50 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/06/07

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

40 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/06/06

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Identification of endocrine disrupting chemicals acting on human aromatase.

Biochim Biophys Acta. 2017 May 31;:

Authors: Baravalle R, Ciaramella A, Baj F, Di Nardo G, Gilardi G

Abstract
Human aromatase is the cytochrome P450 catalysing the conversion of androgens into estrogens playing a key role in the endocrine system. Due to this role, it is likely to be a target of the so-called endocrine disrupting chemicals, a series of compounds able to interfere with the hormone system with toxic effects. If on one side the toxicity of some compounds such as bisphenol A is well known, on the other side the toxic concentrations of such compounds as well as the effect of the many other molecules that are in contact with us in everyday life still need a deep investigation. The availability of biological assays able to detect the interaction of chemicals with key molecular targets of the endocrine system represent a possible solution to identify potential endocrine disrupting chemicals. Here the so-called alkali assay previously developed in our laboratory is applied to test the effect of different compounds on the activity of human aromatase. The assay is based on the detection of the alkali product that forms upon strong alkali treatment of the NADP(+) released upon enzyme turnover. Here it is applied on human aromatase and validated using anastrozole and sildenafil as known aromatase inhibitors. Out of the small library of compounds tested, resveratrol and ketoconazole resulted to inhibit aromatase activity, while bisphenol A and nicotine were found to exert an inhibitory effect at relatively high concentrations (100μM), and other molecules such as lindane and four plasticizers did not show any significant effect. These data are confirmed by quantification of the product estrone in the same reaction mixtures through ELISA. Overall, the results show that the alkali assay is suitable to screen for molecules that interfere with aromatase activity. As a consequence it can also be applied to other molecular targets of EDCs that use NAD(P)H for catalysis in a high throughput format for the fast screening of many different compounds as endocrine disrupting chemicals. This article is part of a Special Issue entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone.

PMID: 28578073 [PubMed - as supplied by publisher]

Systematic identification of cancer-related long noncoding RNAs and aberrant alternative splicing of quintuple-negative lung adenocarcinoma through RNA-Seq.

Lung Cancer. 2017 Jul;109:21-27

Authors: Zhang L, Li S, Choi YL, Lee J, Gong Z, Liu X, Pei Y, Jiang A, Ye M, Mao M, Zhang X, Kim J, Chen R

Abstract
OBJECTIVES: Lung adenocarcinoma (LUAD) is a common subtype of non-small cell lung cancer prevalent in Asia. There is a dearth of understanding regarding the transcriptome landscape of LUAD without primary known driver mutations. In this study, LUAD samples without well-known driver mutations occurring in EGFR, KRAS, ALK, ROS1 or RET (quintuple-negative) were used for transcriptome study with a focus on long noncoding RNAs (lncRNAs), alternative splicing and gene fusions.
MATERIALS AND METHODS: 24 pairs of LUAD and adjacent normal samples and 13 tumor-only samples derived from 37 quintuple-negative patients were used. Differentially expressed lncRNA transcripts were detected by paired t-test and were validated by qPCR. Functions of lncRNAs were predicted by co-expressed mRNAs. Aberrant splicing events in LUAD were identified using MISO. In addition, gene fusions were screened by SOAPfuse.
RESULTS AND CONCLUSION: In total, 90 and 153 up- or down-regulated lncRNA transcripts were detected in LUAD samples in comparison with the adjacent normal samples. The most significantly differentially expressed lncRNA transcript was ENST00000598996.1 (FENDRR) down-regulated in LUAD. By lncRNA-mRNA co-expression analysis, functions of 14 lncRNAs were predicted. The predicted functions included vasculature development, immune response, cell cycle and respiratory gaseous exchange. Furthermore, six co-expressed pairs of lncRNAs and their nearby protein coding genes were identified as associated with lung development. This study also identified two highly recurrent (22 in 24) differential exon skipping events occurring in MYH14 and ESYT2 with exon including isoforms of both genes up-regulated in isoform percentage in LUAD samples. On the other hand, two out of 24 LUAD samples possessed the driver mutation exon 14 skipping of MET. The transcriptional alterations of LUAD samples without well-known driver mutations identified in the study can be used as references for future research. The translational values of these transcriptional changes are also worthy of further investigation.

PMID: 28577945 [PubMed - in process]

European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS).

Redox Biol. 2017 May 18;13:94-162

Authors: Egea J, Fabregat I, Frapart YM, Ghezzi P, Görlach A, Kietzmann T, Kubaichuk K, Knaus UG, Lopez MG, Olaso-Gonzalez G, Petry A, Schulz R, Vina J, Winyard P, Abbas K, Ademowo OS, Afonso CB, Andreadou I, Antelmann H, Antunes F, Aslan M, Bachschmid MM, Barbosa RM, Belousov V, Berndt C, Bernlohr D, Bertrán E, Bindoli A, Bottari SP, Brito PM, Carrara G, Casas AI, Chatzi A, Chondrogianni N, Conrad M, Cooke MS, Costa JG, Cuadrado A, My-Chan Dang P, De Smet B, Debelec-Butuner B, Dias IHK, Dunn JD, Edson AJ, El Assar M, El-Benna J, Ferdinandy P, Fernandes AS, Fladmark KE, Förstermann U, Giniatullin R, Giricz Z, Görbe A, Griffiths H, Hampl V, Hanf A, Herget J, Hernansanz-Agustín P, Hillion M, Huang J, Ilikay S, Jansen-Dürr P, Jaquet V, Joles JA, Kalyanaraman B, Kaminskyy D, Karbaschi M, Kleanthous M, Klotz LO, Korac B, Korkmaz KS, Koziel R, Kračun D, Krause KH, Křen V, Krieg T, Laranjinha J, Lazou A, Li H, Martínez-Ruiz A, Matsui R, McBean GJ, Meredith SP, Messens J, Miguel V, Mikhed Y, Milisav I, Milković L, Miranda-Vizuete A, Mojović M, Monsalve M, Mouthuy PA, Mulvey J, Münzel T, Muzykantov V, Nguyen ITN, Oelze M, Oliveira NG, Palmeira CM, Papaevgeniou N, Pavićević A, Pedre B, Peyrot F, Phylactides M, Pircalabioru GG, Pitt AR, Poulsen HE, Prieto I, Rigobello MP, Robledinos-Antón N, Rodríguez-Mañas L, Rolo AP, Rousset F, Ruskovska T, Saraiva N, Sasson S, Schröder K, Semen K, Seredenina T, Shakirzyanova A, Smith GL, Soldati T, Sousa BC, Spickett CM, Stancic A, Stasia MJ, Steinbrenner H, Stepanić V, Steven S, Tokatlidis K, Tuncay E, Turan B, Ursini F, Vacek J, Vajnerova O, Valentová K, Van Breusegem F, Varisli L, Veal EA, Yalçın AS, Yelisyeyeva O, Žarković N, Zatloukalová M, Zielonka J, Touyz RM, Papapetropoulos A, Grune T, Lamas S, Schmidt HHHW, Di Lisa F, Daiber A

Abstract
The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.

PMID: 28577489 [PubMed - as supplied by publisher]

Disrupting Interactions Between β-Catenin and Activating TCFs Reconstitutes Ground State pluripotency In Mouse Embryonic Stem Cells.

Stem Cells. 2017 Jun 02;:

Authors: Saj A, Chatterjee SS, Zhu B, Cukuroglu E, Gocha T, Zhang X, Göke J, DasGupta R

Abstract
The 2i-media, composed of two small molecule inhibitors (PD0325901 and CHIR99021) against MEK and GSK3-kinases respectively, is known to establish naïve ground state pluripotency in mouse embryonic stem cells (mESCs). These inhibitors block MEK-mediated differentiation, while driving β-catenin dependent de-repression of pluripotency promoting targets. However, accumulating evidence suggest that β-catenin's association with activating TCFs (TCF7 and TCF7L2) can induce expression of several lineage-specific pro-differentiation genes. We posited that CHIR-induced upregulation of β-catenin levels could therefore compromise the stability of the naïve state in long-term cultures. Here, we investigated whether replacing CHIR with iCRT3, a small molecule that abrogates β-catenin-TCF interaction, can still retain ground state pluripotency in mESCs. Our data suggests that iCRT3+PD mediated co-inhibition of MEK and β-catenin/TCF-dependent transcriptional activity over multiple passages significantly reduces expression of differentiation markers, as compared to 2i. Furthermore, the ability to efficiently contribute towards chimera generation and germline transmission suggests that the inhibition of β-catenin's TCF-dependent transcriptional activity, independent of its protein expression level, retains the naïve ground state pluripotency in mESCs. Additionally, growth medium containing iCRT3+PD can provide an alternative to 2i as a stable culture method. This article is protected by copyright. All rights reserved.

PMID: 28577307 [PubMed - as supplied by publisher]

Overexpression of Rice Auxilin-Like Protein, XB21, Induces Necrotic Lesions, up-Regulates Endocytosis-Related Genes, and Confers Enhanced Resistance to Xanthomonas oryzae pv. oryzae.

Rice (N Y). 2017 Dec;10(1):27

Authors: Park CJ, Wei T, Sharma R, Ronald PC

Abstract
BACKGROUND: The rice immune receptor XA21 confers resistance to the bacterial pathogen, Xanthomonas oryzae pv. oryzae (Xoo). To elucidate the mechanism of XA21-mediated immunity, we previously performed a yeast two-hybrid screening for XA21 interactors and identified XA21 binding protein 21 (XB21).
RESULTS: Here, we report that XB21 is an auxilin-like protein predicted to function in clathrin-mediated endocytosis. We demonstrate an XA21/XB21 in vivo interaction using co-immunoprecipitation in rice. Overexpression of XB21 in rice variety Kitaake and a Kitaake transgenic line expressing XA21 confers a necrotic lesion phenotype and enhances resistance to Xoo. RNA sequencing reveals that XB21 overexpression results in the differential expression of 8735 genes (4939 genes up- and 3846 genes down-regulated) (≥2-folds, FDR ≤0.01). The up-regulated genes include those predicted to be involved in 'cell death' and 'vesicle-mediated transport'.
CONCLUSION: These results indicate that XB21 plays a role in the plant immune response and in regulation of cell death. The up-regulation of genes controlling 'vesicle-mediated transport' in XB21 overexpression lines is consistent with a functional role for XB21 as an auxilin.

PMID: 28577284 [PubMed - in process]

Genome-wide association study for agronomic and physiological traits in spring wheat evaluated in a range of heat prone environments.

Theor Appl Genet. 2017 Jun 02;:

Authors: Ogbonnaya FC, Rasheed A, Okechukwu EC, Jighly A, Makdis F, Wuletaw T, Hagras A, Uguru MI, Agbo CU

Abstract
KEY MESSAGE: We identified 27 stable loci associated with agronomic traits in spring wheat using genome-wide association analysis, some of which confirmed previously reported studies. GWAS peaks identified in regions where no QTL for grain yield per se has been mapped to date, provide new opportunities for gene discovery and creation of new cultivars with desirable alleles for improving yield and yield stability in wheat. We undertook large-scale genetic analysis to determine marker-trait associations (MTAs) underlying agronomic and physiological performance in spring wheat using genome-wide association studies (GWAS). Field trials were conducted at seven sites in three countries (Sudan, Egypt, and Syria) over 2-3 years in each country. Twenty-five agronomic and physiological traits were measured on 188 wheat genotypes. After correcting for population structure and relatedness, a total of 245 MTAs distributed over 66 loci were associated with agronomic traits in individual and mean performance across environments respectively; some of which confirmed previously reported loci. Of these, 27 loci were significantly associated with days to heading, thousand kernel weight, grain yield, spike length, and leaf rolling for mean performance across environments. Despite strong QTL by environment interactions, eight of the loci on chromosomes 1A, 1D, 5A, 5D, 6B, 7A, and 7B had pleiotropic effects on days to heading and yield components (TKW, SM(-2), and SNS). The winter-type alleles at the homoeologous VRN1 loci significantly increased days to heading and grain yield in optimal environments, but decreased grain yield in heat prone environments. Top 20 high-yielding genotypes, ranked by additive main effects and multiplicative interaction (AMMI), had low kinship relationship and possessed 4-5 favorable alleles for GY MTAs except two genotypes, Shadi-4 and Qafzah-11/Bashiq-1-2. This indicated different yield stability mechanisms due to potentially favorable rare alleles that are uncharacterized. Our results will enable wheat breeders to effectively introgress several desirable alleles into locally adapted germplasm in developing wheat varieties with high yield stability and enhanced heat tolerance.

PMID: 28577083 [PubMed - as supplied by publisher]

Modeling gene regulation from paired expression and chromatin accessibility data.

Proc Natl Acad Sci U S A. 2017 Jun 02;:

Authors: Duren Z, Chen X, Jiang R, Wang Y, Wong WH

Abstract
The rapid increase of genome-wide datasets on gene expression, chromatin states, and transcription factor (TF) binding locations offers an exciting opportunity to interpret the information encoded in genomes and epigenomes. This task can be challenging as it requires joint modeling of context-specific activation of cis-regulatory elements (REs) and the effects on transcription of associated regulatory factors. To meet this challenge, we propose a statistical approach based on paired expression and chromatin accessibility (PECA) data across diverse cellular contexts. In our approach, we model (i) the localization to REs of chromatin regulators (CRs) based on their interaction with sequence-specific TFs, (ii) the activation of REs due to CRs that are localized to them, and (iii) the effect of TFs bound to activated REs on the transcription of target genes (TGs). The transcriptional regulatory network inferred by PECA provides a detailed view of how trans- and cis-regulatory elements work together to affect gene expression in a context-specific manner. We illustrate the feasibility of this approach by analyzing paired expression and accessibility data from the mouse Encyclopedia of DNA Elements (ENCODE) and explore various applications of the resulting model.

PMID: 28576882 [PubMed - as supplied by publisher]

Isochronous dynamics in pulse coupled oscillator networks with delay.

Chaos. 2017 May;27(5):053103

Authors: Li P, Lin W, Efstathiou K

Abstract
We consider a network of identical pulse-coupled oscillators with delay and all-to-all coupling. We demonstrate that the discontinuous nature of the dynamics induces the appearance of isochronous regions-subsets of the phase space filled with periodic orbits having the same period. For each fixed value of the network parameters, such an isochronous region corresponds to a subset of initial states on an appropriate surface of section with non-zero dimensions such that all periodic orbits in this set have qualitatively similar dynamical behaviour. We analytically and numerically study in detail such an isochronous region, give proof of its existence, and describe its properties. We further describe other isochronous regions that appear in the system.

PMID: 28576100 [PubMed - in process]

40 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/06/03

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/06/02

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

39 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/06/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/05/31

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/05/30

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

30 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/05/30

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

TRPM8 inhibits endothelial cell migration via a non-channel function by trapping the small GTPase Rap1.

J Cell Biol. 2017 May 26;:

Authors: Genova T, Grolez GP, Camillo C, Bernardini M, Bokhobza A, Richard E, Scianna M, Lemonnier L, Valdembri D, Munaron L, Philips MR, Mattot V, Serini G, Prevarskaya N, Gkika D, Pla AF

Abstract
Endothelial cell adhesion and migration are critical steps of the angiogenic process, whose dysfunction is associated with tumor growth and metastasis. The TRPM8 channel has recently been proposed to play a protective role in prostate cancer by impairing cell motility. However, the mechanisms by which it could influence vascular behavior are unknown. Here, we reveal a novel non-channel function for TRPM8 that unexpectedly acts as a Rap1 GTPase inhibitor, thereby inhibiting endothelial cell motility, independently of pore function. TRPM8 retains Rap1 intracellularly through direct protein-protein interaction, thus preventing its cytoplasm-plasma membrane trafficking. In turn, this mechanism impairs the activation of a major inside-out signaling pathway that triggers the conformational activation of integrin and, consequently, cell adhesion, migration, in vitro endothelial tube formation, and spheroid sprouting. Our results bring to light a novel, pore-independent molecular mechanism by which endogenous TRPM8 expression inhibits Rap1 GTPase and thus plays a critical role in the behavior of vascular endothelial cells by inhibiting migration.

PMID: 28550110 [PubMed - as supplied by publisher]

Central Nervous System Involvement in Acute Lymphoblastic Leukemia Is Mediated by Vascular Endothelial Growth Factor.

Blood. 2017 May 26;:

Authors: Münch V, Trentin L, Herzig J, Demir S, Seyfried F, Kraus JM, Kestler HA, Köhler R, Barth TFE, Te Kronnie G, Debatin KM, Meyer LH

Abstract
In acute lymphoblastic leukemia (ALL), central nervous system (CNS) involvement is a major clinical concern. Despite non-detectable CNS leukemia in many cases, prophylactic CNS-directed conventional intrathecal chemotherapy is required for relapse free survival indicating subclinical CNS manifestation in most patients. However, CNS-directed therapy is associated with long-term sequelae including neurocognitive deficits and secondary neoplasms. Therefore, molecular mechanisms and pathways mediating leukemia cell entry into the CNS need to be understood in order to identify targets for prophylactic and therapeutic interventions and develop alternative CNS-directed treatment strategies. In this study, we analyzed leukemia cell entry into the CNS using a primograft ALL mouse model. We found, that primary ALL cells transplanted onto NOD/SCID mice faithfully recapitulate clinical and pathological features of meningeal infiltration seen in ALL patients. ALL cells, which have entered the CNS and are infiltrating the meninges, are characterized by high expression of vascular endothelial growth factor A (VEGF) While cellular viability, growth, proliferation and survival of ALL cells were found to be independent of VEGF, trans-endothelial migration through CNS microvascular endothelial cells was regulated by VEGF. The importance of VEGF produced by ALL cells in mediating leukemia cell entry into the CNS and leptomeningeal infiltration was further demonstrated by specific reduction of CNS leukemia upon in vivo VEGF capture by the anti-VEGF antibody bevacizumab. Thus, we identified a mechanism of ALL cell entry into the CNS, which by targeting of VEGF signaling may serve as a novel strategy to control CNS leukemia in patients replacing conventional CNS-toxic treatment.

PMID: 28550041 [PubMed - as supplied by publisher]

Early transcriptome responses of the bovine midcycle corpus luteum to prostaglandin F2α includes cytokine signaling.

Mol Cell Endocrinol. 2017 May 23;:

Authors: Talbott H, Hou X, Qiu F, Zhang P, Guda C, Yu F, Cushman RA, Wood JR, Wang C, Cupp AS, Davis JS

Abstract
In ruminants, prostaglandin F2alpha (PGF2α)-mediated luteolysis is essential prior to estrous cycle resumption, and is a target for improving fertility. To deduce early PGF2α-provoked changes in the corpus luteum a short time-course (0.5-4 h) was performed on cows at midcycle. A microarray-determined transcriptome was established and examined by bioinformatic pathway analysis. Classic PGF2α effects were evident by changes in early response genes (FOS, JUN, ATF3) and prediction of active pathways (PKC, MAPK). Several cytokine transcripts were elevated and NF-κB and STAT activation were predicted by pathway analysis. Self-organizing map analysis grouped differentially expressed transcripts into ten mRNA expression patterns indicative of temporal signaling cascades. Comparison with two analogous datasets revealed a conserved group of 124 transcripts similarly altered by PGF2α treatment, which both, directly and indirectly, indicated cytokine activation. Elevated levels of cytokine transcripts after PGF2α and predicted activation of cytokine pathways implicate inflammatory reactions early in PGF2α-mediated luteolysis.

PMID: 28549990 [PubMed - as supplied by publisher]

32 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/05/27

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.