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1.
Chaos ; 31(8): 083101, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34470255

RESUMO

Phytoplankton-zooplankton interaction is a topic of high interest among the interrelationships related to marine habitats. In the present manuscript, we attempt to study the dynamics of a three-dimensional system with three types of plankton: non-toxic phytoplankton, toxic producing phytoplankton, and zooplankton. We assume that both non-toxic and toxic phytoplankton are consumed by zooplankton via Beddington-DeAngelis and general Holling type-IV responses, respectively. We also incorporate gestation delay and toxic liberation delay in zooplankton's interactions with non-toxic and toxic phytoplankton correspondingly. First, we have studied the well-posedness of the system. Then, we analyze all the possible equilibrium points and their local and global asymptotic behavior. Furthermore, we assessed the conditions for the occurrence of Hopf-bifurcation and transcritical bifurcation. Using the normal form method and center manifold theorem, the conditions for stability and direction of Hopf-bifurcation are also studied. Various time-series, phase portraits, and bifurcation diagrams are plotted to confirm our theoretical findings. From the numerical simulation, we observe that a limited increase in inhibitory effect of toxic phytoplankton against zooplankton can support zooplankton's growth, and rising predator's interference can also boost zooplankton expansion in contrast to the nature of Holling type IV and Beddington-DeAngelis responses. Next, we notice that on variation of toxic liberation delay, the delayed system switches its stability multiple times and becomes chaotic. Furthermore, we draw the Poincaré section and evaluate the maximum Lyapunov exponent in order to verify the delayed system's chaotic nature. Results presented in this article might be helpful to interpret biological insights into phytoplankton-zooplankton interactions.


Assuntos
Fitoplâncton , Zooplâncton , Animais , Simulação por Computador , Ecossistema , Modelos Biológicos
2.
J Hazard Mater ; 416: 125856, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492805

RESUMO

Inhalation of aerosols such as pharmaceutical aerosols or virus aerosol uptake is of great concern to the human population. To elucidate the underlying aerosol dynamics, the deposition fractions (DFs) of aerosols in healthy and asthmatic human airways of generations 13-15 are predicted. The Navier-stokes equations governing the gaseous phase and the discrete phase model for particles' motion are solved using numerical methods. The main forces responsible for deposition are inertial impaction forces and complex secondary flow velocities. The curvatures and sinusoidal folds in the asthmatic geometry lead to the formation of complex secondary flows and hence higher DFs. The intensities of complex secondary flows are strongest at the generations affected by asthma. The DF in the healthy airways is 0%, and it ranges from 1.69% to 52.93% in the asthmatic ones. From this study, the effects of the pharmaceutical aerosol particle diameters in the treatment of asthma patients can be established, which is conducive to inhibiting the inflammation of asthma airways. Furthermore, with the recent development of COVID-19 which causes pneumonia, the predicted physics and effective simulation methods of bioaerosols delivery to asthma patients are vital to prevent the exacerbation of the chronic ailment and the epidemic.


Assuntos
Asma , COVID-19 , Aerossóis , Asma/tratamento farmacológico , Simulação por Computador , Humanos , Pulmão , Modelos Biológicos , Tamanho da Partícula , SARS-CoV-2
3.
Sci Rep ; 11(1): 17473, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471195

RESUMO

As for all newly-emergent pathogens, SARS-CoV-2 presents with a relative paucity of clinical information and experimental models, a situation hampering both the development of new effective treatments and the prediction of future outbreaks. Here, we find that a simple virus-free model, based on publicly available transcriptional data from human cell lines, is surprisingly able to recapitulate several features of the clinically relevant infections. By segregating cell lines (n = 1305) from the CCLE project on the base of their sole angiotensin-converting enzyme 2 (ACE2) mRNA content, we found that overexpressing cells present with molecular features resembling those of at-risk patients, including senescence, impairment of antibody production, epigenetic regulation, DNA repair and apoptosis, neutralization of the interferon response, proneness to an overemphasized innate immune activity, hyperinflammation by IL-1, diabetes, hypercoagulation and hypogonadism. Likewise, several pathways were found to display a differential expression between sexes, with males being in the least advantageous position, thus suggesting that the model could reproduce even the sex-related disparities observed in the clinical outcome of patients with COVID-19. Overall, besides validating a new disease model, our data suggest that, in patients with severe COVID-19, a baseline ground could be already present and, as a consequence, the viral infection might simply exacerbate a variety of latent (or inherent) pre-existing conditions, representing therefore a tipping point at which they become clinically significant.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , COVID-19/genética , Perfilação da Expressão Gênica/métodos , Regulação para Cima , COVID-19/imunologia , Linhagem Celular , Bases de Dados Genéticas , Feminino , Humanos , Imunidade Inata , Masculino , Modelos Biológicos , Modelos Teóricos , Caracteres Sexuais
4.
J Adv Res ; 32: 27-36, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34484823

RESUMO

Introduction: In long-term induced general anesthesia cases such as those uniquely defined by the ongoing Covid-19 pandemic context, the clearance of hypnotic and analgesic drugs from the body follows anomalous diffusion with afferent drug trapping and escape rates in heterogeneous tissues. Evidence exists that drug molecules have a preference to accumulate in slow acting compartments such as muscle and fat mass volumes. Currently used patient dependent pharmacokinetic models do not take into account anomalous diffusion resulted from heterogeneous drug distribution in the body with time varying clearance rates. Objectives: This paper proposes a mathematical framework for drug trapping estimation in PK models for estimating optimal drug infusion rates to maintain long-term anesthesia in Covid-19 patients. We also propose a protocol for measuring and calibrating PK models, along with a methodology to minimize blood sample collection. Methods: We propose a framework enabling calibration of the models during the follow up of Covid-19 patients undergoing anesthesia during their treatment and recovery period in ICU. The proposed model can be easily updated with incoming information from clinical protocols on blood plasma drug concentration profiles. Already available pharmacokinetic and pharmacodynamic models can be then calibrated based on blood plasma concentration measurements. Results: The proposed calibration methodology allow to minimize risk for potential over-dosing as clearance rates are updated based on direct measurements from the patient. Conclusions: The proposed methodology will reduce the adverse effects related to over-dosing, which allow further increase of the success rate during the recovery period.


Assuntos
Anestesia , COVID-19 , Hipnóticos e Sedativos , Modelos Biológicos , SARS-CoV-2 , Idoso , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacocinética , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Pandemias
6.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445501

RESUMO

Lipid dysregulation in diabetes mellitus escalates endothelial dysfunction, the initial event in the development and progression of diabetic atherosclerosis. In addition, lipid-laden macrophage accumulation in the arterial wall plays a significant role in the pathology of diabetes-associated atherosclerosis. Therefore, inhibition of endothelial dysfunction and enhancement of macrophage cholesterol efflux is the important antiatherogenic mechanism. Rosmarinic acid (RA) possesses beneficial properties, including its anti-inflammatory, antioxidant, antidiabetic and cardioprotective effects. We previously reported that RA effectively inhibits diabetic endothelial dysfunction by inhibiting inflammasome activation in endothelial cells. However, its effect on cholesterol efflux remains unknown. Therefore, in this study, we aimed to assess the effect of RA on cholesterol efflux and its underlying mechanisms in macrophages. RA effectively reduced oxLDL-induced cholesterol contents under high glucose (HG) conditions in macrophages. RA enhanced ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) expression, promoting macrophage cholesterol efflux. Mechanistically, RA differentially regulated ABCA1 expression through JAK2/STAT3, JNK and PKC-p38 and ABCG1 expression through JAK2/STAT3, JNK and PKC-ERK1/2/p38 in macrophages. Moreover, RA primarily stabilized ABCA1 rather than ABCG1 protein levels by impairing protein degradation. These findings suggest RA as a candidate therapeutic to prevent atherosclerotic cardiovascular disease complications related to diabetes by regulating cholesterol efflux in macrophages.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Colesterol/metabolismo , Cinamatos/farmacologia , Depsídeos/farmacologia , Glucose/efeitos adversos , Lipoproteínas LDL/efeitos adversos , Macrófagos/citologia , Transportador 1 de Cassete de Ligação de ATP/química , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Modelos Biológicos , Proteólise/efeitos dos fármacos , Transdução de Sinais , Células THP-1
7.
Hist Philos Life Sci ; 43(3): 103, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34427800

RESUMO

Menopause is an evolutionary mystery: how could living longer with no capacity to reproduce possibly be advantageous? Several explanations have been offered for why female humans, unlike our closest primate relatives, have such an extensive post-reproductive lifespan. Proponents of the so-called "grandmother hypothesis" suggest that older women are able to increase their fitness by helping to care for their grandchildren as allomothers. This paper first distinguishes the grandmother hypothesis from several other hypotheses that attempt to explain menopause, and then develops a formal model by which these hypotheses can be compared and tested by empirical researchers. The model is then modified and used to respond to a common objection to the grandmother hypothesis: that human fathers, rather than grandmothers, are better suited to be allomothers due to their physical strength and a high incentive to invest in their own children. However, fathers-unlike maternal grandmothers-can never be sure that the children they are caring for are their own. Incorporating paternity uncertainty into the model demonstrates the conditions under which the grandmother hypothesis is more plausible than a hypothesis that focuses on the contributions of men.


Assuntos
Família , Avós , Menopausa , Modelos Biológicos , Feminino , Aptidão Genética , Humanos
8.
Nat Commun ; 12(1): 5086, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429404

RESUMO

Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs' recapitulation of human tumors.


Assuntos
Xenoenxertos , Neoplasias/genética , Neoplasias/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Genoma , Genômica , Humanos , Masculino , Camundongos , Modelos Biológicos , Mutação , Transcriptoma
9.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360740

RESUMO

Spinocerebellar ataxia type 3 (SCA3) is a genetic neurodegenerative disease for which a cure is still needed. Growth hormone (GH) therapy has shown positive effects on the exercise behavior of mice with cerebellar atrophy, retains more Purkinje cells, and exhibits less DNA damage after GH intervention. Insulin-like growth factor 1 (IGF-1) is the downstream mediator of GH that participates in signaling and metabolic regulation for cell growth and modulation pathways, including SCA3-affected pathways. However, the underlying therapeutic mechanisms of GH or IGF-1 in SCA3 are not fully understood. In the present study, tissue-specific genome-scale metabolic network models for SCA3 transgenic mice were proposed based on RNA-seq. An integrative transcriptomic and metabolic network analysis of a SCA3 transgenic mouse model revealed that metabolic signaling pathways were activated to compensate for the metabolic remodeling caused by SCA3 genetic modifications. The effect of IGF-1 intervention on the pathology and balance of SCA3 disease was also explored. IGF-1 has been shown to invoke signaling pathways and improve mitochondrial function and glycolysis pathways to restore cellular functions. As one of the downregulated factors in SCA3 transgenic mice, IGF-1 could be a potential biomarker and therapeutic target.


Assuntos
Reprogramação Celular , Perfilação da Expressão Gênica , Fator de Crescimento Insulin-Like I/metabolismo , Doença de Machado-Joseph/metabolismo , Modelos Biológicos , Transdução de Sinais , Animais , Ataxina-3/genética , Ataxina-3/metabolismo , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Fator de Crescimento Insulin-Like I/genética , Doença de Machado-Joseph/genética , Camundongos , Camundongos Transgênicos
10.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360784

RESUMO

In human spermatozoa, calcium dynamics control most of fertilization events. Progesterone, present in the female reproductive system, can trigger several types of calcium responses, such as low-frequency oscillations. Here we aimed to identify the mechanisms of progesterone-induced calcium signaling in human spermatozoa. Progesterone-induced activation of fluorophore-loaded spermatozoa was studied by fluorescent microscopy. Two computational models were developed to describe the spermatozoa calcium responses: a homogeneous one based on a system of ordinary differential equations and a three-dimensional one with added space dimensions and diffusion for the cytosolic species. In response to progesterone, three types of calcium responses were observed in human spermatozoa: a single transient rise of calcium concentration in cytosol, a steady elevation, or low-frequency oscillations. The homogenous model provided qualitative description of the oscillatory and the single spike responses, while the three-dimensional model captured the calcium peak shape and the frequency of calcium oscillations. The model analysis demonstrated that an increase in the calcium diffusion coefficient resulted in the disappearance of the calcium oscillations. Additionally, in silico analysis suggested that the spatial distribution of calcium signaling enzymes governs the appearance of calcium oscillations in progesterone-activated human spermatozoa.


Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Simulação por Computador , Modelos Biológicos , Progesterona/farmacologia , Espermatozoides/enzimologia , Humanos , Masculino , Microscopia de Fluorescência , Espermatozoides/citologia
11.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360838

RESUMO

Drug-induced liver toxicity is one of the significant safety challenges for the patient's health and the pharmaceutical industry. It causes termination of drug candidates in clinical trials and also the retractions of approved drugs from the market. Thus, it is essential to identify hepatotoxic compounds in the initial stages of drug development process. The purpose of this study is to construct quantitative structure activity relationship models using machine learning algorithms and systematical feature selection methods for molecular descriptor sets. The models were built from a large and diverse set of 1253 drug compounds and were validated internally with 10-fold cross-validation. In this study, we applied a variety of feature selection techniques to extract the optimal subset of descriptors as modeling features to improve the prediction performance. Experimental results suggested that the support vector machine-based classifier had achieved a better classification accuracy with reduced molecular descriptors. The final optimal model provides an accuracy of 0.811, a sensitivity of 0.840, a specificity of 0.783 and Mathew's correlation coefficient of 0.623 with an internal validation set. Furthermore, this model outperformed the prior studies while evaluated in both the internal and external test sets. The utilization of distinct optimal molecular descriptors as modeling features produce an in silico model with a superior performance.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Simulação por Computador , Fígado/efeitos dos fármacos , Modelos Biológicos , Relação Quantitativa Estrutura-Atividade , Máquina de Vetores de Suporte , Confiabilidade dos Dados , Humanos , Sensibilidade e Especificidade
12.
Int J Mol Sci ; 22(16)2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34445211

RESUMO

Several poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors are now in clinical use for tumours with defects in BReast CAncer genes BRCA1 or BRCA2 that result in deficient homologous recombination repair (HRR). Use of olaparib, niraparib or rucaparib for the treatment of high-grade serous ovarian cancer, including in the maintenance setting, has extended both progression free and overall survival for women with this malignancy. While different PARP inhibitors (PARPis) are mechanistically similar, differences are apparent in their chemical structures, toxicity profiles, PARP trapping abilities and polypharmacological landscapes. We have treated ovarian cancer cell line models of known BRCA status, including the paired cell lines PEO1 and PEO4, and UWB1.289 and UWB1.289+BRCA1, with five PARPis (olaparib, niraparib, rucaparib, talazoparib and veliparib) and observed differences between PARPis in both cell viability and cell survival. A cell line model of acquired resistance to veliparib showed increased resistance to the other four PARPis tested, suggesting that acquired resistance to one PARPi may not be able to be rescued by another. Lastly, as a proof of principle, HRR proficient ovarian cancer cells were sensitised to PARPis by depletion of BRCA1. In the future, guidelines will need to emerge to assist clinicians in matching specific PARPis to specific patients and tumours.


Assuntos
Proteína BRCA1 , Proteína BRCA2 , Modelos Biológicos , Mutação , Neoplasias Ovarianas , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo
13.
Int J Mol Sci ; 22(16)2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34445219

RESUMO

In the heart, TRPM4 is most abundantly distributed in the conduction system. Previously, a single mutation, 'E7K', was identified in its distal N-terminus to cause conduction disorder because of enhanced cell-surface expression. It remains, however, unclear how this expression increase leads to conduction failure rather than abnormally enhanced cardiac excitability. To address this issue theoretically, we mathematically formulated the gating kinetics of the E7K-mutant TRPM4 channel by a combined use of voltage jump analysis and ionomycin-perforated cell-attached recording technique and incorporated the resultant rate constants of opening and closing into a human Purkinje fiber single-cell action potential (AP) model (Trovato model) to perform 1D-cable simulations. The results from TRPM4 expressing HEK293 cells showed that as compared with the wild-type, the open state is much preferred in the E7K mutant with increased voltage-and Ca2+-sensitivities. These theoretical predictions were confirmed by power spectrum and single channel analyses of expressed wild-type and E7K-mutant TRPM4 channels. In our modified Trovato model, the facilitated opening of the E7K mutant channel markedly prolonged AP duration with concomitant depolarizing shifts of the resting membrane potential in a manner dependent on the channel density (or maximal activity). This was, however, little evident in the wild-type TRPM4 channel. Moreover, 1D-cable simulations with the modified Trovato model revealed that increasing the density of E7K (but not of wild-type) TRPM4 channels progressively reduced AP conduction velocity eventually culminating in complete conduction block. These results clearly suggest the brady-arrhythmogenicity of the E7K mutant channel which likely results from its pathologically enhanced activity.


Assuntos
Mutação com Ganho de Função , Modelos Biológicos , Canais de Cátion TRPM , Células HEK293 , Humanos , Potenciais da Membrana , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo
14.
Life Sci Alliance ; 4(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34353886

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by the new coronavirus (SARS-CoV-2) is currently responsible for more than 3 million deaths in 219 countries across the world and with more than 140 million cases. The absence of FDA-approved drugs against SARS-CoV-2 has highlighted an urgent need to design new drugs. We developed an integrated model of the human cell and SARS-CoV-2 to provide insight into the virus' pathogenic mechanism and support current therapeutic strategies. We show the biochemical reactions required for the growth and general maintenance of the human cell, first, in its healthy state. We then demonstrate how the entry of SARS-CoV-2 into the human cell causes biochemical and structural changes, leading to a change of cell functions or cell death. A new computational method that predicts 20 unique reactions as drug targets from our models and provides a platform for future studies on viral entry inhibition, immune regulation, and drug optimisation strategies. The model is available in BioModels (https://www.ebi.ac.uk/biomodels/MODEL2007210001) and the software tool, findCPcli, that implements the computational method is available at https://github.com/findCP/findCPcli.


Assuntos
COVID-19/tratamento farmacológico , COVID-19/metabolismo , Desenvolvimento de Medicamentos/métodos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/metabolismo , COVID-19/epidemiologia , Biologia Computacional/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Modelos Biológicos , Pandemias
15.
Postepy Biochem ; 67(1): 28-33, 2021 03 31.
Artigo em Polonês | MEDLINE | ID: mdl-34378896

RESUMO

Autism spectrum disorder (ASD) is common early neurodevelopmental disorder characterized by a varied trajectory and symptoms which affects diagnosis and therapy. For this reason, great diagnostic and therapeutic possibilities are seen in genetic studies. The aim of this review is to discuss the genetic architecture of ASD and possible therapeutic strategies.The patterns of ASD inheritance are discussed, genetic variations (including CNV polymorphisms) and the percentage of the ASD patients divided into specific classes of genetic mutations are indicated. The paper shows the most important three basic models of inheritance: polygenic, oligogenic and main gene. Molecular and cellular mechanisms linked to neurobiological models of ASD are also presented. Genetic research confirms the diversity of genetic factors involved in the ASD formation. Model systems based on the genes of the neurodevelopmental syndrome show the ability to reverse some deficits in adult patients.


Assuntos
Transtorno do Espectro Autista , Adulto , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/genética , Humanos , Modelos Biológicos , Mutação
16.
Chaos ; 31(7): 073124, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34340359

RESUMO

The most important issue of concern in a food chain is the stability of species and their nature of persistence against system parameter changes. For understanding the stable dynamics and their response against parameter perturbation, the local stability analysis is an insufficient tool. A global stability analysis by the conventional techniques seems to supplement some of the shortcomings, however, it becomes more challenging for multistable ecosystems. Either of the techniques fails to provide a complete description of the complexity in dynamics that may evolve in the system, especially, when there is any transition between the stable states. A tri-trophic resource-consumer-predator food chain model has been revisited here that shows bistability and transition to monostability via a border collision that leads to a state of predator extinction. Although earlier studies have partially revealed the dynamics of such transitions, we would like to present additional and precise information by analyzing the system from the perspective of basin stability. By drawing different bifurcation diagrams against three important parameters, using different initial conditions, we identify the range of parameter values within which the stability of the states persists and changes to various complex dynamics. We emphasize the changes in the geometry of the basins of attraction and get a quantitative estimate of the nature of relative changes in the area of the basins (basin stability) during the transitions. Furthermore, we demonstrate the presence of a down-up control, in addition to the conventional bottom-up and top-down control phenomena in the food chain. The application of basin stability in food networks will go a long way for accurate analysis of their dynamics.


Assuntos
Ecossistema , Cadeia Alimentar , Animais , Modelos Biológicos , Dinâmica Populacional , Comportamento Predatório
17.
Chaos ; 31(7): 073141, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34340363

RESUMO

In this article, we derive and analyze a novel predator-prey model with account for maturation delay in predators, ratio dependence, and Holling type III functional response. The analysis of the system's steady states reveals conditions on predation rate, predator growth rate, and maturation time that can result in a prey-only equilibrium or facilitate simultaneous survival of prey and predators in the form of a stable coexistence steady state, or sustain periodic oscillations around this state. Demographic stochasticity in the model is explored by means of deriving a delayed chemical master equation. Using system size expansion, we study the structure of stochastic oscillations around the deterministically stable coexistence state by analyzing the dependence of variance and coherence of stochastic oscillations on system parameters. Numerical simulations of the stochastic model are performed to illustrate stochastic amplification, where individual stochastic realizations can exhibit sustained oscillations in the case, where deterministically the system approaches a stable steady state. These results provide a framework for studying realistic predator-prey systems with Holling type III functional response in the presence of stochasticity, where an important role is played by non-negligible predator maturation delay.


Assuntos
Cadeia Alimentar , Modelos Biológicos , Animais , Ecossistema , Dinâmica Populacional , Comportamento Predatório
18.
J Health Care Poor Underserved ; 32(3): 1320-1338, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421034

RESUMO

To describe the dynamics and forecast the main parameters of the COVID-19 pandemic, the time series of daily cases in the World Health Organization African Region (WHOAR) from February 26th to December 29th, 2020 was analyzed. Estimates for expected values of parameters characterizing an epidemic (size of the epidemic, turning point, maximum value of daily cases, and basic reproductive number) were provided for both the first and the second wave, and for the entire ongoing pandemic in WHOAR. To this aim, the classical SIR (Susceptible-Infected-Removed) model and its approximations were applied to each identified wave. Our results suggest that the turning point of the COVID-19 first wave took place around July 20th, 2020. The first wave was expected to disappear by mid-December 2020, with a total of 1,200,000 expected cases. The second wave apparently started around August 19th, with an expected turning point by January 12th, 2021. The second wave is expected to end by August 9th, 2021, with 1,800,000 cumulative cases, and mounting up to 3,000,000 total cases between February 2020 and August 2021. Estimated basic reproduction numbers (R0) were 1.27 (first wave) and 1.15 (second wave); the expected total number of deaths is around 66,000 victims.


Assuntos
COVID-19/epidemiologia , África ao Sul do Saara/epidemiologia , Número Básico de Reprodução , Humanos , Modelos Biológicos , Pandemias , SARS-CoV-2 , Organização Mundial da Saúde
19.
Nat Commun ; 12(1): 4992, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404777

RESUMO

Liquid chromatography-mass spectrometry-based metabolomics studies are increasingly applied to large population cohorts, which run for several weeks or even years in data acquisition. This inevitably introduces unwanted intra- and inter-batch variations over time that can overshadow true biological signals and thus hinder potential biological discoveries. To date, normalisation approaches have struggled to mitigate the variability introduced by technical factors whilst preserving biological variance, especially for protracted acquisitions. Here, we propose a study design framework with an arrangement for embedding biological sample replicates to quantify variance within and between batches and a workflow that uses these replicates to remove unwanted variation in a hierarchical manner (hRUV). We use this design to produce a dataset of more than 1000 human plasma samples run over an extended period of time. We demonstrate significant improvement of hRUV over existing methods in preserving biological signals whilst removing unwanted variation for large scale metabolomics studies. Our tools not only provide a strategy for large scale data normalisation, but also provides guidance on the design strategy for large omics studies.


Assuntos
Metabolômica/métodos , Cromatografia Líquida , Humanos , Espectrometria de Massas/métodos , Modelos Biológicos , Fluxo de Trabalho
20.
Science ; 373(6552): 280-281, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34437141
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