Involvement of Dab1 in APP processing and [beta]-amyloid deposition in sporadic Creutzfeldt-Jakob patients.

Alzheimer"s disease and prion pathologies (e.g., Creutzfeldt-Jakob disease) display profound neural lesions associated with aberrant protein processing and extracellular amyloid deposits. For APP processing, emerging data suggest that the adaptor protein Dab1 plays a relevant role in regulating its intracellular trafficking and secretase-mediated proteolysis. Although some data have been presented, a putative relationship between human prion diseases and Dab1/APP interactions is lacking. Therefore, we have studied the putative relation between Dab1, APP processing and Aβ deposition, targets in sCJD cases. Our biochemical results categorized two groups of sCJD cases, which also correlated with PrPsc types 1 and 2 respectively. One group, with PrPsc type 1 showed increased Dab1 phosphorylation, and lower βCTF production with an absence of Aβ deposition. The second sCJD group, which carried PrPsc type 2, showed lower levels of Dab1 phosphorylation and βCTF production, similar to control cases. Relevant Aβ deposition in the second sCJD group was measured. Thus, a direct correlation between Dab1 phosphorylation, Aβ deposition and PrPsc type in human sCJD is presented for the first time.

APP processing and b-amyloid deposition in sporadic Creutzfeldt-Jakob patients is dependent on Dab1.

Alzheimer"s disease and prion pathologies (e.g., Creutzfeldt-Jakob disease (CJD)) display profound neural lesions associated with aberrant protein processing and extracellular amyloid deposits. Dab1 has been implicated in the regulation of Amyloid Precursor Protein (APP), but a direct link between human prion diseases and Dab1/APP interactions has not been published. Here we examined this putative relationship in seventeen cases of sporadic CJD (sCJD) post mortem. Biochemical analyses of brain tissue revealed two groups, which also correlated with PrPsc types 1 and 2. One group, with PrPsc type 1 showed increased Dab1 phosphorylation, and lower CTF production with an absence of A deposition. The second sCJD group, which carried PrPsc type 2, showed lower levels of Dab1 phosphorylation and CTF production, and A deposition. Thus, the present observations suggest a correlation between Dab1-phosphorylation, A deposition and PrPsc type in sCJD.

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

Usabilitat dels gestors de contingutscom a espai per a la relació-comunicació professor alumne dins la web d'un centre de secundària

Aquest treball fa una incursió en els Gestors de Continguts del mercat especialitzats en entorns educatius i es divideix en dues parts: En la primera es fa una comparativa entre els gestors de continguts Moodle, Atutor i Aula Wiki a través de la seva Avaluació Heurística basada en els principis de Jakob Nielsen.En la segona part, a partir del gestor de continguts que ha obtingut millor puntuació en la Avaluació Heurística, es realitza un Test d'Usuaris amb professors d'ensenyament secundari de diverses Àrees.

Compositional Time Series: An Application

The composition of the labour force is an important economic factor for a country.Often the changes in proportions of different groups are of interest.I this paper we study a monthly compositional time series from the Swedish LabourForce Survey from 1994 to 2005. Three models are studied: the ILR-transformed series,the ILR-transformation of the compositional differenced series of order 1, and the ILRtransformationof the compositional differenced series of order 12. For each of thethree models a VAR-model is fitted based on the data 1994-2003. We predict the timeseries 15 steps ahead and calculate 95 % prediction regions. The predictions of thethree models are compared with actual values using MAD and MSE and the predictionregions are compared graphically in a ternary time series plot.We conclude that the first, and simplest, model possesses the best predictive power ofthe three models

Programa d'habilitats socials pels alumnes de l’Aula Oberta del Primer Cicle d’ESO: IES Vallvera

Treball que recull l'experiència de l’autora durant 4 mesos en l’IES Vallvera. Durant aquest temps ha pogut observar, aprendre i conèixer les tasques dels professionals de la psicopedagogia. L’IES Vallvera és un centre que acull molts alumnes immigrants, i per tant el tracte amb alumnes i l’assessorament d’aquests és el treball del dia a dia de la psicopedagoga del centre

Una pintura d'Antoni Viladomat i Manalt (1678-1755) a Manresa : l'Assumpta de Santa Maria de l'Alba

This painting with an exceptional iconography of the Assumption of the Virgin with All the Saints, was saved from a altarpiece in the church of Santa Maria de l'Alba in Manresa, which was burnt during the Spanish Civil War. The article attributes this painting to Antoni Viladomat i Manalt (1678-1755), one of the most relevant figures in the Catalan artistic scene in the 18th century, and it dates it to the latter years of his extensive artistic career. An analysis of the work shows that the Catalan painter incorporated some figurative elements that he borrowed from an engraving of the Swiss engraver, Jakob Frey (1681-1752), interpreted from a canvas of the Italian painter Sebastiano Conca (1680-1764). This helps to relate the canvas of the Barcelona painter-based on his previous figurative work with high Roman baroque- to the new proposals of the so-called Roman barrochetto. In addition the study hopes to offer the reader an artistically cultural view of Antoni Viladomat, openly concerned by the novelties that constantly reached Catalonia by means of the engravings

Centres diürns d'atenció a la gent gran: grau de satisfacció dels usuaris i familiars

Estudi descriptiu sobre els centres de dia i centres de serveis per a la gent gran, dos recursos que ofereixen atenció diürna, i sobre la satisfacció que comporta assistir a un o a l’altre. OBJECTIUS. Descriure i comparar dos models d’atenció diürna per a la gent gran, i els graus de satisfacció d’aquells que els utilitzen. MÈTODES. Estudi multicèntric descriptiu, de disseny és transversal. Portat a terme entre els mesos d’abril i juny de 2011, en set centres de serveis i un centre de dia, ha inclòs un total de 296 persones. S’ha fet una valoració del grau de satisfacció d’usuaris i familiars mitjançant una enquesta de disseny propi. RESULTATS. Els centres de dia, que es troben situats en zones urbanes, ofereixen un únic servei (servei d’estada), on el 41,94% de les persones tenen una elevada dependència. Els centres de serveis, que estan situats en zones rurals, ofereixen serveis d’estada, ambulatoris, tallers i atenció a domicili, i el 25,58% de les persones mostra una dependència elevada. El grau de satisfacció en els dos tipus de centres és elevada tant en famílies 87,63%, com en usuaris 96.5% . CONCLUSIÓ. Són dos models que tenen similituds, però ofereixen diferents tipus de serveis. Creats amb més de 15 anys de diferència, és possible que el centre de serveis acabi sent l’evolució natural del centre de dia.