scholarly journals Optimal metabolic states in cells

2018 ◽  
Author(s):  
Wolfram Liebermeister
Keyword(s):  
Resource Allocation ◽  
Metabolic Pathways ◽  
Network Models ◽  
Cellular Systems ◽  
Biochemical Network ◽  
Mathematical Form ◽  
Cellular Functions ◽  
Trade Offs ◽  
Metabolic States ◽  
Common Framework

AbstractCells need to make an efficient use of metabolites, proteins, energy, membrane space, and time, and resource allocation is also an important aspect of metabolism. How, for example, should cells distribute their protein budget between different cellular functions, e.g. different metabolic pathways, to maximise growth? Cellular resource allocation can be studied by combining biochemical network models with optimality problems that choose metabolic states by their cost and benefit. Various types of resource allocation problems have been proposed. The underlying mechanistic models may describe different cellular systems (e.g. metabolic pathways, networks, or compromises between metabolism and protein production) on different level of detail and using different mathematical formulations (e.g. stoichiometric or kinetic). The optimality problems may use metabolite levels, enzyme levels, or fluxes as variables, assume different cost or benefit functions, and describe different kinds of trade-offs, in which cell variables are either constrained or treated as optimisation objectives. Due to all these differences, optimality problems may be hard to compare or combine. To bring them under one umbrella, I show that they can be derived from a common framework, and that their optimality conditions all show the same mathematical form. This unified view on metabolic optimality problems can be used to justify and combine various modelling approaches and biochemical optimality problems.

Biosecurity and Public Health Ethics Issues Raised by Biological Threats

2019 ◽  
pp. 773-785
Author(s):  
Nicholas Evans ◽  
Thomas Inglesby
Keyword(s):  
Public Health ◽  
Resource Allocation ◽  
Infectious Diseases ◽  
Ethical Issues ◽  
Emerging Infectious Diseases ◽  
Biological Weapon ◽  
Ethical Values ◽  
Dual Use ◽  
Health Concerns ◽  
Trade Offs

This chapter introduces ethical issues that arise in the context of biosecurity: policies and actions intended to prevent the development or emergence, or mitigate the consequences, of serious biological threats. These threats could include deliberate biological weapon attacks (bioterrorism), pandemics, emerging infectious diseases, or major laboratory accidents. The basic values that underpin these public health concerns are first introduced. Ethical issues that arise before, during, and following a biosecurity crisis are then examined, including issues of resource allocation, dual-use research, and the possibility of quarantine. Their resolution requires trade-offs among different ethical values, including utility, fairness, and liberty.

scholarly journals Computational modeling of anthocyanin pathway evolution

2019 ◽  
Author(s):  
Lucas C. Wheeler ◽  
Stacey D. Smith
Keyword(s):  
Metabolic Pathways ◽  
Flower Color ◽  
Complex Phenotype ◽  
Pathway Evolution ◽  
Anthocyanin Pathway ◽  
Trade Offs ◽  
Wide Range ◽  
Pathway Function ◽  
Simple Kinetic Model ◽  
New Mutations

AbstractAlteration of metabolic pathways is a key component of the evolution of new phenotypes. Flower color is a striking example of the importance of metabolic evolution in a complex phenotype, wherein shifts in the activity of the underlying pathway lead to a wide range of pigments. Although experimental work has identified common classes of mutations responsible for transitions among colors, we lack a unifying model that relates pathway function and activity to the evolution of distinct pigment phenotypes. One challenge in creating such a model is the branching structure of pigment pathways, which may lead to evolutionary trade-offs due to competition for shared substrates. In order to predict the effects of shifts in enzyme function and activity on pigment production, we created a simple kinetic model of a major plant pigmentaion pathway: the anthocyanin pathway. This model describes the production of the three classes of blue, purple and red anthocyanin pigments, and accordingly, includes multiple branches and substrate competition. We first studied the general behavior of this model using a realistic, functional set of parameters. We then stochastically evolved the pathway toward a defined optimum and and analyzed the patterns of fixed mutations. This approach allowed us to quantify the probability density of trajectories through pathway state space and identify the types and number of changes. Finally, we examine whether the observed trajectories and constraints help to explain experimental observations, i.e., the predominance of mutations which change color by altering the function of branching genes in the pathway. These analyses provide a theoretical framework which can be used to predict the consequences of new mutations in terms of both pigment phenotypes and pleiotropic effects.

scholarly journals A Septin Cytoskeleton-Targeting Small Molecule, Forchlorfenuron, Inhibits Epithelial Migration via Septin-Independent Perturbation of Cellular Signaling

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 84 ◽  
Author(s):  
Lei Sun ◽  
Xuelei Cao ◽  
Susana Lechuga ◽  
Alex Feygin ◽  
Nayden G. Naydenov ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cellular Systems ◽  
Model Organisms ◽  
Cellular Functions ◽  
Epithelial Migration ◽  
Cellular Processes ◽  
Dependent Inhibition ◽  
Erk Activity ◽  
Ht 29 ◽  
Target Effects

Septins are GTP-binding proteins that self-assemble into high-order cytoskeletal structures, filaments, and rings. The septin cytoskeleton has a number of cellular functions, including regulation of cytokinesis, cell migration, vesicle trafficking, and receptor signaling. A plant cytokinin, forchlorfenuron (FCF), interacts with septin subunits, resulting in the altered organization of the septin cytoskeleton. Although FCF has been extensively used to examine the roles of septins in various cellular processes, its specificity, and possible off-target effects in vertebrate systems, has not been investigated. In the present study, we demonstrate that FCF inhibits spontaneous, as well as hepatocyte growth factor-induced, migration of HT-29 and DU145 human epithelial cells. Additionally, FCF increases paracellular permeability of HT-29 cell monolayers. These inhibitory effects of FCF persist in epithelial cells where the septin cytoskeleton has been disassembled by either CRISPR/Cas9-mediated knockout or siRNA-mediated knockdown of septin 7, insinuating off-target effects of FCF. Biochemical analysis reveals that FCF-dependent inhibition of the motility of control and septin-depleted cells is accompanied by decreased expression of the c-Jun transcription factor and inhibited ERK activity. The described off-target effects of FCF strongly suggests that caution is warranted while using this compound to examine the biological functions of septins in cellular systems and model organisms.

scholarly journals Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 228 ◽  
Author(s):  
Anne-Laure Tardy ◽  
Etienne Pouteau ◽  
Daniel Marquez ◽  
Cansu Yilmaz ◽  
Andrew Scholey
Keyword(s):  
Vitamin C ◽  
Oxygen Transport ◽  
Metabolic Pathways ◽  
Clinical Evidence ◽  
Psychological Symptoms ◽  
Psychological Processes ◽  
Physical Fatigue ◽  
Cellular Functions ◽  
Muscular Function ◽  
Neuronal Functions

Vitamins and minerals are essential to humans as they play essential roles in a variety of basic metabolic pathways that support fundamental cellular functions. In particular, their involvement in energy-yielding metabolism, DNA synthesis, oxygen transport, and neuronal functions makes them critical for brain and muscular function. These, in turn, translate into effects on cognitive and psychological processes, including mental and physical fatigue. This review is focused on B vitamins (B1, B2, B3, B5, B6, B8, B9 and B12), vitamin C, iron, magnesium and zinc, which have recognized roles in these outcomes. It summarizes the biochemical bases and actions of these micronutrients at both the molecular and cellular levels and connects them with cognitive and psychological symptoms, as well as manifestations of fatigue that may occur when status or supplies of these micronutrients are not adequate.

scholarly journals Resource allocation trade-offs in a mast-seeding conifer: Piñon pine prioritizes reproduction over defense

AoB Plants ◽  
2019 ◽  
Author(s):  
Miranda D Redmond ◽  
Thomas Seth Davis ◽  
Scott M Ferrenberg ◽  
Andreas P Wion
Keyword(s):  
Resource Allocation ◽  
Tree Growth ◽  
Mast Seeding ◽  
Central Component ◽  
Trade Off ◽  
Cone Production ◽  
Resin Duct ◽  
Fitness Traits ◽  
Trade Offs ◽  
Increased Risk

Abstract The cost of plant reproduction or defense at the expense of other fitness traits is a central component of life history theory. Yet the three central resource allocation pathways of growth, reproduction, and defense have rarely been assessed simultaneously nor across individual to landscape scales. This information is critical towards identifying the physiological, environmental, and genetic mechanisms underpinning resource allocation. This study assessed trade-offs in resource allocation between tree growth, defense, and reproduction across scales among piñon pine (Pinusedulis), a widespread mast-seeding conifer of the southwestern USA. Time series (2004-2016) of tree growth (radial and primary shoot growth), defense (resin duct production; a key constitutive defense for this species), and cone production among individual trees from populations across a broad environmental gradient were used to investigate these trade-offs in resource allocation across three scales: individual, population, and landscape. We found evidence for a defense-reproduction trade-off among individuals whereby total resin duct area in annual xylem rings was lower during years of above average cone production. Despite variability in cone and resin duct production across trees within a population and across populations, there was no association between these fitness traits at either of those scales. There was no evidence of trade-offs between cone production and growth at any scales measured, whereas resin duct production and growth were positively related at all scales. Our study suggests that a strategic trade-off occurs whereby investment into defense is temporarily curtailed to favor reproduction, despite increased risk of exposure to natural enemies and the ability of piñon pine to simultaneously allocate carbon to growth and defense. Our study provides new insights into physiological expressions of growth, defense, and reproduction over time in this long-lived masting conifer and indicates the presence of trade-offs with direct importance for individual fitness and population dynamics under global change.

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