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 Computational Modeling of Anthocyanin Pathway Evolution: Biases, Hotspots, and Trade-offs

2019 ◽  
Vol 59 (3) ◽  
pp. 585-598 ◽  
Author(s):  
L C Wheeler ◽  
S D Smith
Keyword(s):  
Flower Color ◽  
Common Mechanism ◽  
Complex Phenotype ◽  
Pathway Evolution ◽  
Anthocyanin Pathway ◽  
Trade Offs ◽  
Wide Range ◽  
Pathway Function ◽  
Simple Kinetic Model ◽  
New Mutations

Abstract The alteration of metabolic pathways is a common mechanism underlying 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 pigmentation 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 naïve set of parameters. We then stochastically evolved the pathway toward a defined optimum 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 examined whether our simulated results qualitatively align with 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 that can be used to predict the consequences of new mutations in terms of both pigment phenotypes and pleiotropic effects.

scholarly journals Fundamental limits of electron and nuclear spin qubit lifetimes in an isolated self-assembled quantum dot

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
George Gillard ◽  
Ian M. Griffiths ◽  
Gautham Ragunathan ◽  
Ata Ulhaq ◽  
Callum McEwan ◽  
...  
Keyword(s):  
Quantum Dot ◽  
Spin Relaxation ◽  
Nuclear Spin ◽  
Operating Conditions ◽  
External Control ◽  
Spin Qubits ◽  
Fundamental Limits ◽  
Trade Offs ◽  
Wide Range ◽  
Spin Qubit

AbstractCombining external control with long spin lifetime and coherence is a key challenge for solid state spin qubits. Tunnel coupling with electron Fermi reservoir provides robust charge state control in semiconductor quantum dots, but results in undesired relaxation of electron and nuclear spins through mechanisms that lack complete understanding. Here, we unravel the contributions of tunnelling-assisted and phonon-assisted spin relaxation mechanisms by systematically adjusting the tunnelling coupling in a wide range, including the limit of an isolated quantum dot. These experiments reveal fundamental limits and trade-offs of quantum dot spin dynamics: while reduced tunnelling can be used to achieve electron spin qubit lifetimes exceeding 1 s, the optical spin initialisation fidelity is reduced below 80%, limited by Auger recombination. Comprehensive understanding of electron-nuclear spin relaxation attained here provides a roadmap for design of the optimal operating conditions in quantum dot spin qubits.

scholarly journals Gene Expression Space Shapes the Bioprocess Trade-Offs among Titer, Yield and Productivity

2021 ◽  
Vol 11 (13) ◽  
pp. 5859
Author(s):  
Fernando N. Santos-Navarro ◽  
Yadira Boada ◽  
Alejandro Vignoni ◽  
Jesús Picó
Keyword(s):  
Gene Expression ◽  
Gene Transcription ◽  
Performance Metrics ◽  
Cell Mass ◽  
Gene Copy ◽  
Substrate Uptake ◽  
Promoter Strength ◽  
Expression Levels ◽  
Trade Offs ◽  
Wide Range

Optimal gene expression is central for the development of both bacterial expression systems for heterologous protein production, and microbial cell factories for industrial metabolite production. Our goal is to fulfill industry-level overproduction demands optimally, as measured by the following key performance metrics: titer, productivity rate, and yield (TRY). Here we use a multiscale model incorporating the dynamics of (i) the cell population in the bioreactor, (ii) the substrate uptake and (iii) the interaction between the cell host and expression of the protein of interest. Our model predicts cell growth rate and cell mass distribution between enzymes of interest and host enzymes as a function of substrate uptake and the following main lab-accessible gene expression-related characteristics: promoter strength, gene copy number and ribosome binding site strength. We evaluated the differential roles of gene transcription and translation in shaping TRY trade-offs for a wide range of expression levels and the sensitivity of the TRY space to variations in substrate availability. Our results show that, at low expression levels, gene transcription mainly defined TRY, and gene translation had a limited effect; whereas, at high expression levels, TRY depended on the product of both, in agreement with experiments in the literature.

P0031AURINE METABOLOMICS: AN EMERGING TOOL FOR DISSECTING BIOLOGICAL ABERRATIONS UNDERLYING RENAL DYSFUNCTION IN BARDET-BIEDL SYNDROME

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Miriam Zacchia ◽  
Emanuela Marchese ◽  
Marianna Caterino ◽  
Margherita Ruoppolo ◽  
Giovambattista Capasso
Keyword(s):  
Lactic Acid ◽  
Kidney Disease ◽  
Renal Disease ◽  
Renal Dysfunction ◽  
Metabolic Pathways ◽  
Healthy Subjects ◽  
Hexadecenoic Acid ◽  
Kidney Dysfunction ◽  
Bardet Biedl Syndrome ◽  
Wide Range

Abstract Background and Aims Bardet Biedl Syndrome (BBS) is a rare genetic disorder characterized by a wide range of organ dysfunction, including kidney disease. The severity of renal dysfunction is highly variable in this setting, ranging from tubular defects to the end stage renal disease, with poor genotype-phenotype correlation. Proteomics and metabolomics are powerful tools able to contribute to the better understanding of molecular basis of disease conditions. Our previous studies demonstrated that the urinary proteomic pattern of BBS patients differed from that of healthy subjects, with a set of deregulated proteins including cell adhesion and extracellular matrix organization proteins (1). The present study aims to characterize urine metabolomic profile of BBS patients, in order to identify both 1) potential disease biomarkers and 2) aberrant metabolic pathways underlying renal disease Method To this end, in the pilot study urine samples have been collected from 14 adult BBS patients and have been compared with healthy volunteers, using an untargeted strategy. In the confirmation study, 24 BBS patients with wide range of kidney dysfunction have been enrolled, and additional control groups, besides healthy subjects, were included: 1) age-gender-matched chronic kidney disease patients by other causes and 2) obese individuals. Results Several metabolites were de-regulated in BBS patients compared with normal subjects (lactic acid, glycolic acid,3-Hydroxypropionic acid, pyruvic acid, 3-hydroxyisobutyric acid, 2-ethyl-3-hydroxy-propionic acid, succinic acid, fumaric acid, erythropentonic acid, 2-hydroxyglutaric acid, 4-hydroxyphenyllactic acid, 3,4-pyridinedicarboxylic acid, retinoic acid, 4-hydroxyphenylacetic acid, palmitic acid, 9-Hexadecenoic acid, oleic acid and 9-Octadecenoic acid). The clusterization performed by MetaboAnalyst tool, revealed a possible deregulation of different metabolic pathways, including glycolysis, TCA cycle, pyruvate metabolism, lipids biosynthesis and glutamate metabolism (p-value <0.01) (figure 1); some of these pathways were described as de-regulated in other ciliopathies (2). In the confirmation study (on-going studies) some metabolites, including lactic acid and intermediates of Krebs cycle, correlated with kidney dysfunction only in the BBS group. Conclusion These findings suggest that urine metabolomic fingerprint of BBS patients is different from that of healthy subjects and indicate a possible deregulation of several metabolic pathways; some urinary molecules correlated with kidney dysfunction only in BBS patients, suggesting the specificity of these results.

scholarly journals Development of cancer metabolism as a therapeutic target: new pathways, patient studies, stratification and combination therapy

2019 ◽  
Vol 122 (1) ◽  
pp. 1-3 ◽  
Author(s):  
Adrian L. Harris
Keyword(s):  
Metabolic Pathways ◽  
Trial Design ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Critical Role ◽  
Therapeutic Approaches ◽  
Preclinical Models ◽  
Wide Range ◽  
Patient Studies

AbstractCancer metabolism has undergone a resurgence in the last decade, 70 years after Warburg described aerobic glycolysis as a feature of cancer cells. A wide range of techniques have elucidated the complexity and heterogeneity in preclinical models and clinical studies. What emerges are the large differences between tissues, tumour types and intratumour heterogeneity. However, synergies with inhibition of metabolic pathways have been found for many drugs and therapeutic approaches, and a critical role of window studies and translational trial design is key to success.

scholarly journals A Transcriptomic Approach to the Metabolism of Tetrapyrrolic Photosensitizers in a Marine Annelid

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3924
Author(s):  
Maria Leonor Santos ◽  
Mariaelena D’Ambrosio ◽  
Ana P. Rodrigo ◽  
A. Jorge Parola ◽  
Pedro M. Costa
Keyword(s):  
Metabolic Pathways ◽  
Molecular Networks ◽  
Bile Pigments ◽  
Rna Seq ◽  
The Past ◽  
Wide Range ◽  
Genes Encoding ◽  
Organ Specific ◽  
Bright Green ◽  
Green Coloration

The past decade has seen growing interest in marine natural pigments for biotechnological applications. One of the most abundant classes of biological pigments is the tetrapyrroles, which are prized targets due their photodynamic properties; porphyrins are the best known examples of this group. Many animal porphyrinoids and other tetrapyrroles are produced through heme metabolic pathways, the best known of which are the bile pigments biliverdin and bilirubin. Eulalia is a marine Polychaeta characterized by its bright green coloration resulting from a remarkably wide range of greenish and yellowish tetrapyrroles, some of which have promising photodynamic properties. The present study combined metabolomics based on HPLC-DAD with RNA-seq transcriptomics to investigate the molecular pathways of porphyrinoid metabolism by comparing the worm’s proboscis and epidermis, which display distinct pigmentation patterns. The results showed that pigments are endogenous and seemingly heme-derived. The worm possesses homologs in both organs for genes encoding enzymes involved in heme metabolism such as ALAD, FECH, UROS, and PPOX. However, the findings also indicate that variants of the canonical enzymes of the heme biosynthesis pathway can be species- and organ-specific. These differences between molecular networks contribute to explain not only the differential pigmentation patterns between organs, but also the worm’s variety of novel endogenous tetrapyrrolic compounds.

Accessibility vs. Feasibility: Optimizing Function Allocation for Accommodation of Heterogeneous Populations

2021 ◽  
pp. 1-36
Author(s):  
Benjamin Knisely ◽  
Monifa Vaughn-Cooke
Keyword(s):  
Optimization Model ◽  
Engineering Students ◽  
Product Variety ◽  
Human Beings ◽  
Heterogeneous Populations ◽  
Trade Offs ◽  
Potential System ◽  
Wide Range ◽  
Need To Evaluate ◽  
Design Case Study

Abstract Human beings are physically and cognitively variable, leading to a wide array of potential system use cases. To design safe and effective systems for highly heterogeneous populations, engineers must cater to this variability to minimize the chance of error and system failure. This can be a challenge because of the increasing costs associated with providing additional product variety. Most guidance for navigating these trade-offs is intended for late-stage design, when significant resources have been expended, thus risking expensive redesign or exclusion of users when new human concerns become apparent. Despite the critical need to evaluate accommodation-cost trade-offs in early stages of design, there is currently a lack of structured guidance. In this work, an approach to function modeling is proposed that allows the simultaneous consideration of human and machine functionality. This modeling approach facilitates the allocation of system functions to humans and machines to be used as an accessible baseline for concept development. Further, a multi-objective optimization model was developed to allocate functions with metrics for accommodation and cost. The model was demonstrated on a design case study. 16 senior mechanical engineering students were recruited and tasked with performing the allocation task manually. The results were compared to the output of the optimization model. Results indicated that participants were unable to produce concepts with the same accommodation-cost efficiency as the optimization model. Further, the optimization model successfully produced a wide range of potential product concepts, demonstrating its utility as a decision-aid.

scholarly journals Robust estimation of vertical symmetry axis models via joint migration inversion: Including multiples in anisotropic parameter estimation

Geophysics ◽  
2019 ◽  
Vol 84 (1) ◽  
pp. C57-C74 ◽  
Author(s):  
Abdulrahman A. Alshuhail ◽  
Dirk J. Verschuur
Keyword(s):  
Symmetry Axis ◽  
Transverse Isotropy ◽  
Half Cycle ◽  
Anisotropic Parameter ◽  
Data Set ◽  
Trade Off ◽  
Trade Offs ◽  
Highly Nonlinear ◽  
Wide Range ◽  
Internal Multiples

Because the earth is predominately anisotropic, the anisotropy of the medium needs to be included in seismic imaging to avoid mispositioning of reflectors and unfocused images. Deriving accurate anisotropic velocities from the seismic reflection measurements is a highly nonlinear and ambiguous process. To mitigate the nonlinearity and trade-offs between parameters, we have included anisotropy in the so-called joint migration inversion (JMI) method, in which we limit ourselves to the case of transverse isotropy with a vertical symmetry axis. The JMI method is based on strictly separating the scattering effects in the data from the propagation effects. The scattering information is encoded in the reflectivity operators, whereas the phase information is encoded in the propagation operators. This strict separation enables the method to be more robust, in that it can appropriately handle a wide range of starting models, even when the differences in traveltimes are more than a half cycle away. The method also uses internal multiples in estimating reflectivities and anisotropic velocities. Including internal multiples in inversion not only reduces the crosstalk in the final image, but it can also reduce the trade-off between the anisotropic parameters because internal multiples usually have more of an imprint of the subsurface parameters compared with primaries. The inverse problem is parameterized in terms of a reflectivity, vertical velocity, horizontal velocity, and a fixed [Formula: see text] value. The method is demonstrated on several synthetic models and a marine data set from the North Sea. Our results indicate that using JMI for anisotropic inversion makes the inversion robust in terms of using highly erroneous initial models. Moreover, internal multiples can contain valuable information on the subsurface parameters, which can help to reduce the trade-off between anisotropic parameters in inversion.

scholarly journals Social network-based ethical analysis of COVID-19 vaccine supply policy in three Central Asian countries              

2021 ◽  
Author(s):  
Timur Aripov ◽  
Daniel Wikler ◽  
Damin Asadov ◽  
Zhangir Tulekov ◽  
Totugul Murzabekova ◽  
...  
Keyword(s):  
Ethical Issues ◽  
Vaccine Coverage ◽  
Scientific Data ◽  
Efficacy And Safety ◽  
Asian Countries ◽  
Ethical Frameworks ◽  
Trade Offs ◽  
Central Asian ◽  
Wide Range ◽  
Central Asian Countries

Abstract Abstract Background In the pandemic time, many low- and middle-income countries are experiencing restricted access to COVID-19 vaccines. An access to imported vaccines or ways to produce them locally becomes the principal source of hope. But developing a strategy for success in obtaining and allocating vaccines is not easy task. The governments in those countries have faced difficult decision whether to accept or reject offers of vaccine diplomacy, weighing price and availability of COVID-19 vaccines against concerns over their efficacy and safety. Our aim was to analyze public opinion regarding the governmental strategies to obtain COVID-19 vaccines in three Central Asian countries, focusing particularly on possible ethical issues. Methods We searched opinions expressed either in Russian or in the respective national languages. We provided data of the debate within three countries, drawn from social media postings and other sources. The opinion data was not restricted by source and time. This allowed to collect a wide range of possible opinions that could be expressed regarding COVID-19 vaccine supply and public’s participation in vaccine trials. We recognized ethical issues and possible questions concerning different ethical frameworks. We also considered additional information or scientific data, in the process of reasoning. Results As a result, public views on their respective government policies on COVID-19 vaccine supply ranged from strongly negative to slightly positive. We extracted most important issues from public debates, for our analysis. The first issue involved trade-offs between quantity, speed, price, freedom, efficacy and safety in the vaccines. The second set of issues arouse in connection with the request to site a randomized trial in one of countries (Uzbekistan). After considering additional evidences, we weighed individual with public risks and benefits to make specific judgements concerning every issue. Conclusions We believe that our analysis would be a helpful example of solving ethical issues that can rise concerning COVID-19 vaccine supply round the world. The public view can be highly critical, helping to spot such issues. An ignoring this view can lead to major problems, which in turn, can become a serious obstacle for the vaccine coverage and epidemics’ control in the countries and regions.

scholarly journals Transgenerational fitness effects of lifespan extension by dietary restriction in Caenorhabditis elegans

2021 ◽  
Vol 288 (1950) ◽  
Author(s):  
Edward R. Ivimey-Cook ◽  
Kris Sales ◽  
Hanne Carlsson ◽  
Simone Immler ◽  
Tracey Chapman ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Dietary Restriction ◽  
Mortality Risk ◽  
Lifespan Extension ◽  
Dietary Interventions ◽  
Negative Effects ◽  
Trade Offs ◽  
Wide Range ◽  
Broad Variety

Dietary restriction (DR) increases lifespan in a broad variety of organisms and improves health in humans. However, long-term transgenerational consequences of dietary interventions are poorly understood. Here, we investigated the effect of DR by temporary fasting (TF) on mortality risk, age-specific reproduction and fitness across three generations of descendants in Caenorhabditis elegans . We show that while TF robustly reduces mortality risk and improves late-life reproduction of the individuals subject to TF (P 0 ), it has a wide range of both positive and negative effects on their descendants (F 1 –F 3 ). Remarkably, great-grandparental exposure to TF in early life reduces fitness and increases mortality risk of F 3 descendants to such an extent that TF no longer promotes a lifespan extension. These findings reveal that transgenerational trade-offs accompany the instant benefits of DR, underscoring the need to consider fitness of future generations in pursuit of healthy ageing.

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