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

<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

A Novel Pathway of TEF Regulation Mediated by MicroRNA-125b Contributes to the Control of Actin Distribution and Cell Shape in Fibroblasts

BACKGROUND: Thyrotroph embryonic factor (TEF), a member of the PAR bZIP family of transcriptional regulators, has been involved in neurotransmitter homeostasis, amino acid metabolism, and regulation of apoptotic proteins. In spite of its relevance, nothing is known about the regulation of TEF. PRINCIPAL FINDINGS: p53-dependent genotoxic agents have been shown to be much more harmful for PAR bZIP-deficient mice as compared to wild type animals. Here we demonstrate that TEF expression is controlled by p53 through upregulation of microRNA-125b, as determined by both regulating the activity of p53 and transfecting cells with microRNA-125b precursors. We also describe a novel role for TEF in controlling actin distribution and cell shape in mouse fibroblasts. Lack of TEF is accompanied by dramatic increase of cell area and decrease of elongation (bipolarity) and dispersion (multipolarity). Staining of actin cytoskeleton also showed that TEF (-/-) cells are characterized by appearance of circumferential actin bundles and disappearance of straight fibers. Interestingly, transfection of TEF (-/-) fibroblasts with TEF induced a wild type-like phenotype. Consistent with our previous findings, transfection of wild type fibroblasts with miR-125b promoted a TEF (-/-)-like phenotype, and a similar but weaker effect was observed following exogenous expression of p53. CONCLUSIONS/SIGNIFICANCE: These findings provide the first evidence of TEF regulation, through a miR-125b-mediated pathway, and describes a novel role of TEF in the maintenance of cell shape in fibroblasts

EGF increases expression and activity of PAs in preimplantation rat embryos and their implantation rate

BACKGROUND: Embryo implantation plays a major role in embryogenesis and the outcome of pregnancy. Plasminogen activators (PAs) have been implicated in mammalian fertilization, early stages of development and embryo implantation. As in-vitro developing embryos resulted in lower implantation rate than those developed in-vivo we assume that a reduced PAs activity may be involved. In the present work we studied the effect of EGF on PAs activity, quantity and embryo implantation. METHODS: Zygotes were flushed from rat oviducts on day one of pregnancy and grown in-vitro in R1ECM supplemented with EGF (10 ng/ml) and were grown up to the blastocyst stage. The control groups were grown in the same medium without EGF. The distribution and quantity of the PAs were examined using fluorescence immunohistochemistry followed by measurement of PAs activity using the chromogenic assay. Implantation rate was studied using the embryo donation model. RESULTS: PAs distribution in the embryos was the same in EGF treated and untreated embryos. Both PAs were localized in the blastocysts' trophectoderm, supporting the assumption that PAs play a role in the implantation process in rats. EGF increased the quantity of uPA at all stages studied but the 8-cell stage as compared with controls. The tissue type PA (tPA) content was unaffected except the 8-cell stage, which was increased. The activity of uPA increased gradually towards the blastocyst stage and more so due to the presence of EGF. The activity of tPA did not vary with the advancing developmental stages although it was also increased by EGF. The presence of EGF during the preimplantation development doubled the rate of implantation of the treated group as compared with controls

Synthesis of an ordered mesoporous carbon with graphitic characteristics and its application for dye adsorption

An ordered mesoporous carbon (OMC) was prepared by a chemical vapor deposition technique using liquid petroleum gas (LPG) as the carbon source. During synthesis, LPG was effectively adsorbed in the ordered mesopores of SBA-15 silica and converted to a graphitic carbon at 800 °C. X-ray diffraction and nitrogen adsorption/desorption data and high-resolution transmission electron microscopy (HRTEM) of the OMC confirmed its ordered mesoporous structure. The OMC was utilized as an adsorbent in the removal of dyes from aqueous solution. A commercial powder activated carbon (AC) was also investigated to obtain comparative data. The efficiency of the OMC for dye adsorption was tested using acidic dye acid orange 8 (AO8) and basic dyes methylene blue (MB) and rhodamine B (RB). The results show that adsorption was affected by the molecular size of the dye, the textural properties of carbon adsorbent and surface-dye interactions. The adsorption capacities of the OMC for acid orange 8 (AO8), methylene blue (MB) and rhodamine B (RB) were determined to be 222, 833, and 233 mg/g, respectively. The adsorption capacities of the AC for AO8, MB, and RB were determined to be 141, 313, and 185 mg/ g, respectively. The OMC demonstrated to be an excellent adsorbent for the removal of MB from wastewater.Web of Scienc

Degradation of HIF-1alpha under Hypoxia Combined with Induction of Hsp90 Polyubiquitination in Cancer Cells by Hypericin: a Unique Cancer Therapy

The perihydroxylated perylene quinone hypericin has been reported to possess potent anti-metastatic and antiangiogenic activities, generated by targeting diverse crossroads of cancer-promoting processes via unique mechanisms. Hypericin is the only known exogenous reagent that can induce forced poly-ubiquitination and accelerated degradation of heat shock protein 90 (Hsp90) in cancer cells. Hsp90 client proteins are thereby destabilized and rapidly degraded. Hsp70 client proteins may potentially be also affected via preventing formation of hsp90-hsp70 intermediate complexes. We show here that hypericin also induces enhanced degradation of hypoxia-inducible factor 1α (HIF-1α) in two human tumor cell lines, U87-MG glioblastoma and RCC-C2VHL−/− renal cell carcinoma and in the non-malignant ARPE19 retinal pigment epithelial cell line. The hypericin-accelerated turnover of HIF-1α, the regulatory precursor of the HIF-1 transcription factor which promotes hypoxic stress and angiogenic responses, overcomes the physiologic HIF-1α protein stabilization which occurs in hypoxic cells. The hypericin effect also eliminates the high HIF-1α levels expressed constitutively in the von-Hippel Lindau protein (pVHL)-deficient RCC-C2VHL−/− renal cell carcinoma cell line. Unlike the normal ubiquitin-proteasome pathway-dependent turnover of HIF-α proteins which occurs in normoxia, the hypericin-induced HIF-1α catabolism can occur independently of cellular oxygen levels or pVHL-promoted ubiquitin ligation of HIF-1α. It is mediated by lysosomal cathepsin-B enzymes with cathepsin-B activity being optimized in the cells through hypericin-mediated reduction in intracellular pH. Our findings suggest that hypericin may potentially be useful in preventing growth of tumors in which HIF-1α plays pivotal roles, and in pVHL ablated tumor cells such as renal cell carcinoma through elimination of elevated HIF-1α contents in these cells, scaling down the excessive angiogenesis which characterizes these tumors

A multi-biometric iris recognition system based on a deep learning approach

YesMultimodal biometric systems have been widely applied in many real-world applications due to its ability to deal with a number of significant limitations of unimodal biometric systems, including sensitivity to noise, population coverage, intra-class variability, non-universality, and vulnerability to spoofing. In this paper, an efficient and real-time multimodal biometric system is proposed based on building deep learning representations for images of both the right and left irises of a person, and fusing the results obtained using a ranking-level fusion method. The trained deep learning system proposed is called IrisConvNet whose architecture is based on a combination of Convolutional Neural Network (CNN) and Softmax classifier to extract discriminative features from the input image without any domain knowledge where the input image represents the localized iris region and then classify it into one of N classes. In this work, a discriminative CNN training scheme based on a combination of back-propagation algorithm and mini-batch AdaGrad optimization method is proposed for weights updating and learning rate adaptation, respectively. In addition, other training strategies (e.g., dropout method, data augmentation) are also proposed in order to evaluate different CNN architectures. The performance of the proposed system is tested on three public datasets collected under different conditions: SDUMLA-HMT, CASIA-Iris- V3 Interval and IITD iris databases. The results obtained from the proposed system outperform other state-of-the-art of approaches (e.g., Wavelet transform, Scattering transform, Local Binary Pattern and PCA) by achieving a Rank-1 identification rate of 100% on all the employed databases and a recognition time less than one second per person

Comparison of gene expression profiles in core biopsies and corresponding surgical breast cancer samples

INTRODUCTION: Gene expression profiling has been successfully used to classify breast cancer into clinically distinct subtypes, and to predict the risk of recurrence and treatment response. The aim of this study was to investigate whether the gene expression profile (GEP) detected in a core biopsy (CB) is representative for the entire tumor, since CB is an important tool in breast cancer diagnosis. Moreover, we investigated whether performing CBs prior to the surgical excision could influence the GEP of the respective tumor. METHODS: We quantified the RNA expression of 60 relevant genes by quantitative real-time PCR in paired CBs and surgical specimens from 22 untreated primary breast cancer patients. Subsequently, expression data were compared with independent GEPs obtained from tumors of 317 patients without preceding CB. RESULTS: In 82% of the cases the GEP detected in the CB correlated very well with the corresponding profile in the surgical sample (r(s )≥ 0.95, p < 0.001). Gene-by-gene analysis revealed four genes significantly elevated in the surgical sample compared to the CB; these comprised genes mainly involved in inflammation and the wound repair process as well as in tumor invasion and metastasis. CONCLUSION: A GEP detected in a CB are representative for the entire tumor and is, therefore, of clinical relevance. The observed alterations of individual genes after performance of CB deserve attention since they might impact the clinical interpretation with respect to prognosis and therapy prediction of the GEP as detected in the surgical specimen following CB performance

Attaching and effacing (A/E) lesion formation by enteropathogenic E. coli on human intestinal mucosa is dependent on non-LEE effectors

Enteropathogenic E. coli (EPEC) is a human pathogen that causes acute and chronic pediatric diarrhea. The hallmark of EPEC infection is the formation of attaching and effacing (A/E) lesions in the intestinal epithelium. Formation of A/E lesions is mediated by genes located on the pathogenicity island locus of enterocyte effacement (LEE), which encode the adhesin intimin, a type III secretion system (T3SS) and six effectors, including the essential translocated intimin receptor (Tir). Seventeen additional effectors are encoded by genes located outside the LEE, in insertion elements and prophages. Here, using a stepwise approach, we generated an EPEC mutant lacking the entire effector genes (EPEC0) and intermediate mutants. We show that EPEC0 contains a functional T3SS. An EPEC mutant expressing intimin but lacking all the LEE effectors but Tir (EPEC1) was able to trigger robust actin polymerization in HeLa cells and mucin-producing intestinal LS174T cells. However, EPEC1 was unable to form A/E lesions on human intestinal in vitro organ cultures (IVOC). Screening the intermediate mutants for genes involved in A/E lesion formation on IVOC revealed that strains lacking non-LEE effector/s have a marginal ability to form A/E lesions. Furthermore, we found that Efa1/LifA proteins are important for A/E lesion formation efficiency in EPEC strains lacking multiple effectors. Taken together, these results demonstrate the intricate relationships between T3SS effectors and the essential role non-LEE effectors play in A/E lesion formation on mucosal surfaces

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN