Juan Manuel Berlanga - Academia.edu (original) (raw)
Papers by Juan Manuel Berlanga
Se reune y se presenta informacion geologica, geohidrologica y geofisica de la cuenca de Maverick... more Se reune y se presenta informacion geologica, geohidrologica y geofisica de la cuenca de Maverick de cuyo analisis se desprende la siguiente conclusion: Considerando la direccion de los vientos dominantes en invierno, el espesor de las formaciones arcillosas bajo el sitio de depositacion, la evidencia de fallas y fracturas asociadas al sistema Luling, la cercania a arroyos de la cuenca geohidrologica del Rio Bravo y fundamentalmente, la direccion del flujo superficial y subterraneo que pudieran contaminarse por la filtracion de los lixiviados del confinamiento de desechos radiactivos que la compania norteamericana Texcor Industries. Inc. propone construir en el poblado de Spofford, condado de Kinney Texas, los suelos y aguas subterraneas en territorio mexicano seran contaminadas radiactivamente por este tipo de confinamientos, ubicados a 28 kilometros de la franja fronteriza que separa a ambos paises.
La fórmula aplicada en la estimación del recurso potencial de gas natural en vetas de carbón es e... more La fórmula aplicada en la estimación del recurso potencial de gas natural en vetas de carbón es el eje alrededor del cual espira la redacción del informe. No es en su comprensión sino en su aplicación donde residen los problemas de evaluación y, para entenderlos, qué mejor que empezar por la descripción de las características que llevan a calificar al gas en el manto de carbón como un yacimiento no convencional. Distantes de los fundamentos, lo que aquí se ofrece son apenas los principios de la teoría de la evaluación del recurso: origen del gas en el proceso de carbonización, el manto como fuente, trampa y sello del gas, modelado de adsorción y desorción, y evaluación de prospectos, en primera instancia. Cómo se evalúan los prospectos de gas asociado a mantos de carbón en países productores y cómo se evalúan, a la luz de la información existente, los prospectos de las cuencas carboníferas de México son interrogantes que abren la puerta al tema de la descripción de los métodos de estimación convencionales y particulares. Cuáles son las cuencas mexicanas evaluadas, cuáles las no evaluadas y, en aquéllas, cuáles sus rasgos geológicos relevantes son puntos abordados en el escrito. Los recursos gasíferos de tres cuencas carboníferas: Sabinas, Fuentes-Río Escondido y Colombia-San Ignacio, las dos primeras representando el 99.9% de la producción nacional de carbón, son evaluados anteponiendo el máximo aprovechamiento de la información existente, recurriendo a una metodología híbrida según la cual, con el área de cada cuenca dividida en celdas, la profundidad del manto al centro de cada celda es interpolada, los valores de ceniza, materia volátil y humedad son aleatoriamente generados, la densidad in situ es inferida de la ceniza y una función de correlación, en tanto que el contenido de gas en el carbón es calculado de una isoterma de Langmuir, análoga a la de otros carbones de rango igual al del evaluado, a la presión del gas en el manto correspondiente a la profundidad estimada,según cierto gradiente preestablecido. El recurso total evaluado asciende a 6,042.2 Bscf de gas natural asociado al carbón, del cual 1,205.2 Bscf es recurso prospectivo, 449.2 Bscf es recurso contingente y 4,387.6 Bscf es volumen no recuperable, éste a 100 psig de presión de abandono. Sabinas contiene el 88.4% del recurso, el 87.1% del recurso prospectivo y el 90.2% del recurso contingente; Río Escondido, el 11.2%, el 12.9% y el 8.7%, respectivamente. Por volumen del recurso, la cuenca de Sabinas es comparable con las
Haematologica, 1998
The relationship between cytokine concentrations and transplant-related complications has been st... more The relationship between cytokine concentrations and transplant-related complications has been studied in bone marrow transplant patients. The changes in TNF-alpha, IL-1 and IL-6 concentrations after transplantation are well documented in the literature but this is not the case for IL-8. The purpose of the present study was to investigate prospectively the plasma concentration of these cytokines and their relationship to transplant-related complications. Pro-inflammatory cytokine (TNF-alpha, IL-1, IL-6 and IL-8) levels in plasma were determined in a group of 53 patients undergoing hematopoietic progenitor transplantation. Plasma samples were collected weekly from day -7 to day +35 and stored at -70 degrees C until assayed by ELISA. The major transplant-related toxicities registered were: veno-occlusive disease (VOD), acute graft-versus-host disease (GVHD), infectious episodes, renal failure and mucositis. In spite of the great variability of plasma cytokine profiles between the diff...
Acta Biotechnologica, 1993
Eukaryotic cells contain an unusually large cytoplasmic pool of P1/P2 phosphoproteins, which form... more Eukaryotic cells contain an unusually large cytoplasmic pool of P1/P2 phosphoproteins, which form the highly flexible 60S subunit stalk that is required to interact with and activate soluble translation factors. In cells, cytoplasmic P1/P2 proteins are exchanged for ribosome-bound proteins in a process that can modulate ribosome function and translation. Here, we analysed different S. cerevisiae stalk mutants grown under stress conditions that result in eIF2a phosphorylation. These mutants either lack a cytoplasmic pool of stalk proteins or contain free but not ribosome-bound proteins. Only cells that contain free P1/P2 proteins induce eIF2 phosphorylation in vivo in response to glucose starvation or osmotic stress. Moreover, we show that free S. cerevisiae P1/P2 proteins can induce in vitro phosphorylation of the initiation factor eIF2 by stimulating the autophosphorylation and activation of GCN2 kinase. Indeed, these ribosomal proteins do not stimulate other eIF2a kinases, such as PKR and HRI. P1/P2 and the known GCN2 activator deacylated tRNA compete for stimulating the eIF2a kinase activity of GCN2, although the P1/P2 proteins are considerably more active. These findings reveal a capacity of free cytoplasmic ribosomal stalk components to stimulate eIF2a phosphorylation, which in turn would modulate translation in response to specific forms of stress that may be linked with the previously described regulatory function of the ribosomal stalk. Citation: Jiménez-Díaz A, Remacha M, Ballesta JPG, Berlanga JJ (2013) Phosphorylation of Initiation Factor eIF2 in Response to Stress Conditions Is Mediated by Acidic Ribosomal P1/P2 Proteins in Saccharomyces cerevisiae. PLoS ONE 8(12): e84219.
PLoS ONE, 2009
Infection of BHK cells by Sindbis virus (SV) gives rise to a profound inhibition of cellular prot... more Infection of BHK cells by Sindbis virus (SV) gives rise to a profound inhibition of cellular protein synthesis, whereas translation of viral subgenomic mRNA that encodes viral structural proteins, continues for hours. To gain further knowledge on the mechanism by which this subgenomic mRNA is translated, the requirements for some initiation factors (eIFs) and for the presence of the initiator AUG were examined both in infected and in uninfected cells. To this end, BHK cells were transfected with different SV replicons or with in vitro made SV subgenomic mRNAs after inactivation of some eIFs. Specifically, eIF4G was cleaved by expression of the poliovirus 2A protease (2A pro ) and the alpha subunit of eIF2 was inactivated by phosphorylation induced by arsenite treatment. Moreover, cellular location of these and other translation components was analyzed in BHK infected cells by confocal microscopy. Cleavage of eIF4G by poliovirus 2A pro does not hamper translation of subgenomic mRNA in SV infected cells, but bisection of this factor blocks subgenomic mRNA translation in uninfected cells or in cell-free systems. SV infection induces phosphorylation of eIF2a, a process that is increased by arsenite treatment. Under these conditions, translation of subgenomic mRNA occurs to almost the same extent as controls in the infected cells but is drastically inhibited in uninfected cells. Notably, the correct initiation site on the subgenomic mRNA is still partially recognized when the initiation codon AUG is modified to other codons only in infected cells. Finally, immunolocalization of different eIFs reveals that eIF2 a and eIF4G are excluded from the foci, where viral RNA replication occurs, while eIF3, eEF2 and ribosomes concentrate in these regions. These findings support the notion that canonical initiation takes place when the subgenomic mRNA is translated out of the infection context, while initiation can occur without some eIFs and even at non-AUG codons in infected cells. Citation: Sanz MÁ , Castelló A, Ventoso I, Berlanga JJ, Carrasco L (2009) Dual Mechanism for the Translation of Subgenomic mRNA from Sindbis Virus in Infected and Uninfected Cells. PLoS ONE 4(3): e4772.
European Journal of Biochemistry, 1999
In eukaryotic cells, protein synthesis is regulated in response to various environmental stresses... more In eukaryotic cells, protein synthesis is regulated in response to various environmental stresses by phosphorylating the a subunit of the eukaryotic initiation factor 2 (eIF2a). Three different eIF2a kinases have been identified in mammalian cells, the heme-regulated inhibitor (HRI), the interferon-inducible RNA-dependent kinase (PKR) and the endoplasmic reticulum-resident kinase (PERK). A fourth eIF2a kinase, termed GCN2, was previously characterized from Saccharomyces cerevisiae, Drosophila melanogaster and Neurospora crassa. Here we describe the cloning of a mouse GCN2 cDNA (MGCN2), which represents the first mammalian GCN2 homolog. MGCN2 has a conserved motif, N-terminal to the kinase subdomain V, and a large insert of 139 amino acids located between subdomains IV and V that are characteristic of the known eIF2a kinases. Furthermore, MGCN2 contains a class II aminoacyl-tRNA synthetase domain and a degenerate kinase segment, downstream and upstream of the eIF2a kinase domain, respectively, and both are singular features of GCN2 protein kinases. MGCN2 mRNA is expressed as a single message of < 5.5 kb in a wide range of different tissues, with the highest levels in the liver and the brain. Specific polyclonal anti-(MGCN2) immunoprecipitated an eIF2a kinase activity and recognized a 190 kDa phosphoprotein in Western blots from either mouse liver or MGCN2transfected 293 cell extracts. Interestingly, serum starvation increased eIF2a phosphorylation in MGCN2transfected human 293T cells. This finding provides evidence that GCN2 is the unique eIF2a kinase present in all eukaryotes from yeast to mammals and underscores the role of MGCN2 kinase in translational control and its potential physiological significance.
The EMBO Journal, 2006
The poly(A)-binding protein (PABP) is a unique translation initiation factor in that it binds to ... more The poly(A)-binding protein (PABP) is a unique translation initiation factor in that it binds to the mRNA 3 0 poly(A) tail and stimulates recruitment of the ribosome to the mRNA at the 5 0 end. PABP activity is tightly controlled by the PABP-interacting protein 2 (Paip2), which inhibits translation by displacing PABP from the mRNA. Here, we describe a close interplay between PABP and Paip2 protein levels in the cell. We demonstrate a mechanism for this co-regulation that involves an E3 ubiquitin ligase, EDD, which targets Paip2 for degradation. PABP depletion by RNA interference (RNAi) causes co-depletion of Paip2 protein without affecting Paip2 mRNA levels. Upon PABP knockdown, Paip2 interacts with EDD, which leads to Paip2 ubiquitination. Supporting a critical role for EDD in Paip2 degradation, knockdown of EDD expression by siRNA leads to an increase in Paip2 protein stability. Thus, we demonstrate that the turnover of Paip2 in the cell is mediated by EDD and is regulated by PABP. This mechanism serves as a homeostatic feedback to control the activity of PABP in cells.
The EMBO Journal, 2006
In mammals, four different protein kinases, heme-regulated inhibitor, double-stranded RNA-depende... more In mammals, four different protein kinases, heme-regulated inhibitor, double-stranded RNA-dependent protein kinase (PKR), general control non-derepressible-2 (GCN2) and PKR-like endoplasmic reticulum kinase, regulate protein synthesis in response to environmental stresses by phosphorylating the a-subunit of the initiation factor 2 (eIF2a). We now report that mammalian GCN2 is specifically activated in vitro upon binding of two nonadjacent regions of the Sindbis virus (SV) genomic RNA to its histidyl-tRNA synthetase-related domain. Moreover, endogenous GCN2 is activated in cells upon SV infection. Strikingly, fibroblasts derived from GCN2 À/À mice possess an increased permissiveness to SV or vesicular stomatitis virus infection. We further show that mice lacking GCN2 are extremely susceptible to intranasal SV infection, demonstrating high virus titers in the brain compared to similarly infected control animals. The overexpression of wild-type GCN2, but not the catalytically inactive GCN2-K618R variant, in NIH 3T3 cells impaired the replication of a number of RNA viruses. We determined that GCN2 inhibits SV replication by blocking early viral translation of genomic SV RNA. These findings point to a hitherto unrecognized role of GCN2 as an early mediator in the cellular response to RNA viruses.
RNA, 2006
The 59 cap and 39 poly(A) tail of eukaryotic mRNAs act synergistically to enhance translation. Th... more The 59 cap and 39 poly(A) tail of eukaryotic mRNAs act synergistically to enhance translation. This synergy is mediated via interactions between eIF4G (a component of the eIF4F cap binding complex) and poly(A) binding protein (PABP). Paip2 (PABPinteracting protein 2) binds PABP and inhibits translation both in vitro and in vivo by decreasing the affinity of PABP for polyadenylated RNA. Here, we describe the functional characteristics of Paip2B, a Paip2 homolog. A full-length brain cDNA of Paip2B encodes a protein that shares 59% identity and 80% similarity with Paip2 (Paip2A), with the highest conservation in the two PABP binding domains. Paip2B acts in a manner similar to Paip2A to inhibit translation of capped and polyadenylated mRNAs both in vitro and in vivo by displacing PABP from the poly(A) tail. Also, similar to Paip2A, Paip2B does not affect the translation mediated by the internal ribosome entry site (IRES) of hepatitis C virus (HCV). However, Paip2A and Paip2B differ with respect to both mRNA and protein distribution in different tissues and cell lines. Paip2A is more highly ubiquitinated than is Paip2B and is degraded more rapidly by the proteasome. Paip2 protein degradation may constitute a primary mechanism by which cells regulate PABP activity in translation.
PLoS ONE, 2009
A number of viral proteases are able to cleave translation initiation factors leading to the inhi... more A number of viral proteases are able to cleave translation initiation factors leading to the inhibition of cellular translation.
PLoS ONE, 2012
The reversible phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2... more The reversible phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2 (eIF2alpha) is a wellcharacterized mechanism of translational control in response to a wide variety of cellular stresses, including viral infection. Beside PKR, the eIF2alpha kinase GCN2 participates in the cellular response against viral infection by RNA viruses with central nervous system tropism. PKR has also been involved in the antiviral response against HIV-1, although this antiviral effect is very limited due to the distinct mechanisms evolved by the virus to counteract PKR action. Here we report that infection of human cells with HIV-1 conveys the proteolytic cleavage of GCN2 and that purified HIV-1 and HIV-2 proteases produce direct proteolysis of GCN2 in vitro, abrogating the activation of GCN2 by HIV-1 RNA. Transfection of distinct cell lines with a plasmid encoding an HIV-1 cDNA clone competent for a single round of replication resulted in the activation of GCN2 and the subsequent eIF2alpha phosphorylation. Moreover, transfection of GCN2 knockout cells or cells with low levels of phosphorylated eIF2alpha with the same HIV-1 cDNA clone resulted in a marked increase of HIV-1 protein synthesis. Also, the over-expression of GCN2 in cells led to a diminished viral protein synthesis. These findings suggest that viral RNA produced during HIV-1 infection activates GCN2 leading to inhibition of viral RNA translation, and that HIV-1 protease cleaves GCN2 to overcome its antiviral effect. Citation: del Pino J, Jiménez JL, Ventoso I, Castelló A, Muñ oz-Fernández MÁ , et al. (2012) GCN2 Has Inhibitory Effect on Human Immunodeficiency Virus-1 Protein Synthesis and Is Cleaved upon Viral Infection. PLoS ONE 7(10): e47272.
Molecular Endocrinology, 1997
The PRL receptor (PRLR) is a member of the cytokine receptor superfamily. Rats and mice express t... more The PRL receptor (PRLR) is a member of the cytokine receptor superfamily. Rats and mice express two forms of PRLR, short (SPRLR) and long (LPRLR), which differ in the length and sequence of their cytoplasmic domains. We have analyzed the ability of each form of rat PRLR to transduce lactogenic signals in a bovine mammary gland epithelial cell line. The rat PRLR forms were expressed and detected by RT-PCR, indirect immunofluorescence, and cell surface ligand binding. When the biological activity of each form of PRLR was assessed by transient transfection, we found that the long form was able to activate the -casein gene promoter and that the short form was inactive. Interestingly, the coexpression of both forms of PRLR resulted in a block of PRL signal to the milk protein gene promoter as a function of the concentration of the SPRLR. Similar results were obtained when LPRLR was coexpressed with totally or partially inactive tyrosine mutants of either the Nb2 form or the LPRLR form. Thus, these results suggest that the SPRLR form has at least one clear biological function, i.e. to silence lactogenic signals and to contribute to a differential and acute PRL effect in rat tissues. Furthermore, the data derived from coexpression of LPRLR and PRLR mutants confirm a crucial role of the C-terminal tyrosine residue in lactogenic signaling and the dimerization
Leukemia Research, 2005
A consecutive series of acute myeloid leukemias (AML) patients was analyzed in conditions which r... more A consecutive series of acute myeloid leukemias (AML) patients was analyzed in conditions which reduce the inter-assay variations (the same flow cytometer, the same observers and the same panel of monoclonal antibodies) in order to investigate the prognostic information provided by flow cytometry. Two hundred and sixty-six bone marrow (BM) samples from 326 patients enrolled in the LMA-99 protocol from the CETLAM group were studied by multiparametric flow cytometry. Immunophenotyping studies were performed on erythrocyte-lysed BM samples. Antigen expression of leukemic cells was analyzed using triple stainings with fluorochrome-conjugated combinations of monoclonal antibodies. CD2 was positive in 21 cases (8%); an associated inv(16) was detected in eight CD2+ cases (38%). Two-year overall survival (OS) rate for CD2+/inv(16)+ patients was 75%, whereas it was 0% for CD2+/inv(16)- patients and 47% for CD2- patients (p=0.0001). CD36 was expressed in 37% of patients (n=98). Two-year leukemia-free survival (LFS) rate was 34% for CD36+ patients and 55% for CD36- patients (p=0.001). In the multivariate analysis, CD2+ (RR=8.4; p=0.0001) and adverse karyotype (RR=10.2; p=0.0001) were associated with a lower CR rate, CD36+ (RR=1.5; p=0.03), CD2+ (RR=2; p=0.04) and adverse karyotype (RR=4; p=0.0001) were associated with a lower OS and CD36+ (RR=2; p=0.002) and adverse karyotype (RR=3.5; p=0.005) predicted a lower LFS. CD2+ patients had a very poor OS when CD2/inv(16)+ cases were excluded. CD36 and CD2 expression at diagnosis can provide prognostically important information in adult de novo AML.
Leukemia, 2006
Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a good prognosis with... more Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a good prognosis with current anthracycline- and cytarabine-based protocols. Tandem analysis with flow cytometry (FC) and real-time RT-PCR (RQ-PCR) was applied to 55 patients, 28 harboring a t(8;21) and 27 an inv(16), including one case with a novel CBFbeta/MYH11 transcript. A total of 31% (n=17) of CR patients relapsed: seven with t(8;21) and 10 with inv(16). The mean amount of minimal residual disease (MRD) detected by FC in relapsed and nonrelapsed patients was markedly different: 0.3 vs 0.08% (P=0.002) at the end of treatment. The mean number of fusion transcript copies/ ABL x 10(4) also differed between relapsed and non-relapsed patients: 2385 vs 122 (P=0.001) after induction, 56 vs 7.6 after intensification (P=0.0001) and 75 vs 3.3 (P=0.0001) at the end of chemotherapy. Relapses were more common in patients with FC MRD level &amp;amp;amp;gt;0.1% at the end of treatment than in patients with &amp;amp;amp;lt; or = 0.1%: cumulative incidence of relapse (CIR) was 67 and 21% (P=0.03), respectively. Likewise, using RQ-PCR, a cutoff level of &amp;amp;amp;gt;10 copies at the end of treatment correlated with a high risk of relapse: CIR was 75% for patients with RQ-PCR &amp;amp;amp;gt;10 compared to 21% for patients with RQ-PCR levels &amp;amp;amp;lt; or = 10 (P=0.04). Combined use of FC and RQ-PCR may improve MRD detection, and provide useful clinical information on relapse kinetics in AML patients.
Leukemia, 2003
The MLL gene, located at 11q23 band, is frequently disrupted by different chromosomal rearrangeme... more The MLL gene, located at 11q23 band, is frequently disrupted by different chromosomal rearrangements that occur in a variety of hematological malignancies. MLL rearrangements are associated with distinct clinical features and a poor prognosis. The aim of this study was to analyze the incidence and the prognostic significance of MLL rearrangements in a consecutive series of adult AML patients and to determine the immunophenotypic features of these cases. The identification of abnormal immunophenotypes could be used for the detection of minimal residual disease (MRD). Ninety-three adult patients with de novo acute myeloid leukemia (AML) were analyzed by Southern blot in order to detect MLL rearrangements (MLL+). RT-PCR and genomic long-range PCR were performed to further characterize MLL partial tandem duplication (PTD) in those patients in whom conventional karyotype did not show 11q23 chromosomal translocations. All the patients were homogeneously immunophenotyped at diagnosis. MLL rearrangements were detected in 13 (14%) patients. Four patients (5%) showed 11q23 translocations by karyotypic conventional analysis. Nine patients (10%) revealed PTD of MLL and one patient showed a MLL cleavage pattern. The MLL+ patients usually expressed myeloid and monocytic antigens CD33 (12/13 cases), CD13 (9/13), CD117 (9/13), CD64 (11/13) and in some cases CD14 (4/11). HLA-DR was also positive in (12/13). Eight out of 13 cases expressed the stem cell marker CD34. Only one patient revealed lymphoid marker reactivity (CD7) and CD56 was expressed in 5/13 cases. All the MLL+ patients showed at least one aberrant phenotype at diagnosis, which allowed us to set out a simple panel for the MRD studies. Twenty-seven samples from eight patients in morphologic complete remission (CR) were analyzed using the aberrant immunologic combinations detected at diagnosis. Phenotypically abnormal cells were detected in all the patients who subsequently relapsed, whereas only one patient with MRD+ remained in CR. Owing to the high level of residual leukemic cells, the MLL+ patients showed a short CR duration and a poor survival. In conclusion, immunophenotyping may be a suitable approach to investigating MRD status in AML patients with PTD of the MLL gene.
Journal of Virology, 2010
The relevance of translational control in the gene expression and oncotropism of the autonomous p... more The relevance of translational control in the gene expression and oncotropism of the autonomous parvoviruses was investigated with MVMp, the prototype strain of minute virus of mice (MVM), infecting normal and transformed rodent and human cells of different tissue origins. Mouse embryo fibroblasts (MEFs) and NIH 3T3 fibroblasts were resistant to MVMp infection, but 3T3 fibroblasts derived from double-stranded RNA (dsRNA)-dependent protein kinase R (PKR) knockout mice (PKR o/o ) behaved in a manner that was highly permissive to productive MVMp replication. NIH 3T3 resistance correlated with significant phosphorylation of eukaryotic translation initiation factor 2 (eIF2) occurring at early time points after infection. Permissive
Journal of Neurochemistry, 2008
An in vitro model of ischemia was obtained by subjecting PC12 cells differentiated with nerve gro... more An in vitro model of ischemia was obtained by subjecting PC12 cells differentiated with nerve growth factor to a combination of glucose deprivation plus anoxia. Immediately after the ischemic period, the protein synthesis rate was significantly inhibited (80%) and western blots of cell extracts revealed a significant accumulation of phosphorylated eukaryotic initiation factor 2, alpha subunit, eIF2(alphaP) (42%). Upon recovery, eIF2(alphaP) levels returned to control values after 30 min, whereas protein synthesis was still partially inhibited (33%) and reached almost control values within 2 h. The activities of the mammalian eIF2alpha kinases, double-stranded RNA-activated protein kinase, mammalian GCN2 homologue, and endoplasmic reticulum-resident kinase, were determined. None of the eIF2alpha kinases studied showed increased activity in ischemic cells as compared with controls. Exposure of cells to cell-permeable inhibitors of protein phosphatases 1 and 2A, calyculin A or tautomycin, induced dose- and time-dependent accumulation of eIF2(alphaP), mimicking an ischemic effect. Protein phosphatase activity, as measured with [(32)P]phosphorylase a as a substrate, diminished during ischemia and returned to control levels upon 30-min recovery. In addition, the rate of eIF2(alphaP) dephosphorylation was significantly lower in ischemic cells, paralleling both the greatest translational inhibition and the highest eIF2(alphaP) levels. The endogenous phosphatase activity from control and ischemic extracts showed different sensitivity to inhibitor 2 and fostriecin in in vitro assays, inhibitor-2 effect in ischemic cells being lower than in control cells. Together these results indicate that an eIF2alpha phosphatase, probably protein phosphatase 1, is implicated in the ischemia-induced eIF2(alphaP) accumulation in PC12 cells.
Se reune y se presenta informacion geologica, geohidrologica y geofisica de la cuenca de Maverick... more Se reune y se presenta informacion geologica, geohidrologica y geofisica de la cuenca de Maverick de cuyo analisis se desprende la siguiente conclusion: Considerando la direccion de los vientos dominantes en invierno, el espesor de las formaciones arcillosas bajo el sitio de depositacion, la evidencia de fallas y fracturas asociadas al sistema Luling, la cercania a arroyos de la cuenca geohidrologica del Rio Bravo y fundamentalmente, la direccion del flujo superficial y subterraneo que pudieran contaminarse por la filtracion de los lixiviados del confinamiento de desechos radiactivos que la compania norteamericana Texcor Industries. Inc. propone construir en el poblado de Spofford, condado de Kinney Texas, los suelos y aguas subterraneas en territorio mexicano seran contaminadas radiactivamente por este tipo de confinamientos, ubicados a 28 kilometros de la franja fronteriza que separa a ambos paises.
La fórmula aplicada en la estimación del recurso potencial de gas natural en vetas de carbón es e... more La fórmula aplicada en la estimación del recurso potencial de gas natural en vetas de carbón es el eje alrededor del cual espira la redacción del informe. No es en su comprensión sino en su aplicación donde residen los problemas de evaluación y, para entenderlos, qué mejor que empezar por la descripción de las características que llevan a calificar al gas en el manto de carbón como un yacimiento no convencional. Distantes de los fundamentos, lo que aquí se ofrece son apenas los principios de la teoría de la evaluación del recurso: origen del gas en el proceso de carbonización, el manto como fuente, trampa y sello del gas, modelado de adsorción y desorción, y evaluación de prospectos, en primera instancia. Cómo se evalúan los prospectos de gas asociado a mantos de carbón en países productores y cómo se evalúan, a la luz de la información existente, los prospectos de las cuencas carboníferas de México son interrogantes que abren la puerta al tema de la descripción de los métodos de estimación convencionales y particulares. Cuáles son las cuencas mexicanas evaluadas, cuáles las no evaluadas y, en aquéllas, cuáles sus rasgos geológicos relevantes son puntos abordados en el escrito. Los recursos gasíferos de tres cuencas carboníferas: Sabinas, Fuentes-Río Escondido y Colombia-San Ignacio, las dos primeras representando el 99.9% de la producción nacional de carbón, son evaluados anteponiendo el máximo aprovechamiento de la información existente, recurriendo a una metodología híbrida según la cual, con el área de cada cuenca dividida en celdas, la profundidad del manto al centro de cada celda es interpolada, los valores de ceniza, materia volátil y humedad son aleatoriamente generados, la densidad in situ es inferida de la ceniza y una función de correlación, en tanto que el contenido de gas en el carbón es calculado de una isoterma de Langmuir, análoga a la de otros carbones de rango igual al del evaluado, a la presión del gas en el manto correspondiente a la profundidad estimada,según cierto gradiente preestablecido. El recurso total evaluado asciende a 6,042.2 Bscf de gas natural asociado al carbón, del cual 1,205.2 Bscf es recurso prospectivo, 449.2 Bscf es recurso contingente y 4,387.6 Bscf es volumen no recuperable, éste a 100 psig de presión de abandono. Sabinas contiene el 88.4% del recurso, el 87.1% del recurso prospectivo y el 90.2% del recurso contingente; Río Escondido, el 11.2%, el 12.9% y el 8.7%, respectivamente. Por volumen del recurso, la cuenca de Sabinas es comparable con las
Haematologica, 1998
The relationship between cytokine concentrations and transplant-related complications has been st... more The relationship between cytokine concentrations and transplant-related complications has been studied in bone marrow transplant patients. The changes in TNF-alpha, IL-1 and IL-6 concentrations after transplantation are well documented in the literature but this is not the case for IL-8. The purpose of the present study was to investigate prospectively the plasma concentration of these cytokines and their relationship to transplant-related complications. Pro-inflammatory cytokine (TNF-alpha, IL-1, IL-6 and IL-8) levels in plasma were determined in a group of 53 patients undergoing hematopoietic progenitor transplantation. Plasma samples were collected weekly from day -7 to day +35 and stored at -70 degrees C until assayed by ELISA. The major transplant-related toxicities registered were: veno-occlusive disease (VOD), acute graft-versus-host disease (GVHD), infectious episodes, renal failure and mucositis. In spite of the great variability of plasma cytokine profiles between the diff...
Acta Biotechnologica, 1993
Eukaryotic cells contain an unusually large cytoplasmic pool of P1/P2 phosphoproteins, which form... more Eukaryotic cells contain an unusually large cytoplasmic pool of P1/P2 phosphoproteins, which form the highly flexible 60S subunit stalk that is required to interact with and activate soluble translation factors. In cells, cytoplasmic P1/P2 proteins are exchanged for ribosome-bound proteins in a process that can modulate ribosome function and translation. Here, we analysed different S. cerevisiae stalk mutants grown under stress conditions that result in eIF2a phosphorylation. These mutants either lack a cytoplasmic pool of stalk proteins or contain free but not ribosome-bound proteins. Only cells that contain free P1/P2 proteins induce eIF2 phosphorylation in vivo in response to glucose starvation or osmotic stress. Moreover, we show that free S. cerevisiae P1/P2 proteins can induce in vitro phosphorylation of the initiation factor eIF2 by stimulating the autophosphorylation and activation of GCN2 kinase. Indeed, these ribosomal proteins do not stimulate other eIF2a kinases, such as PKR and HRI. P1/P2 and the known GCN2 activator deacylated tRNA compete for stimulating the eIF2a kinase activity of GCN2, although the P1/P2 proteins are considerably more active. These findings reveal a capacity of free cytoplasmic ribosomal stalk components to stimulate eIF2a phosphorylation, which in turn would modulate translation in response to specific forms of stress that may be linked with the previously described regulatory function of the ribosomal stalk. Citation: Jiménez-Díaz A, Remacha M, Ballesta JPG, Berlanga JJ (2013) Phosphorylation of Initiation Factor eIF2 in Response to Stress Conditions Is Mediated by Acidic Ribosomal P1/P2 Proteins in Saccharomyces cerevisiae. PLoS ONE 8(12): e84219.
PLoS ONE, 2009
Infection of BHK cells by Sindbis virus (SV) gives rise to a profound inhibition of cellular prot... more Infection of BHK cells by Sindbis virus (SV) gives rise to a profound inhibition of cellular protein synthesis, whereas translation of viral subgenomic mRNA that encodes viral structural proteins, continues for hours. To gain further knowledge on the mechanism by which this subgenomic mRNA is translated, the requirements for some initiation factors (eIFs) and for the presence of the initiator AUG were examined both in infected and in uninfected cells. To this end, BHK cells were transfected with different SV replicons or with in vitro made SV subgenomic mRNAs after inactivation of some eIFs. Specifically, eIF4G was cleaved by expression of the poliovirus 2A protease (2A pro ) and the alpha subunit of eIF2 was inactivated by phosphorylation induced by arsenite treatment. Moreover, cellular location of these and other translation components was analyzed in BHK infected cells by confocal microscopy. Cleavage of eIF4G by poliovirus 2A pro does not hamper translation of subgenomic mRNA in SV infected cells, but bisection of this factor blocks subgenomic mRNA translation in uninfected cells or in cell-free systems. SV infection induces phosphorylation of eIF2a, a process that is increased by arsenite treatment. Under these conditions, translation of subgenomic mRNA occurs to almost the same extent as controls in the infected cells but is drastically inhibited in uninfected cells. Notably, the correct initiation site on the subgenomic mRNA is still partially recognized when the initiation codon AUG is modified to other codons only in infected cells. Finally, immunolocalization of different eIFs reveals that eIF2 a and eIF4G are excluded from the foci, where viral RNA replication occurs, while eIF3, eEF2 and ribosomes concentrate in these regions. These findings support the notion that canonical initiation takes place when the subgenomic mRNA is translated out of the infection context, while initiation can occur without some eIFs and even at non-AUG codons in infected cells. Citation: Sanz MÁ , Castelló A, Ventoso I, Berlanga JJ, Carrasco L (2009) Dual Mechanism for the Translation of Subgenomic mRNA from Sindbis Virus in Infected and Uninfected Cells. PLoS ONE 4(3): e4772.
European Journal of Biochemistry, 1999
In eukaryotic cells, protein synthesis is regulated in response to various environmental stresses... more In eukaryotic cells, protein synthesis is regulated in response to various environmental stresses by phosphorylating the a subunit of the eukaryotic initiation factor 2 (eIF2a). Three different eIF2a kinases have been identified in mammalian cells, the heme-regulated inhibitor (HRI), the interferon-inducible RNA-dependent kinase (PKR) and the endoplasmic reticulum-resident kinase (PERK). A fourth eIF2a kinase, termed GCN2, was previously characterized from Saccharomyces cerevisiae, Drosophila melanogaster and Neurospora crassa. Here we describe the cloning of a mouse GCN2 cDNA (MGCN2), which represents the first mammalian GCN2 homolog. MGCN2 has a conserved motif, N-terminal to the kinase subdomain V, and a large insert of 139 amino acids located between subdomains IV and V that are characteristic of the known eIF2a kinases. Furthermore, MGCN2 contains a class II aminoacyl-tRNA synthetase domain and a degenerate kinase segment, downstream and upstream of the eIF2a kinase domain, respectively, and both are singular features of GCN2 protein kinases. MGCN2 mRNA is expressed as a single message of < 5.5 kb in a wide range of different tissues, with the highest levels in the liver and the brain. Specific polyclonal anti-(MGCN2) immunoprecipitated an eIF2a kinase activity and recognized a 190 kDa phosphoprotein in Western blots from either mouse liver or MGCN2transfected 293 cell extracts. Interestingly, serum starvation increased eIF2a phosphorylation in MGCN2transfected human 293T cells. This finding provides evidence that GCN2 is the unique eIF2a kinase present in all eukaryotes from yeast to mammals and underscores the role of MGCN2 kinase in translational control and its potential physiological significance.
The EMBO Journal, 2006
The poly(A)-binding protein (PABP) is a unique translation initiation factor in that it binds to ... more The poly(A)-binding protein (PABP) is a unique translation initiation factor in that it binds to the mRNA 3 0 poly(A) tail and stimulates recruitment of the ribosome to the mRNA at the 5 0 end. PABP activity is tightly controlled by the PABP-interacting protein 2 (Paip2), which inhibits translation by displacing PABP from the mRNA. Here, we describe a close interplay between PABP and Paip2 protein levels in the cell. We demonstrate a mechanism for this co-regulation that involves an E3 ubiquitin ligase, EDD, which targets Paip2 for degradation. PABP depletion by RNA interference (RNAi) causes co-depletion of Paip2 protein without affecting Paip2 mRNA levels. Upon PABP knockdown, Paip2 interacts with EDD, which leads to Paip2 ubiquitination. Supporting a critical role for EDD in Paip2 degradation, knockdown of EDD expression by siRNA leads to an increase in Paip2 protein stability. Thus, we demonstrate that the turnover of Paip2 in the cell is mediated by EDD and is regulated by PABP. This mechanism serves as a homeostatic feedback to control the activity of PABP in cells.
The EMBO Journal, 2006
In mammals, four different protein kinases, heme-regulated inhibitor, double-stranded RNA-depende... more In mammals, four different protein kinases, heme-regulated inhibitor, double-stranded RNA-dependent protein kinase (PKR), general control non-derepressible-2 (GCN2) and PKR-like endoplasmic reticulum kinase, regulate protein synthesis in response to environmental stresses by phosphorylating the a-subunit of the initiation factor 2 (eIF2a). We now report that mammalian GCN2 is specifically activated in vitro upon binding of two nonadjacent regions of the Sindbis virus (SV) genomic RNA to its histidyl-tRNA synthetase-related domain. Moreover, endogenous GCN2 is activated in cells upon SV infection. Strikingly, fibroblasts derived from GCN2 À/À mice possess an increased permissiveness to SV or vesicular stomatitis virus infection. We further show that mice lacking GCN2 are extremely susceptible to intranasal SV infection, demonstrating high virus titers in the brain compared to similarly infected control animals. The overexpression of wild-type GCN2, but not the catalytically inactive GCN2-K618R variant, in NIH 3T3 cells impaired the replication of a number of RNA viruses. We determined that GCN2 inhibits SV replication by blocking early viral translation of genomic SV RNA. These findings point to a hitherto unrecognized role of GCN2 as an early mediator in the cellular response to RNA viruses.
RNA, 2006
The 59 cap and 39 poly(A) tail of eukaryotic mRNAs act synergistically to enhance translation. Th... more The 59 cap and 39 poly(A) tail of eukaryotic mRNAs act synergistically to enhance translation. This synergy is mediated via interactions between eIF4G (a component of the eIF4F cap binding complex) and poly(A) binding protein (PABP). Paip2 (PABPinteracting protein 2) binds PABP and inhibits translation both in vitro and in vivo by decreasing the affinity of PABP for polyadenylated RNA. Here, we describe the functional characteristics of Paip2B, a Paip2 homolog. A full-length brain cDNA of Paip2B encodes a protein that shares 59% identity and 80% similarity with Paip2 (Paip2A), with the highest conservation in the two PABP binding domains. Paip2B acts in a manner similar to Paip2A to inhibit translation of capped and polyadenylated mRNAs both in vitro and in vivo by displacing PABP from the poly(A) tail. Also, similar to Paip2A, Paip2B does not affect the translation mediated by the internal ribosome entry site (IRES) of hepatitis C virus (HCV). However, Paip2A and Paip2B differ with respect to both mRNA and protein distribution in different tissues and cell lines. Paip2A is more highly ubiquitinated than is Paip2B and is degraded more rapidly by the proteasome. Paip2 protein degradation may constitute a primary mechanism by which cells regulate PABP activity in translation.
PLoS ONE, 2009
A number of viral proteases are able to cleave translation initiation factors leading to the inhi... more A number of viral proteases are able to cleave translation initiation factors leading to the inhibition of cellular translation.
PLoS ONE, 2012
The reversible phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2... more The reversible phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2 (eIF2alpha) is a wellcharacterized mechanism of translational control in response to a wide variety of cellular stresses, including viral infection. Beside PKR, the eIF2alpha kinase GCN2 participates in the cellular response against viral infection by RNA viruses with central nervous system tropism. PKR has also been involved in the antiviral response against HIV-1, although this antiviral effect is very limited due to the distinct mechanisms evolved by the virus to counteract PKR action. Here we report that infection of human cells with HIV-1 conveys the proteolytic cleavage of GCN2 and that purified HIV-1 and HIV-2 proteases produce direct proteolysis of GCN2 in vitro, abrogating the activation of GCN2 by HIV-1 RNA. Transfection of distinct cell lines with a plasmid encoding an HIV-1 cDNA clone competent for a single round of replication resulted in the activation of GCN2 and the subsequent eIF2alpha phosphorylation. Moreover, transfection of GCN2 knockout cells or cells with low levels of phosphorylated eIF2alpha with the same HIV-1 cDNA clone resulted in a marked increase of HIV-1 protein synthesis. Also, the over-expression of GCN2 in cells led to a diminished viral protein synthesis. These findings suggest that viral RNA produced during HIV-1 infection activates GCN2 leading to inhibition of viral RNA translation, and that HIV-1 protease cleaves GCN2 to overcome its antiviral effect. Citation: del Pino J, Jiménez JL, Ventoso I, Castelló A, Muñ oz-Fernández MÁ , et al. (2012) GCN2 Has Inhibitory Effect on Human Immunodeficiency Virus-1 Protein Synthesis and Is Cleaved upon Viral Infection. PLoS ONE 7(10): e47272.
Molecular Endocrinology, 1997
The PRL receptor (PRLR) is a member of the cytokine receptor superfamily. Rats and mice express t... more The PRL receptor (PRLR) is a member of the cytokine receptor superfamily. Rats and mice express two forms of PRLR, short (SPRLR) and long (LPRLR), which differ in the length and sequence of their cytoplasmic domains. We have analyzed the ability of each form of rat PRLR to transduce lactogenic signals in a bovine mammary gland epithelial cell line. The rat PRLR forms were expressed and detected by RT-PCR, indirect immunofluorescence, and cell surface ligand binding. When the biological activity of each form of PRLR was assessed by transient transfection, we found that the long form was able to activate the -casein gene promoter and that the short form was inactive. Interestingly, the coexpression of both forms of PRLR resulted in a block of PRL signal to the milk protein gene promoter as a function of the concentration of the SPRLR. Similar results were obtained when LPRLR was coexpressed with totally or partially inactive tyrosine mutants of either the Nb2 form or the LPRLR form. Thus, these results suggest that the SPRLR form has at least one clear biological function, i.e. to silence lactogenic signals and to contribute to a differential and acute PRL effect in rat tissues. Furthermore, the data derived from coexpression of LPRLR and PRLR mutants confirm a crucial role of the C-terminal tyrosine residue in lactogenic signaling and the dimerization
Leukemia Research, 2005
A consecutive series of acute myeloid leukemias (AML) patients was analyzed in conditions which r... more A consecutive series of acute myeloid leukemias (AML) patients was analyzed in conditions which reduce the inter-assay variations (the same flow cytometer, the same observers and the same panel of monoclonal antibodies) in order to investigate the prognostic information provided by flow cytometry. Two hundred and sixty-six bone marrow (BM) samples from 326 patients enrolled in the LMA-99 protocol from the CETLAM group were studied by multiparametric flow cytometry. Immunophenotyping studies were performed on erythrocyte-lysed BM samples. Antigen expression of leukemic cells was analyzed using triple stainings with fluorochrome-conjugated combinations of monoclonal antibodies. CD2 was positive in 21 cases (8%); an associated inv(16) was detected in eight CD2+ cases (38%). Two-year overall survival (OS) rate for CD2+/inv(16)+ patients was 75%, whereas it was 0% for CD2+/inv(16)- patients and 47% for CD2- patients (p=0.0001). CD36 was expressed in 37% of patients (n=98). Two-year leukemia-free survival (LFS) rate was 34% for CD36+ patients and 55% for CD36- patients (p=0.001). In the multivariate analysis, CD2+ (RR=8.4; p=0.0001) and adverse karyotype (RR=10.2; p=0.0001) were associated with a lower CR rate, CD36+ (RR=1.5; p=0.03), CD2+ (RR=2; p=0.04) and adverse karyotype (RR=4; p=0.0001) were associated with a lower OS and CD36+ (RR=2; p=0.002) and adverse karyotype (RR=3.5; p=0.005) predicted a lower LFS. CD2+ patients had a very poor OS when CD2/inv(16)+ cases were excluded. CD36 and CD2 expression at diagnosis can provide prognostically important information in adult de novo AML.
Leukemia, 2006
Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a good prognosis with... more Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a good prognosis with current anthracycline- and cytarabine-based protocols. Tandem analysis with flow cytometry (FC) and real-time RT-PCR (RQ-PCR) was applied to 55 patients, 28 harboring a t(8;21) and 27 an inv(16), including one case with a novel CBFbeta/MYH11 transcript. A total of 31% (n=17) of CR patients relapsed: seven with t(8;21) and 10 with inv(16). The mean amount of minimal residual disease (MRD) detected by FC in relapsed and nonrelapsed patients was markedly different: 0.3 vs 0.08% (P=0.002) at the end of treatment. The mean number of fusion transcript copies/ ABL x 10(4) also differed between relapsed and non-relapsed patients: 2385 vs 122 (P=0.001) after induction, 56 vs 7.6 after intensification (P=0.0001) and 75 vs 3.3 (P=0.0001) at the end of chemotherapy. Relapses were more common in patients with FC MRD level &amp;amp;amp;gt;0.1% at the end of treatment than in patients with &amp;amp;amp;lt; or = 0.1%: cumulative incidence of relapse (CIR) was 67 and 21% (P=0.03), respectively. Likewise, using RQ-PCR, a cutoff level of &amp;amp;amp;gt;10 copies at the end of treatment correlated with a high risk of relapse: CIR was 75% for patients with RQ-PCR &amp;amp;amp;gt;10 compared to 21% for patients with RQ-PCR levels &amp;amp;amp;lt; or = 10 (P=0.04). Combined use of FC and RQ-PCR may improve MRD detection, and provide useful clinical information on relapse kinetics in AML patients.
Leukemia, 2003
The MLL gene, located at 11q23 band, is frequently disrupted by different chromosomal rearrangeme... more The MLL gene, located at 11q23 band, is frequently disrupted by different chromosomal rearrangements that occur in a variety of hematological malignancies. MLL rearrangements are associated with distinct clinical features and a poor prognosis. The aim of this study was to analyze the incidence and the prognostic significance of MLL rearrangements in a consecutive series of adult AML patients and to determine the immunophenotypic features of these cases. The identification of abnormal immunophenotypes could be used for the detection of minimal residual disease (MRD). Ninety-three adult patients with de novo acute myeloid leukemia (AML) were analyzed by Southern blot in order to detect MLL rearrangements (MLL+). RT-PCR and genomic long-range PCR were performed to further characterize MLL partial tandem duplication (PTD) in those patients in whom conventional karyotype did not show 11q23 chromosomal translocations. All the patients were homogeneously immunophenotyped at diagnosis. MLL rearrangements were detected in 13 (14%) patients. Four patients (5%) showed 11q23 translocations by karyotypic conventional analysis. Nine patients (10%) revealed PTD of MLL and one patient showed a MLL cleavage pattern. The MLL+ patients usually expressed myeloid and monocytic antigens CD33 (12/13 cases), CD13 (9/13), CD117 (9/13), CD64 (11/13) and in some cases CD14 (4/11). HLA-DR was also positive in (12/13). Eight out of 13 cases expressed the stem cell marker CD34. Only one patient revealed lymphoid marker reactivity (CD7) and CD56 was expressed in 5/13 cases. All the MLL+ patients showed at least one aberrant phenotype at diagnosis, which allowed us to set out a simple panel for the MRD studies. Twenty-seven samples from eight patients in morphologic complete remission (CR) were analyzed using the aberrant immunologic combinations detected at diagnosis. Phenotypically abnormal cells were detected in all the patients who subsequently relapsed, whereas only one patient with MRD+ remained in CR. Owing to the high level of residual leukemic cells, the MLL+ patients showed a short CR duration and a poor survival. In conclusion, immunophenotyping may be a suitable approach to investigating MRD status in AML patients with PTD of the MLL gene.
Journal of Virology, 2010
The relevance of translational control in the gene expression and oncotropism of the autonomous p... more The relevance of translational control in the gene expression and oncotropism of the autonomous parvoviruses was investigated with MVMp, the prototype strain of minute virus of mice (MVM), infecting normal and transformed rodent and human cells of different tissue origins. Mouse embryo fibroblasts (MEFs) and NIH 3T3 fibroblasts were resistant to MVMp infection, but 3T3 fibroblasts derived from double-stranded RNA (dsRNA)-dependent protein kinase R (PKR) knockout mice (PKR o/o ) behaved in a manner that was highly permissive to productive MVMp replication. NIH 3T3 resistance correlated with significant phosphorylation of eukaryotic translation initiation factor 2 (eIF2) occurring at early time points after infection. Permissive
Journal of Neurochemistry, 2008
An in vitro model of ischemia was obtained by subjecting PC12 cells differentiated with nerve gro... more An in vitro model of ischemia was obtained by subjecting PC12 cells differentiated with nerve growth factor to a combination of glucose deprivation plus anoxia. Immediately after the ischemic period, the protein synthesis rate was significantly inhibited (80%) and western blots of cell extracts revealed a significant accumulation of phosphorylated eukaryotic initiation factor 2, alpha subunit, eIF2(alphaP) (42%). Upon recovery, eIF2(alphaP) levels returned to control values after 30 min, whereas protein synthesis was still partially inhibited (33%) and reached almost control values within 2 h. The activities of the mammalian eIF2alpha kinases, double-stranded RNA-activated protein kinase, mammalian GCN2 homologue, and endoplasmic reticulum-resident kinase, were determined. None of the eIF2alpha kinases studied showed increased activity in ischemic cells as compared with controls. Exposure of cells to cell-permeable inhibitors of protein phosphatases 1 and 2A, calyculin A or tautomycin, induced dose- and time-dependent accumulation of eIF2(alphaP), mimicking an ischemic effect. Protein phosphatase activity, as measured with [(32)P]phosphorylase a as a substrate, diminished during ischemia and returned to control levels upon 30-min recovery. In addition, the rate of eIF2(alphaP) dephosphorylation was significantly lower in ischemic cells, paralleling both the greatest translational inhibition and the highest eIF2(alphaP) levels. The endogenous phosphatase activity from control and ischemic extracts showed different sensitivity to inhibitor 2 and fostriecin in in vitro assays, inhibitor-2 effect in ischemic cells being lower than in control cells. Together these results indicate that an eIF2alpha phosphatase, probably protein phosphatase 1, is implicated in the ischemia-induced eIF2(alphaP) accumulation in PC12 cells.
Dos pruebas de inyección de CO2 son ejecutadas entre el 19 de julio de 2010 y 31 de marzo del 201... more Dos pruebas de inyección de CO2 son ejecutadas entre el 19 de julio de 2010 y 31 de marzo del 2011. El propósito: encontrar formas de incrementar la recuperación de aceite en campos de la Formación Chicontepec. La primera es una prueba de inyección continua que involucra un pozo inyector y seis productores de la macropera Coyotes 331, del campo Coyotes. En 166 días, 197 MM scf CO2, equivalentes a 93,850 barriles de espacio poroso, ó 1.1 veces el volumen de líquidos producido por los 7 pozos de la macropera a junio de 2010, son inyectados. Un pozo, el Coyotes 312, reacciona a la inyección. Sin
embargo, contrario al orden establecido en flujo continuo: ascenso de presión, incremento de producción e irrupción, el pozo manifiesta surgencia temprana, paulatino incremento de presión y cero cambio en la declinación. En los otros, la declinación permanece sin cambio, composicionalmente el aceite no acusa variación. El que ninguno de los pozos productores haya respondido favorablemente a la inyección sugiere la idea de un yacimiento segmentado en el cual lentes areno arcillosas, impregnadas de aceite y aleatoriamente distribuidas estarían rodeadas por roca estéril, impermeable al flujo de aceite, que no de gas. Reforzada por las experiencias adversas de las pruebas de inyección de agua, tal apreciación llevaría a replantear la prueba de inyección en otra dirección.
Evaluación de Reservas de Sulfato de Sodio, Laguna del Rey, México., 1998
El objetivo principal de este trabajo es la evaluación de las reservas de sulfato de sodio, en su... more El objetivo principal de este trabajo es la evaluación de las reservas de sulfato de sodio, en sus fases líquida y sólida, del yacimiento lacustre Laguna del Rey. Tal objetivo se persigue mediante el reconocimiento de los principales procesos físicos, químicos y geológicos directamente involucrados en la estimación de las reservas de sulfato de sodio, la jerarquización de su importancia y complejidad, y la identificación de las variables descriptivas de tales procesos. Reconocidos estos procesos, se propone una solución integral en la cual se hace uso, hasta donde es posible, de recursos tecnológicos existentes y, donde no, se desarrollan respuestas propias.
Tras 60 años de inyección continua, el proceso de recuperación secundaria implementado en el Comp... more Tras 60 años de inyección continua, el proceso de recuperación secundaria implementado en el Complejo Poza Rica se acerca a su fase terminal. Más del 29% del aceite in situ ha sido recuperado: 20.6% en la etapa primaria, 9.1% en la secundaria. Al ritmo actual de producción (11,100 stb/d de aceite), hacia el 2017 se alcanzará la recuperación final. 3,300 millones de barriles de aceite yacen todavía en el yacimiento y, sin embargo, las alternativas de explotación se agotan. Explotar los bancos de aceite virgen, de por sí pequeños, erráticos y difíciles de ubicar, es una opción de relativamente baja producción y alta incertidumbre.
Hoy, a diferencia de ayer, el aceite que permanece en el yacimiento es más denso y viscoso, reside en los poros más pequeños y siempre adherido a la roca, con el agua congénita ha aumentado la tensión interfacial y constituye la fase discontinua. A las fuerzas capilares se atribuye la baja movilidad de fracciones cada vez más importantes de aceite. Pruebas de laboratorio en muestras de roca y aceite del yacimiento demuestran que, con la adición de surfactantes, se revierte la mojabilidad y el aceite se libera, la tensión interfacial se reduce y el aceite se moviliza. Liberación y movilización ocurren por goteo. Cuanto más baja la tensión interfacial, menor el tamaño de la garganta poral a través de la cual fluyen las gotas de aceite.
Con duración mínima un año, se propone la ejecución, en primera instancia, de tres pruebas de campo. El vehículo es agua de las plantas de tratamiento y de deshidratación, el surfactante de los tipos zwitteriónico y catiónico. El propósito es obtener valores de producción incremental, saturación residual, recuperación adicional y flujo fraccional. Con esto y los costos de capital y de operación que demanda una obra de inyección de 100 mil b/d de agua de mar, se pretende conocer la rentabilidad del proyecto. No será sino hasta entonces cuando se sepa si el proyecto es económicamente viable y cuánto aporta en términos del incremento en la reserva probada.
Partiendo de las ecuaciones de balance de energía y de flujo transitorio se presenta un procedimi... more Partiendo de las ecuaciones de balance de energía y de flujo transitorio se presenta un procedimiento iterativo para el cálculo de los perfiles de presión y calidad del flujo de vapor en tuberías y medio poroso. Vinculado en el fondo del agujero, el procedimiento se ejemplifica con la inyección de vapor en carbonatos fracturados del campo Ébano.
Diseño Prueba Piloto Inyección de Aire en YNF, 2006
Presencia y Trascendencia de Oro Grueso en Yacimiento de Sonora, México., 2001
Anexo Informe Impacto Contaminación Cuenca Rio Escondido, Coahuila., 1992
Impacto Contaminación Radioactiva en Cuenca de Rio Escondido, Coahuila., 1992
La fórmula aplicada en la estimación del recurso potencial de gas natural en vetas de carbón es e... more La fórmula aplicada en la estimación del recurso potencial de gas natural en vetas de carbón es el eje alrededor del cual gira la redacción del informe. No es en su comprensión sino en su aplicación donde residen los problemas de evaluación y, para entenderlos, qué mejor que empezar por la descripción de las características que llevan a calificar al gas en el manto de carbón como un yacimiento no convencional. Distantes de los fundamentos, lo que aquí se ofrece son apenas los principios de la teoría de la evaluación del recurso: origen del gas en el proceso de carbonización, el manto como fuente, trampa y sello del gas, modelado de adsorción y desorción, y evaluación de prospectos, en primera instancia.
Cómo se evalúan los prospectos de gas asociado a mantos de carbón en países productores y cómo se evalúan, a la luz de la información existente, los prospectos de las cuencas carboníferas de México son interrogantes que abren la puerta al tema de la descripción de los métodos de estimación convencionales y particulares. Cuáles son las cuencas mexicanas evaluadas, cuáles las no evaluadas y, en aquéllas, cuáles sus rasgos geológicos relevantes son puntos abordados en el escrito. Los recursos gasíferos de tres cuencas carboníferas: Sabinas, Fuentes-Río Escondido y Colombia-San Ignacio, las dos primeras representando el 99.9% de la producción nacional de carbón, son evaluados anteponiendo el máximo aprovechamiento de la información existente, recurriendo a una metodología híbrida según la cual, con el área de cada cuenca dividida en celdas, la profundidad del manto al centro de cada celda es interpolada, los valores de ceniza, materia volátil y humedad son aleatoriamente generados, la densidad in situ es inferida de la ceniza y una función
de correlación, en tanto que el contenido de gas en el carbón es calculado de una isoterma de Langmuir, análoga a la de otros carbones de rango igual al del evaluado, a la presión del gas en el manto correspondiente a la profundidad estimada,según cierto gradiente preestablecido.
El recurso total evaluado asciende a 6,042.2 Bscf de gas natural asociado al carbón, del cual 1,205.2 Bscf es recurso prospectivo, 449.2 Bscf es recurso contingente y 4,387.6 Bscf es volumen no recuperable, éste a 100 psig de presión de abandono. Sabinas contiene el 88.4% del recurso, el
87.1% del recurso prospectivo y el 90.2% del recurso contingente; Río Escondido, el 11.2%, el 12.9% y el 8.7%, respectivamente. Por volumen del recurso, la cuenca de Sabinas es comparable con las 2 de Southern Appalachian y Arkoma, las de menor tamaño en EU y donde no se reporta plan alguno de explotación comercial de gas natural.
En las condiciones vigentes las zonas evaluadas adolecen de importantes piezas de información sin las cuales no es posible crear un modelo de caracterización más verosímil con el cual incrementar la asertividad de los resultados. Implícito en el concepto de reserva está el del beneficio económico y, en éste, el de la producción de gas y agua. Sin mediciones de porosidad, permeabilidad, anisotropía, saturación de agua, desorción de gas, espesor neto de manto, por mencionar lo obvio, no es posible determinar seria y acertadamente la reserva. Sin el diseño y la ejecución de pruebas piloto en arreglos de, digamos, 5 pozos, no podrá establecerse, con certidumbre, la rentabilidad de las áreas a licitar.
Siendo la más importante reserva probada de CO2 en México, Quebrache es la fuente natural propues... more Siendo la más importante reserva probada de CO2 en México, Quebrache es la fuente natural propuesta en el análisis de dos proyectos de recuperación mejorada. Precedido por un diseño conceptual de transporte, distribución e inyección a pozo, cada proyecto es analizado bajo la lupa económica, preasignando distintos factores de utilización y de recuperación incremental, así como perfiles de producción. Concluido el análisis, un proyecto resulta elegible proponiendo, para él, el diseño y ejecución de una prueba piloto de inyección.
La versión 2018 del plan de captura, uso y secuestro de CO2 contiene 7 propuestas que involucran ... more La versión 2018 del plan de captura, uso y secuestro de CO2 contiene 7 propuestas que involucran 6 fuentes de emisión de gases de efecto invernadero elegidas por su relativa cercanía a campos petroleros. Sea ingrediente de los gases de combustión o producto secundario de procesos industriales, provenga de centrales termoeléctricas o de plantas petroquímicas, es el CO2 la materia a tratar. Precedido por un diseño conceptual de transporte, distribución e inyección a pozo, cada proyecto es analizado bajo la lupa de los resultados económicos obtenidos, preasignando distintos factores de utilización y de recuperación, así como perfiles de producción. Concluido el análisis, dos proyectos resultan elegibles, proponiendo, acto continuo, desarrollar en sus respectivos campos el diseño y ejecución de pruebas piloto de inyección de CO2.
Resumen. En el presente trabajo intervienen cuatro campos: Agua Fría, testigo de la prueba de iny... more Resumen. En el presente trabajo intervienen cuatro campos: Agua Fría, testigo de la prueba de inyección de agua más extensa jamás realizada, y Coapechaca, Corralillo y Tajín, vecinos del primero y parte importante en el análisis del historial de producción de cerca de la mitad de los pozos perforados en el complejo Chicontepec, al día de hoy. Involucra información del gasto diario promedio mensual de aceite, tratándose de producción, y agua, refiriéndose a inyección. La interpretación de los resultados se efectúa en el marco de un modelo geológico según el cual, los yacimientos están constituidos por lentes areno-arcillosas parcialmente cementadas, erráticamente distribuidas, encapsuladas en arenisca impermeable, y donde redes de fracturas subordinadas a distintos elementos tectónicos permitieron que el aceite se emplazara. La recuperación incremental del aceite acreditado en una década de inyección de agua se estima en 0.6%, u 880 mil barriles de aceite, a razón de 38 barriles de agua inyectada por barril de aceite producido. Tres indicadores de productividad y tres de rentabilidad económica, calculados por pozo, campo y conjunto de 4 campos, graficados espacial y temporalmente, permiten discriminar zonas mayor y menormente productivas, por ende, rentables, amén de convalidar el modelo de yacimiento. A diciembre de 2017, fecha del más reciente reporte de producción, Agua Fría y Coapechaca lastran el desempeño del conjunto. A nivel de campo, un buen modelo de declinación de la producción anual es el logarítmico exponencial.
Chicontepec es un proyecto cuya operación reporta pérdidas a la empresa y al estado. Por cada dól... more Chicontepec es un proyecto cuya operación reporta pérdidas a la empresa y al estado. Por cada dólar gastado PEP ha generado 6 centavos de utilidad, antes de impuestos. Por cada 1000 pesos del erario invertido, 640 pesos han sido recobrados, 92% vía endeudamiento. Detrás de Cantarell y Ku Maloob Zap, Chicontepec es el complejo donde mas se ha invertido y al mismo tiempo de dónde menos se ha producido. En la relación inversión-producción, Chicontepec es entre 8 y 20 veces más alta que en los otros complejos del sistema petrolero nacional. Como unidad de inversión, el valor de la producción de los 4,090 pozos de Chicontepec ofrece, en promedio, tasa de retorno negativa (-3.3%), valor presente negativo (-1,315.5 miles de dólares), 6.6% de los pozos TIR > 20%, 11.9% VPN > 0. En nuevos desarrollos, colocar los descubrimientos en la franja económica implica una reducción del costo promedio integrado (57.32 usd/stb) de 33%, en un "buen" yacimiento, o 75%, en un "mal" yacimiento. Sin embargo, ante la carencia de evidencias que sugieran la presencia en el subsuelo de elementos estructurales que permitan al hidrocarburo migrar de la roca generadora a la trampa, no se avizora en los nuevos desarrollos la ocurrencia de "buenos" yacimientos, sino todo lo contrario.
Una prueba piloto de inyección alterna de vapor será ejecutada en dos pozos del campo Altamira, c... more Una prueba piloto de inyección alterna de vapor será ejecutada en dos pozos del campo Altamira, complejo Ébano-Pánuco-Cacalilao, con el propósito de evaluar qué tanto aceite adicional puede ser extraído de las formaciones productoras al agregar calor, elevar la temperatura y disminuir las fuerzas viscosas retentivas. Se propone un modelo estructural según el cual zonas de cizalla asociadas a cuatro sistemas de fallas producto de esfuerzos de corrimiento constituyen el yacimiento. Perfiles de presión, temperatura, calidad del vapor, calor sensible y calor latente son calculados en pozo y yacimiento. Aunado al flujo por conducción y radiante, dos mecanismos de transmisión del calor contenido en el vapor son considerados: lateralmente, convección forzada, verticalmente, convección libre.
Primera prueba piloto de inyección de vapor en el campo Altamira y tercera en el complejo Ébano P... more Primera prueba piloto de inyección de vapor en el campo Altamira y tercera en el complejo Ébano Pánuco Cacalilao que por cuyos resultados el problema de la recuperación térmica de aceite pesado en formaciones carbonatadas naturalmente fracturadas sin impregnación matricial permanece todavía irresuelto. Por qué, en esta prueba huff'n puff, después de haber inyectado 4,300 toneladas de vapor, aguardado el tiempo de remojo y abierto el pozo, se obtuvo, para todo efecto práctico, nula producción de aceite es una interrogante ante la cual se ofrecen, más que respuestas concretas, hipotéticas explicaciones. Para entender cómo es que se llega a éstas se describe el yacimiento, conceptual e hidráulicamente, se presentan las tareas de conversión del pozo productor a inyector, la información recabada durante la inyección, el remojo y la hasta ahora infructuosa inducción en producción. Alejado de la autocomplacencia, el escrito aborda hechos y resultados adversos y aventura dos explicaciones, una de naturaleza geológica, operativa la otra.
Entre plataforma interna, margen de plataforma, talud y cuenca, el talud es, por mucho, el ambien... more Entre plataforma interna, margen de plataforma, talud y cuenca, el talud es, por mucho, el ambiente de depósito más heterogéneo. Ignorarla es una simplificación que puede conducir a falsas interpretaciones, más tratándose de la implementación en campo de prácticas de recuperación mejorada como la inyección de tenso-activos. A escalas de centímetros, decímetros y metros, hasta cinco, y quizá más, órdenes de magnitud son distinguibles en la permeabilidad de los sedimentos, alóctonos y autóctonos, intercalados e interestratificados, que se depositan en este ambiente de transición. Capturada por la permeabilidad, la heterogeneidad local es inferida empleando la transformada indicatriz y un caso es ejemplificado utilizando información del complejo Poza Rica. Dónde inyectar y qué producto utilizar son dos interrogantes que, bajo los criterios establecidos, intentarán ser respondidas.
En cierta porción de área del campo Poza Rica, elegida como zona de aplicación de una prueba de i... more En cierta porción de área del campo Poza Rica, elegida como zona de aplicación de una prueba de inyección de surfactantes, se determina, mediante los recursos que aporta la teoría de flujo fraccional, el beneficio esperado, tanto en términos del incremento en la recuperación de aceite como en la reducción de la producción de agua.