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1.
  • Ahmed, Saheeb, et al. (författare)
  • Mover is a homomeric phospho-protein present on synaptic vesicles
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:5, s. e63474-
  • Tidskriftsartikel (refereegranskat)abstract
    • With remarkably few exceptions, the molecules mediating synaptic vesicle exocytosis at active zones are structurally and functionally conserved between vertebrates and invertebrates. Mover was found in a yeast-2-hybrid assay using the vertebrate-specific active zone scaffolding protein bassoon as a bait. Peptides of Mover have been reported in proteomics screens for self-interacting proteins, phosphorylated proteins, and synaptic vesicle proteins, respectively. Here, we tested the predictions arising from these screens. Using flotation assays, carbonate stripping of peripheral membrane proteins, mass spectrometry, immunogold labelling of purified synaptic vesicles, and immuno-organelle isolation, we found that Mover is indeed a peripheral synaptic vesicle membrane protein. In addition, by generating an antibody against phosphorylated Mover and Western blot analysis of fractionated rat brain, we found that Mover is a bona fide phospho-protein. The localization of Mover to synaptic vesicles is phosphorylation dependent; treatment with a phosphatase caused Mover to dissociate from synaptic vesicles. A yeast-2-hybrid screen, co-immunoprecipitation and cell-based optical assays of homomerization revealed that Mover undergoes homophilic interaction, and regions within both the N- and C- terminus of the protein are required for this interaction. Deleting a region required for homomeric interaction abolished presynaptic targeting of recombinant Mover in cultured neurons. Together, these data prove that Mover is associated with synaptic vesicles, and implicate phosphorylation and multimerization in targeting of Mover to synaptic vesicles and presynaptic sites.
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2.
  • Boix, Virginia (författare)
  • Graphene: Applications in Surface Science Studies
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis addresses how graphene can be a valuable asset for surface science studies. Using a combination of X- ray photoelectron spectroscopy, scanning tunneling microscopy, and low-energy electron diffraction, we take advantage of graphene’s sensitivity to changes in its chemical environment to obtain an atomic scale understanding of different reactions occurring above and below the film.As a substrate, graphene provides an inert base for studying growth mechanisms. Specifically, we use it to investigate the electron-induced dissociation of borazine, a common precursor for Boron Nitride deposition. Thanks to the inert character of graphene, we can discern the dissociation due to the interaction with the electron beam from any surface- induced dissociation processes. Moreover, graphene can be used as an adsorption template for studying reactions between adsorbates and gas phase molecules. Using hydrogen adsorbates, we analyze the stability of different H- structures under mbar pressures of oxygen. We show that graphene acts as a catalyst for water formation by providing the required adsorption configuration that promotes the reaction. This finding paves the way for future research using graphene as an adsorption template for fundamental catalysis studies.Graphene can also be employed as a confining agent to study undercover reactions, a trending topic in the catalysis field due to the reported higher performance of catalysts when placed in confined environments. We use graphene to investigate copper oxidation undercover, revealing that its presence stabilizes a Cu2O phase undercover, delaying the evolution toward complete oxidation (CuO). Graphene is also an ideal model system for studying more fundamental aspects of undercover reactions, such as the coexistence of different molecules undercover or their intercalation kinetics. Specifically, we use graphene to investigate the coexistence of hydrogen and CO with already intercalated oxygen while following the intercalation process in situ with APXPS.Altogether this thesis provides several examples of how graphene can be integrated into surface science studies and paves the way for its implementation in the surface science field.
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3.
  • Eastmond, Marita, 1947 (författare)
  • Between dream and disaster: Asylum-seeking children and transitions to 'home'
  • 2009
  • Ingår i: Presented at Nordic Imer Symposium, Stockholm 27-28 November.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The paper addresses the imaginings of ‘home’ and return of children and their parents in asylum-seeking families, in view of the two (legal) options open them: Either permanent residence in Swedem or return to the country of origin. The hope that many children, as well as their parents, nurture of being able to remain in Sweden, not least given the vast material investments already made, reinforces the dream of Sweden as ‘home’. The deeply felt hope of remaining expressed by some children also seemed to guide their behaviour: Striving to be ‘good’ and successful at school, learning the language, and supporting their parents in assisting the family to make a favourable impression on the authorities, they hoped to influence the asylum decision. Sweden as the hoped-for home is contrasted with the children’s perceptions and negative memories of the ‘home’ left behind. The violence some of the children had suffered before fleeing turned the idea of being deported there into an imagined scenario of disaster. A few of those children responded with attacks of despair, anxiety and sleeplessness as the family received their first rejection on their asylum application. Children’s struggles to ensure a ‘safe place’ – to be good at school, learn the language, support their parents, etc must be compared to the relatively little weight they carry in the asylum determination process. The analysis is based less on sedentarist notions of ‘home’ as a particular place (or a nation-state), or even a given set of social relations, but is seen in more dynamic terms. The strivings of asylum-seeking children in this study resemble the “search for ‘cool ground’” of Mursi refugees in Allen and Turton’s study (1996) : That is, a relatively safe place that would have something to offer in terms of the future. ‘Home’ in this sense challenge more passive notions of home as connected to ‘roots’ and relations of the past; rather, it represents “a sense of possibility” (Hage 1997) which, in its forward-looking quality, provides room for dreaming and imagining. The paper discusses the need for research and other systematic information on children and their families after they have been deported from Sweden.
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4.
  • Figueiredo, Duarte, et al. (författare)
  • Signalling events regulating seed coat development
  • 2014
  • Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 42, s. 358-363
  • Tidskriftsartikel (refereegranskat)abstract
    • The evolution of seeds was a major reason for the rise of angiosperms to ecological dominance. Seeds of angiosperms are composed of three main structures: the embryo, which will give rise to the next generation; the endosperm, a nurturing tissue whose main function is to deliver nutrients from the mother plant to the embryo; and the seed coat (or testa), a tissue that is derived from the maternal integuments and which provides support and protection to the growing embryo. All three seed components need to exchange signals to ensure co-ordinated growth and development. The present review discusses the structure of the seed coat, its interaction with the endosperm, and bidirectional signalling events between endosperm and seed coat that co-ordinate growth of both tissues. Angiosperm seeds are not only of evolutionary significance, but also of major agronomic importance, demanding a thorough understanding of the events governing seed growth and development.
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6.
  • Gatto, Francesco, 1987, et al. (författare)
  • Systematic analysis of overall survival and interactions between tumor mutations and drug treatment
  • 2016
  • Ingår i: Journal of Hematology and Oncology. - : Springer Science and Business Media LLC. - 1756-8722. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Few exceptional responses in cancer treatment were attributed to a genetic predisposition of the tumor. Methods: We analyzed a cohort of 3105 patients from 12 different cancer types and systematically sought the existence of a correlation between overall survival and the interaction of 21 antineoplastic treatments with 6 tumor mutations. Results: We identified a single significant correlation resulting in increased overall survival from temozolomide in lower-grade glioma with IDH1 R132H mutations. The trend could not be attributed to either the treatment or the mutation alone. Univariate and multivariate Cox regression demonstrated that this interaction stood as an independent prognostic predictor of survival. Conclusion: Our results suggest infrequent instances of exceptional responses ascribable to tumor genomics yet corroborate the existence of an interaction of temozolomide with IDH1 mutations in lower-grade glioma.
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7.
  • Ghosh, Rajib, et al. (författare)
  • An investigation of borehole stability in LKAB Malmberget underground mine, Sweden
  • 2013
  • Ingår i: Rock Characterisation, Modelling and Engineering Design Methods -. - Leiden : CRC Press/Balkema. - 9781138000575 ; , s. 747-752
  • Konferensbidrag (refereegranskat)abstract
    • Instability in production blast holes causes poor fragmentation, lower ore recovery, delay in production and higher costs in crushing and grinding. In this investigation, three large ore bodies named Alliansen, Fabian and Vi-Ri were selected. A video camera was used for mapping production blast holessoastofind borehole stability problems. A total of 298 blast holes were filmed. There were eight types of stability problems identified in the blast holes. These are shear zone, loose rock, cave, crack, deformation, stone jammed, spalling and rock breakage. Among these problems, deformation and crack were the most common ones in all the ore bodies. In addition, instability problem in the blast holes were higher around the rings which were blasted last. Further it has been found that the area which is affected by more seismic responses is the same as the one where several boreholes were re-drilled or sheared.
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8.
  • Heimdal, Jimmy, et al. (författare)
  • Protonation of the proximal histidine ligand in heme peroxidases.
  • 2008
  • Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 112:8, s. 2501-2510
  • Tidskriftsartikel (refereegranskat)abstract
    • The heme peroxidases have a histidine group as the axial ligand of iron. This ligand forms a hydrogen bond to an aspartate carboxylate group by the other nitrogen atom in the side chain. The aspartate is not present in the globins and it has been suggested that it gives an imidazolate character to the histidine ligand. Quantum chemical calculations have indicated that the properties of the heme site strongly depend on the position of the proton in this hydrogen bond. Therefore, we have studied the location of this proton in all intermediates in the reaction mechanism, using a set of different quantum mechanical and combined experimental and computational methods. Quantum refinements of a crystal structure of the resting FeIII state in yeast cytochrome c peroxidase show that the geometric differences of the two states are so small that it cannot be unambiguously decided where the proton is in the crystal structure. Vacuum calculations indicate that the position of the proton is sensitive to the surroundings and to the side chains of the porphyrin ring. Combined quantum and molecular mechanics (QM/MM) calculations indicate that the proton prefers to reside on the His ligand in all states in the reaction mechanism of the peroxidases. QM/MM free energy perturbations confirm these results, but reduce the energy difference between the two states to 12-44 kJ/mol.
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9.
  • Lambert, J-C, et al. (författare)
  • Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease
  • 2013
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 18:4, s. 461-470
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n = 2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case-control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43-1.96); P=1.1 x 10(-10)). We finally searched for association between SNPs within the FRMD4A locus and A beta plasma concentrations in three independent non-demented populations (n = 2579). We reported that polymorphisms were associated with plasma A beta 42/A beta 40 ratio (best signal, P=5.4 x 10(-7)). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.
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10.
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