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https://www.readbyqxmd.com/read/28437444/transcriptional-bursting-in-drosophila-development-stochastic-dynamics-of-eve-stripe-2-expression
#1
David M Holloway, Alexander V Spirov
Anterior-posterior (AP) body segmentation of the fruit fly (Drosophila) is first seen in the 7-stripe spatial expression patterns of the pair-rule genes, which regulate downstream genes determining specific segment identities. Regulation of pair-rule expression has been extensively studied for the even-skipped (eve) gene. Recent live imaging, of a reporter for the 2nd eve stripe, has demonstrated the stochastic nature of this process, with 'bursts' in the number of RNA transcripts being made over time. We developed a stochastic model of the spatial and temporal expression of eve stripe 2 (binding by transcriptional activators (Bicoid and Hunchback proteins) and repressors (Giant and Krüppel proteins), transcriptional initiation and termination; with all rate parameters constrained by features of the experimental data) in order to analyze the noisy experimental time series and test hypotheses for how eve transcription is regulated...
2017: PloS One
https://www.readbyqxmd.com/read/28427910/stochasticity-of-gene-expression-as-a-motor-of-epigenetics-in-bacteria-from-individual-to-collective-behavior
#2
REVIEW
Stéphanie Bury-Moné, Bianca Sclavi
Measuring gene expression at the single cell and single molecule level has recently made possible the quantitative measurement of stochasticity of gene expression. This enables identification of the probable sources and roles of noise. Stochastic gene expression can result in bacterial population heterogeneity, offering specific advantages for fitness and survival in various environments. This trait is therefore selected during the evolution of the species, and is consequently regulated by specific genetic network architecture...
April 18, 2017: Research in Microbiology
https://www.readbyqxmd.com/read/28417275/rna-silencing-in-the-life-cycle-of-soybean-multiple-restriction-systems-and-spatiotemporal-variation-associated-with-plant-architecture
#3
Ayumi Mori, Hiroshi Sato, Megumi Kasai, Tetsuya Yamada, Akira Kanazawa
The expression of transgenes introduced into a plant genome is sometimes suppressed by RNA silencing. Although local and systemic spread of RNA silencing have been studied, little is known about the mechanisms underlying spatial and temporal variation in transgene silencing between individual plants or between plants of different generations, which occurs seemingly stochastically. Here, we analyzed the occurrence, spread, and transmission of RNA silencing of the green fluorescent protein (GFP) gene over multiple generations of the progeny of a single soybean transformant...
April 17, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28416680/using-microsecond-single-molecule-fret-to-determine-the-assembly-pathways-of-t4-ssdna-binding-protein-onto-model-dna-replication-forks
#4
Carey Phelps, Brett Israels, Davis Jose, Morgan C Marsh, Peter H von Hippel, Andrew H Marcus
DNA replication is a core biological process that occurs in prokaryotic cells at high speeds (∼1 nucleotide residue added per millisecond) and with high fidelity (fewer than one misincorporation event per 10(7) nucleotide additions). The ssDNA binding protein [gene product 32 (gp32)] of the T4 bacteriophage is a central integrating component of the replication complex that must continuously bind to and unbind from transiently exposed template strands during DNA synthesis. We here report microsecond single-molecule FRET (smFRET) measurements on Cy3/Cy5-labeled primer-template (p/t) DNA constructs in the presence of gp32...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28415290/backward-stochastic-differential-equation-approach-to-modeling-of-gene-expression
#5
Evelina Shamarova, Roman Chertovskih, Alexandre F Ramos, Paulo Aguiar
In this article, we introduce a backward method to model stochastic gene expression and protein-level dynamics. The protein amount is regarded as a diffusion process and is described by a backward stochastic differential equation (BSDE). Unlike many other SDE techniques proposed in the literature, the BSDE method is backward in time; that is, instead of initial conditions it requires the specification of end-point ("final") conditions, in addition to the model parametrization. To validate our approach we employ Gillespie's stochastic simulation algorithm (SSA) to generate (forward) benchmark data, according to predefined gene network models...
March 2017: Physical Review. E
https://www.readbyqxmd.com/read/28414750/effect-of-transcription-factor-resource-sharing-on-gene-expression-noise
#6
Dipjyoti Das, Supravat Dey, Robert C Brewster, Sandeep Choubey
Gene expression is intrinsically a stochastic (noisy) process with important implications for cellular functions. Deciphering the underlying mechanisms of gene expression noise remains one of the key challenges of regulatory biology. Theoretical models of transcription often incorporate the kinetics of how transcription factors (TFs) interact with a single promoter to impact gene expression noise. However, inside single cells multiple identical gene copies as well as additional binding sites can compete for a limiting pool of TFs...
April 17, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28402875/tracking-low-copy-transcription-factors-in-living-bacteria-the-case-of-the-lac-repressor
#7
Federico Garza de Leon, Laura Sellars, Mathew Stracy, Stephen J W Busby, Achillefs N Kapanidis
Transcription factors control the expression of genes by binding to specific sites in DNA and repressing or activating transcription in response to stimuli. The lac repressor (LacI) is a well characterized transcription factor that regulates the ability of bacterial cells to uptake and metabolize lactose. Here, we study the intracellular mobility and spatial distribution of LacI in live bacteria using photoactivated localization microscopy combined with single-particle tracking. Since we track single LacI molecules in live cells by stochastically photoactivating and observing fluorescent proteins individually, there are no limitations on the copy number of the protein under study; as a result, we were able to study the behavior of LacI in bacterial strains containing the natural copy numbers (∼40 monomers), as well as in strains with much higher copy numbers due to LacI overexpression...
April 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28391018/macronuclear-actin-copy-number-variations-in-single-cells-of-different-pseudokeronopsis-alveolata-ciliophora-populations
#8
Lijuan Huang, Xuefen Lu, Changyu Zhu, Xiaofeng Lin, Zhenzhen Yi
Macronuclear chromosomes of ciliates, especially those of Spirotrichea, Armophorea and Phyllopharyngea, are extensively fragmented and their copy numbers vary significantly. A recent study suggested that parental RNA molecules regulate macronuclear copy number in offspring cells after conjugation. However, variations in patterns of macronuclear copy number during vegetative growth are not clear. Previous studies have reported macronuclear copy numbers of population averages, potentially masking individual variation...
March 3, 2017: European Journal of Protistology
https://www.readbyqxmd.com/read/28390082/the-background-puzzle-how-identical-mutations-in-the-same-gene-lead-to-different-disease-symptoms
#9
REVIEW
Jan E Kammenga
Identical disease-causing mutations can lead to different symptoms in different people. The reason for this has been a puzzling problem for geneticists. Differential penetrance and expressivity of mutations has been observed within individuals with different, and those with similar, genetic backgrounds. Attempts have been made to uncover the underlying mechanisms that determine differential phenotypic effects of identical mutations, through studies of model organisms. From these studies evidence is accumulating that to understand disease mechanism or predict disease prevalence an understanding of the influence of genetic background is as important as the putative disease causing mutations of relatively large effect...
April 8, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28386100/petri-net-computational-modelling-of-langerhans-cell-interferon-regulatory-factor-network-predicts-their-role-in-t-cell-activation
#10
Marta E Polak, Chuin Ying Ung, Joanna Masapust, Tom C Freeman, Michael R Ardern-Jones
Langerhans cells (LCs) are able to orchestrate adaptive immune responses in the skin by interpreting the microenvironmental context in which they encounter foreign substances, but the regulatory basis for this has not been established. Utilising systems immunology approaches combining in silico modelling of a reconstructed gene regulatory network (GRN) with in vitro validation of the predictions, we sought to determine the mechanisms of regulation of immune responses in human primary LCs. The key role of Interferon regulatory factors (IRFs) as controllers of the human Langerhans cell response to epidermal cytokines was revealed by whole transcriptome analysis...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28379537/tasic-determining-branching-models-from-time-series-single-cell-data
#11
Sabrina Rashid, Darrell N Kotton, Ziv Bar-Joseph
Motivation: Single cell RNA-Seq analysis holds great promise for elucidating the networks and pathways controlling cellular differentiation and disease. However, the analysis of time series single cell RNA-Seq data raises several new computational challenges. Cells at each time point are often sampled from a mixture of cell types, each of which may be a progenitor of one, or several, specific fates making it hard to determine which cells should be used to reconstruct temporal trajectories...
April 4, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28376782/image-analysis-driven-single-cell-analytics-for-systems-microbiology
#12
Athanasios D Balomenos, Panagiotis Tsakanikas, Zafiro Aspridou, Anastasia P Tampakaki, Konstantinos P Koutsoumanis, Elias S Manolakos
BACKGROUND: Time-lapse microscopy is an essential tool for capturing and correlating bacterial morphology and gene expression dynamics at single-cell resolution. However state-of-the-art computational methods are limited in terms of the complexity of cell movies that they can analyze and lack of automation. The proposed Bacterial image analysis driven Single Cell Analytics (BaSCA) computational pipeline addresses these limitations thus enabling high throughput systems microbiology. RESULTS: BaSCA can segment and track multiple bacterial colonies and single-cells, as they grow and divide over time (cell segmentation and lineage tree construction) to give rise to dense communities with thousands of interacting cells in the field of view...
April 4, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28376755/reconstruction-of-the-evolution-of-microbial-defense-systems
#13
Pere Puigbò, Kira S Makarova, David M Kristensen, Yuri I Wolf, Eugene V Koonin
BACKGROUND: Evolution of bacterial and archaeal genomes is a highly dynamic process that involves intensive loss of genes as well as gene gain via horizontal transfer, with a lesser contribution from gene duplication. The rates of these processes can be estimated by comparing genomes that are linked by an evolutionary tree. These estimated rates of genome dynamics events substantially differ for different functional classes of genes. The genes involved in defense against viruses and other invading DNA are among those that are gained and lost at the highest rates...
April 4, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28370850/competition-and-niche-separation-of-pelagic-bacteria-in-freshwater-habitats
#14
REVIEW
Jakob Pernthaler
Freshwater bacterioplankton assemblages are composed of sympatric populations that can be delineated, e.g., by ribosomal RNA gene relatedness and that differ in key ecophysiological properties. They may be free-living or attached, specialized for particular concentrations or subsets of substrates, or invest a variable amount of their resources in defence traits against protistan predators and viruses. Some may be motile and tactic whereas others are not, with far-reaching implications for their respective life styles and niche partitioning...
March 30, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28369076/transient-chromatin-properties-revealed-by-polymer-models-and-stochastic-simulations-constructed-from-chromosomal-capture-data
#15
Ofir Shukron, David Holcman
Chromatin organization can be probed by Chromosomal Capture (5C) data, from which the encounter probability (EP) between genomic sites is presented in a large matrix. This matrix is averaged over a large cell population, revealing diagonal blocks called Topological Associating Domains (TADs) that represent a sub-chromatin organization. To study the relation between chromatin organization and gene regulation, we introduce a computational procedure to construct a bead-spring polymer model based on the EP matrix...
April 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28365150/environment-tunes-propagation-of-cell-to-cell-variation-in-the-human-macrophage-gene-network
#16
Andrew J Martins, Manikandan Narayanan, Thorsten Prüstel, Bethany Fixsen, Kyemyung Park, Rachel A Gottschalk, Yong Lu, Cynthia Andrews-Pfannkoch, William W Lau, Katherine V Wendelsdorf, John S Tsang
Cell-to-cell variation in gene expression and the propagation of such variation (PoV or "noise propagation") from one gene to another in the gene network, as reflected by gene-gene correlation across single cells, are commonly observed in single-cell transcriptomic studies and can shape the phenotypic diversity of cell populations. While gene network "rewiring" is known to accompany cellular adaptation to different environments, how PoV changes between environments and its underlying regulatory mechanisms are less understood...
March 28, 2017: Cell Systems
https://www.readbyqxmd.com/read/28361666/towards-targeted-combinatorial-therapy-design-for-the-treatment-of-castration-resistant-prostate-cancer
#17
Osama Ali Arshad, Aniruddha Datta
BACKGROUND: Prostate cancer is one of the most prevalent cancers in males in the United States and amongst the leading causes of cancer related deaths. A particularly virulent form of this disease is castration-resistant prostate cancer (CRPC), where patients no longer respond to medical or surgical castration. CRPC is a complex, multifaceted and heterogeneous malady with limited standard treatment options. RESULTS: The growth and progression of prostate cancer is a complicated process that involves multiple pathways...
March 22, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28355056/deconvolution-of-gene-expression-noise-into-spatial-dynamics-of-transcription-factor-promoter-interplay
#18
Ángel Goñi-Moreno, Ilaria Benedetti, Juhyun Kim, Víctor de Lorenzo
Gene expression noise is not only the mere consequence of stochasticity, but also a signal that reflects the upstream physical dynamics of the cognate molecular machinery. Soil bacteria facing recalcitrant pollutants exploit noise of catabolic promoters to deploy beneficial phenotypes such as metabolic bet-hedging and/or division of biochemical labor. Although the role of upstream promoter-regulator interplay in the origin of this noise is little understood, its specifications are probably ciphered in flow cytometry data patterns...
April 17, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28352251/stochastic-and-differential-activation-of-%C3%AF-b-and-prfa-in-listeria-monocytogenes-at-the-single-cell-level-under-different-environmental-stress-conditions
#19
Claudia Guldimann, Veronica Guariglia-Oropeza, Sophia Harrand, David Kent, Kathryn J Boor, Martin Wiedmann
During host infection, the foodborne pathogen Listeria monocytogenes must sense and respond to rapidly changing environmental conditions. Two transcriptional regulators, the alternative sigma factor B (σ(B)) and the Positive Regulatory Factor A (PrfA), are key contributors to the transcriptomic responses that enable bacterial survival in the host gastrointestinal tract and invasion of host duodenal cells. Increases in temperature and osmolarity induce activity of these proteins; such conditions may be encountered in food matrices as well as within the host gastrointestinal tract...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28351398/genome-wide-methylation-analysis-identifies-a-core-set-of-hypermethylated-genes-in-cimp-h-colorectal-cancer
#20
Tyler McInnes, Donghui Zou, Dasari S Rao, Francesca M Munro, Vicky L Phillips, John L McCall, Michael A Black, Anthony E Reeve, Parry J Guilford
BACKGROUND: Aberrant DNA methylation profiles are a characteristic of all known cancer types, epitomized by the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC). Hypermethylation has been observed at CpG islands throughout the genome, but it is unclear which factors determine whether an individual island becomes methylated in cancer. METHODS: DNA methylation in CRC was analysed using the Illumina HumanMethylation450K array. Differentially methylated loci were identified using Significance Analysis of Microarrays (SAM) and the Wilcoxon Signed Rank (WSR) test...
March 28, 2017: BMC Cancer
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