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Causal Loops

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https://www.readbyqxmd.com/read/27997825/slit-robo-repulsive-signaling-extrudes-tumorigenic-cells-from-epithelia
#1
John Vaughen, Tatsushi Igaki
Cells dynamically interact throughout animal development to coordinate growth and deter disease. For example, cell-cell competition weeds out aberrant cells to enforce homeostasis. In Drosophila, tumorigenic cells mutant for the cell polarity gene scribble (scrib) are actively eliminated from epithelia when surrounded by wild-type cells. While scrib cell elimination depends critically on JNK signaling, JNK-dependent cell death cannot sufficiently explain scrib cell extirpation. Thus, how JNK executed cell elimination remained elusive...
December 19, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27967156/random-holographic-large-worlds-with-emergent-dimensions
#2
Carlo A Trugenberger
I propose a random network model governed by a Gaussian weight corresponding to Ising link antiferromagnetism as a model for emergent quantum space-time. In this model, discrete space is fundamental, not a regularization; its spectral dimension d_{s} is not a model input but is, rather, completely determined by the antiferromagnetic coupling constant. Perturbative terms suppressing triangles and favoring squares lead to locally Euclidean ground states that are Ricci flat "large worlds" with power-law extension...
November 2016: Physical Review. E
https://www.readbyqxmd.com/read/27957850/comparative-toxicogenomic-responses-to-the-flame-retardant-mitp-in-developing-zebrafish
#3
Derik E Haggard, Siba R Das, Robert L Tanguay
Monosubstituted isopropylated triaryl phosphate (mITP) is a major component of Firemaster 550, an additive flame retardant mixture commonly used in polyurethane foams. Developmental toxicity studies in zebrafish established mITP as the most toxic component of FM 550, which causes pericardial edema and heart looping failure. Mechanistic studies showed that mITP is an aryl hydrocarbon receptor (AhR) ligand; however, the cardiotoxic effects of mITP were independent of the AhR. We performed comparative whole genome transcriptomics in wild-type and ahr2(hu3335) zebrafish, which lack functional ahr2, to identify transcriptional signatures causally involved in the mechanism of mITP-induced cardiotoxicity...
December 13, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27956748/association-of-rare-missense-variants-in-the-second-intracellular-loop-of-nav1-7-sodium-channels-with-familial-autism
#4
M Rubinstein, A Patowary, I B Stanaway, E McCord, R R Nesbitt, M Archer, T Scheuer, D Nickerson, W H Raskind, E M Wijsman, R Bernier, W A Catterall, Z Brkanac
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder often accompanied by intellectual disability, language impairment and medical co-morbidities. The heritability of autism is high and multiple genes have been implicated as causal. However, most of these genes have been identified in de novo cases. To further the understanding of familial autism, we performed whole-exome sequencing on five families in which second- and third-degree relatives were affected. By focusing on novel and protein-altering variants, we identified a small set of candidate genes...
December 13, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27942761/hand1-loss-of-function-mutation-causes-tetralogy-of-fallot
#5
Juan Wang, Xiao-Qing Hu, Yu-Han Guo, Jian-Yun Gu, Jia-Hong Xu, Yan-Jie Li, Ning Li, Xiao-Xiao Yang, Yi-Qing Yang
As the most prevalent form of birth defect in humans worldwide, congenital heart disease (CHD) is responsible for substantial morbidity and is still the leading cause of birth defect-related demises. Increasing evidence demonstrates that genetic defects play an important role in the pathogenesis of CHD, and mutations in multiple genes, especially in those coding for cardiac core transcription factors, have been causally linked to various CHDs. Nevertheless, CHD is a genetically heterogeneous disease and the genetic determinants underpinning CHD in an overwhelming majority of patients remain elusive...
December 10, 2016: Pediatric Cardiology
https://www.readbyqxmd.com/read/27933079/small-rnas-from-bemisia-tabaci-are-transferred-to-solanum-lycopersicum-phloem-during-feeding
#6
Paula J M van Kleeff, Marc Galland, Robert C Schuurink, Petra M Bleeker
The phloem-feeding whitefly Bemisia tabaci is a serious pest to a broad range of host plants, including many economically important crops such as tomato. These insects serve as a vector for various devastating plant viruses. It is known that whiteflies are capable of manipulating host-defense responses, potentially mediated by effector molecules in the whitefly saliva. We hypothesized that, beside putative effector proteins, small RNAs (sRNA) are delivered by B. tabaci into the phloem, where they may play a role in manipulating host plant defenses...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27926442/intrinsic-motivation-curiosity-and-learning-theory-and-applications-in-educational-technologies
#7
P-Y Oudeyer, J Gottlieb, M Lopes
This chapter studies the bidirectional causal interactions between curiosity and learning and discusses how understanding these interactions can be leveraged in educational technology applications. First, we review recent results showing how state curiosity, and more generally the experience of novelty and surprise, can enhance learning and memory retention. Then, we discuss how psychology and neuroscience have conceptualized curiosity and intrinsic motivation, studying how the brain can be intrinsically rewarded by novelty, complexity, or other measures of information...
2016: Progress in Brain Research
https://www.readbyqxmd.com/read/27906524/the-development-of-autism-spectrum-disorders-variability-and-causal-complexity
#8
REVIEW
Robert H Wozniak, Nina B Leezenbaum, Jessie B Northrup, Kelsey L West, Jana M Iverson
The autism spectrum is highly variable, both behaviorally and neurodevelopmentally. Broadly speaking, four related factors contribute to this variability: (1) genetic processes, (2) environmental events, (3) gene × environment interactions, and (4) developmental factors. Given the complexity of the relevant processes, it appears unlikely that autism spectrum atypicalities can be attributed to any one causal mechanism. Rather, the development of neural atypicality reflects an interaction of genetic and environmental risk factors...
January 2017: Wiley Interdisciplinary Reviews. Cognitive Science
https://www.readbyqxmd.com/read/27895572/plastic-changes-in-human-motor-cortical-output-induced-by-random-but-not-closed-loop-peripheral-stimulation-the-curse-of-causality
#9
Kenneth I Brown, Elizabeth R Williams, Felipe de Carvalho, Stuart N Baker
Previous work showed that repetitive peripheral nerve stimulation can induce plastic changes in motor cortical output. Triggering electrical stimulation of central structures from natural activity can also generate plasticity. In this study, we tested whether triggering peripheral nerve stimulation from muscle activity would likewise induce changes in motor output. We developed a wearable electronic device capable of recording electromyogram (EMG) and delivering electrical stimulation under closed-loop control...
2016: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/27881959/effective-connectivity-within-the-mesocorticolimbic-system-during-resting-state-in-cocaine-users
#10
Suchismita Ray, Xin Di, Bharat B Biswal
Objective: Although effective connectivity between brain regions has been examined in cocaine users during tasks, no effective connectivity study has been conducted on cocaine users during resting-state. In the present functional magnetic resonance imaging study, we examined effective connectivity in resting-brain, between the brain regions within the mesocorticolimbic dopamine system, implicated in reward and motivated behavior, while the chronic cocaine users and controls took part in a resting-state scan by using a spectral Dynamic causal modeling (spDCM) approach...
2016: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/27862484/%C3%AE-1-adrenoceptor-autoantibodies-increase-the-susceptibility-to-ventricular-arrhythmias-involving-abnormal-repolarization-in-guinea-pigs
#11
Yu-Hui Zhao, Hai-Xia Huang, Ping Liu, Yun-Hui Du, Peng Wang, Wen Wang, Ye Wu, Li Wang, Chang-Sheng Ma, Hui-Rong Liu
What is the central question of this study? High titres of autoantibodies against the second extracellular loop of the β1 -adrenergic receptor (β1 -AAs) can be detected in the sera of patients with ventricular arrhythmias, but a causal relationship between β1 -AAs and ventricular arrhythmias has not been established. What is the main finding and its importance? Monoclonal β1 -AAs (β1 -AR mAbs) were used in the experiments. We showed that β1 -AR mAbs increased susceptibility to ventricular arrhythmias and induced repolarization abnormalities...
January 1, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/27861577/identifying-causal-genes-at-the-multiple-sclerosis-associated-region-6q23-using-capture-hi-c
#12
Paul Martin, Amanda McGovern, Jonathan Massey, Stefan Schoenfelder, Kate Duffus, Annie Yarwood, Anne Barton, Jane Worthington, Peter Fraser, Stephen Eyre, Gisela Orozco
BACKGROUND: The chromosomal region 6q23 has been found to be associated with multiple sclerosis (MS) predisposition through genome wide association studies (GWAS). There are four independent single nucleotide polymorphisms (SNPs) associated with MS in this region, which spans around 2.5 Mb. Most GWAS variants associated with complex traits, including these four MS associated SNPs, are non-coding and their function is currently unknown. However, GWAS variants have been found to be enriched in enhancers and there is evidence that they may be involved in transcriptional regulation of their distant target genes through long range chromatin looping...
2016: PloS One
https://www.readbyqxmd.com/read/27859579/sixty-hertz-stimulation-improves-bradykinesia-and-amplifies-subthalamic-low-frequency-oscillations
#13
REVIEW
Zack Blumenfeld, Mandy Miller Koop, Thomas E Prieto, Lauren A Shreve, Anca Velisar, Emma J Quinn, Megan H Trager, Helen Brontë-Stewart
BACKGROUND: The objective of this study was to investigate the hypothesis that attenuation of subthalamic nucleus (STN) alpha-/beta-band oscillations is causal to improvement in bradykinesia. METHODS: STN local field potentials from a sensing neurostimulator (Activa(®) PC+S; Medtronic, Inc.) and kinematics from wearable sensors were recorded simultaneously during 60- and 140-Hz deep brain stimulation (DBS) in 9 freely moving PD subjects (15 STNs) performing repetitive wrist flexion-extension...
November 8, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27835976/an-integrated-risk-and-vulnerability-assessment-framework-for-climate-change-and-malaria-transmission-in-east-africa
#14
Esther Achieng Onyango, Oz Sahin, Alex Awiti, Cordia Chu, Brendan Mackey
BACKGROUND: Malaria is one of the key research concerns in climate change-health relationships. Numerous risk assessments and modelling studies provide evidence that the transmission range of malaria will expand with rising temperatures, adversely impacting on vulnerable communities in the East African highlands. While there exist multiple lines of evidence for the influence of climate change on malaria transmission, there is insufficient understanding of the complex and interdependent factors that determine the risk and vulnerability of human populations at the community level...
November 11, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27829840/antioxidant-functions-of-the-aryl-hydrocarbon-receptor
#15
REVIEW
Cornelia Dietrich
The aryl hydrocarbon receptor (AhR) is a transcription factor belonging to the basic helix-loop-helix/PER-ARNT-SIM family. It is activated by a variety of ligands, such as environmental contaminants like polycyclic aromatic hydrocarbons or dioxins, but also by naturally occurring compounds and endogenous ligands. Binding of the ligand leads to dimerization of the AhR with aryl hydrocarbon receptor nuclear translocator (ARNT) and transcriptional activation of several xenobiotic phase I and phase II metabolizing enzymes...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27799070/capture-hi-c-identifies-a-novel-causal-gene-il20ra-in-the-pan-autoimmune-genetic-susceptibility-region-6q23
#16
Amanda McGovern, Stefan Schoenfelder, Paul Martin, Jonathan Massey, Kate Duffus, Darren Plant, Annie Yarwood, Arthur G Pratt, Amy E Anderson, John D Isaacs, Julie Diboll, Nishanthi Thalayasingam, Caroline Ospelt, Anne Barton, Jane Worthington, Peter Fraser, Stephen Eyre, Gisela Orozco
BACKGROUND: The identification of causal genes from genome-wide association studies (GWAS) is the next important step for the translation of genetic findings into biologically meaningful mechanisms of disease and potential therapeutic targets. Using novel chromatin interaction detection techniques and allele specific assays in T and B cell lines, we provide compelling evidence that redefines causal genes at the 6q23 locus, one of the most important loci that confers autoimmunity risk...
November 1, 2016: Genome Biology
https://www.readbyqxmd.com/read/27788224/quantifying-a-systems-map-network-analysis-of-a-childhood-obesity-causal-loop-diagram
#17
Jaimie McGlashan, Michael Johnstone, Doug Creighton, Kayla de la Haye, Steven Allender
Causal loop diagrams developed by groups capture a shared understanding of complex problems and provide a visual tool to guide interventions. This paper explores the application of network analytic methods as a new way to gain quantitative insight into the structure of an obesity causal loop diagram to inform intervention design. Identification of the structural features of causal loop diagrams is likely to provide new insights into the emergent properties of complex systems and analysing central drivers has the potential to identify leverage points...
2016: PloS One
https://www.readbyqxmd.com/read/27760050/insulin-receptor-thr1160-phosphorylation-mediates-lipid-induced-hepatic-insulin-resistance
#18
Max C Petersen, Anila K Madiraju, Brandon M Gassaway, Michael Marcel, Ali R Nasiri, Gina Butrico, Melissa J Marcucci, Dongyan Zhang, Abudukadier Abulizi, Xian-Man Zhang, William Philbrick, Stevan R Hubbard, Michael J Jurczak, Varman T Samuel, Jesse Rinehart, Gerald I Shulman
Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D), but whether NAFLD plays a causal role in the pathogenesis of T2D is uncertain. One proposed mechanism linking NAFLD to hepatic insulin resistance involves diacylglycerol-mediated (DAG-mediated) activation of protein kinase C-ε (PKCε) and the consequent inhibition of insulin receptor (INSR) kinase activity. However, the molecular mechanism underlying PKCε inhibition of INSR kinase activity is unknown. Here, we used mass spectrometry to identify the phosphorylation site Thr1160 as a PKCε substrate in the functionally critical INSR kinase activation loop...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27757231/emergency-department-crowding-in-singapore-insights-from-a-systems-thinking-approach
#19
Lukas K Schoenenberger, Steffen Bayer, John P Ansah, David B Matchar, Rajagopal L Mohanavalli, Sean Sw Lam, Marcus Eh Ong
OBJECTIVES: Emergency Department crowding is a serious and international health care problem that seems to be resistant to most well intended but often reductionist policy approaches. In this study, we examine Emergency Department crowding in Singapore from a systems thinking perspective using causal loop diagramming to visualize the systemic structure underlying this complex phenomenon. Furthermore, we evaluate the relative impact of three different policies in reducing Emergency Department crowding in Singapore: introduction of geriatric emergency medicine, expansion of emergency medicine training, and implementation of enhanced primary care...
2016: SAGE Open Medicine
https://www.readbyqxmd.com/read/27754484/modulation-of-motor-inhibition-by-subthalamic-stimulation-in-obsessive-compulsive-disorder
#20
A Kibleur, G Gras-Combe, D Benis, J Bastin, T Bougerol, S Chabardès, M Polosan, O David
High-frequency deep brain stimulation of the subthalamic nucleus can be used to treat severe obsessive-compulsive disorders that are refractory to conventional treatments. The mechanisms of action of this approach possibly rely on the modulation of associative-limbic subcortical-cortical loops, but remain to be fully elucidated. Here in 12 patients, we report the effects of high-frequency stimulation of the subthalamic nucleus on behavior, and on electroencephalographic responses and inferred effective connectivity during motor inhibition processes involved in the stop signal task...
October 18, 2016: Translational Psychiatry
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