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https://www.readbyqxmd.com/read/28437094/rational-design-of-an-ultrasensitive-quorum-sensing-switch
#1
Weiqian Zeng, Pei Du, Qiuli Lou, Lili Wu, Haoqian M Zhang, Chunbo Lou, Hongli Wang, Qi Ouyang
One of the purposes of synthetic biology is to develop rational methods that accelerate the design of genetic circuits, saving time and effort spent on experiments and providing reliably predictable circuit performance. We applied a reverse engineering approach to design an ultrasensitive transcriptional quorum-sensing switch. We want to explore how systems biology can guide synthetic biology in the choice of specific DNA sequences and their regulatory relations to achieve a targeted function. The workflow comprises network enumeration that achieves the target function robustly, experimental restriction of the obtained candidate networks, global parameter optimization via mathematical analysis, selection and engineering of parts based on these calculations, and finally, circuit construction based on the principles of standardization and modularization...
April 24, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28434950/an-arabidopsis-lipid-flippase-is-required-for-timely-recruitment-of-defenses-to-the-host-pathogen-interface-at-the-plant-cell-surface
#2
William Underwood, Andrew Ryan, Shauna C Somerville
Deposition of cell wall-reinforcing papillae is an integral component of the plant immune response. The Arabidopsis PENETRATION 3 (PEN3) ATP binding cassette (ABC) transporter plays a role in defense against numerous pathogens and is recruited to sites of pathogen detection where it accumulates within papillae. However, the trafficking pathways and regulatory mechanisms contributing to recruitment of PEN3 and other defenses to the host-pathogen interface are poorly understood. Here, we report a confocal microscopy-based screen to identify mutants with altered localization of PEN3-GFP after inoculation with powdery mildew fungi...
April 18, 2017: Molecular Plant
https://www.readbyqxmd.com/read/28433919/identification-of-differentially-expressed-mirnas-through-high-throughput-sequencing-in-the-chicken-lung-in-response-to-mycoplasma-gallisepticum-hs
#3
Yabo Zhao, Yue Hou, Kang Zhang, Bo Yuan, Xiuli Peng
Mycoplasma gallisepticum (MG) infects chickens, causes chronic respiratory diseases (CRD) and severely damages the poultry industry. It has been suggested that micro-ribonucleic acids (miRNAs) are involved in microbial pathogenesis. Here, we identified miRNAs that are associated with MG infection in chicken lungs at 3 and 10days post-infection by deep sequencing. Thirty-six down-regulated and 9 up-regulated miRNAs belonging to 31 miRNA families were detected at 3days post-infection, whereas 50 down-regulated and 18 up-regulated miRNAs belonging to 41 miRNA families were found at 10days post-infection...
April 12, 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/28433707/genetic-susceptibility-to-toxicologic-lung-responses-among-inbred-mouse-strains-following-exposure-to-carbon-nanotubes-and-profiling-of-underlying-gene-networks
#4
Evan A Frank, Vinicius S Carreira, Kumar Shanmukhappa, Mario Medvedovic, Daniel R Prows, Jagjit S Yadav
The risk of human exposure to fiber nanoparticles has risen in recent years due to increases in the manufacture and utilization of carbon nanotubes (CNTs). CNTs are present as airborne particulates in occupational settings and their hazard potential has been demonstrated in experimental lung exposure studies using inbred mouse strains. However, it is not known whether different inbred strains differ in lung responses to CNTs by virtue of their genetics. In this work, common inbred strains (BALB/c, C57Bl/6, DBA/2, and C3H/He) were exposed to CNTs via oropharyngeal aspiration and lung histology and bronchoalveolar lavage (BAL) samples were evaluated over 28days with the objective of evaluating sensitivity/resistance among strains...
April 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28433674/montreal-accord-on-patient-reported-outcomes-use-series-paper-6-creating-national-initiatives-to-support-patient-reported-outcomes-pro-development-and-use-the-promis-example
#5
Susan J Bartlett, James Witter, David Cella, Sara Ahmed
BACKGROUND: PRO data are beneficial to a range of stakeholders including patients, clinicians, researchers, national funding and regulatory agencies, health system administrators, and policymakers. OBJECTIVE: Because stakeholders represent diverse groups and needs, it is challenging to reach consensus on how to advance PRO development and harmonize data across settings to enable use for multiple secondary purposes. Collaborative national networks can facilitate the sharing of expertise, resources and necessary infrastructure; create development, use, and reporting standards; optimize formats to efficiently store and transfer data; and disseminate tools and information for widespread uptake...
April 19, 2017: Journal of Clinical Epidemiology
https://www.readbyqxmd.com/read/28432965/spatiotemporal-description-of-btex-volatile-organic-compounds-in-a-middle-eastern-megacity-tehran-study-of-exposure-prediction-for-environmental-health-research-tehran-sepehr
#6
Heresh Amini, Vahid Hosseini, Christian Schindler, Hossein Hassankhany, Masud Yunesian, Sarah B Henderson, Nino Künzli
The spatiotemporal variability of ambient volatile organic compounds (VOCs) in Tehran, Iran, is not well understood. Here we present the design, methods, and results of the Tehran Study of Exposure Prediction for Environmental Health Research (Tehran SEPEHR) on ambient concentrations of benzene, toluene, ethylbenzene, p-xylene, m-xylene, o-xylene (BTEX), and total BTEX. To date, this is the largest study of its kind in a low- and middle-income country and one of the largest globally. We measured BTEX concentrations at five reference sites and 174 distributed sites identified by a cluster analytic method...
April 19, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28432260/dual-histone-reader-zmynd8-inhibits-cancer-cell-invasion-by-positively-regulating-epithelial-genes
#7
Moitri Basu, Isha Sengupta, Wasim Khan, Dushyant Kumar Srivastava, Partha Chakrabarti, Siddhartha Roy, Chandrima Das
Enhanced migratory potential and invasiveness of cancer cells attribute crucially.in cancer progression. These phenotypes are achieved by precise alteration of invasion-associated genes through local epigenetic modifications which are recognized by a class of proteins termed as chromatin reader. ZMYND8 (zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8), a key component of transcription regulatory network, has been recently shown to be a novel reader of H3.1K36Me2/H4K16Ac marks. Through differential gene expression analysis upon silencing this chromatin reader, we identified a subset of genes involved in cell proliferation and invasion/migration regulated by ZMYND8...
April 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28432122/dual-regulation-of-stat1-and-stat3-by-the-tumor-suppressor-protein-pml-contributes-to-ifn%C3%AE-mediated-inhibition-of-angiogenesis
#8
Kuo-Sheng Hsu, Xuan Zhao, Xiwen Cheng, Dongyin Guan, Ganapati H Mahabeleshwar, Yu Liu, Ernest Borden, Mukesh K Jain, Hung-Ying Kao
IFNs are effective in inhibiting angiogenesis in preclinical models and in treating several angio-proliferative disorders. However, the detailed mechanisms of IFNα-mediated anti-angiogenesis are not completely understood. Stat1/2/3 and PML are IFNα downstream effectors and are pivotal regulators of angiogenesis. Here, we investigated PML's role in the regulation of Stat1/2/3 activity. In Pml knockout (KO) mice, ablation of Pml largely reduces IFNα angiostatic ability in Matrixgel plug assays. This suggested an essential role for PML in IFNα's anti-angiogenic function...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28432079/regulation-of-microtubule-associated-motors-drives-intermediate-filament-network-polarization
#9
Cécile Leduc, Sandrine Etienne-Manneville
Intermediate filaments (IFs) are key players in the control of cell morphology and structure as well as in active processes such as cell polarization, migration, and mechanoresponses. However, the regulatory mechanisms controlling IF dynamics and organization in motile cells are still poorly understood. In this study, we investigate the mechanisms leading to the polarized rearrangement of the IF network along the polarity axis. Using photobleaching and photoconversion experiments in glial cells expressing vimentin, glial fibrillary acidic protein, and nestin, we show that the distribution of cytoplasmic IFs results from a continuous turnover based on the cooperation of an actin-dependent retrograde flow and anterograde and retrograde microtubule-dependent transports...
April 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28431938/selective-inhibition-of-ezh2-by-a-small-molecule-inhibitor-regulates-microglial-gene-expression-essential-for-inflammation
#10
Sarder Arifuzzaman, Amitabh Das, Sun Hwa Kim, Taeho Yoon, Young Seek Lee, Kyoung Hwa Jung, Young Gyu Chai
Multiple studies have documented that Enhancer of zeste homolog 2 (EZH2) could play a role in inflammation and a wide range of malignancies; however, the underlying mechanisms remain largely unaddressed. Microglial activation is a key process in the production and release of numerous pro-inflammatory mediators that play important roles in inflammation and neurodegeneration in the central nervous system (CNS). Therefore, our aim was to investigate whether inhibition of EZH2 with the selective small molecule inhibitor EPZ-6438 protects against neonatal microglial activation...
April 18, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28431495/iron-regulated-small-rna-expression-as-neisseria-gonorrhoeae-fa-1090-transitions-into-stationary-phase-growth
#11
Lydgia A Jackson, Michael Day, Jennie Allen, Edgar Scott, David W Dyer
BACKGROUND: For most pathogens, iron (Fe) homeostasis is crucial for maintenance within the host and the ability to cause disease. The primary transcriptional regulator that controls intracellular Fe levels is the Fur (ferric uptake regulator) protein, which exerts its action on transcription by binding to a promoter-proximal sequence termed the Fur box. Fur-regulated transcriptional responses are often fine-tuned at the post-transcriptional level through the action of small regulatory RNAs (sRNAs)...
April 21, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28431272/specific-microrna-mrna-regulatory-network-of-colon-cancer-invasion-mediated-by-tissue-kallikrein-related-peptidase-6
#12
Earlphia Sells, Ritu Pandey, Hwudaurw Chen, Bethany A Skovan, Haiyan Cui, Natalia A Ignatenko
Metastatic colon cancer is a major cause of deaths among colorectal cancer (CRC) patients. Elevated expression of kallikrein 6 (KLK6), a member of a kallikrein subfamily of peptidase S1 family serine proteases, has been reported in CRC and is associated with low patient survival rates and poor disease prognosis. We knocked down KLK6 expression in HCT116 colon cancer cells to determine the significance of KLK6 expression for metastatic dissemination and to identify the KLK6-associated microRNAs (miRNAs) signaling networks in metastatic colon cancer...
April 18, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28431241/akt-pkb-signaling-navigating-the-network
#13
REVIEW
Brendan D Manning, Alex Toker
The Ser and Thr kinase AKT, also known as protein kinase B (PKB), was discovered 25 years ago and has been the focus of tens of thousands of studies in diverse fields of biology and medicine. There have been many advances in our knowledge of the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of AKT, and the complex circuitry of this dynamically branching and looping signaling network that is ubiquitous to nearly every cell in our body...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431175/minepath-org-a-free-interactive-pathway-analysis-web-server
#14
Lefteris Koumakis, Panos Roussos, George Potamias
Minepath (www.minepath.org) is a web-based platform that elaborates on, and radically extends the identification of differentially expressed sub-paths in molecular pathways. Besides the network topology, the underlying MinePath algorithmic processes exploit exact gene-gene molecular relationships (e.g. activation, inhibition) and are able to identify differentially expressed pathway parts. Each pathway is decomposed into all its constituent sub-paths, which in turn are matched with corresponding gene expression profiles...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28430877/the-accessible-chromatin-landscape-during-conversion-of-human-embryonic-stem-cells-to-trophoblast-by-bmp4
#15
Yajun Liu, Dewu Ding, Hongde Liu, Xiao Sun
Human embryonic stem cells (hESC) exposed to the growth factor bone morphogenic protein 4 (BMP4) in the absence of FGF2 have been used as a model to study the development of placental development. However, little is known about the cis-regulatory mechanisms underlying this important process. In this study, we used the public available chromatin accessibility data of hESC H1 cells and BMP4-induced trophoblast (TB)cell lines to identify DNase I hypersensitive sites (DHSs) in the two cell lines, as well as the transcription factor binding sites within the DHSs...
April 18, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28430819/estimating-optimal-sparseness-of-developmental-gene-networks-using-a-semi-quantitative-model
#16
Natsuhiro Ichinose, Tetsushi Yada, Hiroshi Wada
To estimate gene regulatory networks, it is important that we know the number of connections, or sparseness of the networks. It can be expected that the robustness to perturbations is one of the factors determining the sparseness. We reconstruct a semi-quantitative model of gene networks from gene expression data in embryonic development and detect the optimal sparseness against perturbations. The dense networks are robust to connection-removal perturbation, whereas the sparse networks are robust to misexpression perturbation...
2017: PloS One
https://www.readbyqxmd.com/read/28430700/prescriber-compliance-with-liver-monitoring-guidelines-for-pazopanib-in-the-postapproval-setting-results-from-a-distributed-research-network
#17
Sumitra Shantakumar, Beth L Nordstrom, Susan A Hall, Luc Djousse, Myrthe P P van Herk-Sukel, Kathy H Fraeman, David R Gagnon, Karen Chagin, Jeanenne J Nelson
OBJECTIVES: Pazopanib received US Food and Drug Administration approval in 2009 for advanced renal cell carcinoma. During clinical development, liver chemistry abnormalities and adverse hepatic events were observed, leading to a boxed warning for hepatotoxicity and detailed label prescriber guidelines for liver monitoring. As part of postapproval regulatory commitments, a cohort study was conducted to assess prescriber compliance with liver monitoring guidelines. METHODS: Over a 4-year period, a distributed network approach was used across 3 databases: US Veterans Affairs Healthcare System, a US outpatient oncology community practice database, and the Dutch PHARMO Database Network...
April 20, 2017: Journal of Patient Safety
https://www.readbyqxmd.com/read/28430586/epidermal-growth-factor-receptor-egfr-a-rising-star-in-the-era-of-precision-medicine-of-lung-cancer
#18
REVIEW
Xiaomin Liu, Ping Wang, Caiyan Zhang, Zhongliang Ma
Lung cancer is a leading cause of cancer mortality worldwide. In tumors, the important role of noncoding RNA regulatory networks has been more and more reveal. EGFR has been identified as an oncogenic driver of NSCLC, especially activating mutations EGFR and its inhibition with specific TKIs can generate dramatic tumor responses. Studies have shown that EGFR plays significant roles in the progression of NSCLC. Subset analysis of the small proportion of patients with EGFR-mutant lung cancer showed a disease-free survival benefit, but was underpowered to detect a survival advantage...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430547/enhancing-insights-into-pulmonary-vascular-disease-pvd-through-a-precision-medicine-approach-a-joint-nhlbi-cmref-workshop-report
#19
John H Newman, Stuart Rich, Steven H Abman, John H Alexander, John Barnard, Gerald J Beck, Raymond L Benza, Todd M Bull, Stephen Y Chan, Hyung J Chun, Declan Doogan, Jocelyn Dupuis, Serpil C Erzurum, Robert P Frantz, Mark Geraci, Hunter Gillies, Mark Gladwin, Michael P Gray, Anna R Hemnes, Roy S Herbst, Adrian F Hernandez, Nicholas S Hill, Evelyn M Horn, Kendall Hunter, Zhi-Cheng Jing, Roger Johns, Sanjay Kaul, Steven M Kawut, Tim Lahm, Jane A Leopold, Greg D Lewis, Stephen C Mathai, Vallerie V McLaughlin, Evangelos D Michelakis, Steven D Nathan, William Nichols, Grier Page, Marlene Rabinovitch, Jonathan Rich, Franz Rischard, Sharon Rounds, Sanjiv J Shah, Victor F Tapson, Naomi Lowy, Norman Stockbridge, Gail Weinmann, Lei Xiao
The Division of Lung Diseases of the National Heart, Lung and Blood Institute, (NHLBI) and the Cardiovascular Medical Education and Research Fund (CMREF), held a workshop to discuss to leverage of the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension (PH) through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program. PVDOMICS is a protocol driven network to analyze PH patient populations to define novel pulmonary vascular disease (PVD) phenotypes. Basic, translational and clinical investigators, patient advocacy organizations, regulatory agencies, and pharmaceutical industry experts discussed the application of precision medicine to PVD clinical trials...
April 21, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28430108/a-network-physiology-approach-to-the-assessment-of-the-link-between-sinoatrial-and-ventricular-cardiac-controls
#20
Alberto Porta, Vlasta Bari, Beatrice De Maria, Mathias Baumert
A network physiology approach to evaluate the strength of the directed interactions among cardiac controls at sinoatrial and ventricular levels and respiration (R) is proposed. The network is composed of three nodes (i.e. sinoatrial and ventricular cardiac controls and R) and their activity is exemplified by the variability of heart period (HP), the variability of the duration of the electrical activity of the heart approximated as the temporal distance between Q-wave onset and T-wave end or apex (i.e. QTe or QTa) and thoracic movements respectively...
April 21, 2017: Physiological Measurement
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