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Cell Systems

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https://www.readbyqxmd.com/read/28342718/noisy-response-to-antibiotic-stress-predicts-subsequent-single-cell-survival-in-an-acidic-environment
#1
Karin Mitosch, Georg Rieckh, Tobias Bollenbach
Antibiotics elicit drastic changes in microbial gene expression, including the induction of stress response genes. While certain stress responses are known to "cross-protect" bacteria from other stressors, it is unclear whether cellular responses to antibiotics have a similar protective role. By measuring the genome-wide transcriptional response dynamics of Escherichia coli to four antibiotics, we found that trimethoprim induces a rapid acid stress response that protects bacteria from subsequent exposure to acid...
March 21, 2017: Cell Systems
https://www.readbyqxmd.com/read/28342717/slow-chromatin-dynamics-allow-polycomb-target-genes-to-filter-fluctuations-in-transcription-factor-activity
#2
Scott Berry, Caroline Dean, Martin Howard
Genes targeted by Polycomb repressive complex 2 (PRC2) are regulated in cis by chromatin modifications and also in trans by diffusible regulators such as transcription factors. Here, we introduce a mathematical model in which transcription directly antagonizes Polycomb silencing, thereby linking these cis- and trans-regulatory inputs to gene expression. The model is parameterized by recent experimental data showing that PRC2-mediated repressive chromatin modifications accumulate extremely slowly. The model generates self-perpetuating, bistable active and repressed chromatin states that persist through DNA replication, thereby ensuring high-fidelity transmission of the current chromatin state...
March 21, 2017: Cell Systems
https://www.readbyqxmd.com/read/28330616/systematic-analysis-of-human-protein-phosphatase-interactions-and-dynamics
#3
Leena Yadav, Fitsum Tamene, Helka Göös, Audrey van Drogen, Riku Katainen, Ruedi Aebersold, Matthias Gstaiger, Markku Varjosalo
Coordinated activities of protein kinases and phosphatases ensure phosphorylation homeostasis, which, when perturbed, can instigate diseases, including cancer. Yet, in contrast to kinases, much less is known about protein phosphatase functions and their interactions and complexes. Here, we used quantitative affinity proteomics to assay protein-protein interactions for 54 phosphatases distributed across the three major protein phosphatase families, with additional analysis of their 12 co-factors. We identified 838 high-confidence interactions, of which 631, to our knowledge, have not been reported before...
March 15, 2017: Cell Systems
https://www.readbyqxmd.com/read/28330615/differential-aging-analysis-in-human-cerebral-cortex-identifies-variants-in-tmem106b-and-grn-that-regulate-aging-phenotypes
#4
Herve Rhinn, Asa Abeliovich
Human age-associated traits, such as cognitive decline, can be highly variable across the population, with some individuals exhibiting traits that are not expected at a given chronological age. Here we present differential aging (Δ-aging), an unbiased method that quantifies individual variability in age-associated phenotypes within a tissue of interest, and apply this approach to the analysis of existing transcriptome-wide cerebral cortex gene expression data from several cohorts totaling 1,904 autopsied human brain samples...
March 15, 2017: Cell Systems
https://www.readbyqxmd.com/read/28330614/a-predictive-3d-multi-scale-model-of-biliary-fluid-dynamics-in-the-liver-lobule
#5
Kirstin Meyer, Oleksandr Ostrenko, Georgios Bourantas, Hernan Morales-Navarrete, Natalie Porat-Shliom, Fabian Segovia-Miranda, Hidenori Nonaka, Ali Ghaemi, Jean-Marc Verbavatz, Lutz Brusch, Ivo Sbalzarini, Yannis Kalaidzidis, Roberto Weigert, Marino Zerial
Bile, the central metabolic product of the liver, is transported by the bile canaliculi network. The impairment of bile flow in cholestatic liver diseases has urged a demand for insights into its regulation. Here, we developed a predictive 3D multi-scale model that simulates fluid dynamic properties successively from the subcellular to the tissue level. The model integrates the structure of the bile canalicular network in the mouse liver lobule, as determined by high-resolution confocal and serial block-face scanning electron microscopy, with measurements of bile transport by intravital microscopy...
March 15, 2017: Cell Systems
https://www.readbyqxmd.com/read/28334575/cell-factory-engineering
#6
REVIEW
Anne Mathilde Davy, Helene Faustrup Kildegaard, Mikael Rørdam Andersen
Rational approaches to modifying cells to make molecules of interest are of substantial economic and scientific interest. Most of these efforts aim at the production of native metabolites, expression of heterologous biosynthetic pathways, or protein expression. Reviews of these topics have largely focused on individual strategies or cell types, but collectively they fall under the broad umbrella of a growing field known as cell factory engineering. Here we condense >130 reviews and key studies in the art into a meta-review of cell factory engineering...
March 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28334574/microscopy-meet-big-data
#7
Antony Orth, Diane Schaak, Ethan Schonbrun
The analysis of massive microscopy datasets using deep neural networks provides an alternative to molecular labeling to characterize cellular states.
March 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28334573/what-is-your-conceptual-definition-of-cell-type-in-the-context-of-a-mature-organism
#8
(no author information available yet)
No abstract text is available yet for this article.
March 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28334572/principles-of-systems-biology-no-15
#9
(no author information available yet)
This month: seeing systems through evolution's lens (Thomas/Prakash/Landry), single-cell analysis across space and time (Izkovitz/Melosh), simplicity revealed in E. coli metabolism (Sauer), and understanding smell (Fussenegger/Meyer).
March 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28334571/clouds-continuums-and-cells
#10
EDITORIAL
H Craig Mak
No abstract text is available yet for this article.
March 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28237797/identification-of-nascent-memory-cd8-t-cells-and-modeling-of-their-ontogeny
#11
Fabien Crauste, Julien Mafille, Lilia Boucinha, Sophia Djebali, Olivier Gandrillon, Jacqueline Marvel, Christophe Arpin
Primary immune responses generate short-term effectors and long-term protective memory cells. The delineation of the genealogy linking naive, effector, and memory cells has been complicated by the lack of phenotypes discriminating effector from memory differentiation stages. Using transcriptomics and phenotypic analyses, we identify Bcl2 and Mki67 as a marker combination that enables the tracking of nascent memory cells within the effector phase. We then use a formal approach based on mathematical models describing the dynamics of population size evolution to test potential progeny links and demonstrate that most cells follow a linear naive→early effector→late effector→memory pathway...
March 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28237796/permanganate-s1-nuclease-footprinting-reveals-non-b-dna-structures-with-regulatory-potential-across-a-mammalian-genome
#12
Fedor Kouzine, Damian Wojtowicz, Laura Baranello, Arito Yamane, Steevenson Nelson, Wolfgang Resch, Kyong-Rim Kieffer-Kwon, Craig J Benham, Rafael Casellas, Teresa M Przytycka, David Levens
DNA in cells is predominantly B-form double helix. Though certain DNA sequences in vitro may fold into other structures, such as triplex, left-handed Z form, or quadruplex DNA, the stability and prevalence of these structures in vivo are not known. Here, using computational analysis of sequence motifs, RNA polymerase II binding data, and genome-wide potassium permanganate-dependent nuclease footprinting data, we map thousands of putative non-B DNA sites at high resolution in mouse B cells. Computational analysis associates these non-B DNAs with particular structures and indicates that they form at locations compatible with an involvement in gene regulation...
March 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28237795/iterative-modeling-reveals-evidence-of-sequential-transcriptional-control-mechanisms
#13
Christine S Cheng, Marcelo S Behar, Gajendra W Suryawanshi, Kristyn E Feldman, Roberto Spreafico, Alexander Hoffmann
Combinatorial control of gene expression is presumed to be mediated by molecular interactions between coincident transcription factors (TFs). While information on the genome-wide locations of TFs is available, the genes they regulate and whether they function combinatorially often remain open questions. Here, we developed a mechanistic, rather than statistical, modeling approach to elucidate TF control logic from gene expression data. Applying this approach to hundreds of genes in 85 datasets measuring the transcriptional responses of murine fibroblasts and macrophages to cytokines and pathogens, we found that stimulus-responsive TFs generally function sequentially in logical OR gates or singly...
March 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28215528/a-systematic-evaluation-of-methods-for-tailoring-genome-scale-metabolic-models
#14
Sjoerd Opdam, Anne Richelle, Benjamin Kellman, Shanzhong Li, Daniel C Zielinski, Nathan E Lewis
Genome-scale models of metabolism can illuminate the molecular basis of cell phenotypes. Since some enzymes are only active in specific cell types, several algorithms use omics data to construct cell-line- and tissue-specific metabolic models from genome-scale models. However, these methods are often not rigorously benchmarked, and it is unclear how algorithm and parameter selection (e.g., gene expression thresholds, metabolic constraints) affects model content and predictive accuracy. To investigate this, we built hundreds of models of four different cancer cell lines using six algorithms, four gene expression thresholds, and three sets of metabolic constraints...
March 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28215527/chromosome-wise-protein-interaction-patterns-and-their-impact-on-functional-implications-of-large-scale-genomic-aberrations
#15
Isa Kristina Kirk, Nils Weinhold, Kirstine Belling, Niels Erik Skakkebæk, Thomas Skøt Jensen, Henrik Leffers, Anders Juul, Søren Brunak
Gene copy-number changes influence phenotypes through gene-dosage alteration and subsequent changes of protein complex stoichiometry. Human trisomies where gene copy numbers are increased uniformly over entire chromosomes provide generic cases for studying these relationships. In most trisomies, gene and protein level alterations have fatal consequences. We used genome-wide protein-protein interaction data to identify chromosome-specific patterns of protein interactions. We found that some chromosomes encode proteins that interact infrequently with each other, chromosome 21 in particular...
March 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28189581/construction-and-analysis-of-two-genome-scale-deletion-libraries-for-bacillus-subtilis
#16
Byoung-Mo Koo, George Kritikos, Jeremiah D Farelli, Horia Todor, Kenneth Tong, Harvey Kimsey, Ilan Wapinski, Marco Galardini, Angelo Cabal, Jason M Peters, Anna-Barbara Hachmann, David Z Rudner, Karen N Allen, Athanasios Typas, Carol A Gross
A systems-level understanding of Gram-positive bacteria is important from both an environmental and health perspective and is most easily obtained when high-quality, validated genomic resources are available. To this end, we constructed two ordered, barcoded, erythromycin-resistance- and kanamycin-resistance-marked single-gene deletion libraries of the Gram-positive model organism, Bacillus subtilis. The libraries comprise 3,968 and 3,970 genes, respectively, and overlap in all but four genes. Using these libraries, we update the set of essential genes known for this organism, provide a comprehensive compendium of B...
March 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28231450/protein-networks-in-alzheimer-s-disease
#17
Eva Meier Carlsen, Rune Rasmussen
Overlap of RNA and protein networks reveals glia cells as key players for the development of symptomatic Alzheimer's disease in humans.
February 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28231449/synthetic-gene-circuits-learn-to-classify
#18
Andriy Didovyk, Lev S Tsimring
An efficient computational algorithm is developed to design microRNA-based synthetic cell classifiers and to optimize their performance.
February 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28231448/finding-the-optimal-tradeoffs
#19
Shibin Mathew, Amy E Thurber, Suzanne Gaudet
Computational analyses of a half-million circuit topologies provide a rationale for why certain fold-change detection topologies are more prevalent in nature.
February 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28231447/from-yeast-to-patients-the-audacity-and-vision-of-susan-lindquist
#20
LETTER
Vikram Khurana, Chee Yeun Chung, Daniel F Tardiff
No abstract text is available yet for this article.
February 22, 2017: Cell Systems
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