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https://www.readbyqxmd.com/read/28213833/molecular-imaging-in-synthetic-biology-and-synthetic-biology-in-molecular-imaging
#1
REVIEW
Assaf A Gilad, Mikhail G Shapiro
Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies...
February 17, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28212375/epilepsy-associated-gene-nedd4-2-mediates-neuronal-activity-and-seizure-susceptibility-through-ampa-receptors
#2
Jiuhe Zhu, Kwan Young Lee, Kathryn A Jewett, Heng-Ye Man, Hee Jung Chung, Nien-Pei Tsai
The neural precursor cell expressed developmentally down-regulated gene 4-2, Nedd4-2, is an epilepsy-associated gene with at least three missense mutations identified in epileptic patients. Nedd4-2 encodes a ubiquitin E3 ligase that has high affinity toward binding and ubiquitinating membrane proteins. It is currently unknown how Nedd4-2 mediates neuronal circuit activity and how its dysfunction leads to seizures or epilepsies. In this study, we provide evidence to show that Nedd4-2 mediates neuronal activity and seizure susceptibility through ubiquitination of GluA1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, (AMPAR)...
February 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28211790/flpstop-a-tool-for-conditional-gene-control-in-drosophila
#3
Yvette Erica Fisher, Helen H Yang, Jesse Isaacman-Beck, Marjorie Xie, Daryl M Gohl, Thomas R Clandinin
Manipulating gene function cell type-specifically is a common experimental goal in Drosophila research and has been central to studies of neural development, circuit computation, and behavior. However, current cell type-specific gene disruption techniques in flies often reduce gene activity incompletely or rely on cell division. Here we describe FlpStop, a generalizable tool for conditional gene disruption and rescue in post-mitotic cells. In proof-of-principle experiments, we manipulated apterous, a regulator of wing development...
February 17, 2017: ELife
https://www.readbyqxmd.com/read/28202516/modeling-the-genetic-regulation-of-cancer-metabolism-interplay-between-glycolysis-and-oxidative-phosphorylation
#4
Linglin Yu, Mingyang Lu, Dongya Jia, Jianpeng Ma, Eshel Ben-Jacob, Herbert Levine, Benny A Kaipparettu, Jose' N Onuchic
Abnormal metabolism is a hallmark of cancer, yet its regulation remains poorly understood. Cancer cells were considered to utilize primarily glycolysis for ATP production, referred to as the Warburg effect. However, recent evidence suggests that oxidative phosphorylation (OXPHOS) plays a crucial role during cancer progression. Here we utilized a systems biology approach to decipher the regulatory principle of glycolysis and OXPHOS. Integrating information from literature, we constructed a regulatory network of genes and metabolites from which we extracted a core circuit containing HIF-1, AMPK, and ROS...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28196412/mapk3-at-the-autism-linked-human-16p11-2-locus-influences-precise-synaptic-target-selection-at-drosophila-larval-neuromuscular-junctions
#5
Sang Mee Park, Hae Ryoun Park, Ji Hye Lee
Proper synaptic function in neural circuits requires precise pairings between correct pre- and post-synaptic partners. Errors in this process may underlie development of neuropsychiatric disorders, such as autism spectrum disorder (ASD). Development of ASD can be influenced by genetic factors, including copy number variations (CNVs). In this study, we focused on a CNV occurring at the 16p11.2 locus in the human genome and investigated potential defects in synaptic connectivity caused by reduced activities of genes located in this region at Drosophila larval neuromuscular junctions, a well-established model synapse with stereotypic synaptic structures...
February 15, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28195208/a-pupal-transcriptomic-screen-identifies-ral-as-a-target-of-store-operated-calcium-entry-in-drosophila-neurons
#6
Shlesha Richhariya, Siddharth Jayakumar, Katharine Abruzzi, Michael Rosbash, Gaiti Hasan
Transcriptional regulation by Store-operated Calcium Entry (SOCE) is well studied in non-excitable cells. However, the role of SOCE has been poorly documented in neuronal cells with more complicated calcium dynamics. Previous reports demonstrated a requirement for SOCE in neurons that regulate Drosophila flight bouts. We refine this requirement temporally to the early pupal stage and use RNA-sequencing to identify SOCE mediated gene expression changes in the developing Drosophila pupal nervous system. Down regulation of dStim, the endoplasmic reticular calcium sensor and a principal component of SOCE in the nervous system, altered the expression of 131 genes including Ral, a small GTPase...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28191902/dynamic-regulation-of-metabolic-flux-in-engineered-bacteria-using-a-pathway-independent-quorum-sensing-circuit
#7
Apoorv Gupta, Irene M Brockman Reizman, Christopher R Reisch, Kristala L J Prather
Metabolic engineering of microorganisms to produce desirable products on an industrial scale can result in unbalanced cellular metabolic networks that reduce productivity and yield. Metabolic fluxes can be rebalanced using dynamic pathway regulation, but few broadly applicable tools are available to achieve this. We present a pathway-independent genetic control module that can be used to dynamically regulate the expression of target genes. We apply our module to identify the optimal point to redirect glycolytic flux into heterologous engineered pathways in Escherichia coli, resulting in titers of myo-inositol increased 5...
February 13, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28186666/impaired-intracortical-transmission-in-g2019s-leucine-rich-repeat-kinase-parkinson-patients
#8
Viviana Ponzo, Francesco Di Lorenzo, Livia Brusa, Tommaso Schirinzi, Stefania Battistini, Claudia Ricci, Manolo Sambucci, Carlo Caltagirone, Giacomo Koch
OBJECTIVES: A mutation in leucine-rich repeat kinase 2 is the most common cause of hereditary Parkinson's disease (PD), yet the neural mechanisms and the circuitry potentially involved are poorly understood. METHODS: We used different transcranial magnetic stimulation protocols to explore in the primary motor cortex the activity of intracortical circuits and cortical plasticity (long-term potentiation) in patients with the G2019S leucine-rich repeat kinase 2 gene mutation when compared with idiopathic PD patients and age-matched healthy subjects...
February 10, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28179641/shank-proteins-roles-at-the-synapse-and-in-autism-spectrum-disorder
#9
REVIEW
Patricia Monteiro, Guoping Feng
Several large-scale genomic studies have supported an association between cases of autism spectrum disorder and mutations in the genes SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2 and SHANK3, which encode a family of postsynaptic scaffolding proteins that are present at glutamatergic synapses in the CNS. An evaluation of human genetic data, as well as of in vitro and in vivo animal model data, may allow us to understand how disruption of SHANK scaffolding proteins affects the structure and function of neural circuits and alters behaviour...
March 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28179143/how-s-the-flu-getting-through-landscape-genetics-suggests-both-humans-and-birds-spread-h5n1-in-egypt
#10
Sean G Young, Margaret Carrel, Andrew Kitchen, George P Malanson, James Tamerius, Mohamad Ali, Ghazi Kayali
First introduced to Egypt in 2006, H5N1 highly pathogenic avian influenza has resulted in the death of millions of birds and caused over 350 infections and at least 117 deaths in humans. After a decade of viral circulation, outbreaks continue to occur and diffusion mechanisms between poultry farms remain unclear. Using landscape genetics techniques, we identify the distance models most strongly correlated with the genetic relatedness of the viruses, suggesting the most likely methods of viral diffusion within Egyptian poultry...
February 4, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28178750/prolonged-maternal-separation-attenuates-bdnf-erk-signaling-correlated-with-spine-formation-in-the-hippocampus-during-early-brain-development
#11
Ken-Ichi Ohta, Shingo Suzuki, Katsuhiko Warita, Tomohiro Kaji, Takashi Kusaka, Takanori Miki
Maternal separation (MS) is known to affect hippocampal function such as learning and memory, yet the molecular mechanism remains unknown. We hypothesized that these impairments are attributed to abnormities of neural circuit formation by MS, and focused on brain-derived neurotrophic factor (BDNF) as key factor because BDNF signaling has an essential role in synapse formation during early brain development. Using rat offspring exposed to MS for 6 h/day during postnatal days (PD) 2-20, we estimated BDNF signaling in the hippocampus during brain development...
February 8, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28170426/chronic-social-stress-in-pigs-impairs-intestinal-barrier-and-nutrient-transporter-function-and-alters-neuro-immune-mediator-and-receptor-expression
#12
Yihang Li, Zehe Song, Katelyn A Kerr, Adam J Moeser
Psychosocial stress is a major factor driving gastrointestinal (GI) pathophysiology and disease susceptibility in humans and animals. The mechanisms governing susceptibility to stress-induced GI disease remain poorly understood. In the present study, we investigated the influence of chronic social stress (CSS) in pigs, induced by 7 d of chronic mixing/crowding stress, on intestinal barrier and nutrient transport function, corticotropin releasing factor (CRF) signaling and immunological responses. Results from this study showed that CSS resulted in a significant impairment of ileal and colonic barrier function indicated by reduced transepithelial electrical resistance (TER) in the ileum and increased FD4 flux in the ileum (by 0...
2017: PloS One
https://www.readbyqxmd.com/read/28167863/biomechanical-cell-regulatory-networks-as-complex-adaptive-systems-in-relation-to-cancer
#13
REVIEW
Liviu Feller, Razia Abdool Gafaar Khammissa, Johan Lemmer
Physiological structure and function of cells are maintained by ongoing complex dynamic adaptive processes in the intracellular molecular pathways controlling the overall profile of gene expression, and by genes in cellular gene regulatory circuits. Cytogenetic mutations and non-genetic factors such as chronic inflammation or repetitive trauma, intrinsic mechanical stresses within extracellular matrix may induce redirection of gene regulatory circuits with abnormal reactivation of embryonic developmental programmes which can now drive cell transformation and cancer initiation, and later cancer progression and metastasis...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28167805/transgenic-line-for-the-identification-of-cholinergic-release-sites-in-drosophila-melanogaster
#14
Katarina Pankova, Alexander Borst
The identification of neurotransmitter type used by a neuron is important for the functional dissection of neuronal circuits. In the model organism Drosophila melanogaster, several methods for discerning the neurotransmitter systems are available. Here, we expanded the toolbox for the identification of cholinergic neurons by generating a new line FRT-STOP-FRT-VAChT::HA that is a conditional tagged knock-in of the VAChT gene in its endogenous locus. Importantly, in comparison to already available tools for the detection of cholinergic neurons, the FRT-STOP-FRT-VAChT::HA allele also allows for identification of the subcellular localization of the cholinergic presynaptic release sites in a cell-specific manner...
February 6, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28167162/disparate-response-to-microoxia-and-nitrogen-oxides-of-the-bradyrhizobium-japonicum-napedabc-nirk-and-norcbqd-denitrification-genes
#15
Emilio Bueno, Eloy F Robles, María J Torres, Tino Krell, Eulogio J Bedmar, María J Delgado, Socorro Mesa
Expression of the Bradyrhizobium japonicum napEDABC, nirK and norCBQD denitrification genes requires low oxygen (O2) tension and nitrate (NO3(-)), through a regulatory network comprised of two coordinated cascades, FixLJ-FixK2-NnrR and RegSR-NifA. To precisely understand how these signals are integrated in the FixLJ-FixK2-NnrR circuit, we analyzed β-Galactosidase activities from napE-lacZ, nirK-lacZ and norC-lacZ fusions and performed analyses of NapC and NorC levels as well as periplasmic nitrate reductase (Nap) activity, in B...
February 3, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28166866/genetic-control-of-encoding-strategy-in-a-food-sensing-neural-circuit
#16
Giovanni Diana, Dhaval S Patel, Eugeni V Entchev, Mei Zhan, Hang Lu, QueeLim Ch'ng
Neuroendocrine circuits encode environmental information via changes in gene expression and other biochemical activities to regulate physiological responses. Previously, we showed that daf-7 TGFβ and tph-1 tryptophan hydroxylase expression in specific neurons encode food abundance to modulate lifespan in Caenorhabditis elegans, and uncovered cross- and self-regulation among these genes (Entchev et al., 2015). Here, we now extend these findings by showing that these interactions between daf-7 and tph-1 regulate redundancy and synergy among neurons in food encoding through coordinated control of circuit-level signal and noise properties...
February 7, 2017: ELife
https://www.readbyqxmd.com/read/28163913/where-does-axon-guidance-lead-us
#17
REVIEW
Esther Stoeckli
During neural circuit formation, axons need to navigate to their target cells in a complex, constantly changing environment. Although we most likely have identified most axon guidance cues and their receptors, we still cannot explain the molecular background of pathfinding for any subpopulation of axons. We lack mechanistic insight into the regulation of interactions between guidance receptors and their ligands. Recent developments in the field of axon guidance suggest that the regulation of surface expression of guidance receptors comprises transcriptional, translational, and post-translational mechanisms, such as trafficking of vesicles with specific cargos, protein-protein interactions, and specific proteolysis of guidance receptors...
2017: F1000Research
https://www.readbyqxmd.com/read/28158178/dynamic-maternal-gradients-control-timing-and-shift-rates-for-drosophila-gap-gene-expression
#18
Berta Verd, Anton Crombach, Johannes Jaeger
Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded by bicoid (bcd) and caudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern...
February 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28155242/sensory-neuron-regulation-of-gastrointestinal-inflammation-and-bacterial-host-defence
#19
N Y Lai, K Mills, I M Chiu
Sensory neurons in the gastrointestinal tract have multifaceted roles in maintaining homeostasis, detecting danger and initiating protective responses. The gastrointestinal tract is innervated by three types of sensory neurons: dorsal root ganglia, nodose/jugular ganglia and intrinsic primary afferent neurons. Here, we examine how these distinct sensory neurons and their signal transducers participate in regulating gastrointestinal inflammation and host defence. Sensory neurons are equipped with molecular sensors that enable neuronal detection of diverse environmental signals including thermal and mechanical stimuli, inflammatory mediators and tissue damage...
February 2, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28153094/a-synthetic-biology-inspired-therapeutic-strategy-for-targeting-and-treating-hepatogenous-diabetes
#20
Shuai Xue, Jianli Yin, Jiawei Shao, Yuanhuan Yu, Linfeng Yang, Yidan Wang, Mingqi Xie, Martin Fussenegger, Haifeng Ye
Hepatogenous diabetes is a complex disease that is typified by the simultaneous presence of type 2 diabetes and many forms of liver disease. The chief pathogenic determinant in this pathophysiological network is insulin resistance (IR), an asymptomatic disease state in which impaired insulin signaling in target tissues initiates a variety of organ dysfunctions. However, pharmacotherapies targeting IR remain limited and are generally inapplicable for liver disease patients. Oleanolic acid (OA) is a plant-derived triterpenoid that is frequently used in Chinese medicine as a safe but slow-acting treatment in many liver disorders...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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