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https://www.readbyqxmd.com/read/28231449/synthetic-gene-circuits-learn-to-classify
#1
Andriy Didovyk, Lev S Tsimring
An efficient computational algorithm is developed to design microRNA-based synthetic cell classifiers and to optimize their performance.
February 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28228643/a-chemical-probe-toolbox-for-dissecting-the-cancer-epigenome
#2
REVIEW
Jake Shortt, Christopher J Ott, Ricky W Johnstone, James E Bradner
Cancer cell hallmarks are underpinned by transcriptional programmes operating in the context of a dynamic and complicit epigenomic environment. Somatic alterations of chromatin modifiers are among the most prevalent cancer perturbations. There is a pressing need for targeted chemical probes to dissect these complex, interconnected gene regulatory circuits. Validated chemical probes empower mechanistic research while providing the pharmacological proof of concept that is required to translate drug-like derivatives into therapy for cancer patients...
February 23, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28228252/complete-disruption-of-the-kainate-receptor-gene-family-results-in-corticostriatal-dysfunction-in-mice
#3
Jian Xu, John J Marshall, Herman B Fernandes, Toshihiro Nomura, Bryan A Copits, Daniele Procissi, Susumu Mori, Lei Wang, Yongling Zhu, Geoffrey T Swanson, Anis Contractor
Kainate receptors are members of the glutamate receptor family that regulate synaptic function in the brain. They modulate synaptic transmission and the excitability of neurons; however, their contributions to neural circuits that underlie behavior are unclear. To understand the net impact of kainate receptor signaling, we generated knockout mice in which all five kainate receptor subunits were ablated (5ko). These mice displayed compulsive and perseverative behaviors, including over-grooming, as well as motor problems, indicative of alterations in striatal circuits...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28227099/a-large-scale-detailed-neuronal-model-of-electrical-stimulation-of-the-dentate-gyrus-and-perforant-path-as-a-platform-for-electrode-design-and-optimization
#4
Clayton S Bingham, Kyle Loizos, Gene Yu, Andrew Gilbert, Jean-Marie Bouteiller, Dong Song, Gianluca Lazzi, Theodore W Berger, Clayton S Bingham, Kyle Loizos, Gene Yu, Andrew Gilbert, Jean-Marie Bouteiller, Dong Song, Gianluca Lazzi, Theodore W Berger, Kyle Loizos, Gene Yu, Theodore W Berger, Gianluca Lazzi, Jean-Marie Bouteiller, Clayton S Bingham, Dong Song, Andrew Gilbert
Owing to the dramatic rise in treatment of neurological disorders with electrical micro-stimulation it has become apparent that the major technological limitation in deploying effective devices lies in the process of designing efficient, safe, and outcome specific electrode arrays. The time-consuming and low-fidelity nature of gathering test data using experimental means and the immense control and flexibility of computational models, has prompted us and others to build models of electrical stimulation of neural networks that can be simulated in a computer...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226784/parameter-estimation-for-gene-regulatory-networks-a-two-stage-mcmc-bayesian-approach
#5
Niannan Xue, Wei Pan, Yike Guo, Niannan Xue, Wei Pan, Yike Guo, Wei Pan, Yike Guo, Niannan Xue
Genetic regulatory networks have emerged as a useful way to elucidate the biochemical pathways for biological functions. Yet, determination of the exact parametric forms for these models remain a major challenge. In this paper, we present a novel computational approach implemented in C++ to solve this inverse problem. This takes the form of an optimization stage first after which Bayesian filtering takes place. The key advantage of such a flexible, general and robust approach is that it provides us with a joint probability distribution of the model parameters instead of single estimates, which we can propagate to final predictions...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28223460/mechanism-of-h2s-oxidation-by-the-dissimilatory-perchlorate-reducing-microorganism-azospira-suillum-ps
#6
Misha G Mehta-Kolte, Dana Loutey, Ouwei Wang, Matthew D Youngblut, Christopher G Hubbard, Kelly M Wetmore, Mark E Conrad, John D Coates
The genetic and biochemical basis of perchlorate-dependent H2S oxidation (PSOX) was investigated in the dissimilatory perchlorate-reducing microorganism (DPRM) Azospira suillum PS (PS). Previously, it was shown that all known DPRMs innately oxidize H2S, producing elemental sulfur (S(o)). Although the process involving PSOX is thermodynamically favorable (ΔG°' = -206 kJ ⋅ mol(-1) H2S), the underlying biochemical and genetic mechanisms are currently unknown. Interestingly, H2S is preferentially utilized over physiological electron donors such as lactate or acetate although no growth benefit is obtained from the metabolism...
February 21, 2017: MBio
https://www.readbyqxmd.com/read/28221369/chemistry-based-molecular-signature-underlying-the-atypia-of-clozapine
#7
T Cardozo, E Shmelkov, K Felsovalyi, J Swetnam, T Butler, D Malaspina, S V Shmelkov
The central nervous system is functionally organized as a dynamic network of interacting neural circuits that underlies observable behaviors. At higher resolution, these behaviors, or phenotypes, are defined by the activity of a specific set of biomolecules within those circuits. Identification of molecules that govern psychiatric phenotypes is a major challenge. The only organic molecular entities objectively associated with psychiatric phenotypes in humans are drugs that induce psychiatric phenotypes and drugs used for treatment of specific psychiatric conditions...
February 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28220022/using-metaphors-to-explain-molecular-testing-to-cancer-patients
#8
Ana P M Pinheiro, Rachel H Pocock, Margie D Dixon, Walid L Shaib, Suresh S Ramalingam, Rebecca D Pentz
BACKGROUND: Molecular testing to identify targetable molecular alterations is routine practice for several types of cancer. Explaining the underlying molecular concepts can be difficult, and metaphors historically have been used in medicine to provide a common language between physicians and patients. Although previous studies have highlighted the use and effectiveness of metaphors to help explain germline genetic concepts to the general public, this study is the first to describe the use of metaphors to explain molecular testing to cancer patients in the clinical setting...
February 20, 2017: Oncologist
https://www.readbyqxmd.com/read/28219675/tcf7l2-plays-crucial-roles-in-forebrain-development-through-regulation-of-thalamic-and-habenular-neuron-identity-and-connectivity
#9
Myungsin Lee, Jiyeon Yoon, Hobeom Song, Bumwhee Lee, Lam Tri Duc, Jaeseung Yoon, Kwanghee Baek, Hans Clevers, Yongsu Jeong
The thalamus acts as a central integrator for processing and relaying sensory and motor information to and from the cerebral cortex, and the habenula plays pivotal roles in emotive decision making by modulating dopaminergic and serotonergic circuits. These neural compartments are derived from a common developmental progenitor domain, called prosomere 2, in the caudal forebrain. Thalamic and habenular neurons exhibit distinct molecular profile, neurochemical identity, and axonal circuitry. However, the mechanisms of how their progenitors in prosomere 2 give rise to these two populations of neurons and contribute to the forebrain circuitry remains unclear...
February 17, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28219373/a-new-efficient-approach-to-fit-stochastic-models-on-the-basis-of-high-throughput-experimental-data-using-a-model-of-irf7-gene-expression-as-case-study
#10
Luis U Aguilera, Christoph Zimmer, Ursula Kummer
BACKGROUND: Mathematical models are used to gain an integrative understanding of biochemical processes and networks. Commonly the models are based on deterministic ordinary differential equations. When molecular counts are low, stochastic formalisms like Monte Carlo simulations are more appropriate and well established. However, compared to the wealth of computational methods used to fit and analyze deterministic models, there is only little available to quantify the exactness of the fit of stochastic models compared to experimental data or to analyze different aspects of the modeling results...
February 20, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28218915/one-step-optogenetics-with-multifunctional-flexible-polymer-fibers
#11
Seongjun Park, Yuanyuan Guo, Xiaoting Jia, Han Kyoung Choe, Benjamin Grena, Jeewoo Kang, Jiyeon Park, Chi Lu, Andres Canales, Ritchie Chen, Yeong Shin Yim, Gloria B Choi, Yoel Fink, Polina Anikeeva
Optogenetic interrogation of neural pathways relies on delivery of light-sensitive opsins into tissue and subsequent optical illumination and electrical recording from the regions of interest. Despite the recent development of multifunctional neural probes, integration of these modalities in a single biocompatible platform remains a challenge. We developed a device composed of an optical waveguide, six electrodes and two microfluidic channels produced via fiber drawing. Our probes facilitated injections of viral vectors carrying opsin genes while providing collocated neural recording and optical stimulation...
February 20, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28218624/loss-of-microrna-7a2-induces-hypogonadotropic-hypogonadism-and-infertility
#12
Kashan Ahmed, Mary P LaPierre, Emanuel Gasser, Rémy Denzler, Yinjie Yang, Thomas Rülicke, Jukka Kero, Mathieu Latreille, Markus Stoffel
MicroRNAs (miRNAs) are negative modulators of gene expression that fine-tune numerous biological processes. miRNA loss-of-function rarely results in highly penetrant phenotypes, but rather, influences cellular responses to physiologic and pathophysiologic stresses. Here, we have reported that a single member of the evolutionarily conserved miR-7 family, miR-7a2, is essential for normal pituitary development and hypothalamic-pituitary-gonadal (HPG) function in adulthood. Genetic deletion of mir-7a2 causes infertility, with low levels of gonadotropic and sex steroid hormones, small testes or ovaries, impaired spermatogenesis, and lack of ovulation in male and female mice, respectively...
February 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28217742/piericidin-a1-blocks-yersinia-ysc-type-iii-secretion-system-needle-assembly
#13
Jessica M Morgan, Miles C Duncan, Kevin S Johnson, Andreas Diepold, Hanh Lam, Allison J Dupzyk, Lexi R Martin, Weng Ruh Wong, Judith P Armitage, Roger G Linington, Victoria Auerbuch
The type III secretion system (T3SS) is a bacterial virulence factor expressed by dozens of Gram-negative pathogens but largely absent from commensals. The T3SS is an attractive target for antimicrobial agents that may disarm pathogenic bacteria while leaving commensal populations intact. We previously identified piericidin A1 as an inhibitor of the Ysc T3SS in Yersinia pseudotuberculosis. Piericidins were first discovered as inhibitors of complex I of the electron transport chain in mitochondria and some bacteria...
January 2017: MSphere
https://www.readbyqxmd.com/read/28215559/soxc-transcription-factors-promote-contralateral-retinal-ganglion-cell-differentiation-and-axon-guidance-in-the-mouse-visual-system
#14
Takaaki Kuwajima, Célia A Soares, Austen A Sitko, Véronique Lefebvre, Carol Mason
Transcription factors control cell identity by regulating diverse developmental steps such as differentiation and axon guidance. The mammalian binocular visual circuit is comprised of projections of retinal ganglion cells (RGCs) to ipsilateral and contralateral targets in the brain. A transcriptional code for ipsilateral RGC identity has been identified, but less is known about the transcriptional regulation of contralateral RGC development. Here we demonstrate that SoxC genes (Sox4, 11, and 12) act on the progenitor-to-postmitotic transition to implement contralateral, but not ipsilateral, RGC differentiation, by binding to Hes5 and thus repressing Notch signaling...
February 14, 2017: Neuron
https://www.readbyqxmd.com/read/28215088/mechanistic-modeling-of-genetic-circuits-for-arsr-arsenic-regulation
#15
Yves Berset, Davide Merulla, Aurélie Joublin, Vassily Hatzimanikatis, Jan Roelof van der Meer
Bioreporters are living cells that generate an easily measurable signal in the presence of a chemical compound. They acquire their functionality from synthetic gene circuits, whose configuration defines the response signal and signal-to-noise ratio. Bioreporters based on the Escherichia coli ArsR system have raised significant interest for quantifying arsenic pollution, but they need to be carefully optimized to accurately work in the required low concentration range (1-10 µg arsenite L-1). In order to better understand the general functioning of ArsR-based genetic circuits, we developed a comprehensive mechanistic model that was empirically tested and validated in E...
February 19, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28213833/molecular-imaging-in-synthetic-biology-and-synthetic-biology-in-molecular-imaging
#16
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
#17
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
#18
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
#19
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
#20
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
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