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"systems biology"

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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.

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"systems biology"

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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.

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

"systems biology"

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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.

41 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 2018/05/16

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.

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

"systems biology"

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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.

43 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 2018/05/15

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.

Imaging Mass Spectrometry for Characterization of Atrial Fibrillation Subtypes.

Proteomics Clin Appl. 2018 May 13;:e1700155

Authors: Klein O, Hanke T, Nerbrich G, Yan J, Schubert B, Giavalisco P, Noack F, Thiele H, Mohamed SA

Abstract
PURPOSE: Atrial fibrillation (AF) is a cardiac arrhythmia characterized by a rapid and irregular heart rhythm. AF types, paroxysmal (PX), persistent (PE) and long-lasting persistent (LSP), requires differences in clinical management. Unfortunately, a significant proportion of AF patients are clinical misclassified. Therefore, our study aim that MALDI-Imaging (IMS) is valuable as a diagnostic aid in AF subtypes assessment.
EXPERIMENTAL DESIGN: Patients were clinically classified according guidelines of the European Society of Cardiology. FFPE tissue specimens from PE, PX and LSP subtype were analysed by MALDI-IMS and evaluated by multi-statistical testing. Proteins were subsequent identified using LC-MS/MS and findings were confirmed by immunohistochemistry and through the determination of potential fibrosis via histopathology RESULT: : Determined characteristic peptide signatures and peptide values facilitate to distinguish between PE, PE and LSP arterial fibrillation subtypes. In particular, peptide values from alpha 1 type I collagen were identified that were significantly higher in LSP and PE tissue but not in PX myocardial AF tissue. These findings were confirmed by immunohistochemistry and through the determination of potential fibrosis via histopathology.
CONCLUSION AND RELEVANCE: Our results represent an improvement in AF risk stratification by using MALDI-IMS as a promising approach for AF tissue assessment. This article is protected by copyright. All rights reserved.

PMID: 29754423 [PubMed - as supplied by publisher]

Targeting TWIST1 through loss of function inhibits tumorigenicity of human glioblastoma.

Mol Oncol. 2018 May 13;:

Authors: Mikheev AM, Mikheeva SA, Severs LJ, Funk CC, Huang L, McFaline-Figueroa JL, Schwensen J, Trapnell C, Price ND, Wong S, Rostomily RC

Abstract
Twist1 (TW) is a bHLH transcription factor (TF) and master regulator of the epithelial to mesenchymal transition (EMT). In vitro, TW promotes mesenchymal change, invasion and self-renewal in glioblastoma (GBM) cells. However the potential therapeutic relevance of TW has not been established through loss of function studies in human GBM cell xenograft models. The effects of TW loss of function (gene editing and knock down) on inhibition of tumorigenicity of U87MG and GBM4 glioma stem cells were tested in orthotopic xenograft models and conditional knockdown in established flank xenograft tumors. RNAseq and the analysis of tumors investigated putative TW associated mechanisms. Multiple bioinformatics tools revealed significant alteration of ECM, membrane receptors, signaling transduction kinases and cytoskeleton dynamics leading to identification of PI3K/AKT signaling. We experimentally show alteration of AKT activity and periostin (POSTN) expression in vivo and/or in vitro. For the first time we show that effect of TW knockout inhibits AKT activity in U87MG cells in vivo independent of PTEN mutation. The clinical relevance of TW and candidate mechanisms was established by analysis of the TCGA and ENCODE databases. TW expression was associated with decreased patient survival and LASSO regression analysis identified POSTN as one of top targets of TW in human GBM. While we previously demonstrated the role of TW in promoting EMT and invasion of glioma cells, these studies provide direct experimental evidence supporting pro-tumorigenic role of TW independent of invasion in vivo and the therapeutic relevance of targeting TW in human GBM. Further, the role of TW driving POSTN expression and AKT signaling suggests actionable targets, which could be leveraged to mitigate the oncogenic effects of TW in GBM.

PMID: 29754406 [PubMed - as supplied by publisher]

Automated Visualization of Genetic Designs Using DNAplotlib.

Methods Mol Biol. 2018;1772:399-409

Authors: Bartoli V, Dixon DOR, Gorochowski TE

Abstract
Visualization of complex genetic systems can help efficiently communicate important design features and clearly illustrate overall structures. To aid in the creation of such diagrams, standards such as the Synthetic Biology Open Language Visual (SBOLv) have been established to ensure that specific symbols and shapes convey the same meaning for genetic parts across the field. Here, we describe several ways that the computational tool DNAplotlib can be used to automate the generation of SBOLv standard-compliant diagrams covering simple genetic designs to large libraries of genetic constructs.

PMID: 29754241 [PubMed - in process]

Bio-Algorithmic Workflows for Standardized Synthetic Biology Constructs.

Methods Mol Biol. 2018;1772:363-372

Authors: Goñi-Moreno A, de Lorenzo V

Abstract
A synthetic biology workflow covers the roadmap from conceptualization of a genetic device to its construction and measurement. It is composed of databases that provide DNA parts/plasmids, wet-lab methods , software tools to design circuits, simulation packages , and tools to analyze circuit performance. The interdisciplinary nature of such a workflow requires that experimental results and their in-silico counterparts proceed alongside, with constant feedback between them. We present an end-to-end use case for engineering a simple synthetic device, where information standards maintain coherence throughout the workflow. These are the Standard European Vector Architecture (SEVA), the Synthetic Biology Open Language (SBOL), and the Systems Biology Markup Language (SBML).

PMID: 29754239 [PubMed - in process]

Construction and Integration of a Synthetic MicroRNA Cluster for Multiplex RNA Interference in Mammalian Cells.

Methods Mol Biol. 2018;1772:347-359

Authors: Wang T, Xie Z

Abstract
Basic biological research and biomedical applications often require studying the multiple interactions between genes or proteins while multiplex RNA interference (RNAi) technology is still challenging in mammalian cells. In mammalian genomes, the natural microRNA (miRNA) clusters, of which the miRNAs often share similar expression patterns and target diverse genes, would provide a potential multiplex RNAi scaffold. Based on the natural pri-miR-155 precursor, we have developed and characterized a multiplex RNAi method by engineering synthetic miRNA clusters, among which the maturation and function of individual miRNA precursors are independent of their positions in the cluster. And the synthetic miRNA clusters are assembled by an efficient hierarchical Golden-Gate cloning method. Here, we describe the design rules and the hierarchical cloning methods to construct synthetic miRNA cluster, and the brief protocol for the integration of synthetic miRNA clusters into the mammalian genome.

PMID: 29754238 [PubMed - in process]

Negative Regulation Gene Circuits for Efflux Pump Control.

Methods Mol Biol. 2018;1772:25-43

Authors: Charlebois DA, Diao J, Nevozhay D, Balázsi G

Abstract
Synthetic biologists aim to design biological systems for a variety of industrial and medical applications, ranging from biofuel to drug production. Synthetic gene circuits regulating efflux pump protein expression can achieve this by driving desired substrates such as biofuels, pharmaceuticals, or other chemicals out of the cell in a precisely controlled manner. However, efflux pumps may introduce implicit negative feedback by pumping out intracellular inducer molecules that control gene circuits, which then can alter gene circuit function. Therefore, synthetic gene circuits must be carefully designed and constructed for precise efflux control. Here, we provide protocols for quantitatively modeling and building synthetic gene constructs for efflux pump regulation.

PMID: 29754221 [PubMed - in process]

Long-term hindlimb unloading causes a preferential reduction of medullary thymic epithelial cells expressing autoimmune regulator (Aire).

Biochem Biophys Res Commun. 2018 May 10;:

Authors: Horie K, Kudo T, Yoshinaga R, Akiyama N, Sasanuma H, Kobayashi TJ, Shimbo M, Jeon H, Miyao T, Miyauchi M, Shirakawa M, Shiba D, Yoshida N, Muratani M, Takahashi S, Akiyama T

Abstract
Hindlimb unloading (HU) of rodents has been used as a ground-based model of spaceflight. In this study, we investigated the detailed impact of 14-day HU on the murine thymus. Thymic mass and cell number were significantly reduced after 14 days of hindlimb unloading, which was accompanied by an increment of plasma corticosterone. Although corticosterone reportedly causes selective apoptosis of CD4+CD8+ thymocytes (CD4+CD8+DPs) in mice treated with short-term HU, the reduction of thymocyte cellularity after the 14-day HU was not selective for CD4+CD8+DPs. In addition to the thymocyte reduction, the cellularity of thymic epithelial cells (TECs) was also reduced by the 14-day HU. Flow cytometric and RNA-sequencing analysis suggested that medullary TECs (mTECs) were preferentially reduced after HU. Moreover, immunohistochemical staining suggested that the 14-day HU caused a reduction of the mTECs expressing autoimmune regulator (Aire). Our data suggested that HU impacts both thymocytes and TECs. Consequently, these data imply that thymic T cell repertoire formation could be disturbed during spaceflight-like stress.

PMID: 29753741 [PubMed - as supplied by publisher]

Reserve Flux Capacity in the Pentose Phosphate Pathway Enables Escherichia coli's Rapid Response to Oxidative Stress.

Cell Syst. 2018 May 02;:

Authors: Christodoulou D, Link H, Fuhrer T, Kochanowski K, Gerosa L, Sauer U

Abstract
To counteract oxidative stress and reactive oxygen species (ROS), bacteria evolved various mechanisms, primarily reducing ROS through antioxidant systems that utilize cofactor NADPH. Cells must stabilize NADPH levels by increasing flux through replenishing metabolic pathways like pentose phosphate (PP) pathway. Here, we investigate the mechanism enabling the rapid increase in NADPH supply by exposing Escherichia coli to hydrogen peroxide and quantifying the immediate metabolite dynamics. To systematically infer active regulatory interactions governing this response, we evaluated ensembles of kinetic models of glycolysis and PP pathway, each with different regulation mechanisms. Besides the known inactivation of glyceraldehyde 3-phosphate dehydrogenase by ROS, we reveal the important allosteric inhibition of the first PP pathway enzyme by NADPH. This NADPH feedback inhibition maintains a below maximum-capacity PP pathway flux under non-stress conditions. Relieving this inhibition instantly increases PP pathway flux upon oxidative stress. We demonstrate that reducing cells' capacity to rapidly reroute their flux through the PP pathway increases their oxidative stress sensitivity.

PMID: 29753645 [PubMed - as supplied by publisher]

Human Parasitology and Parasitic Diseases: Heading Towards 2050.

Adv Parasitol. 2018;100:29-38

Authors: Hotez PJ

Abstract
By 2050 our civilized planet may be comprised predominantly of networked megacities embedded in warm subtropical and tropical climates, and under stress from climate change and catastrophic weather events. Urban slum areas in these cities, including those found in wealthier middle- and high-income nations (blue marble health), will be especially vulnerable to disease. Moreover, regional conflicts fought over shifting and limited resources, including water, will collapse health systems infrastructures to further promote disease emergence and reemergence. Thus while by 2050 we might congratulate ourselves for successfully eliminating some key parasitic and neglected tropical diseases such as dracunculiasis, lymphatic filariasis, onchocerciasis, and human African trypanosomiasis, there could be a commensurate rise in other parasitic diseases based on the scenarios highlighted above. Of particular concern are urban and newly urbanized helminth infections, including schistosomiasis and some soil-transmitted helminth infections, as well zoonotic helminthiases, such as toxocariasis, food-borne trematodiases, and cysticercosis. Protozoan infections persisting in urban environments, including leishmaniasis, Chagas disease, malaria, and intestinal protozoan infections, will also remain, as will zoonotic diseases such as toxoplasmosis. Our best hope to counteract the parasitic diseases emerging in our steaming 21st century megacities is to develop new and innovative technologies through gene editing, systems biology, and immunology, and the new single-celled OMICs. However, success on this front will require our ability to contain the globalization of antiscience beliefs and sentiments.

PMID: 29753341 [PubMed - in process]

Voltammetric determination of 4-nitrophenol using a glassy carbon electrode modified with a gold-ZnO-SiO2 nanostructure.

Mikrochim Acta. 2018 May 11;185(6):296

Authors: Ghazizadeh AJ, Afkhami A, Bagheri H

Abstract
A nanostructured material of the type Au-ZnO-SiO2 is described that consists of ZnO and gold nanoparticles (NPs) dispersed into a silica matrix and used to construct a voltammetric sensor for 4-nitrophenol. The AuNPs and ZnO NPs are anchored onto the silica network which warrants the nanostructures to be stable in various environments. It also facilitates the electron transfer between the electrolyte and the glassy carbon electrode (GCE). The properties of the nanostructure as a modifier for the GCE were investigated by energy dispersive spectrometry, X-ray diffraction spectroscopy, and transmission electron microscopy. It is shown that the nanostructure increases the surface area. Hence, the cathodic and anodic current in differential pulse voltammetry of 4-nitrophenol are considerably enhanced in comparison to a bare GCE. Under optimum conditions, the currents for oxidation and reduction are proportional to the concentration of 4-nitrophenol in the 0.05-3.5 μM and 0.01-1.2 μM concentration ranges, with 13.7 and 2.8 nM detection limits, respectively. The sensor has excellent sensitivity, fast response, long-term stability, and good reproducibility. It is perceived to be a valuable tool for monitoring 4-nitrophenol in real water samples. Graphical abstract Schematic of voltammetric sensor for 4-nitrophenol. It is based on GCE modified with gold-ZnO-SiO2 nanostructure. It exhibited the improvement in performance for both oxidation and reduction peaks in terms of linearity, concentration range, detection limit, and sensitivity.

PMID: 29752544 [PubMed - in process]

Publisher Correction: Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex.

Nat Neurosci. 2018 May 11;:

Authors: Hrvatin S, Hochbaum DR, Nagy MA, Cicconet M, Robertson K, Cheadle L, Zilionis R, Ratner A, Borges-Monroy R, Klein AM, Sabatini BL, Greenberg ME

Abstract
In the version of this article initially published, the x-axis labels in Fig. 3c read Vglut, Gad1/2, Aldh1l1 and Pecam1; they should have read Vglut+, Gad1/2+, Aldh1l1+ and Pecam1+. In Fig. 4, the range values were missing from the color scales; they are, from left to right, 4-15, 0-15, 4-15 and 0-15 in Fig. 4a and 4-15, 4-15 and 4-8 in Fig. 4h. In the third paragraph of the main text, the phrase reading "Previous approaches have analyzed a limited number of inhibitory cell types, thus masking the full diversity of excitatory populations" should have read "Previous approaches have analyzed a limited number of inhibitory cell types and masked the full diversity of excitatory populations." In the second paragraph of Results section "Diversity of experience-regulated ERGs," the phrase reading "thus suggesting considerable divergence within the gene expression program responding to early stimuli" should have read "thus suggesting considerable divergence within the early stimulus-responsive gene expression program." In the fourth paragraph of Results section "Excitatory neuronal LRGs," the sentence reading "The anatomical organization of these cell types into sublayers, coupled with divergent transcriptional responses to a sensory stimulus, suggested previously unappreciated functional subdivisions located within the laminae of the mouse visual cortex and resembling the cytoarchitecture in higher mammals" should have read "The anatomical organization of these cell types into sublayers, coupled with divergent transcriptional responses to a sensory stimulus, suggests previously unappreciated functional subdivisions located within the laminae of the mouse visual cortex, resembling the cytoarchitecture in higher mammals." In the last sentence of the Results, "sensory-responsive genes" should have read "sensory-stimulus-responsive genes." The errors have been corrected in the HTML and PDF versions of the article.

PMID: 29752482 [PubMed - as supplied by publisher]

Assigning matrix metalloproteinase roles in ischaemic cardiac remodelling.

Nat Rev Cardiol. 2018 May 11;:

Authors: Lindsey ML

Abstract
Matrix metalloproteinases (MMPs) and their endogenous inhibitors have been studied in the myocardium for the past 2 decades. An incomplete knowledge base and experimental design issues with inhibitors have hampered attempts at translation, but clinical interest remains high because of strong associations between MMPs and outcomes after myocardial infarction (MI) as well as mechanistic studies showing MMP involvement at multiple stages of the MI wound-healing process. This Review focuses on how our understanding of MMPs has evolved from a one-dimensional early focus on measuring MMP activity, monitoring MMP:inhibitor ratios, and evaluating one MMP-substrate pair to the current use of systems biology approaches to integrate the whole MMP repertoire of roles in the left ventricular response to MI. MMP9 is used as an example MMP to explain these concepts and to provide a template for examining MMPs as mechanistic mediators of cardiac remodelling.

PMID: 29752454 [PubMed - as supplied by publisher]

Prescription Drug Shortages: Implications for Ambulatory Pediatrics.

J Pediatr. 2018 May 08;:

Authors: Donnelly KA, Zocchi MS, Katy TA, Fox ER, van den Anker JN, Mazer-Amirshahi ME

Abstract
OBJECTIVE: To describe contemporary drug shortages affecting general ambulatory pediatrics.
STUDY DESIGN: Data from January 2001 to December 2015 were obtained from the University of Utah Drug Information Service. Two pediatricians reviewed drug shortages and identified agents used in ambulatory pediatrics. Shortage data were analyzed by the type of drug, formulation, reason for shortage, duration, marketing status, if a pediatric friendly-formulation was available, or if it was a single-source product. The availability of an alternative, and whether that alternative was affected by a shortage, also was noted.
RESULTS: Of 1883 products in shortage during the study period, 314 were determined to be used in ambulatory pediatrics. The annual number of new pediatric shortages decreased initially but then increased to a high of 38 in 2011. Of the 314 pediatric shortages, 3.8% were unresolved at the end of the study. The median duration of resolved shortages was 7.6 months. The longest shortage was for ciprofloxacin 500-mg tablets. The most common class involved was infectious disease drugs. Pediatric-friendly dosage forms were affected in 19.1% of shortages. An alternative agent was available for 86% drugs; however, 29% of these also were affected. The most common reason for shortage was manufacturing problems.
CONCLUSIONS: Drug shortages affected a substantial number of agents used in general ambulatory pediatrics. Shortages for single-source products are a concern if a suitable alternative is unavailable. Providers working in the ambulatory setting must be aware of current shortages and implement mitigation strategies to optimize patient care.

PMID: 29752177 [PubMed - as supplied by publisher]