University of Coimbra

About: University of Coimbra is a education organization based out in Coimbra, Portugal. It is known for research contribution in the topics: Population & Context (language use). The organization has 14318 authors who have published 43067 publications receiving 994733 citations. The organization is also known as: UC & Universidade dos Estudos Gerais.

DYT16, a novel young-onset dystonia-parkinsonism disorder: identification of a segregating mutation in the stress-response protein PRKRA

Abstract: Summary Background Dystonia and parkinsonism may present as part of the same genetic disorder. Identification of the genetic mutations that underlie these diseases may help to shed light on the aetiological processes involved. Methods We identified two unrelated families with members with an apparent autosomal recessive, novel, young-onset, generalised form of dystonia parkinsonism. We did autozygosity mapping and candidate gene sequencing in these families. Findings High-density genome-wide SNP genotyping revealed a disease-segregating region containing 277 homozygous markers identical by state across all affected members from both families. This novel disease locus, designated DYT16 , covers 1·2 Mb at chromosome 2q31.2. The crucial interval contains 11 genes or predicted transcripts. Sequence analysis of every exon of all of these transcripts revealed a single disease-segregating mutation, c.665C>T (P222L), in the stress-response gene PRKRA , which encodes the protein kinase, interferon-inducible double-stranded RNA-dependent activator. Interpretation We describe a mutation within the gene PRKRA that segregates with a novel, autosomal recessive, dystonia parkinsonism syndrome. These patients have progressive, generalised, early-onset dystonia with axial muscle involvement, oromandibular (sardonic smile), laryngeal dystonia and, in some cases, parkinsonian features, and do not respond to levodopa therapy.

Tumor infiltrating immune cells in gliomas and meningiomas

Abstract: Tumor-infiltrating immune cells are part of a complex microenvironment that promotes and/or regulates tumor development and growth. Depending on the type of cells and their functional interactions, immune cells may play a key role in suppressing the tumor or in providing support for tumor growth, with relevant effects on patient behavior. In recent years, important advances have been achieved in the characterization of immune cell infiltrates in central nervous system (CNS) tumors, but their role in tumorigenesis and patient behavior still remain poorly understood. Overall, these studies have shown significant but variable levels of infiltration of CNS tumors by macrophage/microglial cells (TAM) and to a less extent also lymphocytes (particularly T-cells and NK cells, and less frequently also B-cells). Of note, TAM infiltrate gliomas at moderate numbers where they frequently show an immune suppressive phenotype and functional behavior; in contrast, infiltration by TAM may be very pronounced in meningiomas, particularly in cases that carry isolated monosomy 22, where the immune infiltrates also contain greater numbers of cytotoxic T and NK-cells associated with an enhanced anti-tumoral immune response. In line with this, the presence of regulatory T cells, is usually limited to a small fraction of all meningiomas, while frequently found in gliomas. Despite these differences between gliomas and meningiomas, both tumors show heterogeneous levels of infiltration by immune cells with variable functionality. In this review we summarize current knowledge about tumor-infiltrating immune cells in the two most common types of CNS tumors-gliomas and meningiomas-, as well as the role that such immune cells may play in the tumor microenvironment in controlling and/or promoting tumor development, growth and control.

Future Mobility Survey

Abstract: The Future Mobility Survey (FMS) is a smartphone-based prompted-recall travel survey that aims to support data collection initiatives for transport-modeling purposes. This paper details the considerations that have gone into the survey's development, including the smartphone apps for iPhone and Android platforms, the online activity diary and user interface, and the background intelligence for processing collected data into activity locations and travel traces. The various trade-offs concerning user comprehension, resource use, and participant burden, including findings from usability tests and a pilot study, are discussed. Close attention should be paid to the simplicity of the user interaction, determinations of activity locations (such as the false positive and false negative trade-off in their automatic classification), and the clarity of interactions in the activity diary. The FMS system design and implementation provide pragmatic, useful insights into the development of similar platforms and approac...

ATP as a multi-target danger signal in the brain.

Abstract: ATP is released in an activity-dependent manner from different cell types in the brain, fulfilling different roles as a neurotransmitter, neuromodulator, astrocyte-to-neuron communication, propagating astrocytic responses and formatting microglia responses This involves the activation of different ATP P2 receptors (P2R) as well as adenosine receptors upon extracellular ATP catabolism by ecto-nucleotidases Notably, brain noxious stimuli trigger a sustained increase of extracellular ATP, which plays a key role as danger signal in the brain This involves a combined action of extracellular ATP in different cell types, namely increasing the susceptibility of neurons to damage, promoting astrogliosis and recruiting and formatting microglia to mount neuroinflammatory responses Such actions involve the activation of different receptors, as heralded by neuroprotective effects resulting from blockade mainly of P2X7R, P2Y1R and adenosine A2A receptors (A2AR), which hierarchy, cooperation and/or redundancy is still not resolved These pleiotropic functions of ATP as a danger signal in brain damage prompt a therapeutic interest to multi-target different purinergic receptors to provide maximal opportunities for neuroprotection

Climatic significance of tree-ring width and intra-annual density fluctuations in Pinus pinea from a dry Mediterranean area in Portugal

Abstract: In Mediterranean climates trees may go through two periods of dormancy, resulting in special anatomical features such as false rings and other intra-annual density fluctuations (IADFs). In this paper, ring growth and the presence of IADFs were studied in Pinus pinea L. growing in the coastal and inland regions of Alentejo (southern Portugal). In order to identify the triggering factors associated with the IADFs, a new classification was proposed for the IADFs in P. pinea: Type E (latewoodlike cells within earlywood); Type E+ (transition cells between earlywood and latewood); Type L (earlywoodlike cells within latewood) and Type L+ (earlywoodlike cells between latewood and earlywood of the next tree ring). Response function analyses showed that radial growth of P. pinea was strongly correlated with precipitation in southern Portugal. The climatic response of P. pinea was higher in the inland area where the summer drought is more severe, the winter temperatures are lower and the soils have low water-holding capacity, in comparison with the coastal area. IADFs were frequent in P. pinea and most of the IADFs were observed in latewood. The presence of IADFs was correlated with fluctuations in climate parameters during the growing season. The IADF type E+ was linked to precipitation events early in summer. The IADF type L and L+ were associated with above-average precipitation in early autumn.