A Computational Model for Calcium Signaling in Osteocyte Cell Cultures Under Mechanical Stimulation

Bone is a highly complex and organized tissue that is composed of an abundance of cells including the osteocyte. While it is known that osteocytes are responsible for the control of the bone remodeling process and the maintenance of calcium (Ca2+) homeostasis using their network of gap junction connections, their complete role is not yet fully understood. It is also known that various bone related diseases as well as cancer demonstrate an alteration of Ca2+ homeostasis during the progression of the disease. Previous researchers have combined computational modeling with experimental studies to gain a better understanding of cell-to-cell Ca2+ signaling within the osteocyte network in hopes of developing new diagnostic and therapeutic methods for bone related diseases. In this work, we connect and expand previously developed computational models of Ca2+ propagation within cell populations with the goal to gain more insight of cell-to-cell signaling amongst in vitro osteocyte network cultures that mimic their native environment. Our work demonstrates that unique signal response patterns displayed amongst osteocyte networks are attributed to varying specific kinetic parameters. We were also able to determine the arrangement of two connected osteocytes with differing signal response patterns from our experimental studies using our computational model. The insight of osteocyte heterogeneity gained can contribute to future efforts to develop diagnostic and therapeutic treatments for bone related diseases and cancer

Analysis of network models with neuron-astrocyte interactions

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Impacto da Doen?a de Alzheimer sobre Diferentes Topologias de Astr?citos em um Sistema de Comunica??o Molecular

A Internet das Bio Nano-Coisas ? um novo paradigma que visa proporcionar novas t?cnicas remotamente controladas de detec??o e atua??o dentro do corpo humano. Para o desenvolvimento desse paradigma, ? necess?rio que sejam modelados e investigados modelos capazes de conduzir a uma melhor compreens?o e uma detec??o precoce de doen?as. A doen?a de Alzheimer ? uma doen?a neuro degenerativa cr?nica que causa perda de mem?ria e n?o tem cura, sendo desenvolvida pelo ac?mulo de placas do pept?dio -amil?ide. Essa doen?a causa s?rios danos em neur?nios e tamb?m em c?lulas da glia, como os astr?citos. Por esse motivo, o presente trabalho investiga o efeito das placas de amil?ide em astr?citos com doen?a de Alzheimer. Para tal, foi desenvolvido um modelo computacional para a simula??o de um sistema de comunica??o molecular baseado na sinaliza??o de Ca2+, composto de astr?citos saud?veis e, tamb?m, de astr?citos acometidos pela Doen?a de Alzheimer. O simulador foi constru?do a partir de modelos matem?ticos concebidos por meio de resultados experimentais, os quais levam em considera??o a din?mica intracelular do astr?cito, a din?mica do IP3, as jun??es comunicantes, os canais de c?lcio controlados por tens?o e o volume dos astr?citos. O simulador implementado tamb?m leva em considera??o as diferentes topologias de redes de astr?citos, incluindo a rede de Grau Regular, rede de Raio de Liga??o, rede de Atalho e a rede Erd?s-R?nyi. Um resolvedor estoc?stico proposto em v?rias escalas captura a rela??o entre as rea??es intracelulares e intercelulares. Com isso, foram avaliadas algumas m?tricas que s?o capazes de avaliar o desempenho deste sistema de comunica??o, a saber, a extens?o de propaga??o, o atraso molecular, o ganho de canal, a capacidade do canal e o ru?do da comunica??o. Os resultados revelam que as oscila??es mais inst?veis, mas ao mesmo tempo mais baixas, das redes de astr?citos sob a influ?ncia da Doen?a de Alzheimer podem criar um efeito em v?rias escalas na comunica??o entre astr?citos com o maior atraso molecular, maior ru?do na comunica??o, menor ganho de canal e menor capacidade de canal em compara??o com astr?citos saud?veis.IFP

Reproducibility and Comparability of Computational Models for Astrocyte Calcium Excitability

The scientific community across all disciplines faces the same challenges of ensuring accessibility, reproducibility, and efficient comparability of scientific results. Computational neuroscience is a rapidly developing field, where reproducibility and comparability of research results have gained increasing interest over the past years. As the number of computational models of brain functions is increasing, we chose to address reproducibility using four previously published computational models of astrocyte excitability as an example. Although not conventionally taken into account when modeling neuronal systems, astrocytes have been shown to take part in a variety of in vitro and in vivo phenomena including synaptic transmission. Two of the selected astrocyte models describe spontaneous calcium excitability, and the other two neurotransmitter-evoked calcium excitability. We specifically addressed how well the original simulation results can be reproduced with a reimplementation of the models. Additionally, we studied how well the selected models can be reused and whether they are comparable in other stimulation conditions and research settings. Unexpectedly, we found out that three of the model publications did not give all the necessary information required to reimplement the models. In addition, we were able to reproduce the original results of only one of the models completely based on the information given in the original publications and in the errata. We actually found errors in the equations provided by two of the model publications; after modifying the equations accordingly, the original results were reproduced more accurately. Even though the selected models were developed to describe the same biological event, namely astrocyte calcium excitability, the models behaved quite differently compared to one another. Our findings on a specific set of published astrocyte models stress the importance of proper validation of the models against experimental wet-lab data from astrocytes as well as the careful review process of models. A variety of aspects of model development could be improved, including the presentation of models in publications and databases. Specifically, all necessary mathematical equations, as well as parameter values, initial values of variables, and stimuli used should be given precisely for successful reproduction of scientific results.publishedVersionPeer reviewe

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)