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Search Results: 1 - 10 of 42464 matches for " Enrique Hernández-Lemus "
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Nonequilibrium Thermodynamics of Cell Signaling
Enrique Hernández-Lemus
Journal of Thermodynamics , 2012, DOI: 10.1155/2012/432143
Abstract: Signal transduction inside and across the cells, also called cellular signaling, is key to most biological functions and is ultimately related with both life and death of the organisms. The processes giving rise to the propagation of biosignals are complex and extremely cooperative and occur in a far-from thermodynamic equilibrium regime. They are also driven by activation kinetics strongly dependent on local energetics. For these reasons, a nonequilibrium thermodynamical description, taking into account not just the activation of second messengers, but also transport processes and dissipation is desirable. Here we present a proposal for such a formalism, that considers cells as small thermodynamical systems and incorporates the role of fluctuations as intrinsic to the dynamics in a spirit guided by mesoscopic nonequilibrium thermodynamics. We present also a minimal model for cellular signaling that includes contributions from activation, transport, and intrinsic fluctuations. We finally illustrate its feasibility by considering the case of FAS signaling which is a vital signal transduction pathway that determines either cell survival or death by apoptosis.
Nonequilibrium Thermodynamics of Cell Signaling
Enrique Hernández-Lemus
Journal of Thermodynamics , 2012, DOI: 10.1155/2012/432143
Abstract: Signal transduction inside and across the cells, also called cellular signaling, is key to most biological functions and is ultimately related with both life and death of the organisms. The processes giving rise to the propagation of biosignals are complex and extremely cooperative and occur in a far-from thermodynamic equilibrium regime. They are also driven by activation kinetics strongly dependent on local energetics. For these reasons, a nonequilibrium thermodynamical description, taking into account not just the activation of second messengers, but also transport processes and dissipation is desirable. Here we present a proposal for such a formalism, that considers cells as small thermodynamical systems and incorporates the role of fluctuations as intrinsic to the dynamics in a spirit guided by mesoscopic nonequilibrium thermodynamics. We present also a minimal model for cellular signaling that includes contributions from activation, transport, and intrinsic fluctuations. We finally illustrate its feasibility by considering the case of FAS signaling which is a vital signal transduction pathway that determines either cell survival or death by apoptosis. 1. Introduction Survival of living organisms is intimately linked to their ability to react quite efficiently to even extremely weak external signals. Common examples are the reaction of the human eye to single light photons [1, 2], the reaction of a male butterfly to a single pheromone molecule coming from a female at a distance that sometimes is in the order of kilometers [3], and so forth. Cellular receptors react to hormones, cytokines, or antigens at very low concentrations. This strong reaction to a weak impulse is attained by an amplification process which is performed by means of special pathways of free energy transduction. Mechanisms such as immune system response, thermal-shock inhibitions, and cardiovascular rearrangement in response to environmental changes are all mediated by signaling processes. Signal transduction (information flow) is, thus, equally important, if not more important, for the functioning of a living organisms than metabolism and energy flow. Signal transduction or cell signaling is the generic name of the set of concatenated processes or stages in which a cell transforms a certain signal or stimulus—either intercellular or intracellular—into another signal or a specific response. Cell signaling affects the complex arrangement of biochemical reactions inside the cell that takes place by means of enzymes that are bounded to other molecules called second messengers. Each
Health Systems as Complex Systems  [PDF]
Mireya Martínez-García, Enrique Hernández-Lemus
American Journal of Operations Research (AJOR) , 2013, DOI: 10.4236/ajor.2013.31A011
Abstract:

Health systems are paradigmatic examples of human organizations that blend a multitude of different professional and disciplinary features within a critically performance environment. Communication failure and defective processes in health systems have a tremendous impact in society, both in the financial and human aspects. Traditionally, health systems have been regarded as linear hierarchic structures. However, recent developments in the sciences of complexity point out to health systems as complex entities governed by non-linear interaction laws, self-organization and emergent phenomena. In this work we review some aspects of complexity behind health systems and how they can be applied to improve the performance of healthcare organizations.

Non-Equilibrium Hyperbolic Transport in Transcriptional Regulation
Enrique Hernández-Lemus,María D. Correa-Rodríguez
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0021558
Abstract: In this work we studied memory and irreversible transport phenomena in a non-equilibrium thermodynamical model for genomic transcriptional regulation. Transcriptional regulation possess an extremely complex phenomenology, and it is, of course, of foremost importance in organismal cell development and in the pathogenesis of complex diseases. A better understanding of the way in which these processes occur is mandatory to optimize the construction of gene regulatory networks, but also to connect these networks with multi-scale phenomena (e.g. metabolism, signalling pathways, etc.) under an integrative Systems Biology-like vision. In this paper we analyzed three simple mechanisms of genetic stimulation: an instant pulse, a periodic biochemical signal and a saturation process with sigmoidal kinetics and from these we derived the system's thermodynamical response, in the form of, for example, anomalous transcriptional bursts.
Hysteresis in Pressure-Driven DNA Denaturation
Enrique Hernández-Lemus, Luz Adriana Nicasio-Collazo, Ramón Casta?eda-Priego
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0033789
Abstract: In the past, a great deal of attention has been drawn to thermal driven denaturation processes. In recent years, however, the discovery of stress-induced denaturation, observed at the one-molecule level, has revealed new insights into the complex phenomena involved in the thermo-mechanics of DNA function. Understanding the effect of local pressure variations in DNA stability is thus an appealing topic. Such processes as cellular stress, dehydration, and changes in the ionic strength of the medium could explain local pressure changes that will affect the molecular mechanics of DNA and hence its stability. In this work, a theory that accounts for hysteresis in pressure-driven DNA denaturation is proposed. We here combine an irreversible thermodynamic approach with an equation of state based on the Poisson-Boltzmann cell model. The latter one provides a good description of the osmotic pressure over a wide range of DNA concentrations. The resulting theoretical framework predicts, in general, the process of denaturation and, in particular, hysteresis curves for a DNA sequence in terms of system parameters such as salt concentration, density of DNA molecules and temperature in addition to structural and configurational states of DNA. Furthermore, this formalism can be naturally extended to more complex situations, for example, in cases where the host medium is made up of asymmetric salts or in the description of the (helical-like) charge distribution along the DNA molecule. Moreover, since this study incorporates the effect of pressure through a thermodynamic analysis, much of what is known from temperature-driven experiments will shed light on the pressure-induced melting issue.
Multichannel Detrended Fluctuation Analysis Reveals Synchronized Patterns of Spontaneous Spinal Activity in Anesthetized Cats
Erika E. Rodríguez, Enrique Hernández-Lemus, Benjamín A. Itzá-Ortiz, Ismael Jiménez, Pablo Rudomín
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0026449
Abstract: The analysis of the interaction and synchronization of relatively large ensembles of neurons is fundamental for the understanding of complex functions of the nervous system. It is known that the temporal synchronization of neural ensembles is involved in the generation of specific motor, sensory or cognitive processes. Also, the intersegmental coherence of spinal spontaneous activity may indicate the existence of synaptic neural pathways between different pairs of lumbar segments. In this study we present a multichannel version of the detrended fluctuation analysis method (mDFA) to analyze the correlation dynamics of spontaneous spinal activity (SSA) from time series analysis. This method together with the classical detrended fluctuation analysis (DFA) were used to find out whether the SSA recorded in one or several segments in the spinal cord of the anesthetized cat occurs either in a random or in an organized manner. Our results are consistent with a non-random organization of the sets of neurons involved in the generation of spontaneous cord dorsum potentials (CDPs) recorded either from one lumbar segment (DFA- mean = 1.040.09) or simultaneously from several lumbar segments (mDFA- mean = 1.010.06), where = 0.5 indicates randomness while 0.5 indicates long-term correlations. To test the sensitivity of the mDFA method we also examined the effects of small spinal lesions aimed to partially interrupt connectivity between neighboring lumbosacral segments. We found that the synchronization and correlation between the CDPs recorded from the L5 and L6 segments in both sides of the spinal cord were reduced when a lesion comprising the left dorsal quadrant was performed between the segments L5 and L6 (mDFA- = 0.992 as compared to initial conditions mDFA- = 1.186). The synchronization and correlation were reduced even further after a similar additional right spinal lesion (mDFA- = 0.924). In contrast to the classical methods, such as correlation and coherence quantification that define a relation between two sets of data, the mDFA method properly reveals the synchronization of multiple groups of neurons in several segments of the spinal cord. This method is envisaged as a useful tool to characterize the structure of higher order ensembles of cord dorsum spontaneous potentials after spinal cord or peripheral nerve lesions.
Performance Activism at the Borderlands: Minutemen, Anzaldúa, Gómez-Pe?a
Hernández-Lemus, Alberto;
Política y cultura , 2006,
Abstract: the borderlands shared by the united states and mexico are a deposit of signs of diverse cultures that have crossed through them: native, spanish, mexican and anglo-saxon. three types of political or artistic activism take control selectively of some of those signs to proclaim own identities. by means of the action of border patrolling, the minutemen safeguard the purity of the project of nativist identity based on the doctrine of manifest destiny. anzaldúa (test) and gómez-pe?a (action art), however, stimulate the proliferation of combinations of signs that give rise to new identities and mestizations.
Biophysics of Active Vesicle Transport, an Intermediate Step That Couples Excitation and Exocytosis of Serotonin in the Neuronal Soma
Francisco F. De-Miguel, Iván Santamaría-Holek, Paula Noguez, Carlos Bustos, Enrique Hernández-Lemus, J. Miguel Rubí
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0045454
Abstract: Transmitter exocytosis from the neuronal soma is evoked by brief trains of high frequency electrical activity and continues for several minutes. Here we studied how active vesicle transport towards the plasma membrane contributes to this slow phenomenon in serotonergic leech Retzius neurons, by combining electron microscopy, the kinetics of exocytosis obtained from FM1-43 dye fluorescence as vesicles fuse with the plasma membrane, and a diffusion equation incorporating the forces of local confinement and molecular motors. Electron micrographs of neurons at rest or after stimulation with 1 Hz trains showed cytoplasmic clusters of dense core vesicles at 1.5±0.2 and 3.7±0.3 μm distances from the plasma membrane, to which they were bound through microtubule bundles. By contrast, after 20 Hz stimulation vesicle clusters were apposed to the plasma membrane, suggesting that transport was induced by electrical stimulation. Consistently, 20 Hz stimulation of cultured neurons induced spotted FM1-43 fluorescence increases with one or two slow sigmoidal kinetics, suggesting exocytosis from an equal number of vesicle clusters. These fluorescence increases were prevented by colchicine, which suggested microtubule-dependent vesicle transport. Model fitting to the fluorescence kinetics predicted that 52–951 vesicles/cluster were transported along 0.60–6.18 μm distances at average 11–95 nms?1 velocities. The ATP cost per vesicle fused (0.4–72.0), calculated from the ratio of the ΔGprocess/ΔGATP, depended on the ratio of the traveling velocity and the number of vesicles in the cluster. Interestingly, the distance-dependence of the ATP cost per vesicle was bistable, with low energy values at 1.4 and 3.3 μm, similar to the average resting distances of the vesicle clusters, and a high energy barrier at 1.6–2.0 μm. Our study confirms that active vesicle transport is an intermediate step for somatic serotonin exocytosis by Retzius neurons and provides a quantitative method for analyzing similar phenomena in other cell types.
The Role of Master Regulators in the Metabolic/Transcriptional Coupling in Breast Carcinomas
Karol Baca-López, Miguel Mayorga, Alfredo Hidalgo-Miranda, Nora Gutiérrez-Nájera, Enrique Hernández-Lemus
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042678
Abstract: Metabolic transformations have been reported as involved in neoplasms survival. This suggests a role of metabolic pathways as potential cancer pharmacological targets. Modulating tumor's energy production pathways may become a substantial research area for cancer treatment. The significant role of metabolic deregulation as inducing transcriptional instabilities and consequently whole-system failure, is thus of foremost importance. By using a data integration approach that combines experimental evidence for high-throughput genome wide gene expression, a non-equilibrium thermodynamics analysis, nonlinear correlation networks as well as database mining, we were able to outline the role that transcription factors MEF2C and MNDA may have as main master regulators in primary breast cancer phenomenology, as well as the possible interrelationship between malignancy and metabolic dysfunction. The present findings are supported by the analysis of 1191 whole genome gene expression experiments, as well as probabilistic inference of gene regulatory networks, and non-equilibrium thermodynamics of such data. Other evidence sources include pathway enrichment and gene set enrichment analyses, as well as motif comparison with a comprehensive gene regulatory network (of homologue genes) in Arabidopsis thaliana. Our key finding is that the non-equilibrium free energies provide a realistic description of transcription factor activation that when supplemented with gene regulatory networks made us able to find deregulated pathways. These analyses also suggest a novel potential role of transcription factor energetics at the onset of primary tumor development. Results are important in the molecular systems biology of cancer field, since deregulation and coupling mechanisms between metabolic activity and transcriptional regulation can be better understood by taking into account the way that master regulators respond to physicochemical constraints imposed by different phenotypic conditions.
Mapping the Structure and Dynamics of Genomics-Related MeSH Terms Complex Networks
Jesús M. Siqueiros-García, Enrique Hernández-Lemus, Rodrigo García-Herrera, Andrea Robina-Galatas
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0092639
Abstract: It has been proposed that the history and evolution of scientific ideas may reflect certain aspects of the underlying socio-cognitive frameworks in which science itself is developing. Systematic analyses of the development of scientific knowledge may help us to construct models of the collective dynamics of science. Aiming at scientific rigor, these models should be built upon solid empirical evidence, analyzed with formal tools leading to ever-improving results that support the related conclusions. Along these lines we studied the dynamics and structure of the development of research in genomics as represented by the entire collection of genomics-related scientific papers contained in the PubMed database. The analyzed corpus consisted in more than 49,000 articles published in the years 1987 (first appeareance of the term Genomics) to 2011, categorized by means of the Medical Subheadings (MeSH) content-descriptors. Complex networks were built where two MeSH terms were connected if they are descriptors of the same article(s). The analysis of such networks revealed a complex structure and dynamics that to certain extent resembled small-world networks. The evolution of such networks in time reflected interesting phenomena in the historical development of genomic research, including what seems to be a phase-transition in a period marked by the completion of the first draft of the Human Genome Project. We also found that different disciplinary areas have different dynamic evolution patterns in their MeSH connectivity networks. In the case of areas related to science, changes in topology were somewhat fast while retaining a certain core-stucture, whereas in the humanities, the evolution was pretty slow and the structure resulted highly redundant and in the case of technology related issues, the evolution was very fast and the structure remained tree-like with almost no overlapping terms.
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