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1.
Nat Commun ; 11(1): 5062, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033254

RESUMO

Septins are GTP-binding proteins involved in diverse cellular processes including division and membrane remodeling. Septins form linear, palindromic heteromeric complexes that can assemble in filaments and higher-order structures. Structural studies revealed various septin architectures, but questions concerning assembly-dynamics and -pathways persist. Here we used high-speed atomic force microscopy (HS-AFM) and kinetic modeling which allowed us to determine that septin filament assembly was a diffusion-driven process, while formation of higher-order structures was complex and involved self-templating. Slightly acidic pH and increased monovalent ion concentrations favor filament-assembly, -alignment and -pairing. Filament-alignment and -pairing further favored diffusion-driven assembly. Pairing is mediated by the septin N-termini face, and may occur symmetrically or staggered, likely important for the formation of higher-order structures of different shapes. Multilayered structures are templated by the morphology of the underlying layers. The septin C-termini face, namely the C-terminal extension of Cdc12, may be involved in membrane binding.


Assuntos
Microscopia de Força Atômica , Septinas/metabolismo , Simulação por Computador , Difusão , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Cinética , Lipídeos/química , Domínios Proteicos , Septinas/ultraestrutura , Eletricidade Estática
4.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2227-2230, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018450

RESUMO

Organ-on-a-chip has the potential to replace preclinical trials which have been problematic for decades due to unaffordable cost and time. The performance of in vitro tumor-on-a-chip depends on how accurately the system represents analogous tumor-microenvironment (TME) and TME associated phenomena. In this study, we have focused on angiogenesis, one of the most significant features of TME for tumor growth and metastasis. Angiogenesis in TME is triggered through cascaded interactions among TME associated neighboring cells including immune cells, tumor cells, and fibroblast cells [1]. Therefore, temporally-controlled TME-on-a-chip is desired for an accurate representation of angiogenesis. However, conventional microfluidic devices cannot temporarily manipulate the condition of interacting cells and secreted signal molecules. Here, we proposed a hydrogel-based variable TME-on-a-chip with diffusion switch channels. The channels between hydrogel walls enable temporal diffusion control by controlling inflow. The diffusion control was observed in diffusion experiment with a fluorescent dye. Furthermore, experiment of HUVEC's migration toward diffused VEGF also confirmed that TME-on-a-chip is capable of reproducing an angiogenic switch triggering through temporal diffusion control. Due to a simple fabrication procedure, the design of the microfluidic device can be easily modified to represent more complex variable TME models.


Assuntos
Doenças Hematológicas , Neoplasias , Difusão , Humanos , Dispositivos Lab-On-A-Chip , Microambiente Tumoral
5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2279-2282, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018462

RESUMO

Simulations that are meant to determine the steady-state distribution of a diffusible solute such as oxygen in tissues have typically used finite difference methods to solve the diffusion equation. Finite difference methods require a tissue mesh with enough points to resolve oxygen gradients near and between discrete blood vessels. The large number of points that are typically required can make these calculations very slow. In this paper, we investigate a numerical method known as the Green's function method which is not bound by the same constraint. The Green's function method is expected to yield an accurate oxygen distribution more quickly by requiring fewer mesh points. Both methods were applied to calculate the steady state oxygen distribution in a model simulation region. When the Green's function calculation used meshes with 1/2, 1/4 and, 1/8 of the resolution required for the finite-difference mesh, there was good agreement with the finite difference calculation in all cases. When the volume of the domain was increased 8-fold the Green's function method was able to calculate the O2 field in 22 minutes, whereas the finite difference calculation is expected to take approximately 1 week. The number of steps required for the Green's function calculation increases quadratically with the number of points in the tissue mesh. As a result, small meshes are calculated very quickly using Green's functions, while for larger mesh sizes this method experiences a significant decrease in efficiency.


Assuntos
Algoritmos , Oxigênio , Cor , Difusão , Fenômenos Físicos
6.
J Perioper Pract ; 30(9): 277-282, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32869726

RESUMO

INTRODUCTION: COVID-19 has changed the approach to operating on breast cancer for the benefit of patients, staff and the general population. One approach involves the switch from operating under general to local anaesthetic. We assess whether diluational local anaesthetic is as effective as the current standard approach. METHODS: Postoperative pain was recorded in prospective, consecutive patients undergoing wide local excision under dilutional local anaesthetic (concentration < 1mg/ml). Pain scores were documented at 0, 30 and 60 minutes and compared to a control group consisting of combined general with local anaesthetic. RESULTS: Pain significantly increased in the control group during the postoperative recovery. This was not seen in the dilutional local anaesthetic group that was non-inferior to the standard approach at 0, 30 and 60 minutes. CONCLUSION: Dilutional local anaesthetic provides a safe and effective alternative approach to operating on breast cancer patients whilst avoiding risky general anaesthetic in a COVID-19 pandemic environment.


Assuntos
Anestesia Local/métodos , Anestésicos Locais/uso terapêutico , Neoplasias da Mama/cirurgia , Infecções por Coronavirus , Dor Pós-Operatória/prevenção & controle , Pandemias , Pneumonia Viral , Estudos de Casos e Controles , Difusão , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Chaos ; 30(8): 081104, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32872802

RESUMO

The coronavirus 2019 (COVID-19) respiratory disease is caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which uses the enzyme ACE2 to enter human cells. This disease is characterized by important damage at a multi-organ level, partially due to the abundant expression of ACE2 in practically all human tissues. However, not every organ in which ACE2 is abundant is affected by SARS-CoV-2, which suggests the existence of other multi-organ routes for transmitting the perturbations produced by the virus. We consider here diffusive processes through the protein-protein interaction (PPI) network of proteins targeted by SARS-CoV-2 as an alternative route. We found a subdiffusive regime that allows the propagation of virus perturbations through the PPI network at a significant rate. By following the main subdiffusive routes across the PPI network, we identify proteins mainly expressed in the heart, cerebral cortex, thymus, testis, lymph node, kidney, among others of the organs reported to be affected by COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Modelos Biológicos , Pneumonia Viral/fisiopatologia , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteoma , Biomarcadores/metabolismo , Infecções por Coronavirus/metabolismo , Difusão , Humanos , Pandemias , Pneumonia Viral/metabolismo , Fatores de Tempo
8.
PLoS Comput Biol ; 16(9): e1008159, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32925923

RESUMO

Intracellular spatial heterogeneity is frequently observed in bacteria, where the chromosome occupies part of the cell's volume and a circuit's DNA often localizes within the cell. How this heterogeneity affects core processes and genetic circuits is still poorly understood. In fact, commonly used ordinary differential equation (ODE) models of genetic circuits assume a well-mixed ensemble of molecules and, as such, do not capture spatial aspects. Reaction-diffusion partial differential equation (PDE) models have been only occasionally used since they are difficult to integrate and do not provide mechanistic understanding of the effects of spatial heterogeneity. In this paper, we derive a reduced ODE model that captures spatial effects, yet has the same dimension as commonly used well-mixed models. In particular, the only difference with respect to a well-mixed ODE model is that the association rate constant of binding reactions is multiplied by a coefficient, which we refer to as the binding correction factor (BCF). The BCF depends on the size of interacting molecules and on their location when fixed in space and it is equal to unity in a well-mixed ODE model. The BCF can be used to investigate how spatial heterogeneity affects the behavior of core processes and genetic circuits. Specifically, our reduced model indicates that transcription and its regulation are more effective for genes located at the cell poles than for genes located on the chromosome. The extent of these effects depends on the value of the BCF, which we found to be close to unity. For translation, the value of the BCF is always greater than unity, it increases with mRNA size, and, with biologically relevant parameters, is substantially larger than unity. Our model has broad validity, has the same dimension as a well-mixed model, yet it incorporates spatial heterogeneity. This simple-to-use model can be used to both analyze and design genetic circuits while accounting for spatial intracellular effects.


Assuntos
Bactérias , Redes Reguladoras de Genes/genética , Genes Bacterianos/genética , Modelos Biológicos , Bactérias/química , Bactérias/citologia , Bactérias/genética , Biologia Computacional , Difusão , Espaço Intracelular/química , Espaço Intracelular/genética
9.
Nat Commun ; 11(1): 4450, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895379

RESUMO

Hollow multishelled structures (HoMSs), with relatively isolated cavities and hierarchal pores in the shells, are structurally similar to cells. Functionally inspired by the different transmission forms in living cells, we studied the mass transport process in HoMSs in detail. In the present work, after introducing the antibacterial agent methylisothiazolinone (MIT) as model molecules into HoMSs, we discover three sequential release stages, i.e., burst release, sustained release and stimulus-responsive release, in one system. The triple-shelled structure can provide a long sterility period in a bacteria-rich environment that is nearly 8 times longer than that of the pure antimicrobial agent under the same conditions. More importantly, the HoMS system provides a smart responsive release mechanism that can be triggered by environmental changes. All these advantages could be attributed to chemical diffusion- and physical barrier-driven temporally-spatially ordered drug release, providing a route for the design of intelligent nanomaterials.


Assuntos
Antibacterianos/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Portadores de Fármacos/química , Nanoestruturas/química , Antibacterianos/farmacocinética , Preparações de Ação Retardada/farmacocinética , Difusão , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microesferas , Tiazóis/administração & dosagem , Tiazóis/farmacocinética
10.
Chemosphere ; 258: 127357, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32947670

RESUMO

Diffusive isotope fractionation of non- and perdeuterated benzenes and toluenes in aqueous solution was investigated. The experimental method was based on a Stokes diaphragm cell. The isotope composition of diffusate and retentate was found to be identical within a range of uncertainty of ±5‰ for benzene and ±10‰ for toluene. These data are consistent with a previous fractionation study using phase-transition kinetics as the potentially fractionating step. The present study contributes to strengthening the data base for diffusive isotope fractionation of organic compounds in aqueous solution. According to the presented data, diffusion of naturally occurring, monodeuterated organic compounds does not significantly affect their hydrogen isotope pattern.


Assuntos
Hidrocarbonetos/química , Poluentes Químicos da Água/química , Benzeno , Isótopos de Carbono , Fracionamento Químico/métodos , Difusão , Hidrogênio , Isótopos , Cinética , Tolueno , Água
11.
J Perioper Pract ; 30(9): 277-282, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: covidwho-737644

RESUMO

INTRODUCTION: COVID-19 has changed the approach to operating on breast cancer for the benefit of patients, staff and the general population. One approach involves the switch from operating under general to local anaesthetic. We assess whether diluational local anaesthetic is as effective as the current standard approach. METHODS: Postoperative pain was recorded in prospective, consecutive patients undergoing wide local excision under dilutional local anaesthetic (concentration < 1mg/ml). Pain scores were documented at 0, 30 and 60 minutes and compared to a control group consisting of combined general with local anaesthetic. RESULTS: Pain significantly increased in the control group during the postoperative recovery. This was not seen in the dilutional local anaesthetic group that was non-inferior to the standard approach at 0, 30 and 60 minutes. CONCLUSION: Dilutional local anaesthetic provides a safe and effective alternative approach to operating on breast cancer patients whilst avoiding risky general anaesthetic in a COVID-19 pandemic environment.


Assuntos
Anestesia Local/métodos , Anestésicos Locais/uso terapêutico , Neoplasias da Mama/cirurgia , Infecções por Coronavirus , Dor Pós-Operatória/prevenção & controle , Pandemias , Pneumonia Viral , Estudos de Casos e Controles , Difusão , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
12.
Chaos ; 30(8): 081104, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: covidwho-740056

RESUMO

The coronavirus 2019 (COVID-19) respiratory disease is caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which uses the enzyme ACE2 to enter human cells. This disease is characterized by important damage at a multi-organ level, partially due to the abundant expression of ACE2 in practically all human tissues. However, not every organ in which ACE2 is abundant is affected by SARS-CoV-2, which suggests the existence of other multi-organ routes for transmitting the perturbations produced by the virus. We consider here diffusive processes through the protein-protein interaction (PPI) network of proteins targeted by SARS-CoV-2 as an alternative route. We found a subdiffusive regime that allows the propagation of virus perturbations through the PPI network at a significant rate. By following the main subdiffusive routes across the PPI network, we identify proteins mainly expressed in the heart, cerebral cortex, thymus, testis, lymph node, kidney, among others of the organs reported to be affected by COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Modelos Biológicos , Pneumonia Viral/fisiopatologia , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteoma , Biomarcadores/metabolismo , Infecções por Coronavirus/metabolismo , Difusão , Humanos , Pandemias , Pneumonia Viral/metabolismo , Fatores de Tempo
13.
Adv Exp Med Biol ; 1267: 15-43, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32894475

RESUMO

Diffusion within bacteria is often thought of as a "simple" random process by which molecules collide and interact with each other. New research however shows that this is far from the truth. Here we shed light on the complexity and importance of diffusion in bacteria, illustrating the similarities and differences of diffusive behaviors of molecules within different compartments of bacterial cells. We first describe common methodologies used to probe diffusion and the associated models and analyses. We then discuss distinct diffusive behaviors of molecules within different bacterial cellular compartments, highlighting the influence of metabolism, size, crowding, charge, binding, and more. We also explicitly discuss where further research and a united understanding of what dictates diffusive behaviors across the different compartments of the cell are required, pointing out new research avenues to pursue.


Assuntos
Bactérias/metabolismo , Fenômenos Biofísicos , Difusão
15.
Phys Rev Lett ; 125(5): 058101, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32794890

RESUMO

Diffusion of tracer particles in the cytoplasm of mammalian cells is often anomalous with a marked heterogeneity even within individual particle trajectories. Despite considerable efforts, the mechanisms behind these observations have remained largely elusive. To tackle this problem, we performed extensive single-particle tracking experiments on quantum dots in the cytoplasm of living mammalian cells at varying conditions. Analyses of the trajectories reveal a strong, microtubule-dependent subdiffusion with antipersistent increments and a substantial heterogeneity. Furthermore, particles stochastically switch between different mobility states, most likely due to transient associations with the cytoskeleton-shaken endoplasmic reticulum network. Comparison to simulations highlight that all experimental observations can be fully described by an intermittent fractional Brownian motion, alternating between two states of different mobility.


Assuntos
Citoplasma/metabolismo , Modelos Biológicos , Citoesqueleto de Actina/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Simulação por Computador , Citocalasina D/farmacologia , Citoplasma/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Difusão , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Células HeLa , Humanos , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Nocodazol/farmacologia , Pontos Quânticos , Processos Estocásticos , Tiazolidinas/farmacologia
16.
Phys Rev Lett ; 125(7): 078102, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32857533

RESUMO

Diffusion-mediated surface phenomena are crucial for human life and industry, with examples ranging from oxygen capture by lung alveolar surface to heterogeneous catalysis, gene regulation, membrane permeation, and filtration processes. Their current description via diffusion equations with mixed boundary conditions is limited to simple surface reactions with infinite or constant reactivity. In this Letter, we propose a probabilistic approach based on the concept of boundary local time to investigate the intricate dynamics of diffusing particles near a reactive surface. Reformulating surface-particle interactions in terms of stopping conditions, we obtain in a unified way major diffusion-reaction characteristics such as the propagator, the survival probability, the first-passage time distribution, and the reaction rate. This general formalism allows us to describe new surface reaction mechanisms such as for instance surface reactivity depending on the number of encounters with the diffusing particle that can model the effects of catalyst fooling or membrane degradation. The disentanglement of the geometric structure of the medium from surface reactivity opens far-reaching perspectives for modeling, optimization, and control of diffusion-mediated surface phenomena.


Assuntos
Modelos Biológicos , Modelos Químicos , Membrana Celular/química , DNA/química , Difusão , Proteínas/química , Propriedades de Superfície , Termodinâmica
17.
Sci Total Environ ; 738: 140096, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32806372

RESUMO

According to ISO 17402:2008 more knowledge is needed on processes controlling bioavailability of organic species so as to close the still existing gap between chemical measurements and biological effects. The bioavailability concept encompasses the investigation of the degree of penetration of target species across biological membranes. In addition, REACH (Registration, Evaluation, Authorisation and restriction of Chemicals) guidelines promote the use of in-vitro methods against conventional ecotoxicological tests because of the ethical controversy of in-vivo tests. This work is aimed at filling the gap by proposing a multidisciplinary approach based on high-resolution and low-resolution empirical techniques, and theoretical quantum mechanics for the in-vitro investigation of the bioavailability and membranotropic effects of organic emerging contaminants, including bioaccumulation, via passive diffusion across lipid bilayers. Phosphatidylcholine (PC) liposomes are selected as biomembrane surrogates, and contaminant effects are explored by (i) fluorescence anisotropy and generalized polarization assays using membrane fluorescence probes (laurdan and prodan) and UV-Vis spectroscopy, (ii) 1H NMR measurements to ascertain supramolecular interactions with PC and (iii) molecular dynamics simulations. In particular, un-regulated model compounds with distinct physico-chemical properties that are representative of three different classes of emerging contaminants in environmental compartments are chosen for validation of the holistic approach: (i) diclofenac as a model of anti-inflammatory drug; (ii) triclosan as an anti-microbial agent; and (iii) bisphenol A as a plastic-borne compound, and compared with chlorpyrifos as a legacy insecticide. Laurdan anisotropic measurements are in good agreement with 1H NMR data and both approaches pinpoint that triclosan and chlorpyrifos are highly bioaccumulative in membranes. Molecular dynamic studies indicate that the lateral diffusion of the lipid bilayer is much lower with the incorporation of either triclosan or chlorpyrifos into the bilayer. The theoretical simulations also allowed estimating absolute bioavailability data under passive diffusion (<0.1%, 63%, 73% and 89% for diclofenac, bisphenol A, triclosan and chlorpyrifos, respectively) given as the percentage of time that a given species is located in the region of the fatty acyl chains. Our findings indicate that PC-based liposome assays serve as a fast and cost-effective in-vitro approach, notwithstanding its low resolution features, for environmental bioavailability studies of emerging contaminants for which insufficient or inconsistent ecotoxicological data are identified in the literature.


Assuntos
Lipossomos , Triclosan , Disponibilidade Biológica , Difusão , Fosfatidilcolinas
18.
J Chromatogr A ; 1626: 461283, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32797812

RESUMO

Two-dimensional liquid chromatography is increasingly being used to address challenging separations in fields ranging from pharmaceutical analysis to the food industry. A significant impediment to development of more methods is the lack of a complete theoretical foundation upon which sound development decisions can be made. One parameter that is currently not fully understood is the extent of filling of sampling loops in the case where effluent from the first dimension separation is transferred to the second dimension separation through this type of open loop interface. This is a highly important parameter because it is connected to several other variables in a 2D-LC system, including the first dimension flow rate, the sampling (modulation) time, and the loop volume. In this study we have used both numerical simulation methods and experimental measurements to understand the extent to which sampling loops can be filled before a significant fraction of the analyte is lost from the end of the loop. Variables included in the study are the analyte diffusion coefficient (Dmol), loop filling rate (Ffill), loop inner diameter or radius (Rloop) and loop volume (Vloop). For a straight loop capillary we find that analyte breakthrough curves (as measured at the loop outlet) depend only on a single the dimensionless parameter t*=VloopFfill·DmolRloop2 . As a function of this parameter, the fraction of analyte lost from the loop outlet for different extents of loop filling could be calculated, allowing to develop guidelines for the maximum permissible extent of filling before a specified level of analyte loss is reached. Breakthrough measurements using a coiled loop capillary show that less breakthrough is observed compared to the straight capillary at high filling flow rates, presumably due to secondary flows that increase radial dispersion. These measurements enabled the calculation of apparent radial diffusion coefficients for use with coiled capillaries such that the same relation for t* can be used to predict analyte loss due to breakthrough. These results should be very useful to practitioners of 2D-LC, enabling them to make rational decisions about the extent of loop filling on the basis of experimental conditions and analyte type.


Assuntos
Cromatografia Líquida/métodos , Cromatografia Líquida/instrumentação , Difusão , Modelos Teóricos
19.
J Chromatogr A ; 1626: 461319, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32797815

RESUMO

The aim of this study is to model, describe and predict the mass transfer of IgG as a function of the agarose concentration in the protein A stationary phase, taking into account the influence of adsorption on the pore size. Therefore, particle size distribution, bed and bead porosities were examined by light microscopy, pressure-flow behavior and iSEC. Three agarose protein A stationary phases (2 wt%, 4 wt%, 6 wt%) were investigated. The pore size decreased from 116 nm for 2 wt% to 54 nm for 6 wt% and the porosity for the target molecule IgG was reduced by 25%. A shrinking core model approach was used to assess the influence of IgG adsorption on the pore size of the stationary phase and the diffusivity of IgG. Due to IgG adsorption, the pore diameter reduced by 24 nm, which is approximately two times its hydrodynamic diameter. Effective pore diffusivities of IgG were obtained by fitting the general rate model to breakthrough curves. They were in the range between 3.96·10-12m2/s and 6.5·10-12m2/s, decreasing as the agarose concentration increased. The DBC1% has a maximum for the 4 wt% agarose gel, showing optimal tradeoffs between accessibility, specific surface and diffusive mass transfer for IgG. A simple geometrical model was developed to describe the change in pore and filament diameters due to adsorption. The diffusion measured in protein A agarose beads can be described by a modification of the Ogston model. This enables the diffusion measured in protein A agarose networks to be predicted.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Sefarose/química , Adsorção , Cromatografia em Gel , Difusão , Imunoglobulina G/metabolismo , Tamanho da Partícula , Porosidade , Ligação Proteica , Proteína Estafilocócica A/metabolismo
20.
PLoS One ; 15(8): e0238253, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857812

RESUMO

The origins of life on Earth have been the subject of inquiry since the early days of philosophical thought and are still intensively investigated by the researchers around the world. One of the theories explaining the life emergence, that gained the most attention recently is the RNA World hypothesis, which assumes that life on Earth was sparked by replicating RNA chains. Since wet lab analysis is time-consuming, many mathematical and computational approaches have been proposed that try to explain the origins of life. Recently proposed one, based on the work by Takeuchi and Hogeweg, addresses the problem of interplay between RNA replicases and RNA parasitic species, which is crucial for understanding the first steps of prebiotic evolution. In this paper, the aforementioned model has been extended and modified by introducing RNA sequence (structure) information and mutation rate close to real one. It allowed to observe the simple evolution mechanisms, which could have led to the more complicated systems and eventually, to the formation of the first cells. The main goal of this study was to determine the conditions that allowed the spontaneous emergence and evolution of the prebiotic replicases equipped with simple functional domains within a large population. Here we show that polymerase ribozymes could have appeared randomly and then quickly started to copy themselves in order for the system to reach equilibrium. It has been shown that evolutionary selection works even in the simplest systems.


Assuntos
Sequência de Bases , Simulação por Computador , Modelos Teóricos , Conformação de Ácido Nucleico , Origem da Vida , RNA , Algoritmos , Difusão , Hidrólise , Mutação , RNA/química , RNA Replicase/química , RNA Replicase/genética
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