University of Lisbon

About: University of Lisbon is a education organization based out in Lisbon, Lisboa, Portugal. It is known for research contribution in the topics: Population & European union. The organization has 19122 authors who have published 48503 publications receiving 1102623 citations. The organization is also known as: Universidade de Lisboa & Lisbon University.

The spinal muscular atrophy disease gene product, SMN: A link between snRNP biogenesis and the Cajal (coiled) body.

Abstract: The spliceosomal snRNAs U1, U2, U4, and U5 are synthesized in the nucleus, exported to the cytoplasm to assemble with Sm proteins, and reimported to the nucleus as ribonucleoprotein particles. Recently, two novel proteins involved in biogenesis of small nuclear ribonucleoproteins (snRNPs) were identified, the Spinal muscular atrophy disease gene product (SMN) and its associated protein SIP1. It was previously reported that in HeLa cells, SMN and SIP1 form discrete foci located next to Cajal (coiled) bodies, the so-called “gemini of coiled bodies” or “gems.” An intriguing feature of gems is that they do not appear to contain snRNPs. Here we show that gems are present in a variable but small proportion of rapidly proliferating cells in culture. In the vast majority of cultured cells and in all primary neurons analyzed, SMN and SIP1 colocalize precisely with snRNPs in the Cajal body. The presence of SMN and SIP1 in Cajal bodies is confirmed by immunoelectron microscopy and by microinjection of antibodies that interfere with the integrity of the structure. The association of SMN with snRNPs and coilin persists during cell division, but at the end of mitosis there is a lag period between assembly of new Cajal bodies in the nucleus and detection of SMN in these structures, suggesting that SMN is targeted to preformed Cajal bodies. Finally, treatment of cells with leptomycin B (a drug that blocks export of U snRNAs to the cytoplasm and consequently import of new snRNPs into the nucleus) is shown to deplete snRNPs (but not SMN or SIP1) from the Cajal body. This suggests that snRNPs flow through the Cajal body during their biogenesis pathway.

Extracellular Alpha-Synuclein Oligomers Modulate Synaptic Transmission and Impair LTP Via NMDA-Receptor Activation

Abstract: Parkinson's disease (PD) is the most common representative of a group of disorders known as synucleinopathies, in which misfolding and aggregation of α-synuclein (a-syn) in various brain regions is the major pathological hallmark. Indeed, the motor symptoms in PD are caused by a heterogeneous degeneration of brain neurons not only in substantia nigra pars compacta but also in other extrastriatal areas of the brain. In addition to the well known motor dysfunction in PD patients, cognitive deficits and memory impairment are also an important part of the disorder, probably due to disruption of synaptic transmission and plasticity in extrastriatal areas, including the hippocampus. Here, we investigated the impact of a-syn aggregation on AMPA and NMDA receptor-mediated rat hippocampal (CA3-CA1) synaptic transmission and long-term potentiation (LTP), the neurophysiological basis for learning and memory. Our data show that prolonged exposure to a-syn oligomers, but not monomers or fibrils, increases basal synaptic transmission through NMDA receptor activation, triggering enhanced contribution of calcium-permeable AMPA receptors. Slices treated with a-syn oligomers were unable to respond with further potentiation to theta-burst stimulation, leading to impaired LTP. Prior delivery of a low-frequency train reinstated the ability to express LTP, implying that exposure to a-syn oligomers drives the increase of glutamatergic synaptic transmission, preventing further potentiation by physiological stimuli. Our novel findings provide mechanistic insight on how a-syn oligomers may trigger neuronal dysfunction and toxicity in PD and other synucleinopathies.

Atmospheric River Tracking Method Intercomparison Project(ARTMIP): Project Goals and Experimental Design

Abstract: . The Atmospheric River Tracking Method Intercomparison Project (ARTMIP) is an international collaborative effort to understand and quantify the uncertainties in atmospheric river (AR) science based on detection algorithm alone. Currently, there are many AR identification and tracking algorithms in the literature with a wide range of techniques and conclusions. ARTMIP strives to provide the community with information on different methodologies and provide guidance on the most appropriate algorithm for a given science question or region of interest. All ARTMIP participants will implement their detection algorithms on a specified common dataset for a defined period of time. The project is divided into two phases: Tier 1 will utilize the Modern-Era Retrospective analysis for Research and Applications, version 2 (MERRA-2) reanalysis from January 1980 to June 2017 and will be used as a baseline for all subsequent comparisons. Participation in Tier 1 is required. Tier 2 will be optional and include sensitivity studies designed around specific science questions, such as reanalysis uncertainty and climate change. High-resolution reanalysis and/or model output will be used wherever possible. Proposed metrics include AR frequency, duration, intensity, and precipitation attributable to ARs. Here, we present the ARTMIP experimental design, timeline, project requirements, and a brief description of the variety of methodologies in the current literature. We also present results from our 1-month “proof-of-concept” trial run designed to illustrate the utility and feasibility of the ARTMIP project.