Ab initio modeling and molecular dynamics simulation of the alpha 1b-adrenergic receptor activation.

This work describes the ab initio procedure employed to build an activation model for the alpha 1b-adrenergic receptor (alpha 1b-AR). The first version of the model was progressively modified and complicated by means of a many-step iterative procedure characterized by the employment of experimental validations of the model in each upgrading step. A combined simulated (molecular dynamics) and experimental mutagenesis approach was used to determine the structural and dynamic features characterizing the inactive and active states of alpha 1b-AR. The latest version of the model has been successfully challenged with respect to its ability to interpret and predict the functional properties of a large number of mutants. The iterative approach employed to describe alpha 1b-AR activation in terms of molecular structure and dynamics allows further complications of the model to allow prediction and interpretation of an ever-increasing number of experimental data.

Análisis y diseño de filtros apilados basados en resonadores acústicos

Durant els últims anys la demanda de filtres pas banda de ràdio freqüència, de reduïdes dimensions, lleugers i d'elevades prestacions destinats a sistemes de comunicacions inalàmbriques s'ha incrementat de forma significativa. Aquests sistemes principalment són els sistemes de telefonia mòbil de tercera generació UMTS y el sistema de navegació GPS. Els filtres actuals, basats en ressonadors SAW (Surface Acoustic Wave), tenen unes dimensions reduïdes però estan limitats en freqüència (3 GHz) i la seva tecnologia no és compatible amb les tecnologies estàndards de circuits integrats. Per aquestes raons s'espera que els filtres basats en ressonadors BAW (Bulk Acoustic Wave) substitueixin als SAW. Els dos tenen dimensions similars, però els filtres BAW poden funcionar a freqüències superiors a 3 GHz, poden treballar amb nivells de potència majors, i és important destacar el fet que la seva tecnologia és compatible amb les tecnologies estàndards de circuits integrats. La investigació en l'àmbit dels filtres BAW s'ha centrat en millorar els processos tecnològics i la qualitat dels materials, però s'ha treballat poc en l'adaptació de les tècniques sistemàtiques de disseny de filtres a les particularitats d'aquesta tecnologia, per tant el principal objectiu d'aquest treball és presentar mètodes sistemàtics per al disseny de filtres BAW, centrant-se en l'estudi d’estructures apilades.

Peroxisome proliferator-activated receptor structures: ligand specificity, molecular switch and interactions with regulators.

Peroxisome proliferator-activated receptors (PPARs) compose a family of nuclear receptors that mediate the effects of lipidic ligands at the transcriptional level. In this review, we highlight advances in the understanding of the PPAR ligand binding domain (LBD) structure at the atomic level. The overall structure of PPARs LBD is described, and important protein ligand interactions are presented. Structure-activity relationships between isotypes structures and ligand specificity are addressed. It is shown that the numerous experimental three-dimensional structures available, together with in silico simulations, help understanding the role played by the activating function-2 (AF-2) in PPARs activation and its underlying molecular mechanism. The relation between the PPARs constitutive activity and the intrinsic stability of the active conformation is discussed. Finally, the interactions of PPARs LBD with co-activators or co-repressors, as well as with the retinoid X receptor (RXR) are described and considered in relation to PPARs activation.

El Sistema de financiación de las comunidades autónomas de régimen común: un análisis crítico y algunas propuestas de reforma

We identify a number of elements of the current Spanish system of regional financing that do not conform satisfactorily to the principles of equity, autonomy and efficiency that should inspire its design. Our main conclusion is that although the system presents a series of shortcomings that would require an in-depth reform, its basic focus on the equalization of the service provision capacity of all regional governments should be preserved because it is in accordance with the constitutional guarantee of equal rights for all citizens and with notions of horizontal equity that are widely shared in our country. In fact, the main shortcoming of the system is, in our opinion, that it does not fully guarantee such equality in practice. Additional weaknesses of the system are its lack of transparency, the absence of mechanisms to maintain vertical equilibrium across the different levels of the administration and a significant deficit of fiscal autonomy and responsibility on the pa

Molecular estimation of dispersal for ecology and population genetics

The dispersal process, by which individuals or other dispersing agents such as gametes or seeds move from birthplace to a new settlement locality, has important consequences for the dynamics of genes, individuals, and species. Many of the questions addressed by ecology and evolutionary biology require a good understanding of species' dispersal patterns. Much effort has thus been devoted to overcoming the difficulties associated with dispersal measurement. In this context, genetic tools have long been the focus of intensive research, providing a great variety of potential solutions to measuring dispersal. This methodological diversity is reviewed here to help (molecular) ecologists find their way toward dispersal inference and interpretation and to stimulate further developments.

Análisis textual y discursivo de dos relatos del posmodernismo mexicano en la segunda mitad del siglo XX: Nuevas fronteras del género a través de la experimentación intertextual y metaficcional.

La labor principal del presente trabajo de investigación consiste en el análisis de dos relatos del “posmodernismo mexicano” de la segunda mitad del siglo XX. Para ello, y en primer lugar, se parte de la acotación y definición de términos y nociones ligados a la “posmodernidad”, el “posmodernismo” y “lo posmoderno”. En segundo lugar, se lleva a cabo una lectura crítica de propuestas teóricas de autores como Fredric Jameson y Lauro Zavala, destinadas a describir fenómenos y prácticas relacionadas con la posmodernidad como forma discursiva y del relato posmoderno mexicano, respectivamente. En último término, se analizan los relatos mencionados bajo dos aspectos principales de experimentación: la intertextualidad y la metaficcionalidad y de los cuales se desprenden fenómenos privilegiados como “la hibridación genérica”, “el uso del pastiche”, “la superposición de códigos narrativos”, “la fragmentación del tiempo”, así como toda una serie de estrategias discursivas destinadas a expandir las fronteras del género relato en el contexto de enunciación mencionado.

Aplicación de técnicas de citogenética molecular para la detección de aneuploidía y clastogenicidad en células humanas expuestas a arsénico

Los objetivos de esta investigación son: a) Determinar la potencialidad genotóxica de diversos compuestos de arsénico (incluyendo inorgánicos y sus formas metiladas) con el ensayo de micronúcleos utilizando cultivos de células humanas; y b)Estudiar la posible acción aneugénica y clastogénica de los compuestos analizados, determinando el origen de los micronúcleos inducidos mediante la técnica FISH, utilizando sondas pancentroméricas.

Molecular variation at a candidate gene implicated in the regulation of fire ant social behavior

The fire ant Solenopsis invicta and its close relatives display an important social polymorphism involving differences in colony queen number. Colonies are headed by either a single reproductive queen (monogyne form) or multiple queens (polygyne form). This variation in social organization is associated with variation at the gene Gp-9, with monogyne colonies harboring only B-like allelic variants and polygyne colonies always containing b-like variants as well. We describe naturally occurring variation at Gp-9 in fire ants based on 185 full-length sequences, 136 of which were obtained from S. invicta collected over much of its native range. While there is little overall differentiation between most of the numerous alleles observed, a surprising amount is found in the coding regions of the gene, with such substitutions usually causing amino acid replacements. This elevated coding-region variation may result from a lack of negative selection acting to constrain amino acid replacements over much of the protein, different mutation rates or biases in coding and non-coding sequences, negative selection acting with greater strength on non-coding than coding regions, and/or positive selection acting on the protein. Formal selection analyses provide evidence that the latter force played an important role in the basal b-like lineages coincident with the emergence of polygyny. While our data set reveals considerable paraphyly and polyphyly of S. invicta sequences with respect to those of other fire ant species, the b-like alleles of the socially polymorphic species are monophyletic. An expanded analysis of colonies containing alleles of this clade confirmed the invariant link between their presence and expression of polygyny. Finally, our discovery of several unique alleles bearing various combinations of b-like and B-like codons allows us to conclude that no single b-like residue is completely predictive of polygyne behavior and, thus, potentially causally involved in its expression. Rather, all three typical b-like residues appear to be necessary.

Análisis de la calidad lingüística en los diarios españoles

Aquest treball analitza quines deficiències es poden detectar en el diaris generalistes espanyols, tant des del punt de vista lingüístic com organitzatiu, i com la interrelació entre aquestes carències influeix en detriment de la qualitat lingüística dels textos periodístics que es publiquen.

Cost-effectiveness of low-molecular-weight heparin for secondary prophylaxis of cancer-related venous thromboembolism.

Although extended secondary prophylaxis with low-molecular-weight heparin was recently shown to be more effective than warfarin for cancer-related venous thromboembolism, its cost-effectiveness compared to traditional prophylaxis with warfarin is uncertain. We built a decision analytic model to evaluate the clinical and economic outcomes of a 6-month course of low-molecular-weight heparin or warfarin therapy in 65-year-old patients with cancer-related venous thromboembolism. We used probability estimates and utilities reported in the literature and published cost data. Using a US societal perspective, we compared strategies based on quality-adjusted life-years (QALYs) and lifetime costs. The incremental cost-effectiveness ratio of low-molecular-weight heparin compared with warfarin was 149,865 dollars/QALY. Low-molecular-weight heparin yielded a quality-adjusted life expectancy of 1.097 QALYs at the cost of 15,329 dollars. Overall, 46% (7108 dollars) of the total costs associated with low-molecular-weight heparin were attributable to pharmacy costs. Although the low-molecular-weigh heparin strategy achieved a higher incremental quality-adjusted life expectancy than the warfarin strategy (difference of 0.051 QALYs), this clinical benefit was offset by a substantial cost increment of 7,609 dollars. Cost-effectiveness results were sensitive to variation of the early mortality risks associated with low-molecular-weight heparin and warfarin and the pharmacy costs for low-molecular-weight heparin. Based on the best available evidence, secondary prophylaxis with low-molecular-weight heparin is more effective than warfarin for cancer-related venous thromboembolism. However, because of the substantial pharmacy costs of extended low-molecular-weight heparin prophylaxis in the US, this treatment is relatively expensive compared with warfarin.

Despliegue y análisis de la cobertura de una red WiMAX basada en IEEE 802.16-2004

Aquest projecte tracta de l’estudi de la cobertura WiMAX basada en la variant 802.16-2004 en la que opera a 3.5 GHz en diferents escenaris d’un campus universitari. Primerament es realitza una introducció general a WiMAX i es defineixen els equips utilitzats. Posteriorment es comença a dur a terme un estudi de la cobertura WiMAX en diferents escenaris: indoor y outdoor per tal de poder extreure models empírics simplificats de path loss a partir de mesures realitzades amb els terminals WiMAX. Per últim, s’introdueix al projecte InterRural del Ministeri d'Indústria, Turisme i Comerç dut a terme durant els mesos Octubre 2007 - Març 2008 amb altres empreses col·laboradores: Telefònica, Hispasat, Gigle i Iber-X. La finalitat del projecte InterRural és comparar diferents tecnologies wireless de banda ample com alternatives per un bucle local ràdio de la última milla. En concret es comparen experimentalment les tecnologies WiMAX i WiFI 802.11a en diferents escenaris: LOS i NLOS.

Ant genomics sheds light on the molecular regulation of social organization.

Ants are powerful model systems for the study of cooperation and sociality. In this review, we discuss how recent advances in ant genomics have contributed to our understanding of the evolution and organization of insect societies at the molecular level.

Genomic, Epigenomic and Transcriptomic Molecular Characterization of Splenic Marginal Zone Lymphoma Reveals Recurrent Abnormalities in miR-182

Splenic marginal zone lymphoma (SMZL) is a low grade B-cell non-Hodgkin's lymphoma. The molecular pathology of this entity remains poorly understood. To characterise this lymphoma at the molecular level, we performed an integrated analysis of 1) genome wide genetic copy number alterations 2) gene expression profiles and 3) epigenetic DNA methylation profiles.We have previously shown that SMZL is characterised by recurrent alterations of chromosomes 7q, 6q, 3q, 9q and 18; however, gene resolution oligonucleotide array comparative genomic hybridisation did not reveal evidence of cryptic amplification or deletion in these regions. The most frequently lost 7q32 region contains a cluster of miRNAs. qRT-PCR revealed that three of these (miR-182/96/183) show underexpression in SMZL, and miR-182 is somatically mutated in >20% of cases of SMZL, as well as in >20% of cases of follicular lymphoma, and between 5-15% of cases of chronic lymphocytic leukaemia, MALT-lymphoma and hairy cell leukaemia. We conclude that miR-182 is a strong candidate novel tumour suppressor miRNA in lymphoma.The overall gene expression signature of SMZL was found to be strongly distinct fromthose of other lymphomas. Functional analysis of gene expression data revealed SMZL to be characterised by abnormalities in B-cell receptor signalling (especially through the CD19/21-PI3K/AKT pathway) and apoptotic pathways. In addition, genes involved in the response to viral infection appeared upregulated. SMZL shows a unique epigenetic profile, but analysis of differentially methylated genes showed few with methylation related transcriptional deregulation, suggesting that DNA methylation abnormalities are not a critical component of the SMZL malignant phenotype.