Publikationer från Umeå universitet
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High-resolution mapping of sigma factor DNA-binding sequences using artificial promoters, RNA aptamers, and deep sequencing
No full textThe variable sigma (σ) subunit of the bacterial RNA polymerase holoenzyme determines promoter specificity and facilitates open complex formation during transcription initiation. Understanding σ-factor binding sequences is therefore crucial for deciphering bacterial gene regulation. Here, we present a data-driven high-throughput approach that utilizes an extensive library of 1.54 million DNA templates providing artificial promoters and 5 untranslated region sequences for σ-factor DNA-binding motif discovery. This method combines the generation of extensive DNA libraries, in vitro transcription, RNA aptamer, and deep DNA and RNA sequencing. It allows direct assessment of promoter activity, identification of transcription start sites, and quantification of promoter strength based on mRNA production levels. We applied this approach to map σ54 DNA-binding sequences in Pseudomonas putida. Deep sequencing of the enriched RNA pool revealed 64 966 distinct σ54 binding motifs, significantly expanding the known repertoire. This data-driven approach surpasses traditional methods by directly evaluating promoter function and avoiding selection bias based solely on binding affinity. This comprehensive dataset enhances our understanding of σ-factor binding sequences and their regulatory roles, opening avenues for new research in biology and biotechnology
Micropollutant removal from domestic wastewater effluent by softwood-biochar and sludge-biochar for safe reuse applications
No full textThe reuse of domestic treated wastewater in agriculture poses a significant challenge as a result of the incomplete removal of micropollutants, with considerable public health, economic, and environmental consequences. Post-treatment of the treated wastewater by sorption-based technologies using biochar can mitigate these micropollutant-related concerns. Therefore, this study aims to evaluate the efficacy of various biochar types in eliminating micropollutants from treated wastewater to ensure safe reuse practices. The biochar utilised in this study was made from softwood and hygienized sewage sludge. Five indicator micropollutants were used to assess the removal efficiency of the different biochars. The experimental campaign consisted of two steps, starting with a preliminary assessment of the removal efficiency of various biochar types under constant operational conditions. This approach identified the biochar type that achieved the highest removal efficiency. Second, a response surface methodology study was then carried out to explore the interactive impacts of operational variables on the removal of selected micropollutants using the selected biochar type, softwood-biochar. This study showed that softwood-biochar can remove benzotriazole, carbamazepine, diclofenac, irbesartan, and metformin with 98, 92, 94, 90, and 99% efficiency, respectively. These findings pave the way for the development of a low-cost sorption-based micropollutant removal technique for safe reuse
Glimpses of diagnostic tools and treatment of asthma in Sweden, Norway, and Finland from a medico-historical perspective
No full textDuring the last decades, there has been an accelerating development of diagnostic and treatment possibilities. This paper aims to remind readers of significant milestones in the medical history of asthma. In the early 1800s, important tools for auscultation of the lungs and assessment of vital capacity were developed when Laennec invented the stethoscope and Hutchinson the spirometer. Tests of allergic sensitisation were developed later; the skin prick test in the 1920s, while immunoglobulin E, IgE, was discovered in the 1960s. Dating back to ancient times, asthma has been treated using the sympathomimetic ephedrine and the anticholinergic belladonna. Asthma cigarettes act via anticholinergic effects of Datura stramonium (common name thorn apple), which contains hyoscyamine, scopolamine, and atropine. From the 1930s, ephedrine was replaced by adrenergic agents (e.g., adrenaline) and its further developments. The first selective β2-agonist, salbutamol, was introduced in 1969, followed by long-acting β2-agonists. From the 1920s until 1990, theophylline was frequently used as a bronchodilator, while cromolyn was used as a non-corticosteroid treatment of asthma in the 1970s and 1980s. Introducing inhaled corticosteroids (ICS) in the mid-1970s revolutionised asthma treatment. The use of ICS gathered momentum in the mid-1980s, with improved asthma morbidity and reduced need for hospital treatment. Recent introduction of ICS-formoterol in all treatment steps of asthma further contribute to improved adherence, asthma control and lower risk of exacerbations. At last, in management of severe asthma, monoclonal antibodies targeting IgE or different T2-cytokines, provide significant improvements in symptom control, exacerbation rate, and quality of life for patients
Förstärkningsinlärning som designer av anläggningsmaskinens motorutrymme
No full textDesigning an engine compartment of a construction machine in CAD is today mainly a manual and time-consuming process and there are few automated tools available within design software programs. Therefore, it is investigated how reinforcement learning (RL) could be applied to design the complex engine compartment, with a focus on the placement of components and the routing of wires between them. A practical example is presented where the policy gradient method PPO was applied to learning an agent that would place five different objects in a discrete two-dimensional area bounded by several conditions. The results showed success to some extent, however due to conflicts among the reward functions the agent had difficulty achieving the objectives. Further, multi-agent RL (MARL) was investigated in combination with deep learning, curriculum learning, feudal RL and transfer-learning with the hope of finding an approach that leads to a harmonious merging of component placement and joint drawing
Patient-reported outcome measures and satisfaction after laminectomy for degenerative cervical myelopathy in octogenarians : an observational study from the national Swedish spine registry
No full textBackground: Global demographics show a steady increase in the number of octogenarians. Consequently, the number of degenerative spine procedures in the elderly has significantly increased. This study aims to describe patient satisfaction, the patient-reported health-related quality-of-life, and complications, following posterior cervical laminectomy for degenerative cervical myelopathy (DCM) in octogenarians based on the national Swedish experience. Methods: The national Swedish spine registry, Swespine was reviewed between January 2006 and December 2020 for patients who underwent laminectomy for DCM. Complication rates, patient satisfaction, and Patient-Reported Outcome Measures (PROMs) one year after surgery, were analyzed and compared between propensity score matched octogenarian (≥ 80) and younger adult cohorts (< 80 years). Results: A total of 1,382 patients, 162 octogenarians, and 1,220 younger patients were identified. At one-year after surgery there were no significant difference in patient satisfaction rate or in any of the other PROMS (Eq. 5D, NRS neck pain, NRS arm pain, EQ-VAS, Neck Disability Index (NDI), the European Myelopathy Score (EMS). Complication rates were also comparable, 8.0% in octogenarians (n = 13) and 11% in younger adults (n = 51), respectively. The length of hospital stay was significantly longer in the octogenarian group, with a mean hospitalization of 5.08 days (SD ± 4.86) compared to 3.76 days (SD ± 3.93) in the younger adult cohort (p < 0.001). Conclusions: Octogenarians undergoing cervical spine surgery for DCM experience outcomes comparable to younger adults in terms of satisfaction, pain relief, and quality of life, indicating that age alone should not hinder surgical treatment. Level of evidence: IV, Retrospective observational cohort study.Correction: El-Hajj, V.G., Staartjes, V.E., Charalampidis, A. et al. Correction: Answer to the Letter to the Editor of J. Tu, et al. concerning “Patient reported outcome measures and satisfaction after laminectomy for degenerative cervical myelopathy in octogenarians: an observational study from the National Swedish spine registry”DOI: 10.1007/s00586-025-09372-0</p
Disregard. distort or discard : A study of the representation of jews in history textbooks
No full textThis thesis has explored history textbooks for upper secondary students in Sweden, with a focus on Jewish representation. The study aimed to address how many times, in which historical context and in what manner Jews are mentioned and described in textbooks, by employing both a qualitative and a quantitative analysis. Michael Apples theory of Official Knowledge as well as Norman Faircloughs three-dimensional model for critical discourse analysis were used to analyse and interpret the findings from the empirical data. The methodology consisted of reading all eight textbooks, noting every mention of Jews and sorting them into seven categories (ethnic group, national minority, victims of violence and persecutions, in relation to Nazi-Germany, conspiracies, Jewish state and specific Jewish people). This allowed for a comprehensive assessment of which context Jews were most often depicted within. The findings revealed that Jews are by far most often mentioned in relation to Nazi Germany, and that passive constructions are often used, suggesting that the textbooks often rehash the stereotype of Jews as victims. Furthermore, the analysis highlighted that Jewish history is told in fragmented extra parts of the textbook, not in the main narrative and that some textbooks main emphasis is the morality lessons the Holocaust can teach, rather than what happened
Community preparedness for people in vulnerable situations : Capacity for collaboration of the assistance needs of people experiencing homelessness in combination with substance abuse
No full textPersoner som är hemlösa lever inte sällan utan en annan social problematik. En sådan utsatthet är substansmissbruk och för personer med båda dessa problembilder innebär detta en social utsatthet i dubbel bemärkelse. Studiens syfte är därför att undersöka vilka möjligheter det finns i Umeå kommun att med adekvat hjälp bistå personer i hemlöshet med substansmissbruk. För att besvara studiens syfte används en kvalitativ forskningsansats genom semi-strukturerade intervjuer med yrkesverksamma på regional, kommunal och ideell samhällsnivå i Umeå kommun. Resultatet analyseras därefter genom deskriptiv diskursanalys med stigmatiseringsteori och domänteori som teoretiska förklaringsmodeller. Fokuset för analysen blir att undersöka hur respektive nivå beskriver begreppen; hemlöshet, substansmissbruk, behov, resurser och samverkan. I resultatet framkommer olika diskurser för hur respektive begrepp betraktas och förstås på de olika nivåerna. I resultatet framkommer att de olika nivåerna beskriver hemlöshet och substansmissbruk på olika sätt; vilket blir avgörande för om stigmatisering av målgruppen förstärks. Behov beskrivs av de olika nivåerna utifrån graden av hemlöshet, vilket leder till att det främst är det akuta behoven som avses. I fråga om resurser beskriver respondenterna hur olika nivåer besitter olika typer av makt, kompetens och materiella resurser. Detta resulterar i att respondenterna i fråga om samverkan beskriver att samarbete mellan deras olika verksamheter är avgörande för att kunna bemöta behoven hos en medborgagrupp med multipel problematik
BIT FOR BIT TO LESS WASTE : CHALLENGES FOR MUNICIPAL FACILITIES IN EMBRACING DATA DRIVEN WORK
No full textThis study aims to map and understand general challenges that municipalities can come to face when engaging in data-driven business development. This is done through a qualitative study and analysis of an initiative on this subject taken by Umeå municipality. This initiative resulted in a data-driven tool developed through the collaboration of three different municipal functions. Furthermore, this study aims to address these challenges and how to manage them.While many guides exist for guiding organizations through the transformation process into becoming data driven, the variation in size and organizational structure of Swedish municipalities makes such guides difficult to follow. Umeå municipality has in the past few years begun testing its proficiency in data driven work and has recently completed its biggest data driven project yet. However, Umeå municipality is far from data driven. The study was conducted through six interviews with seven interviewees who have had a prominent role in the previously mentioned data project. The result and analysis of said interviews show what challenges Umeå municipality must handle at the time of writing, and how they have evolved to overcome these. For instance, the results show that Umeå municipality and its functions have very real and recurring problems with sharing sensitive data within its organization due to data becoming public documents when crossing function borders. The study then discusses what actions need to be taken for municipalities in similar situations that aspire to become data driven
The role of myoblasts in tendon healing
No full textBackground: Exercise is widely recognized for its health benefits, including the release of bioactive proteins into the bloodstream, which exert systemic effects on various organs. Previous research has demonstrated that certain types of exercise can promote tendon healing, however, the specific exercise modalities that yield the most beneficial effects, as well as the underlying mechanisms, remain poorly understood. This thesis project aimed to address these knowledge gaps by utilizing an in vitro cell loading model to simulate exercise and investigate how different types and intensities of mechanical loading on myoblasts (muscle cells) influence the secretion (i.e. production and release) of bioactive proteins that may enhance tendon healing. Aim: This thesis comprised four studies. The first study aimed to determine whether the secretome, derived from statically or dynamically loaded myoblasts, has a greater impact on tendon wound healing. This was assessed through measuring key processes, such as tenocyte (tendon cell) migration, proliferation, healing phenotype, and collagen production. The second and third studies sought to identify the optimal intensity of static loading that induces the secretion of proteins with potential roles in tendon healing. The fourth study employed a three-dimensional (3D) tendon formation model to elucidate how factors secreted by mechanically loaded myoblasts influence tendon cell phenotype, extracellular matrix (ECM) protein production, tendon structure, and the underlying molecular mechanisms. Results: The Paper I demonstrated that secretory factors from statically loaded myoblasts significantly enhanced tenocyte migration, increased the type I/III collagen ratio and induced a myofibroblast-like phenotype in tenocytes compared with both dynamically loaded myoblasts and unloaded controls. These results suggest that molecules secreted from statically loaded myoblasts play a crucial role in tendon healing. In the Papers II and III, RNA sequencing and proteomic analyses, followed by validation experiments, identified insulin-like growth factor 1 (IGF-1) and neuroblastoma suppressor of tumorigenicity 1 (NBL1) as key factors secreted from myoblasts subjected to low-intensity (2%) static loading as compared with mild (5%) and high (10%) intensity loading and unloaded control. IGF-1 was found to enhance tenocyte proliferation, while NBL1 promoted tenocyte migration. The Paper IV revealed that secretome derived from myoblasts under 2% static loading increased the expression of key ECM proteins in tenocytes, including type I and III collagen, while also upregulated the expression of tenocyte-specific markers using an in vitro 3D tendon formation model. Conclusion: This thesis work showed that the secretome derived from myoblasts subjected to low-intensity static loading improved tendon healing related parameters in tenocytes. This presents a potential novel strategy to support tendon healing during the critical immobilization phase following tendon injury. By stimulating the secretion of bioactive proteins into the circulation through targeted muscle loading—without directly subjecting the injured tendon to mechanical stress—this approach presents a promising method for promoting tendon healing. Furthermore, IGF-1 and NBL1 may serve as potential therapeutic targets for enhancing tendon healing
AMPK activator ATX-304 reduces oxidative stress and improves MASLD via metabolic switching
No full textMetabolic dysfunction–associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide for which there is only one approved treatment. Adenosine monophosphate–activated protein kinase (AMPK) is an interesting therapeutic target since it acts as a central regulator of cellular metabolism. Despite efforts to target AMPK, no direct activators have yet been approved for treatment of this disease. This study investigated the effect of the AMPK activator ATX-304 in a preclinical mouse model of progressive fatty liver disease. The data demonstrated that ATX-304 diminishes body fat mass, lowers blood cholesterol levels, and mitigates general liver steatosis and the development of liver fibrosis, but with pronounced local heterogeneities. The beneficial effects of ATX-304 treatment were accompanied by a shift in the liver metabolic program, including increased fatty acid oxidation, reduced lipid synthesis, as well as remodeling of cholesterol and lipid transport. We also observed variations in lipid distribution among liver lobes in response to ATX-304, and a shift in the zonal distribution of lipid droplets upon treatment. Taken together, our data suggested that ATX-304 holds promise as a potential treatment for MASLD