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Jorge Velázquez-Castro

Publications and source records attributed to Jorge Velázquez-Castro.

11 recordsLinked to original sources

Left-lateralized reduced white matter structural connectivity in young women with obesity: analysis of graph theory applied to inter-tract correlation matrices

Objective: Differences in WM structural connectivity were sought by comparing graph measures from young women with normal weight ($D_\mathrm{norm}$) and obesity ($D_\mathrm{over}$), studying FA-based inter-tract correlation matrices. Methods: Undirected binary adjacency matrices were created from WM inter-tract correlation matrices. Sixteen global graph measures were compared between the $D_\mathrm{norm}$ and $D_\mathrm{over}$ groups. At the nodal level, four graph measures were compared. Optimal community structures were calculated using the Louvain community detection algorithm. This was done considering all network, as well as the left and right hemispheres separately. Results: At the global level and considering all network, the $D_\mathrm{over}$ group had significantly reduced global efficiency compared to the $D_\mathrm{norm}$ group. Considering only the right hemisphere, none of the graph measures were significantly different between the two groups. Studying only the left hemisphere, the $D_\mathrm{over}$ group obtained significantly reduced measures compared to the $D_\mathrm{norm}$ group in five global graph measures. At the nodal level, the $D_\mathrm{over}$ group obtained significantly reduced graph measures in WM tracts when studying all network and the left hemisphere separately. These tracts were mainly involved in the reward network. The optimal community structures calculated were consistent with the results reported. Conclusion: The $D_\mathrm{over}$ group showed altered and reduced structural connectivity in WM tracts compared to the $D_\mathrm{norm}$ group. The reported tracts are involved in reward processing, inhibitory control, executive decision-making, and cognitive processing. In addition to obtaining results consistent with those reported in the literature, it was additionally observed that the results were lateralized to the left hemisphere.

physics.med-ph↗

Oscillations and Spatial Patterns in Large-Scale Stochastic Gene Regulatory Networks

Gene regulatory networks (GRNs) are fundamental to cellular growth and tissue formation, orchestrating spatially and temporally regulated gene expression during development. These networks are inherently subject to intrinsic fluctuations arising from molecular noise, making the analysis of their stability essential for understanding robust pattern formation and developmental dynamics of the organism. In this study, we analyze the stability and dynamics of cyclic GRNs with negative feedback and diffusion, considering both deterministic and stochastic approaches. In the deterministic case, the system exhibits a bifurcation between stability and instability, leading to Hopf instability in the absence of diffusion and to Turing-Hopf instability when diffusion is included. It was observed that the discretization of the spatial domain introduces additional unstable modes, enabling a wider range of patterns. The stochastic framework based on the second-moment approach, which incorporates intrinsic fluctuations, reveals that for small system sizes, fluctuations can dominate the dynamics and induce stochastic Turing instability, even when the system is stable in the absence of diffusion. Notably, Turing instabilities can emerge even when all variables have the same diffusion rate. The developed framework provides a systematic method for analyzing the stability of high-dimensional stochastic systems with diffusion, thereby simplifying the prediction of Turing and Turing-Hopf instabilities. These findings contribute to a deeper understanding of the complex dynamics and pattern formation in GRNs, with potential implications for biological processes, such as cellular differentiation and development.

q-bio.MN↗

Oscillation Criteria in Large-Scale Gene Regulatory Networks with Intrinsic Fluctuations

Gene Regulatory Networks(GRNs) with feedback are essential components of many cellular processes and may exhibit oscillatory behavior. Analyzing such systems becomes increasingly complex as the number of components increases. Since gene regulation often involves a small number of molecules, fluctuations are inevitable. Therefore, it is important to understand how fluctuations affect the oscillatory dynamics of cellular processes, as this will allow comprehension of the mechanisms that enable cellular functions to remain even in the presence of fluctuations or, failing that, to determine the limit of fluctuations that permits various cellular functions. In this study, we investigated the conditions under which GRNs with feedback and intrinsic fluctuations exhibit oscillatory behavior. Our focus was on developing a procedure that would be both manageable and practical, even for extensive regulatory networks, that is, those comprising numerous nodes. Using the second-moment approach, we described the stochastic dynamics through a set of ordinary differential equations for the mean concentration and its second central moment. The system can attain either a stable equilibrium or oscillatory behavior, depending on its scale and, consequently, the intensity of fluctuations. To illustrate the procedure, we analyzed two relevant systems: a repressilator with three nodes and a system with five nodes, both incorporating intrinsic fluctuations. In both cases, it was observed that for very small systems, which therefore exhibit significant fluctuations, oscillatory behavior is inhibited. The procedure presented here for analyzing the stability of oscillations under fluctuations enables the determination of the critical minimum size of GRNs at which intrinsic fluctuations do not eliminate their cyclical behavior.

q-bio.MN↗

An Exact Moment-Based Approach for Chemical Reaction-Diffusion Networks: From Mass Action to Hill Functions

Biochemical systems are inherently stochastic, particularly those with small-molecule populations. The spatial distribution of molecules plays a critical role and requires the inclusion of spatial coordinates in their analysis. Stochastic models such as the chemical master equation are commonly used to study these systems. However, analytical solutions are limited to specific cases, and stochastic simulations require significant computational resources. To mitigate these challenges, approximation methods, such as the moment approach, reduce the system to a set of ordinary differential equations, thereby lowering the computational requirements. This study investigates the conditions under which the second-moment approach yields exact results during the dynamic evolution of chemical reaction-diffusion networks. The analysis encompasses second-order or higher-order reactions and Hill functions without relying on higher-order moment estimations or closure approximations. Starting with stationary states, we extended the analysis to a dynamic evolution. An enzymatic process and an antithetic feedback system were examined for purely reactive systems, demonstrating the approach's accuracy in capturing system behavior and quantifying errors. The study was further extended to genetic regulatory networks governed by Hill functions, including both purely reactive and reaction-diffusion systems, validating the method in spatially distributed contexts. This framework enables precise characterization of biochemical systems, avoiding information loss typically associated with approximations and allowing for stability analysis under fluctuations. These findings optimize computational strategies while providing insights into intracellular signaling and regulatory processes, paving the way for efficient and accurate stochastic modeling in biochemical systems.

q-bio.MN↗

Relationship between Decimal Hill Coefficient, Intermediate Processes and Mesoscopic Fluctuations

The Hill function is relevant for describing enzyme binding and other processes in gene regulatory networks. Despite its theoretical foundation, it is often empirically used as a useful fitting function. Theoretical predictions suggest that the Hill coefficient should be an integer. However, it is often assigned a decimal value. The deterministic approximation of binding processes leads to the derivation of the Hill function, which can be expanded around the fluctuation magnitude to derive mesoscopic corrections. This study establishes the relationships between intermediate processes and the decimal Hill coefficient through a direct relationship between the dissociation constants, both with and without fluctuations. This outcome contributes to a deeper understanding of the underlying processes associated with the decimal Hill coefficient while also enabling the prediction of an effective value of the Hill coefficient from the underlying mechanism. This procedure allows us to have a simplified effective description of complex systems.

q-bio.MN↗

Corrected Hill Function in Stochastic Gene Regulatory Networks

Describing reaction rates in stochastic bio-circuits is commonly done by directly introducing the deterministically deduced Hill function into the master equation. However, when fluctuations in enzymatic reaction rates are not neglectable, the Hill function must be derived, considering all the involved stochastic reactions. In this work, we derived the stochastic version of the Hill function from the master equation of the complete set of reactions that, in the macroscopic limit, lead to the Hill function reaction rate. We performed a series expansion around the average values of the concentrations, which allowed us to find corrections for the deterministic Hill function. This process allowed us to quantify the fluctuations of enzymatic reactions. We found that the underlying variability in propensity rates of gene regulatory networks has an important non-linear effect that reduces the intrinsic fluctuations of the mRNA and protein concentrations.

q-bio.MN↗

Extrinsic Fluctuations in the p53 Cycle

Fluctuations are inherent to biological systems, arising from the stochastic nature of molecular interactions, and influence various aspects of system behavior, stability, and robustness. These fluctuations can be categorized as intrinsic, stemming from the system's inherent structure and dynamics, and extrinsic, arising from external factors, such as temperature variations. Understanding the interplay between these fluctuations is crucial for obtaining a comprehensive understanding of biological phenomena. However, studying these effects poses significant computational challenges. In this study, we used an underexplored methodology to analyze the effect of extrinsic fluctuations in stochastic systems using ordinary differential equations instead of solving the Master Equation with stochastic parameters. By incorporating temperature fluctuations into reaction rates, we explored the impact of extrinsic factors on system dynamics. We constructed a master equation and calculated the equations for the dynamics of the first two moments, offering computational efficiency compared with directly solving the chemical master equation. We applied this approach to analyze a biological oscillator, focusing on the p53 model and its response to temperature-induced extrinsic fluctuations. Our findings underscore the impact of extrinsic fluctuations on the nature of oscillations in biological systems, with alterations in oscillatory behavior depending on the characteristics of extrinsic fluctuations. We observed an increased oscillation amplitude and frequency of the p53 concentration cycle. This study provides valuable insights into the effects of extrinsic fluctuations on biological oscillations and highlights the importance of considering them in more complex systems to prevent unwanted scenarios related to health issues.

q-bio.MN↗

Exact Solutions for Small Systems: Urns Models

In this study, we analyzed urn models by solving the discrete-time master equation using an expansion in moments. This approach is a viable alternative to conventional methods, such as system-size expansion, allowing for the determination of analytical expressions for the mean and variance in an exact form and thus valid for any system size. In particular, this approach was used to study Bernoulli-Laplace and Ehrenfest urns, for which analytic expressions describing their evolution were found. This approach and the results will contribute to a more comprehensive understanding of stochastic systems and statistical physics for small-sized systems, where the thermodynamic limit cannot be assumed.

cond-mat.stat-mech↗

Mobility strategies based on percolation theory to avoid the spread of diseases: COVID-19

Human mobility is an important factor in the propagation of infectious diseases. In particular, the spatial spread of a disease is a consequence of human mobility. On the other hand, the control strategies based on mobility restrictions are generally unpopular and costly. These high social and economic costs make it very important to design global protocols where the cost is minimized and effects maximized. In this work, we calculate the percolation threshold of the spread in a network of a disease. In particular, we found the number of roads to close and regions to isolate in the Puebla State, Mexico, to avoid the global spread of COVID-19. Computational simulations taking into account the proposed strategy show a potential reduction of 94% of infections. This methodology can be used in broader and different areas to help in the design of health policies. -- La movilidad de las personas es uno de los principales factores que propician la propagación de epidemias. En particular, es el factor que genera el esparcimiento de la enfermedad en diferentes regiones. Las medidas de control epidemiológico basadas en la restricción de movilidad son generalmente poco populares y las consecuencias económicas pueden llegar a ser muy grandes. Debido a los altos costos de estas medidas, es de gran relevancia tener estrategias globales que optimicen las medidas minimizando los costos. En este trabajo, se calcula el umbral de percolación de la propagación de enfermedades en redes. De manera particular, se encuentra el número de caminos a restringir y localidades que tienen que ser aisladas para limitar la propagación global de COVID-19 en el Estado de Puebla, México. Simulaciones computacionales donde se implementan las medidas de restricción de movilidad entre los diferentes municipios, junto con las medidas de confinamiento, muestran que es posible reducir un 94% de la población afectada comparado con el caso en el que no se implementa ninguna medida. Esta metodología puede ser aplicada a distintas zonas para ayudar a las autoridades de salud en la toma de decisiones.

physics.soc-ph↗

Vector-borne disease risk indexes in spatially structured populations

There are economic and physical limitations when applying prevention and control strategies for urban vector borne diseases. Consequently, there are increasing concerns and interest in designing efficient strategies and regulations that health agencies can follow in order to reduce the imminent impact of viruses like Dengue, Zika and Chikungunya. That includes fumigation, abatization, reducing the hatcheries, picking up trash, information campaigns. A basic question that arise when designing control strategies is about which and where these ones should focus. In other words, one would like to know whether preventing the contagion or decrease vector population, and in which area of the city, is more efficient. In this work, we propose risk indexes based on the idea of secondary cases from patch to patch. Thus, they take into account human mobility and indicate which patch has more chance to be a corridor for the spread of the disease and which is more vulnerable. They can also indicate the neighborhood where hatchery control will reduce more the number of potential cases. In order to illustrate the usefulness of these indexes, we run a set of numerical simulations in a mathematical model that takes into account the urban mobility and the differences in population density among the areas of a city. If i is a particular neighborhood, the transmission risk index TR_i measures the potential secondary cases caused by a host in that neighborhood. The vector transmission risk index VTR_i measures the potential secondary cases caused by a vector. Finally, the vulnerability risk index VR_i measures the potential secondary cases in the neighborhood. Transmission indexes can be used to give geographical priority to some neighborhoods when applying prevention and control measures. On the other hand, the vulnerability index can be useful to implement monitoring campaigns or public health investment.

q-bio.PE↗

Increased Efficiency in the Second-Hand Tire Trade Provides Opportunity for Dengue Control

Dengue fever is increasing in geographical range, spread by invasion of its vector mosquitoes. The trade in second-hand tires has been implicated as a factor in this process as they act as mobile reservoirs of mosquito eggs and larvae. Regional transportation of tires can create linkages between rural areas with dengue to disease-free urban areas, potentially giving rise to outbreaks even in areas with strong local control measures. In this work we sought to model the dynamics of mosquito transportation via the tire trade, in particular to predict its role in causing unexpected dengue outbreaks through vertical transmission of the virus across generations of mosquitoes. We also aimed to identify strategies for regulating the trade in second-hand tires, improving disease control. We created a mathematical model which captures the dynamics of dengue between rural and urban areas, taking into account the movement, storage time of tires, and mosquito diapause. We simulate a series of scenarios. First a mosquito population is introduced to a dengue-free area via movement of tires, either as single or multiple events, increasing the likelihood of a dengue outbreak. An endemic state can be induced regardless of whether urban conditions for an outbreak are met, and an existing endemic state can be enhanced by vector input. Finally we assess the potential for regulation of tire processing as a means of reducing the transmission of dengue fever using a specific case study from Puerto Rico. Our work demonstrates the importance of the second-hand tire trade in modulating the spread of dengue fever across regions, in particular its role in introducing dengue to disease-free areas. We propose that regulation of tire storage and movement can play a crucial role in containing outbreaks and dengue spread.

q-bio.PE↗