238 research outputs found

    Coordinations between gene modules control the operation of plant amino acid metabolic networks

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Being sessile organisms, plants should adjust their metabolism to dynamic changes in their environment. Such adjustments need particular coordination in branched metabolic networks in which a given metabolite can be converted into multiple other metabolites via different enzymatic chains. In the present report, we developed a novel "Gene Coordination" bioinformatics approach and use it to elucidate adjustable transcriptional interactions of two branched amino acid metabolic networks in plants in response to environmental stresses, using publicly available microarray results.</p> <p>Results</p> <p>Using our "Gene Coordination" approach, we have identified in Arabidopsis plants two oppositely regulated groups of "highly coordinated" genes within the branched Asp-family network of Arabidopsis plants, which metabolizes the amino acids Lys, Met, Thr, Ile and Gly, as well as a single group of "highly coordinated" genes within the branched aromatic amino acid metabolic network, which metabolizes the amino acids Trp, Phe and Tyr. These genes possess highly coordinated adjustable negative and positive expression responses to various stress cues, which apparently regulate adjustable metabolic shifts between competing branches of these networks. We also provide evidence implying that these highly coordinated genes are central to impose intra- and inter-network interactions between the Asp-family and aromatic amino acid metabolic networks as well as differential system interactions with other growth promoting and stress-associated genome-wide genes.</p> <p>Conclusion</p> <p>Our novel Gene Coordination elucidates that branched amino acid metabolic networks in plants are regulated by specific groups of highly coordinated genes that possess adjustable intra-network, inter-network and genome-wide transcriptional interactions. We also hypothesize that such transcriptional interactions enable regulatory metabolic adjustments needed for adaptation to the stresses.</p

    Comparison of Land Cover/Land Use and Habitat Classification Systems for Habitat Mapping from Space: Strengths and Weaknesses Evidenced in Mediterranean Sites of Natura 2000 Network

    Get PDF
    At a global level, protected sites have been established for the primary purpose of conserving biodiversity, with survey and monitoring of habitats undertaken largely within their boundaries. However, because of increasing human populations with greater access to resources, there is a need to now consider monitoring anthropic activities in the surrounding landscapes as pressures and disturbances are impacting on the functioning and biodiversity values of many protected sites. Earth Observation (EO) data acquired across a range of spatial and temporal scales offer new opportunities for monitoring biodiversity over varying time-scales, either through direct or indirect mapping of species or habitats. However, Land Cover (LC) and/or Land Use (LU), rather than habitat maps are generated in many national and international programs and, whilst the translation from one classification to the other is desirable, differences in definitions and criteria have so far limited the establishment of a unified approach. Focusing on both natural and non-natural environments associated with Natura 2000 sites in the Mediterranean, this paper considers the extent to which three common LC/LU taxonomies (CORINE, the Food and Agricultural Organisation (FAO) Land Cover Classification System (FAO-LCCS) and the IGBP) can be translated to habitat taxonomies with minimum use of additional environmental attributes and/or in situ data. A qualitative and quantitative analysis based on the Jaccard's index established the FAO-LCCS as being the most useful taxonomy for harmonizing LC/LU maps with different legends and dealing with the complexity of habitat description and as a framework for translating EO-derived LC/LU to habitat categories. As demonstration, a habitat map of a wetland site is obtained through translation of the LCCS taxonomy

    Tumor Invasion of Salmonella enterica Serovar Typhimurium Is Accompanied by Strong Hemorrhage Promoted by TNF-α

    Get PDF
    BACKGROUND:Several facultative anaerobic bacteria with potential therapeutic abilities are known to preferentially colonize solid tumors after systemic administration. How they efficiently find and invade the tumors is still unclear. However, this is an important issue to be clarified when bacteria should be tailored for application in cancer therapy. METHODOLOGY/PRINCIPAL FINDINGS:We describe the initial events of colonization of an ectopic transplantable tumor by Salmonella enterica serovar Typhimurium. Initially, after intravenous administration, bacteria were found in blood, spleen, and liver. Low numbers were also detected in tumors associated with blood vessels as could be observed by immunohistochemistry. A rapid increase of TNF-alpha in blood was observed at that time, in addition to other pro-inflammatory cytokines. This induced a tremendous influx of blood into the tumors by vascular disruption that could be visualized in H&E stainings and quantified by hemoglobin measurements of tumor homogenate. Most likely, together with the blood, bacteria were flushed into the tumor. In addition, blood influx was followed by necrosis formation, bacterial growth, and infiltration of neutrophilic granulocytes. Depletion of TNF-alpha retarded blood influx and delayed bacterial tumor-colonization. CONCLUSION:Our findings emphasize similarities between Gram-negative tumor-colonizing bacteria and tumor vascular disrupting agents and show the involvement of TNF-alpha in the initial phase of tumor-colonization by bacteria

    The Role of Magnetic Resonance Imaging in Diagnosis and Management of Breast Cancer

    Get PDF
    A review of the literature on the current applications of breast magnetic resonance imaging (MRI) indications, their rationale and their place in diagnosis and management of breast cancer was given. Contrast-enhanced breast MRI is developing as a valuable adjunct to mammography and sonography. Its high sensitivity for invasive breast cancer establishes its superiority in evaluation of multifocality/multicentricity, tumor response to neoadjuvant chemotherapy, detection of recurrence, and staging. Emerging applications include spectroscopy, usage of new contrast agents, and MRI-guided interventions, including noninvasive treatment of breast cancer. Its potential benefit in screening high-risk women has yet to be established with prospective studies, particularly with regard to false positive results

    Non-homologous DNA end joining in normal and cancer cells and its dependence on break structures

    Get PDF
    DNA double-strand breaks (DSBs) are a serious threat to the cell, for if not or miss-repaired, they can lead to chromosomal aberration, mutation and cancer. DSBs in human cells are repaired via non-homologous DNA end joining (NHEJ) and homologous recombination repair pathways. In the former process, the structure of DNA termini plays an important role, as does the genetic constitution of the cells, through being different in normal and pathological cells. In order to investigate the dependence of NHEJ on DSB structure in normal and cancer cells, we used linearized plasmids with various, complementary or non-complementary, single-stranded or blunt DNA termini, as well as whole-cell extract isolated from normal human lymphocytes, chronic myeloid leukemia K562 cells and lung cancer A549 cells. We observed a pronounced variability in the efficacy of NHEJ reaction depending on the type of ends. Plasmids with complementary and blunt termini were more efficiently repaired than the substrate with 3' protruding single-strand ends. The hierarchy of the effectiveness of NHEJ was on average, from the most effective to the least, A549/ normal lymphocytes/ K562. Our results suggest that the genetic constitution of the cells together with the substrate terminal structure may contribute to the efficacy of the NHEJ reaction. This should be taken into account on considering its applicability in cancer chemo- or radiotherapy by pharmacologically modulating NHEJ cellular responses

    Application of prolonged microdialysis sampling in carboplatin-treated cancer patients

    Get PDF
    Purpose: To better understand the mechanisms underlying (in)sensitivity of tumors to anticancer drugs, assessing intra-tumor drug pharmacokinetics (PKs) could be important. We explored the feasibility of microdialysis in tumor tissue for multiple days in a clinical setting, using carboplatin as model drug. Methods: Plasma and microdialysate samples from tumor and adipose normal tissues were collected up to 47 h after dosing in eight carboplatin-treated patients with an accessible (sub)cutaneous tumor. Results: Pharmacokinetics were evaluable in tumor tissue in 6/8 patients and in adipose normal tissue in 3/8 patients. Concentration-time curves of unbound platinum in both the tissues followed the pattern of the curves in plasma, with exposure ratios of tissue versus plasma ranging from 0.64 to 1.46. Conclusions: Microdialysis can be successfully employed in ambulant patients for multiple days, which enables one to study tissue PK of anticancer drugs in normal and malignant tissues in more detail

    Genome-Wide Integration on Transcription Factors, Histone Acetylation and Gene Expression Reveals Genes Co-Regulated by Histone Modification Patterns

    Get PDF
    N-terminal tails of H2A, H2B, H3 and H4 histone families are subjected to posttranslational modifications that take part in transcriptional regulation mechanisms, such as transcription factor binding and gene expression. Regulation mechanisms under control of histone modification are important but remain largely unclear, despite of emerging datasets for comprehensive analysis of histone modification. In this paper, we focus on what we call genetic harmonious units (GHUs), which are co-occurring patterns among transcription factor binding, gene expression and histone modification. We present the first genome-wide approach that captures GHUs by combining ChIP-chip with microarray datasets from Saccharomyces cerevisiae. Our approach employs noise-robust soft clustering to select patterns which share the same preferences in transcription factor-binding, histone modification and gene expression, which are all currently implied to be closely correlated. The detected patterns are a well-studied acetylation of lysine 16 of H4 in glucose depletion as well as co-acetylation of five lysine residues of H3 with H4 Lys12 and H2A Lys7 responsible for ribosome biogenesis. Furthermore, our method further suggested the recognition of acetylated H4 Lys16 being crucial to histone acetyltransferase ESA1, whose essential role is still under controversy, from a microarray dataset on ESA1 and its bypass suppressor mutants. These results demonstrate that our approach allows us to provide clearer principles behind gene regulation mechanisms under histone modifications and detect GHUs further by applying to other microarray and ChIP-chip datasets. The source code of our method, which was implemented in MATLAB (http://www.mathworks.com/), is available from the supporting page for this paper: http://www.bic.kyoto-u.ac.jp/pathway/natsume/hm_detector.htm
    corecore