¿Hi ha diferències emocionals entre els TGD?

Aquest treball final de grau s'ha plantejat amb el principal objectiu de realitzar una recerca bibliogràfica, el més actualitzada possible, on es recullin les característiques fonamentals dels trastorns generalitzats del desenvolupament (avaluació, diagnòstic, tractament, etc.).

Comparative analysis of amino acid repeats in rodents and humans

Amino acid tandem repeats, also called homopolymeric tracts, are extremely abundant in eukaryotic proteins. To gain insight into the genome-wide evolution of these regions in mammals, we analyzed the repeat content in a large data set of rat-mouse-human orthologs. Our results show that human proteins contain more amino acid repeats than rodent proteins and that trinucleotide repeats are also more abundant in human coding sequences. Using the human species as an outgroup, we were able to address differences in repeat loss and repeat gain in the rat and mouse lineages. In this data set, mouse proteins contain substantially more repeats than rat proteins, which can be at least partly attributed to a higher repeat loss in the rat lineage. The data are consistent with a role for trinucleotide slippage in the generation of novel amino acid repeats. We confirm the previously observed functional bias of proteins with repeats, with overrepresentation of transcription factors and DNA-binding proteins. We show that genes encoding amino acid repeats tend to have an unusually high GC content, and that differences in coding GC content among orthologs are directly related to the presence/absence of repeats. We propose that the different GC content isochore structure in rodents and humans may result in an increased amino acid repeat prevalence in the human lineage.

Evolutionary analysis of genetic variants involved in rare diseases

Next-generation sequencing techniques such as exome sequencing can successfully detect all genetic variants in a human exome and it has been useful together with the implementation of variant filters to identify causing-disease mutations. Two filters aremainly used for the mutations identification: low allele frequency and the computational annotation of the genetic variant. Bioinformatic tools to predict the effect of a givenvariant may have errors due to the existing bias in databases and sometimes show a limited coincidence among them. Advances in functional and comparative genomics are needed in order to properly annotate these variants.The goal of this study is to: first, functionally annotate Common Variable Immunodeficiency disease (CVID) variants with the available bioinformatic methods in order to assess the reliability of these strategies. Sencondly, as the development of new methods to reduce the number of candidate genetic variants is an active and necessary field of research, we are exploring the utility of gene function information at organism level as a filter for rare disease genes identification. Recently, it has been proposed that only 10-15% of human genes are essential and therefore we would expect that severe rare diseases are mostly caused by mutations on them. Our goal is to determine whether or not these rare and severe diseases are caused by deleterious mutations in these essential genes. If this hypothesis were true, taking into account essential genes as a filter would be an interesting parameter to identify causingdisease mutations.

Propuesta de programa de prevención de trastornos de la conducta alimentaria y la obesidad dirigido a profesores de educación física de secundaria

En la actual concepción bio-psico-social, los Trastornos del Comportamiento Alimentario (TCA) y la obesidad están plurideterminados por factores biológicos, psicológicos y socioculturales que actúan como elementos perpetuantes en el tiempo. Se pueden modificar actitudes contraproducentes con un programa de prevención multidisciplinar y disminuir de modo significativo la población con riesgo de obesidad y de padecer un TCA. Para ello, es necesario desarrollar dichos programas de prevención, previos a la atención primaria, y la estrategia para lograrlo es la intervención ante factores de riesgo, integrada en un conjunto de actividades de educación para la salud más global. Esta propuesta educativa pretende brindar a los profesores de Educación Física una revisión bibliográfica sobre la dimensión que desde la cultura occidental se tiene de los Trastornos del Comportamiento Alimentario (TCA) y la obesidad, al tiempo que promueve la reflexión sobre las posibilidades de intervención que ofrece la Educación Física desde el ámbito educativo en cuanto a la prevención de la obesidad, de los TCA, y de las conductas de riesgo. La presente propuesta de proyecto de prevención quiere destacar la función que cumplen docentes, tutores y tutoras, como acompañantes de los estudiantes, su posición privilegiada para conocerlos de cerca y estar así atentos a sus vivencias y la posibilidad de identificar oportunamente conductas no saludables en estudiantes que necesiten ciertas pautas para mejorar su estilo de vida, modificar sus habitos, o ser derivados para una atención especializada. Por ese motivo, en esta propuesta educativa se invita a los docentes y tutores a revisar sus convicciones personales y cuestionar la manera de pensar sobre la belleza física y el cuidado corporal. Esta reflexión junto a las pautas metodológicas permitirá abordar el tema de los TCA y la obesidad con tacto, respeto y la atención necesaria frente a los sentimientos de los y las estudiantes que se encuentran en un periodo de cambios importantes y con interrogantes en torno a su identidad e imagen corporal

L'occità i el català comparats a partir de l'oralitat cinematogràfica

El present treball consisteix en una descripció de les característiques d'una varietat gascona parlada a la vall de Varossa, situada al sud est de Gascunya. Aquest estudi s'ha realitzat a partir d'un documental etnogràfic gravat en aquesta zona. En primer lloc, s'introdueix el document estudiat i la zona on s'emmarca. Tot seguit, s'exposen els comentaris lingüístics, que han estat dividits en cinc apartats: trets generals del document, aspectes de fonètica i fonologia, morfologia, sintaxi i lèxic amb referències específiques al contacte de llengües. També s'ha inclòs un apartat de qüestions relatives al contacte de llengües i a la interferència. Aquest tipus d'estudi, que cal remarcar que no és exhaustiu, pot servir d'introducció a un altre de més ampli, i explora un mètode d'investigació original amb força possibilitats.

Convenient synthesis of C75, an inhibitor of FAS and CPT1

C75 is a synthetic racemic α-methylene-γ-butyrolactone exhibiting anti-tumoral properties in vitro and in vivo as well as inducing hypophagia and weight loss in rodents. These interesting properties are thought to be a consequence of the inhibition of the key enzymes FAS and CPT1 involved in lipid metabolism. The need for larger amounts of this compound for biological evaluation prompted us to develop a convenient and reliable route to multigram quantities of C75 from easily available ethyl penta-3,4-dienoate 6. A recently described protocol for the addition of 6 to a mixture of dicyclohexylborane and nonanal followed by acidic treatment of the crude afforded lactone 8, as a mixture of cis and trans isomers, in good yield. The DBU-catalyzed isomerization of the methyl esters 9 arising from 8 gave a 10:1 trans/cis mixture from which the trans isomer was isolated and easily transformed into C75. The temporary transformation of C75 into a phenylseleno ether derivative makes its purification, manipulation and storage easier.

Convenient synthesis of C75, an inhibitor of FAS and CPT1

C75 is a synthetic racemic α-methylene-γ-butyrolactone exhibiting anti-tumoral properties in vitro and in vivo as well as inducing hypophagia and weight loss in rodents. These interesting properties are thought to be a consequence of the inhibition of the key enzymes FAS and CPT1 involved in lipid metabolism. The need for larger amounts of this compound for biological evaluation prompted us to develop a convenient and reliable route to multigram quantities of C75 from easily available ethyl penta-3,4-dienoate 6. A recently described protocol for the addition of 6 to a mixture of dicyclohexylborane and nonanal followed by acidic treatment of the crude afforded lactone 8, as a mixture of cis and trans isomers, in good yield. The DBU-catalyzed isomerization of the methyl esters 9 arising from 8 gave a 10:1 trans/cis mixture from which the trans isomer was isolated and easily transformed into C75. The temporary transformation of C75 into a phenylseleno ether derivative makes its purification, manipulation and storage easier.

The problem of nitrogen disposal in the obese

Amino-N is preserved because of the scarcity and nutritional importance of protein. Excretion requires its conversion to ammonia, later incorporated into urea. Under conditions of excess dietary energy, the body cannot easily dispose of the excess amino-N against the evolutively adapted schemes that prevent its wastage; thus ammonia and glutamine formation (and urea excretion) are decreased. High lipid (and energy) availability limits the utilisation of glucose, and high glucose spares the production of ammonium from amino acids, limiting the synthesis of glutamine and its utilisation by the intestine and kidney. The amino acid composition of the diet affects the production of ammonium depending on its composition and the individual amino acid catabolic pathways. Surplus amino acids enhance protein synthesis and growth, and the synthesis of non-protein-N-containing compounds. But these outlets are not enough; consequently, less-conventional mechanisms are activated, such as increased synthesis of NO∙ followed by higher nitrite (and nitrate) excretion and changes in the microbiota. There is also a significant production of N(2) gas, through unknown mechanisms. Health consequences of amino-N surplus are difficult to fathom because of the sparse data available, but it can be speculated that the effects may be negative, largely because the fundamental N homeostasis is stretched out of normalcy, forcing the N removal through pathways unprepared for that task. The unreliable results of hyperproteic diets, and part of the dysregulation found in the metabolic syndrome may be an unwanted consequence of this N disposal conflict.

Logopèdia i educació

Aquest article té per objectiu descriure com, des de la practica logopèdica i a partir d'una determinada manera d'entendre l'adquisició del llenguatge, s'orienta un model de treball inclusiu per abordar les dificultats del llenguatge en el context escolar. Es revisa breument el marc teòric i els principis de la intervenció naturalista i els nous reptes que aquest enfocament planteja pel que fa a l'avaluació i a la intervenció en contextos naturals i vinculats amb el currículum.

Estudi d’adaptació de clons de pollancre (Populus sp.) mitjançant models mitxes en la vall intermèdia de l’Ebre

Durant la dècada dels 80 la DGA (Diputación General de Aragon), va engegar una xarxa d’assaigs experimentals. La major part d’aquests assaigs es troben a la vall de l’Ebre. Padró el 1992 publica les dades de creixement i aporta informació sobre el comportament clonal de cada assaig. Malgrat tot, la enorme desestructura dels assaigs dificultà, en el seu moment, l’anàlisi simultani de les dades. En el treball es proposa un reanàlisi de les dades de la xarxa de la DGA basat en l’ús de models mitxes, amb l’objecte d’interpretar patrons adaptatius i amb especial interès en la descripció de la interacció genotip-ambient. S’utilitzen el models de estabilitat de Shukla, regressions de Finlay-Wilkinson y Eberhart-Russell, AMMI a on el factor ambient és aleatori i el genotip fixe.

Preparation of alpha-labeled aldehydes by base-catalyzed exchange reactions

A simple, efficient protocol for the preparation of α-labeled aldehydes based on H/D exchange catalyzed by 4-(N,N-dimethylamino)pyridine or Et3N is described. High chemical yields and ratios of isotope incorporation were obtained even when small amounts (1 mmol) of aldehyde were used.

Preparation of alpha-labeled aldehydes by base-catalyzed exchange reactions

A simple, efficient protocol for the preparation of α-labeled aldehydes based on H/D exchange catalyzed by 4-(N,N-dimethylamino)pyridine or Et3N is described. High chemical yields and ratios of isotope incorporation were obtained even when small amounts (1 mmol) of aldehyde were used.

Coexistence of protease sensitive and resistant prion protein in 129VV homozygous sporadic Creutzfeldt-Jakob disease: a case report

Introduction: The coexistence of different molecular types of classical protease-resistant prion protein in the same individual have been described, however, the simultaneous finding of these with the recently described protease-sensitive variant or variably protease-sensitive prionopathy has, to the best of our knowledge, not yet been reported. Case presentation: A 74-year-old Caucasian woman showed a sporadic Creutzfeldt-Jakob disease clinical phenotype with reactive depression, followed by cognitive impairment, akinetic-rigid Parkinsonism with pseudobulbar syndrome and gait impairment with motor apraxia, visuospatial disorientation, and evident frontal dysfunction features such as grasping, palmomental reflex and brisk perioral reflexes. She died at age 77. Neuropathological findings showed: spongiform change in the patient"s cerebral cortex, striatum, thalamus and molecular layer of the cerebellum with proteinase K-sensitive synaptic-like, dot-like or target-like prion protein deposition in the cortex, thalamus and striatum; proteinase K-resistant prion protein in the same regions; and elongated plaque-like proteinase K-resistant prion protein in the molecular layer of the cerebellum. Molecular analysis of prion protein after proteinase K digestion revealed decreased signal intensity in immunoblot, a ladder-like protein pattern, and a 71% reduction of PrPSc signal relative to non-digested material. Her cerebellum showed a 2A prion protein type largely resistant to proteinase K. Genotype of polymorphism at codon 129 was valine homozygous. Conclusion: Molecular typing of prion protein along with clinical and neuropathological data revealed, to the best of our knowledge, the first case of the coexistence of different protease-sensitive prion proteins in the same patient in a rare case that did not fulfill the current clinical diagnostic criteria for either probable or possible sporadic Creutzfeldt-Jakob disease. This highlights the importance of molecular analyses of several brain regions in order to correctly diagnose rare and atypical prionopathies

A common BACE1 polymorphism is a risk factor for sporadic Creutzfeldt-Jakob disease

The β site APP cleaving enzyme 1 (BACE1) is the rate-limiting β-secretase enzyme in the amyloidogenic processing of APP and Aβ formation, and therefore it has a prominent role in Alzheimer"s disease (AD) pathology. Recent evidence suggests that the prion protein (PrP) interacts directly with BACE1 regulating its β-secretase activity. Moreover, PrP has been proposed as the cellular receptor involved in the impairment of synaptic plasticity and toxicity caused by Aβ oligomers. Provided that common pathophysiologic mechanisms are shared by Alzheimer"s and Creutzfeldt-Jakob (CJD) diseases, we investigated for the first time to the best of our knowledge a possible association of a common synonymous BACE1 polymorphism (rs638405) with sporadic CJD (sCJD). Our results indicate that BACE1 C-allele is associated with an increased risk for developing sCJD, mainly in PRNP M129M homozygous subjects with early onset. These results extend the very short list of genes (other than PRNP) involved in the development of human prion diseases; and support the notion that similar to AD, in sCJD several loci may contribute with modest overall effects to disease risk. These findings underscore the interplay in both pathologies of APP, Aβ oligomers, ApoE, PrP and BACE1, and suggest that aging and perhaps vascular risk factors may modulate disease pathologies in part through these key players

Liver Glucokinase A456V induces potent hypoglycemia without dyslipidemia through a paradoxical induction of the catalytic subunit of glucose-6-phosphatase

Recent reports point out the importance of the complex GK-GKRP in controlling glucose and lipid homeostasis. Several GK mutations affect GKRP binding, resulting in permanent activation of the enzyme. We hypothesize that hepatic overexpression of a mutated form of GK, GKA456V, described in a patient with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) and could provide a model to study the consequences of GK-GKRP deregulation in vivo. GKA456V was overexpressed in the liver of streptozotocin diabetic mice. Metabolite profiling in serum and liver extracts, together with changes in key components of glucose and lipid homeostasis, were analyzed and compared to GK wild-type transfected livers. Cell compartmentalization of the mutant but not the wild-type GK was clearly affected in vivo, demonstrating impaired GKRP regulation. GKA456V overexpression markedly reduced blood glucose in the absence of dyslipidemia, in contrast to wild-type GK-overexpressing mice. Evidence in glucose utilization did not correlate with increased glycogen nor lactate levels in the liver. PEPCK mRNA was not affected, whereas the mRNA for the catalytic subunit of glucose-6-phosphatase was upregulated ~4 folds in the liver of GKA456V-treated animals, suggesting that glucose cycling was stimulated. Our results provide new insights into the complex GK regulatory network and validate liver-specific GK activation as a strategy for diabetes therapy.