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https://www.readbyqxmd.com/read/29150615/balancing-a-genetic-toggle-switch-by-real-time-feedback-control-and-periodic-forcing
#1
Jean-Baptiste Lugagne, Sebastián Sosa Carrillo, Melanie Kirch, Agnes Köhler, Gregory Batt, Pascal Hersen
Cybergenetics is a novel field of research aiming at remotely pilot cellular processes in real-time with to leverage the biotechnological potential of synthetic biology. Yet, the control of only a small number of genetic circuits has been tested so far. Here we investigate the control of multistable gene regulatory networks, which are ubiquitously found in nature and play critical roles in cell differentiation and decision-making. Using an in silico feedback control loop, we demonstrate that a bistable genetic toggle switch can be dynamically maintained near its unstable equilibrium position for extended periods of time...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29149607/classifying-drosophila-olfactory-projection-neuron-subtypes-by-single-cell-rna-sequencing
#2
Hongjie Li, Felix Horns, Bing Wu, Qijing Xie, Jiefu Li, Tongchao Li, David J Luginbuhl, Stephen R Quake, Liqun Luo
The definition of neuronal type and how it relates to the transcriptome are open questions. Drosophila olfactory projection neurons (PNs) are among the best-characterized neuronal types: different PN classes target dendrites to distinct olfactory glomeruli, while PNs of the same class exhibit indistinguishable anatomical and physiological properties. Using single-cell RNA sequencing, we comprehensively characterized the transcriptomes of most PN classes and unequivocally mapped transcriptomes to specific olfactory function for six classes...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29149479/cripsr-cas-expands-dynamic-range-of-gene-expression-from-t7rnap-promoters
#3
Sean R McCutcheon, Kwan Lun Chiu, Daniel D Lewis, Cheemeng Tan
BACKGROUND: Reducing leaky gene expression is critical for improving protein yield of recombinant bacteria and stability of engineered cellular circuits in synthetic biology. Leaky gene expression occurs when a genetic promoter is not fully repressed, leading to unintended protein synthesis in the absence of stimuli. Existing work has devised specific molecular strategies for reducing leaky gene expression of each promoter. Main Method and Results: In contrast, we describe a repurposed, modular CRISPRi system that attenuates leaky gene expression using a series of single-guide RNAs targeting the PT7/LacO1 ...
November 17, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/29144600/engineering-mammalian-designer-cells-for-the-treatment-of-metabolic-diseases
#4
REVIEW
Yidan Wang, Meiyan Wang, Kaili Dong, Haifeng Ye
Synthetic biology applies engineering principles to biological systems and has significantly advanced the design of synthetic gene circuits that can reprogram cell activities to perform new functions. The ability to engineer mammalian designer cells with robust therapeutic behaviors has brought new opportunities for treating metabolic diseases. In this review, we highlight the most recent advances in the development of synthetic designer cells uploaded with open-loop gene circuits or closed-loop gene circuits for the treatment of metabolic disorders including diabetes, hypertension, hyperuricemia and obesity, and discuss the current technologies and future perspectives in applying these designer cells for clinical applications...
November 16, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/29142298/shaping-bacterial-population-behavior-through-computer-interfaced-control-of-individual-cells
#5
Remy Chait, Jakob Ruess, Tobias Bergmiller, Gašper Tkačik, Călin C Guet
Bacteria in groups vary individually, and interact with other bacteria and the environment to produce population-level patterns of gene expression. Investigating such behavior in detail requires measuring and controlling populations at the single-cell level alongside precisely specified interactions and environmental characteristics. Here we present an automated, programmable platform that combines image-based gene expression and growth measurements with on-line optogenetic expression control for hundreds of individual Escherichia coli cells over days, in a dynamically adjustable environment...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142232/tdp-43-misexpression-causes-defects-in-dendritic-growth
#6
Josiah J Herzog, Mugdha Deshpande, Leah Shapiro, Avital A Rodal, Suzanne Paradis
Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) share overlapping genetic causes and disease symptoms, and are linked neuropathologically by the RNA binding protein TDP-43 (TAR DNA binding protein-43 kDa). TDP-43 regulates RNA metabolism, trafficking, and localization of thousands of target genes. However, the cellular and molecular mechanisms by which dysfunction of TDP-43 contributes to disease pathogenesis and progression remain unclear. Severe changes in the structure of neuronal dendritic arbors disrupt proper circuit connectivity, which in turn could contribute to neurodegenerative disease...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29140243/a-versatile-genetic-tool-for-post-translational-control-of-gene-expression-in-drosophila-melanogaster
#7
Sachin Sethi, Jing W Wang
Several techniques have been developed to manipulate gene expression temporally in intact neural circuits. However, the applicability of current tools developed for in vivo studies in Drosophila is limited by their incompatibility with existing GAL4 lines and side effects on physiology and behavior. To circumvent these limitations, we adopted a strategy to reversibly regulate protein degradation with a small molecule by using a destabilizing domain (DD). We show that this system is effective across different tissues and developmental stages...
November 15, 2017: ELife
https://www.readbyqxmd.com/read/29137267/tumacrophage-macrophages-transformed-into-tumor-stem-like-cells-by-virulent-genetic-material-from-tumor-cells
#8
Yizhuang Zhang, Na Zhou, Xiuyan Yu, Xuehui Zhang, Shanxin Li, Zhen Lei, Ruobi Hu, Hui Li, Yiqing Mao, Xi Wang, Jinshu Zhang, Yuan Li, Hongyan Guo, David M Irwin, Gang Niu, Huanran Tan
Tumor-associated macrophages are regarded as tumor-enhancers as they have key roles in the subversion of adaptive immunity and in inflammatory circuits that promote tumor progression. Here, we show that cancer cells can subvert macrophages yielding cells that have gained pro-tumor functions. When macrophages isolated from mice or humans are co-cultured with dead cancer cell line cells, induced to undergo apoptosis to mimic chemotherapy, up-regulation of pro-tumor gene expression was identified. Phagocytosis of apoptotic cancer cells by macrophages resulted in their transformation into tumor stem (initiating)-like cells, as indicated by the expression of epithelial markers (e...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136012/regional-knockdown-of-ndufs4-implicates-a-thalamocortical-circuit-mediating-anesthetic-sensitivity
#9
Renjini Ramadasan-Nair, Jessica Hui, Pavel I Zimin, Leslie S Itsara, Philip G Morgan, Margaret M Sedensky
Knockout of the mitochondrial complex I protein, NDUFS4, profoundly increases sensitivity of mice to volatile anesthetics. In mice carrying an Ndufs4lox/lox gene, adeno-associated virus expressing Cre recombinase was injected into regions of the brain postulated to affect sensitivity to volatile anesthetics. These injections generated otherwise phenotypically wild type mice with region-specific, postnatal inactivation of Ndufs4, minimizing developmental effects of gene loss. Sensitivities to the volatile anesthetics isoflurane and halothane were measured using loss of righting reflex (LORR) and movement in response to tail clamp (TC) as endpoints...
2017: PloS One
https://www.readbyqxmd.com/read/29133926/genetic-programs-can-be-compressed-and-autonomously-decompressed-in-live-cells
#10
Nicolas Lapique, Yaakov Benenson
Fundamental computer science concepts have inspired novel information-processing molecular systems in test tubes (1-13) and genetically encoded circuits in live cells (14-21) . Recent research has shown that digital information storage in DNA, implemented using deep sequencing and conventional software, can approach the maximum Shannon information capacity (22) of two bits per nucleotide (23) . In nature, DNA is used to store genetic programs, but the information content of the encoding rarely approaches this maximum (24) ...
November 13, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/29133396/repression-of-mir-31-by-bcl6-stabilizes-the-helper-function-of-human-follicular-helper-t-cells
#11
A Ripamonti, E Provasi, M Lorenzo, M De Simone, V Ranzani, S Vangelisti, S Curti, R J P Bonnal, L Pignataro, S Torretta, J Geginat, G Rossetti, M Pagani, S Abrignani
Follicular helper T cells (TFHs) are a key component of adaptive immune responses as they help antibody production by B cells. Differentiation and function of TFH cells are controlled by the master gene BCL6, but it is largely unclear how this transcription repressor specifies the TFH program. Here we asked whether BCL6 controlled helper function through down-regulation of specific microRNAs (miRNAs). We first assessed miRNA expression in TFH cells and defined a TFH-specific miRNA signature. We report that hsa-miR-31-5p (miR-31) is down-regulated in TFH; we showed that BCL6 suppresses miR-31 expression by binding to its promoter; and we demonstrated that miR-31 inhibits the expression of molecules that control T-helper function, such as CD40L and SAP...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29130174/identification-of-ahl-and-bdsf-controlled-proteins-in-burkholderia-cenocepacia-by-proteomics
#12
Yilei Liu, Gabriella Pessi, Katharina Riedel, Leo Eberl
We used comparative proteome analysis to determine the target genes of the two quorum sensing (QS) circuits in the opportunistic pathogen Burkholderia cenocepacia: the N-acyl homoserine lactone (AHL)-based CepIR system and the BDSF (B urkholderia diffusible signal factor, cis-2-dodecenoic acid)-based RpfFR system. In this book chapter, we focus on the description of the practical procedure we currently use in the laboratory to perform a sensitive GeLC-MS/MS shotgun proteomics experiment; we also briefly describe the downstream bioinformatic data analysis...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29127518/identifying-molecular-mediators-of-environmentally-enhanced-neurogenesis
#13
REVIEW
Brian E Eisinger, Xinyu Zhao
Adult hippocampal neurogenesis occurs throughout life and supports healthy brain functions. The production of new neurons decreases with age, and deficiencies in adult neurogenesis are associated with neurodevelopmental and degenerative disease. The rate of neurogenesis is dynamically sensitive to an individual's environmental conditions and experiences, and certain stimuli are known robustly to enhance neurogenesis in rodent models, including voluntary exercise, enriched environment, and electroconvulsive shock...
November 10, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29122925/genetic-circuit-characterization-and-debugging-using-rna-seq
#14
Thomas E Gorochowski, Amin Espah Borujeni, Yongjin Park, Alec Ak Nielsen, Jing Zhang, Bryan S Der, D Benjamin Gordon, Christopher A Voigt
Genetic circuits implement computational operations within a cell. Debugging them is difficult because their function is defined by multiple states (e.g., combinations of inputs) that vary in time. Here, we develop RNA-seq methods that enable the simultaneous measurement of: (i) the states of internal gates, (ii) part performance (promoters, insulators, terminators), and (iii) impact on host gene expression. This is applied to a three-input one-output circuit consisting of three sensors, five NOR/NOT gates, and 46 genetic parts...
November 9, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/29121403/mechanisms-of-radial-glia-progenitor-cell-lineage-progression
#15
REVIEW
Robert Beattie, Simon Hippenmeyer
The mammalian cerebral cortex is responsible for higher cognitive functions such as perception, consciousness, and acquiring and processing information. The neocortex is organized into six distinct laminae, each composed of a rich diversity of cell types which assemble into highly complex cortical circuits. Radial glia progenitors (RGPs) are responsible for producing all neocortical neurons and certain glia lineages. Here, we discuss recent discoveries emerging from clonal lineage analysis at the single RGP cell level that provide us with an inaugural quantitative framework of RGP lineage progression...
November 9, 2017: FEBS Letters
https://www.readbyqxmd.com/read/29120735/the-rewiring-of-transcription-circuits-in-evolution
#16
REVIEW
Alexander D Johnson
The binding of transcription regulators to cis-regulatory sequences is a key step through which all cells regulate expression of their genes. Due to gains and losses of cis-regulatory sequences and changes in the transcription regulators themselves, the binding connections between regulators and their target genes rapidly change over evolutionary time and constitute a major source of biological novelty. This review covers recent work, carried out in a wide range of species, that addresses the overall extent of these evolutionary changes, their consequences, and some of the molecular mechanisms that lie behind them...
November 7, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29120463/compartmentalized-partnered-replication-for-the-directed-evolution-of-genetic-parts-and-circuits
#17
Zhanar Abil, Jared W Ellefson, Jimmy D Gollihar, Ella Watkins, Andrew D Ellington
Compartmentalized partnered replication (CPR) is an emulsion-based directed evolution method based on a robust and modular phenotype-genotype linkage. In contrast to other in vivo directed evolution approaches, CPR largely mitigates host fitness effects due to a relatively short expression time of the gene of interest. CPR is based on gene circuits in which the selection of a 'partner' function from a library leads to the production of a thermostable polymerase. After library preparation, bacteria produce partner proteins that can potentially lead to enhancement of transcription, translation, gene regulation, and other aspects of cellular metabolism that reinforce thermostable polymerase production...
December 2017: Nature Protocols
https://www.readbyqxmd.com/read/29119927/gene-environment-interactions-in-late-life-linking-psychosocial-stress-with-brain-aging
#18
Anthony S Zannas
Gene-environment interactions (GxE) can have lasting consequences on brain structure and function, potentially contributing to diverse neuropsychiatric phenotypes. This has been extensively demonstrated by studies examining GxE in childhood and early adulthood, whereas much fewer studies have addressed this question in late life. The relative paucity of studies examining GxE in late life may stem from the working hypothesis that brains become less malleable to environmental inputs as life progresses. However, while some components of brain plasticity decline with increasing age, others are retained and may even become more pronounced in old ages...
November 9, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/29118761/immunological-and-clinical-effect-of-diet-modulation-of-the-gut-microbiome-in-multiple-sclerosis-patients-a-pilot-study
#19
Marina Saresella, Laura Mendozzi, Valentina Rossi, Franca Mazzali, Federica Piancone, Francesca LaRosa, Ivana Marventano, Domenico Caputo, Giovanna E Felis, Mario Clerici
Pathogenesis of autoimmune disorders, including multiple sclerosis (MS), has been linked to an alteration of the resident microbial commensal community and of the interplay between the microbiota and the immune system. Dietary components such as fiber, acting on microbiota composition, could, in principle, result in immune modulation and, thus, could be used to obtain beneficial outcomes for patients. We verified this hypothesis in a pilot study involving two groups of clinically similar relapsing-remitting (RR) MS patients who had undergone either a high-vegetable/low-protein diet (HV/LP diet group; N = 10) or a "Western Diet" (WD group; N = 10) for at least 12 months...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29118206/social-origins-of-developmental-risk-for-mental-and-physical-illness
#20
Judy L Cameron, Kathie L Eagleson, Nathan A Fox, Takao K Hensch, Pat Levitt
Adversity in early childhood exerts an enduring impact on mental and physical health, academic achievement, lifetime productivity, and the probability of interfacing with the criminal justice system. More science is needed to understand how the brain is affected by early life stress (ELS), which produces excessive activation of stress response systems broadly throughout the child's body (toxic stress). Our research examines the importance of sex, timing and type of stress exposure, and critical periods for intervention in various brain systems across species...
November 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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