| 1. |
- Aad, G, et al.
(author)
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- 2015
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swepub:Mat__t
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| 2. |
- Andersson, Annika, 1966-
(author)
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Second language acquisition in 6- to 8-year-old native Spanish-speaking children : ERP studies of phonological awareness, semantics, and syntax
- 2012
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Doctoral thesis (other academic/artistic)abstract
- Most people in the world and about a fifth of all school-aged Americans speak at least two languages. Nevertheless, little is known about second language (L2) processing in development, even though language proficiency is strongly related to success in almost all domains. Whereas behavioral studies of L2 acquisition in children are abundant, neurocognitive studies of L2 processing typically are limited to adults with several years of exposure, who may use general cognitive mechanisms to compensate for any difficulties in L2 processing. Research on bilingual adults suggests that age of acquisition (AoA) and proficiency have different effects on different aspects of L2 processing. The present study therefore recorded event-related brain potentials (ERPs) in order to index processes of phonological awareness (Rhyming effect: RE), semantics (N400), and syntax (LAN, P600) in bilingual and monolingual children 6-8 years of age. Even though behaviorally, bilingual children with an average AoA of 4 years had lower English proficiency than monolingual children, proficiency predicted similar differences in ERPs across groups: greater proficiency was linked with shorter latencies and higher amplitudes of all ERP components. Latency in these cases represents speed of processing while amplitude of ERP effects in children can be thought of as an indication of detection of the introduced violations. The appearance of the anterior rhyming effect, latency of the posterior rhyming effect, along with the distribution of the anterior ERP effect for phrase structure violations were related to AoA. More specifically, bilingual 6- to 8-year olds of higher English proficiency processed rhyming nonwords slower than 3- to 5-year-old monolingual children, which could have a strong impact on later vocabulary acquisition. Differences across lingualism groups in distribution of the anterior negativity elicited by phrase structure violations could indicate different neural generators for processing of syntax. Noteworthy is that differences in processing as illustrated by these ERP effects were recorded even though in both these cases bilingual children's English proficiency were within the normal range expected of monolingual children of similar age. Early acquisition was thus important for processing of rhyming and for more automatic syntactic processing as revealed by differences in the anterior negativity.
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| 3. |
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| 4. |
- Brehony, Carina, et al.
(author)
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Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development
- 2014
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In: Clinical and Vaccine Immunology. - : American Society for Microbiology. - 1556-6811 .- 1556-679X. ; 21:6, s. 847-853
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Journal article (peer-reviewed)abstract
- New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and >= 25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups.
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| 5. |
- Kern, Christoph, et al.
(author)
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Halogen oxide measurements at Masaya Volcano, Nicaragua using active long path differential optical absorption spectroscopy
- 2009
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In: Bulletin of Volcanology. - 0258-8900 .- 1432-0819. ; 71, s. 659-670
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Journal article (peer-reviewed)abstract
- Active Long Path Differential Optical Absorption Spectroscopy (LP-DOAS) measurements of halogen oxides were conducted at Masaya Volcano, in Nicaragua from April 14 to 26, 2007. The active LP-DOAS system allowed night-time halogen measurements and reduced the ClO detection limit by an order of magnitude when compared to previous passive DOAS measurements, as wavelengths below 300 nm could be used for the DOAS retrievals. BrO was detected with an average BrO/SO2 molecular ratio of approximately 3 × 10−5 during the day. However, BrO values were below the detection limit of the instrument for all night-time measurements, a strong indication that BrO is not directly emitted, but rather the result of photochemical formation in the plume itself according to the autocatalytic “bromine explosion” mechanism. Despite the increased sensitivity, both ClO and OClO could not be detected. The achieved upper limits for the X/SO2 ratios were 5 × 10−3 and 7 × 10−6, respectively. A rough calculation suggests that ClO and OClO should be present at similar abundances in volcanic plumes. Since the DOAS technique is orders of magnitude more sensitive for OClO than for ClO, this indicates that OClO should always be detectable in plumes in which ClO is found. However, further LP-DOAS studies are needed to conclusively clarify the role of chlorine oxides in volcanic plumes.
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| 6. |
- Lewis, Lisa A., et al.
(author)
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Defining targets for complement components C4b and C3b on the pathogenic neisseriae
- 2008
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In: Infection and Immunity. - 1098-5522. ; 76:1, s. 339-350
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Journal article (peer-reviewed)abstract
- Complement is a key arm of the innate immune defenses against the pathogenic neisseriae. We previously identified lipooligosaccharide on Neisseria meningitidis as an acceptor for complement C4b. Little is known about other neisserial targets for complement proteins C3 and C4, which covalently attach to bacterial surfaces and initiate opsonization and killing. In this study we demonstrate that N. gonorrhoeae porin (Por) 1B selectively binds C4b via amide linkages and C3b via ester linkages. Using strains expressing hybrid Por1A/1B molecules, a region spanned by loops 4 and 5 of Por1B was identified as the preferred binding site for C4b. We also identified the opacity protein (Opa), a major adhesin of pathogenic neisseriae, as a target for C4b and C3b on both N. meningitidis and N. gonorrhoeae. Using N. gonorrhoeae variants that predominately expressed individual Opa proteins, we found that all expressed Opa proteins tested (A, B, C, D, E, F and I) bound C4b and C3b via amide and ester linkages, respectively. Amide linkages with Por1B and Opa were confirmed using serum containing only the C4A isoform, which exclusively forms amide linkages with targets. While monomers and heterodimers of C4Ab were detected on bacterial targets, C4Bb appeared to preferentially participate in heterodimer (C5 convertase) formation. Our data provide another explanation for enhanced serum sensitivity of Por1B-bearing gonococci. The binding of C3b and C4b to Opa provide a rationale for the recovery of predominantly 'transparent' (Opa negative) neisserial isolates from persons with invasive disease where the bacteria encounter high levels of complement.
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| 7. |
- Lübcke, Peter, et al.
(author)
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BrO/SO2 molar ratios from scanning DOAS measurements in the NOVAC network
- 2014
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In: Solid Earth. - : Copernicus GmbH. - 1869-9510 .- 1869-9529. ; 5:1, s. 409-424
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Journal article (peer-reviewed)abstract
- The molar ratio of BrO to SO2 is, like other halogen/sulfur ratios, a possible precursor for dynamic changes in the shallow part of a volcanic system. While the predictive significance of the BrO/SO2 ratio has not been well constrained yet, it has the major advantage that this ratio can be readily measured using the remote-sensing technique differential optical absorption spectroscopy (DOAS) in the UV. While BrO/SO2 ratios have been measured during several short-term field campaigns, this article presents an algorithm that can be used to obtain long-term time series of BrO/SO2 ratios from the scanning DOAS instruments of the Network for Observation of Volcanic and Atmospheric Change (NOVAC) or comparable networks. Parameters of the DOAS retrieval of both trace gases are given. The influence of co-adding spectra on the retrieval error and influences of radiative transfer will be investigated. Difficulties in the evaluation of spectroscopic data from monitoring instruments in volcanic environments and possible solutions are discussed. The new algorithm is demonstrated by evaluating data from the NOVAC scanning DOAS systems at Nevado del Ruiz, Colombia, encompassing almost 4 years of measurements between November 2009 and end of June 2013. This data set shows variations of the BrO/SO2 ratio several weeks prior to the eruption on 30 June 2012.
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| 8. |
- Romgard, Jan, 1966-
(author)
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Embracing Science : Sino-Swedish Collaborations in the Field Sciences, 1902–1935
- 2013
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Doctoral thesis (other academic/artistic)abstract
- In 1902, a Swedish professor at Shanxi University started to study the region’s geology and in 1913, he suggested to the Chinese Republican Government an expansion of these surveys nationwide. As a result, the Head of the Geological Survey of Sweden, J. G. Andersson, was employed as a geological adviser to the Chinese Government. With the formation of the Geological Survey of China in 1916, headed by Ding Wenjiang, this collaboration soon evolved into a bilateral scientific project involving a large number of Swedish naturalists. It culminated in the highly interdisciplinary Sino-Swedish Expedition (1927–1935), in which Chinese and Swedish scientists spent eight years surveying China’s northwest.This study shows that the Chinese goals for the project were closely related to domestic striving to modernize and strengthen the nation by the use of modern science. The Swedes provided funding and expertise for mapping the nation’s geology, while the publication of the scientific results in Chinese bulletins promoted both the spread of modern science in the country and China’s scientific advancement internationally. As the domestic research community grew, the collaboration became a scientific joint venture that was controlled by the new Academia Sinica, formed in 1928.The dissertation further illustrates how the Swedish participants were closely connected to the Polar research community that reallocated resources from Polar exploration to China. As China offered an alternative field for research and access to data that could help solve the issues on the Swedish scientific agenda, these resources enabled the fieldwork to reach unprecedented proportions. The project was framed in nationalistic rhetoric to attract further funding for continued fieldwork, while the primary goal was to explore the major research issues.
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| 9. |
- Speliotes, Elizabeth K., et al.
(author)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Journal article (peer-reviewed)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 10. |
- Taha, Muhamed-Kheir, et al.
(author)
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Defining the breakpoint for resistance to rifampicin in Neisseria meningitidis by rpoB sequencing
- 2009
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Other publication (other academic/artistic)abstract
- Clinical isolates of Neisseria meningitidis resistant to rifampicin are important to identify asthey lead to failure of chemoprophylaxis of meningococcal disease. However, theidentification of these isolates is hindered by the absence of a harmonized breakpoint despiteefforts of standardization. In the present study, a large number (n=352) of clinical N.meningitidis isolates from 12 mainly European countries and spanning over 25 years (1984 to2009) were examined. The collection comprised all clinical isolates with MIC 0.25 mg/lreceived by the national reference laboratories for meningococci in the participating countries(n=161). In addition, representative isolates displaying MIC of rifampicin <0.25 mg/l wereexamined (n=191). Phenotyping and genotyping of isolates were performed and a 660 bpDNA fragment of the rpoB gene was sequenced in all the included isolates. Sequencesdiffering by at least one nucleotide were defined as a unique rpoB allele (n=55). Geometricmeans of MIC were calculated for isolates displaying the same allele. All the clinical isolatesdisplaying MIC >1 mg/l of rifampicin possessed rpoB alleles with critical mutations (in total21 alleles), resulting in substitutions at the codon H552 and less frequently at nearby codons(S548 and S557). These alterations were absent in the alleles (n=34) found in all isolates withMIC 1 mg/l. Based on these findings, rifampicin susceptible isolates could be defined asthose with MIC 1 mg/l. A new web site was created based on the data from this work (http://neisseria.org/nm/typing/rpoB). The rifampicin resistant isolates belonged to diversegenetic lineages and provoked lower bacteremia levels in mice. This biological cost mayexplain the non-expansion of the rifampicin resistant isolates.
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| 11. |
- Taha, Muhamed-Kheir, et al.
(author)
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Interlaboratory Comparison of PCR-Based Identification and Genogrouping of Neisseria meningitidis
- 2005
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In: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 43:1, s. 144-149
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Journal article (peer-reviewed)abstract
- Twenty clinical samples (18 cerebrospinal fluid samples and 2 articular fluid samples) were sent to 11 meningococcus reference centers located in 11 different countries. Ten of these laboratories are participating in the EU-MenNet program (a European Union-funded program) and are members of the European Monitoring Group on Meningococci. The remaining laboratory was located in Burkina Faso. Neisseria meningitidis was sought by detecting several meningococcus-specific genes (crgA, ctrA, 16S rRNA, and porA). The PCR-based nonculture method for the detection of N. meningitidis gave similar results between participants with a mean sensitivity and specificity of 89.7 and 92.7%, respectively. Most of the laboratories also performed genogrouping assays (siaD and mynB/sacC). The performance of genogrouping was more variable between laboratories, with a mean sensitivity of 72.7%. Genogroup B gave the best correlation between participants, as all laboratories routinely perform this PCR. The results for genogroups A and W135 were less similar between the eight participating laboratories that performed these PCRs.
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| 12. |
- Thienel, Manuela, et al.
(author)
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Immobility-associated thromboprotection is conserved across mammalian species from bear to human
- 2023
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6641, s. 178-187
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Journal article (peer-reviewed)abstract
- Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a major cause of morbidity and mortality. Short-term immobility-related conditions are a major risk factor for the development of VTE. Paradoxically, long-term immobilized free-ranging hibernating brown bears and paralyzed spinal cord injury (SCI) patients are protected from VTE. We aimed to identify mechanisms of immobility-associated VTE protection in a cross-species approach. Mass spectrometry-based proteomics revealed an antithrombotic signature in platelets of hibernating brown bears with heat shock protein 47 (HSP47) as the most substantially reduced protein. HSP47 down-regulation or ablation attenuated immune cell activation and neutrophil extracellular trap formation, contributing to thromboprotection in bears, SCI patients, and mice. This cross-species conserved platelet signature may give rise to antithrombotic therapeutics and prognostic markers beyond immobility-associated VTE.
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| 13. |
- Vogel, Stephanie, et al.
(author)
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Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64(+) cells
- 2015
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Journal article (peer-reviewed)abstract
- Treatment of PBMC with the CD4-specific mAb BT-061 induces CD4 down-modulation of T cells. Here we report that addition of BT-061 to purified T cells did not confer this effect, whereas incubation of T cells in BT-061 coated wells restored CD4 down-modulation. These results implied that Fc gamma receptor mediated cell-cell interactions played a role. In consistence with this hypothesis PBMC depleted of CD64(+) monocytes did not confer CD4 down-modulation of BT-061 decorated T cells. Strikingly, CD4 down-modulation was observed in BT-061 treated synovial fluid punctuated from patients' inflamed joints that comprised enhanced numbers of CD64(+) cells. In contrast, in a circulating whole blood system injection of BT-061 did not induce CD4 down-modulation, due to CD64 saturation by serum IgG. Similarly, tonsil derived mononuclear cells devoid of CD64(+) cells did not show CD4 down-modulation, whereas addition of blood derived monocytes restored the effect. Thus, the interaction of BT-061 decorated T cells with CD64(+) cells is needed for CD4 down-modulation, implying that in patients BT-061 would primarily induce CD4 down-modulation at inflammatory sites. These results highlight the need not only to examine the interaction of a given mAb with single Fc gamma R, but also the immunological environment that is appropriate to support such interactions.
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| 14. |
- Weininger, Ulrich, et al.
(author)
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Protein conformational exchange measured by H-1 R-1 rho relaxation dispersion of methyl groups
- 2013
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In: Journal of Biomolecular NMR. - : Springer Verlag (Germany). - 0925-2738 .- 1573-5001. ; 57:1, s. 47-55
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Journal article (peer-reviewed)abstract
- Activated dynamics plays a central role in protein function, where transitions between distinct conformations often underlie the switching between active and inactive states. The characteristic time scales of these transitions typically fall in the microsecond to millisecond range, which is amenable to investigations by NMR relaxation dispersion experiments. Processes at the faster end of this range are more challenging to study, because higher RF field strengths are required to achieve refocusing of the exchanging magnetization. Here we describe a rotating-frame relaxation dispersion experiment for H-1 spins in methyl (CHD2)-C-13 groups, which improves the characterization of fast exchange processes. The influence of H-1-H-1 rotating-frame nuclear Overhauser effects (ROE) is shown to be negligible, based on a comparison of R (1 rho) relaxation data acquired with tilt angles of 90A degrees and 35A degrees, in which the ROE is maximal and minimal, respectively, and on samples containing different H-1 densities surrounding the monitored methyl groups. The method was applied to ubiquitin and the apo form of calmodulin. We find that ubiquitin does not exhibit any H-1 relaxation dispersion of its methyl groups at 10 or 25 A degrees C. By contrast, calmodulin shows significant conformational exchange of the methionine methyl groups in its C-terminal domain, as previously demonstrated by H-1 and C-13 CPMG experiments. The present R (1 rho) experiment extends the relaxation dispersion profile towards higher refocusing frequencies, which improves the definition of the exchange correlation time, compared to previous results.
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| 15. |
- Weininger, Ulrich, et al.
(author)
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Rotamer jumps, proton exchange, and amine inversion dynamics of dimethylated lysine residues in proteins resolved by ph-dependent 1h and 13c nmr relaxation dispersion
- 2019
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 123:46, s. 9742-9750
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Journal article (peer-reviewed)abstract
- Post-translational methylation of lysine side chains is of great importance for protein regulation, including epigenetic control. Here, we present specific 13CHD2 labeling of dimethylated lysines as a sensitive probe of the structure, interactions, and dynamics of these groups, and outline a theoretical and experimental framework for analyzing their conformational dynamics using 1H and 13C CPMG relaxation dispersion experiments. Dimethylated lysine side chains in calcium-loaded calmodulin show a marked pH dependence of their Carr-Purcell-Meiboom-Gill (CPMG) dispersion profiles, indicating complex exchange behavior. Combined analysis of 1H and 13C CPMG relaxation dispersions requires consideration of 12-state correlated exchange of the two methyl groups due to circular three-state rotamer jumps around the Cϵ-Nζ axis combined with proton exchange and amine inversion. Taking into account a number of fundamental constraints, the exchange model can be reduced to include only three fitted parameters, namely, the geometric average of the rotamer-jump rate constants, the rate constant of deprotonation of Nζ, and the chemical shift difference between the trans and gauge positions of the 13C or 1H nuclei. The pH dependence indicates that protonation of the end group dramatically slows down rotamer exchange for some lysine residues, whereas deprotonation leads to rapid amine inversion coupled with rotamer scrambling. The observed variation among residues in their exchange behavior appears to depend on the structural environment of the side chain. Understanding this type of exchange process is critical to correctly interpreting NMR spectra of methylated lysine side chains. The exchange model presented here forms the basis for studying the structure and dynamics of epigenetically modified lysine side chains and perturbations caused by changes in pH or interactions with target proteins.
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| 16. |
- Weininger, Ulrich, et al.
(author)
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Specific (CD2CD2SCHD2)-C-12-D-beta-C-12-D-gamma-C-13-H-epsilon Isotopomer Labeling of Methionine To Characterize Protein Dynamics by H-1 and C-13 NMR Relaxation Dispersion
- 2012
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 134:45, s. 18562-18565
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Journal article (peer-reviewed)abstract
- Protein dynamics on the micro- to millisecond time scale is increasingly found to be critical for biological function, as demonstrated by numerous NMR relaxation dispersion studies. Methyl groups are excellent probes of protein interactions and dynamics because of their favorable NMR relaxation properties, which lead to sharp signals in the H-1 and C-13 NMR spectra. Out of the six different methyl-bearing amino acid residue types in proteins; methionine plays a special role because of its extensive side chain flexibility and the high polarizability of the sulfur atom. Methionine is over-represented:in many protein-protein recognition sites making the methyl group of this, residue type an important probe of the relationships among dynamics, Interactions, and biological function. Here we present a straightforward method to label methionine residues with specific (CHD2)-C-13 methyl isotopomers against a deuterated background. The resulting protein samples yield NMR spectra with improved sensitivity due to the essentially 100% population of the desired (CHD2)-C-13 methyl isotopomer, which is ideal for H-1 and C-13 spin relaxation experiments to investigate protein dynamics in general and conformational exchange in particular. We demonstrate the approach by measuring H-1 and C-13 CPMG relaxation dispersion for the nine methionines in calcium free calmodulin (apo-CaM). The results. show that the C- terminal domain, but not the N-terminal domain, of apo-CaM undergoes fast exchange between the ground state and a high-energy state. Since target proteins are known to bind specifically to the C-terminal domain of apo-CaM, we speculate that the high energy state might be involved in target binding through conformational selection.
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| 17. |
- Willerton, Laura, et al.
(author)
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Geographically widespread invasive meningococcal disease caused by a ciprofloxacin resistant non-groupable strain of the ST-175 clonal complex
- 2020
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In: Journal of Infection. - : W. B. Saunders Company. - 0163-4453 .- 1532-2742. ; 81:4, s. 575-584
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Invasive meningococcal disease (IMD) caused by non-serogroupable (NG) strains mainly affects immunocompromised individuals. Reduced susceptibility to penicillin in meningococci is increasing in Europe but ciprofloxacin resistance remains rare. In 2019, three travel-related meningococcal disease cases caused by a ciprofloxacin-resistant NG strain were identified in England, leading Germany to report four additional IMD cases (2016 to 2019). We describe these and newly identified cases and characterise the strain responsible.METHODS: Cases were identified as part of national surveillance and by analysing available genomes using PubMLST tools.RESULTS: Of the cases identified in England in 2019, two geographically distinct cases developed conjunctivitis after returning from Mecca (Kingdom of Saudi Arabia) and a third linked case presented with IMD. Of the four cases from Germany, three occurred in asylum seekers - two familial and a further geographically distinct case. Further IMD cases were identified in Italy (n=2; 2017-2018), Sweden (n=1; 2016) and England (n=1; 2015). A single ST-175 clonal complex (cc175) strain with genosubtype P1.22-11,15-25 was responsible. Decreased susceptibility to penicillin was widespread with three ciprofloxacin resistant subclusters. Constituent isolates were potentially covered by subcapsular vaccines.CONCLUSION: This disease associated NG cc175 strain exhibits resistance to antibiotics commonly used to prevent IMD but is potentially covered by subcapsular (meningococcal B) vaccines.
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