| 1. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 6. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 7. |
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| 8. |
- Dujon, B, et al.
(författare)
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The nucleotide sequence of Saccharomyces cerevisiae chromosome XV
- 1997
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 387:6632, s. 98-102
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Tidskriftsartikel (refereegranskat)abstract
- Chromosome XV was one of the last two chromosomes of Saccharomyces cerevisiae to be discovered(1). It is the third-largest yeast chromosome after chromosomes XII and IV, and is very similar in size to chromosome VII. It alone represents 9% of the yeast genome (8% if ribosomal DNA is included). When systematic sequencing of chromosome XV was started, 93 genes or markers were identified, and most of them were mapped(2). However, very little else was known about chromosome XV which, in contrast to shorter chromosomes, had not been the object of comprehensive genetic or molecular analysis. It was therefore decided to start sequencing chromosome XV only in the third phase of the European Yeast Genome Sequencing Programme, after experience was gained on chromosomes III, XI and II (refs 3-5). The sequence of chromosome XV has been determined from a set of partly overlapping cosmid clones derived from a unique yeast strain, and physically mapped at 3.3-kilobase resolution before sequencing. As well as numerous new open reading frames (ORFs) and genes encoding tRNA or small RNA molecules, the sequence of 1,091,283 base pairs confirms the high proportion of orphan genes and reveals a number of ancestral and successive duplications with other yeast chromosomes.
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| 11. |
- Fissolo, N., et al.
(författare)
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Serum biomarker levels predict disability progression in patients with primary progressive multiple sclerosis
- 2024
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - 0022-3050. ; 95:5, s. 410-418
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWe aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS).MethodsA total of 141 patients with PPMS from 18 European MS centres were included. Disability progression was investigated using change in Expanded Disability Status Scale (EDSS) score over three time intervals: baseline to 2 years, 6 years and to the last follow-up. Serum levels of neurofilament light chain (sNfL), glial fibrillar acidic protein (sGFAP) and chitinase 3-like 1 (sCHI3L1) were measured using single-molecule array assays at baseline. Correlations between biomarker levels, and between biomarkers and age were quantified using Spearman's r. Univariable and multivariable linear models were performed to assess associations between biomarker levels and EDSS change over the different time periods.ResultsMedian (IQR) age of patients was 52.9 (46.4-58.5) years, and 58 (41.1%) were men. Median follow-up time was 9.1 (7.0-12.6) years. Only 8 (5.7%) patients received treatment during follow-up. sNfL and sGFAP levels were moderately correlated (r=0.43) and both weakly correlated with sCHI3L1 levels (r=0.19 and r=0.17, respectively). In multivariable analyses, levels of the three biomarkers were associated with EDSS changes across all time periods. However, when analysis was restricted to non-inflammatory patients according to clinical and radiological parameters (n=64), only sCHI3L1 levels remained associated with future EDSS change.ConclusionsLevels of sNfL, sGFAP and sCHI3L1 are prognostic biomarkers associated with disability progression in patients with PPMS, being CHI3L1 findings less dependent on the inflammatory component associated with disease progression.
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| 12. |
- Hernandez-Molina, F. J., et al.
(författare)
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Oceanographic processes and morphosedimentary products along the Iberian margins: A new multidisciplinary approach
- 2016
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Ingår i: Marine Geology. - : Elsevier BV. - 0025-3227. ; 378, s. 127-156
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Tidskriftsartikel (refereegranskat)abstract
- Our understanding of bottom-currents and associated oceanographic processes (e.g., overflows, barotropic tidal currents) including intermittent processes (e.g., vertical eddies, deep sea storms, horizontal vortices, internal waves and tsunamis) is rapidly evolving. Many deep-water processes remain poorly understood due to limited direct observations, but can generate significant depositional and erosional features on both short and long term time scales. This paper represents a review work, which describes for the first time these oceanographic processes and examines their potential role in the sedimentary features along the Iberian continental margins. This review explores the implications of the studied processes, given their secondary role relative to other factors such as mass-transport and turbiditic processes, and highlights three major results: a) contourite depositional and erosional features are ubiquitous along the margins, indicating that bottom currents and associated oceanographic processes control the physiography and sedimentation; b) the position of interfaces between major water masses and their vertical and spatial variation in time specifically appears to exert primary control in determining major morphologic changes along the slope gradient, including the contourite terraces development; and c) contourites deposits exhibit greater variation than the established fades model suggests. Therefore, a consistent facies model however faces substantial challenges in terms of the wide range of oceanographic processes that can influence in their development. An integrated interpretation of these oceanographic processes requires an understanding of contourites, seafloor features, their spatial and temporal evolution, and the near-bottom flows that form them. This approach will synthesize oceanographic data, seafloor morphology, sediments and seismic images to improve our knowledge of permanent and intermittent processes around Iberia, and evaluate their conceptual and regional role in the margin's sedimentary evolution. Given their complexes, three-dimensional and temporally-variable nature, integration of these processes into sedimentary, oceanographic and climatological frameworks will require a multidisciplinary approach that includes Geology, Physical oceanography, Paleoceanography and Benthic Biology.
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| 13. |
- Hernandez Molina, Javier, et al.
(författare)
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Oceanographic processes and products around the Iberian margin: a new multidisciplinary approach : Procesos oceanográficos y sus productos alrededor del margen de Iberia: una nueva aproximación multidisciplinar
- 2015
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Ingår i: Boletín Geológico y Minero. - 0366-0176 .- 0366-0176. ; 126:2-3, s. 279-326
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Tidskriftsartikel (refereegranskat)abstract
- Our understanding of the role of bottom-current and associated oceanographic processes (as overflows, barotropic currents, tides or intermittent processes like giant vertical eddies, deep sea storms, horizontal vortices, internal waves and tsunamis) is rapidly improving. But, most of these oceanographic deep-water processes remains poorly understood and have been rarely observed but believed to be capable of generating depositional and erosional features in many contexts at both short and long term. In present compilation we described these oceanographic processes including examples or their potential role in the sedimentation processes around the Iberia margin. Importance of these processes is highlighted and its implication discussed to demonstrate that these oceanographic processes are very important is affecting the shape and evolution of the Iberian continental margin and adjacent oceanic basins although is not still considered as important as other factors as mass-transport deposits and turbiditic processes. To have a better understanding on the implication of all these oceanographic processes connections have to be made between (contourite) sea-floor features, their spatial and temporal evolution, and the near-bottom flows that form them. The only way to achieve that in next decades is by a more intensive collaboration between specialist from Geology, Oceanography and Benthic Biology in new multi-disciplinary studies. Consequently, further multi-disciplinary approach uses oceanographic data, sea-floor morphology, sediments and seismic characterization will be essential for improve our knowledge of these permanent and intermittent processes around Iberia and evaluate their conceptual and regional role in the margins evolution over time and space.
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| 14. |
- Yannuzzi, M., et al.
(författare)
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TEFIS: A Single Access Point for Conducting Multifaceted Experiments on Heterogeneous Test Facilities
- 2014
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Ingår i: Computer Networks. - : Elsevier BV. - 1389-1286 .- 1872-7069. ; 63, s. 147-172
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Tidskriftsartikel (refereegranskat)abstract
- A few years ago, an experimental facility composed of networking gear and simulation tools was sufficient for testing the main features of a prototype before the final product could be launched to the Internet market. This paradigm has certainly changed, but the lack of platforms enabling the realistic assessment of the different facets of a product, including cross-cutting trials across different testbeds, poses strong limitations for researchers and developers. In light of this, we present an open platform that offers a versatile combination of heterogeneous experimental facilities called “TEstbed for Future Internet Services” (TEFIS). TEFIS provides a single access point for conducting cutting-edge experiments on testbeds that supply different capabilities, including testbeds dedicated to network performance, software performance, grid computing, and living labs. We shall show that TEFIS covers the entire life-cycle of a multifaceted experiment, with the advantage that a single testrun can seamlessly execute across different experimental facilities. In order to demonstrate the potential and versatility of the TEFIS platform, we describe the deployment of four distinct experiments and provide a set of results highlighting the benefits of using TEFIS. The experiments described in this article cover: i) the experimentation with an open API called OPENER (which is an open and programmable environment for managing experimentation with SDN applications); ii) an application for skiers and tourists at the Megève ski resort in France; iii) an application that can dynamically adapt the Quality of Experience (QoE) of multimedia services for mobile users; and iv) an augmented reality workspace for remote education and learning purposes based on videoconferencing.
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| 15. |
- Bolivar, Juan M, et al.
(författare)
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Coating of soluble and immobilized enzymes with ionic polymers : full stabilization of the quaternary structure of multimeric enzymes
- 2009
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 10:4, s. 742-747
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Tidskriftsartikel (refereegranskat)abstract
- This paper shows a simple and effective way to avoid the dissociation of multimeric enzymes by coating their surface with a large cationic polymer (e.g., polyethylenimine (PEI)) by ionic exchange. As model enzymes, glutamate dehydrogenase (GDH) from Thermus thermophilus and formate dehydrogenase (FDH) from Pseudomonas sp. were used. Both enzymes are very unstable at acidic pH values due to the rapid dissociation of their subunits (half-life of diluted preparations is few minutes at pH 4 and 25 degrees C). GDH and FDH were incubated in the presence of PEI yielding an enzyme-PEI composite with full activity. To stabilize the enzyme-polymer composite, a treatment with glutaraldehyde was required. These enzyme-PEI composites can be crosslinked with glutaraldehyde by immobilizing previously the composite onto a weak cationic exchanger. The soluble GDH-PEI composite was much more stable than unmodified GDH at pH 4 and 30 degrees C (retaining over 90% activity after 24 h incubation) with no effect of the GDH concentration in the inactivation course. The composite could be very strongly, but reversibly, adsorbed on cationic exchangers. Similarly, FDH could be treated with PEI and glutaraldehyde after adsorption on cationic exchangers, This permitted a stabilized FDH preparation. In this way, the coating of the enzymes surfaces with PEI is used as a simple and efficient strategy to prevent enzyme dissociation of multimeric enzymes. These composites can be used as a soluble catalyst or reversibly immobilized onto a cationic exchanger (e.g., CM-agarose).
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| 16. |
- Bolivar, Juan M, et al.
(författare)
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Immobilization-stabilization of a new recombinant glutamate dehydrogenase from Thermus thermophilus
- 2008
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Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 0175-7598 .- 1432-0614. ; 80:1, s. 49-58
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Tidskriftsartikel (refereegranskat)abstract
- The genome of Thermus thermophilus contains two genes encoding putative glutamate dehydrogenases. One of these genes (TTC1211) was cloned and overexpressed in Escherichia coli. The purified enzyme was a trimer that catalyzed the oxidation of glutamate to alpha-ketoglutarate and ammonia with either NAD+ or NADP+ as cofactors. The enzyme was also able to catalyze the inverse reductive reaction. The thermostability of the enzyme at neutral pH was very high even at 70 degrees C, but at acidic pH values, the dissociation of enzyme subunits produced the rapid enzyme inactivation even at 25 degrees C. The immobilization of the enzyme on glyoxyl agarose permitted to greatly increase the enzyme stability under all conditions studied. It was found that the multimeric structure of the enzyme was stabilized by the immobilization (enzyme subunits could be not desorbed from the support by boiling it in the presence of sodium dodecyl sulfate). This makes the enzyme very stable at pH 4 (e.g., the enzyme activity did not decrease after 12 h at 45 degrees C) and even improved the enzyme stability at neutral pH values. This immobilized enzyme can be of great interest as a biosensor or as a biocatalyst to regenerate both reduced and oxidized cofactors.
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| 17. |
- Hidalgo, Aurelio, et al.
(författare)
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Thermus thermophilus as a cell factory for the production of a thermophilic Mn-dependent catalase which fails to be synthesized in an active form in Escherichia coli
- 2004
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Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 70:7, s. 3839-3844
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Tidskriftsartikel (refereegranskat)abstract
- Thermostable Mn-dependent catalases are promising enzymes in biotechnological applications as H(2)O(2)-detoxifying systems. We cloned the genes encoding Mn-dependent catalases from Thermus thermophilus HB27 and HB8 and a less thermostable mutant carrying two amino acid replacements (M129V and E293G). When the wild-type and mutant genes were overexpressed in Escherichia coli, unmodified or six-His-tagged proteins of the expected size were overproduced as inactive proteins. Several attempts to obtain active forms or to activate the overproduced proteins were unsuccessful, even when soluble and thermostable proteins were used. Therefore, a requirement for a Thermus-specific activation factor was suggested. To overcome this problem, the Mn-dependent catalase genes were overexpressed directly in T. thermophilus under the control of the Pnar promoter. This promoter belongs to a respiratory nitrate reductase from of T. thermophilus HB8, whose transcription is activated by the combined action of nitrate and anoxia. Upon induction in T. thermophilus HB8, a 20- to 30-fold increase in catalase specific activity was observed, whereas a 90- to 110-fold increase was detected when the laboratory strain T. thermophilus HB27::nar was used as the host. The thermostability of the overproduced wild-type catalase was identical to that previously reported for the native enzyme, whereas decreased stability was detected for the mutant derivative. Therefore, our results validate the use of T. thermophilus as an alternative cell factory for the overproduction of thermophilic proteins that fail to be expressed in well-known mesophilic hosts.
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| 18. |
- Mathiesen, T, et al.
(författare)
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Takanori Fukushima 1942 - 2024
- 2024
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Ingår i: Acta neurochirurgica. - 0942-0940. ; 166:1, s. 186-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 19. |
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