| 1. |
- Börgeson, Emma, et al.
(författare)
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Challenges in PhD education due to COVID-19-disrupted supervision or business as usual: a cross-sectional survey of Swedish biomedical sciences graduate students
- 2021
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Ingår i: Bmc Medical Education. - : Springer Science and Business Media LLC. - 1472-6920. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background It remains unclear to what extent the SARS-CoV-2/COVID-19 pandemic disrupted the normal progression of biomedical and medical science graduate programs and if there was a lasting impact on the quality and quantity of supervision of PhD-students. To date, multiple editorials and commentaries indicate the severity of the disruption without providing sufficient evidence with quantifiable data. Methods An online survey was submitted to the administrative offices of biomedical and medical PhD-programs at eight major universities in Sweden to gauge the impact of the pandemic on the students. It consisted of multiple-choice and open-ended questions where students could provide examples of positive and/or negative supervision strategies. Open answered questions were coded as either examples of positive or negative support. Results PhD students were divided into two groups: those with improved or unchanged supervision during the pandemic (group 1, n = 185), versus those whose supervision worsened (group 2, n = 69). Group 1 received more help from supervisors and more frequent supervision via both online and alternative platforms (email/messages and telephone). There was no significant difference in educational-stage, gender or caretaking responsibilities between the groups. Conclusions It is important for the scientific community to learn how to provide the best possible supervision for PhD students during the pandemic. Our data suggests that more frequent supervision, and using a diverse array of meeting platforms is helpful. In addition, it is important for the students to feel that they have their supervisor's emotional support. Several students also expressed that they would benefit from an extension of their PhD programs due to delays caused by the pandemic.
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| 2. |
- Fleming, J. R., et al.
(författare)
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Exploring Obscurin and SPEG Kinase Biology
- 2021
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Three members of the obscurin protein family that contain tandem kinase domains with important signaling functions for cardiac and striated muscles are the giant protein obscurin, its obscurin-associated kinase splice isoform, and the striated muscle enriched protein kinase (SPEG). While there is increasing evidence for the specific roles that each individual kinase domain plays in cross-striated muscles, their biology and regulation remains enigmatic. Our present study focuses on kinase domain 1 and the adjacent low sequence complexity inter-kinase domain linker in obscurin and SPEG. Using Phos-tag gels, we show that the linker in obscurin contains several phosphorylation sites, while the same region in SPEG remained unphosphorylated. Our homology modeling, mutational analysis and molecular docking demonstrate that kinase 1 in obscurin harbors all key amino acids important for its catalytic function and that actions of this domain result in autophosphorylation of the protein. Our bioinformatics analyses also assign a list of putative substrates for kinase domain 1 in obscurin and SPEG, based on the known and our newly proposed phosphorylation sites in muscle proteins, including obscurin itself.
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| 3. |
- Khan, Muhammad Tanweer, et al.
(författare)
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Synergy and oxygen adaptation for development of next-generation probiotics
- 2023
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Ingår i: Nature. - 0028-0836. ; 620:7973
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Tidskriftsartikel (refereegranskat)abstract
- The human gut microbiota has gained interest as an environmental factor that may contribute to health or disease(1). The development of next-generation probiotics is a promising strategy to modulate the gut microbiota and improve human health; however, several key candidate next-generation probiotics are strictly anaerobic(2) and may require synergy with other bacteria for optimal growth. Faecalibacterium prausnitzii is a highly prevalent and abundant human gut bacterium associated with human health, but it has not yet been developed into probiotic formulations(2). Here we describe the co-isolation of F. prausnitzii and Desulfovibrio piger, a sulfate-reducing bacterium, and their cross-feeding for growth and butyrate production. To produce a next-generation probiotic formulation, we adapted F. prausnitzii to tolerate oxygen exposure, and, in proof-of-concept studies, we demonstrate that the symbiotic product is tolerated by mice and humans (ClinicalTrials.gov identifier: ) and is detected in the human gut in a subset of study participants. Our study describes a technology for the production of next-generation probiotics based on the adaptation of strictly anaerobic bacteria to tolerate oxygen exposures without a reduction in potential beneficial properties. Our technology may be used for the development of other strictly anaerobic strains as next-generation probiotics.
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| 4. |
- Kraft, Jamie D.
(författare)
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Endogenous and microbial modulators of inflammation
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiometabolic disease is characterized by dysregulated, chronic inflammation, that may result from impaired resolution pathways or alterations in the gut microbiota. Thus, restoring specialized pro-resolving mediators (SPMs) or intestinal bacteria with immunomodulatory properties represent potential therapeutic strategies for patients. First, we investigated the ability of the SPMs, lipoxins, to modulate neutrophils from individuals with atherosclerosis. Treatment of neutrophils from patients with atherosclerosis with lipoxins attenuated elevated reactive oxygen species production and expression of the high-affinity conformation of CD11b/18 integrin, and enhanced lymphatic migration. The potential therapeutic effect of lipoxins in atherosclerosis was demonstrated, along with the need to tailor treatment to the requirements of the individual. Second, for the development of a next-generation probiotic supplementation, we co-isolated Faecalibacterium prausnitzii with Desulfovibrio piger and demonstrated a cross-feeding mechanism that enhanced growth and butyrate production. F. prausnitzii is a highly prevalent and abundant human gut bacteria with immunomodulatory properties and associations with health. For development into a next-generation probiotic, F. prausnitzii was adapted to tolerate exposure to oxygen. F. prausnitzii and D. piger formulation was well tolerated by mice and humans. We demonstrated a method by which strict anaerobic bacteria can be adapted to tolerate oxygen without impacting potential beneficial properties. Finally, D. piger has been found to be both ubiquitous among individuals but has also been associated with disease. To identify if the discrepancies lie in inter-strain variation, we isolated a D. piger strain with genomic similarity to FI11049, previously isolated from a patient with colitis, to compare with the strain co-isolated with F. prausnitzii. Anti-inflammatory properties and phenotypic differences were found between the strains. Further studies are required to investigate inter-strain variation to understand disease associations.
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| 5. |
- Kraft, Jamie D., et al.
(författare)
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Lipoxins modulate neutrophil oxidative burst, integrin expression and lymphatic transmigration differentially in human health and atherosclerosis
- 2022
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Ingår i: FASEB Journal. - Hoboken, NJ, United States : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 36:3
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Tidskriftsartikel (refereegranskat)abstract
- Dysregulated chronic inflammation plays a crucial role in the pathophysiology of atherosclerosis and may be a result of impaired resolution. Thus, restoring levels of specialized pro-resolving mediators (SPMs) to promote the resolution of inflammation has been proposed as a therapeutic strategy for patients with atherosclerosis, in addition to standard clinical care. Herein, we evaluated the effects of the SPM lipids, lipoxin A4 (LXA4) and lipoxin B4 (LXB4), on neutrophils isolated from patients with atherosclerosis compared with healthy controls. Patients displayed altered endogenous SPM production, and we demonstrated that lipoxin treatment in whole blood from atherosclerosis patients attenuates neutrophil oxidative burst, a key contributor to atherosclerotic development. We found the opposite effect in neutrophils from healthy controls, indicating a potential mechanism whereby lipoxins aid the endogenous neutrophil function in health but reduce its excessive activation in disease. We also demonstrated that lipoxins attenuated upregulation of the high-affinity conformation of the CD11b/CD18 integrin, which plays a central role in clot activation and atherosclerosis. Finally, LXB4 enhanced lymphatic transmigration of human neutrophils isolated from patients with atherosclerosis. This finding is noteworthy, as impaired lymphatic function is now recognized as an important contributor to atherosclerosis. Although both lipoxins modulated neutrophil function, LXB4 displayed more potent effects than LXA4 in humans. This study highlights the therapeutic potential of lipoxins in atherosclerotic disease and demonstrates that the effect of these SPMs may be specifically tailored to the need of the individual. © 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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| 6. |
- Kraft, Jamie D., et al.
(författare)
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Specialized Pro-Resolving Mediators and the Lymphatic System
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067 .- 1661-6596. ; 22:5
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Tidskriftsartikel (refereegranskat)abstract
- Diminished lymphatic function and abnormal morphology are common in chronic inflammatory diseases. Recent studies are investigating whether it is possible to target chronic inflammation by promoting resolution of inflammation, in order to enhance lymphatic function and attenuate disease. Resolution of inflammation is an active process regulated by bioactive lipids known as specialized pro-resolving mediators (SPMs). SPMs can modulate leukocyte migration and function, alter cytokine/chemokine release, modify autophagy, among other immune-related activities. Here, we summarize the role of the lymphatics in resolution of inflammation and lymphatic impairment in chronic inflammatory diseases. Furthermore, we discuss the current literature describing the connection between SPMs and the lymphatics, and the possibility of targeting the lymphatics with innovative SPM therapy to promote resolution of inflammation and mitigate disease.
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| 7. |
- Schöler, Marc, 1987, et al.
(författare)
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The interplay between dietary fatty acids and gut microbiota influences host metabolism and hepatic steatosis
- 2023
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Ingår i: NATURE COMMUNICATIONS. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Dietary lipids can affect metabolic health through gut microbiota-mediated mechanisms, but the influence of lipid-microbiota interaction on liver steatosis is largely unknown. We investigate the impact of dietary lipids on human gut microbiota composition and the effects of microbiota-lipid interactions on steatosis in male mice. In humans, low intake of saturated fatty acids (SFA) is associated with increased microbial diversity independent of fiber intake. In mice, poorly absorbed dietary long-chain SFA, particularly stearic acid, induce a shift in bile acid profile and improved metabolism and steatosis. These benefits are dependent on the gut microbiota, as they are transmitted by microbial transfer. Diets enriched in polyunsaturated fatty acids are protective against steatosis but have minor influence on the microbiota. In summary, we find that diets enriched in poorly absorbed long-chain SFA modulate gut microbiota profiles independent of fiber intake, and this interaction is relevant to improve metabolism and decrease liver steatosis. Here, Schoeler et al. investigate how interaction between dietary lipids and the gut microbiota affect hepatic steatosis and host metabolism, showing that dietary lipids impact the gut microbiota composition independent on fiber intake in humans and mice.
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| 8. |
- Sotak, Matus, et al.
(författare)
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Lipoxins reduce obesity-induced adipose tissue inflammation in 3D-cultured human adipocytes and explant cultures
- 2022
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:7
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Tidskriftsartikel (refereegranskat)abstract
- Adipose tissue inflammation drives obesity-related cardiometabolic diseases. Enhancing endogenous resolution mechanisms through administration of lipoxin A4, a specialized pro-resolving lipid mediator, was shown to reduce adipose inflammation and subsequently protects againstobesity-inducedsystemic disease inmice. Here, we demonstrate that lipoxins reduce inflammation in 3D-cultured human adipocytes and adipose tissue explants from obese patients. Approximately 50% of patients responded particularlywell to lipoxins by reducing inflammatory cytokines and promoting an anti-inflammatory M2 macrophage phenotype. Responding patients were characterized by elevated systemic levels of C-reactive protein, which causes inflammation in cultured human adipocytes. Responders appeared more prone to producing anti-inflammatory oxylipins and displayed elevated prostaglandin D2 levels, which has been interlinked with transcription of lipoxin-generatingenzymes. Using explant cultures, this study provides the first proof-of-concept evidence supporting the therapeutic potential of lipoxins in reducing human adipose tissue inflammation. Our data further indicate that lipoxin treatment may require a tailored personalized-medicine approach.
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| 9. |
- Vahkal, B., et al.
(författare)
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Review of Methodological Approaches to Human Milk Small Extracellular Vesicle Proteomics
- 2021
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Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Proteomics can map extracellular vesicles (EVs), including exosomes, across disease states between organisms and cell types. Due to the diverse origin and cargo of EVs, tailoring methodological and analytical techniques can support the reproducibility of results. Proteomics scans are sensitive to in-sample contaminants, which can be retained during EV isolation procedures. Contaminants can also arise from the biological origin of exosomes, such as the lipid-rich environment in human milk. Human milk (HM) EVs and exosomes are emerging as a research interest in health and disease, though the experimental characterization and functional assays remain varied. Past studies of HM EV proteomes have used data-dependent acquisition methods for protein detection, however, improvements in data independent acquisition could allow for previously undetected EV proteins to be identified by mass spectrometry. Depending on the research question, only a specific population of proteins can be compared and measured using isotope and other labelling techniques. In this review, we summarize published HM EV proteomics protocols and suggest a methodological workflow with the end-goal of effective and reproducible analysis of human milk EV proteomes.
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