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Míriam R. García

Publications and source records attributed to Míriam R. García.

3 recordsLinked to original sources

Conditions for Bacterial Selection and Extinction Driven by Growth-Kill Trade-Off in Cyclic Antimicrobial Treatments

Antimicrobial protocols - using substances such as antibiotics or disinfectants - remain the preferred option for preventing the spread of pathogenic bacteria. However, bacteria can develop mechanisms to reduce their antimicrobial susceptibility, which can lead to treatment failure and the selection of resistance or tolerance. In this work, we propose a minimal population dynamics model to study bacterial selection during cyclic antimicrobial application, a commonly used protocol. Selection in bacterial populations with heterogeneous antimicrobial susceptibility is modelled here as a trade-off between survival advantage (reduction in antimicrobial killing) and potential fitness costs (reduction in growth rate) of the less susceptible strains. The proposed model allows us to derive useful expressions for determining the success of cyclic antimicrobial treatments based on two bacterial traits: growth and kill rates. The results obtained here are directly applicable to preventing the selection and spread of resistant and tolerant bacterial strains in real-life protocols.

q-bio.PE↗

A reaction-diffusion model for the progression of Parkinson's disease

The temporal and spatial development of Parkinson's disease has been characterised as the progressive formation of α-synuclein aggregations through susceptible neuronal pathways. This article describes a new model for this progression mechanism in which Parkinsonian damage moves over time through the nervous system by the combined effect of the reaction kinetics of pathogenesis and molecular diffusion. In the reaction-diffusion model, the change from a healthy state to the disease state advances through the nervous system as a wave front of Parkinsonian damage, marking its path by accumulations of damaged α-synuclein and neurotoxic levels of oxidative species. Progression according to this model follows the most vulnerable routes through the nervous system as described by Braak's staging theory and predicts that damage will advance at differing speeds depending upon the level and number of risk factors, in a manner that gives new insights into the variations with which Parkinson's disease develops.

q-bio.NC↗

Biological mechanism and identifiability of a class of stationary conductance model for Voltage-gated Ion channels

The physiology of voltage gated ion channels is complex and insights into their gating mechanism is incomplete. Their function is best represented by Markov models with relatively large number of distinct states that are connected by thermodynamically feasible transitions. On the other hand, popular models such as the one of Hodgkin and Huxley have empirical assumptions that are generally unrealistic. Experimental protocols often dictate the number of states in proposed Markov models, thus creating disagreements between various observations on the same channel. Here we aim to propose a limit to the minimum number of states required to model ion channels by employing a paradigm to define stationary conductance in a class of ion-channels. A simple expression is generated using concepts in elementary thermodynamics applied to protein conformational transitions. Further, it matches well many published channel current-voltage characteristics and parameters of the model are found to be identifiable and easily determined from usual experimental protocols.

q-bio.SC↗