| 1. |
- Aleksandrova, Elena V, et al.
(författare)
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Structural basis of Cfr-mediated antimicrobial resistance and mechanisms for its evasion
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The ribosome is an essential drug target as many classes of clinically important antibiotics bind and inhibit its functional centers. The catalytic peptidyl transferase center (PTC) is targeted by the broadest array of inhibitors belonging to several chemical classes. One of the most abundant and clinically prevalent mechanisms of resistance to PTC-acting drugs is C8-methylation of the universally conserved adenine residue 2503 (A2503) of the 23S rRNA by the methyltransferase Cfr. Despite its clinical significance, a sufficient understanding of the molecular mechanisms underlying Cfr-mediated resistance is currently lacking. In this work, we developed a method to express a functionally-active Cfr-methyltransferase in the thermophilic bacterium Thermus thermophilus and report a set of high-resolution structures of the Cfr-modified 70S ribosome containing aminoacyl- and peptidyl-tRNAs. Our structures reveal that an allosteric rearrangement of nucleotide A2062 upon Cfr-methylation of A2503 is likely responsible for the inability of some PTC inhibitors to bind to the ribosome, providing additional insights into the Cfr resistance mechanism. Lastly, by determining the structures of the Cfr-methylated ribosome in complex with the antibiotics iboxamycin and tylosin, we provide the structural bases behind two distinct mechanisms of evading Cfr-mediated resistance.
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| 2. |
- Aleksandrova, Krasimira, et al.
(författare)
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Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer : results from the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2014
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 29:4, s. 261-275
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Tidskriftsartikel (refereegranskat)abstract
- A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60 % of the overall biomarker variance. In multivariable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95 % CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95 % CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95 % CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95 % CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development.
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| 3. |
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Balansen mellan skärmtid, rörelse och hjärnhälsa hos unga
- 2024
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Rapport (populärvet., debatt m.m.)abstract
- Gymnastik- och idrottshögskolan (GIH) har sedan 2017 arbetat i en serie forskningsstudier finansierade av Stiftelsen för kunskaps- och kompetensutveckling, KKS. Studierna har fokuserat på både barn, vuxna och äldre. Sedan 2021 finns vid GIH ett forskningscentrum med fokus på fysisk aktivitet och hjärnhälsa, det vill säga goda kognitiva funktioner och god psykisk hälsa, kallat E-PABS (Center of Excellence in Physical Activity, Healthy Brain Functions and Sustainability). Forskningen inom E-PABS täcker många ämnesområden och innefattar epidemiologi, beteendeförändring, kognitiv neurovetenskap, fysiologi och molekylär biokemi.Denna rapport bygger på studier inom projektet ”Fysisk aktivitet och hälsosamma hjärnfunktioner hos skolungdomar”, som genomfördes under 2017–2023. Projektet hade tre delar, en epidemiologisk, en fysiologisk och en etnografisk del som tillsammans syftade till att svara på frågorna ”Vilket är sambandet mellan fysisk aktivitet, stillasittande beteende, kost och hälsosamma hjärnfunktioner hos barn och ungdomar, och hur kan fysisk aktivitet som främjar sunda hjärnfunktioner långsiktigt hållbart implementeras i skolor?”
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| 4. |
- Baltar, Federico, et al.
(författare)
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Cell-free extracellular enzymatic activity is linked to seasonal temperature changes : a case study in the Baltic Sea
- 2016
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 13:9, s. 2815-2821
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular enzymatic activities (EEA) are a crucial step on the degradation of organic matter. Dissolved (cell-free) extracellular enzymes in seawater can make up a significant contribution of the bulk EEA. However, the factors controlling the proportion of dissolved EEA in the marine environment remain unknown. Here we studied the seasonal changes in the proportion of dissolved relative to total EEA (of alkaline phosphatase [APase], β-glucosidase, [BGase], and leucine aminopeptidase, [LAPase]), in the Baltic Sea for 18 months. The proportio n of dissolved EEA ranged between 37-100%, 0-100%, 34-100% for APase, BGase and LAPase, respectively. A consistent seasonal pattern in the proportion of dissolved EEA was found among all the studied enzymes, with values up to 100% during winter and <40% du ring summer. A significant negative relation was found between the 21proportion of dissolved EEA and temperature, indicating that temperature might be a critical factor controlling the proportion of dissolved relative to total EEA in marine environments. Our results suggest a strong decoupling of hydrolysis rates from mi crobial dynamics in cold waters. This implies that under cold conditions, cell-free enzymes can contribute to substrate availability at large distances from the producing cell, increasing the dissociation between the hydrolysis of organic compounds and the actual microbes producing the enzymes. This also indicates that global warming could come to affect the hydrolysis of organic matter by reducing the hydrolytic activity of cell-free enzymes.
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| 5. |
- Berndt, Kurt D, et al.
(författare)
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Designed replacement of an internal hydration water molecule in BPTI : structural and functional implications of a glycine-to-serine mutation.
- 1993
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 32, s. 4564-4570
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Tidskriftsartikel (refereegranskat)abstract
- The three-dimensional structure of the basic pancreatic trypsin inhibitor (BPTI) contains four internal water molecules, which form a total of nine intermolecular hydrogen bonds with the BPTI polypeptide chain. To investigate the effect of such internal hydration on protein structure and stability, we displaced one of the internal water molecules in a recombinant BPTI analogue, BPTI(G36S), in which Gly 36 is replaced by serine. The replacement of a water molecule by the seryl side chain was established by the absence of the protein-water nuclear Overhauser effects (NOE) that had been attributed to the water molecule near Gly 36 in wild-type BPTI and by the presence of new, intramolecular NOEs to the hydroxyl proton of Ser 36. BPTI(G36S) has slightly reduced thermal stability compared to BPTI, corresponding to a destabilization by delta (delta G) approximately 0.7 kcal/M in 6 M guanidinium hydrochloride solution. Additionally, the stabilities of the complexes formed between BPTI(G36S) and trypsin, plasmin, or kallikrein are significantly reduced when compared to the corresponding complexes with wild-type BPTI.
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| 6. |
- Boffa, Eleonora, et al.
(författare)
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Development and application of an Integrated Business Model framework to describe the digital transformation of manufacturing - a bibliometric analysis
- 2023
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Ingår i: Production & Manufacturing Research. - : Informa UK Limited. - 2169-3277. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The digitalisation trend is affecting the manufacturing industry byadopting several emerging technologies that can increase the efficiencyand output of production processes and operations. A growingbody of literature shows that this trend demands a structuralrethink of how companies do business. However, there is a lack ofholistic contributions describing how aspects of manufacturing digitalisationalign with the Business Model Innovation process. Thisstudy uses a bibliometric mapping approach to analyse the literatureon manufacturing digital transformation through the IntegratedBusiness Model (IBM) lens. The results identify the major researchtopics discussed in the analysed domain and propose an enrichedIBM framework with specific descriptions and connections amongthe components and their relative strengths. Holistically, the resultingenhanced model may ultimately assist practitioners in understandingthe innovation process of the BM triggered bytechnological shifts in their manufacturing, enabling an alignmentof the manufacturing strategy with IBM’s components.
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| 7. |
- Buchholz, Margret, 1968, et al.
(författare)
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Text messaging with pictures and speech synthesis for adolescents and adults with cognitive and communicative disabilities – professionals’ views about user satisfaction and participation.
- 2013
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Ingår i: Technology and Disability. - 1055-4181 .- 1878-643X. ; 25:2, s. 87-98
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Complex communication needs and problems with accessibility may restrict people who use augmentative and alternative communication (AAC) to communicate on the phone. New technology is promising. People with limited skills in reading and writing can communicate on the phone by using symbols representing words or phrases. METHODS: This interview study examines professionals' views of satisfaction, participation and involvement in daily life in seven individuals with cognitive and communicative disabilities who tried text messaging with picture symbols and speech synthesis in smartphones. The users' experiences of text-messaging are reported elsewhere. RESULTS: The results suggest that texting with picture symbols and speech can increase independence and participation in adults with cognitive and communicative disabilities. Results also point to the necessity of individual assessments. Important factors for user satisfaction include products which can be adapted according to the individual's needs. Speech synthesis, user friendly lay-out and functions making devices easy to handle are necessary. CONCLUSIONS: This study is promising and informative for professionals working with communication technology. It supports enabling of texting today as well as future development of smartphone applications for persons with cognitive and communicative disabilities.
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| 8. |
- Buchholz, Margret, 1968, et al.
(författare)
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"That is how I speak nowadays" - experiences of remote communication among persons with communicative and cognitive disabilities.
- 2018
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Ingår i: Disability and rehabilitation. - : Informa UK Limited. - 1464-5165 .- 0963-8288. ; 40:12, s. 1468-1479
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to explore the experiences of remote communication (i.e., communication between persons who are not in the same place) among people with communicative and cognitive disabilities.Eleven adolescents and adults were interviewed using Talking Mats and interview data was analyzed qualitatively with systematic text condensation.The use of remote communication varies between the participants. The participants also value remote communication differently. Having the possibility to choose between different means of remote communication is important. Being able to determine whether to communicate independently or with support from another person is also valued as relevant. Strategies used to manage remote communication include facilitating for the communication partner and preparing for future communication situations. Those who are able to use writing as an alternative to problematic spoken remote communication like phone calls, for example by using chat or text messaging. Decisions regarding means of communication and human support relate to the concept of self-determination.Better access to remote communication trough assistive technology such as speech synthesis and picture symbols would make remote communication easier and facilitate participation for people with communicative and cognitive disabilities. Implications for rehabilitation People with communicative and cognitive disabilities face challenges with access to remote communication. Access to communication technology including remote communication is important for self-determination, for personal safety and for overall participation in society. Communication technology should be considered in the rehabilitation process and training is crucial. To understand the possible benefits of remote communication, people with communicative and cognitive disability need to get the possibility to practice. Professionals play a key role in the assessment and intervention of remote communication for their patients.
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| 9. |
- Bucken-Knapp, Gregg, et al.
(författare)
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The eye of the beholder: Narrating crisis in the ongoing Swedish labor migration policy debate
- 2015
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Ingår i: Korkut, U., Buchen-Knapp, G., Cox, R.H., Mahndran, K. (Eds.). Discursive Governance in Politics, Policy, and the Public Sphere. - London : Palgrave Macmillan. ; , s. 127-144
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Bokkapitel (refereegranskat)
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| 10. |
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