Evidence for fungal infection in cerebrospinal fluid and brain tissue from patients with amyotrophic lateral sclerosis

Among neurogenerative diseases, amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by a progressive motor neuron dysfunction in the motor cortex, brainstem and spinal cord. ALS is the most common form of motor neuron disease; yet, to date, the exact etiology of ALS remains unknown. In the present work, we have explored the possibility of fungal infection in cerebrospinal fluid (CSF) and in brain tissue from ALS patients. Fungal antigens, as well as DNA from several fungi, were detected in CSF from ALS patients. Additionally, examination of brain sections from the frontal cortex of ALS patients revealed the existence of immunopositive fungal antigens comprising punctate bodies in the cytoplasm of some neurons. Fungal DNA was also detected in brain tissue using PCR analysis, uncovering the presence of several fungal species. Finally, proteomic analyses of brain tissue demonstrated the occurrence of several fungal peptides. Collectively, our observations provide compelling evidence of fungal infection in the ALS patients analyzed, suggesting that this infection may play a part in the etiology of the disease or may constitute a risk factor for these patientsThe financial support of Fundación ONCE (Organización Nacional de Ciegos Españoles) is acknowledged. We acknowledge an institutional grant to Centro de Biología Molecular “Severo Ochoa” from the Fundación Ramón Arece

Revisión bioestratigráfica de las pizarras del Ordovícico Medio en el noroeste de España (zonas Cantábrica, Asturoccidental-leonesa y Centroibérica septentrional)

A complete review of more than one hundred Middle Ordovician fossil localities, distributed within the north western part of the Hesperian Massif, shows that the sedimentation of the dark shales (Luarca Fo rmation and equivalents) that overlie Arenig quartzites with Cruziana (the 'Armorican Quartzite' facies) was not as uniform as it has been supposed for the whole NW Spain. These shales were mainly deposited during the Oretanian in the West Asturian-Leonese Zone and in nort h e rn Central-Iberian Zone (Domain of the Ollo de Sapo Antiform). In these zones, the top of the unit is close to the Oretanian/Dobrotivian boundary, without any fossils with proved Dobrotivian age. In the Cantabrian Zone, clay sedimentation started in the latest Oretanian and continued during the Dobrotivian. Several local or regional stratigraphic gaps are proposed and characterized for the whole study area. In addition, the most recent paleog e ographical reconstructions proposed are discussed, in accordance with new paleoecological and paleobiog e ographical data. These data indicate that sedimentation took place in open shelf areas, relative ly deeper than in the southern Central Iberian shelf, and with trough areas where some mesopelagic elements are recorded. We identified a total of 97 different fossil taxa (67 from Oretanian rocks and 45 from Dobrotivian rocks), remarkable among which are the first known appearance of certain trilobites and ostracodes, the latest record of other taxa, and also the presence of some taxa in common with Avalonia and Baltica, that were previously unknown from any area of SW Europe

Ordovician and Silurian geological heritage of the Arouca region (Portugal)

4 páginas, 3 figuras.-- Trabajo presentado en la 44ª Sesión Científica, Jaén, 2008.The studied region is situated in the Aveiro district, about 50 km SW of Oporto (northern Portugal) and has a rich geological, biological and cultural heritage. The Arouca Geopark was formally established there in late 2007, under the auspices of Arouca’s Municipal Chamber, to reunite 36 geosites from which some of them involve remarkable Ordovician and Silurian rocks and fossils. Outcrops of both periods belong to the Valongo- Tamames syncline of the Central Iberian Zone. Lower Palaeozoic rocks around the Canelas Slate Quarry are of special interest, leading to the creation of a geotouristic route visiting three Ordovician units (Santa Justa quartzites, Valongo shales and Sobrido quartzite plus glaciomarine diamictites) and one Silurian (graptolitic black shales), as well as a Roman gold mine dug in the Lower Ordovician quartzites. However, the most outstanding geosite is the quarry itself, where Middle Ordovician giant trilobites (up to 70 cm in size) and trilobite clusters (up to thousands of specimens) occur in large slabs of slate and are recovered during the exploitation. The Geological Interpretation Centre of Canelas, located near the quarry and open since 2006, is one of the main tourist attractions of the Arouca Geopark, created to preserve and disseminate knowledge about trilobites and the Ordovician world, and having received more than 10,000 visitors in its first 17 months.La empresa Ardósias Valério & Figueiredo Lda., por su apoyo continuado al trabajo paleontológico en la cantera de Canelas. A la Câmara Municipal de Arouca, por su sensibilidad en la gestión del patrimonio geológico y la financiación (a D.R.) para su inventario. Este trabajo es una contribución a los proyectos CGL2006-07628/BTE y PTDC/CTE-GEX/64966/2006, financiados por el Ministerio de Educación y Ciencia español y la Fundación de Ciencia y Tecnología de Portugal, respectivamente.Peer reviewe

A Sox2–Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells

Increased cancer stem cell content during development of resistance to tamoxifen in breast cancer is driven by multiple signals, including Sox2-dependent activation of Wnt signalling. Here, we show that Sox2 increases and estrogen reduces the expression of the transcription factor Sox9. Gain and loss of function assays indicate that Sox9 is implicated in the maintenance of human breast luminal progenitor cells. CRISPR/Cas knockout of Sox9 reduces growth of tamoxifen-resistant breast tumours in vivo. Mechanistically, Sox9 acts downstream of Sox2 to control luminal progenitor cell content and is required for expression of the cancer stem cell marker ALDH1A3 and Wnt signalling activity. Sox9 is elevated in breast cancer patients after endocrine therapy failure. This new regulatory axis highlights the relevance of SOX family transcription factors as potential therapeutic targets in breast cancer

Las sucesiones estratigráficas del Paleozoico inferior y medio

13 páginas, 20 páginas.-- Editor: García Cortés, Angel.-- Capítulo 2.Peer reviewe

Estimation of time dedication to a pathophysiology practice

Resúmenes IV Congreso VetDoc de Docencia Veterinaria, León 2017 (6-7 de Julio)[ES] El objetivo de este trabajo fue comprobar si la carga lectiva real de la práctica “estudio de caso” correspondiente a la parte de fisiopatología se correlacionaba adecuadamente con la establecida en el plan docente

Cannabinoid receptor CB2 ablation protects against TAU induced neurodegeneration.

Tauopathies are a group of neurodegenerative diseases characterized by the alteration/aggregation of TAU protein, for which there is still no effective treatment. Therefore, new pharmacological targets are being sought, such as elements of the endocannabinoid system (ECS). We analysed the occurrence of changes in the ECS in tauopathies and their implication in the pathogenesis. By integrating gene expression analysis, immunofluorescence, genetic and adeno-associated virus expressing TAU mouse models, we found a TAU-dependent increase in CB2 receptor expression in hippocampal neurons, that occurs as an early event in the pathology and was maintained until late stages. These changes were accompanied by alterations in the endocannabinoid metabolism. Remarkably, CB2 ablation in mice protects from neurodegeneration induced by hTAU P301L overexpression, corroborated at the level of cognitive behaviour, synaptic plasticity, and aggregates of insoluble TAU. At the level of neuroinflammation, the absence of CB2 did not produce significant changes in concordance with a possible neuronal location rather than its classic glial expression in these models. These findings were corroborated in post-mortem samples of patients with Alzheimer’s disease, the most common tauopathy. Our results show that neurons with accumulated TAU induce the expression of the CB2 receptor, which enhances neurodegeneration. These results are important for our understanding of disease mechanisms, providing a novel therapeutic strategy to be investigated in tauopathiespost-print8580 K