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Records with Subject: Biosystems
Showing records 1 to 25 of 33. [First] Page: 1 2 Last
Prospecting for Oleaginous and Robust Chlorella spp. for Coal-Fired Flue-Gas-Mediated Biodiesel Production
Bohwa Kim, Ramasamy Praveenkumar, Eunji Choi, Kyubock Lee, Sang Goo Jeon, You-Kwan Oh
September 21, 2018 (v1)
Subject: Biosystems
Keywords: biodiesel property, Chlorella, coal-fired flue-gas, mixotrophic cultivation, screening
Prospecting for robust and high-productivity strains is a strategically important step in the microalgal biodiesel process. In this study, 30 local strains of Chlorella were evaluated in photobioreactors for biodiesel production using coal-fired flue-gas. Three strains (M082, M134, and KR-1) were sequentially selected based on cell growth, lipid content, and fatty acid composition under autotrophic and mixotrophic conditions. Under autotrophic conditions, M082 and M134 showed comparable lipid contents (ca. 230 mg FAME [fatty acid methyl esters derived from microalgal lipids]/g cell) and productivities (ca. 40 mg FAME/L·d) versus a reference strain (KR-1) outdoors with actual flue-gas (CO₂, 13%). Interestingly, under mixotrophic conditions, M082 demonstrated, along with maximal lipid content (397 mg FAME/g cell), good tolerance to high temperature (40 °C). Furthermore, the fatty acid methyl esters met important international standards under all of the tested culture conditions. Thus, it... [more]
Dynamic Sequence Specific Constraint-Based Modeling of Cell-Free Protein Synthesis
David Dai, Nicholas Horvath, Jeffrey Varner
August 28, 2018 (v1)
Subject: Biosystems
Keywords: cell-free protein synthesis, dynamic constraint-based modeling, systems biology
Cell-free protein expression has emerged as an important approach in systems and synthetic biology, and a promising technology for personalized point of care medicine. Cell-free systems derived from crude whole cell extracts have shown remarkable utility as a protein synthesis technology. However, if cell-free platforms for on-demand biomanufacturing are to become a reality, the performance limits of these systems must be defined and optimized. Toward this goal, we modeled E. coli cell-free protein expression using a sequence specific dynamic constraint-based approach in which metabolite measurements were directly incorporated into the flux estimation problem. A cell-free metabolic network was constructed by removing growth associated reactions from the iAF1260 reconstruction of K-12 MG1655 E. coli. Sequence specific descriptions of transcription and translation processes were then added to this metabolic network to describe protein production. A linear programming problem was then sol... [more]
The Role of Immune Response in Optimal HIV Treatment Interventions
Hernán Darío Toro-Zapata, Angélica Caicedo-Casso, Sunmi Lee
August 28, 2018 (v1)
Subject: Biosystems
Keywords: anti-retroviral treatment, cytotoxic immune response, HIV transmission dynamics within a host, optimal control theory
A mathematical model for the transmission dynamics of human immunodeficiency virus (HIV) within a host is developed. Our model focuses on the roles of immune response cells or cytotoxic lymphocytes (CTLs). The model includes active and inactive cytotoxic immune cells. The basic reproduction number and the global stability of the virus free equilibrium is carried out. The model is modified to include anti-retroviral treatment interventions and the controlled reproduction number is explored. Their effects on the HIV infection dynamics are investigated. Two different disease stage scenarios are assessed: early-stage and advanced-stage of the disease. Furthermore, optimal control theory is employed to enhance healthy CD4+ T cells, active cytotoxic immune cells and minimize the total cost of anti-retroviral treatment interventions. Two different anti-retroviral treatment interventions (RTI and PI) are incorporated. The results highlight the key roles of cytotoxic immune response in the HIV... [more]
Sequential Parameter Estimation for Mammalian Cell Model Based on In Silico Design of Experiments
Zhenyu Wang, Hana Sheikh, Kyongbum Lee, Christos Georgakis
August 28, 2018 (v1)
Subject: Biosystems
Keywords: Design of Experiments, Mammalian Cell Culture, parameter estimation, Pharmaceutical Processes, sensitivity analysis
Due to the complicated metabolism of mammalian cells, the corresponding dynamic mathematical models usually consist of large sets of differential and algebraic equations with a large number of parameters to be estimated. On the other hand, the measured data for estimating the model parameters are limited. Consequently, the parameter estimates may converge to a local minimum far from the optimal ones, especially when the initial guesses of the parameter values are poor. The methodology presented in this paper provides a systematic way for estimating parameters sequentially that generates better initial guesses for parameter estimation and improves the accuracy of the obtained metabolic model. The model parameters are first classified into four subsets of decreasing importance, based on the sensitivity of the model’s predictions on the parameters’ assumed values. The parameters in the most sensitive subset, typically a small fraction of the total, are estimated first. When estimating the... [more]
Alternatives for Chemical and Biochemical Lignin Valorization: Hot Topics from a Bibliometric Analysis of the Research Published During the 2000⁻2016 Period
Ricardo Abejón, Heriberto Pérez-Acebo, Leonardo Clavijo
August 28, 2018 (v1)
Subject: Biosystems
Keywords: bibliometric analysis, lignin uses, lignin valorization, lignocellulosic biomass, research trends
A complete bibliometric analysis of the Scopus database was performed to identify the research trends related to lignin valorization from 2000 to 2016. The results from this analysis revealed an exponentially increasing number of publications and a high relevance of interdisciplinary collaboration. The simultaneous valorization of the three main components of lignocellulosic biomass (cellulose, hemicellulose, and lignin) has been revealed as a key aspect and optimal pretreatment is required for the subsequent lignin valorization. Research covers the determination of the lignin structure, isolation, and characterization; depolymerization by thermal and thermochemical methods; chemical, biochemical and biological conversion of depolymerized lignin; and lignin applications. Most methods for lignin depolymerization are focused on the selective cleavage of the β-O-4 linkage. Although many depolymerization methods have been developed, depolymerization with sodium hydroxide is the dominant pr... [more]
Modelling and Simulation of Biochemical Processes Using Petri Nets
Safae Cherdal, Salma Mouline
August 28, 2018 (v1)
Subject: Biosystems
Keywords: biochemical processes, diseases, HFPN, metabolic pathway, Methionine cycle, Petri nets, Simulation
Systems composed of many components which interact with each other and lead to unpredictable global behaviour, are considered as complex systems. In a biological context, complex systems represent living systems composed of a large number of interacting elements. In order to study these systems, a precise mathematical modelling was typically used in this context. However, this modelling has limitations in the structural understanding and the behavioural study. In this sense, formal computational modelling is an approach that allows to model and to simulate dynamical properties of these particular systems. In this paper, we use Hybrid Functional Petri Net (HFPN), a Petri net extension dedicated to study and verify biopathways, to model and study the Methionine metabolic pathway. Methionine and its derivatives play significant roles in human bodies. We propose a set of simulations for the purpose of studying and analysing the Methionine pathway’s behaviour. Our simulation results have sh... [more]
Prediction of Metabolite Concentrations, Rate Constants and Post-Translational Regulation Using Maximum Entropy-Based Simulations with Application to Central Metabolism of Neurospora crassa
William R. Cannon, Jeremy D. Zucker, Douglas J. Baxter, Neeraj Kumar, Scott E. Baker, Jennifer M. Hurley, Jay C. Dunlap
July 31, 2018 (v1)
Subject: Biosystems
Keywords: mass action kinetics, maximum entropy production, metabolism, statistical thermodynamics
We report the application of a recently proposed approach for modeling biological systems using a maximum entropy production rate principle in lieu of having in vivo rate constants. The method is applied in four steps: (1) a new ordinary differential equation (ODE) based optimization approach based on Marcelin’s 1910 mass action equation is used to obtain the maximum entropy distribution; (2) the predicted metabolite concentrations are compared to those generally expected from experiments using a loss function from which post-translational regulation of enzymes is inferred; (3) the system is re-optimized with the inferred regulation from which rate constants are determined from the metabolite concentrations and reaction fluxes; and finally (4) a full ODE-based, mass action simulation with rate parameters and allosteric regulation is obtained. From the last step, the power characteristics and resistance of each reaction can be determined. The method is applied to the central metabolism... [more]
Special Issue: Microbial Community Modeling: Prediction of Microbial Interactions and Community Dynamics
Hyun-Seob Song
July 31, 2018 (v1)
Subject: Biosystems
Keywords: Community Dynamics, Microbial Modeling
Special Issue: Microbial Community Modeling: Prediction of Microbial Interactions and Community Dynamics
ADAR Mediated RNA Editing Modulates MicroRNA Targeting in Human Breast Cancer
Justin T. Roberts, Dillon G. Patterson, Valeria M. King, Shivam V. Amin, Caroline J. Polska, Dominika Houserova, Aline Crucello, Emmaline C. Barnhill, Molly M. Miller, Timothy D. Sherman, Glen M. Borchert
July 31, 2018 (v1)
Subject: Biosystems
Keywords: ADAR, breast, cancer, inosine, microRNA, microRNA targeting, RNA editing
RNA editing by RNA specific adenosine deaminase acting on RNA (ADAR) is increasingly being found to alter microRNA (miRNA) regulation. Editing of miRNA transcripts can affect their processing, as well as which messenger RNAs (mRNAs) they target. Further, editing of target mRNAs can also affect their complementarity to miRNAs. Notably, ADAR editing is often increased in malignancy with the effect of these RNA changes being largely unclear. In addition, numerous reports have now identified an array of miRNAs that directly contribute to various malignancies although the majority of their targets remain largely undefined. Here we propose that modulating the targets of miRNAs via mRNA editing is a frequent occurrence in cancer and an underappreciated participant in pathology. In order to more accurately characterize the relationship between these two regulatory processes, this study examined RNA editing events within mRNA sequences of two breast cancer cell lines (MCF-7 and MDA-MB-231) and... [more]
FluxVisualizer, a Software to Visualize Fluxes through Metabolic Networks
Tim Daniel Rose, Jean-Pierre Mazat
July 31, 2018 (v1)
Subject: Biosystems
Keywords: elementary flux modes visualization, flux balance analysis, metabolic modelling, metabolic network visualization
FluxVisualizer (Version 1.0, 2017, freely available at https://fluxvisualizer.ibgc.cnrs.fr) is a software to visualize fluxes values on a scalable vector graphic (SVG) representation of a metabolic network by colouring or increasing the width of reaction arrows of the SVG file. FluxVisualizer does not aim to draw metabolic networks but to use a customer’s SVG file allowing him to exploit his representation standards with a minimum of constraints. FluxVisualizer is especially suitable for small to medium size metabolic networks, where a visual representation of the fluxes makes sense. The flux distribution can either be an elementary flux mode (EFM), a flux balance analysis (FBA) result or any other flux distribution. It allows the automatic visualization of a series of pathways of the same network as is needed for a set of EFMs. The software is coded in python3 and provides a graphical user interface (GUI) and an application programming interface (API). All functionalities of the progr... [more]
Measuring Cellular Biomass Composition for Computational Biology Applications
Ashley E. Beck, Kristopher A. Hunt, Ross P. Carlson
July 31, 2018 (v1)
Subject: Biosystems
Keywords: biomass reaction, computational biology, macromolecular composition, metabolic model, methods
Computational representations of metabolism are increasingly common in medical, environmental, and bioprocess applications. Cellular growth is often an important output of computational biology analyses, and therefore, accurate measurement of biomass constituents is critical for relevant model predictions. There is a distinct lack of detailed macromolecular measurement protocols, including comparisons to alternative assays and methodologies, as well as tools to convert the experimental data into biochemical reactions for computational biology applications. Herein is compiled a concise literature review regarding methods for five major cellular macromolecules (carbohydrate, DNA, lipid, protein, and RNA) with a step-by-step protocol for a select method provided for each macromolecule. Additionally, each method was tested on three different bacterial species, and recommendations for troubleshooting and testing new species are given. The macromolecular composition measurements were used to... [more]
Genome-Scale In Silico Analysis for Enhanced Production of Succinic Acid in Zymomonas mobilis
Hanifah Widiastuti, Na-Rae Lee, Iftekhar A. Karimi, Dong-Yup Lee
July 31, 2018 (v1)
Subject: Biosystems
Keywords: gene deletion, genome-scale metabolic model, succinic acid, systems biology, Zymomonas mobilis
Presented herein is a model-driven strategy for characterizing the production capability of expression host and subsequently identifying targets for strain improvement by resorting to network structural comparison with reference strain and in silico analysis of genome-scale metabolic model. The applicability of the strategy was demonstrated by exploring the capability of Zymomonas mobilis, as a succinic acid producer. Initially, the central metabolism of Z. mobilis was compared with reference producer, Mannheimia succiniciproducens, in order to identify gene deletion targets. It was followed by combinatorial gene deletion analysis. Remarkably, resultant in silico strains suggested that knocking out pdc, ldh, and pfl genes encoding pyruvate-consuming reactions as well as the cl gene leads to fifteen-fold increase in succinic acid molar yield. The current exploratory work could be a promising support to wet experiments by providing guidance for metabolic engineering strategies and loweri... [more]
Steam Explosion and Vibrating Membrane Filtration to Improve the Processing Cost of Microalgae Cell Disruption and Fractionation
Esther Lorente, Monika Hapońska, Ester Clavero, Carles Torras, Joan Salvadó
July 31, 2018 (v1)
Subject: Biosystems
Keywords: cell disruption, costs, dynamic membrane filtration, fractionation, microalgae, steam explosion
The aim of this study is to explore an innovative downstream route for microalgae processing to reduce cost production. Experiments have been carried out on cell disruption and fractionation stages to recover lipids, sugars, and proteins. Steam explosion and dynamic membrane filtration were used as unit operations. The species tested were Nannochloropsis gaditana, Chlorella sorokiniana, and Dunaliella tertiolecta with different cell wall characteristics. Acid-catalysed steam explosion permitted cell disruption, as well as the hydrolysis of carbohydrates and partial hydrolysis of proteins. This permitted a better access to non-polar solvents for lipid extraction. Dynamic filtration was used to moderate the impact of fouling. Filtration enabled two streams: A permeate containing water and monosaccharides and a low-volume retentate containing the lipids and proteins. The necessary volume of solvent to extract the lipids is thus much lower. An estimation of operational costs of both steam... [more]
An Automatic Monitoring System for High-Frequency Measuring and Real-Time Management of Cyanobacterial Blooms in Urban Water Bodies
Viet Tran Khac, Yi Hong, Denis Plec, Bruno J. Lemaire, Philippe Dubois, Mohamed Saad, Brigitte Vinçon-Leite
July 31, 2018 (v1)
Subject: Biosystems
Keywords: automatic monitoring, cyanobacteria bloom, data transfer platform, high-frequency measuring, real-time management, urban lake
Urban lakes mitigate the negative impacts on the hydrological cycle and improve the quality of life in cities. Worldwide, the concern increases for the protection and management of urban water bodies. Since the physical-chemical and biological conditions of a small aquatic ecosystem can vary rapidly over time, traditional low frequency measurement approaches (weekly or monthly sampling) limits the knowledge and the transfer of research outcomes to management decision-making. In this context, this paper presents an automatic monitoring system including a full-scale experimental site and a data transfer platform for high-frequency observations (every 5 min) in a small and shallow urban lake (Lake Champs-sur-Marne, Paris, France, 10.3 ha). Lake stratification and mixing periods can be clearly observed, these periods are compared with the dynamic patterns of chlorophyll-a, phycocyanin, dissolved oxygen and pH. The results indicate that the phytoplankton growth corresponds with dissolved ox... [more]
In Silico Identification of Microbial Partners to Form Consortia with Anaerobic Fungi
St. Elmo Wilken, Mohan Saxena, Linda R. Petzold, Michelle A. O’Malley
July 31, 2018 (v1)
Subject: Biosystems
Keywords: anaerobic fungi, dynamic flux balance analysis, in silico modeling, lignocellulose, microbial consortia, non-model organism
Lignocellulose is an abundant and renewable resource that holds great promise for sustainable bioprocessing. However, unpretreated lignocellulose is recalcitrant to direct utilization by most microbes. Current methods to overcome this barrier include expensive pretreatment steps to liberate cellulose and hemicellulose from lignin. Anaerobic gut fungi possess complex cellulolytic machinery specifically evolved to decompose crude lignocellulose, but they are not yet genetically tractable and have not been employed in industrial bioprocesses. Here, we aim to exploit the biomass-degrading abilities of anaerobic fungi by pairing them with another organism that can convert the fermentable sugars generated from hydrolysis into bioproducts. By combining experiments measuring the amount of excess fermentable sugars released by the fungal enzymes acting on crude lignocellulose, and a novel dynamic flux balance analysis algorithm, we screened potential consortia partners by qualitative suitabilit... [more]
RNA-Seq as an Emerging Tool for Marine Dinoflagellate Transcriptome Analysis: Process and Challenges
Muhamad Afiq Akbar, Asmat Ahmad, Gires Usup, Hamidun Bunawan
July 31, 2018 (v1)
Subject: Biosystems
Keywords: dinoflagellates, next-generation sequencing, RNA-seq, transcriptome analysis, transcriptomics
Dinoflagellates are the large group of marine phytoplankton with primary studies interest regarding their symbiosis with coral reef and the abilities to form harmful algae blooms (HABs). Toxin produced by dinoflagellates during events of HABs cause severe negative impact both in the economy and health sector. However, attempts to understand the dinoflagellates genomic features are hindered by their complex genome organization. Transcriptomics have been employed to understand dinoflagellates genome structure, profile genes and gene expression. RNA-seq is one of the latest methods for transcriptomics study. This method is capable of profiling the dinoflagellates transcriptomes and has several advantages, including highly sensitive, cost effective and deeper sequence coverage. Thus, in this review paper, the current workflow of dinoflagellates RNA-seq starts with the extraction of high quality RNA and is followed by cDNA sequencing using the next-generation sequencing platform, dinoflagel... [more]
Individual-Based Modelling of Invasion in Bioaugmented Sand Filter Communities
Aisling J. Daly, Jan M. Baetens, Johanna Vandermaesen, Nico Boon, Dirk Springael, Bernard De Baets
July 31, 2018 (v1)
Subject: Biosystems
Keywords: bioaugmentation, engineered community, individual-based model, invasion
Using experimental data obtained from in vitro bioaugmentation studies of a sand filter community of 13 bacterial species, we develop an individual-based model representing the in silico counterpart of this synthetic microbial community. We assess the inter-species interactions, first by identifying strain identity effects in the data then by synthesizing these effects into a competition structure for our model. Pairwise competition outcomes are determined based on interaction effects in terms of functionality. We also consider non-deterministic competition, where winning probabilities are assigned based on the relative intrinsic competitiveness of each strain. Our model is able to reproduce the key qualitative dynamics observed in in vitro experiments with similar synthetic sand filter communities. Simulation outcomes can be explained based on the underlying competition structures and the resulting spatial dynamics. Our results highlight the importance of community diversity and in pa... [more]
Dynamics of the Bacterial Community Associated with Phaeodactylum tricornutum Cultures
Fiona Wanjiku Moejes, Antonella Succurro, Ovidiu Popa, Julie Maguire, Oliver Ebenhöh
July 31, 2018 (v1)
Subject: Biosystems
Keywords: algal biotechnology, diatoms, host-microbe interactions, mathematical modelling, microbial communities, synthetic ecology
The pennate diatom Phaeodactylum tricornutum is a model organism able to synthesize industrially-relevant molecules. Commercial-scale cultivation currently requires large monocultures, prone to bio-contamination. However, little is known about the identity of the invading organisms. To reduce the complexity of natural systems, we systematically investigated the microbiome of non-axenic P. tricornutum cultures from a culture collection in reproducible experiments. The results revealed a dynamic bacterial community that developed differently in “complete” and “minimal” media conditions. In complete media, we observed an accelerated “culture crash”, indicating a more stable culture in minimal media. The identification of only four bacterial families as major players within the microbiome suggests specific roles depending on environmental conditions. From our results we propose a network of putative interactions between P. tricornutum and these main bacterial factions. We demonstrate that,... [more]
Stochasticity in the Parasite-Driven Trait Evolution of Competing Species Masks the Distinctive Consequences of Distance Metrics
Christian Alvin H. Buhat, Dylan Antonio S. J. Talabis, Anthony L. Cueno, Maica Krizna A. Gavina, Ariel L. Babierra, Genaro A. Cuaresma, Jomar F. Rabajante
July 31, 2018 (v1)
Subject: Biosystems
Keywords: Chebyshev norm, egalitarianism, Euclidean norm, evolutionary dynamics, exploitation, Manhattan norm, parasitism, quantitative trait
Various distance metrics and their induced norms are employed in the quantitative modeling of evolutionary dynamics. Minimization of these distance metrics, when applied to evolutionary optimization, are hypothesized to result in different outcomes. Here, we apply the different distance metrics to the evolutionary trait dynamics brought about by the interaction between two competing species infected by parasites (exploiters). We present deterministic cases showing the distinctive selection outcomes under the Manhattan, Euclidean, and Chebyshev norms. Specifically, we show how they differ in the time of convergence to the desired optima (e.g., no disease), and in the egalitarian sharing of carrying capacity between the competing species. However, when randomness is introduced to the population dynamics of parasites and to the trait dynamics of the competing species, the distinctive characteristics of the outcomes under the three norms become indistinguishable. Our results provide theore... [more]
Dispersal-Based Microbial Community Assembly Decreases Biogeochemical Function
Emily B. Graham, James C. Stegen
July 31, 2018 (v1)
Subject: Biosystems
Keywords: deterministic, ecosystem function, microbial ecology, null model, Simulation, stochastic
Ecological mechanisms influence relationships among microbial communities, which in turn impact biogeochemistry. In particular, microbial communities are assembled by deterministic (e.g., selection) and stochastic (e.g., dispersal) processes, and the relative balance of these two process types is hypothesized to alter the influence of microbial communities over biogeochemical function. We used an ecological simulation model to evaluate this hypothesis, defining biogeochemical function generically to represent any biogeochemical reaction of interest. We assembled receiving communities under different levels of dispersal from a source community that was assembled purely by selection. The dispersal scenarios ranged from no dispersal (i.e., selection-only) to dispersal rates high enough to overwhelm selection (i.e., homogenizing dispersal). We used an aggregate measure of community fitness to infer a given community’s biogeochemical function relative to other communities. We also used ecol... [more]
A Reaction Database for Small Molecule Pharmaceutical Processes Integrated with Process Information
Emmanouil Papadakis, Amata Anantpinijwatna, John M. Woodley, Rafiqul Gani
July 31, 2018 (v1)
Subject: Biosystems
Keywords: “green” metrics analysis, organic solvents, pharmaceutical process engineering, reaction database
This article describes the development of a reaction database with the objective to collect data for multiphase reactions involved in small molecule pharmaceutical processes with a search engine to retrieve necessary data in investigations of reaction-separation schemes, such as the role of organic solvents in reaction performance improvement. The focus of this reaction database is to provide a data rich environment with process information available to assist during the early stage synthesis of pharmaceutical products. The database is structured in terms of reaction classification of reaction types; compounds participating in the reaction; use of organic solvents and their function; information for single step and multistep reactions; target products; reaction conditions and reaction data. Information for reactor scale-up together with information for the separation and other relevant information for each reaction and reference are also available in the database. Additionally, the ret... [more]
Modeling Microbial Communities: A Call for Collaboration between Experimentalists and Theorists
Marco Zaccaria, Sandra Dedrick, Babak Momeni
July 31, 2018 (v1)
Subject: Biosystems
Keywords: community ecology, interspecies interactions, mathematical modeling, mechanistic modeling, microbial communities, phenomenological modeling
With our growing understanding of the impact of microbial communities, understanding how such communities function has become a priority. The influence of microbial communities is widespread. Human-associated microbiota impacts health, environmental microbes determine ecosystem sustainability, and microbe-driven industrial processes are expanding. This broad range of applications has led to a wide range of approaches to analyze and describe microbial communities. In particular, theoretical work based on mathematical modeling has been a steady source of inspiration for explaining and predicting microbial community processes. Here, we survey some of the modeling approaches used in different contexts. We promote classifying different approaches using a unified platform, and encourage cataloging the findings in a database. We believe that the synergy emerging from a coherent collection facilitates a better understanding of important processes that determine microbial community functions. W... [more]
Characterizing Gene and Protein Crosstalks in Subjects at Risk of Developing Alzheimer’s Disease: A New Computational Approach
Kanchana Padmanabhan, Kelly Nudelman, Steve Harenberg, Gonzalo Bello, Dongwha Sohn, Katie Shpanskaya, Priyanka Tiwari Dikshit, Pallavi S. Yerramsetty, Rudolph E. Tanzi, Andrew J. Saykin, Jeffrey R. Petrella, P. Murali Doraiswamy, Nagiza F. Samatova, Alzheimer’s Disease Neuroimaging Initiative
July 31, 2018 (v1)
Subject: Biosystems
Keywords: Alzheimer’s disease, biomarker, disease prediction, pathway crosstalk
Alzheimer’s disease (AD) is a major public health threat; however, despite decades of research, the disease mechanisms are not completely understood, and there is a significant dearth of predictive biomarkers. The availability of systems biology approaches has opened new avenues for understanding disease mechanisms at a pathway level. However, to the best of our knowledge, no prior study has characterized the nature of pathway crosstalks in AD, or examined their utility as biomarkers for diagnosis or prognosis. In this paper, we build the first computational crosstalk model of AD incorporating genetics, antecedent knowledge, and biomarkers from a national study to create a generic pathway crosstalk reference map and to characterize the nature of genetic and protein pathway crosstalks in mild cognitive impairment (MCI) subjects. We perform initial studies of the utility of incorporating these crosstalks as biomarkers for assessing the risk of MCI progression to AD dementia. Our analysis... [more]
Stoichiometric Network Analysis of Cyanobacterial Acclimation to Photosynthesis-Associated Stresses Identifies Heterotrophic Niches
Ashley E. Beck, Hans C. Bernstein, Ross P. Carlson
July 31, 2018 (v1)
Subject: Biosystems
Keywords: cross-feeding, cyanobacteria, elementary flux mode analysis, irradiance, resource allocation, RuBisCO, stress acclimation
Metabolic acclimation to photosynthesis-associated stresses was examined in the thermophilic cyanobacterium Thermosynechococcus elongatus BP-1 using integrated computational and photobioreactor analyses. A genome-enabled metabolic model, complete with measured biomass composition, was analyzed using ecological resource allocation theory to predict and interpret metabolic acclimation to irradiance, O₂, and nutrient stresses. Reduced growth efficiency, shifts in photosystem utilization, changes in photorespiration strategies, and differing byproduct secretion patterns were predicted to occur along culturing stress gradients. These predictions were compared with photobioreactor physiological data and previously published transcriptomic data and found to be highly consistent with observations, providing a systems-based rationale for the culture phenotypes. The analysis also indicated that cyanobacterial stress acclimation strategies created niches for heterotrophic organisms and that heter... [more]
Closed-Loop Characterization of Neuronal Activation Using Electrical Stimulation and Optical Imaging
Michelle L. Kuykendal, Gareth S. Guvanasen, Steve M. Potter, Martha A. Grover, Stephen P. DeWeerth
July 31, 2018 (v1)
Subject: Biosystems
Keywords: activation curve, closed-loop, dissociated culture, extracellular electrical stimulation, micro-electrode array (MEA), optical recording, strength-duration
We have developed a closed-loop, high-throughput system that applies electrical stimulation and optical recording to facilitate the rapid characterization of extracellular, stimulus-evoked neuronal activity. In our system, a microelectrode array delivers current pulses to a dissociated neuronal culture treated with a calcium-sensitive fluorescent dye; automated real-time image processing of high-speed digital video identifies the neuronal response; and an optimized search routine alters the applied stimulus to achieve a targeted response. Action potentials are detected by measuring the post-stimulus, calcium-sensitive fluorescence at the neuronal somata. The system controller performs directed searches within the strength⁻duration (SD) stimulus-parameter space to build probabilistic neuronal activation curves. This closed-loop system reduces the number of stimuli needed to estimate the activation curves when compared to the more commonly used open-loop approach. This reduction allows t... [more]
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