Tidal Volume (TV) post-process obtained with electrical impedance tomography on a group of chronic obstructive pulmonary disease (COPD) patients. Use of adjust equations

Equations used to estimate ventilation out of EIT images, validated on healthy volunteers show a significant bias and a larger variance when were applied on a COPD patients group. The differences in estimation values were found to be highly correlated with anthropometric parameters. Two groups of 13 and 4 COPD male patients (FEV1/FVC<70% and FVC ≥ 80%) were used in this study. We have measured different anthropometric parameters like age, weight, height and skinfolds. The EIT system (TIE4sys) and a pneumotach were simultaneously connected to monitor tidal volume. The main anthropometric parameters values of 13 COPD patients were: age: 67±9 years, height: 1.65±0.05 m, weight: 72±11 kg, BMI: 26.4±3.3; and the subscapular skinfold thickness was 23±9mm. The mean tidal volume estimated with TIE4sys and the pneumotach were: 0.580±0.212 L and 0.774±0.173 L r = 0.861 (p<0.01). The mean difference was 0.196±0.096 L (p<0.01). On this group we have found out an adjust equation and we have validated it on an independent group of 4 COPD patients. The equation was Diff=-1478+15.6(weight). The mean tidal volume values obtained with pneumotach and TIE4sys on the second group of COPD patients (M:4) were: 0.798±0.395 L and 0.732±0.327 L. The mean of the differences was 0.066±0.114L. The differences of determinations estimated with pneumotach and TIE4sys can be attributed to changes of anthropometric characteristics like subscapular skinfold.Peer ReviewedPostprint (author’s final draft

Effects of neurosteroids on a model membrane including cholesterol: A micropipette aspiration study

Amphiphilic molecules supposed to affect membrane protein activity could strongly interact also with the lipid component of the membrane itself. Neurosteroids are amphiphilic molecules that bind to plasma membrane receptors of cells in the central nervous system but their effect on membrane is still under debate. For this reason it is interesting to investigate their effects on pure lipid bilayers as model systems. Using the micropipette aspiration technique (MAT), here we studied the effects of a neurosteroid, allopregnanolone (3α,5α-tetrahydroprogesterone or Allo) and of one of its isoforms, isoallopregnanolone (3β,5α-tetrahydroprogesterone or isoAllo), on the physical properties of pure lipid bilayers composed by DOPC/bSM/chol. Allo is a well-known positive allosteric modulator of GABAA receptor activity while isoAllo acts as a non-competitive functional antagonist of Allo modulation. We found that Allo, when applied at nanomolar concentrations (50-200 nM) to a lipid bilayer model system including cholesterol, induces an increase of the lipid bilayer area and a decrease of the mechanical parameters. Conversely, isoAllo, decreases the lipid bilayer area and, when applied, at the same nanomolar concentrations, it does not affect significantly its mechanical parameters. We characterized the kinetics of Allo uptake by the lipid bilayer and we also discussed its aspects in relation to the slow kinetics of Allo gating effects on GABAA receptors. The overall results presented here show that a correlation exists between the modulation of Allo and isoAllo of GABAA receptor activity and their effects on a lipid bilayer model system containing cholesterol

Systematic characterization of maturation time of fluorescent proteins in living cells

Slow maturation time of fluorescent proteins limits accurate measurement of rapid gene expression dynamics and effectively reduces fluorescence signal in growing cells. We used high-precision time-lapse microscopy to characterize, at two different temperatures in E. coli, the maturation kinetics of 50 FPs that span the visible spectrum. We identified fast-maturing FPs that yield the highest signal-to-noise ratio and temporal resolution in individual growing cells

tidal volume monitoring by electrical impedance tomography (EIT) using different regions of interest (ROI): calibration equations

set of calibration equations was previously obtained to transform the lung impedance changes obtained by electrical impedance tomography (EIT), using all frame's elements, into a measurable volume signal. In order to study the goodness of the use of regions of interest (ROI) for lung ventilation monitoring, we considered 6 different ROI to obtain a calibration equation for each area. Our aim was to compare the results, determined by these areas, and those obtained by using all EIT image elements. Two ROI's were defined by those pixels with an impedance change higher than 30% and 70% of the maximum change value. These areas were called P30 and P70, respectively. Two other ROI were defined by bounding two areas by mouse, resembling P30 and P70 regions, which were called M30 and M70, respectively. The remainder was defined by two elliptical areas with an eccentricity of 0.8, and 25 and 32 pixels of mayor axis (E25p and E32p, respectively). Twenty healthy males and 24 chronic obstructive pulmonary disease (COPD) patients were considered. For small region (P30 and M30) we obtained a large dispersion in volume measurement, concluding that small regions are not suitable for monitoring the tidal changes in lung volume even for healthy subjects. The results obtained by the remainder areas, and by using EIT image were similar. Even a slight improvement in data dispersion was obtained by using some ROI. These optimal results, for healthy people, were those corresponding to P70 and M70 (volume dispersion improved from 12% with the whole EIT image to 9% using ROI), and for COPD patients improves volume dispersion from 32% using the whole EIT image to 27% by using E25p. Using not so small ROI, it is possible to estimate the total lung ventilation.Peer ReviewedPostprint (author’s final draft

Contribución del estado de Zacatecas (México) a la conservación de la riqueza florística del Desierto Chihuahuense

The Chihuahuan Desert (DCH) is the largest and floristically richest arid zone in northern Mexico. The DCH includes territories of seven Mexican states, including Zacatecas and San Luis Potosí where its southern limit is located. Zacatecas harbors 46% of the vascular flora recorded in the DCH and the Asteraceae family is an important component of such richness, both throughout the DCH as a whole and within its Zacatecan portion. Unfortunately, Zacatecas has not been adequately considered in the different conservation strategies proposed to protect the floristic richness of the DCH. In this paper we describe a selection of sites in Zacatecas that are important for the conservation of floristic richness, using 198 species of Asteraceae as a surrogate of the entire flora and dividing the fraction of the DCH in the state into 26 squares of 30 minutes latitude and longitude. The sites were identified by means of an iterative method, the results of which indicate the necessity of protecting 18 squares to ensure the conservation of the totality of species. The location of the most important squares identified, as well as the role that Zacatecas may potentially play in the conservation of the biodiversity of the DCH are discussed.El Desierto Chihuahuense (DCH) es la zona árida más extensa y más rica florísticamente de las regiones secas del norte de México. El DCH forma parte de los territorios de siete estados del país, incluyendo Zacatecas que junto con San Luis Potosí representan su extremo sur. Zacatecas contiene alrededor de 46% de la flora vascular del DCH y la familia Asteraceae es un miembro importante de esta riqueza, tanto a nivel de todo el DCH como en su fracción en la entidad. Desafortunadamente, no se ha reconocido el valor del mencionado estado en las estrategias de conservación de la biodiversidad propuestas hasta ahora para la protección de la flora del DCH. En este trabajo se hace una selección de sitios considerados importantes para la conservación de la riqueza florística del DCH en Zacatecas, utilizando 198 especies de Asteraceae como variable substituta de la diversidad vegetal total y una división de la porción del DCH en el estado en 26 cuadros de 30 minutos de latitud y longitud. La selección de sitios se realizó mediante la aplicación de un método iterativo que indicó la existencia de 18 cuadros que son importantes para la protección de 100% de las especies de esta familia. Se discute la ubicación de los cuadros más importantes identificados con este procedimiento así como la importancia de Zacatecas para la conservación de la biodiversidad del DCH

Structural Determinants for Ligand Accommodation in Voltage Sensors

After ligand binding, many ion channels undergo rearrangements at the voltage sensor domain (VSD) that often modulate their gating activity with important physiological repercussions. Since the VSD is dynamic, it is interesting to establish a correlation between the potential mobility of this element in terms of its intrinsic flexibility and its ability to accommodate several ligands by induced-fit mechanisms. We presume that these associations are not causal since the flexibility of the VSD could have an important impact on the ligand coupling event. Many significantly flexible ion channels show a general architecture and composition compatible with important conformational changes and capable of accommodating chemically diverse agonists. In this contribution, the structural bases of this subtle and probably unexpected relationship between the VSD flexibility and its influence during the dynamic coupling of the ligand are exposed. Thus, given its physiological relevance, the study of ion channel malfunction can be associated with ligand accommodation events to the VSD, which could depend on its local flexibility. This could contribute to a better understanding of the molecular bases of a variety of physiological disorders. In consequence, considering these effects during the protein/ligand interaction could be determinant to the rational design of novel drugs

The Influence of Canalization on the Robustness of Boolean Networks

Time- and state-discrete dynamical systems are frequently used to model molecular networks. This paper provides a collection of mathematical and computational tools for the study of robustness in Boolean network models. The focus is on networks governed by $k$-canalizing functions, a recently introduced class of Boolean functions that contains the well-studied class of nested canalizing functions. The activities and sensitivity of a function quantify the impact of input changes on the function output. This paper generalizes the latter concept to $c$-sensitivity and provides formulas for the activities and $c$-sensitivity of general $k$-canalizing functions as well as canalizing functions with more precisely defined structure. A popular measure for the robustness of a network, the Derrida value, can be expressed as a weighted sum of the $c$-sensitivities of the governing canalizing functions, and can also be calculated for a stochastic extension of Boolean networks. These findings provide a computationally efficient way to obtain Derrida values of Boolean networks, deterministic or stochastic, that does not involve simulation.Comment: 16 pages, 2 figures, 3 table

Scaling laws in bacterial genomes: A side-effect of selection of mutational robustness?

In the past few years, numerous research projects have focused on identifying and understanding scaling properties in the gene content of prokaryote genomes and the intricacy of their regulation networks. Yet, and despite the increasing amount of data available, the origins of these scalings remain an open question. The RAevol model, a digital genetics model, provides us with an insight into the mechanisms involved in an evolutionary process. The results we present here show that (i) our model reproduces qualitatively these scaling laws and that (ii) these laws are not due to differences in lifestyles but to differences in the spontaneous rates of mutations and rearrangements. We argue that this is due to an indirect selective pressure for robustness that constrains the genome size

The effect of network topology on the stability of discrete state models of genetic control

Boolean networks have been proposed as potentially useful models for genetic control. An important aspect of these networks is the stability of their dynamics in response to small perturbations. Previous approaches to stability have assumed uncorrelated random network structure. Real gene networks typically have nontrivial topology significantly different from the random network paradigm. In order to address such situations, we present a general method for determining the stability of large Boolean networks of any specified network topology and predicting their steady-state behavior in response to small perturbations. Additionally, we generalize to the case where individual genes have a distribution of `expression biases,' and we consider non-synchronous update, as well as extension of our method to non-Boolean models in which there are more than two possible gene states. We find that stability is governed by the maximum eigenvalue of a modified adjacency matrix, and we test this result by comparison with numerical simulations. We also discuss the possible application of our work to experimentally inferred gene networks.Comment: 25 pages, 4 figures; added supplementary information, fixed typos and figure, reformatte