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June 2010

An important goal of computational approaches in aging is to develop integrated systems models, predicting progression of aging phenotypes grounded on molecular mechanisms. The authors assemble a rule-based, fuzzy-logic cell systems model that considers the interplay of damage, metabolism, and stress signaling by positive and negative feedback-loop motifs. This artistic montage, which shows part of the network model on the left and a simulation outcome on the right, reflects the ability to investigate, rapidly and repeatedly, complex and interlocked molecular mechanisms progressing over an entire lifespan (see Kriete et al., doi:10.1371/journal.pcbi.1000820).

Image Credit: Andres Kriete

Message from ISCB

2010 ISCB Overton Prize Awarded to Steven E. Brenner

BJ Morrison McKay, Clare Sansom

Education

Perspective

The Roots of Bioinformatics

David B. Searls

Research Articles

Constraint-Based Model of Shewanella oneidensis MR-1 Metabolism: A Tool for Data Analysis and Hypothesis Generation

Grigoriy E. Pinchuk, Eric A. Hill, Oleg V. Geydebrekht, Jessica De Ingeniis, Xiaolin Zhang, Andrei Osterman, James H. Scott, Samantha B. Reed, Margaret F. Romine, Allan E. Konopka, Alexander S. Beliaev, Jim K. Fredrickson, Jennifer L. Reed

Computational Prediction and Experimental Assessment of Secreted/Surface Proteins from Mycobacterium tuberculosis H37Rv

Carolina Vizcaíno, Daniel Restrepo-Montoya, Diana Rodríguez, Luis F. Niño, Marisol Ocampo, Magnolia Vanegas, María T. Reguero, Nora L. Martínez, Manuel E. Patarroyo, Manuel A. Patarroyo

Slope-Based Stochastic Resonance: How Noise Enables Phasic Neurons to Encode Slow Signals

Yan Gai, Brent Doiron, John Rinzel

Mammalian Sleep Dynamics: How Diverse Features Arise from a Common Physiological Framework

Andrew J. K. Phillips, Peter A. Robinson, David J. Kedziora, Romesh G. Abeysuriya

Multiscale Coarse-Graining of the Protein Energy Landscape

Ronald D. Hills Jr, Lanyuan Lu, Gregory A. Voth

Plato's Cave Algorithm: Inferring Functional Signaling Networks from Early Gene Expression Shadows

Yishai Shimoni, Marc Y. Fink, Soon-gang Choi, Stuart C. Sealfon

The 20S Proteasome Splicing Activity Discovered by SpliceMet

Juliane Liepe, Michele Mishto, Kathrin Textoris-Taube, Katharina Janek, Christin Keller, Petra Henklein, Peter Michael Kloetzel, Alexey Zaikin

Nonlinearity of Mechanochemical Motions in Motor Proteins

Yuichi Togashi, Toshio Yanagida, Alexander S. Mikhailov

NeuroML: A Language for Describing Data Driven Models of Neurons and Networks with a High Degree of Biological Detail

Padraig Gleeson, Sharon Crook, Robert C. Cannon, Michael L. Hines, Guy O. Billings, Matteo Farinella, Thomas M. Morse, Andrew P. Davison, Subhasis Ray, Upinder S. Bhalla, Simon R. Barnes, Yoana D. Dimitrova, R. Angus Silver

Revisiting Date and Party Hubs: Novel Approaches to Role Assignment in Protein Interaction Networks

Sumeet Agarwal, Charlotte M. Deane, Mason A. Porter, Nick S. Jones

Fast- or Slow-inactivated State Preference of Na+ Channel Inhibitors: A Simulation and Experimental Study

Robert Karoly, Nora Lenkey, Andras O. Juhasz, E. Sylvester Vizi, Arpad Mike

A Cell-Based Model for Quorum Sensing in Heterogeneous Bacterial Colonies

Pontus Melke, Patrik Sahlin, Andre Levchenko, Henrik Jönsson

Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses

Andres Kriete, William J. Bosl, Glenn Booker

Enhancement of Transport Selectivity through Nano-Channels by Non-Specific Competition

Anton Zilman, Stefano Di Talia, Tijana Jovanovic-Talisman, Brian T. Chait, Michael P. Rout, Marcelo O. Magnasco

Functional Rotation of the Transporter AcrB: Insights into Drug Extrusion from Simulations

Robert Schulz, Attilio V. Vargiu, Francesca Collu, Ulrich Kleinekathöfer, Paolo Ruggerone

The Organization of Local and Distant Functional Connectivity in the Human Brain

Jorge Sepulcre, Hesheng Liu, Tanveer Talukdar, Iñigo Martincorena, B. T. Thomas Yeo, Randy L. Buckner

Polarizable Water Model for the Coarse-Grained MARTINI Force Field

Semen O. Yesylevskyy, Lars V. Schäfer, Durba Sengupta, Siewert J. Marrink

Does Mutational Robustness Inhibit Extinction by Lethal Mutagenesis in Viral Populations?

Eamon B. O'Dea, Thomas E. Keller, Claus O. Wilke

Combinatorial Gene Regulation Using Auto-Regulation

Rutger Hermsen, Bas Ursem, Pieter Rein ten Wolde

Optimal Workloop Energetics of Muscle-Actuated Systems: An Impedance Matching View

Waleed A. Farahat, Hugh M. Herr

Maturation of GABAergic Inhibition Promotes Strengthening of Temporally Coherent Inputs among Convergent Pathways

Sandra J. Kuhlman, Jiangteng Lu, Matthew S. Lazarus, Z. Josh Huang

Expansion of the Protein Repertoire in Newly Explored Environments: Human Gut Microbiome Specific Protein Families

Kyle Ellrott, Lukasz Jaroszewski, Weizhong Li, John C. Wooley, Adam Godzik

Characterization of Growth and Metabolism of the Haloalkaliphile Natronomonas pharaonis

Orland Gonzalez, Tanja Oberwinkler, Locedie Mansueto, Friedhelm Pfeiffer, Eduardo Mendoza, Ralf Zimmer, Dieter Oesterhelt

Optimality of Mutation and Selection in Germinal Centers

Jingshan Zhang, Eugene I. Shakhnovich

Symmetric Allosteric Mechanism of Hexameric Escherichia coli Arginine Repressor Exploits Competition between L-Arginine Ligands and Resident Arginine Residues

Rebecca Strawn, Milan Melichercik, Michael Green, Thomas Stockner, Jannette Carey, Rüdiger Ettrich

Achieving Optimal Growth through Product Feedback Inhibition in Metabolism

Sidhartha Goyal, Jie Yuan, Thomas Chen, Joshua D. Rabinowitz, Ned S. Wingreen

Bistable, Irregular Firing and Population Oscillations in a Modular Attractor Memory Network

Mikael Lundqvist, Albert Compte, Anders Lansner