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https://www.readbyqxmd.com/read/28319101/a-vibrio-cholerae-autoinducer-receptor-pair-that-controls-biofilm-formation
#1
Kai Papenfort, Justin E Silpe, Kelsey R Schramma, Jian-Ping Cong, Mohammad R Seyedsayamdost, Bonnie L Bassler
Quorum sensing (QS) is a cell-cell communication process that enables bacteria to track cell population density and orchestrate collective behaviors. QS relies on the production and detection of, and the response to, extracellular signal molecules called autoinducers. In Vibrio cholerae, multiple QS circuits control pathogenesis and biofilm formation. Here, we identify and characterize a new QS autoinducer-receptor pair. The autoinducer is 3,5-dimethylpyrazin-2-ol (DPO). DPO is made from threonine and alanine, and its synthesis depends on threonine dehydrogenase (Tdh)...
March 20, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28315412/engineering-bacterial-translation-initiation-do-we-have-all-the-tools-we-need
#2
REVIEW
Justin Vigar, Hans-Joachim Wieden
BACKGROUND: Reliable tools that allow precise and predictable control over gene expression are critical for the success of nearly all bioengineering applications. Translation initiation is the most regulated phase during protein biosynthesis, and is therefore a promising target for exerting control over gene expression. At the translational level, the copy number of a protein can be fine-tuned by altering the interaction between the translation initiation region of an mRNA and the ribosome...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28300664/gene-expression-changes-in-immune-response-pathways-following-oral-administration-of-tetrabromobisphenol-a-tbbpa-in-female-wistar-han-rats
#3
Samantha M Hall, Sherry J Coulter, Gabriel A Knudsen, J Michael Sanders, Linda S Birnbaum
Tetrabromobisphenol A (TBBPA) is a brominated flame retardant used globally at high volumes, primarily in the epoxy resin of circuit boards. It has been detected in the environment and in humans. The National Toxicology Program found that chronic oral TBBPA treatment of 250mg/kg and higher caused an increased incidence of uterine lesions in female Wistar Han rats. The present laboratory has previously reported changes in gene expression associated with estrogen homeostasis in liver and uterine tissue of adult female Wistar Han rats after five days of gavage with 250mg/kg of TBBPA...
March 11, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28299699/synthetic-cell-based-sensors-with-programmed-selectivity-and-sensitivity
#4
Elvis Bernard, Baojun Wang
Bacteria live in an ever changing environment and, to adapt their physiology, they have to sense the changes. Our current understanding of the mechanisms and elements involved in the detection and processing of these environmental signals grant us access to an array of genetic components able to process such information. As engineers can use different electronic components to build a circuit, we can rewire the cellular components to create digital logic and analogue gene circuits that will program cell behaviour in a designed manner in response to a specific stimulus...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28299654/roles-of-runx-genes-in-nervous-system-development
#5
Jae Woong Wang, Stefano Stifani
Runt-related (Runx) transcription factors play essential roles during development and adult tissue homeostasis and are responsible for several human diseases. They regulate a variety of biological mechanisms in numerous cell lineages. Recent years have seen significant progress in our understanding of the functions performed by Runx proteins in the developing and postnatal mammalian nervous system. In both central and peripheral nervous systems, Runx1 and Runx3 display remarkably specific expression in mostly non-overlapping groups of postmitotic neurons...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28289210/phosphorylation-induced-conformational-dynamics-in-an-intrinsically-disordered-protein-and-potential-role-in-phenotypic-heterogeneity
#6
Prakash Kulkarni, Mohit Kumar Jolly, Dongya Jia, Steven M Mooney, Ajay Bhargava, Luciane T Kagohara, Yihong Chen, Pengyu Hao, Yanan He, Robert W Veltri, Alexander Grishaev, Keith Weninger, Herbert Levine, John Orban
Intrinsically disordered proteins (IDPs) that lack a unique 3D structure and comprise a large fraction of the human proteome play important roles in numerous cellular functions. Prostate-Associated Gene 4 (PAGE4) is an IDP that acts as a potentiator of the Activator Protein-1 (AP-1) transcription factor. Homeodomain-Interacting Protein Kinase 1 (HIPK1) phosphorylates PAGE4 at S9 and T51, but only T51 is critical for its activity. Here, we identify a second kinase, CDC-Like Kinase 2 (CLK2), which acts on PAGE4 and hyperphosphorylates it at multiple S/T residues, including S9 and T51...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28286216/a-resource-dependent-protein-synthesis-model-for-evaluating-synthetic-circuits
#7
Wolfgang Halter, Jan Maximilian Montenbruck, Zoltan A Tuza, Frank Allgöwer
Reliable in silico design of synthetic gene networks necessitates novel approaches to model the process of protein synthesis under the influence of limited resources. We present such a novel protein synthesis model which originates from the Ribosome Flow Model and among other things describes the movement of RNA-polymerase and ribosomes on mRNA and DNA templates, respectively. By analyzing the convergence properties of this model based upon geometric considerations, we present additional insights into the dynamic mechanisms of the process of protein synthesis...
March 9, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28286179/formation-of-hippocampal-mhtt-aggregates-leads-to-impaired-spatial-memory-hippocampal-activation-and-adult-neurogenesis
#8
L C Schwab, K Richetin, R A Barker, N Déglon
Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by a triad of motor, psychiatric and cognitive deficits with the latter classically attributed to disruption of fronto-striatal circuits. However, emerging evidence suggests that some of the cognitive deficits in HD may have their origin in other structures including the hippocampus. Hippocampal abnormalities have been reported in HD mouse models particularly in terms of performance on the Morris Water Maze. However, in these animals, it is difficult to be certain whether the spatial memory deficits are due to local pathology within this structure or their poor mobility and motivation...
March 9, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28285855/insights-in-the-regulation-of-the-degradation-of-pahs-in-novosphingobium-sp-hr1a-and-utilization-of-this-regulatory-system-as-a-tool-for-the-detection-of-pahs
#9
Ana Segura, Verónica Hernández-Sánchez, Silvia Marqués, Lázaro Molina
Novosphingobium sp. HR1a is able to grow using diverse polycyclic aromatic hydrocarbons (PAHs) as the sole carbon sources. We have identified two transposons that contain genes encoding several ring-hydroxylating dioxygenases and we have demonstrated the crucial role of one of these dioxygenases in the PAH metabolism in this strain; a mutant in the large subunit of this dioxygenase was unable to growth with 2-, 3-, or 4-rings aromatic hydrocarbons. Using a construction of lacZ gene fused with the pathway promoter, we determined that the expression of the dioxygenase gene was specifically induced in the presence of some PAHs and intermediates of their metabolic pathway...
March 9, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28285822/astrocytes-control-circadian-timekeeping-in-the-suprachiasmatic-nucleus-via-glutamatergic-signaling
#10
Marco Brancaccio, Andrew P Patton, Johanna E Chesham, Elizabeth S Maywood, Michael H Hastings
The suprachiasmatic nucleus (SCN) of the hypothalamus orchestrates daily rhythms of physiology and behavior in mammals. Its circadian (∼24 hr) oscillations of gene expression and electrical activity are generated intrinsically and can persist indefinitely in temporal isolation. This robust and resilient timekeeping is generally regarded as a product of the intrinsic connectivity of its neurons. Here we show that neurons constitute only one "half" of the SCN clock, the one metabolically active during circadian daytime...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28285767/large-scale-trans-eqtls-affect-hundreds-of-transcripts-and-mediate-patterns-of-transcriptional-co-regulation
#11
Boel Brynedal, JinMyung Choi, Towfique Raj, Robert Bjornson, Barbara E Stranger, Benjamin M Neale, Benjamin F Voight, Chris Cotsapas
Efforts to decipher the causal relationships between differences in gene regulation and corresponding differences in phenotype have been stymied by several basic technical challenges. Although detecting local, cis-eQTLs is now routine, trans-eQTLs, which are distant from the genes of origin, are far more difficult to find because millions of SNPs must currently be compared to thousands of transcripts. Here, we demonstrate an alternative approach: we looked for SNPs associated with the expression of many genes simultaneously and found that hundreds of trans-eQTLs each affect hundreds of transcripts in lymphoblastoid cell lines across three African populations...
March 1, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28284789/hypoxia-responsive-transgene-expression-system-using-rtp801-promoter-and-synthetic-transactivator-fused-with-oxygen-dependent-degradation-domain
#12
Akihiko Ono, Akira Ito, Tomonaga Sato, Masaki Yamaguchi, Taiga Suzuki, Yoshinori Kawabe, Masamichi Kamihira
Precise control of gene expression using an artificial gene circuit is a major challenge in the application of synthetic biology. Here, we designed a hypoxia-responsive transgene expression system by combining a hypoxia-inducible RTP801 promoter and a tetracycline-responsive transactivator fused with an oxygen-dependent degradation domain (TA-ODD). The reporter gene expression was highly induced by hypoxia when a transactivator-expression plasmid, pRTP801/TA-ODD, harboring a TA-ODD gene driven by the RTP801 promoter, was cotransfected with a reporter plasmid, pTRE/EGFP, harboring an EGFP gene controlled under the transactivator-responsive promoter...
March 9, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28283561/alteration-of-neuronal-excitability-and-short-term-synaptic-plasticity-in-the-prefrontal-cortex-of-a-mouse-model-of-mental-illness
#13
Gregg W Crabtree, Ziyi Sun, Mirna Kvajo, Jantine Ac Broek, Karine Fénelon, Heather McKellar, Lan Xiao, Bin Xu, Sabine Bahn, James M O'Donnell, Joseph A Gogos
Employing a genetic mouse model that faithfully recapitulates a DISC1 genetic alteration strongly associated with schizophrenia and other psychiatric disorders, we examined the impact of this mutation within the prefrontal cortex. Although cortical layering, cytoarchitecture and proteome were found to be largely unaffected, electrophysiological examination of the mPFC revealed both neuronal hyper-excitability and alterations in short-term synaptic plasticity consistent with enhanced neurotransmitter release...
March 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28283558/gene-expression-profiling-with-cre-conditional-pseudorabies-virus-reveals-a-subset-of-midbrain-neurons-that-participate-in-reward-circuitry
#14
Lisa E Pomeranz, Mats I Ekstrand, Kaamashri N Latcha, Gregory A Smith, Lynn W Enquist, Jeffrey M Friedman
The mesolimbic dopamine pathway receives inputs from numerous regions of the brain as part of a neural system that detects rewarding stimuli and coordinates a behavioral response. The capacity to simultaneously map and molecularly define the components of this complex multisynaptic circuit would thus advance our understanding of the determinants of motivated behavior. To accomplish this, we have constructed pseudorabies virus (PRV) strains in which viral propagation and fluorophore expression are activated only after exposure to Cre recombinase...
March 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28280884/social-defeat-disrupts-reward-learning-and-potentiates-striatal-nociceptin-orphanin-fq-mrna-in-rats
#15
Andre Der-Avakian, Manoranjan S D'Souza, David N Potter, Elena H Chartoff, William A Carlezon, Diego A Pizzagalli, Athina Markou
RATIONALE: Mood disorders can be triggered by stress and are characterized by deficits in reward processing, including disrupted reward learning (the ability to modulate behavior according to past rewards). Reward learning is regulated by the anterior cingulate cortex (ACC) and striatal circuits, both of which are implicated in the pathophysiology of mood disorders. OBJECTIVES: Here, we assessed in rats the effects of a potent stressor (social defeat) on reward learning and gene expression in the ACC, ventral tegmental area (VTA), and striatum...
March 9, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28280483/outer-plexiform-layer-structures-are-not-altered-following-aav-mediated-gene-transfer-in-healthy-rat-retina
#16
Bert C Giers, Daniela Klein, Alexandra Mendes-Madeira, Carolina Isiegas, Birgit Lorenz, Silke Haverkamp, Knut Stieger
Ocular gene therapy approaches have been developed for a variety of different diseases. In particular, clinical gene therapy trials for RPE65 mutations, X-linked retinoschisis, and choroideremia have been conducted at different centers in recent years, showing that adeno-associated virus (AAV)-mediated gene therapy is safe, but limitations exist as to the therapeutic benefit and long-term duration of the treatment. The technique of vector delivery to retinal cells relies on subretinal injection of the vector solution, causing a transient retinal detachment...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28279351/single-cell-profiling-of-an-in%C3%A2-vitro-model-of-human-interneuron-development-reveals-temporal-dynamics-of-cell-type-production-and-maturation
#17
Jennie L Close, Zizhen Yao, Boaz P Levi, Jeremy A Miller, Trygve E Bakken, Vilas Menon, Jonathan T Ting, Abigail Wall, Anne-Rachel Krostag, Elliot R Thomsen, Angel M Nelson, John K Mich, Rebecca D Hodge, Soraya I Shehata, Ian A Glass, Susan Bort, Nadiya V Shapovalova, N Kiet Ngo, Joshua S Grimley, John W Phillips, Carol L Thompson, Sharad Ramanathan, Ed Lein
GABAergic interneurons are essential for neural circuit function, and their loss or dysfunction is implicated in human neuropsychiatric disease. In vitro methods for interneuron generation hold promise for studying human cellular and functional properties and, ultimately, for therapeutic cell replacement. Here we describe a protocol for generating cortical interneurons from hESCs and analyze the properties and maturation time course of cell types using single-cell RNA-seq. We find that the cell types produced mimic in vivo temporal patterns of neuron and glial production, with immature progenitors and neurons observed early and mature cortical neurons and glial cell types produced late...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28278176/cuzd1-is-a-critical-mediator-of-the-jak-stat5-signaling-pathway-that-controls-mammary-gland-development-during-pregnancy
#18
Janelle Mapes, Quanxi Li, Athilakshmi Kannan, Lavanya Anandan, Mary Laws, John P Lydon, Indrani C Bagchi, Milan K Bagchi
In the mammary gland, genetic circuits controlled by estrogen, progesterone, and prolactin, act in concert with pathways regulated by members of the epidermal growth factor family to orchestrate growth and morphogenesis during puberty, pregnancy and lactation. However, the precise mechanisms underlying the crosstalk between the hormonal and growth factor pathways remain poorly understood. We have identified the CUB and zona pellucida-like domain-containing protein 1 (CUZD1), expressed in mammary ductal and alveolar epithelium, as a novel mediator of mammary gland proliferation and differentiation during pregnancy and lactation...
March 9, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28275159/enduring-memory-impairments-provoked-by-developmental-febrile-seizures-are-mediated-by-functional-and-structural-effects-of-neuronal-restrictive-silencing-factor
#19
Katelin P Patterson, Jeremy M Barry, Megan M Curran, Akanksha Singh-Taylor, Gary Brennan, Neggy Rismanchi, Matias Page, Yoav Noam, Gregory L Holmes, Tallie Z Baram
In a subset of children experiencing prolonged febrile seizures (FS), the most common type of childhood seizures, cognitive outcomes are compromised. However, the underlying mechanisms are unknown. Here we identified significant, enduring spatial memory problems in male rats following experimental prolonged FS (febrile status epilepticus; eFSE). Remarkably, these deficits were abolished by transient, post hoc interference with the chromatin binding of the transcriptional repressor neuron restrictive silencing factor (NRSF or REST)...
March 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28273070/hypersensitive-termination-of-the-hypoxic-response-by-a-disordered-protein-switch
#20
Rebecca B Berlow, H Jane Dyson, Peter E Wright
The cellular response to hypoxia is critical for cell survival and is fine-tuned to allow cells to recover from hypoxic stress and adapt to heterogeneous or fluctuating oxygen levels. The hypoxic response is mediated by the α-subunit of the transcription factor HIF-1 (HIF-1α), which interacts through its intrinsically disordered C-terminal transactivation domain with the TAZ1 (also known as CH1) domain of the general transcriptional coactivators CBP and p300 to control the transcription of critical adaptive genes...
March 16, 2017: Nature
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