Systems Biology
"systems biology"; +25 new citations
25 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2018/06/20
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.
"systems biology"; +39 new citations
39 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2018/06/19
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.
NEDD8-its role in the regulation of Cullin-RING ligases.
NEDD8-its role in the regulation of Cullin-RING ligases.
Curr Opin Plant Biol. 2018 Jun 14;45(Pt A):112-119
Authors: Schwechheimer C
Abstract
The ubiquitin-related protein NEDD8 is conjugated and deconjugated to and from proteins in processes related to ubiquitin conjugation and deconjugation. Neddylation is a well-studied posttranslational modification of Cullin-RING E3 ligases (CRLs). Biochemical and structural studies aiming at understanding the role of NEDD8 in CRL function have now resulted in a convincing model of how neddylation and deneddylation antagonistically regulate CRL stability, conformation, activity as well as degradation substrate receptor exchange. Studies of the Arabidopsis thaliana deneddylation-deficient den1 mutant led to the identification of many low abundant, non-Cullin NEDD8 conjugates. Examination of neddylated AUXIN RESISTANT1 (AXR1), a prominent neddylated protein in den1, suggests, however, that AXR1 neddylation may be an auto-catalytic side-reaction of Cullin-targeted neddylation and that DEN1 may serve to antagonize non-productive, auto-neddylation from substrates to provide free NEDD8 for CRL regulation.
PMID: 29909289 [PubMed - as supplied by publisher]
Light and temperature shape nuclear architecture and gene expression.
Light and temperature shape nuclear architecture and gene expression.
Curr Opin Plant Biol. 2018 Jun 14;45(Pt A):103-111
Authors: Kaiserli E, Perrella G, Davidson ML
Abstract
Environmental stimuli play a major role in modulating growth and development throughout the life-cycle of a plant. Quantitative and qualitative variations in light and temperature trigger changes in gene expression that ultimately shape plant morphology for adaptation and survival. Although the phenotypic and transcriptomic basis of plant responses to the constantly changing environment have been examined for decades, the relationship between global changes in nuclear architecture and adaption to environmental stimuli is just being uncovered. This review presents recent discoveries investigating how changes in light and temperature trigger changes in chromatin structure and nuclear organization with a focus on the role of gene repositioning and chromatin accessibility in regulating gene expression.
PMID: 29909288 [PubMed - as supplied by publisher]
Basic functional trade-offs in cognition: An integrative framework.
Basic functional trade-offs in cognition: An integrative framework.
Cognition. 2018 Jun 14;179:56-70
Authors: Del Giudice M, Crespi BJ
Abstract
Trade-offs between advantageous but conflicting properties (e.g., speed vs. accuracy) are ubiquitous in cognition, but the relevant literature is conceptually fragmented, scattered across disciplines, and has not been organized in a coherent framework. This paper takes an initial step toward a general theory of cognitive trade-offs by examining four key properties of goal-directed systems: performance, efficiency, robustness, and flexibility. These properties define a number of basic functional trade-offs that can be used to map the abstract "design space" of natural and artificial cognitive systems. Basic functional trade-offs provide a shared vocabulary to describe a variety of specific trade-offs including speed vs. accuracy, generalist vs. specialist, exploration vs. exploitation, and many others. By linking specific features of cognitive functioning to general properties such as robustness and efficiency, it becomes possible to harness some powerful insights from systems engineering and systems biology to suggest useful generalizations, point to under-explored but potentially important trade-offs, and prompt novel hypotheses and connections between disparate areas of research.
PMID: 29909281 [PubMed - as supplied by publisher]
Stochastic Endogenous Replication Stress Causes ATR-Triggered Fluctuations in CDK2 Activity that Dynamically Adjust Global DNA Synthesis Rates.
Stochastic Endogenous Replication Stress Causes ATR-Triggered Fluctuations in CDK2 Activity that Dynamically Adjust Global DNA Synthesis Rates.
Cell Syst. 2018 Jun 04;:
Authors: Daigh LH, Liu C, Chung M, Cimprich KA, Meyer T
Abstract
Faithful DNA replication is challenged by stalling of replication forks during S phase. Replication stress is further increased in cancer cells or in response to genotoxic insults. Using live single-cell image analysis, we found that CDK2 activity fluctuates throughout an unperturbed S phase. We show that CDK2 fluctuations result from transient ATR signals triggered by stochastic replication stress events. In turn, fluctuating endogenous CDK2 activity causes corresponding decreases and increases in DNA synthesis rates, linking changes in stochastic replication stress to fluctuating global DNA replication rates throughout S phase. Moreover, cells that re-enter the cell cycle after mitogen stimulation have increased CDK2 fluctuations and prolonged S phase resulting from increased replication stress-induced CDK2 suppression. Thus, our study reveals a dynamic control principle for DNA replication whereby CDK2 activity is suppressed and fluctuates throughout S phase to continually adjust global DNA synthesis rates in response to recurring stochastic replication stress events.
PMID: 29909278 [PubMed - as supplied by publisher]
Close Encounters of Three Kinds: Bacteriophages, Commensal Bacteria, and Host Immunity.
Close Encounters of Three Kinds: Bacteriophages, Commensal Bacteria, and Host Immunity.
Trends Microbiol. 2018 Jun 13;:
Authors: Keen EC, Dantas G
Abstract
Recent years have witnessed an explosion of interest in the human microbiota. Although commensal bacteria have dominated research efforts to date, mounting evidence suggests that endogenous viral populations (the 'virome') play key roles in basic human physiology. The most numerous constituents of the human virome are not eukaryotic viruses but rather bacteriophages, viruses that infect bacteria. Here, we review phages' interactions with their immediate (prokaryotic) and extended (eukaryotic) hosts and with each other, with a particular emphasis on the temperate phages and prophages which dominate the human virome. We also discuss key outstanding questions in this emerging field and emphasize the urgent need for functional studies in animal models to complement previous in vitro work and current computational approaches.
PMID: 29909042 [PubMed - as supplied by publisher]
Is there a mutation gradient along vertebrate mitochondrial genome mediated by genome replication?
Is there a mutation gradient along vertebrate mitochondrial genome mediated by genome replication?
Mitochondrion. 2018 Jun 14;:
Authors: Xia X
Abstract
There is a long-held belief that a mutation gradient exists along vertebrate mtDNA, mediated by mitochondrial replication that leaves different parts of the H-strand exposed in single-stranded state for different durations (DssH). However, the predicted mutation gradient and its tests suffer from both conceptual and empirical problems. I assembled representative mammalian, avian and crocodilian mtDNA to test this prediction. I measured substitution rates at codon positions 1 and 2 (S12) and at codon position 3 (S3), as well as synonymous and nonsynonymous substitution rates, and checked their change along the hypothetical gradient. Mammalian species do not support the predicted mutation gradient, although they should according to the model. Crocodilian species exhibit a pattern closest to the prediction, although they should not because their OL, if present, is not at a fixed position. Correlation between S3 and DssH is much weaker than that between S12 and DssH (contrary to the prediction). This is not due to substitution saturation but is instead due to differential gene conservation, e.g., COX1 is far more conserved than ND6 in all metazoans no matter where they are located along mtDNA. In vertebrates, conserved genes such as COX1 happen to have small DssH and variables genes such as ND6 happen to have large DssH. The observed "mutation gradient" is driven by nonsynonymous substitutions, with synonymous substitutions associated with a much weaker "mutation gradient" likely caused by differential codon re-adaptation after nonsynonymous substitutions. The mammalian and avian results are also confirmed by a much larger compilation and analysis of 691 mammalian and 462 avian mtDNAs. The results, however, does not reject paper is not a test of the strand-displacement model (SDM) of mtDNA replication because a mutation gradient is not a necessary consequence of SDM.
PMID: 29909015 [PubMed - as supplied by publisher]
The emerging potential for network analysis to inform precision cancer medicine.
The emerging potential for network analysis to inform precision cancer medicine.
J Mol Biol. 2018 Jun 14;:
Authors: Ozturk K, Dow M, Carlin DE, Bejar R, Carter H
Abstract
Precision cancer medicine promises to tailor clinical decisions to patients using genomic information. Indeed, successes of drugs targeting genetic alterations in tumors, such as imatinib that targets BCR-ABL in chronic myelogenous leukemia, have demonstrated the power of this approach. However biological systems are complex, and patients may differ not only by the specific genetic alterations in their tumor, but by more subtle interactions among such alterations. Systems biology and more specifically, network analysis, provides a framework for advancing precision medicine beyond clinical actionability of individual mutations. Here we discuss applications of network analysis to study tumor biology, early methods for N-of-1 tumor genome analysis and the path for such tools to the clinic.
PMID: 29908887 [PubMed - as supplied by publisher]
Exploring the multi-drug resistance in Escherichia coli O157:H7 by gene interaction network: A systems biology approach.
Exploring the multi-drug resistance in Escherichia coli O157:H7 by gene interaction network: A systems biology approach.
Genomics. 2018 Jun 13;:
Authors: Miryala SK, Ramaiah S
Abstract
In the present study, we have constructed an interaction network of 29 antibiotic resistant genes along with 777 interactions in E. coli O157:H7. Gene ontology analysis reveals that 94, 89 and 67 genes have roles in the cellular process, biological process and molecular function respectively. Gene complexes related to tripartite efflux pumps mdtEF-tolC and ABC family efflux pump macAB-tolC play key roles in multidrug efflux systems. It is noteworthy to mention that, 19 genes are involved in multi-efflux pumps and they play a significant role in multidrug resistance (MDR); while 18 genes are vital for fatty acid synthesis. Interestingly, we found that the four genes arnABCD are involved in both MDR and in fatty acid synthesis. Hence these genes could be targeted for new drug discovery. On the whole, our results provide a detailed understanding of the mode of MDR mechanisms in E.coli O157:H7.
PMID: 29908320 [PubMed - as supplied by publisher]
Alterations of mTOR signaling impact metabolic stress resistance in colorectal carcinomas with BRAF and KRAS mutations.
Alterations of mTOR signaling impact metabolic stress resistance in colorectal carcinomas with BRAF and KRAS mutations.
Sci Rep. 2018 Jun 15;8(1):9204
Authors: Fritsche-Guenther R, Zasada C, Mastrobuoni G, Royla N, Rainer R, Roßner F, Pietzke M, Klipp E, Sers C, Kempa S
Abstract
Metabolic reprogramming is as a hallmark of cancer, and several studies have reported that BRAF and KRAS tumors may be accompanied by a deregulation of cellular metabolism. We investigated how BRAFV600E and KRASG12V affect cell metabolism, stress resistance and signaling in colorectal carcinoma cells driven by these mutations. KRASG12V expressing cells are characterized by the induction of glycolysis, accumulation of lactic acid and sensitivity to glycolytic inhibition. Notably mathematical modelling confirmed the critical role of MCT1 designating the survival of KRASG12V cells. Carcinoma cells harboring BRAFV600E remain resistant towards alterations of glucose supply or application of signaling or metabolic inhibitors. Altogether these data demonstrate that an oncogene-specific decoupling of mTOR from AMPK or AKT signaling accounts for alterations of resistance mechanisms and metabolic phenotypes. Indeed the inhibition of mTOR in BRAFV600E cells counteracts the metabolic predisposition and demonstrates mTOR as a potential target in BRAFV600E-driven colorectal carcinomas.
PMID: 29907857 [PubMed - in process]
In planta proximity dependent biotin identification (BioID).
In planta proximity dependent biotin identification (BioID).
Sci Rep. 2018 Jun 15;8(1):9212
Authors: Khan M, Youn JY, Gingras AC, Subramaniam R, Desveaux D
Abstract
Proximity dependent biotin identification (BioID) has emerged as a powerful tool for studies of proteome architecture, including insoluble or membrane-associated proteins. The technique has been well established in mammalian cells but has yet to be applied to whole plant systems. Here we demonstrate the application of BioID on leaf tissues of the model plant Arabidopsis thaliana, thereby expanding the versatility of this important technique and providing a powerful proteomics tool for plant biologists.
PMID: 29907827 [PubMed - in process]
A gene co-expression network model identifies yield-related vicinity networks in Jatropha curcas shoot system.
A gene co-expression network model identifies yield-related vicinity networks in Jatropha curcas shoot system.
Sci Rep. 2018 Jun 15;8(1):9211
Authors: Govender N, Senan S, Mohamed-Hussein ZA, Wickneswari R
Abstract
The plant shoot system consists of reproductive organs such as inflorescences, buds and fruits, and the vegetative leaves and stems. In this study, the reproductive part of the Jatropha curcas shoot system, which includes the aerial shoots, shoots bearing the inflorescence and inflorescence were investigated in regard to gene-to-gene interactions underpinning yield-related biological processes. An RNA-seq based sequencing of shoot tissues performed on an Illumina HiSeq. 2500 platform generated 18 transcriptomes. Using the reference genome-based mapping approach, a total of 64 361 genes was identified in all samples and the data was annotated against the non-redundant database by the BLAST2GO Pro. Suite. After removing the outlier genes and samples, a total of 12 734 genes across 17 samples were subjected to gene co-expression network construction using petal, an R library. A gene co-expression network model built with scale-free and small-world properties extracted four vicinity networks (VNs) with putative involvement in yield-related biological processes as follow; heat stress tolerance, floral and shoot meristem differentiation, biosynthesis of chlorophyll molecules and laticifers, cell wall metabolism and epigenetic regulations. Our VNs revealed putative key players that could be adapted in breeding strategies for J. curcas shoot system improvements.
PMID: 29907786 [PubMed - in process]
The tumour suppressor OPCML promotes AXL inactivation by the phosphatase PTPRG in ovarian cancer.
The tumour suppressor OPCML promotes AXL inactivation by the phosphatase PTPRG in ovarian cancer.
EMBO Rep. 2018 Jun 15;:
Authors: Antony J, Zanini E, Kelly Z, Tan TZ, Karali E, Alomary M, Jung Y, Nixon K, Cunnea P, Fotopoulou C, Paterson A, Roy-Nawathe S, Mills GB, Huang RY, Thiery JP, Gabra H, Recchi C
Abstract
In ovarian cancer, the prometastatic RTK AXL promotes motility, invasion and poor prognosis. Here, we show that reduced survival caused by AXL overexpression can be mitigated by the expression of the GPI-anchored tumour suppressor OPCML Further, we demonstrate that AXL directly interacts with OPCML, preferentially so when AXL is activated by its ligand Gas6. As a consequence, AXL accumulates in cholesterol-rich lipid domains, where OPCML resides. Here, phospho-AXL is brought in proximity to the lipid domain-restricted phosphatase PTPRG, which de-phosphorylates the RTK/ligand complex. This prevents AXL-mediated transactivation of other RTKs (cMET and EGFR), thereby inhibiting sustained phospho-ERK signalling, induction of the EMT transcription factor Slug, cell migration and invasion. From a translational perspective, we show that OPCML enhances the effect of the phase II AXL inhibitor R428 in vitro and in vivo We therefore identify a novel mechanism by which two spatially restricted tumour suppressors, OPCML and PTPRG, coordinate to repress AXL-dependent oncogenic signalling.
PMID: 29907679 [PubMed - as supplied by publisher]
Towards a sustainable bio-based economy: Redirecting primary metabolism to new products with plant synthetic biology.
Towards a sustainable bio-based economy: Redirecting primary metabolism to new products with plant synthetic biology.
Plant Sci. 2018 Aug;273:84-91
Authors: Shih PM
Abstract
Humans have domesticated many plant species as indispensable sources of food, materials, and medicines. The dawning era of synthetic biology represents a means to further refine, redesign, and engineer crops to meet various societal and industrial needs. Current and future endeavors will utilize plants as the foundation of a bio-based economy through the photosynthetic production of carbohydrate feedstocks for the microbial fermentation of biofuels and bioproducts, with the end goal of decreasing our dependence on petrochemicals. As our technological capabilities improve, metabolic engineering efforts may expand the utility of plants beyond sugar feedstocks through the direct production of target compounds, including pharmaceuticals, renewable fuels, and commodity chemicals. However, relatively little work has been done to fully realize the potential in redirecting central carbon metabolism in plants for the engineering of novel bioproducts. Although our ability to rationally engineer and manipulate plant metabolism is in its infancy, I highlight some of the opportunities and challenges in applying synthetic biology towards engineering plant primary metabolism.
PMID: 29907312 [PubMed - in process]
Opisthorchis viverrini Draft Genome - Biomedical Implications and Future Avenues.
Opisthorchis viverrini Draft Genome - Biomedical Implications and Future Avenues.
Adv Parasitol. 2018;101:125-148
Authors: Young ND, Gasser RB
Abstract
Opisthorchiasis is a neglected tropical disease of major proportion, caused by the carcinogenic, Asian liver fluke, Opisthorchis viverrini. This hepatobiliary disease is known to be associated with malignant cancer (cholangiocarcinoma, CCA) and affects millions of people in Southeast Asia. No vaccine is available, and only one drug (praziquantel) is routinely employed against the parasite. Despite technological advances, little is known about the molecular biology of the fluke itself and the disease complex that it causes in humans. The advent of high-throughput nucleic acid sequencing and bioinformatic technologies is enabling researchers to gain global insights into the molecular pathways and processes in parasites. The principal aims of this chapter are to (1) review molecular research of O. viverrini and opisthorchiasis; (2) provide an account of recent advances in the sequencing and characterization of the genome and transcriptomes of O. viverrini; (3) describe the complex life of this worm in the biliary system of the definitive (human) host and how the fluke interacts with this host and causes disease at the molecular level; (4) discuss the implications of systems biological research and (5) consider how progress in genomics and informatics might enable explorations of O. viverrini and related worms and the discovery of new interventions against opisthorchiasis and CCA.
PMID: 29907252 [PubMed - in process]
Active crystals on a sphere.
Active crystals on a sphere.
Phys Rev E. 2018 May;97(5-1):052615
Authors: Praetorius S, Voigt A, Wittkowski R, Löwen H
Abstract
Two-dimensional crystals on curved manifolds exhibit nontrivial defect structures. Here we consider "active crystals" on a sphere, which are composed of self-propelled colloidal particles. Our work is based on a phase-field-crystal-type model that involves a density and a polarization field on the sphere. Depending on the strength of the self-propulsion, three different types of crystals are found: a static crystal, a self-spinning "vortex-vortex" crystal containing two vortical poles of the local velocity, and a self-translating "source-sink" crystal with a source pole where crystallization occurs and a sink pole where the active crystal melts. These different crystalline states as well as their defects are studied theoretically here and can in principle be confirmed in experiments.
PMID: 29906962 [PubMed - in process]
Emergence of diversity in homogeneous coupled Boolean networks.
Emergence of diversity in homogeneous coupled Boolean networks.
Phys Rev E. 2018 May;97(5-1):052415
Authors: Kang C, Aguilar B, Shmulevich I
Abstract
The origin of multicellularity in metazoa is one of the fundamental questions of evolutionary biology. We have modeled the generic behaviors of gene regulatory networks in isogenic cells as stochastic nonlinear dynamical systems-coupled Boolean networks with perturbation. Model simulations under a variety of dynamical regimes suggest that the central characteristic of multicellularity, permanent spatial differentiation (diversification), indeed can arise. Additionally, we observe that diversification is more likely to occur near the critical regime of Lyapunov stability.
PMID: 29906914 [PubMed - in process]
"systems biology"; +20 new citations
20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2018/06/16
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.
"systems biology"; +20 new citations
20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2018/06/16
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.