| 1. |
- Altincekic, Nadide, et al.
(författare)
-
Targeting the Main Protease (Mpro, nsp5) by Growth of Fragment Scaffolds Exploiting Structure-Based Methodologies
- 2024
-
Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 19:2, s. 563-574
-
Tidskriftsartikel (refereegranskat)abstract
- The main protease Mpro, nsp5, of SARS-CoV-2 (SCoV2) is one of its most attractive drug targets. Here, we report primary screening data using nuclear magnetic resonance spectroscopy (NMR) of four different libraries and detailed follow-up synthesis on the promising uracil-containing fragment Z604 derived from these libraries. Z604 shows time-dependent binding. Its inhibitory effect is sensitive to reducing conditions. Starting with Z604, we synthesized and characterized 13 compounds designed by fragment growth strategies. Each compound was characterized by NMR and/or activity assays to investigate their interaction with Mpro. These investigations resulted in the four-armed compound 35b that binds directly to Mpro. 35b could be cocrystallized with Mpro revealing its noncovalent binding mode, which fills all four active site subpockets. Herein, we describe the NMR-derived fragment-to-hit pipeline and its application for the development of promising starting points for inhibitors of the main protease of SCoV2.
|
|
| 2. |
- Badam, Tejaswi, et al.
(författare)
-
CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases
- 2022
-
Ingår i: Epigenetics. - : Taylor & Francis Group. - 1559-2294 .- 1559-2308. ; 17:9, s. 1040-1055
-
Tidskriftsartikel (refereegranskat)abstract
- Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases.
|
|
| 3. |
- Berg, Ingrid, et al.
(författare)
-
Recensioner
- 2023
-
Ingår i: Fornvännen. - Stockholm : Kungl. Vitterhets Historie och Antikvitets Akademien. - 0015-7813 .- 1404-9430. ; 118:4, s. 273-276
-
Tidskriftsartikel (refereegranskat)abstract
- Recensioner av:Jes Wienberg, Heritopia: World Heritage and modernity. Lund 2021. 323 s. ISBN 978-91-984699-3-6.Axel Christophersen, Under Trondheim: Fortellingerfra bygrunnen. Trondheim 2020. 415 s. ISBN 9788283050875.
|
|
| 4. |
- Berg, Jessica, et al.
(författare)
-
Shared mobility services in Swedish rural areas : Development and demonstration of the KomILand-concept
- 2021
-
Ingår i: 2021 International Transport Forum (ITF) Pre-Summit Research Day.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Transport accounts for a large share of global green-house gas emissions. Research efforts are being made to identify, develop, and test new types of resource efficient solutions that meet peoples’ mobility needs. A growing trend within this realm is so called shared mobility services – such as car-sharing, bicycle rental, and ride-sourcing – which is expected to have the potential to complement and strengthen public transport and support less car-centric lifestyles. Shared mobility has become an integral part of the dominant discourse around the future of transport (autonomous-connected-electric-shared), and although their modal shares still are minor, recent years have seen significant growth of shared mobility services.However, eforts to develop shared mobility services have predominantly been made in urban areas where the services are expected to have greater impact on green-house gas reduction. Further, most research on shared mobility has focused on urban areas . Consequently, there is a lack of empirical research on how shared mobility services can be organized in rural areas, and what effects they can have on aspects such as of car ownership, green-house gas emissions, and quality of life.The KomILand project set out to address these knowledge gaps by developing and testing the KomILand concept – a regional Mobility-as-a-Service platform that enable rural dwellers to put together shared mobility service offerings that are tailored to the specific needs of their communities. An initial pre-study (2017-2018) paved the way for a trial of the concept by identifying suitable rural towns, likely user groups and their demands, key service components, and possible business models. Subsequently, the ongoing trial phase of the project (2019-2021) aims to develop a functional prototype and to test it in collaboration with civic associations in three rural towns with 800-900 inhabitants in Västra Götaland in West Sweden.In the following, this extended abstract first presents key findings from the pre-study. Thereafter, a few insights from the ongoing trial are provided prior to a concluding discussion on possible pathways for the journey from a temporary, small-scale trial towards a region-wide and continuous operation.
|
|
| 5. |
- Berg, Malin, 1976, et al.
(författare)
-
A national study of health-related quality of life in patients with cancer of the base of the tongue compared to the general population and to patients with tonsillar carcinoma
- 2021
-
Ingår i: Head and Neck-Journal for the Sciences and Specialties of the Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 43:12, s. 3843-3856
-
Tidskriftsartikel (refereegranskat)abstract
- Background This exploratory, registry-based, cross-sectional study aimed to evaluate patients' health-related quality of life (HRQOL) in a subsite of oropharyngeal cancer: cancer of the base of the tongue (CBT). Methods CBT patients, treated with curative intent, completed the EORTC QLQ-C30 and QLQ-H&N35 questionnaires 15 months after diagnosis. The HRQOL of CBT patients was compared to reference scores from the general population and to that of tonsillar carcinoma patients. Results The 190 CBT patients scored significantly worse than members of the general population on most scales. CBT patients with human papilloma virus (HPV)-positive tumors had significantly better HRQOL on 8 of 28 scales than HPV-negative patients. Compared to 405 tonsillar carcinoma patients, CBT patients had significantly worse HRQOL on 8 of the 28 scales, the majority local head and neck related problems. Conclusion One year after treatment, CBT patients' HRQOL was significantly worse in many areas compared to that of the general population and slightly worse than that of tonsillar carcinoma patients.
|
|
| 6. |
- Björnson Skogström, Lisa, 1980, et al.
(författare)
-
Women’s Experiences of Physical Features in a Specially Designed Birthing Room: A Mixed-Methods Study in Sweden
- 2022
-
Ingår i: HERD. - : SAGE Publications. - 2167-5112 .- 1937-5867. ; 15:3, s. 193-205
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To explore women’s experiences of physical features in a birthing room designed to be adaptable to personal wishes and needs during labor and birth. Background: Childbirth is a central life event influenced by numerous factors, including the healthcare environment; however, there is insufficient knowledge on how the physical design affects women during birth. Methods: This study was part of a randomized controlled trial in the Room4Birth research project, including women randomized to receive care in a new birthing room designed with physical features changeable according to personal wishes. Data consisted of responses to two questions analyzed with descriptive statistics (n = 202) and semi-structured interviews analyzed for content (n = 19). Results: A total of 93.6% (n = 189) assessed the physical features in the birthing room as meaningful to a very high or high extent. The overall impression of the room was positive and exceeded women’s expectations. They felt welcomed and strengthened by the room, which shifted the focus to a more positive emotional state. The room differed from traditional hospital birthing rooms, contained familiar features that maintained integrity, and had space for companions. The variety of physical features was appreciated. Of nine listed physical features, the bathtub was ranked most important, followed by the projection of nature scenery, and dimmable lighting, but the room as a whole appeared most important. Conclusions: When planning and designing hospital-based birthing rooms, it is crucial to offer possibilities to adapt the room and physical features according to personal wishes.
|
|
| 7. |
- Cheng, Shibin, et al.
(författare)
-
Novel blood test for early biomarkers of preeclampsia and Alzheimers disease
- 2021
-
Ingår i: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- A non-invasive and sensitive blood test has long been a goal for early stage disease diagnosis and treatment for Alzheimers disease (AD) and other proteinopathy diseases. We previously reported that preeclampsia (PE), a severe pregnancy complication, is another proteinopathy disorder with impaired autophagy. We hypothesized that induced autophagy deficiency would promote accumulation of pathologic protein aggregates. Here, we describe a novel, sensitive assay that detects serum protein aggregates from patients with PE (n=33 early onset and 33 late onset) and gestational age-matched controls (n=77) as well as AD in both dementia and prodromal mild cognitive impairment (MCI, n=24) stages with age-matched controls (n=19). The assay employs exposure of genetically engineered, autophagy-deficient human trophoblasts (ADTs) to serum from patients. The aggregated protein complexes and their individual components, including transthyretin, amyloid beta -42, alpha -synuclein, and phosphorylated tau231, can be detected and quantified by co-staining with ProteoStat, a rotor dye with affinity to aggregated proteins, and respective antibodies. Detection of protein aggregates in ADTs was not dependent on transcriptional upregulation of these biomarkers. The ROC curve analysis validated the robustness of the assay for its specificity and sensitivity (PE; AUC: 1, CI: 0.949-1.00; AD; AUC: 0.986, CI: 0.832-1.00). In conclusion, we have developed a novel, noninvasive diagnostic and predictive assay for AD, MCI and PE.
|
|
| 8. |
- Gerdin, Göran, 1980-, et al.
(författare)
-
Despite good intentions : The elusiveness of social justice in health and physical education curricula across different contexts
- 2024
-
Ingår i: European Physical Education Review. - : Sage Publications. - 1356-336X .- 1741-2749.
-
Tidskriftsartikel (refereegranskat)abstract
- This paper draws on critical discourse analysis to examine how health and physical education (HPE) curricula from Sweden, Norway, South Africa, Australia, and New Zealand may influence possibilities for the enactment of social justice in schools. The findings highlight the presence of social justice intentions across the five curricula as related to embodied movement experiences, social cohesion, and activism. That said, the findings simultaneously suggest that the language used to orient teaching towards social justice objectives is often elusive. In this paper, we contend that despite the presence of social justice intentions in these five HPE curricula, the articulation and function of the language within the curriculum documents do not necessarily support the enactment of this in practice. To conclude, we therefore suggest that more work is needed to ensure that curricula and other supporting artefacts and resources can better support both teachers' practice and students' learning in raising awareness of, and addressing, social justice outcomes in HPE.
|
|
| 9. |
|
|
| 10. |
- Goldkuhl, Lisa, 1983, et al.
(författare)
-
Effekten av att föda barn i ett speciellt utformat födslorum: En randomiserad kontrollerad studie
- 2023
-
Ingår i: Konferensbidrag Reproduktiv Hälsa, Karlstad.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Bakgrund: Den upplevda miljön har betydelse för födselns fysiologiska processer hos kvinnor. Då majoriteten barn föds på sjukhus är det därav betydelsefullt att utforma sjukhusmiljön utifrån aspekter som främjar trygghet och förtrogenhet. Syfte: Att utvärdera om ett speciellt utformat rum ger bättre utfall i samband med födsel, i jämförelse med standardrum. Metod: En randomiserad kontrollerad studie genomfördes under åren 2019–2020 vid ett sjukhus i västra Sverige. Förstföderskor med en singelgraviditet i fullgången tid lottades till att vårdas antingen i ett rum speciellt utformat för att stödja födselns fysiologiska processer (testrummet) eller i ett standardrum. Hypotesen var att det primära kompositutfallet skulle uppfyllas hos fler kvinnor i testrummet, det vill säga: vaginal spontan födsel, ingen användning av oxytocindropp, positiv förlossningsupplevelse, samt blödning <1000ml. För att kunna påvisa en skillnad på 8% mellan de randomiserade grupperna i det primära utfallet, krävdes 1274 studiedeltagare. Bland sekundära utfall fanns andra perinatala utfall samt självskattad förlossningsupplevelse upp till ett år efter födsel. Resultat: Studien avslutades i förtid på grund av Covid-19-pandemin, vilket gjorde att 406 kvinnor randomiserades totalt. Därav uppnåddes inte tillräcklig styrka för att kunna påvisa en statistiskt signifikant skillnad mellan grupperna avseende det primära utfallet. I testrummet uppfylldes det primära utfallet hos 42% av kvinnorna jämfört med 35% i standardrummet (odds ratio: 1.35, 95% CI 0.90–2.01). Kvinnor i testrummet använde epiduralanalgesi i lägre utsträckning. De rapporterade även mer positiva förlossningsupplevelser 3 och 12 månader efter födsel i jämförelse med kvinnor i standardrummen. Konklusion: Denna för tidigt avslutade studie kunde inte verifiera om testrummet förbättrar det primära utfallet. Däremot använde kvinnor i det testrummet i lägre grad farmakologisk smärtlindring och skattade bättre förlossningsupplevelse över tid. Finansiering: Vetenskapsrådet (2018–02406), Institutionen för Vårdvetenskap och Hälsa, Göteborgs Universitet.
|
|
