB responsive genes/proteins observed to be differentially expressed in A. fumigatus may be further explored for novel drug development. | [ PoonamGautam, JataShankar, TarunaMadan, RaviSirdeshmukh, Curam SreenivasacharluSundaram, Wasudev NamdeoGade, Seemi FarhatBasir, Puranam UshaSarma] | Antimicrobial Agents and Chemotherapy | 2008-10-6 | |
| pmc2527912 | Transcriptional profiling of endogenous germ layer precursor cells identifies dusp4 as an essential gene in zebrafish endoderm specification | A major goal for developmental biologists is to define the behaviors and molecular contents of differentiating cells. We have devised a strategy for isolating cells from diverse embryonic regions and stages in the zebrafish, using computer-guided laser photoconversion of injected Kaede protein and flow cytometry. This strategy enabled us to perform a genome-wide transcriptome comparison of germ layer precursor cells. Mesendoderm and ectoderm precursors cells isolated by this method differentiated appropriately in transplantation assays. Microarray analysis of these cells reidentified known genes at least as efficiently as previously reported strategies that relied on artificial mesendoderm activation or inhibition. We also identified a large set of uncharacterized mesendoderm-enriched genes as well as ectoderm-enriched genes. Loss-of-function studies revealed that one of these genes, the MAP kinase inhibitor dusp4, is essential for early development. Embryos injected with antisense morpholino oligonucleotides that targeted Dusp4 displayed necrosis of head tissues. Marker analysis during late gastrulation revealed a specific loss of sox17, but not of other endoderm markers, and analysis at later stages revealed a loss of foregut and pancreatic endoderm. This specific loss of sox17 establishes a new class of endoderm specification defect. | [ Jamie L.Brown, MiritSnir, HoutanNoushmehr, MarthaKirby, Sung-KookHong, Abdel G.Elkahloun, BenjaminFeldman] | Proceedings of the National Academy of Sciences of the United States of America | 2008-8-21 | |
| pmc2217654 | Systemic and Intracellular Responses to Photooxidative Stress in Arabidopsis[W] | As the sun tracks daily through the sky from east to west, different parts of the canopy are exposed to high light (HL). The extent of and mechanisms by which a systemic acquired acclimation (SAA) response might preacclimate shaded leaves that will be subsequently exposed to full sunlight is largely undefined. We investigated the role of an Arabidopsis thaliana zinc finger transcription factor, ZAT10, in SAA. ZAT10 overexpression resulted in enhanced tolerance to photoinhibitory light and exogenous H2O2, increased expression of antioxidative genes whose products are targeted to multiple subcellular compartments. Partial HL exposure of a leaf or leaves rapidly induced ZAT10 mRNA in distal, shaded photosynthetic tissues, including the floral stem, cauline leaves, and rosette, but not in roots. Fully 86% of fivefold HL-upregulated and 71% of HL-downregulated genes were induced and repressed, respectively, in distal, shaded leaves. Between 15 and 23% of genes whose expression changed in the HL and/or distal tissues were coexpressed in the ZAT10 overexpression plants, implicating ZAT10 in modulating the expression of SAA-regulated genes. The SAA response was detectable in plants with mutations in abscisic acid, methyl jasmonate, or salicylic acid synthesis or perception, and systemic H2O2 diffusion was not detected. Hence, SAA is distinct from pathogen-stimulated systemic acquired resistance and apparently involves a novel signal or combination of signals that preacclimate photosynthetic tissues to HL. | [ Jan BartRossel, Pip B.Wilson, DawarHussain, Nick S.Woo, Matthew J.Gordon, Osman P.Mewett, Katharine A.Howell, JimWhelan, KemalKazan, Barry J.Pogson] | The Plant Cell | | |
| pmc2121100 | An Early Requirement for Maternal FoxH1 during Zebrafish Gastrulation | The Forkhead Box H1 (FoxH1) protein is a co-transcription factor recruited by phosphorylated Smad2 downstream of several TGFβs, including Nodal-related proteins. We have reassessed the function of zebrafish FoxH1 using antisense morpholino oligonucleotides (MOs). MOs targeting translation of foxH1 disrupt embryonic epiboly movements during gastrulation and cause death on the first day of development. The FoxH1 morphant phenotype is much more severe than that of zebrafish carrying foxh1/schmalspur (sur) DNA-binding domain mutations, FoxH1 splice-blocking morphants or other Nodal pathway mutants, and it cannot be altered by concomitant perturbations in Nodal signaling. Apart from disrupting epiboly, FoxH1 MO treatment disrupts convergence and internalization movements. Late gastrula-stage FoxH1 morphants exhibit delayed mesoderm and endoderm marker gene expression and failed patterning of the central nervous system. Probing FoxH1 morphant RNA by microarray, we identified a cohort of five keratin genes – cyt1, cyt2, krt4, krt8 and krt18 - that are normally transcribed in the embryo’s enveloping layer (EVL) and which have significantly reduced expression in FoxH1-depleted embryos. Simultaneously disrupting these keratins with a mixture of MOs reproduces the FoxH1 morphant phenotype. Our studies thus point to an essential role for maternal FoxH1 and downstream keratins during gastrulation that is epistatic to Nodal signaling. | [ WuhongPei, HoutanNoushmehr, JustinCosta, Maia V.Ouspenskaia, Abdel G.Elkahloun, BenjaminFeldman] | Developmental biology | 2007-7-19 | |
| pmc1865555 | Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process | Prostate cancer is characterized by heterogeneity in the clinical course that often does not correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer, and to date there are no reliable morphologic features or serum biomarkers that can reliably predict which patients are at higher risk of developing metastatic disease. Understanding the differences in the biology of metastatic and organ confined primary tumors is essential for developing new prognostic markers and therapeutic targets.MethodsUsing Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors.ResultsThe metastatic samples are highly heterogenous in expression; however, differential expression analysis shows that 415 genes are upregulated and 364 genes are downregulated at least 2 fold in every patient with metastasis. The expression profile of metastatic samples reveals changes in expression of a unique set of genes representing both the androgen ablation related pathways and other metastasis related gene networks such as cell adhesion, bone remodelling and cell cycle. The differentially expressed genes include metabolic enzymes, transcription factors such as Forkhead Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1).ConclusionWe hypothesize that these genes have a role in the biology of metastatic disease and that they represent potential therapeutic targets for prostate cancer. | [ Uma RChandran, ChangqingMa, RajivDhir, MichelleBisceglia, MaureenLyons-Weiler, WenjingLiang, GeorgeMichalopoulos, MichaelBecich, Federico AMonzon] | BMC Cancer | 2007-4-12 | 3.3 |
| pmc1851844 | F-Box Proteins in Rice. Genome-Wide Analysis, Classification, Temporal and Spatial Gene Expression during Panicle and Seed Development, and Regulation by Light and Abiotic Stress1[W][OA] | F-box proteins constitute a large family in eukaryotes and are characterized by a conserved F-box motif (approximately 40 amino acids). As components of the Skp1p-cullin-F-box complex, F-box proteins are critical for the controlled degradation of cellular proteins. We have identified 687 potential F-box proteins in rice (Oryza sativa), the model monocotyledonous plant, by a reiterative database search. Computational analysis revealed the presence of several other functional domains, including leucine-rich repeats, kelch repeats, F-box associated domain, domain of unknown function, and tubby domain in F-box proteins. Based upon their domain composition, they have been classified into 10 subfamilies. Several putative novel conserved motifs have been identified in F-box proteins, which do not contain any other known functional domain. An analysis of a complete set of F-box proteins in rice is presented, including classification, chromosomal location, conserved motifs, and phylogenetic relationship. It appears that the expansion of F-box family in rice, in large part, might have occurred due to localized gene duplications. Furthermore, comprehensive digital expression analysis of F-box protein-encoding genes has been complemented with microarray analysis. The results reveal specific and/or overlapping expression of rice F-box protein-encoding genes during floral transition as well as panicle and seed development. At least 43 F-box protein-encoding genes have been found to be differentially expressed in rice seedlings subjected to different abiotic stress conditions. The expression of several F-box protein-encoding genes is also influenced by light. The structure and function of F-box proteins in plants is discussed in light of these results and the published information. These data will be useful for prioritization of F-box proteins for functional validation in rice. | [ MukeshJain, AashimaNijhawan, RitaArora, PinkyAgarwal, SwatismitaRay, PoojaSharma, SanjayKapoor, Akhilesh K.Tyagi, Jitendra P.Khurana] | Plant Physiology | | |
| pmc1780192 | Up-Regulation of Dicer, a Component of the MicroRNA Machinery, in Prostate Adenocarcinoma | MicroRNAs are small noncoding 18- to 24-nt RNAs that are predicted to regulate expression of as many as 30% of protein-encoding genes. In prostate adenocarcinoma, 39 microRNAs are up-regulated, and six microRNAs are down-regulated. Production and function of microRNA requires coordinated processing by proteins of the microRNA machinery. Dicer, an RNase III endonuclease, is an essential component of the microRNA machinery. From a gene array analysis of 16 normal prostate tissue samples, 64 organ-confined, and four metastatic prostate adenocarcinomas, we identified an up-regulation of major components of the microRNA machinery, including Dicer, in metastatic prostate adenocarcinoma. Immunohistochemical studies on a tissue microarray consisting of 232 prostate specimens confirmed up-regulation of Dicer in prostatic intraepithelial neoplasia and in 81% of prostate adenocarcinoma. The increased Dicer level in prostate adenocarcinoma correlated with clinical stage, lymph node status, and Gleason score. Western blot analysis of benign and neoplastic prostate cell lines further confirmed Dicer up-regulation in prostate adenocarcinoma. Dicer up-regulation may explain an almost global increase of microRNA expression in prostate adenocarcinoma. The presence of up-regulated microRNA machinery may predict the susceptibility of prostate adenocarcinoma to RNA interference-based therapy. | [ SimionChiosea, ElenaJelezcova, UmaChandran, MarieAcquafondata, TeresaMcHale, Robert W.Sobol, RajivDhir] | The American Journal of Pathology | | |
| pmc1867595 | In Vitro Transcription Amplification and Labeling Methods Contribute to the Variability of Gene Expression Profiling with DNA Microarrays | The effect of different amplification and labeling methods on DNA microarray expression results has not been previously delineated. To analyze the variation associated with widely accepted T7-based RNA amplificationand labeling methods, aliquots of the Stratagene Human Universal Reference RNA were labeled using three eukaryotic target preparation methods followed by uniform replicate array hybridization (Affymetrix U95Av2). Method-dependent variability was observed in the yield and size distribution of labeled products, as well as in the gene expression results. A significant increase in short transcripts, when compared to unamplified mRNA, was observed in methods with long in vitro transcription reactions. Intramethod reproducibility showed correlation coefficients >0.99, whereas intermethod comparisons showed coefficients ranging from 0.94 to 0.98 and a nearly twofold increase in coefficient of variation. Fold amplification for each method positively correlated with the number of genes present. Our experiments uncovered two factors that introduced significant bias in gene expression data: the number of labeled nucleotides, which introduces sequence-dependent bias, and the length of the in vitro transcription reaction, which introduces transcript size-dependent bias. This study provides evidence that variability in expression data may be caused, in part, by differences in amplification and labeling protocols. | [ ChangqingMa, MaureenLyons-Weiler, WenjingLiang, WilliamLaFramboise, John R.Gilbertson, Michael J.Becich, Federico A.Monzon] | The Journal of molecular diagnostics : JMD | | |
| pmc1860290 | Specific epitopes of the structural and hypothetical proteins elicit variable humoral responses in SARS patients | Severe acute respiratory syndrome (SARS) is an infectious disease which was caused by a novel coronavirus (SARS‐CoV). SARS has caused an outbreak in the world during 2003 and 2004, with 8098 individuals being infected and a death toll of 774 in 28 regions around the world. Specific humoral responses to viral infection remain unclear.ObjectiveTo analyse the antigenicity of the SARS‐CoV genome and identify potential antigenic epitopes in the structural proteins.MethodsPotential antigenic epitopes were identified in the structural proteins (nucleocapsid, membrane, spike, and small envelope proteins) and hypothetical proteins (SARS3a, 3b, 6, 7a, and 9b) that are specific for SARS‐CoV. A peptide chip platform was created and the profiles of antibodies to these epitopes were investigated in 59 different SARS patients' sera obtained 6–103 days after the onset of the illness. Serial sera from five additional patients were also studied.ResultsEpitopes at the N‐terminus of the membrane protein and the C‐terminus of nucleocapsid protein elicited strong antibody responses. Epitopes on the spike protein were only moderately immunogenic but the effects were persistent. Antibodies were also detected for some putative proteins, noticeably the C‐termini of SARS3a and SARS6.ConclusionsImportant epitopes of the SARS‐CoV genome that may serve as potential markers for the viral infection are identified. These specific antigenic sites may also be important for vaccine development against this new fatal infectious disease. | [ S C SChow, C Y SHo, T T YTam, CWu, TCheung, P K SChan, M H LNg, P KHui, H KNg, D M YAu, A W ILo] | Journal of Clinical Pathology | | |
| pmc1449999 | Homocysteine- and cysteine-mediated growth defect is not associated with induction of oxidative stress response genes in yeast | Intracellular thiols like cysteine, homocysteine and glutathione play a critical role in the regulation of important cellular processes. Alteration of intracellular thiol concentration results in many diseased states; for instance, elevated levels of homocysteine are considered to be an independent risk factor for cardiovascular disease. Yeast has proved to be an excellent model system for studying many human diseases since it carries homologues of nearly 40% of human disease genes and many fundamental pathways are highly conserved between the two organisms. In the present study, we demonstrate that cysteine and homocysteine, but not glutathione, inhibit yeast growth in a concentration-dependent manner. Using deletion strains (str2Δ and str4Δ) we show that cysteine and homocysteine independently inhibit yeast growth. Transcriptional profiling of yeast treated with cysteine and homocysteine revealed that genes coding for antioxidant enzymes like glutathione peroxidase, catalase and superoxide dismutase were down-regulated. Furthermore, transcriptional response to homocysteine did not show any similarity to the response to H2O2. We also failed to detect induction of reactive oxygen species in homocysteine- and cysteine-treated cells, using fluorogenic probes. These results indicate that homocysteine- and cysteine-induced growth defect is not due to the oxidative stress. However, we found an increase in the expression of KAR2 (karyogamy 2) gene, a well-known marker of ER (endoplasmic reticulum) stress and also observed HAC1 cleavage in homocysteine- and cysteinetreated cells, which indicates that homocysteine- and cysteine-mediated growth defect may probably be attributed to ER stress. Transcriptional profiling also revealed that genes involved in one-carbon metabolism, glycolysis and serine biosynthesis were up-regulated on exogenous addition of cysteine and homocysteine, suggesting that cells try to reduce the intracellular concentration of thiols by up-regulating the genes involved in their metabolism. | [ ArunKumar, LijoJohn, Md. MahmoodAlam, AnkitGupta, GayatriSharma, BeenaPillai, ShantanuSengupta] | Biochemical Journal | 2006-4-26 | |
| pmc1421426 | Evaluation of MetriGenix custom 4D™ arrays applied for detection of breast cancer subtypes | Previously, a total of five breast cancer subtypes have been identified based on variation in gene expression patterns. These expression profiles were also shown to be associated with different prognostic value. In this study tumour samples from 27 breast cancer patients, previously subtyped by expression analysis using DNA microarrays, and four controls from normal breast tissue were included. A new MetriGenix 4D™ array proposed for diagnostic use was evaluated.MethodsWe applied MetriGenix custom 4D™ arrays for the detection of previously defined molecular subtypes of breast cancer. MetriGenix 4D™ arrays have special features including probe immobilization in microchannels with chemiluminescence detection that enable shorter hybridization time.ResultsThe MetriGenix 4D™ array platform was evaluated with respect to both the accuracy in classifying the samples as well as the performance of the system itself. In a cross validation analysis using "Nearest Shrunken Centroid classifier" and the PAM software, 77% of the samples were classified correctly according to earlier classification results.ConclusionThe system shows potential for fast screening; however, improvements are needed. | [ Aslaug AamodtMuggerud, HildeJohnsen, Debra ABarnes, AdamSteel, Per EysteinLønning, BjørnNaume, ThereseSørlie, Anne-LiseBørresen-Dale] | BMC Cancer | 2006-3-15 | |
| pmc1947970 | MADS-box gene family in rice: genome-wide identification, organization and expression profiling during reproductive development and stress | MADS-box transcription factors, besides being involved in floral organ specification, have also been implicated in several aspects of plant growth and development. In recent years, there have been reports on genomic localization, protein motif structure, phylogenetic relationships, gene structure and expression of the entire MADS-box family in the model plant system, Arabidopsis. Though there have been some studies in rice as well, an analysis of the complete MADS-box family along with a comprehensive expression profiling was still awaited after the completion of rice genome sequencing. Furthermore, owing to the role of MADS-box family in flower development, an analysis involving structure, expression and functional aspects of MADS-box genes in rice and Arabidopsis was required to understand the role of this gene family in reproductive development.ResultsA genome-wide molecular characterization and microarray-based expression profiling of the genes encoding MADS-box transcription factor family in rice is presented. Using a thorough annotation exercise, 75 MADS-box genes have been identified in rice and categorized into MIKCc, MIKC*, Mα, Mβ and Mγ groups based on phylogeny. Chromosomal localization of these genes reveals that 16 MADS-box genes, mostly MIKCc-type, are located within the duplicated segments of the rice genome, whereas most of the M-type genes, 20 in all, seem to have resulted from tandem duplications. Nine members belonging to the Mβ group, which was considered absent in monocots, have also been identified. The expression profiles of all the MADS-box genes have been analyzed under 11 temporal stages of panicle and seed development, three abiotic stress conditions, along with three stages of vegetative development. Transcripts for 31 genes accumulate preferentially in the reproductive phase, of which, 12 genes are specifically expressed in seeds, and six genes show expression specific to panicle development. Differential expression of seven genes under stress conditions is also evident. An attempt has been made to gain insight into plausible functions of rice MADS-box genes by collating the expression data of functionally validated genes in rice and Arabidopsis.ConclusionOnly a limited number of MADS genes have been functionally validated in rice. A comprehensive annotation and transcriptome profiling undertaken in this investigation adds to our understanding of the involvement of MADS-box family genes during reproductive development and stress in rice and also provides the basis for selection of candidate genes for functional validation studies. | [ RitaArora, PinkyAgarwal, SwatismitaRay, Ashok KumarSingh, Vijay PalSingh, Akhilesh KTyagi, SanjayKapoor] | BMC Genomics | 2007-7-18 | |
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| sciencedirectS0022510X11007520 | A novel mutation in SCN4A causes severe myotonia and school-age-onset paralytic episodes | Mutations in the pore-forming subunit of the skeletal muscle sodium channel (SCN4A) are responsible for hyperkalemic periodic paralysis, paramyotonia congenita and sodium channel myotonia. These disorders are classified based on their cardinal symptoms, myotonia and/or paralysis. We report the case of a Japanese boy with a novel mutation of SCN4A, p.I693L, who exhibited severe episodic myotonia from infancy and later onset mild paralytic attack. He started to have apneic episodes with generalized hypertonia at age of 11 months, then developed severe episodic myotonia since 2 years of age. He presented characteristic generalized features which resembled Schwarz–Jampel syndrome. After 7 years old, paralytic episodes occurred several times a year. The compound muscle action potential did not change during short and long exercise tests. Functional analysis of the mutant channel expressed in cultured cell revealed enhancement of the activation and disruption of the slow inactivation, which were consistent with myotonia and paralytic attack. The severe clinical features in his infancy may correspond to myotonia permanence, however, he subsequently experienced paralytic attacks. This case provides an example of the complexity and overlap of the clinical features of sodium channel myotonic disorders. | [Harumi Yoshinagaa, Shunichi Sakodab, Jean-Marc Goodc, Masanori P. Takahashic, Tomoya Kubotac, Eri Arikawa-Hirasawad, Tomohiko Nakatae, Kinji Ohnoe, Tetsuro Kitamuraf, Katsuhiro Kobayashia, Yoko Ohtsukaa] | Journal of the Neurological Sciences | | |
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| sciencedirectS0024320511001317 | Xanthorrhizol attenuates dextran sulfate sodium-induced colitis via the modulation of the expression of inflammatory genes in mice | AimsThe aim of this study was to investigate the effects of xanthorrhizol (5-(1,5-dimethyl-4-hexenyl)-2-methylphenol, XA) in a mouse model of dextran sulfate sodium (DSS)-induced colitis.Main methodsExperimental colitis was induced by exposing male BALB/c mice to 5% DSS in drinking water for 7 days. XA (10 or 100 mg/kg) was administered orally once a day, together with the DSS. We evaluated body weight, colon length, histological changes, and myeloperoxidase (MPO) activity. A cDNA microarray was used to assess the gene expression profiles that were affected by XA and DSS treatment and a co-citation analysis was used to examine the biological relationship between XA-responsive genes and colitis.Key findingsDecreased body weight, shortened colon length, and damaged colon were observed in the group that was exposed to DSS. Oral administration of XA (10 or 100 mg/kg) rescued these symptomatic and histopathological features. The DSS-induced increase in MPO activity, which was used as an index of neutrophil infiltration, was significantly decreased after treatment with XA. Microarray analysis revealed that XA treatment regulated the expression of 34 genes that were altered by exposure to DSS, and that these XA-responsive genes were associated with colonic inflammation. Furthermore, co-citation analysis and graphing of XA-responsive genes revealed a network associated with the gene that encodes for MPO.SignificanceThese results suggest that XA attenuates acute DSS-induced colitis, possibly by modulating the expression of genes mostly associated with colonic inflammation. | [Jae Young Choa, Jae-Kwan Hwangb, Hyang Sook Chuna] | Life Sciences | 9 May 2011 | |
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| sciencedirectS0378874110003284 | Identification of anti-inflammatory target genes of Rhizoma coptidis extract in lipopolysaccharide-stimulated RAW264.7 murine macrophage-like cells | Aim of the studyRhizoma coptidis is used widely in traditional Oriental medicine to treat inflammatory diseases. The aim of this study was to identify the anti-inflammatory target genes of Rhizoma coptidis extract (CEX) in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage-like cells.Materials and methodsRAW264.7 cells were treated with CEX in the absence or presence of LPS for 6 h, and changes in gene expression profiles were analyzed using oligonucleotide DNA microarrays. The results of microarray analysis were validated by semiquantitative reverse transcription-polymerase chain reaction. To confirm the anti-inflammatory activity of CEX, the concentrations of cytokines released into the media were measured by sandwich ELISA, NO production was assessed using the Griess reagent, and iNOS expression levels were determined using immunoblot analysis.ResultsMicroarray analysis revealed that activation of RAW264.7 cells with LPS elicited marked changes in mRNA expression of numerous genes known to be associated with inflammatory responses. Treatment of the cells with CEX suppressed the expression of various cytokines/chemokines, cell surface molecules, adhesion molecules, and growth factors. An ELISA also showed a decrease in the secretion of IL-1?, GM-CSF, and IL-6 but not of TNF-?. iNOS protein expression and NO production were also reduced by CEX treatment.ConclusionsThe data obtained in this study demonstrate that CEX exerts its anti-inflammatory effect by inhibiting the expression of various proinflammatory cytokines and cell surface molecules involved in inflammatory responses at the transcriptional level. These data support the traditional use of CEX as an anti-inflammatory agent and should provide useful information for the understanding of the pharmacological effects of CEX. | [Jong Min Kima, Hyun Ah Jungb, Jae Sue Choib, Na Gyong Leea] | Journal of Ethnopharmacology | 20 July 2010 | |
| sciencedirectS0014299910002189 | Possible protective role of pregnenolone-16?-carbonitrile in lithocholic acid-induced hepatotoxicity through enhanced hepatic lipogenesis | Lithocholic acid (LCA) feeding causes both liver parenchymal and cholestatic damages in experimental animals. Although pregnenolone-16?-carbonitrile (PCN)-mediated protection against LCA-induced hepatocyte injury may be explained by induction of drug metabolizing enzymes, the protection from the delayed cholestasis remains incompletely understood. Thus, the PCN-mediated protective mechanism has been studied from the point of modification of lipid metabolism. At an early stage of LCA feeding, an imbalance of biliary bile acid and phospholipid excretion was observed. Co-treatment with PCN reversed the increase in serum alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities and hepatic hydrophobic bile acid levels. LCA feeding decreased hepatic mRNA levels of several fatty acid- and phospholipid-related genes before elevation of serum ALT and ALP activities. On the other hand, PCN co-treatment reversed the decrease in the mRNA levels and hepatic levels of phospholipids, triglycerides and free fatty acids. PCN co-treatment also reversed the decrease in biliary phospholipid output in LCA-fed mice. Treatment with PCN alone increased hepatic phospholipid, triglyceride and free fatty acid concentrations. Hepatic fatty acid and phosphatidylcholine synthetic activities increased in mice treated with PCN alone or PCN and LCA, compared to control mice, whereas these activities decreased in LCA-fed mice. These results suggest the possibility that PCN-mediated stimulation of lipogenesis contributes to the protection from lithocholic acid-induced hepatotoxicity. | [Masaaki Miyataa, Masahiro Nomotoa b, Fumiaki Sotodatea, Tomohiro Mizukia, Wataru Horia, Miho Nagayasua, Shinya Yokokawac, Shin-ichi Ninomiyac, Yasushi Yamazoea d] | European Journal of Pharmacology | 25 June 2010 | |
| sciencedirectS1090023309001245 | Microarray analysis of differential expression of cell cycle and cell differentiation genes in cells infected with Lawsonia intracellularis | Infection of intestinal crypt epithelial cells by the obligate intracellular bacterium Lawsonia intracellularis is directly linked to marked proliferation of the infected enterocytes within 3–5 days post-infection. The virulence factor for this unique host cell-proliferative response is not known, but is considered to involve altered crypt cell cycle or differentiation events. McCoy mouse fibroblast cells were infected with L. intracellularis, and then harvested for expressed mRNA at daily time points, with matching non-infected control cell cultures.Mouse DNA microarray (>44,000 transcript targets) analysis of cDNA derived from matching mRNA samples showed over 40 identifiable genes with at least 4-fold changes between days 0 and 3 after infection with L. intracellularis. These included altered transcription of typical host cell ‘alarm’ response genes, such as interferon-related response genes Isgf3g and Igtp, known to be associated with invading microbial agents. Altered transcription of several genes in these cells known to be active in regulation of the cell cycle or cell differentiation genes, including usp18, Hr, Elavl2 and Slfn2, were also detected. The altered transcription of several of these genes via RT-PCR analysis was confirmed. The microarray-detected altered transcription of cell cycle and cell differentiation genes is of possible interest for links to Lawsonia-related disturbances in epithelial cell differentiation within the intestinal crypt, but this would need to be confirmed in intestinal epithelial cell studies. | [Yu-Sik Oha, Joong-Bok Leea, Steven McOristb] | The Veterinary Journal | June 2010 | |
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| sciencedirectS0734975009001906 | A special report on India's biotech scenario: Advancement in biopharmaceutical and health care sectors | India's biotechnology industry has been growing towards new heights in conjunction with the recent economic outburst. The country has the potential to revolutionize biopharmaceutical and healthcare sectors. In this review, we have highlighted the achievements of India's biotechnology industry, especially biopharmaceutical and healthcare sectors that include therapeutics, diagnostics, stem cell research, human healthcare related bioinformatics and animal health care. We have also described regulatory mechanisms involved in India's health care biotech including manpower development. | [Chiranjib Chakrabortya, Govindasamy Agoramoorthyb] | Biotechnology Advances | January–February 2010 | |
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| sciencedirectS105898130900040X | Interventional cardiovascular MR—The next stage in pediatric cardiology | Real-time magnetic resonance imaging is attractive to guide minimally invasive treatment of structural heart disease not only because it can spare radiation but also because soft tissue imaging may add value. Interventional cardiovascular magnetic resonance imaging will allow simple as well as novel non-surgical treatments of structural heart disease in children. Real-time MRI tools already are available. Catheter tools are emerging. A handful of pediatrics hospitals are installing investigational systems now to explore this promising technology. | [Kanishka Ratnayakaa b, Robert J. Ledermanb] | Progress in Pediatric Cardiology | January 2010 | |
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| sciencedirectS0166445X09001258 | Gene expression profiling of copper-induced responses in the intertidal copepod Tigriopus japonicus using a 6K oligochip microarray | The intertidal copepod Tigriopus japonicus has shown promising results in classical acute and chronic toxicity studies. Recently, a large number of genes have been identified from this species and their mRNA expression has been studied independently against exposure to marine environmental pollutants. T. japonicus is a promising organism for the study of mechanistic aspects of marine environmental pollutants using genomics. In this study, a 6K oligochip for T. japonicus that included mostly unique sets of genes from ∼26K ESTs, was developed. A total of 5463 spots (2313 mRNAs upregulated and 3150 downregulated) were identified to be significantly expressed on microarray by hierarchical clustering of genes after exposure to copper for different time durations (10 ?g/L for 6, 12 and 24 h). However, mRNAs of only 138 and 375 genes were observed to be consistently upregulated and downregulated, respectively, at all time points. Most of the changes of mRNA expression were observed at the short exposure of 6 h. It was observed that mRNA expression of several genes involved in growth, metabolism, reproduction and hormonal regulation was modulated in Cu-exposed T. japonicus. mRNA expression of genes involved in detoxification and antioxidant functions was also modulated. This indicates that Cu-induced gene transcription is complicated in T. japonicus similar to other crustaceans. Cu specifically upregulated mRNAs of genes of some isoforms of cytochrome P450 (CYP). On the other hand, a majority of downregulated mRNAs were of genes encoding for proteins important for growth and development. The expression profile of mRNAs of selected genes was verified by the quantitative real time RT-PCR. The mRNA expression profiles provide insight into the mechanism of action of copper in T. japonicus. These results demonstrate the suitability of a T. japonicus oligochip microarray for risk assessment of trace metals in the marine environment. As yet, major breakthroughs in invertebrate toxicogenomics have mainly been in Daphnia and Drosophila. Daphnia's use is limited to freshwater ecotoxicogenomics. Here we propose an oligochip microarray-based approach for risk assessment of trace metals in a potential model marine test species. | [Jang-Seu Kia, Sheikh Raisuddina, Kyun-Woo Leea, Dae-Sik Hwangb, Jeonghoon Hanb, Jae-Sung Rheeb, Il-Chan Kimc, Heum Gi Parkd, Jae-Chun Ryue, Jae-Seong Leea] | Aquatic Toxicology | 26 July 2009 | |
| sciencedirectS0960077907009605 | Detrended fluctuation analysis in natural languages using non-corpus parametrization | The existence of long-range correlation in English and Korean had been reported by Montemurro et al. and Jaemi Bhan et al. This work extends this line of research to other languages (mainly Turkish), compares the differences between a meaningful text and a randomly created text by means of detrended fluctuation analysis and diffusion entropy analysis using a newly proposed parametrization which does not depend on corpus. The results imply a unique long-range correlation for each language analyzed, although similarities exist for languages of the same family. | [Gökhan ?ahina, Murat Erentürkb, Avadis Hacinliyanb] | Chaos, Solitons & Fractals | 15 July 2009 | |
| sciencedirectS0925443909000611 | Insulin induced alteration in post-translational modifications of histone H3 under a hyperglycemic condition in L6 skeletal muscle myoblasts | Chromatin remodelling events, especially histone modifications are proposed to form the mainstay for most of the biological processes. However, the role of these histone modifications in the progression of diabetes is still unknown. Hyperglycemia plays a major role in diabetes and its complications. The present study was undertaken to check the effect of insulin on alterations in post-translational modifications of histone H3 in L6 myoblasts under a hyperglycemic condition. We provide first evidence that insulin under hyperglycemic condition alters multiple histone modifications by enhanced production of reactive oxygen species. Insulin induces dose dependent changes in Lysine 4 and 9 methylation, Ser 10 phosphorylation and acetylation of histone H3. Interestingly, insulin induced generation of reactive oxygen species induces dephosphorylation and deacetylation of histone H3. Preincubation with catalase and DPI prevents these changes in post-translational modifications of histone H3. Furthermore, changes in histone H3 phosphorylation was found to be independent of ERK, p38, RSK2 and MSK1. Moreover, serine/threonine phosphatase inhibitor, okadaic acid attenuates insulin induced dephosphorylation and deacetylation of histone H3, suggesting a role of serine/threonine phosphatases in altering modifications of histone H3. These changes in epigenetic modifications can provide new insights into pathogenesis of diabetes. | [Dhiraj G. Kabra, Jeena Gupta, Kulbhushan Tikoo] | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | June 2009 | |
| sciencedirectS0887233309000605 | Cytotoxicity of 5-fluorouracil: Effect on endothelial differentiation via cell cycle inhibition in mouse embryonic stem cells | Embryonic stem cells (ESCs) are known to characteristics for pluripotency and self-renewal, but the precise mechanisms of ES-derived cells to specific toxicants have not been determined. Here, we evaluated the cytotoxicity of 5-fluorouracil (5-FU) and see its effect on cell viability, proliferation, and differentiation in mouse ESC-derived endothelial differentiation. Mouse ESCs were exposed to 5-FU (10 ?M) and combined with probucol (50 ?M) for 24 h, which is an antagonist of 5-FU. Changes in gene expression as a result of 5-FU exposure in mouse ESC-derived endothelial precursor cells (ES-EPCs) were assessed using an oligonucleotide microarray (AB1700). The expression of Oct-4 was decreased during the differentiation of mouse ESCs into endothelial cells; otherwise, the expression of PECAM was increased. Mouse ES-EPCs were shown to have a decrease in viability (49.8%) and PECAM expression, and induce G1/S phase (31.1%/60.6%) when compared with/without treatment of 5-FU. Expression of cell cycle-related proteins was increased in endothelial precursor cells exposed to 5-FU without probucol treatment. From theses results suggest that 5-FU inhibit endothelial differentiation as well as inducing the G1/S phase arrest. We propose that mouse ES-EPCs might be a useful tool for screening the cytotoxicity of compounds in endothelial cells. | [Gi Dae Kima, Gyu-Seek Rheeb, Hyung-Min Chungc, Kew-Mahn Cheea 1, Gi Jin Kimc 1] | Toxicology in Vitro | June 2009 | |
| sciencedirectS1043466609000210 | Chemokine and chemokine receptor gene expression in the mesenteric adipose tissue of KKAy mice | Objective: To investigate chemokines and their receptors gene expression in the intra-abdominal adipose tissue of diabetic/obese mice. Methods: KKAy mice were fed either by a high-fat diet (HFD) or a low-fat diet (LFD) and obese characteristics were analyzed. Various adipose tissues were isolated from HFD-fed obese KKAy mice and from obese controls. We carried out RT-PCR, GeneChip microarray, and real-time PCR analyses on samples derived from the adipose tissues. Results: The HFD-feded obese KKAy mice had the physiological characteristics of obese animal and had increased levels of the transcripts of several chemokine and chemokine receptor genes, such as CCL5, CCL19, CCL25, CXCL10, CXCL13, CCR6, and CCR7, in their intra-abdominal adipose tissue. The strong expression of CCR6 and CCR7 was verified by microarray and quantitative real-time PCR analysis. The HFD increased CCR6 and CCR7 expression only in mesenteric (ME) adipose tissue, not in subcutaneous (SC) adipose tissue. Discussion: Since the enhanced expression of such molecules is likely to contribute to the inflammation in chronic inflammatory disease, our data suggest that the increased levels of CCR6 and CCR7 are involved in the inflammation response in the intra-abdominal adipose tissue of the obese/diabetic mice. | [Han-Sam Leea, Jin-Hee Parka, Ji-Hye Kangb, Teruo Kawadac, Rina Yub, In-Seob Hana] | Cytokine | May 2009 | |
| sciencedirectS0014299908011436 | Desmethylanhydroicaritin inhibits NF-?B-regulated inflammatory gene expression by modulating the redox-sensitive PI3K/PTEN/Akt pathway | We investigated the effect of desmethylanhydroicaritin (DMAI), a major compound of the Chinese herbal medicine Epimedium, on inflammatory gene expression and the NF-?B signaling pathway. We found that DMAI suppressed the expression of NF-?B-responsive genes, such as inducible nitric oxide synthase, cyclooxygenase-2, interleukin-1?, and tumor necrosis factor-?, in lipopolysaccharide (LPS)-stimulated macrophages and endotoxemic mice as well as protected mice against LPS-induced lethality. DMAI inhibited NF-?B activation through the inhibition of I?B kinase (IKK) activation, I?B phosphorylation and degradation, and NF-?B nuclear translocation in LPS-stimulated macrophages. This compound inhibited in vitro and in vivo LPS-induced phosphatidylinositol 3-kinase (PI3K) activation, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) oxidation, and Akt phosphorylation, which are upstream modulators of IKK activation. Moreover, treatment with DMAI was not observed to affect the interaction between the Toll-like receptor 4, MyD88, and TRAF6 as well as mitogen-activated protein kinase activation. DMAI also suppressed intracellular H2O2 accumulation, hydroxyl radical production, and glutathione oxidation without affecting superoxide generation and accumulation by NADPH oxidase. Moreover, DMAI inhibited redox-sensitive activation of the PI3K/PTEN/Akt pathway and NF-?B activation in macrophages treated with H2O2. These results indicate that DMAI negatively regulates canonical NF-?B-regulated inflammatory gene expression by functioning as an inhibitor of the NF-?B pathway through the suppression of redox-based PI3K activation and PTEN inactivation and therefore can be considered as a potential drug for inflammatory diseases. | [Ji-Hee Kima b 1, Gwangsoo Leea b 1, Young-Lai Choa b, Chun-Ki Kima b, Sanghwa Hanc, Hansoo Leec, Jae Sue Choid, Jongseon Choea, Moo-Ho Wone, Young-Guen Kwonf, Kwon-Soo Haa b, Young-Myeong Kima b] | European Journal of Pharmacology | 14 January 2009 | |
| sciencedirectS0888754308001894 | Molecular signatures associated with transformation and progression to breast cancer in the isogenic MCF10 model | Comparative microarray analyses provided insight into understanding transcript changes during cancer progression; however, a reproducible signature underlying breast carcinogenesis has yet to be little available. We utilized gene expression profiling to define molecular signatures associated with transformation and cancer progression in a series of isogenic human breast cancer cell lines including a normal, benign, noninvasive and invasive carcinoma. Clustering analysis revealed four distinct expression patterns based on upregulation or downregulation patterns. These profiles proved quite useful for describing breast cancer tumorigenesis and invasiveness. Downregulation of TNFSF7, S100A4, S100A7, S100A8, and S100A9 (calcium-binding protein family), and upregulation of kallikrein-5 and thrombospondin-1 were associated with transformation and progression of breast cancer cells. Importantly, downregulation of the genes was reversed by treatment with silencing inhibitors, implying the potential roles of epigenetic inactivation in breast carcinogenesis. Exogenous expressions of S100A8 and S100A9 inhibit growth in benign and noninvasive carcinoma cells, suggesting their negative role in cell proliferation. The data presented here may facilitate the identification and functional analyses of prognostic biomarkers for breast cancer. | [Dong Keun Rheea b 1, Su Hyung Parka b 1, Yeun Kyu Janga b] | Genomics | December 2008 | |
| sciencedirectS138266890800046X | Simultaneous application of t-test and fold change criteria to identify acetaminophen and carbon tetrachloride affected genes in mice liver | t-Test and fold change criteria were employed simultaneously following acute exposure to acetaminophen and carbon tetrachloride to provide high statistical confidence in the identification of affected genes in mice livers. Furthermore, gene expression data was also investigated with either t-test or fold change criteria alone. Gene expression studies were also accompanied by liver histological and serum biochemical studies for toxicity evaluation.We identified a large number of affected genes using both filtering criteria (p < 0.01 and twofold) simultaneously following both the hepatotoxicants. In some cases gene expression studies provided the earliest evidence of tissue response in the absence of traditional markers at histological and biochemical level.We conclude that simultaneous application of t-test and fold change criteria helps to identify important genes with greater statistical confidence than the use of either of them alone, however, this approach results in the reduction of identified probes. Thus, data analysis at different statistical stringencies is needed to know exact outcome of any toxicological event. | [Sanjeev Noel, Sharad Sharma, Srikanta K. Rath] | Environmental Toxicology and Pharmacology | September 2008 | |
| sciencedirectS0890850808000340 | Microarray for molecular typing of Salmonella enterica serovars | We describe the development of a spotted array for the delineation of the most common 14 disease-causing Salmonella serovars in the United States. Our array consists of 414 70 mers targeting core genes of Salmonella enterica, subspecies I specific genes, fimbrial genes, pathogenicity islands, Gifsy elements and other variable genes. Using this array we were able to identify a unique gene presence/absence profile for each of the targeted serovar which was used as the serovar differentiating criteria. Based on this profile, we developed a Matlab programme that compares the profile of an unknown sample to all 14 reference serovar profiles and give out the closest serovar match. Since we have included probes targeting most of the virulence genes and variable genes in Salmonella, in addition to using for serovar detection this array could also be used for studying the virulence gene content and also for evaluating the genetic relation between different isolates of Salmonella. | [Joy Scariaa, Raghavan U.M. Palaniappana, David Chiua, Julie Ann Phana, Lalit Ponnalab, Patrick McDonougha, Yrjo T. Grohna, Steffen Porwollikc, Michael McClellandc, Chien-Shun Chioud, Chishih Chue, Yung-Fu Changa] | Molecular and Cellular Probes | August 2008 | |
| sciencedirectS1874939908000515 | A microarray approach for comparative expression profiling of the discrete maturation zones of mouse growth plate cartilage | In vertebrates, longitudinal bone growth is the consequence of a complex series of events that take place in a specialized structure, the growth plate cartilage. Within the growth plate chondrocytes undergo a sequential maturation program from resting cells to proliferative, pre-hypertrophic, and ultimately hypertrophic end-stage chondrocytes. This process of chondrocyte maturation is under the control of the temporally and spatially regulated expression of a myriad of signaling molecules, transmembrane receptors, transcription factors, and structural extracellular matrix (ECM) proteins. One approach to the comprehensive definition of the key components of such complex interrelated pathways is the use of microarray expression profiling to catalogue transcriptome changes during chondrocyte maturation in the individual developmental zones of the mouse growth plate cartilage. However, this has not been achieved because of the difficulty in obtaining sufficient quantities of the individual growth plate cartilage zones to all microarray analysis. In this study we describe the development of microdissection methods for the isolation of tissue from the proliferative, pre-hypertrophic, and proliferative zone from one single mouse femur, RNA extraction and linear amplification of the RNA to allow interrogation of NIA 15k microarrays to generate comparative expression profiles. Verification of a subset of differentially expressed genes by RT-PCR and by in situ hybridization confirmed the reliability of this approach. | [Daniele Belluoccio, Bianca C. Bernardo, Lynn Rowley, John F. Bateman] | Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms | May 2008 | |
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| sciencedirectS0306452208000882 | Inhibiting activator protein-1 activity alters cocaine-induced gene expression and potentiates sensitization | We have expressed A-FOS, an inhibitor of activator protein-1 (AP-1) DNA binding, in adult mouse striatal neurons. We observed normal behavior including locomotion and exploratory activities. Following a single injection of cocaine, locomotion increased similarly in both the A-FOS expressing and littermate controls. However, following repeated injections of cocaine, the A-FOS expressing mice showed increased locomotion relative to littermate controls, an increase that persisted following a week of withdrawal and subsequent cocaine administration. These results indicate that AP-1 suppresses this behavioral response to cocaine. We analyzed mRNA from the striatum before and 4 and 24 h after a single cocaine injection in both A-FOS and control striata using Affymetrix microarrays (430 2.0 Array) to identify genes mis-regulated by A-FOS that may mediate the increased locomotor sensitization to cocaine. A-FOS expression did not change gene expression in the basal state or 4 h following cocaine treatment relative to controls. However, 24 h after an acute cocaine treatment, 84 genes were identified that were differentially expressed between the A-FOS and control mice. Fifty-six genes are down-regulated while 28 genes are up-regulated including previously identified candidates for addiction including brain-derived neurotrophic factor and period homolog 1. Using a random sample of identified genes, quantitative PCR was used to verify the microarray studies. The chromosomal location of these 84 genes was compared with human genome scans of addiction to identify potential genes in humans that are involved in addiction. | [R.F. Paletzkia 1, M.V. Myakishevb, O. Polesskayac, A. Oroszb, S.E. Hymana 1, C. Vinsonb] | Neuroscience | 9 April 2008 | |
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| sciencedirectS0168945207003135 | Tuning the orchestra: Selective gene regulation and orange fruit quality | Orange fruit quality is highly dependent on time-specific expression of developmental genes in peel tissues, especially those controlling physical structure and synthesis of pigments and aromatic secondary metabolites. Using a custom microarray platform, we examined expression of 366 genes of interest in peel pericarp and endocarp during three developmental stages of Washington Navel orange fruit (Citrus sinensis L. Osbeck). We examined in detail 28 of these genes that showed strong differential expression over time and across tissues. Genes putatively associated with metabolism of flavonoids, carotenoids, aroma compounds, and ascorbic acid were differentially expressed over time in specific tissues, while genes likely associated with disease resistance, photosynthesis, stress responses, and cell wall synthesis were differentially expressed over both tissue and time. Most highly differentially expressed transcripts within peel likely function to modify the cell wall architecture during growth and to develop color and aroma. | [Danielle Goudeaua, Sandra L. Uratsua, Kentaro Inouea, Francisco Goes daSilvab, Anna Leslieb, Doug Cookb, Russell L. Reagana, Abhaya M. Dandekara] | Plant Science | March 2008 | |
| sciencedirectS0890850807000515 | Expressed transcripts associated with high rates of egg production in chicken ovarian follicles | The purpose of this study was to characterize differentially expressed transcripts associated with varying rates of egg production in Taiwan country chickens. Ovarian follicles were isolated from two strains of chicken which showed low (B) or high (L2) rates of egg production, then processed for RNA extraction and cDNA library construction. Three thousand and eight forty clones were randomly selected from the cDNA library and amplified by PCR, then used in microarray analysis. Differentially expressed transcripts (P<0.05, log2?1.75) were sequenced, and aligned using GenBank. This analysis revealed 20 non-redundant sequences which corresponded to known transcripts. Eight transcripts were expressed at a higher level in ovarian tissue prepared from chicken strain B, and 12 transcripts were expressed at a higher level in L2 birds. These differential patterns of expression were confirmed by semi-quantitative RT-PCR. We show that transcripts of cyclin B2 (cycB2), ferritin heavy polypeptide 1 (FTH1), Gag-Pol polyprotein, thymosin ?4 (TB4) and elongation factor 1 ?1 (EEF1A1) were enriched in B strain ovarian follicles. In contrast, thioredoxin (TXN), acetyl-CoA dehydrogenase long chain (ACADL), inhibitor of growth family member 4 (ING4) and annexin II (ANXA2) were expressed in at higher levels in the L2 strain. We suggest that our approach may lead to the isolation of effective molecular markers that can be used in selection programs in Taiwan country chickens. | [K.T. Yanga b, C.Y. Lina, H.L. Huanga, J.S. Lioua, C.Y. Chiena, C.P. Wuc, C.W. Huanga, B.R. Oud, C.F. Chena, Y.P. Leea, E.C. Line, P.C. Tanga, W.C. Leef, S.T. Dinge, W.T.K. Chenge, M.C. Huanga] | Molecular and Cellular Probes | February 2008 | |
| sciencedirectS1875213608702705 | Transcatheter aortic valve implantation: technical aspects, results and indications | SummaryThe development of the percutaneous heart valve (PHV) may become a primary therapeutic modality for the high risk and inoperable patients with critical symptomatic aortic stenosis. The first human percutaneous aortic valve implant was performed by our group in April 2002. To date, more than 500 Cribier-Edwards-PHV have been implanted worldwide using arterial trans-femoral or trans-apical approach. Data on the retrograde transfemoral approach is growing with more than 270 patients implanted as of October 2007. Procedural success rate is high (86%) and the 30-day mortality is 12%. Today, 2 patients are alive at a follow-up of more than 4 years. The same Cribier-Edwards-PHV can be implanted using trans-apical approach. In this procedure, PHV is introduced under direct vision into the left ventricle via a mini-thoracotomy. This obviates the concerns regarding vascular access in the presence of small caliber vessels and/or vascular occlusive disease. More than 200 patients have been treated with this approach. In the European experience 30-day mortality is 14%.There is intense interest in PHV technology, and there are multiple devices at various stages of development in animals and humans. The most developed is the CoreValve Revalving® Technology. More than 350 patients have been treated with this technique. The immediate and mid-term results with this device are promising with a procedural success of 92% and a 30-day mortality of 15%.The future of this technology and its application is dependent on the continued collaboration between general internists, cardiologists, surgeons, engineers, and industry. | [H. Eltchaninoffa, A. Zajariasa, C. Trona, P.Y. Litzlerb, B. Baalaa, M. Godina, J.P. Bessoub, A. Cribiera] | Archives of Cardiovascular Diseases | January 2008 | |
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| sciencedirectS0887233307001919 | Identification of interspecies concordance of mechanisms of arsenic-induced bladder cancer | Exposure to arsenic causes cancer by inducing a variety of responses that affect the expression of genes associated with numerous biological pathways leading to altered cell growth and proliferation, signaling, apoptosis and oxidative stress response. Affymetrix GeneChip® arrays were used to detect gene expression changes following dimethylarsinic acid (DMA) exposure to human bladder cells (UROtsa) or rat bladder cells (MYP3) and rat bladder epithelium in vivo at comparable doses. Using different experimental models coupled with transcriptional profiling allowed investigation of the correlation of mechanisms of DMA-induced toxicity between in vitro and in vivo treatment and across species. Our observations suggest that DMA-induced gene expression in UROtsa cells is distinct from that observed in the MYP3 cells. Principal component analysis shows a more distinct separation by treatment and dose in MYP3 cells as compared to UROtsa cells. However, at the level of pathways and biological networks, DMA affects both common and unique processes in the bladder transitional cells of human and rats. Twelve pathways were found common between human in vitro, rat in vitro and rat in vivo systems. These included signaling pathways involved in adhesion, cellular growth and differentiation. Fifty-five genes found to be commonly expressed between rat in vivo and rat in vitro systems were involved in diverse functions such as cell cycle regulation, lipid metabolism and protein degradation. Many of the genes, processes and pathways have previously been associated with arsenic-induced toxicity. Our finding reiterates and also identifies new biological processes that might provide more information regarding the mechanisms of DMA-induced toxicity. The results of our analysis further suggest that gene expression profiles can address pertinent issues of relevance to risk assessment, namely interspecies extrapolation of mechanistic information as well as comparison of in vitro to in vivo response. | [Banalata Sena, Douglas C. Wolfa, Yaron Turpazb, Andrej Bugrimc, Jacques Retiefd, Susan D. Hestera] | Toxicology in Vitro | December 2007 | |
| sciencedirectS0012160607011864 | An early requirement for maternal FoxH1 during zebrafish gastrulation | The Forkhead Box H1 (FoxH1) protein is a co-transcription factor recruited by phosphorylated Smad2 downstream of several TGF?s, including Nodal-related proteins. We have reassessed the function of zebrafish FoxH1 using antisense morpholino oligonucleotides (MOs). MOs targeting translation of foxH1 disrupt embryonic epiboly movements during gastrulation and cause death on the first day of development. The FoxH1 morphant phenotype is much more severe than that of zebrafish carrying foxh1/schmalspur (sur) DNA-binding domain mutations, FoxH1 splice-blocking morphants or other Nodal pathway mutants, and it cannot be altered by concomitant perturbations in Nodal signaling. Apart from disrupting epiboly, FoxH1 MO treatment disrupts convergence and internalization movements. Late gastrula-stage FoxH1 morphants exhibit delayed mesoderm and endoderm marker gene expression and failed patterning of the central nervous system. Probing FoxH1 morphant RNA by microarray, we identified a cohort of five keratin genes – cyt1, cyt2, krt4, krt8 and krt18 – that are normally transcribed in the embryo's enveloping layer (EVL) and which have significantly reduced expression in FoxH1-depleted embryos. Simultaneously disrupting these keratins with a mixture of MOs reproduces the FoxH1 morphant phenotype. Our studies thus point to an essential role for maternal FoxH1 and downstream keratins during gastrulation that is epistatic to Nodal signaling. | [Wuhong Pei, Houtan Noushmehr, Justin Costa, Maia V. Ouspenskaia, Abdel G. Elkahloun, Benjamin Feldman] | Developmental Biology | 1 October 2007 | |
| sciencedirectS0300483X07004349 | Primaquine-induced differential gene expression analysis in mice liver using DNA microarrays | Primaquine (PQ), a clinically important derivative of 8-aminoquinoline used against the hepatic stages (hypnozoites) of Plasmodium vivax and Plasmodium ovale, was studied to evaluate and compare between mRNA expression, and biochemical and histological parameters of hepatic stress in adult Swiss mice (Mus musculus). Following single oral dose of PQ (40 mg/kg, bw), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) along with hematoxylin and eosin stained liver sections did not show any signs of hepatic stress at 6, 12 and 24 h except for ALT activity at 6 h. However, analysis at RNA transcript level revealed consistent and significant deregulation (p < 0.01 and two-fold) of 16 probes corresponding to important cellular processes such as protein transportation, transcription regulation, intracellular signaling, protein synthesis, hematopoiesis, cell adhesion and cell proliferation. Pathway analysis identified large number of affected genes corresponding to 40 Gene Ontology terms having a z score greater than 2. These results indicate that PQ at high doses may affect gene expression in liver and may produce undesirable outcomes if consumed for longer durations. | [Sanjeev Noela, Sharad Sharmaa, Rishi Shankerb, Srikanta Kumar Ratha] | Toxicology | 24 September 2007 | |
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| sciencedirectS0304394007002212 | Genetic modification does not affect the stemness of neural stem cells in nestin promoter-GFP transgenic mice | Because nestin promoter-GFP mice have frequently been used in neural stem cell (NSC) research, it is essential to prove that there is no alteration in the stemness of NSCs derived from this transgenic model for the interpretation and validity of the data. We compared the stemness of NSCs derived from transgenic mice expressing GFP driven by the nestin enhancer with those from wild-type (C57BL/6) mice with respect to the general gene expression profile, expression of neural stem cell markers as nestin and Sox2, and responsiveness to neurotrophins (BDNF, PDGF-BB, and NT-3). The gene expression profile analysis showed that the coefficient of correlation between the two groups was very high (r = 0.9865) in the total genes. We found that 23 genes were either up- or down-regulated more than two-fold in the NSCs from the transgenic mice (p < 0.05), without any obvious functional relatedness among them. Likewise, there was no difference between the two mouse groups in the expression of nestin or Sox2, the ability to form neurospheres and the neuronal differentiation of NSCs by neurotrophins. Taken together, the self-renewal and neuronal differentiation ability of NSCs from the transgenic mice showed the great similarity to those from wild-type mice. Such information will be useful when the properties of NSCs are evaluated following genetic modification in such a nestin-GFP Tg model. | [Jae Hyun Parka, Joon Ik Ahna, So Young Kima, Ki Sook Parka, Young Don Leeb, Masahiro Yamaguchic, Hye Joo Chunga] | Neuroscience Letters | 29 June 2007 | |
| sciencedirectS0165022X07000085 | Sensitively recorded breathing signals of rats and their nonlinear dynamics | Nonlinear dynamical properties of sensitively recorded breathing signals (SRBS), which include cardiac induced air flow pulsations so-called pneumocardiogram (PNCG) signals, are investigated, in this methodological study. For this purpose, we assessed the SRBS of laboratory rat. The nonlinear behaviors of SRBS were investigated by the reconstructing phase space, using the autocorrelation function and the false nearest neighbor method. The chaotic SRBS attractors were discussed from the point of view of the cardiopulmonary system. This method can be used to assess the heart performance and respiratory mechanics, and might be useful to design for the physiological studies of cardiorespiratory system in small laboratory animals. | [Tamer Zerena, Mustafa Özbekb, Nuran Ekerbiçerb, G. Çi?dem Yalç?nc, K. Gediz Akdenizc] | Journal of Biochemical and Biophysical Methods | 10 June 2007 | |
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| sciencedirectS0065242307440082 | Gene Expression Assays | 1. The study of the profile of gene expression in a cell or tissue at a particular moment gives an insight into the plans of the cell for protein synthesis. Recent technological advances make it possible to analyze the expression of the entire genome in a single experiment. These “gene expression assays” complement or replace previous assays which measured the gene expression of only one gene, or a select group of genes. Within this chapter we outline the development of the gene expression assay and provide examples of the wide range of disciplines in which it is used. An overview of the current technologies is given, and includes an introduction to laser capture microdissection and linear amplification of RNA, both of which have extended the application of gene expression assays. Illustrative examples in the field of cancer and neuroscience highlight the scientific achievements. This technology has made in understanding the pathogenesis of diseases, including breast cancer, Huntington's disease, and schizophrenia. With recent advances including exon arrays to investigate alternative splicing, tiling arrays to investigate novel transcription start sites, and on?chip chromatin immunoprecipitation to investigate DNA–protein interactions, the future of gene expression assays is set to further our understanding of the complexities of gene expression. | [Janine Kirby*, Paul R. Heath*, Pamela J. Shaw*, Freddie C. Hamdy†] | Advances in Clinical Chemistry | | |
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| sciencedirectS0020722597000670 | Simulating a dynamical system in the presence of a 1/f noise | Chaotic systems that possess strange attractors or exhibit type I or III intermittencies are known to yield a 1/f noise in their power spectra. In this work, simulation of such systems is considered, and bounds for the sampling frequencies on them are sought. Also, several limits on the duration of simulation are discussed. Developed ideas are demonstrated over work bench chaotic systems. | [Inanç Birol, Avadis Hacinliyan, N. Ziya Perdahçi] | International Journal of Engineering Science | 1 February 1998 | |
| sciencedirect001046559290013O | A REDUCE program for the integration of differential polynomials | A differential polynomial F[u] is a polynomial expression of the derivatives of the function u(x). A REDUCE program for the integration of differential polynomials is given. The program is tested on the computation of the conserved densities of polynomial evolution equations. Input and output from the test runs are included in the library files. | [Ay?e Hümeyra Bilge] | Computer Physics Communications | September 1992 | |
| sciencedirect0889540689902564 | Vertical dimensional changes of the lips in the North American black patient after four first-pemolar extractions | The purpose of this investigation was to evaluate the vertical dimensional changes of the lips in the North American black patient after four first-premolar oxtrao1iena. A sample of 15 patients treated at the Orthodontic Clinic of Howard University College of Dentistry was selected. Pretreatment and postreatment lateral cephalograms were traced on acetate tracing paper: landmarks of the skeletal and soft tissues were identified, and angular and linear measurements were made. Changes in the vertical dimensions of the lips used the Frankfort horizontal as a reference plane and changes in the horizontal dimensions of the lips used the p→ygoid plane as a reference plane. Statistical significance was tested by means of two-tailed t tests and Pearson's r correlations. Findings indicated that retraction of the maxillary incisors correlated with an increase in upper lip depth, an increase interlabial vertical dimension, and an increase in the inferomentolabial angle. The increase in interlabial vertical dimension correlated with an increase in the horizontal dimension of the upper lip relative to upper incisor retraction. This increase in interlabial vertical dimension relative to upper incisor retraction differed significantly from the results of the study by Jacobs on a sample of white patients treated with four first-premolar extractions. It is necessary to investigate this difference in future aWdioe using larger sample sizes. | [Susan Park DDS ∗, Earl M. Kudlick DDSMS∗∗, Avadis Abrahamian DDSMS∗∗∗] | American Journal of Orthodontics and Dentofacial Orthopedics | August 1989 | |
| sciencedirect0165607488900518 | Design of the Hermix distributed operating system: Structural aspects | Hermix is a distributed operating system currently being designed at the Department of Computer Science of the K.U. Leuven. Two fundamental problem areas, arising in the framework of this project, are analyzed and solutions are proposed. The first problem area must be situated within the overall design of distributed operating systems. Many such systems are structured as a set of servers which in mutual collaboration offer the services of the system. One possibility to realize such a design, is to implement each server as a process. The problems arising in this context are analyzed and a process structure is discussed which overcomes the encountered problems.The problems in the second area are a consequence of the complexity of distributed operating systems in general. A well known method to deal with complex software and to make it understandable and as verifiable as possible consists in structuring the system in a hierarchical way. Up till now this principle has not been elaborated in the field of distributed operating systems. To illustrate such a design we discuss those parts of Hermix which are related to memory management.Our design has been implemented on a bare machine and on top of a UNIX® system. | [Yolande Berbers, Pierre Verbaeten] | Microprocessing and Microprogramming | August 1988 | |
| sciencedirectS0300908473802299 | Aspects génétiques et biochimiques de la régulation de la transcription chez la bactérie E. coli et ses phages | | [Jean-Pierre Lecocq(*)] | Biochimie | 16 March 1973 | |
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