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Causal Loops

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...
October 17, 2016: Journal of Clinical Investigation
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
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
Marina V Sysoeva, Lyudmila V Vinogradova, Galina D Kuznetsova, Ilya V Sysoev, Clementina M van Rijn
PURPOSE: Spike-and-wave discharges (SWDs) recorded in the cortical EEGs of WAG/Rij rats are the hallmark for absence epilepsy in this model. Although this type of epilepsy was long regarded as a form of primary generalized epilepsy, it is now recognized that there is an initiation zone - the perioral region of the somatosensory cortex. However, networks involved in spreading the seizure are not yet fully known. Previously, the dynamics of coupling between different layers of the perioral cortical region and between these zones and different thalamic nuclei was studied in time windows around the SWDs, using nonlinear Granger causality...
October 8, 2016: Epilepsy & Behavior: E&B
Miguel Aguilera, Manuel G Bedia, Xabier E Barandiaran
The hypothesis that brain organization is based on mechanisms of metastable synchronization in neural assemblies has been popularized during the last decades of neuroscientific research. Nevertheless, the role of body and environment for understanding the functioning of metastable assemblies is frequently dismissed. The main goal of this paper is to investigate the contribution of sensorimotor coupling to neural and behavioral metastability using a minimal computational model of plastic neural ensembles embedded in a robotic agent in a behavioral preference task...
2016: Frontiers in Systems Neuroscience
Fernando G Zampieri, Alexandre B Libório, Alexandre B Cavalcanti
PURPOSE OF REVIEW: To describe recent advances in the understanding of the role of fluid composition in renal outcomes in critically ill patients. RECENT FINDINGS: The debate on fluid composition is now focused in a pragmatic discussion on fluid electrolyte composition. The resurgence of this debate was propelled by several observational studies that suggested that balanced (i.e., low chloride) solutions were associated with less acute kidney injury in critically ill patients...
September 28, 2016: Current Opinion in Critical Care
Bonhee Chung
Poor subsistence farmers who live in a semi-arid area of northern Ethiopia build irrigation systems to overcome water shortages. However, there is a high risk of malaria transmission when increased standing water provides more favorable habitats for mosquito breeding. This is a serious problem because there are many barriers to malaria control measures and health care systems in the area. Using a causal loop diagram and computer simulations, the author attempted to visually illustrate positive and negative feedbacks between mosquito and human populations in the context of Simret, which is a small village located in northern Ethiopia and is generally considered a malaria-free area...
August 2016: Korean Journal of Parasitology
Jan-Christian Reil, Marcus Tauchnitz, Qinghai Tian, Mathias Hohl, Dominik Linz, Martin Oberhofer, Lars Kaestner, Gert-Hinrich Reil, Holger Thiele, Paul Steendijk, Michael Böhm, Hans-Ruprecht Neuberger, Peter Lipp
Patients with hypertension and hyperaldosteronism show an increased risk of stroke compared with patients with essential hypertension. Aim of the study was to assess the effects of aldosterone on left atrial function in rats as a potential contributor to thromboembolism. Osmotic mini-pumps delivering 1.5 μg aldosterone/h were implanted in rats subcutaneously (Aldo, n = 39; controls, n = 38). After 8 wk, left ventricular pressure-volume analysis of isolated working hearts was performed, and left atrial systolic and diastolic function was also assessed by atrial pressure-diameter loops...
October 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Congcong Li, Huabin He, An Liu, Huazhen Liu, Haibo Huang, Changzhi Zhao, Lu Jing, Juan Ni, Lilin Yin, Suqin Hu, Hui Wu, Xinyun Li, Shuhong Zhao
miR-155 has been confirmed to be a key factor in immune responses in humans and other mammals. Therefore, investigation of variations in miR-155 could be useful for understanding the differences in immunity between individuals. In this study, four SNPs in miR-155 were identified in mice (Mus musculus) and humans (Homo sapiens). In mice, the four SNPs were closely linked and formed two miR-155 haplotypes (A and B). Ten distinct types of blood parameters were associated with miR-155 expression under normal conditions...
2016: Frontiers in Immunology
Deborah A Cohen, Bing Han, Kelly R Evenson, Catherine Nagel, Thomas L McKenzie, Terry Marsh, Stephanie Williamson, Peter Harnik
BACKGROUND: Previous studies indicate that the design of streets and sidewalks can influence physical activity among residents. Park features also influence park use and park-based physical activity. Although individuals can walk on streets and sidewalks, walking loops in parks offer a setting to walk in nature and to avoid interruptions from traffic. OBJECTIVES: To describe the use of walking loops in parks and compare the number of park users and their physical activity in urban neighborhood parks with and without walking loops...
August 12, 2016: Environmental Health Perspectives
Ajaz Ahmad Bhat, Vishwanathan Mohan, Giulio Sandini, Pietro Morasso
Emerging studies indicate that several species such as corvids, apes and children solve 'The Crow and the Pitcher' task (from Aesop's Fables) in diverse conditions. Hidden beneath this fascinating paradigm is a fundamental question: by cumulatively interacting with different objects, how can an agent abstract the underlying cause-effect relations to predict and creatively exploit potential affordances of novel objects in the context of sought goals? Re-enacting this Aesop's Fable task on a humanoid within an open-ended 'learning-prediction-abstraction' loop, we address this problem and (i) present a brain-guided neural framework that emulates rapid one-shot encoding of ongoing experiences into a long-term memory and (ii) propose four task-agnostic learning rules (elimination, growth, uncertainty and status quo) that correlate predictions from remembered past experiences with the unfolding present situation to gradually abstract the underlying causal relations...
July 2016: Journal of the Royal Society, Interface
Ahmad Alhourani, Anna Korzeniewska, Thomas A Wozny, Efstathios Kondylis, Witold J Lipski, Donald Crammond, R Mark Richardson
INTRODUCTION: Beta oscillations play an important role in gating movement. Because pathological oscillatory changes in the beta band represent a hallmark of Parkinson disease (PD), tracking oscillatory changes in this band has been proposed as a marker for closed-loop stimulation. However, the dynamics of casual influences across the motor circuit during movement remain unknown. Using intracranial local field potential (LFP) recordings, we used both standard functional connectivity and event-related causality (ERC) techniques to explore these interactions...
August 2016: Neurosurgery
Melissa Rotunno, Mary L McMaster, Joseph Boland, Sara Bass, Xijun Zhang, Laurie Burdett, Belynda Hicks, Sarangan Ravichandran, Brian T Luke, Meredith Yeager, Laura Fontaine, Paula L Hyland, Alisa M Goldstein, Stephen J Chanock, Neil E Caporaso, Margaret A Tucker, Lynn R Goldin
Hodgkin lymphoma shows strong familial aggregation but no major susceptibility genes have been identified to date. The goal of this study was to identify high-penetrance variants using whole exome sequencing in 17 Hodgkin lymphoma prone families with three or more affected cases or obligate carriers (69 individuals), followed by targeted sequencing in an additional 48 smaller HL families (80 individuals). Alignment and variant calling were performed using standard methods. Dominantly segregating, rare, coding or potentially functional variants were further prioritized based on predicted deleteriousness, conservation, and potential importance in lymphoid malignancy pathways...
July 2016: Haematologica
Xiangjiu Kong, Wentao Qin, Xiaoqing Huang, Fanfang Kong, Cor D Schoen, Jie Feng, Zhongyue Wang, Hao Zhang
A rapid LAMP (loop-mediated isothermal amplification) detection method was developed on the basis of the ITS sequence of P. viticola, the major causal agent of grape downy mildew. Among the 38 fungal and oomycete species tested, DNA isolated exclusively from P. viticola resulted in a specific product after LAMP amplification. This assay had high sensitivity and was able to detect the presence of less than 33 fg of genomic DNA per 25-μL reaction within 30 min. The infected leaves may produce sporangia that serve as a secondary inoculum...
2016: Scientific Reports
Wessel van der Loo, Maria João Magalhaes, Ana Lemos de Matos, Joana Abrantes, Fumio Yamada, Pedro J Esteves
Studies of the process of pseudogenization have widened our understanding of adaptive evolutionary change. In Rabbit, an alteration at the second extra-cellular loop of the CCR5 chemokine receptor was found to be associated with the pseudogenization of one of its prime ligands, the chemokine CCL8. This relationship has raised questions about the existence of a causal link between both events, which would imply adaptive gene loss. This hypothesis is evaluated here by tracing back the history of the genetic modifications underlying the chemokine pseudogenization...
August 2016: Journal of Molecular Evolution
Lamia Wahba, Lorenzo Costantino, Frederick J Tan, Anjali Zimmer, Douglas Koshland
R loops form when transcripts hybridize to homologous DNA on chromosomes, yielding a DNA:RNA hybrid and a displaced DNA single strand. R loops impact the genome of many organisms, regulating chromosome stability, gene expression, and DNA repair. Understanding the parameters dictating R-loop formation in vivo has been hampered by the limited quantitative and spatial resolution of current genomic strategies for mapping R loops. We report a novel whole-genome method, S1-DRIP-seq (S1 nuclease DNA:RNA immunoprecipitation with deep sequencing), for mapping hybrid-prone regions in budding yeast Saccharomyces cerevisiae Using this methodology, we identified ∼800 hybrid-prone regions covering 8% of the genome...
June 1, 2016: Genes & Development
Yorka Muñoz, Carlos M Carrasco, Joaquín D Campos, Pabla Aguirre, Marco T Núñez
Mitochondrial dysfunction, iron accumulation, and oxidative damage are conditions often found in damaged brain areas of Parkinson's disease. We propose that a causal link exists between these three events. Mitochondrial dysfunction results not only in increased reactive oxygen species production but also in decreased iron-sulfur cluster synthesis and unorthodox activation of Iron Regulatory Protein 1 (IRP1), a key regulator of cell iron homeostasis. In turn, IRP1 activation results in iron accumulation and hydroxyl radical-mediated damage...
2016: Parkinson's Disease
Alexandra Lelia Dima, Marijn de Bruin, Eric Van Ganse
BACKGROUND: Whether people with asthma gain and maintain control over their condition depends not only on the availability of effective drugs, but also on multiple patient and health care professional (HCP) behaviors. Research in asthma rarely considers how these behaviors interact with each other and drug effectiveness to determine health outcomes, which may limit real-life applicability of findings. OBJECTIVE: The objective of this study was to develop a logic process model (Asthma Care Model; ACM) that explains how patient and HCP behaviors impact on the asthma care process...
September 2016: Journal of Allergy and Clinical Immunology in Practice
Jonathan A Beagan, Jennifer E Phillips-Cremins
CRISPR/Cas9 genome editing studies have recently shed new light into the causal link between the linear DNA sequence and 3-D chromatin architecture. Here we describe current models for the folding of genomes into a nested hierarchy of higher-order structures and discuss new insights into the organizing principles governing genome folding at each length scale. WIREs Syst Biol Med 2016, 8:286-299. doi: 10.1002/wsbm.1338 For further resources related to this article, please visit the WIREs website.
July 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Gustavo Nigenda, Luz María González-Robledo, Clara Juárez-Ramírez, Taghreed Adam
BACKGROUND: In 2003, Mexico's Seguro Popular de Salud (SPS), was launched as an innovative financial mechanism implemented to channel new funds to provide health insurance to 50 million Mexicans and to reduce systemic financial inequities. The objective of this article is to understand the complexity and dynamics that contributed to the adaptation of the policy in the implementation stage, how these changes occurred, and why, from a complex and adaptive systems perspective. METHODS: A complex adaptive systems (CAS) framework was used to carry out a secondary analysis of data obtained from four SPS's implementation evaluations...
2016: Implementation Science: IS
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