El gran juego: la guerra secreta por el control de Asia Central (1836-1919)

Durant el segle XIX i les primeres dècades del XX, Àsia Central va patir de primera mà la rivalitat entre les dues grans potències europees del moment: Anglaterra i Rússia. Aquest enfrontament va ser batejat pels seus propis participants amb el nom d'El Gran Joc. A diferència d'altres lluites històriques prèvies, el Gran Joc no es va resumir en una guerra, sinó en un cúmul d'elles, que es van succeir al llarg del temps en diferents territoris del centre del continent asiàtic i a les que van acompanyar accions diplomàtiques igualment nombroses. Tot i l'extensió del conflicte, Afganistan es va erigir com el punt clau més rellevant al voltant del qual l'Imperi rus i el britànic van desenvolupar les seves intrigues. Els dos poders europeus, amb els seus respectius objectius en ment, no van dubtar a dur a terme un dels majors desplegaments estratègics mai vist a la zona, valent-se, a més dels seus efectius, dels habitants asiàtics com peons al tauler del seu joc i marcant profundament el futur de les nacions centreasiàtiques, així com establint un precedent en la manera de fer la guerra on la victòria d'una facció sobre una altra mai estaria clara.

Mejoras de funcionalidades en la gestión de usuariosde la plataforma K-PAX

Esta memoria trata de las mejoras propuestas en la plataforma educativa kPax de la UOC referentes a la gestión de usuarios.

WhereIs

Trabajo final de carrera sobre el desarrollo de una aplicación para móviles, específicamente para el sistema operativo Android, llamada WhereIs. Se trata de una aplicación que almacena ubicaciones de lugares interesantes, mostrándolos en un mapa por cercanía y puntuación de otros usuarios de la aplicación.

An olfactory receptor for food-derived odours promotes male courtship in Drosophila.

Many animals attract mating partners through the release of volatile sex pheromones, which can convey information on the species, gender and receptivity of the sender to induce innate courtship and mating behaviours by the receiver. Male Drosophila melanogaster fruitflies display stereotyped reproductive behaviours towards females, and these behaviours are controlled by the neural circuitry expressing male-specific isoforms of the transcription factor Fruitless (FRU(M)). However, the volatile pheromone ligands, receptors and olfactory sensory neurons (OSNs) that promote male courtship have not been identified in this important model organism. Here we describe a novel courtship function of Ionotropic receptor 84a (IR84a), which is a member of the chemosensory ionotropic glutamate receptor family, in a previously uncharacterized population of FRU(M)-positive OSNs. IR84a-expressing neurons are activated not by fly-derived chemicals but by the aromatic odours phenylacetic acid and phenylacetaldehyde, which are widely found in fruit and other plant tissues that serve as food sources and oviposition sites for drosophilid flies. Mutation of Ir84a abolishes both odour-evoked and spontaneous electrophysiological activity in these neurons and markedly reduces male courtship behaviour. Conversely, male courtship is increased--in an IR84a-dependent manner--in the presence of phenylacetic acid but not in the presence of another fruit odour that does not activate IR84a. Interneurons downstream of IR84a-expressing OSNs innervate a pheromone-processing centre in the brain. Whereas IR84a orthologues and phenylacetic-acid-responsive neurons are present in diverse drosophilid species, IR84a is absent from insects that rely on long-range sex pheromones. Our results suggest a model in which IR84a couples food presence to the activation of the fru(M) courtship circuitry in fruitflies. These findings reveal an unusual but effective evolutionary solution to coordinate feeding and oviposition site selection with reproductive behaviours through a specific sensory pathway.

Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders

Eating disorders (EDs) are complex psychiatric diseases that include anorexia nervosa and bulimia nervosa, and have higher than 50% heritability. Previous studies have found association of BDNF and NTRK2 to ED, while animal models suggest that other neurotrophin genes might also be involved in eating behavior. We have performed a family-based association study with 151 TagSNPs covering 10 neurotrophin signaling genes: NGFB, BDNF, NTRK1, NGFR/p75, NTF4/5, NTRK2, NTF3, NTRK3, CNTF and CNTFR in 371 ED trios of Spanish, French and German origin. Besides several nominal associations, we found a strong significant association after correcting for multiple testing (P = 1.04 × 10−4) between ED and rs7180942, located in the NTRK3 gene, which followed an overdominant model of inheritance. Interestingly, HapMap unrelated individuals carrying the rs7180942 risk genotypes for ED showed higher levels of expression of NTRK3 in lymphoblastoid cell lines. Furthermore, higher expression of the orthologous murine Ntrk3 gene was also detected in the hypothalamus of the anx/anx mouse model of anorexia. Finally, variants in NGFB gene appear to modify the risk conferred by the NTRK3 rs7180942 risk genotypes (P = 4.0 × 10−5) showing a synergistic epistatic interaction. The reported data, in addition to the previous reported findings for BDNF and NTRK2, point neurotrophin signaling genes as key regulators of eating behavior and their altered cross-regulation as susceptibility factors for EDs.

Blood levels of brain-derived neurotrophic factor correlate with several psychopathological symptoms in anorexia nervosa patients

Background: Evidence of a role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of eating disorders (ED) has been provided by association studies and by murine models. BDNF plasma levels have been found altered in ED and in psychiatric disorders that show comorbidity with ED. Aims: Since the role of BDNF levels in ED-related psychopathological symptoms has not been tested, we investigatedthe correlation of BDNF plasma levels with the Symptom Checklist 90 Revised (SCL-90R) questionnaire in a total of 78 ED patients. Methods: BDNF levels, measured bythe enzyme-linked immunoassay system, and SCL-90R questionnaire, were assessed in a total of 78 ED patients. The relationship between BDNF levels and SCL-90R scales was calculated using a general linear model. Results: BDNF plasma levels correlated with the Global Severity Index and the Positive Symptom Distress Index global scales and five of the nine subscales in the anorexia nervosa patients. BDNF plasma levels were able to explain, in the case of the Psychoticism subscale, up to 17% of the variability (p = 0.006). Conclusion: Our data suggest that BDNF levels could be involved in the severity of the disease through the modulation of psychopathological traits that are associated with the ED phenotype.

Altered brain-derived neurotrophic factor blood levels and gene variability are associated with anorexia and bulimia

Murine models and association studies in eating disorder (ED) patients have shown a role for the brain-derived neurotrophic factor (BDNF) in eating behavior. Some studies have shown association of BDNF -270C/T single-nucleotide polymorphism (SNP) with bulimia nervosa (BN), while BDNF Val66Met variant has been shown to be associated with both BN and anorexia nervosa (AN). To further test the role of this neurotrophin in humans, we screened 36 SNPs in the BDNF gene and tested for their association with ED and plasma BDNF levels as a quantitative trait. We performed a family-based association study in 106 ED nuclear families and analyzed BDNF blood levels in 110 ED patients and in 50 sib pairs discordant for ED. The rs7124442T/rs11030102C/rs11030119G haplotype was found associated with high BDNF levels (mean BDNF TCG haplotype carriers = 43.6 ng/ml vs. mean others 23.0 ng/ml, P = 0.016) and BN (Z = 2.64; P recessive = 0.008), and the rs7934165A/270T haplotype was associated with AN (Z =-2.64; P additive = 0.008). The comparison of BDNF levels in 50 ED discordant sib pairs showed elevated plasma BDNF levels for the ED group (mean controls = 41.0 vs. mean ED = 52.7; P = 0.004). Our data strongly suggest that altered BDNF levels modulated by BDNF gene variability are associated with the susceptibility to ED, providing physiological evidence that BDNF plays a role in the development of AN and BN, and strongly arguing for its involvement in eating behavior and body weight regulation.

Allele variants in functional MicroRNA target sites of the neurotrophin-3 receptor gene (NTRK3) as susceptibility factors for anxiety disorders

Genetic and functional data indicate that variation in the expression of the neurotrophin-3 receptor gene (NTRK3) may have an impact on neuronal plasticity, suggesting a role for NTRK3 in the pathophysiology of anxiety disorders. MicroRNA (miRNA) posttranscriptional gene regulators act by base-pairing to specific sequence sites, usually at the 3'UTR of the target mRNA. Variants at these sites might result in gene expression changes contributing to disease susceptibility. We investigated genetic variation in two different isoforms of NTRK3 as candidate susceptibility factors for anxiety by resequencing their 3'UTRs in patients with panic disorder (PD), obsessive-compulsive disorder (OCD), and in controls. We have found the C allele of rs28521337, located in a functional target site for miR-485-3p in the truncated isoform of NTRK3, to be significantly associated with the hoarding phenotype of OCD. We have also identified two new rare variants in the 3'UTR of NTRK3, ss102661458 and ss102661460, each present only in one chromosome of a patient with PD. The ss102661458 variant is located in a functional target site for miR-765, and the ss102661460 in functional target sites for two miRNAs, miR-509 and miR-128, the latter being a brain-enriched miRNA involved in neuronal differentiation and synaptic processing. Interestingly, these two variants significantly alter the miRNA-mediated regulation of NTRK3, resulting in recovery of gene expression. These data implicate miRNAs as key posttranscriptional regulators of NTRK3 and provide a framework for allele-specific miRNA regulation of NTRK3 in anxiety disorders.

Predicting cancer involvement of genes from heterogeneous data

Background: Systematic approaches for identifying proteins involved in different types of cancer are needed. Experimental techniques such as microarrays are being used to characterize cancer, but validating their results can be a laborious task. Computational approaches are used to prioritize between genes putatively involved in cancer, usually based on further analyzing experimental data. Results: We implemented a systematic method using the PIANA software that predicts cancer involvement of genes by integrating heterogeneous datasets. Specifically, we produced lists of genes likely to be involved in cancer by relying on: (i) protein-protein interactions; (ii) differential expression data; and (iii) structural and functional properties of cancer genes. The integrative approach that combines multiple sources of data obtained positive predictive values ranging from 23% (on a list of 811 genes) to 73% (on a list of 22 genes), outperforming the use of any of the data sources alone. We analyze a list of 20 cancer gene predictions, finding that most of them have been recently linked to cancer in literature. Conclusion: Our approach to identifying and prioritizing candidate cancer genes can be used to produce lists of genes likely to be involved in cancer. Our results suggest that differential expression studies yielding high numbers of candidate cancer genes can be filtered using protein interaction networks.

Characterization of myocardial deformation in patients with different etiologies of left ventricular hypertrophy by using strain distribution from Magnetic Resonance Imaging

Introducción y objetivos. Se ha señalado que, en la miocardiopatía hipertrófica (MCH), la desorganización de las fibras regionales da lugar a segmentos en los que la deformación es nula o está gravemente reducida, y que estos segmentos tienen una distribución no uniforme en el ventrículo izquierdo (VI). Esto contrasta con lo observado en otros tipos de hipertrofia como en el corazón de atleta o la hipertrofia ventricular izquierda hipertensiva (HVI-HT), en los que puede haber una deformación cardiaca anormal, pero nunca tan reducida como para que se observe ausencia de deformación. Así pues, proponemos el empleo de la distribución de los valores de strain para estudiar la deformación en la MCH. Métodos. Con el empleo de resonancia magnética marcada (tagged), reconstruimos la deformación sistólica del VI de 12 sujetos de control, 10 atletas, 12 pacientes con MCH y 10 pacientes con HVI-HT. La deformación se cuantificó con un algoritmo de registro no rígido y determinando los valores de strain sistólico máximo radial y circunferencial en 16 segmentos del VI. Resultados. Los pacientes con MCH presentaron unos valores medios de strain significativamente inferiores a los de los demás grupos. Sin embargo, aunque la deformación observada en los individuos sanos y en los pacientes con HVI-HT se concentraba alrededor del valor medio, en la MCH coexistían segmentos con contracción normal y segmentos con una deformación nula o significativamente reducida, con lo que se producía una mayor heterogeneidad de los valores de strain. Se observaron también algunos segmentos sin deformación incluso en ausencia de fibrosis o hipertrofia. Conclusiones. La distribución de strain caracteriza los patrones específicos de deformación miocárdica en pacientes con diferentes etiologías de la HVI. Los pacientes con MCH presentaron un valor medio de strain significativamente inferior, así como una mayor heterogeneidad de strain (en comparación con los controles, los atletas y los pacientes con HVI-HT), y tenían regiones sin deformación.

El patró “no dipper” i la rigidesa arterial, poden estar relacionats amb les lesions glomerulars incipients dels pacients amb obesitat mòrbida?

La monitorització ambulatòria de la pressió arterial (MAPA) és la millor tècnica pel diagnòstic d’hipertensió arterial i es relaciona millor amb l’afectació d’òrgans diana respecte la pressió arterial clínica. Recentment, s’ha descrit un indicador de rigidesa arterial que s’ estima a partir de la MAPA, l’ Ambulatory Arterial Stiffnes Index (AASI). En aquest treball es valora si els pacients amb obesitat mòrbida presenten rigidesa arterial mesurada a través de la MAPA i s’identifiquen factors de risc associats amb la lesió glomerular i vascular.

Biana: a software framework for compiling biological interactions and analyzing networks

Background: The analysis and usage of biological data is hindered by the spread of information across multiple repositories and the difficulties posed by different nomenclature systems and storage formats. In particular, there is an important need for data unification in the study and use of protein-protein interactions. Without good integration strategies, it is difficult to analyze the whole set of available data and its properties.Results: We introduce BIANA (Biologic Interactions and Network Analysis), a tool for biological information integration and network management. BIANA is a Python framework designed to achieve two major goals: i) the integration of multiple sources of biological information, including biological entities and their relationships, and ii) the management of biological information as a network where entities are nodes and relationships are edges. Moreover, BIANA uses properties of proteins and genes to infer latent biomolecular relationships by transferring edges to entities sharing similar properties. BIANA is also provided as a plugin for Cytoscape, which allows users to visualize and interactively manage the data. A web interface to BIANA providing basic functionalities is also available. The software can be downloaded under GNU GPL license from http://sbi.imim.es/web/BIANA.php.Conclusions: BIANA's approach to data unification solves many of the nomenclature issues common to systems dealing with biological data. BIANA can easily be extended to handle new specific data repositories and new specific data types. The unification protocol allows BIANA to be a flexible tool suitable for different user requirements: non-expert users can use a suggested unification protocol while expert users can define their own specific unification rules.

Pre-play communication and credibility: A test of Aumann's conjecture

The effectiveness of pre-play communication in achieving efficientoutcomes has long been a subject of controversy. In some environments,cheap talk may help to achieve coordination. However, Aumannconjectures that, in a variant of the Stag Hunt game, a signal forefficient play is not self-enforcing and concludes that an "agreementto play [the efficient outcome] conveys no information about what theplayers will do." Harsanyi and Selten (1988) cite this example as anillustration of risk-dominance vs. payoff-dominance. Farrell and Rabin(1996) agree with the logic, but suspect that cheap talk willnonetheless achieve efficiency. The conjecture is tested with one-waycommunication. When the sender first chooses a signal and then anaction, there is impressive coordination: a 94% probability for thepotentially efficient (but risky) play, given a signal for efficientplay. Without communication, efforts to achieve efficiency wereunsuccessful, as the proportion of B moves is only 35%. I also test ahypothesis that the order of the action and the signal affects theresults, finding that the decision order is indeed important. WhileAumann s conjecture is behaviorally disconfirmed when the signal isdetermined initially, the signal s credibility seems to be much moresuspect when the sender is known to have first chosen an action, andthe results are not statistically distinguishable from those whenthere is no signal. Some applications and issues in communication andcoordination are discussed.