Pequeño comercio y vitalidad urbana en Zaragoza. La ciudad contra la anti-ciudad

Saragossa és una ciutat densa i compacta. Els fluxos de vianants són molt intensos. El sistema d'autobusos és eficient i econòmic. El petit comerciant és la peça clau per entendre la dinàmica de la ciutat: fan el carrer segur, la ciutat més humana, el passeig més bonic i ecològic ja que els saragossans/nes no han d'utilitzar el cotxe. Tot això contrasta amb l'anticiutat dispersa, on dominen les grans superfícies comercials que fomenten el transport en automòbil i converteixen el carrer en un lloc sense vida, insegur i hostil. Però en el futur, Saragossa ha d'enfrontar-se al dilema

Epigenetic Research of Neurodegenerative Disorders Using Patient iPSC-Based Models

Epigenetic mechanisms play a role in human disease but their involvement in pathologies from the central nervous system has been hampered by the complexity of the brain together with its unique cellular architecture and diversity. Until recently, disease targeted neural types were only available as postmortem materials after many years of disease evolution. Current in vitro systems of induced pluripotent stem cells (iPSCs) generated by cell reprogramming of somatic cells from patients have provided valuable disease models recapitulating key pathological molecular events. Yet whether cell reprogramming on itself implies a truly epigenetic reprogramming, the epigenetic mechanisms governing this process are only partially understood. Moreover, elucidating epigenetic regulation using patient-specific iPSC-derived neural models is expected to have a great impact to unravel the pathophysiology of neurodegenerative diseases and to hopefully expand future therapeutic possibilities. Here we will critically review current knowledge of epigenetic involvement in neurodegenerative disorders focusing on the potential of iPSCs as a promising tool for epigenetic research of these diseases

Weak Reproductive Solutions for a Convection-Diffusion Model Describing a Binary Alloy Solidification Processes

We study the existence of reproductive weak solutions for a system of equations describing a solidification process of a binary alloy confined into a bounded and regular domain in $\mathbb{R}^3$, having mixed boundary conditions

Programa psicoeducativo para familiares de pacientes con trastorno bipolar

El Trastorno Bipolar es una enfermedad crónica, deteriorante y estigmatizante, en la cual pueden presentarse episodios maníacos, hipomaníacos, depresivos y mixtos. Afecta gravemente a los enfermos y a sus familiares. La atención a la familia cada vez se tiene más en cuenta debido a sus beneficios en el tratamiento a largo plazo y en la reinserción del paciente en la sociedad. Objetivos: Realizar una revisión sobre la atención por parte de los profesionales de enfermería a los familiares de pacientes con Trastorno Bipolar y diseñar un programa de educación para la salud dirigido a estas familias. Metodología: Se realizó una revisión bibliográfica sobre el Trastorno Bipolar y cómo influye la enfermedad en las relaciones familiares de estos pacientes. A continuación se diseñó un programa de educación para la salud enfocado a familiares de pacientes con Trastorno Bipolar. Conclusiones: Actualmente, no existen planes de actuación que posibiliten a los profesionales de enfermería desarrollar competencias de psicoeducación, formación y apoyo. Se debería incentivar el trabajo con las familias desde las Unidades de Corta Estancia debido a los beneficios que reporta

Le rôle du merveilleux dans les lais de Marie de France.

Marie de France a écrit à la fin du XIIème siècle douze lais en octosyllabes où elle mettait l’accent sur les effets de l’amour courtois et où le monde merveilleux, qui est notre objet d'étude, perce avec clarté. La lecture de ces lais révèle une interaction directe des éléments merveilleux avec l'amour. Le merveilleux peut favoriser l'amour, mais il peut aussi le détruire. Pour cette raison, ce travail est divisé en deux parties, selon l'interaction de ces éléments. Nous verrons comment à travers son utilisation, l'auteure a cherché quelque chose au-delà de l'introduction de faits fantastiques : nous essaierons d'établir les limites de l'usage du merveilleux, comment ils apparaissent, comment ils interagissent avec l’entourage, quel est sa fonction et nous justifierons son utilisation à travers certains extraits qui accompagneront notre explication pour tirer des conclusions qui nous montreront l’importance du merveilleux pour introduire certains thèmes qui à l’époque étaient mal vus. <br /

Parkin loss of function contributes to RTP801 elevation and neurodegeneration in Parkinson"s disease

Mutations in the PARK2 gene are associated with an autosomal recessive form of juvenile parkinsonism (AR-JP). These mutations affect parkin solubility and impair its E3 ligase activity, leading to a toxic accumulation of proteins within susceptible neurons that results in a slow but progressive neuronal degeneration and cell death. Here, we report that RTP801/REDD1, a pro-apoptotic negative regulator of survival kinases mTOR and Akt, is one of such parkin substrates. We observed that parkin knockdown elevated RTP801 in sympathetic neurons and neuronal PC12 cells, whereas ectopic parkin enhanced RTP801 poly-ubiquitination and proteasomal degradation. In parkin knockout mouse brains and in human fibroblasts from AR-JP patients with parkin mutations, RTP801 levels were elevated. Moreover, in human postmortem PD brains with mutated parkin, nigral neurons were highly positive for RTP801. Further consistent with the idea that RTP801 is a substrate for parkin, the two endogenous proteins interacted in reciprocal co-immunoprecipitates of cell lysates. A potential physiological role for parkin-mediated RTP801 degradation is indicated by observations that parkin protects neuronal cells from death caused by RTP801 overexpression by mediating its degradation, whereas parkin knockdown exacerbates such death. Similarly, parkin knockdown enhanced RTP801 induction in neuronal cells exposed to the Parkinson's disease mimetic 6-hydroxydopamine and increased sensitivity to this toxin. This response to parkin loss of function appeared to be mediated by RTP801 as it was abolished by RTP801 knockdown. Taken together these results indicate that RTP801 is a novel parkin substrate that may contribute to neurodegeneration caused by loss of parkin expression or activity

Brain and Cerebrospinal Fluid α-Synuclein Real-Time Quaking-Induced Conversion Identifies Lewy Body Pathology in LRRK2-PD

ABSTRACTBackground&lt;jats:p/&gt;The neuropathology of Parkinson's disease (PD) associated with leucine‐rich repeat kinase 2 (LRRK2) mutations (LRRK2‐PD) is heterogeneous and varies with the type of mutation. There are only a few studies evaluating seeding aggregation assays to detect α‐synuclein (α‐syn) in patients with LRRK2‐PD.Objective&lt;jats:p/&gt;We aimed to investigate whether α‐syn real‐time quaking induced conversion (RT‐QuIC) is a sensitive biomarker of synucleinopathy in LRRK2‐PD.Methods&lt;jats:p/&gt;We studied α‐syn RT‐QuIC in brain tissue and postmortem ventricular cerebrospinal fluid (CSF) of LRRK2‐PD cases with and without Lewy‐type pathology.Results&lt;jats:p/&gt;The accuracy of α‐syn RT‐QuIC in substantia nigra and CSF samples of patients with LRRK2‐PD was 100%. The test also obtained 100% sensitivity to detect misfolded α‐syn in substantia nigra of cases with idiopathic PD and was negative in the substantia nigra of all the control brains without Lewy‐type pathology.Conclusions&lt;jats:p/&gt;Substantia nigra and ventricular CSF RT‐QuIC discriminates with high sensitivity and specificity LRRK2 cases with Lewy‐type pathology from those without it. RT‐QuIC assay could be of particular interest in the selection of cases for clinical trials in this genetic form of PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Ubiquitin-negative mini-pick like bodies in the dentate gyrus of p30l tauopathy.

Neuropathological and biochemical findings are reported in a patient who had suffered from frontotemporal dementia associated with a P310L mutation in the tau gene and included in the H1 haplotype. Tau accumulation, as revealed with phospho-specific anti-tau antibodies Thr181, Ser199, Ser202, Ser214, Ser262, Ser396, Ser422 and AT8 (Ser202 and Thr205), was found in neurons with pre-tangles, and astrocytes and oligodendrocytes through the brain. The most characteristic feature was tau immunoreactivity decorating the perinuclear region and small cytoplasmic aggregates designed as mini-Pick-like bodies, mainly in the dentate gyrus. Inclusions were not stained with anti-ubiquitin antibodies and did not recruit tubulins. Tau accumulation in individual cells was associated with increased expression of kinases linked with tau phosphorylation, mainly active (phosphorylated) stress kinases SAPK/JNK and p38 (SAPK/JNK-P and p38-P). Phosphorylated GSK-3 beta at Ser9 (GSK-3 beta-P), that inactivates the kinase, was particularly abundant in mini-Pick-like bodies, thus suggesting alternative roles of GSK-3 probably involved in cell survival. Western blots of sarkosyl-insoluble fractions revealed a double band pattern of phospho-tau of 68/66 kDa and 64 kDa in the hippocampus and white matter in the P310L mutation. Sarkosyl-insoluble fractions of the hippocampus were enriched in p38-P and GSK-3 beta-P in Alzheimer's disease (AD) cases, processed in parallel for comparative purposes, but not in the P310L mutation. In addition, no bands of high molecular weight were found in P310L in contrast with AD in these fractions. These findings indicate that the major sites of tau phosphorylation, and the expression of kinases involved in tau phosphorylation are active in P310L mutation as in AD and other tauopathies. Yet the P310L mutation has particular phospho-tau inclusions that are not tag with ubiquitin and appear to be rather soluble when compared with AD