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Stochastic gene

Shayan Falasiri, Tasnif Rahman, Yaping N Tu, Timothy J Fawcett, George Blanck
BACKGROUND: Human mutagenesis has a large stochastic component. Thus, large coding regions, especially cytoskeletal and extra-cellular matrix protein (CECMP) coding regions are particularly vulnerable to mutations. Recent results have verified a high level of somatic mutations in the CECMP coding regions in the cancer genome atlas (TCGA), and a relatively common occurrence of germline, deleterious mutations in the TCGA breast cancer dataset. METHODS: The objective of this study was to determine the correlations of CECMP coding region, germline nucleotide variations with both overall survival (OS) and disease-free survival (DFS)...
May 17, 2018: Gene
John D West, Richard L Mort, Robert E Hill, Steven D Morley, J Martin Collinson
The use of mice that are mosaic for reporter gene expression underlies many lineage-tracing studies in stem cell biology. For example, using mosaic LacZ reporter mice, it was shown that limbal epithelial stem cells (LESCs) around the periphery of the cornea maintain radial sectors of the corneal epithelium and that radial stripe numbers declined with age. Originally, the corneal results were interpreted as progressive, age-related loss or irreversible inactivation of some LESC clones. In this study we used computer simulations to show that these results could also be explained by stochastic replacement of LESCs by neighbouring LESCs, leading to neutral drift of LESC populations...
May 13, 2018: Stem Cell Research
David J Jörg, Luis G Morelli, Frank Jülicher
We introduce a stochastic model of coupled genetic oscillators in which chains of chemical events involved in gene regulation and expression are represented as sequences of Poisson processes. We characterize steady states by their frequency, their quality factor, and their synchrony by the oscillator cross correlation. The steady state is determined by coupling and exhibits stochastic transitions between different modes. The interplay of stochasticity and nonlinearity leads to isolated regions in parameter space in which the coupled system works best as a biological pacemaker...
March 2018: Physical Review. E
Guillermo Rodrigo
Gene expression programs in living cells are highly dynamic due to spatiotemporal molecular signaling and inherent biochemical stochasticity. Here we study a mechanism based on molecule-to-molecule variability at the RNA level for the generation of bursts of protein production, which can lead to heterogeneity in a cell population. We develop a mathematical framework to show numerically and analytically that genes regulated post transcriptionally by small RNA molecules can exhibit such bursts due to different states of translation activity (on or off), mostly revealed in a regime of few molecules...
March 2018: Physical Review. E
Marc Rullan, Dirk Benzinger, Gregor W Schmidt, Andreas Milias-Argeitis, Mustafa Khammash
Transcription is a highly regulated and inherently stochastic process. The complexity of signal transduction and gene regulation makes it challenging to analyze how the dynamic activity of transcriptional regulators affects stochastic transcription. By combining a fast-acting, photo-regulatable transcription factor with nascent RNA quantification in live cells and an experimental setup for precise spatiotemporal delivery of light inputs, we constructed a platform for the real-time, single-cell interrogation of transcription in Saccharomyces cerevisiae...
May 17, 2018: Molecular Cell
Evelina L Tarragona, Patrick S Sebastian, María N Saracho Bottero, Emilia I Martinez, Valeria N Debárbora, Atilio J Mangold, Alberto A Guglielmone, Santiago Nava
The aim of this work was to generate knowledge on ecological aspects of Amblyomma sculptum in Argentina, such as seasonal dynamics, geographical range size, hosts, genetic diversity and phylogeography. Adult and immature A. sculptum ticks were collected in different localities of Argentina to know the geographical range size and hosts. The genetic diversity of this tick was studied through analyses of 16S rDNA sequences. To describe the seasonal dynamics, free-living ticks were monthly collected from October 2013 to October 2015...
April 27, 2018: Ticks and Tick-borne Diseases
Eric D Morrell, Alice Wiedeman, S Alice Long, Sina A Gharib, T Eoin West, Shawn J Skerrett, Mark M Wurfel, Carmen Mikacenic
Studies in human peripheral blood monocyte-derived macrophages in vitro have shown clear evidence that multiple macrophage polarization states exist. The extent to which different alveolar macrophage (AM) polarization states exist in homeostasis or in the setting of severe injury such as acute respiratory distress syndrome (ARDS) is largely unknown. We applied single-cell cytometry TOF (CyTOF) to simultaneously measure 36 cell-surface markers on CD45+ cells present in bronchoalveolar lavage from healthy volunteers, as well as mechanically ventilated subjects with and without ARDS...
May 17, 2018: JCI Insight
Magda Lewandowska, Krystyna Jędrychowska-Dańska, Tomasz Płoszaj, Piotr Witas, Alicja Zamerska, Hanna Mańkowska-Pliszka, Henryk W Witas
The last decade has seen sharp progress in the field of human evolutionary genetics and a great amount of genetic evidence of natural selection has been provided so far. Since host-pathogen co-evolution is difficult to trace due to the polygenic nature of human susceptibility to microbial diseases, of particular interest is any signal of natural selection in response to the strong selective pressure exerted by pathogens. Analysis of ancient DNA allows for the direct insight into changes of a gene pool content over time and enables monitoring allele frequency fluctuations...
May 12, 2018: Infection, Genetics and Evolution
Joseph J Wanford, Luke R Green, Jack Aidley, Christopher D Bayliss
Pathogenic Neisseria are responsible for significantly higher levels of morbidity and mortality than their commensal relatives despite having similar genetic contents. Neisseria possess a disparate arsenal of surface determinants that facilitate host colonisation and evasion of the immune response during persistent carriage. Adaptation to rapid changes in these hostile host environments is enabled by phase variation (PV) involving high frequency, stochastic switches in expression of surface determinants. In this study, we analysed 89 complete and 79 partial genomes, from the NCBI and Neisseria PubMLST databases, representative of multiple pathogenic and commensal species of Neisseria using PhasomeIt, a new program that identifies putatively phase-variable genes and homology groups by the presence of simple sequence repeats (SSR)...
2018: PloS One
Jacques P Bothma, Matthew R Norstad, Simon Alamos, Hernan G Garcia
Embryonic cell fates are defined by transcription factors that are rapidly deployed, yet attempts to visualize these factors in vivo often fail because of slow fluorescent protein maturation. Here, we pioneer a protein tag, LlamaTag, which circumvents this maturation limit by binding mature fluorescent proteins, making it possible to visualize transcription factor concentration dynamics in live embryos. Implementing this approach in the fruit fly Drosophila melanogaster, we discovered stochastic bursts in the concentration of transcription factors that are correlated with bursts in transcription...
April 26, 2018: Cell
Armin Scheben, David Edwards
The rate of crop improvement must increase to meet rising global demand for food. Crop breeding pipelines can be hampered by the imprecision and multi-generational timeframe of methods such as intercrossing and stochastic mutagenesis used to generate variation. Genome editing can generate targeted allelic series of trait-related genes and regulatory elements, creating a series of variable phenotypes for breeding within a single generation. Disrupting genic and regulatory regions is particularly effective for engineering quantitative traits...
May 8, 2018: Current Opinion in Plant Biology
Lifu Qian, Hui Wang, Jie Yan, Tao Pan, Shanqun Jiang, Dingqi Rao, Baowei Zhang
BACKGROUND: Mitochondrial DNA sequences have long been used in phylogenetic studies. However, little attention has been paid to the changes in gene arrangement patterns in the snake's mitogenome. Here, we analyzed the complete mitogenome sequences and structures of 65 snake species from 14 families and examined their structural patterns, organization and evolution. Our purpose was to further investigate the evolutionary implications and possible rearrangement mechanisms of the mitogenome within snakes...
May 10, 2018: BMC Genomics
Sandeep Choubey, Jane Kondev, Alvaro Sanchez
Transcription is the dominant point of control of gene expression. Biochemical studies have revealed key molecular components of transcription and their interactions, but the dynamics of transcription initiation in cells is still poorly understood. This state of affairs is being remedied with experiments that observe transcriptional dynamics in single cells using fluorescent reporters. Quantitative information about transcription initiation dynamics can also be extracted from experiments that use electron micrographs of RNA polymerases caught in the act of transcribing a gene (Miller spreads)...
May 8, 2018: Biophysical Journal
Chao Li, Jiaquan Yu, Jennifer Schehr, Scott M Berry, Ticiana A Leal, Joshua M Lang, David J Beebe
The concept of high liquid repellency in multi-liquid-phase systems (e.g., aqueous droplets in an oil background) has been applied to areas of biomedical research to realize intrinsic advantages not available in single-liquid-phase systems. Such advantages have included minimizing analyte loss, facile manipulation of single-cell samples, elimination of biofouling, and ease of use regarding loading and retrieving of the sample. In this paper, we present generalized design rules for predicting the wettability of solid-liquid-liquid systems (especially for discrimination between exclusive liquid repellency (ELR) and finite liquid repellency) to extend the applications of ELR...
May 8, 2018: ACS Applied Materials & Interfaces
Yunyan Guo, Min Liu, Lemian Liu, Xuan Liu, Huihuang Chen, Jun Yang
In freshwater systems, both antibiotic resistance genes (ARGs) and cyanobacterial blooms attract global public health concern. Cyanobacterial blooms can greatly impact bacterial taxonomic communities, but very little is known about the influence of the blooms on antibiotic resistance functional community. In this study, the ARGs in both free-living (FL) and particle-attached (PA) bacteria under bloom and non-bloom conditions were simultaneously investigated in a subtropical reservoir using high-throughput approaches...
May 4, 2018: Environment International
David Capper, Nils W Engel, Damian Stichel, Matt Lechner, Stefanie Glöss, Simone Schmid, Christian Koelsche, Daniel Schrimpf, Judith Niesen, Annika K Wefers, David T W Jones, Martin Sill, Oliver Weigert, Keith L Ligon, Adriana Olar, Arend Koch, Martin Forster, Sebastian Moran, Oscar M Tirado, Miguel Sáinz-Japeado, Jaume Mora, Manel Esteller, Javier Alonso, Xavier Garcia Del Muro, Werner Paulus, Jörg Felsberg, Guido Reifenberger, Markus Glatzel, Stephan Frank, Camelia M Monoranu, Valerie J Lund, Andreas von Deimling, Stefan Pfister, Rolf Buslei, Julika Ribbat-Idel, Sven Perner, Volker Gudziol, Matthias Meinhardt, Ulrich Schüller
Olfactory neuroblastoma/esthesioneuroblastoma (ONB) is an uncommon neuroectodermal neoplasm thought to arise from the olfactory epithelium. Little is known about its molecular pathogenesis. For this study, a retrospective cohort of n = 66 tumor samples with the institutional diagnosis of ONB was analyzed by immunohistochemistry, genome-wide DNA methylation profiling, copy number analysis, and in a subset, next-generation panel sequencing of 560 tumor-associated genes. DNA methylation profiles were compared to those of relevant differential diagnoses of ONB...
May 5, 2018: Acta Neuropathologica
Ping Xie, Zi Yi Wu, Jiang Yan Zhao, Yan Fang Sang, Jie Chen
A stochastic hydrological process is influenced by both stochastic and deterministic factors. A hydrological time series contains not only pure random components reflecting its inheri-tance characteristics, but also deterministic components reflecting variability characteristics, such as jump, trend, period, and stochastic dependence. As a result, the stochastic hydrological process presents complicated evolution phenomena and rules. To better understand these complicated phenomena and rules, this study described the inheritance and variability characteristics of an inconsistent hydrological series from two aspects: stochastic process simulation and time series analysis...
April 2018: Ying Yong Sheng Tai Xue Bao, the Journal of Applied Ecology
Ziyi Yu, Christian R Boehm, Julian M Hibberd, Chris Abell, Jim Haseloff, Steven J Burgess, Ivan Reyna-Llorens
Droplet-based microfluidics has been used to facilitate high-throughput analysis of individual prokaryote and mammalian cells. However, there is a scarcity of similar workflows applicable to rapid phenotyping of plant systems where phenotyping analyses typically are time-consuming and low-throughput. We report on-chip encapsulation and analysis of protoplasts isolated from the emergent plant model Marchantia polymorpha at processing rates of >100,000 cells per hour. We use our microfluidic system to quantify the stochastic properties of a heat-inducible promoter across a population of transgenic protoplasts to demonstrate its potential for assessing gene expression activity in response to environmental conditions...
2018: PloS One
Caitlin M A Simopoulos, Elizabeth A Weretilnyk, G Brian Golding
BACKGROUND: In plants, long non-protein coding RNAs are believed to have essential roles in development and stress responses. However, relative to advances on discerning biological roles for long non-protein coding RNAs in animal systems, this RNA class in plants is largely understudied. With comparatively few validated plant long non-coding RNAs, research on this potentially critical class of RNA is hindered by a lack of appropriate prediction tools and databases. Supervised learning models trained on data sets of mostly non-validated, non-coding transcripts have been previously used to identify this enigmatic RNA class with applications largely focused on animal systems...
May 2, 2018: BMC Genomics
Haitham A Shaban, Roman Barth, Kerstin Bystricky
Intrinsic dynamics of chromatin contribute to gene regulation. How chromatin mobility responds to genomic processes, and whether this response relies on coordinated chromatin movement is still unclear. Here, we introduce an approach called Dense Flow reConstruction and Correlation (DFCC), to quantify correlation of chromatin motion with sub-pixel sensitivity at the level of the whole nucleus. DFCC reconstructs dense global flow fields of fluorescent images acquired in real-time. We applied our approach to analyze stochastic movements of DNA and histones, based on direction and magnitude at different time lags in human cells...
April 30, 2018: Nucleic Acids Research
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