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Gene circuits

Henry Reyer, Michael Oster, Elizabeth Magowan, Eduard Murani, Helga Sauerwein, Dirk Dannenberger, Björn Kuhla, Siriluck Ponsuksili, Klaus Wimmers
Feed efficiency (FE) is a measure of the rate between feed intake and body weight gain and is subject to constant progress in pigs, based on extensive performance tests and analyses of physiological parameters. However, endocrine regulatory circuits which comprise the sensation and perception of intrinsic requirements and appropriate systemic responses have not yet been fully elucidated. It is hypothesized that the gut-brain-axis, which is a network of hierarchical anterior regulatory tissues, contributes largely to variations in FE...
June 15, 2018: Physiological Genomics
Bor Luen Tang
The mechanism of intercellular transmission of pathological agents in neurodegenerative diseases has received much recent attention. Huntington's disease (HD) is caused by a monogenic mutation in the gene encoding Huntingtin (HTT). Mutant HTT (mHTT) harbors a CAG repeat extension which encodes an abnormally long polyglutamine (polyQ) repeat at HTT's N-terminus. Neuronal pathology in HD is largely due to the toxic gain-of-function by mHTT and its proteolytic products, which forms both nuclear and cytoplasmic aggregates that perturb nuclear gene transcription, RNA splicing and transport as well cellular membrane dynamics...
June 14, 2018: Cells
Luka Horvat, Mariastefania Antica, Maja Matulić
Differentiation of blood cells is one of the most complex processes in the body. It is regulated by the action of transcription factors in time and space which creates a specific signaling network. In the hematopoietic signaling system, Notch is one of the main regulators of lymphocyte development. The aim of this study was to get insight into the regulation of Notch signalization and the influence of poly(ADP-ribose)polymerase (PARP) activity on this process in three leukemia cell lines obtained from B and T cells...
June 14, 2018: Cells
Valerio Zerbi, Giovanna D Ielacqua, Marija Markicevic, Matthias Georg Haberl, Mark H Ellisman, Arjun A-Bhaskaran, Andreas Frick, Markus Rudin, Nicole Wenderoth
Autism spectrum disorders (ASD) are a set of complex neurodevelopmental disorders for which there is currently no targeted therapeutic approach. It is thought that alterations of genes regulating migration and synapse formation during development affect neural circuit formation and result in aberrant connectivity within distinct circuits that underlie abnormal behaviors. However, it is unknown whether deviant developmental trajectories are circuit-specific for a given autism risk-gene. We used MRI to probe changes in functional and structural connectivity from childhood to adulthood in Fragile-X (Fmr1-/y) and contactin-associated (CNTNAP2-/-) knockout mice...
July 1, 2018: Cerebral Cortex
Pabitra K Parua, Gregory T Booth, Miriam Sansó, Bradley Benjamin, Jason C Tanny, John T Lis, Robert P Fisher
The end of the RNA polymerase II (Pol II) transcription cycle is strictly regulated to prevent interference between neighbouring genes and to safeguard transcriptome integrity 1 . The accumulation of Pol II downstream of the cleavage and polyadenylation signal can facilitate the recruitment of factors involved in mRNA 3'-end formation and termination 2 , but how this sequence is initiated remains unclear. In a chemical-genetic screen, human protein phosphatase 1 (PP1) isoforms were identified as substrates of positive transcription elongation factor b (P-TEFb), also known as the cyclin-dependent kinase 9 (Cdk9)-cyclin T1 (CycT1) complex 3 ...
June 13, 2018: Nature
Norio Chihara, Asaf Madi, Takaaki Kondo, Huiyuan Zhang, Nandini Acharya, Meromit Singer, Jackson Nyman, Nemanja D Marjanovic, Monika S Kowalczyk, Chao Wang, Sema Kurtulus, Travis Law, Yasaman Etminan, James Nevin, Christopher D Buckley, Patrick R Burkett, Jason D Buenrostro, Orit Rozenblatt-Rosen, Ana C Anderson, Aviv Regev, Vijay K Kuchroo
The expression of co-inhibitory receptors, such as CTLA-4 and PD-1, on effector T cells is a key mechanism for ensuring immune homeostasis. Dysregulated expression of co-inhibitory receptors on CD4+ T cells promotes autoimmunity, whereas sustained overexpression on CD8+ T cells promotes T cell dysfunction or exhaustion, leading to impaired ability to clear chronic viral infections and diseases such as cancer1,2 . Here, using RNA and protein expression profiling at single-cell resolution in mouse cells, we identify a module of co-inhibitory receptors that includes not only several known co-inhibitory receptors (PD-1, TIM-3, LAG-3 and TIGIT) but also many new surface receptors...
June 13, 2018: Nature
Annalisa Paolino, Laura R Fenlon, Rodrigo Suárez, Linda J Richards
Long-range projection neurons of the neocortex form the major tracts of the mammalian brain and are crucial for sensory-motor, associative and executive functions. Development of such circuits involves neuronal proliferation, specification and migration, as well as axonal elongation, navigation and targeting, where growing axons encounter multiple guidance cues and integrate these signals to execute guidance decisions. The complexity of axon guidance mechanisms in the formation of long-range neuronal projections has suggested that they might be under control of transcription factors, which are DNA-binding proteins that regulate the expression of downstream genes...
June 9, 2018: Current Opinion in Neurobiology
Javier J How, Saket Navlakha
Biological networks have long been known to be modular, containing sets of nodes that are highly connected internally. Less emphasis, however, has been placed on understanding how intermodule connections are distributed within a network. Here, we borrow ideas from engineered circuit design and study Rentian scaling, which states that the number of external connections between nodes in different modules is related to the number of nodes inside the modules by a power-law relationship. We tested this property in a broad class of molecular networks, including protein interaction networks for six species and gene regulatory networks for 41 human and 25 mouse cell types...
June 12, 2018: Neural Computation
Seaim Lwin Aye, Kei Fujiwara, Nobuhide Doi
Engineering and design of genetic circuit in living cell is critical in accessing the beneficial application of synthetic biology. Directed evolution can avoid the complicated rational design of such circuit by screening or selecting functional circuit from non-functional one. Here we proposed a positive-negative selection system for selecting a transcription factor that activates gene expression in response to arsenic in solution. First, we developed a whole cell biosensor for sensing arsenite in liquid using a regulator (ArsR) and a reporter (GFP), and evaluated its performance...
June 8, 2018: Journal of Biochemistry
Zohreh Fattahi, Taimoor I Sheikh, Luciana Musante, Memoona Rasheed, Ibrahim Ihsan Taskiran, Ricardo Harripaul, Hao Hu, Somayeh Kazeminasab, Muhammad Rizwan Alam, Masoumeh Hosseini, Farzaneh Larti, Zhila Ghaderi, Arzu Celik, Muhammad Ayub, Muhammad Ansar, Mohammad Haddadi, Thomas F Wienker, Hans Hilger Ropers, Kimia Kahrizi, John B Vincent, H Najmabadi
Exploring genes and pathways underlying Intellectual Disability (ID) provides insight into brain development and function, clarifying the complex puzzle of how cognition develops. As part of ongoing systematic studies to identify candidate ID genes, linkage analysis and next generation sequencing revealed ZBTB11, as a novel candidate ID gene. ZBTB11 encodes a less-studied transcription regulator and the two identified missense variants in this study may disrupt canonical Zn2+-binding residues of its C2H2 zinc finger domain, leading to possible altered DNA binding...
June 8, 2018: Human Molecular Genetics
Agata Michalska, Katarzyna Blaszczyk, Joanna Wesoly, Hans A R Bluyssen
Interferon (IFN)-I and IFN-II both induce IFN-stimulated gene (ISG) expression through Janus kinase (JAK)-dependent phosphorylation of signal transducer and activator of transcription (STAT) 1 and STAT2. STAT1 homodimers, known as γ-activated factor (GAF), activate transcription in response to all types of IFNs by direct binding to IFN-II activation site (γ-activated sequence)-containing genes. Association of interferon regulatory factor (IRF) 9 with STAT1-STAT2 heterodimers [known as interferon-stimulated gene factor 3 (ISGF3)] or with STAT2 homodimers (STAT2/IRF9) in response to IFN-I, redirects these complexes to a distinct group of target genes harboring the interferon-stimulated response element (ISRE)...
2018: Frontiers in Immunology
David Karig, K Michael Martini, Ting Lu, Nicholas A DeLateur, Nigel Goldenfeld, Ron Weiss
The origin of biological morphology and form is one of the deepest problems in science, underlying our understanding of development and the functioning of living systems. In 1952, Alan Turing showed that chemical morphogenesis could arise from a linear instability of a spatially uniform state, giving rise to periodic pattern formation in reaction-diffusion systems but only those with a rapidly diffusing inhibitor and a slowly diffusing activator. These conditions are disappointingly hard to achieve in nature, and the role of Turing instabilities in biological pattern formation has been called into question...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Xueting Chen, Yuanyuan Wang, Wenjun Wu, Ke Dong, Zhaonong Hu
Pyrethroid insecticides modify the gating of voltage-gated sodium channels, thus disrupting the function of the nervous system. In Drosophila melanogaster, para encodes a functional sodium channel. Drosophila Sodium Channel 1 (DSC1), although considered as a putative sodium channel gene for decades due to its high sequence similarity with sodium channels, encodes a voltage-gated cation channel with high permeability to Ca2+ . Previous study showed that knockout of the DSC1 gene (DSC1-/- ) caused Drosophila adults to be more susceptible to pyrethroids and the adult giant fiber (GF) neural circuit were more susceptible to pyrethroids...
June 2018: Pesticide Biochemistry and Physiology
Jing Sun, Xiaoyu Pan, Line I Christiansen, Xiao-Long Yuan, Kerstin Skovgaard, Dereck E W Chatterton, Sanne S Kaalund, Fei Gao, Per T Sangild, Stanislava Pankratova
BACKGROUND: Necrotizing enterocolitis (NEC) is an acute gut inflammatory disorder that occurs in preterm infants in the first weeks after birth. Infants surviving NEC often show impaired neurodevelopment. The mechanisms linking NEC lesions with later neurodevelopment are poorly understood but may include proinflammatory signaling in the immature brain. Using preterm pigs as a model for preterm infants, we hypothesized that severe intestinal NEC lesions are associated with acute effects on the developing hippocampus...
June 9, 2018: Journal of Neuroinflammation
Sriram Bandi, Sanchit Gupta, Tatyana Tchaikovskaya, Sanjeev Gupta
Understanding mechanisms in lineage differentiation is critical for organ development, pathophysiology and oncogenesis. To determine whether microRNAs (miRNA) may serve as drivers or adjuncts in hepatic differentiation, we studied human embryonic stem cell-derived hepatocytes and primary hepatocytes representing fetal or adult stages. Model systems were used for hepatic lineage advancement or regression under culture conditions with molecular assays. Profiles of miRNA in primary fetal and adult hepatocytes shared similarities and distinctions from pluripotent stem cells or stem cell-derived early fetal-like hepatocytes...
June 5, 2018: Experimental Cell Research
Koudai Morishita, Masafumi Iwami, Taketoshi Kiya
In the central nervous system of insects, motor patterns are generated in the thoracic ganglia under the control of brain, where sensory information is integrated and behavioral decisions are made. Previously, we established neural activity-mapping methods using an immediate early gene, BmHr38, as a neural activity marker in the brain of male silkmoth Bombyx mori. In the present study, to gain insights into neural mechanisms of motor-pattern generation in the thoracic ganglia, we investigated expression of BmHr38 in response to sex pheromone-induced courtship behavior...
June 2018: Zoological Science
Davide Roncarati, Vincenzo Scarlato
The ability to gauge the surroundings and modulate gene expression accordingly is a crucial feature for the survival bacterial pathogens. In this respect, the heat-shock response, a universally conserved mechanism of protection, allows bacterial cells to adapt rapidly to hostile conditions and to survive during environmental stresses. The important and widespread human pathogen Helicobacter pylori enrolls a collection of highly conserved heat-shock proteins to preserve cellular proteins and to maintain their homeostasis, allowing the pathogen to adapt and survive in the hostile niche of the human stomach...
June 7, 2018: International Journal of Molecular Sciences
Matthew J Blake, John A Trinder, Nicholas B Allen
There is robust evidence of an association between insomnia, anxiety, and depression in adolescence. The aim of this review is to describe and synthesize potential mechanisms underlying this association and explore implications for the design of adolescent behavioral sleep interventions. Specifically, we examine whether insomnia symptoms are a mechanism for the development of internalizing symptoms in adolescence and whether sleep interventions are an effective treatment for both insomnia and internalizing symptoms in adolescence because they target the shared mechanisms underlying these disorders...
May 28, 2018: Clinical Psychology Review
Youssef El Mouali, Tania Gaviria-Cantin, María Antonia Sánchez-Romero, Marta Gibert, Alexander J Westermann, Jörg Vogel, Carlos Balsalobre
Invasion of epithelial cells by Salmonella enterica requires expression of genes located in the pathogenicity island I (SPI-1). The expression of SPI-1 genes is very tightly regulated and activated only under specific conditions. Most studies have focused on the regulatory pathways that induce SPI-1 expression. Here, we describe a new regulatory circuit involving CRP-cAMP, a widely established metabolic regulator, in silencing of SPI-1 genes under non-permissive conditions. In CRP-cAMP-deficient strains we detected a strong upregulation of SPI-1 genes in the mid-logarithmic growth phase...
June 2018: PLoS Genetics
Mengmeng Sun, Xu Feng, Zhenzhen Liu, Wenyuan Han, Yun Xiang Liang, Qunxin She
While bacteria and eukaryotes show distinct mechanisms of DNA damage response (DDR) regulation, investigation of ultraviolet (UV)-responsive expression in a few archaea did not yield any conclusive evidence for an archaeal DDR regulatory network. Nevertheless, expression of Orc1-2, an ortholog of the archaeal origin recognition complex 1/cell division control protein 6 (Orc1/Cdc6) superfamily proteins was strongly activated in Sulfolobus solfataricus and Sulfolobus acidocaldarius upon UV irradiation. Here, a series of experiments were conducted to investigate the possible functions of Orc1-2 in DNA damage repair in Sulfolobus islandicus...
June 7, 2018: Nucleic Acids Research
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