Hector Riveros-Rosas
Universidad Nacional Autónoma de México, Bioquimica, Faculty Member
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<p>For additional details see caption of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0166851#pone.0166851.g005" target="_blank">Fig 5</a>.</p
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The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are encoded by a family of four genes (HCN1-4). All isoforms are expressed in the heart, HCN4 being the most abundant in the sinoatrial node (SAN). HCN channels are... more
The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are encoded by a family of four genes (HCN1-4). All isoforms are expressed in the heart, HCN4 being the most abundant in the sinoatrial node (SAN). HCN channels are responsible for the "funny" current (If) associated with the generation and autonomic control of the diastolic depolarization phase of cardiac action potential. In this work we performed a proteomic analysis of HCN4 transfected in HEK293 cells. Most of the identified proteins in the HCN4 network belonged to mitochondria. The subcellular localization of HCN channels was predicted in plasma membrane, mitochondria and nucleus. Experimentally, HCN2 (full-length, truncated), HCN3 (full-length, truncated) and HCN4 (truncated) were detected in rat heart mitochondria by immunoblotting. If sensitive to ZD7288, was recorded by patch-clamp in mitoplasts from cardiomyocytes. Mitochondrial membrane potential (ΔΨm) assessment in H9c2 cells revealed that ZD7288 induced almost 50% higher hyperpolarization respect to control at 30 min. Furthermore, ZD7288 reduced oxygen consumption attributed to ATP synthesis in H9c2 cells. In conclusion, we identify for the first time functional HCN channels in mammalian cardiac mitochondria and demonstrate their impact on ΔΨm and respiration.
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Abstract Lipid molecules have received traditionally very little attention as components of general metabolism and cellular signaling in eukaryotes. Originally, lipid function was established as cellular/bodily energy storage and... more
Abstract Lipid molecules have received traditionally very little attention as components of general metabolism and cellular signaling in eukaryotes. Originally, lipid function was established as cellular/bodily energy storage and structural components of biological ...
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Reactive oxygen species participate in regulating intracellular signaling pathways. Herein, we investigated the reported opposite effects of hydrogen peroxide (H2O2) on metabolic signaling mediated by activated α1‐ and β‐adrenoceptors... more
Reactive oxygen species participate in regulating intracellular signaling pathways. Herein, we investigated the reported opposite effects of hydrogen peroxide (H2O2) on metabolic signaling mediated by activated α1‐ and β‐adrenoceptors (ARs) in hepatocytes. In isolated rat hepatocytes, stimulation of α1‐AR increases H2O2 production via NADPH oxidase 2 (NOX2) activation. We find that the H2O2 thus produced is essential for α1‐AR‐mediated activation of the classical hepatic glycogenolytic, gluconeogenic, and ureagenic responses. However, H2O2 inhibits β‐AR‐mediated activation of these metabolic responses. We show that H2O2 mediates its effects on α1‐AR and β‐AR by permeating cells through aquaporin 8 (AQP8) channels and promoting Ca2+ mobilization. Thus, our findings reveal a novel NOX2‐H2O2‐AQP8‐Ca2+ signaling cascade acting downstream of α1‐AR in hepatocytes, which, by negatively regulating β‐AR signaling, establishes negative crosstalk between the two pathways.
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Iron-containing alcohol dehydrogenases (Fe-ADH) were initially found only in microorganisms. These enzymes catalyze different reactions, all of them assorted as dehydrogenases-reductases. Later, a Fe-ADH was discovered in humans and... more
Iron-containing alcohol dehydrogenases (Fe-ADH) were initially found only in microorganisms. These enzymes catalyze different reactions, all of them assorted as dehydrogenases-reductases. Later, a Fe-ADH was discovered in humans and animals. This Fe-ADH has been characterized in rats and humans displaying activity as a hydroxyacid-oxoacid transhydrogenase (HOT), however, its metabolic role is not completely understood. The aim of our study was obtain insights to understand how an ancient iron-containing dehydrogenase/reductase was converted into a HOT in animals. Our study included an exhaustive bioinformatic analysis that comprise structural, phylogenetic and synteny analyses, as well as intracellular location prediction and positive selection analysis. Fe-ADH sequence analysis in animals showed that these enzymes possess three amino acids insertion, probably related to the new HOT function developed by these enzymes, since these insertion are absent in other non-eukaryotic Fe-ADHs. Phylogenetic analysis...
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<p>These proteins belong to five different FeADH protein subfamilies (sorted inside blue rectangles according to the protein subfamily to which they belong). Below each structure the scientific name of the organisms where the... more
<p>These proteins belong to five different FeADH protein subfamilies (sorted inside blue rectangles according to the protein subfamily to which they belong). Below each structure the scientific name of the organisms where the protein is found, as well as the PDB accession number is indicated in parenthesis. In a red rectangle are included representative structures of proteins of homolog protein families that belong to the DHQ-FeADH protein superfamily (cd07766). For reference, a structure prediction (performed with I-TASSER server; [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0166851#pone.0166851.ref077" target="_blank">77</a>]) of human ADHFE1 (accession NP_653251), which belongs to HOT subfamily (cd08190), is also included. Numbers in dark red show sequence identity (I) and similarity (S) between human ADHFE1 sequence and the indicated proteins. Secondary structure elements are colored in rainbow successive colors, starting from blue for the N-terminus and ending with red at the C-terminus. Protein structures were drawn using UCSF Chimera version 1.9 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0166851#pone.0166851.ref078" target="_blank">78</a>]</p
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<p>The evolutionary history was inferred using the Maximum Likelihood method based on the Le-Gascuel model [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0166851#pone.0166851.ref001"... more
<p>The evolutionary history was inferred using the Maximum Likelihood method based on the Le-Gascuel model [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0166851#pone.0166851.ref001" target="_blank">1</a>]. The tree with the highest log likelihood (-3414819.0869) is shown. Initial tree(s) for the heuristic search was/were obtained automatically applying Neighbor-Join and BioNJ algorithms to a matrix of pairwise distances estimated using a JTT model, and then selecting the topology with superior log likelihood value. A discrete Gamma distribution was used to model evolutionary rate differences among sites (5 categories (+G, parameter = 0.4901)). The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. The analysis involved 1219 amino acid sequences. There were a total of 996 positions in the final dataset.</p
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<p>The unrooted phylogenetic tree was inferred using the Maximum Likelihood method based on the Le-Gascuel model [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0166851#pone.0166851.ref049"... more
<p>The unrooted phylogenetic tree was inferred using the Maximum Likelihood method based on the Le-Gascuel model [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0166851#pone.0166851.ref049" target="_blank">49</a>]. Branches are colored according to the Conserved Domain Database Fe-ADH subfamily they belong. The tree with the highest log likelihood (-2505413,5328) is shown. Similar trees were obtained with maximum-parsimony, minimum-evolution and neighbour-joining methods. A discrete Gamma distribution was used to model evolutionary rate differences among sites (5 categories (+G, parameter = 0.8682)). The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. There were a total of 783 positions in the final dataset. The proportion of replicate trees in which the associated taxa clustered together in a bootstrap test (500 replicates) is given in color next to selected branches. Rectangles and triangles adjacent to each Fe-ADH subfamily name, indicate the presence of protein sequences from archaea domain (triangles), or eukarya domain (rectangles with A (animals), F (fungi), V (viridiplantae), and P (other eukaryotes) in each subfamily. Protein sequences from bacteria are present in all FeADH subfamilies.</p
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<p>These proteins belong to five different subfamilies of the FeADH family. For comparison, ADHFE1 sequence from human is included in the alignment, as well as four glycerol dehydrogenase sequences with a known three-dimensional... more
<p>These proteins belong to five different subfamilies of the FeADH family. For comparison, ADHFE1 sequence from human is included in the alignment, as well as four glycerol dehydrogenase sequences with a known three-dimensional structure. PDB accession number of each sequence is indicated at the left side of alignment, whereas the protein subfamily to which each sequence belongs, is in the right side of the alignment. Conserved β-strands and α-helices for each structure are indicated in yellow and green, respectively. Residue position determinant for coenzyme specificity is indicated with a red square. Residues involved in the binding of Fe atom are highlighted in pink; residues involved in the binding of Zinc atom in glicerol dehydrogenases are highlighted in grey. Amino acid residues from human ADHFE1 sequence, highlighted in blue and grey indicate positions that belong to the N-terminal or C-terminal domains, respectively. The three-dimensional alignment of FeADH structures was performed using the VAST tool at the NCBI’s server [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0166851#pone.0166851.ref043" target="_blank">43</a>].</p
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Oxidative stress is a factor that contributes to the development of complications in diabetes; however, its effects can be counteracted using exogenous antioxidants that are found in some plants, which is why people turn to traditional... more
Oxidative stress is a factor that contributes to the development of complications in diabetes; however, its effects can be counteracted using exogenous antioxidants that are found in some plants, which is why people turn to traditional medicines in the search for therapeutic treatment. Justicia spicigera has been demonstrated to have the capacity to reduce glycemic levels; however, its effects on non-insulin-dependent organs such as the liver have not been reported. During 30 days of administration of Justicia spicigera ethanol extract, the blood glucose and weight of rats were measured every 5 days. Once the treatment was concluded, the rats were sacrificed. Corporal weight, blood glucose, cholesterol, very-low-density lipoprotein (VLDL), triglycerides, total lipids, and liver profile were reduced in the diabetic condition and normalized with the application of ethanol extract from J. spicigera (EJS). Additionally, there was a significant increase in catalase and superoxide dismuta...
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The ALDH27 family of the aldehyde dehydrogenase superfamily comprises bacterial enzymes poorly studied so far in spite of seemingly being widely distributed, and of their putative important metabolic roles. With the double aim of... more
The ALDH27 family of the aldehyde dehydrogenase superfamily comprises bacterial enzymes poorly studied so far in spite of seemingly being widely distributed, and of their putative important metabolic roles. With the double aim of exploring their occurrence within bacteria and investigating their physiological functions, we performed comprehensive phylogenetic and genomic context analyses. We also biochemically and structurally characterized the three ALDH27 enzymes present in Pseudomonas aeruginosa PAO1 and tested the growth of PAO1 mutant strains on compounds that produce the putative substrate aldehydes. We retrieved 245 non‐redundant ALDH27 sequences from 149 reference genomes, most of them from αβγ‐proteobacteria, some from actinobacteria and a few from firmicutes. These sequences formed two subfamilies: ALDH27A and ALDH27B, which in turn consists of three clades. The neighboring gene of the aldh27A locus is a class I aldolase not characterized so far. Therefore, we could not in...
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Cardiovascular diseases (CVD) (such as occlusion of the coronary arteries, hypertensive heart diseases and strokes) are diseases that generate thousands of patients with a high mortality rate worldwide. Many of these cardiovascular... more
Cardiovascular diseases (CVD) (such as occlusion of the coronary arteries, hypertensive heart diseases and strokes) are diseases that generate thousands of patients with a high mortality rate worldwide. Many of these cardiovascular pathologies, during their development, generate a state of oxidative stress that leads to a deterioration in the patient’s conditions associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Within these reactive species we find superoxide anion (O2•–), hydroxyl radical (•OH), nitric oxide (NO•), as well as other species of non-free radicals such as hydrogen peroxide (H2O2), hypochlorous acid (HClO) and peroxynitrite (ONOO–). A molecule that actively participates in counteracting the oxidizing effect of reactive species is reduced glutathione (GSH), a tripeptide that is present in all tissues and that its synthesis and/or regeneration is very important to be able to respond to the increase in oxidizing agents. I...
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Pseudomonas is one of the most complex bacterial genera and is currently the genus of Gram‐negative bacteria with the largest number of species. Pseudomonas include a metabolically versatile group of organisms that are known to occupy... more
Pseudomonas is one of the most complex bacterial genera and is currently the genus of Gram‐negative bacteria with the largest number of species. Pseudomonas include a metabolically versatile group of organisms that are known to occupy numerous ecological niches. Pseudomonas putida is a non‐pathogenic, soil bacterium with a flexible and robust metabolism. P. putida KT2440 possesses a large genome (5,564 genes), lending to its adaptability to varying environments. The repertoire of P. putida genes, which are substantially conserved among different strains, is populated with sophisticated regulatory systems that are foundational to respond and adapt to diverse environments. P. putida KT2440 possesses an unexpected high number (32) of aldehyde dehydrogenase (aldh) genes (by comparison humans possess only 19 different aldh genes), but only a few of these ALDHs have been characterized. To obtain insights about the metabolic role performed by each one of the 32 ALDHs found in P. putida KT2...
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Spatiotemporal regulation of cAMP within the cell is required to achieve receptor‐specific responses. The mechanism through which the cell selects a specific response to newly synthesized cAMP is not fully understood. In hepatocyte plasma... more
Spatiotemporal regulation of cAMP within the cell is required to achieve receptor‐specific responses. The mechanism through which the cell selects a specific response to newly synthesized cAMP is not fully understood. In hepatocyte plasma membranes, we identified two functional and independent cAMP‐responsive signaling protein macrocomplexes that produce, use, degrade, and regulate their own nondiffusible (sequestered) cAMP pool to achieve their specific responses. Each complex responds to the stimulation of an adenosine G protein‐coupled receptor (Ado‐GPCR), bound to either A2A or A2B, but not simultaneously to both. Each isoprotein involved in each signaling cascade was identified by measuring changes in cAMP levels after receptor activation, and its participation was confirmed by antibody‐mediated inactivation. A2A‐Ado‐GPCR selective stimulation activates adenylyl cyclase 6 (AC6), which is bound to AKAP79/150, to synthesize cAMP which is used by two other AKAP79/150‐tethered prot...
Research Interests: Biology, Calcium, Cell Biology, Medicine, Signal Transduction, and 13 morecyclic AMP, Animals, Male, Phosphodiesterase Inhibitors, Rats, Hepatocytes, Wistar Rats, Primary Cell Culture, Biochemistry and cell biology, Gene Expression Regulation, Adenylyl Cyclase, Cell Membrane, and Medical biochemistry and metabolomics
In vertebrates, ethanol metabolism is performed through the concerted action of two enzymes: a Zn-dependent alcohol dehydrogenase (Zn-ADH) that oxidizes ethanol to acetaldehyde, and an aldehyde deh...
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Membrane fatty acid composition has an important role in yeast stress resistance, particularly in temperature tolerance. Most studies investigating temperature and membrane fatty acids use the yeast Saccharomyces cerevisiae without... more
Membrane fatty acid composition has an important role in yeast stress resistance, particularly in temperature tolerance. Most studies investigating temperature and membrane fatty acids use the yeast Saccharomyces cerevisiae without considering other yeasts, such as Kluyveromyces marxianus, which has physiological differences and industrial advantages with respect to S. cerevisiae. One of the primary traits of K. marxianus is its thermotolerance. The effect of fatty acid addition (oleic acid, linoleic acid, linolenic acid and araquidic acid) on the thermotolerance of the K. marxianus strain SLP1 was evaluated. SLP1 yeast exhibited temperature tolerance of up to 50°C; at 55°C, viability was reduced significantly, probably due to an increase in the generation of reactive oxygen chemical species. Externally added fatty acids were incorporated in the yeast membrane, increasing their proportion to approximately 70%, thereby changing membrane fluidity. SLP1 cells supplemented with polyunsa...
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Triosephosphate isomerase (TIM) is a ubiquitous enzyme, which appeared early in evolution. TIM is responsible for obtaining net ATP from glycolysis and producing an extra pyruvate molecule for each glucose molecule, under aerobic and... more
Triosephosphate isomerase (TIM) is a ubiquitous enzyme, which appeared early in evolution. TIM is responsible for obtaining net ATP from glycolysis and producing an extra pyruvate molecule for each glucose molecule, under aerobic and anaerobic conditions. It is placed in a metabolic crossroad that allows a quick balance of the triose phosphate aldolase produced by glycolysis, and is also linked to lipid metabolism through the alternation of glycerol-3-phosphate and the pentose cycle. TIM is one of the most studied enzymes with more than 199 structures deposited in the PDB. The interest for this enzyme stems from the fact that it is involved in glycolysis, but also in aging, human diseases and metabolism. TIM has been a target in the search for chemical compounds against infectious diseases and is a model to study catalytic features. Until February 2017, 62% of all residues of the protein have been studied by mutagenesis and/or using other approaches. Here, we present a detailed and ...
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The catalytic mechanism of the NAD(P)(+)-dependent aldehyde dehydrogenases (ALDHs) involves the nucleophilic attack of the essential cysteine (Cys302, mature HsALDH2 numbering) on the aldehyde substrate. Although oxidation of Cys302 will... more
The catalytic mechanism of the NAD(P)(+)-dependent aldehyde dehydrogenases (ALDHs) involves the nucleophilic attack of the essential cysteine (Cys302, mature HsALDH2 numbering) on the aldehyde substrate. Although oxidation of Cys302 will inactivate these enzymes, it is not yet well understood how this oxidation is prevented. In this work we explore possible mechanisms of protection by systematically analyzing the reported three-dimensional structures and amino acid sequences of the enzymes of the ALDH superfamily. Specifically, we considered the Cys302 conformational space, the structure and residues conservation of the catalytic loop where Cys302 is located, the observed oxidation states of Cys302, the ability of physiological reductants to revert its oxidation, and the presence of vicinal Cys in the catalytic loop. Our analyses suggested that: 1) In the apo-enzyme, the thiol group of Cys302 is quite resistant to oxidation by ambient O2 or mild oxidative conditions, because the pro...
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Research Interests: Drug interactions, Signal Transduction, Glucose, Liver, Epinephrine, and 15 moreAnimals, Male, Ethanol, Triglycerides, European, Spectrum, Rats, Oxidative phosphorylation, PIROXICAM, Lactic Acid, Oxygen Consumption, Adenosine Diphosphate, Mitochondrion, Rat Liver, and Pharmacology and pharmaceutical sciences
Research Interests: Biochemistry, Microbiology, Oxidative Stress, DNA damage, Humans, and 15 moreBacterial resistance, Animals, Heavy Metal, Membrane transport, Chromium, Iron, Pseudomonas aeruginosa, Enzyme, Oxidative Damage, Biometals, Pseudomonas Aeruginosa, Membrane Potential, Chromium Compounds, Biochemistry and cell biology, and Cell Membrane
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Research Interests: Drug interactions, Signal Transduction, Glucose, Liver, Epinephrine, and 15 moreAnimals, Male, Ethanol, Triglycerides, European, Spectrum, Rats, Oxidative phosphorylation, PIROXICAM, Lactic Acid, Oxygen Consumption, Adenosine Diphosphate, Mitochondrion, Rat Liver, and Pharmacology and pharmaceutical sciences
Research Interests: Evolutionary Biology, Genetics, Zoology, Computational Biology, Phylogeny, and 13 moreMitochondrial DNA, Cluster Analysis, Molecular Phylogenetics and Evolution, Cytochrome oxidase, Cell nucleus, Codon, Species Specificity, Amino Acid Sequence, Base Sequence, Chlorophyta, Gene Migration, Likelihood Functions, and Molecular Sequence Data
ACTUALMENTE EXISTE UNA GRAN DIVERSIDAD DE PRODUCTOS PARA EL CUIDADO DE LA PIEL, COMO CREMAS FACIALES, LOCIONES, CHAMPÚS, TOALLAS DESMAQUILLANTES E INCLUSO JABONES, QUE CONTIENEN ENTRE SUS INGREDIENTES VITAMINAS. LOS FABRICANTES PROCLAMAN... more
ACTUALMENTE EXISTE UNA GRAN DIVERSIDAD DE PRODUCTOS PARA EL CUIDADO DE LA PIEL, COMO CREMAS FACIALES, LOCIONES, CHAMPÚS, TOALLAS DESMAQUILLANTES E INCLUSO JABONES, QUE CONTIENEN ENTRE SUS INGREDIENTES VITAMINAS. LOS FABRICANTES PROCLAMAN QUE ESTO TIENE DIVERSOS BENEFICIOS PARA EL CONSUMIDOR, DESDE LA PROTECCIÓN DE LA PIEL CONTRA LAS AGRESIONES DEL AMBIENTE O LA DISMINUCIÓN DE LAS LINEAS DE EXPRESIÓN, HASTA LA PREVENCIÓN DEL ENVEJECIMIENTO PREMATURO DE LA PIEL Y LA CAPACIDAD DE ACLARARLA “MÁS ALLA DEL TONO GENÉTICO”. PERO ES MUY POCO LO QUE SE INFORMA AL PÚBLICO SOBRE LA VERACIDAD DE ESTAS AFIRMACIONES.
In fungi, heterotrimeric G proteins are key regulators of biological processes such as mating, virulence, morphology, among others. Mucor circinelloides is a model organism for many biological processes, and its genome contains the... more
In fungi, heterotrimeric G proteins are key regulators of biological processes such as mating, virulence, morphology, among others. Mucor circinelloides is a model organism for many biological processes, and its genome contains the largest known repertoire of genes that encode putative heterotrimeric G protein subunits in the fungal kingdom: twelve Gα (McGpa1-12), three Gβ (McGpb1-3), and three Gγ (McGpg1-3). Phylogenetic analysis of fungal Gα showed that they are divided into four distinct groups as reported previously. Fungal Gβ and Gγ are also divided into four phylogenetic groups, and to our understanding this is the first report of a phylogenetic classification for fungal Gβ and Gγ subunits. Almost all genes that encode putative heterotrimeric G subunits in M. circinelloides are differentially expressed during dimorphic growth, except for McGpg1 (Gγ) that showed very low mRNA levels at all developmental stages. Moreover, several of the subunits are expressed in a similar pattern and at the same level, suggesting that they constitute discrete complexes. For example, McGpb3 (Gβ), and McGpg2 (Gγ), are co-expressed during mycelium growth, and McGpa1, McGpb2, and McGpg2, are co-expressed during yeast development. These findings provide the conceptual framework to study the biological role of these genes during M. circinelloides morphogenesis.
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Nobel por sus descubrimientos sobre la transducción de señales en el sistema nervioso y en especial por la caracterización de la transmisión sináptica lenta y la memoria de corto plazo a través de fosforilación y defosforilación de... more
Nobel por sus descubrimientos sobre la transducción de señales en el sistema nervioso y en especial por la caracterización de la transmisión sináptica lenta y la memoria de corto plazo a través de fosforilación y defosforilación de proteínas. 1995 10 años J. Craig Venter y sus colegas publican la primera secuencia completa del genoma de un organismo de vida libre: Haemophilus influenzae. 1995 1 10 años Edward Lewis, Christiane Nüsslein-Volhard y Eric Wieschaus reciben el premio Nobel por sus descubrimientos concernientes al control genético de las etapas tempranas del desarrollo embrionario. 1990 15 años Andrew Simon Bell, David Brown y Nicholas Kenneth Terrett patentan un compuesto dilatador de los vasos sanguíneos, el sildenafil citrato, comercializado con el nombre de Viagra, que es empleado para tratar la disfunción eréctil. 1 Es difícil dejar de hacer mención que hace 10 años, también en 1995 el mexicano Mario Molina, junto con Sherwood Rowland y Paul Crutzen recibieron el prem...