| 1. |
- Almung, Magnus, et al.
(författare)
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I solitärens skugga : Nyttobyggnadens kreativa restaurering
- 2015
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Rapport (populärvet., debatt m.m.)abstract
- Ekonomibyggnader har alltid behövts för de huvudbyggnader som finns inom våra bevarade kulturmiljöer. Några nyttobyggnader uppskattas och används fortfarande, andra betraktas som problematiska överloppsbyggnader, många rivs. Alltför få har dokumenterats eller fått sin historia klarlagd vilket undanhållit viktig kunskap om samhällets framväxt. Vi vill synliggöra och betona vikten av att bevara och utveckla hela bebyggelsemiljöer, ofta med ett antal hus utöver huvudbyggnaden och tillhörande yttre miljö i staden eller på landet. Denna rapport visar kursdeltagarnas projektarbeten om nyttobyggnader. De har dokumenterat med traditionella och nya arbetsmetoder, inventerat och intervjuat, läst och besökt arkiv, värderat, analyserat och därefter föreslagit hur man ska ta hand om och utveckla nyttobyggnaderna i sina kulturmiljöer.
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| 2. |
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| 3. |
- Pandzic, Tatjana, et al.
(författare)
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Somatic PRDM2 c.4467delA mutations in colorectal cancers control histone methylation and tumor growth
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:58, s. 98646-98659
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Tidskriftsartikel (refereegranskat)abstract
- The chromatin modifier PRDM2/RIZ1 is inactivated by mutation in several forms of cancer and is a putative tumor suppressor gene. Frameshift mutations in the C-terminal region of PRDM2, affecting (A)8 or (A)9 repeats within exon 8, are found in one third of colorectal cancers with microsatellite instability, but the contribution of these mutations to colorectal tumorigenesis is unknown. To model somatic mutations in microsatellite unstable tumors, we devised a general approach to perform genome editing while stabilizing the mutated nucleotide repeat. We then engineered isogenic cell systems where the PRDM2 c.4467delA mutation in human HCT116 colorectal cancer cells was corrected to wild-type by genome editing. Restored PRDM2 increased global histone 3 lysine 9 dimethylation and reduced migration, anchorage-independent growth and tumor growth in vivo. Gene set enrichment analysis revealed regulation of several hallmark cancer pathways, particularly of epithelial-to-mesenchymal transition (EMT), with VIM being the most significantly regulated gene. These observations provide direct evidence that PRDM2 c.4467delA is a driver mutation in colorectal cancer and confirms PRDM2 as a cancer gene, pointing to regulation of EMT as a central aspect of its tumor suppressive action.
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| 4. |
- Bergman, Erik, et al.
(författare)
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BERT based natural language processing for triage of adverse drug reaction reports shows close to human-level performance
- 2023
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Ingår i: PLOS Digital Health. - : Public Library of Science (PLoS). - 2767-3170. ; 2:12
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Tidskriftsartikel (refereegranskat)abstract
- Post-marketing reports of suspected adverse drug reactions are important for establishing the safety profile of a medicinal product. However, a high influx of reports poses a challenge for regulatory authorities as a delay in identification of previously unknown adverse drug reactions can potentially be harmful to patients. In this study, we use natural language processing (NLP) to predict whether a report is of serious nature based solely on the free-text fields and adverse event terms in the report, potentially allowing reports mislabelled at time of reporting to be detected and prioritized for assessment. We consider four different NLP models at various levels of complexity, bootstrap their train-validation data split to eliminate random effects in the performance estimates and conduct prospective testing to avoid the risk of data leakage. Using a Swedish BERT based language model, continued language pre-training and final classification training, we achieve close to human-level performance in this task. Model architectures based on less complex technical foundation such as bag-of-words approaches and LSTM neural networks trained with random initiation of weights appear to perform less well, likely due to the lack of robustness that a base of general language training provides.
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| 5. |
- Bergquist, Helen, 1979-, et al.
(författare)
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Structure-Specific Recognition of Friedreich’s Ataxia (GAA)n Repeats by Benzoquinoquinoxaline Derivatives
- 2009
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Ingår i: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 10:16, s. 2629-2637
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Tidskriftsartikel (refereegranskat)abstract
- Expansion of GAA triplet repeats in intron 1 of the FXN gene reduces frataxin expression and causes Friedreich's ataxia. (GAA)nrepeats form non-B-DNA structures, including triple helix H-DNA and higher-order structures (sticky DNA). In the proposed mechanisms of frataxin gene silencing, central unanswered questions involve the characterization of non-B-DNA structure(s) that are strongly suggested to play a role in frataxin expression. Here we examined (GAA)nbinding by triplex-stabilizing benzoquinoquinoxaline (BQQ) and the corresponding triplex-DNA-cleaving BQQ-1,10-phenanthroline (BQQ-OP) compounds. We also examined the ability of these compounds to act as structural probes for H-DNA formation within higher-order structures at pathological frataxin sequences in plasmids. DNA-complex-formation analyses with a gel-mobility-shift assay and sequence-specific probing of H-DNA-forming (GAA)nsequences by single-strand oligonucleotides and triplex-directed cleavage demonstrated that a parallel pyrimidine (rather than purine) triplex is the more stable motif formed at (GAA)nrepeats under physiologically relevant conditions.
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| 6. |
- Björk, Jonas, et al.
(författare)
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Accuracy of GFR estimating equations combining standardized cystatin C and creatinine assays: a cross-sectional study in Sweden
- 2015
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 53:3, s. 403-414
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Tidskriftsartikel (refereegranskat)abstract
- Background: The recently established international cystatin C calibrator makes it possible to develop non-laboratory specific glomerular filtration rate (GFR) estimating (eGFR) equations. This study compares the performance of the arithmetic mean of the revised Lund-Malmo creatinine and CAPA cystatin C equations (MEAN(LM-REV+CAPA)), the arithmetic mean of the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) creatinine and cystatin C equations (MEAN(CKD-EPI)), and the composite CKD-EPI equation (CKD-EPICREA+CYSC) with the corresponding single marker equations using internationally standardized calibrators for both cystatin C and creatinine. Methods: The study included 1200 examinations in 1112 adult Swedish patients referred for measurement of GFR (mGFR) 2008-2010 by plasma clearance of iohexol (median 51 mL/min/1.73 m(2)). Bias, precision (interquartile range, IQR) and accuracy (percentage of estimates +/- 30% of mGFR; P-30) were compared. Results: Combined marker equations were unbiased and had higher precision and accuracy than single marker equations. Overall results of MEAN(LM-REV+CAPA)/MEAN(CKD-EPI)/CKD-EPICREA+CYSC were: median bias -2.2%/-0.5%/-1.6%, IQR 9.2/9.2/8.8 mL/min/1.73 m(2), and P-30 91.3%/91.0%/91.1%. The P-30 figures were about 7-14 -percentage points higher than the single marker equations. The combined equations also had a more stable performance across mGFR, age and BMI intervals, generally with P-30 >= 90% and never <80%. Combined equations reached P-30 of 95% when the difference between eGFR(CREA) and eGFR(CYSC) was <10% but decreased to 82% at a difference of >= 40%. Conclusions: Combining cystatin C and creatinine assays improves GFR estimations with P-30 >= 90% in adults. Reporting estimates of both single and combined marker equations in clinical settings makes it possible to assess the validity of the combined equation based on the agreement between the single marker equations.
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| 7. |
- Blomqvist, Kerstin, 1953-, et al.
(författare)
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What happens when you involve patients as experts? : a participatory action research project at a renal failure unit
- 2010
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Ingår i: Nursing Inquiry. - 1320-7881 .- 1440-1800. ; 17:4, s. 317-323
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Tidskriftsartikel (refereegranskat)abstract
- Although there is a trend towards developing health care in a patient-centred direction, changes are usually planned by the professionals without involving the patients. This paper presents an ongoing participatory action research project where patients with chronic renal failure, nurses at a specialist renal failure unit, a hospital manager and a researcher worked together to develop patient-centred care. The project combined the expertise of patients in their own experiences of living with a chronic condition with the professional expertise of nurses, the manager and the researcher. As the workload on the unit was uneven, the development work needed to be low in intensity but long-term. Based on a number of dialogues in focus groups, four main development areas were identified; access to test results, prerequisites for postponing the progress of the illness, general awareness and understanding of living with chronic renal failure, and family-focused care. A number of changes have been planned or implemented, such as developing a prototype for a web-based feed-back system, expanding patient education to newly diagnosed patients, steering the nurses' role towards a guiding and family-focused function, and planning a digital story-telling workshop. Involving committed people who have the mandate to change practices were prerequisites for success.
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| 8. |
- Blomqvist, Kerstin, et al.
(författare)
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What happens when you involve patients as experts? : a participatory action research project at a renal failure unit
- 2010
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Ingår i: Nursing Inquiry. - : Wiley-Blackwell Publishing Ltd. - 1320-7881 .- 1440-1800. ; 17:4, s. 317-323
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Tidskriftsartikel (refereegranskat)abstract
- Although there is a trend towards developing health care in a patient-centred direction, changes are usually planned by the professionals without involving the patients. This paper presents an ongoing participatory action research project where patients with chronic renal failure, nurses at a specialist renal failure unit, a hospital manager and a researcher worked together to develop patient-centred care. The project combined the expertise of patients in their own experiences of living with a chronic condition with the professional expertise of nurses, the manager and the researcher. As the workload on the unit was uneven, the development work needed to be low in intensity but long-term. Based on a number of dialogues in focus groups, four main development areas were identified; access to test results, prerequisites for postponing the progress of the illness, general awareness and understanding of living with chronic renal failure, and family-focused care. A number of changes have been planned or implemented, such as developing a prototype for a web-based feed-back system, expanding patient education to newly diagnosed patients, steering the nurses' role towards a guiding and family-focused function, and planning a digital story-telling workshop. Involving committed people who have the mandate to change practices were prerequisites for success.
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| 9. |
- Che, Karlhans F, et al.
(författare)
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HIV-1 impairs in vitro priming of naïve T cells and gives rise to contact-dependent suppressor T cells
- 2010
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 40:8, s. 2248-2258
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Tidskriftsartikel (refereegranskat)abstract
- Priming of T cells in lymphoid tissues of HIV-infected individuals occurs in the presence of HIV-1. DC in this milieu activate T cells and disseminate HIV-1 to newly activated T cells, the outcome of which may have serious implications in the development of optimal antiviral responses. We investigated the effects of HIV-1 on DC-naïve T-cell interactions using an allogeneic in vitro system. Our data demonstrate a dramatic decrease in the primary expansion of naïve T cells when cultured with HIV-1-exposed DC. CD4(+) and CD8(+) T cells showed enhanced expression of PD-1 and TRAIL, whereas CTLA-4 expression was observed on CD4(+) T cells. It is worth noting that T cells primed in the presence of HIV-1 suppressed priming of other naïve T cells in a contact-dependent manner. We identified PD-1, CTLA-4, and TRAIL pathways as responsible for this suppresion, as blocking these negative molecules restored T-cell proliferation to a higher degree. In conclusion, the presence of HIV-1 during DC priming produced cells with inhibitory effects on T-cell activation and proliferation, i.e. suppressor T cells, a mechanism that could contribute to the enhancement of HIV-1 pathogenesis.
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| 10. |
- Davis, Hope C., et al.
(författare)
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Time between anterior cruciate ligament injury and reconstruction and cartilage metabolism six-months following reconstruction
- 2018
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Ingår i: Knee. - : Elsevier BV. - 0968-0160. ; 25:2, s. 296-305
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Tidskriftsartikel (refereegranskat)abstract
- Background: To determine the association between time from injury to ACL reconstruction (TimeInjury-ACLR) and biochemical markers of cartilage metabolism and inflammation six months following ACL reconstruction (ACLR). Methods: Individuals with a unilateral ACL injury were enrolled at initial presentation in the orthopedic clinic; blood was collected six months following ACLR. Enzyme-linked immunosorbent assays were used to analyze the ratio of serum concentrations of type-II collagen breakdown (C2C) to synthesis (CPII), plasma matrix metalloproteinase-3 (MMP-3), interleukin-6 (IL-6), and serum aggrecan neoepitope (ARGS). We used separate linear regressions to assess associations between biochemical markers and TimeInjury-ACLR. Results: Twenty-two participants (50% females, mean [SD], age 21.9 [4.5] years old; BMI 23.8 [2.6] kg/m2) completed the study. TimeInjury-ACLR ranged from nine to 67days (31.0 [14.4days]). Greater TimeInjury-ACLR predicted greater serum C2C:CPII ratios six months following ACLR (C2C:CPII=0.15 [0.02], R2 =0.213, P=0.030). Males (R2 =0.733, P=0.001) but not females (R2 =0.030, P=0.609) demonstrated a significant association between greater C2C:CPII and TimeInjury-ACLR at the six-month follow-up exam. TimeInjury-ACLR did not associate with IL-6, MMP-3, or ARGS at six months. Conclusions: Greater time between injury and ACL reconstruction was associated with greater serum C2C:CPII six months following ACLR in males but not females, and IL-6, MMP-3, and ARGS levels were not associated with TimeInjury-ACLR in males or females. The time between ACL injury and ACLR may affect collagen metabolism in males and should be further investigated in a larger study along with other patient-relevant outcomes.
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| 11. |
- Erlandsson, Johan, et al.
(författare)
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Macro- and mesoporous nanocellulose beads for use in energy storage devices
- 2016
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Ingår i: APPLIED MATERIALS TODAY. - : Elsevier. - 2352-9407. ; 5, s. 246-254
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Tidskriftsartikel (refereegranskat)abstract
- Chemically cross-linked, wet-stable cellulose nanofibril (CNF) aerogel beads were fabricated using a novel procedure. The procedure facilitated controlled production of millimetre-sized CNF aerogel beads without freeze-drying or critical point drying, while still retaining a highly porous structure with low density. The aerogel beads were mechanically robust in the dry state, supporting loads of 1.3 N at 70% compression, even after being soaked in water and re-dried. Furthermore, they displayed both a good stability in water and a remarkably good shape recovery after wet compression. Owing to the stability in water, the entire surface of the highly porous aerogel beads could be successfully functionalized with polyelectrolytes and carboxyl-functionalized single-wall carbon nanotubes (CF-SWCNTs) using the Layer-by-Layer technique, introducing a significant electrical conductivity (1.6 mS/cm) to the aerogel beads. The functionalized, electrically conducting aerogel beads could carry as much as 2 kA/cm(2) and act as electrodes in a supercapacitor displaying a stabilized charge storage capacity of 9.8 F/g after 50 charging-discharging cycles.
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| 12. |
- Figueroa, Ricardo, et al.
(författare)
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A transmembrane inner nuclear membrane protein in the mitotic spindle
- 2010
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Ingår i: Nucleus (Austin). - 1949-1042. ; 1:3, s. 249-253
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Tidskriftsartikel (refereegranskat)abstract
- We have recently characterized a novel transmembrane protein of the inner nuclear membrane of mammalian cells. The protein has two very interesting features. First, despite being an integral membrane protein it is able to concentrate in the membranes colocalizing with the mitotic spindle in metaphase and anaphase. Hence, the protein was named Samp1, Spindle associated membrane protein 1. Secondly, it displays a functional connection to centrosomes. This article discusses various aspects of Samp1 in relation to possible cellular function(s).
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| 13. |
- Forsberg, Linda, et al.
(författare)
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A comparison of administration and discontinuation of Natalizuamb in Sweden over time for patients treated with either sucutaneous (SC) or intravenous (IV) administration methods since July 2021
- 2023
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 29:Suppl. 3, s. 617-617
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing multiple sclerosis (RMS) originally launched as an intravenous (IV) therapy in Sweden in August 2006. A new subcutaneous (SC) administration method for NTZ was launched in April 2021.Objectives/Aims: To investigate how the administration of NTZ has evolved in Sweden since the introduction of SC NTZ in 2021, and to explore potential differences in treatment discontinuation patterns between the SC or IV administration modalities.Methods: Descriptive data will be presented from the “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) study cohort. Data is collected from the nationwide Swedish Neuro Registry (NeuroReg). The drug survival is assessed using the Kaplan Meier one-year drug survival curve and Breslow Wilcoxon test of equality distribution.Results: A total of 4011 NTZ participants were included in the IMSE 1 study from August 2006 until March 2023 (72% female; mean age 36 years; 80% RRMS; mean treatment duration 49 months), including 295 since July 2021, of which 264 had available data on method of administration. In this cohort, 109 (41%) initiated IV NTZ, of which 16 (15%) later switched to SC administration, and 155 (59%) initiated treatment with SC NTZ. The distribution between administration methods altered over time, where IV was more common in Q3 2021 (70%) and then successively dropped to 31% in Q1 2023.The mean age at treatment start was 36 years (35 for IV and 37 for SC) and 69% (70% IV, 68% SC) were female.Out of 264 participants, 73 (28%) later discontinued treatment. Discontinuation was numerically more common in the IV group compared with the SC group, but differences in the one-year drug survival rate did not reach statistical significance.The most common reason for discontinuation in the IV group was “other reason; unspecified” followed by positive JC-virus serology (JCV+). In the SC group JCV+ was the most common reason for discontinuation. Four patients discontinued due to neutralizing NTZ antibodies; 2 in each group.Conclusion: The SC administration has become the preferred administration method for NTZ since its launch in the spring of 2021, with 59% of NTZ treatment initiations being administered using SC method. We did not find significant differences in discontinuation rates between the two administration methods. Longer observation periods will be needed to assess possible differences in tolerability and treatment adherence between the two administration modalities.
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| 14. |
- Forsberg, Linda, et al.
(författare)
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Improved clinical outcomes in patients treated with Natalizumab for at least 11 years - Real-world data from a Swedish national post-marketing surveillance study (IMSE 1)
- 2023
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 29:Suppl. 3, s. 965-966
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing multiple sclerosis (RMS). Post-marketing surveillance is important to evaluate the long-term safety and effectiveness in a real-world setting. To this end the “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) was initiated upon launch of NTZ in Sweden (Aug 2006).Objectives/Aims: To follow-up the long-term effectiveness and safety of NTZ in a real-world setting.Methods: Adverse events (AEs), Serious AEs (SAEs), John Cunningham virus status (JCV) and clinical effectiveness measures; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT) and Multiple Sclerosis Impact Scale (MSIS-29) data were collected from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test.Results: A total of 4011 NTZ patients were included in the IMSE 1 study from August 2006 until March 2023 (72% female; mean age 36 years; 80% RRMS; mean treatment duration 52 months) and 249 had been treated for at least 132 months. Of the 132-month cohort, 75% were female, the mean age was 36 years, 88% had RRMS, and the mean treatment duration was 160 months. The majority were treated with interferons and glatiramer acetate prior to NTZ (68%), where 30% (74/249) discontinued NTZ treatment; 43% (32/74) due to being JCV positive (JCV+), with a mean JCV index of 1.1±0.9 (n=66). Annualized relapse rates dropped from 0.40 in the year before treatment start to 0.04 during treatment, where 68% were entirely free of relapses and 21% had only 1 relapse during the entire treatment period (17% missing data). All clinical effectiveness measures, except EDSS showed statistically significant improvement between baseline and 132 months (p<0.05).From the entire IMSE1 cohort (N=4011), 132 SAEs have been reported to the Swedish MPA, including 9 cases (2 fatal) of progressive multifocal leukoencephalopathy (PML) of which 8 occurred between 2008 and 2012, and one in 2018.Conclusion: NTZ is generally well tolerated and displays sustained effectiveness regarding cognitive, physical and psychological measures, as well as relapse-control. Introduction of JCV testing has led to fewer treated JCV+ patients, likely explaining a drastically reduced incidence of PML.
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| 15. |
- Galgani, Mario, et al.
(författare)
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Meta-Immunological Profiling of Children With Type 1 Diabetes Identifies New Biomarkers to Monitor Disease Progression
- 2013
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:7, s. 2481-2491
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes is characterized by autoimmurte destruction of pancreatic beta-cells in genetically susceptible individuals. Triggers of islet autoimmunity, time course, and the precise mechanisms responsible for the progressive beta-cell failure are not completely understood. The recent escalation of obesity in affluent countries has been suggested to contribute to the increased incidence of type 1 diabetes. Understanding the link between metabolism and immune tolerance could lead to the identification of new markers for the monitoring of disease onset and progression. We studied several immune cell subsets and factors with high metabolic impact as markers associated with disease progression in high-risk subjects and type 1 diabetic patients at onset and at 12 and 24 months after diagnosis. A multiple correlation matrix among different parameters was evaluated statistically and assessed visually on two-dimensional graphs. Markers to predict residual beta-cell function up to 1 year after diagnosis were identified in multivariate logistic regression models. The meta-immunological profile changed significantly over time in patients, and a specific signature that was associated with worsening disease was identified. A multivariate logistic regression model measuring age, BMI, fasting C-peptide, number of circulating CD3(+)CD16(+)CD56(+) cells, and the percentage of CD1c(+)CD19(-)CD14(-)CD303(-) type 1 myeloid dendritic cells at disease onset had a significant predictive value. The identification of a specific meta-immunological profile associated with disease status may contribute to our understanding of the basis of diabetes progression.
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| 16. |
- Grubb, Anders, et al.
(författare)
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Generation of a new cystatin C-based estimating equation for glomerular filtration rate by use of 7 assays standardized to the international calibrator
- 2014
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 60:7, s. 974-986
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Many different cystatin C-based equations exist for estimating glomerular filtration rate. Major reasons for this are the previous lack of an international cystatin C calibrator and the nonequivalence of results from different cystatin C assays.METHODS:Use of the recently introduced certified reference material, ERM-DA471/IFCC, and further work to achieve high agreement and equivalence of 7 commercially available cystatin C assays allowed a substantial decrease of the CV of the assays, as defined by their performance in an external quality assessment for clinical laboratory investigations. By use of 2 of these assays and a population of 4690 subjects, with large subpopulations of children and Asian and Caucasian adults, with their GFR determined by either renal or plasma inulin clearance or plasma iohexol clearance, we attempted to produce a virtually assay-independent simple cystatin C-based equation for estimation of GFR.RESULTS:We developed a simple cystatin C-based equation for estimation of GFR comprising only 2 variables, cystatin C concentration and age. No terms for race and sex are required for optimal diagnostic performance. The equation, [Formula: see text] is also biologically oriented, with 1 term for the theoretical renal clearance of small molecules and 1 constant for extrarenal clearance of cystatin C.CONCLUSIONS:A virtually assay-independent simple cystatin C-based and biologically oriented equation for estimation of GFR, without terms for sex and race, was produced.
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| 17. |
- Gudise, Santhosh, et al.
(författare)
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Samp1 is functionally associated with the LINC complex and A-type lamina networks
- 2011
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 124, s. 2077-2085
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Tidskriftsartikel (refereegranskat)abstract
- The transmembrane inner nuclear membrane (INM) protein Samp1 is required for anchoring centrosomes near the nuclei. Using high-resolution fluorescence microscopy we show that Samp1 is distributed in a distinct and characteristic pattern in the nuclear envelope (NE), where it partially colocalizes with the LINC complex protein Sun1. By studying the localization of Samp1 deletion mutants and fusion proteins, we conclude that the cysteine-rich N-terminal half of Samp1 is nucleoplasmically exposed and is responsible for targeting to the INM. It contains four conserved CxxC motifs with the potential to form zinc fingers. The distribution of cysteine-to-alanine substitution mutants, designed to prevent zinc finger formation, showed that NE localization of Samp1 depends on intact CxxC motifs. Overexpression of Samp1 zinc finger mutants produced an abnormal dominant phenotype characterized by disrupted organization of a selective subset NE proteins, including emerin, Sun1, endogenous Samp1 and, in some cases, lamin A/C, but not lamin B, Sun2 or nucleoporins. Silencing of Samp1 expression showed that emerin depends on Samp1 for its correct localization in the NE. Our results demonstrate that Samp1 is functionally associated with the LINC complex protein Sun1 and proteins of the A-type lamina network.
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| 18. |
- Gupta, Anindya, et al.
(författare)
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Weakly-supervised prediction of cell migration modes in confocal microscopy images using bayesian deep learning
- 2020
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Ingår i: 2020 IEEE 17th International Symposium on Biomedical Imaging (ISBI). - 9781538693308 - 9781538693315 ; , s. 1626-1629
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Konferensbidrag (refereegranskat)abstract
- Cell migration is pivotal for their development, physiology and disease treatment. A single cell on a 2D surface can utilize continuous or discontinuous migration modes. To comprehend the cell migration, an adequate quantification for single cell-based analysis is crucial. An automatized approach could alleviate tedious manual analysis, facilitating large-scale drug screening. Supervised deep learning has shown promising outcomes in computerized microscopy image analysis. However, their implication is limited due to the scarcity of carefully annotated data and uncertain deterministic outputs. We compare three deep learning models to study the problem of learning discriminative morphological representations using weakly annotated data for predicting the cell migration modes. We also estimate Bayesian uncertainty to describe the confidence of the probabilistic predictions. Amongst three compared models, DenseNet yielded the best results with a sensitivity of 87.91%±13.22 at a false negative rate of 1.26%±4.18.
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| 19. |
- Hederström, Veronica, et al.
(författare)
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Dispersal and spatiotemporal distribution of Protapion fulvipes in white clover fields : implications for pest management
- 2022
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Ingår i: Journal of Pest Science. - : Springer Science and Business Media LLC. - 1612-4758 .- 1612-4766. ; 95:2, s. 917-930
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Tidskriftsartikel (refereegranskat)abstract
- Yield loss caused by insect pests remains a substantial problem in agriculture. Chemical control, with potential negative effects on non-target organisms, is still the main tool for pest management. For pest species with limited dispersal capacity, rotation of the crop in time and space has potential as an alternative management measure. This is particularly important in organic farming, where most agrochemicals are prohibited, but also relevant as a complementary pest management strategy in conventional agriculture. Clover is an important crop used for animal feed and as green manure; however, seed-eating weevils can severely limit the seed yield. We hypothesized that the previous year’s clover seed fields constitute the major sources of weevil pests. Consequently, a greater distance to, and a smaller pest load from, this source should reduce the number of weevils colonizing the new seed fields. To map population dynamics and dispersal range of Protapion fulvipes, an economically important seed weevil specialized on white clover, we conducted field studies over four years in 45 white clover seed fields. We found that P. fulvipes overwinters close to its source field and disperses to new fields in early spring the following year. Pest abundance increased with pest load in the previous year’s seed field, but decreased by 68% per km distance to the previous year’s field. Thus, separation of seed production fields between years by 2–3 km would create a spatiotemporal pest management tool to reduce the pest infestation below the estimated economic injury level.
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| 20. |
- Hederström, Veronica, et al.
(författare)
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Do plant ploidy and pollinator tongue length interact to cause low seed yield in red clover?
- 2021
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Ingår i: Ecosphere. - : Wiley. - 2150-8925. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- The loss of long-tongued pollinator species and dominance of a few short-tongued generalist species, related to agricultural intensification in recent decades, may have consequences for the quality, quantity, and stability of yields in insect-pollinated crops. Interestingly, the changes in pollinator community coincide with an increase in poor and variable seed yield in red clover, an important crop for green manure and forage production. However, to date we lack a holistic understanding of the factors that drive seed yield in red clover crops. To remedy this, we related plant and pollinator traits to pollinator visitation, behavior, and pollination efficiency in four diploid and five tetraploid red clover cultivars during three years in a common garden setting. Tetraploid cultivars produced 52% fewer seeds and 41% lower seed weight per flower head compared with diploid cultivars. They also had fewer flower heads per plant, larger florets, and lower pollen viability than diploids. Pollinator species with shorter tongues visited diploid cultivars more frequently than tetraploid cultivars. Pollinator species with longer tongues deposited more pollen and showed higher pollination efficiency in terms of seeds produced after single visits. Our results suggest that while both diploid and tetraploid red clover cultivars benefit from the presence of longer-tongued pollinator species, seed yield in tetraploid cultivars may be more sensitive to the loss of these bumble bee species in intensively cultivated agricultural landscapes.
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| 21. |
- Hederström, Veronica, et al.
(författare)
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White clover pollinators and seed set in relation to local management and landscape context
- 2024
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Ingår i: Agriculture, Ecosystems and Environment. - 0167-8809 .- 1873-2305. ; 365
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Tidskriftsartikel (refereegranskat)abstract
- Bees are declining, which is worrisome since they both have intrinsic conservation value and play a major role as pollinators in both natural and managed ecosystems. Land use change and lack of suitable habitats are often suggested as driving forces of bee decline. To propose mitigation measures to halt bee decline, it is important to understand how land use relates to bee abundance and diversity, and to explore consequences for their provision of pollination services. White clover, Trifolium repens, is an outcrossing mass-flowering crop, which could serve as an abundant, although ephemeral, food resource for bees. We investigated how the bee community in 39 fields of white clover grown for seed, related to local field management (organic, conventional without insecticides and conventional with insecticides) and landscape context (proportion semi-natural land), and how this pollinator community related to white clover seed set. The honey bee, Apis mellifera, was the most commonly observed bee species, and two generalist bumble bee species, Bombus terrestris and B. lapidarius, were the subsequently most common. We observed fewer non-Apis bees, and a lower bee species richness in organic white clover seed fields compared to conventional fields independent of insecticide treatment. Bee species richness in both conventional and organic fields were positively related to the proportion of semi-natural land in the landscape, likely because of a larger species pool in such landscapes. Initial seed set in immature inflorescences was positively related to bee abundance, whereas final seed set in mature inflorescences was unrelated to bee abundance, possibly as a consequence of seed-eating weevils consuming a large proportion of the seeds. We conclude that both bee visitation and seed set in white clover benefit from conventional management and that landscapes rich in semi-natural habitats will make future crop production more resilient. The observed positive relationship between bee abundance and initial seed set suggests that if we can mitigate pest impacts and increase bee abundance in clover seed fields, the final seed yield can be increased. Thus, bee decline should be considered and mitigated both to maintain biodiversity in general and for crop seed production specifically.
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| 22. |
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| 23. |
- Huerta Buitrago, Belinda, et al.
(författare)
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Ecotoxicological characterization of sediments from a constructed wetland system for treatment of landfill leachate
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Ingår i: Ecological Engineering. - 0925-8574 .- 1872-6992.
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Tidskriftsartikel (refereegranskat)abstract
- In this study a bioassay test battery was used to assess the toxicity and the presence of dioxin-like compounds in 8 sediment samples obtained from a surface flow wetland system for treatment of municipal landfill leachate. The wetland system consists of sediment traps at the inlet followed by 10 ponds connected with overflows. In the 6 day solid phase microbiotest with the sediment-dwelling crustacean Heterocypris incongruens both acute and chronic effects were observed with a gradual decrease and loss of toxicity with treatment in the wetland system. Some samples showed low toxicity in pore water but no toxicity was observed in the whole sediment when assessed with Aliivibrio fischeri (Vibro fischeri). No genotoxicity was detected in the umu test with or without metabolic activation. The toxicity response in the H4IIE- luc test evaluating the presence of dioxin-like compounds was significantly higher in the samples closer to the inlet of the system; the first sample was found to be a 177 times more potent Ah-receptor (AhR) inducer in comparison to the other samples. In conclusion; no toxicity, low levels of dioxin-like compounds and low levels of heavy metals were detected in the sediments from the last part of the wetland. The results indicate that the surface flow wetland system has an effective design for concentrating toxic substances associated with particulate matter in a small area of the wetland. The battery of tests used provided a comprehensive assessment of the ecotoxicological status of this aquatic system.
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| 24. |
- Huerta Buitrago, B., et al.
(författare)
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Hazard assessment of sediments from a wetland system for treatment of landfill leachate using bioassays
- 2013
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Ingår i: Ecotoxicology and Environmental Safety. - Maryland Heights, MO : Elsevier BV. - 0147-6513 .- 1090-2414. ; 97, s. 255-262
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Tidskriftsartikel (refereegranskat)abstract
- Four bioassays were used in this study for the hazard assessment of sediments from sediment traps and several ponds in a treatment wetland for landfill leachate at Atleverket, Sweden. In the 6-day solid phase microbiotest with the sediment-dwelling crustacean Heterocypris incongruens both acute and chronic effects were observed with a gradual decrease and loss of toxicity with treatment in the wetland system. Some samples showed a low toxicity in porewater and only one sample was weakly toxic in the whole sediment test when assessed with Aliivibrio fischeri (Vibro fischeri). No genotoxicity was detected in the umu test. The toxicity response in the H4IIE- luc test evaluating the presence of dioxin-like compounds was considerably higher in the samples from the sediment traps. The hazard of the sediment therefore appears to be highest in the sediment traps and pond 1 with the methods employed. The result indicates that the wetland system has a design supporting the concentration and sequestration of toxic substances in the first part of the wetland. Based upon the results we suggest that hazard assessment of sediments from other treatment wetlands for landfill leachate should be conducted.
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| 25. |
- Jafferali, Mohammed Hakim, et al.
(författare)
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MCLIP, an effective method to detect interactions of transmembrane proteins of the nuclear envelope in live cells
- 2014
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Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736 .- 1879-2642 .- 0006-3002. ; 1838:10, s. 2399-2403
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Tidskriftsartikel (refereegranskat)abstract
- Investigating interactions of proteins in the nuclear envelope (NE) using co-immunoprecipitation (Co-IP) has previously been difficult or even impossible due to their inherent resistance to extraction. We have developed a novel method, MCLIP (Membrane protein Cross-Link ImmunoPrecipitation), which takes advantage of a cell permeable crosslinker to enable effective detection and analysis of specific interactions of NE proteins in live cells using Western blot. Using MCLIP we show that, in U2OS cells, the integral inner nuclear membrane protein Samp1 interacts with Lamin B1, the LINC (Linker of nucleoskeleton and cytoskeleton) complex protein, Sun1 and the soluble small GTPase Ran. The results show that the previously detected in vitro interaction between Samp1 and Emerin also takes place in live cells. In vitro pull down experiments show, that the nucleoplasmic domains of Samp1 and Emerin can bind directly to each other. We also, show that MCLIP is suitable to coprecipitate protein interactions in different stages of the cell cycle.
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| 26. |
- Jägare, Veronica
(författare)
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A Challenge-driven Framework for Innovations in Railways
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The railway is often perceived as an industry where new technology is not utilised to its full potential. However, the future of the railway and its ability to respond to future transportation demands lies in its ability to adopt, adapt, implement, and integrate emerging technology. These technologies are expected to lead to, e.g. intelligent asset lifecycle management with a whole-life asset approach and digital railway industry supply chain management. The technology transformation and digitalisation affect not only the technical systems, e.g. railway infrastructure and rolling stock, but also regulations, organisations, processes, and individuals. The railway industry needs to recognise the challenges and define strategies, which enable the successful implementation of innovations in railway. Thus, the purpose of this research work is to study, explore, and investigate how implementation of innovations in a multi-stakeholder environment such as railway maintenance, can be facilitated through a systematic approach. Further, the main objective of this research is to develop and provide, a challenge-driven framework that can be used to facilitate implementation of innovations in the Swedish railway. To achieve the purpose of this research, nine (9) descriptive and exploratory case studies have been carried out. In these case studies, issues and challenges have been identified, related to: a) Lead times; b) Complex multi-stakeholder environment; c) Business incentives; d) Governance for data sharing; e) Regulations and maintenance; f) Technology; g) Assessment of innovations; h) Business models; i) Responsibilities, and j) Implementation.To overcome the identified challenges, several artefacts have been developed and provided in this research, i.e. a) A challenge-driven mission-based framework; b) A methodology for evaluating innovations; c) Strategies and guidelines for data governance; d) Strategies and guidelines for innovation in maintenance contracts; and e) Railway domain systemic aspects for the implementation pathway. The findings and artefacts of this study may be used as a framework and a road map in any industry by providing scientific guidance in the implementation of innovations. Some of the expected benefits for organisations are: a) Reduced development and production costs; b) Increased efficiency in testing, implementing, and utilising existing innovations; c) Increased awareness in data sharing; and d) Increased implementation support. Furthermore, in the context of railway maintenance, the artefacts from this study are expected to improve the overall effectiveness and efficiency through facilitating the implementation of innovations that support digitalisation of railway maintenance. The digitalisation of railway maintenance enables fact-based decision support utilising enhanced analytics aimed for nowcasting and forecasting. These capabilities will lead to: a) Improved knowledge and information exchange between railway stakeholders to enable efficient asset management; b) Enhanced condition monitoring; c) Improved risk management; and d) Improved sustainability.
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| 27. |
- Jägare, Veronica, et al.
(författare)
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Change management in digitalised operation and maintenance of railway
- 2019
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Ingår i: PROCEEDINGS: International Heavy Haul Association Conference June 2019. - 9780911382716 - 9780911382709 ; , s. 904-911
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Konferensbidrag (refereegranskat)abstract
- Globally, railway is experiencing a major technology transformation (or paradigm shift), triggered by the enhanced utilisation of digital technology. This technological transformation affects not only the technical systems, i.e. railway infrastructure and rolling stock, but also regulations, organisations, processes,and individuals. Hence, hardware, software, but also liveware (i.e. humans) are affected. Today, the digitalisation of railway is characterised by digital services. There are also a range of challenges, e.g. data acquisition,transformation, modelling, processing, visualisation, safety, security, quality, and information assurance. To deal with these challenges, the railway industry needs to define strategies, which enable a smooth transformation of the existing configuration to a digitalised system. Digital railway requires a holistic change management approach based on system-of-systems thinking and a set of appropriate technologies and methodologies. The railway digitalisation strategy should be based on systematic risk management that address aspects of, e.g., information security, traffic safety and project risk. In addition, managing changes for a digitalised railway effectively and efficiently also requires a framework for aspects such as needs finding, requirement identification, and impact of changes for individual, teams and organisation. In this work a major case studywithin the ePilot, has been performed in context of the operation and maintenance processes of the Swedish railway. Therefore, this paper aims to propose a framework for implementing innovations and driving change in a digitalised railway.
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| 28. |
- Koller, Volkmar, et al.
(författare)
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Critical Step in the HCl Oxidation Reaction over Single-Crystalline CeO2-x(111) : Peroxo-Induced Site Change of Strongly Adsorbed Surface Chlorine
- 2023
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Ingår i: ACS Catalysis. - 2155-5435. ; 13:19, s. 12994-13007
-
Tidskriftsartikel (refereegranskat)abstract
- The catalytic oxidation of HCl by molecular oxygen (Deacon process) over ceria allows the recovery of molecular chlorine from the omnipresent HCl waste produced in various industrial processes. In previous density functional theory (DFT) model-calculations by Amrute et al. [ J. Catal. 2012, 286, 287−297.], it was proposed that the most critical reaction step in this process is the displacement of tightly bound chlorine at a vacant oxygen position on the CeO2(111) surface (Clvac) toward a less strongly bound cerium on-top (Cltop) position. This step is highly endothermic by more than 2 eV. On the basis of a dedicated model study, namely the reoxidation of a chlorinated single-crystalline Clvac-CeO2-x(111)-(Formula Presented × Formula Presented)R30° surface structure, we provide in situ synchrotron-based spectroscopic data (high resolution core level spectroscopy (HRCLS) and X-ray adsorption near edge structure (XANES)) for this oxygen-induced dechlorination process. Combined with theoretical evidence from DFT calculations, the Clvac → Cltop displacement reaction is predicted to be induced by an adsorbed peroxo species (O22-), making the displacement step concerted and exothermic by 0.6 eV with an activation barrier of only 1.04 eV. The peroxo species is shown to be important for the reoxidation of Clvac-CeO2-x(111) and is considered essential for understanding the function of ceria in oxidation catalysis.
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| 29. |
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| 30. |
- Larsson, Martin, et al.
(författare)
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Prehospital exenatide in hyperglycemic stroke : A randomized trial
- 2019
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Ingår i: Acta Neurologica Scandinavica. - Copenhagen, Denmark : Munksgaard Forlag. - 0001-6314 .- 1600-0404. ; 140:6, s. 443-448
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Hyperglycemia is a predictor for poor stroke outcome. Hyperglycemic stroke patients treated with thrombolysis have an increased risk of intracranial hemorrhage. Insulin is the gold standard for treating hyperglycemia but comes with a risk of hypoglycemia. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are drugs used in type 2 diabetes that have a low risk of hypoglycemia and have been shown to exert neuroprotective effects. The primary objective was to determine whether prehospital administration of the GLP-1RA exenatide could lower plasma glucose in stroke patients. Secondary objective was to study tolerability and safety.MATERIALS & METHODS: Randomized controlled trial comparing exenatide administrated prehospitally with a control group receiving standard care for hyperglycemia. Patients with Face Arm Speech Test ≥1 and glucose ≥8 mmol/L were randomized. Glucose was monitored for 24 hours. All adverse events were recorded.RESULTS: Nineteen patients were randomized, eight received exenatide. An interim recruitment failure analysis with subsequent changes of the protocol was made. The study was stopped prematurely due to slow inclusion. No difference was observed in the main outcome of plasma glucose at 4 hours, control vs exenatide (mean, SD); 7.0 ± 1.9 vs 7.6 ± 1.6; P = .56). No major adverse events were reported.CONCLUSIONS: We found no evidence that prehospital exenatide had effect on hyperglycemia. However, it was given without adverse events in this study with limited sample size that was prematurely stopped due to slow inclusion.
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| 31. |
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| 32. |
- Larsson, Veronica, et al.
(författare)
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CLADCOMS- CLADribine tablets long-term Control Of MS - a post-marketing investigator driven study
- 2023
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 29:Suppl. 3, s. 968-969
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Cladribine is a deoxyadenosine analogue prodrug that induces immune reconstitution by selectively targeting B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for patients with relapsing multiple sclerosis (RMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. CLADCOMS (CLADribine tablets long-term Control Of MS) is a post-marketing investigator driven study. Here we report two year prospectively obtained data on the first 100 patients included in the study until April 2021.Objectives/Aims: To investigate number of patients free of disease activity until April 2023 among the first 100 RMS patients included.Methods: CLADCOMS includes patients with RMS from eight academic neurology clinics of Sweden starting Cladribine treatment after 23rd of March 2018. Data was prospectively registered in the Swedish Neuroregistry using highly structured yearly follow-up routines. Descriptive data on relapses, MRI activity, and Patient Reported Outcome Measures from the first 100 patient included in the study were obtained from the registry.Results: By April 2023, 206 patients were included in the CLADCOMS study. In April 2021 the first 100 patients had entered the study including 30% treatment naïve, 26% switched from natalizumab, 10% from dimethyl fumarate and 7% from rituximab. After the first two years after treatment initiation 87% were relapse free. MRI-activity during the first two years after treatment initiation will be analyzed.Analysis of CD19+ B-cells counts over time showed a significant drop from baseline before first dose (0.38x109/L ±0.68) to year one (0.15x109/L ±0.12) and year two (0.13x109/L ±0.09). The proportion of memory B-cells dropped from 11.8% ±9.33% at baseline to 3.0% ±2.8% after the first year and to 2.6% ±2.4% after the second year of treatment. The proportions of naïve B-cells raised over time from 61% ±18.3% at baseline to 76.8% ±18.7 year one and 78.6% ±12.3 after two years of treatment.Conclusion: CladT treatment demonstrates clinical stability during the first two years after treatment initiation. The unique immune depletion helps to explain the durability of effects of Cladribine. However, continued follow-up is needed to assess the effectiveness and safety of treatment with Cladribine to investigate time to disease re-activation after full treatment.
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| 33. |
- Larsson, Veronica, et al.
(författare)
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Clinical Effectiveness and Safety of Cladribine Tablets for Patients Treated at least 24 Months in the Swedish post-market surveillance study "Immunomodulation and Multiple Sclerosis Epidemiology 10"(IMSE 10)
- 2023
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 29:Suppl. 3, s. 616-616
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Cladribine is a deoxyadenosine analogue prodrug targeting proliferating B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for patients with remitting multiple sclerosis (RMS). CladT is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology substudy 10” (IMSE 10).Objectives/Aims: To assess safety and effectiveness of CladT with focus on 24 months treatment outcomes.Methods: Data on Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life -5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) scores, and relapses and Adverse Events (AEs) were collected from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures and relapse rates were assessed using Wilcoxon Signed Rank Test.Results: A total of 287 CladT exposed Persons with MS (PwMS) have been included in IMSE 10 since the launch of CladT in April 2018. In this cohort 90.6% remained with CladT while 27 patients (9%) discontinued treatment at any time after initiation. The most common reason for discontinuation was lack of effect (78%). A total of 24 AEs were reported to the Swedish Medical Products Agency, of which 10 were serious. The most common AE reported were infection and infestation.A total of 137 patients had CladT exposure for ⩾24 months of which 30 % being treatment naïve, 19% switched from Tysabri, 10 % from dimethyl fumarate and 7% from rituximab, prior CLadT treatment. In this cohort 91.9% remained with CladT. The ⩾24 months’ cohort demonstrated clinical stability with a non-significant trend for improvement in mean MSSS, SDMT, MSIS-29 Psychological/Physical scores compared with baseline. All other outcomes remained stable. The mean annual relapse rate (ARR) decreased significantly (p<0.05) during all treatment years compared to the ARR one-year prior treatment.Lymphocyte levels decreased from a mean of 1.9 x 109/L at treatment start to 1.11 x 109/L at 12 Months and 0.87 x 109/L at 24 months of treatment.Conclusion: Most PwMS exposed for ⩾24 months to CladT display clinical stability and a tendency for improvement compared with baseline in several of the investigated outcomes. Longer observation times will be needed to assess the effectiveness and safety of CladT beyond 24 month exposure.
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| 34. |
- Larsson, Veronica J., 1980-
(författare)
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Characterization of the inner nuclear membrane protein Samp1, during interphase and mitosis
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The nucleus, a hallmark in eukaryotic cells, contains the genome separating it from molecules in the cytoplasm. The nucleus is surrounded by a nuclear envelope consisting of two concentric membranes, the outer nuclear membrane and the inner nuclear membrane, the nuclear lamina and nuclear pore complexes. The cytoskeleton is physically connected with the nucleoskeleton by the LINC complexes, spanning the nuclear envelope. In this way, the cell surface is linked directly to chromatin. There are hundreds of unique inner nuclear membrane proteins, but today we only know the functions of a handful. The best characterized inner nuclear membrane proteins are involved in chromatin organization and gene regulation.This thesis focuses on Samp1, an integral membrane protein that localizes to the inner nuclear membrane during interphase. During mitosis, a fraction localizes to the mitotic spindle, which is responsible for accurate segregation of chromosomes.It is difficult to investigate inner nuclear membrane protein-protein interactions, because transmembrane proteins are often associated with the “hard-to-solubilize” nuclear lamina. MCLIP was developed as a method to detect interactions between proteins of the nuclear envelope in live cells. MCLIP has been valuable in identifying interaction partners of Samp1. In interphase, Samp1 distributes in distinct micro-domains of the inner nuclear membrane and interacts with the nuclear lamina, emerin and the LINC complex protein SUN1, suggesting that Samp1 might have a functional role associated with both the nucleoskeleton and cytoskeleton.In mitosis Samp1 distributes in filamentous membrane structures partially overlapping with kinetochore microtubules of the mitotic spindle. Samp1 binds directly to γ-tubulin and recruits γ-tubulin and Haus6 to the mitotic spindle and thus contributes to spindle assembly. Samp1 also interacts with Aurora B, a kinase important for k-fiber error correction at the kinetochores. Depletion of Samp1 caused an increased activation and distribution of Aurora B at the metaphase plate, decreased formation of stable k-fibers, metaphase prolongation and increased chromosome mis-segregation. Samp1 is the first transmembrane protein found to be involved in mitotic spindle assembly and stability, important for correct segregation of chromosomes.
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| 35. |
- Larsson, Veronica J., et al.
(författare)
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Kinetochore microtubule stability is dependent on the integral nuclear membrane protein, Samp1
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We have previously shown that the transmembrane inner nuclear membrane protein, Samp1, localises to the mitotic spindle during metaphase, where it recruits γ-tubulin, which promotes spindle assembly by increasing the β-tubulin density. Samp1 depleted cells displayed signs of spindle destabilisation, such as increased spindle length, prolonged metaphase and chromosome mis-segregation. Here we show that Samp1 partially localise to cold resistant kinetochore fibres of the mitotic spindle. Posttranscriptional silencing of Samp1 decreased the number of kinetochore fibres and resulted in mis-aligned chromosomes, phenotypes that were rescued by Samp1YFP overexpression. We also show that Samp1 interacts with the Aurora B kinase and that Samp1 depletion increased the distribution of Aurora B in the metaphase plate and increased its activity. The effects of Samp1 on Aurora B increases our understanding of the kinetochore fibres and spindle stability.
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| 36. |
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| 37. |
- Larsson, Veronica J., et al.
(författare)
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Mitotic spindle assembly and γ-tubulin localisation depend on the integral nuclear membrane protein, Samp1
- 2018
-
Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 131:8
-
Tidskriftsartikel (refereegranskat)abstract
- We have investigated a possible role of the inner nuclear membrane protein, Samp1, in the mitotic machinery. Live cell imaging showed that Samp1aYFP distributed as filamentous structures in the mitotic spindle, partially co-localising with ß-tubulin. Samp1 depletion resulted in an increased frequency of cells with signs of chromosomal mis-segregation and prolonged metaphase, indicating problems with spindle assembly and/or chromosomal alignment. Consistently, mitotic spindles in Samp1 depleted cells contained significantly lower levels of ß-tubulin and γ-tubulin, phenotypes which were rescued by overexpression of Samp1aYFP. We found that Samp1 can bind directly to γ-tubulin and that Samp1 co-precipitated with γ-tubulin and HAUS6 of the Augmin complex in live cells. The levels of Haus6, in the mitotic spindle also decreased after Samp1 depletion. We show that Samp1 is involved in the recruitment of Haus6 and γ-tubulin to the mitotic spindle. Samp1 is the first inner nuclear membrane protein shown to have a function in mitotic spindle assembly.
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| 38. |
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| 39. |
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| 40. |
- Larsson, Veronica J.
(författare)
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The roles of inner nuclear membrane proteins during interphase and mitosis
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The nuclear envelope (NE) consists of two concentric membranes, the outer nuclear membrane (ONM) and the inner nuclear membrane (INM). The LINC (linker of nucleoskeleton and cytoskeleton) complex spans both the ONM and the INM connecting the cytoskeleton to the nucleoskeleton and chromatin. Only a few of the known INM proteins have been functionally characterized and shown to have important roles in chromatin organisation. Defects in the genes coding for proteins in the INM and the nuclear lamina give rise to serious human diseases, called envelopathies.In 2009 (Buch et al. 2009) our group made two major discoveries. We showed for the first time, that an integral INM protein distributed along the microtubules of the mitotic spindle. This protein was therefore named Samp1, Spindle Associated Membrane Protein 1. The second discovery was that depletion of Samp1 caused detachment of the centrosome from the NE, suggesting that Samp1 is associated with the microtubule cytoskeleton both in interphase and mitosis.In this thesis we continued to investigate Samp1´s role during interphase. We also wanted to investigate the localisation of Samp1 in the mitotic spindle and possible function during mitosis. We show that the expression of Samp1 mutants and depletion of Samp1 affects the distribution and organisation of A-type lamins, the LINC complex protein Sun1 and the LINC complex associated protein emerin. Thus, in interphase Samp1 is functionally connected to the LINC complex and the A-type lamina network. The LINC complex can help explain how the centrosomes detach from the NE in Samp1 depleted cells. In mitotic cells, we found that depletion of Samp1 caused prolonged metaphase and aberrant mitotic phenotypes such as bi-nucleation, enlarged nuclei and micronuclei. We also showed that Samp1 interacts with RanGTPase and importin-β, which are key players in assembling the mitotic spindle. Samp1 also modulates the levels of importin-β and NuMA in the mitotic spindle, which could explain the mitotic phenotypes that we se in Samp1 depleted cells. Here we present evidence showing, for the first time, that an INM protein is present on kinetochore microtubules and have an essential role for correct chromosome segregation and spindle assembly.
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| 41. |
- Leebens-Mack, James H., et al.
(författare)
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One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
-
Tidskriftsartikel (refereegranskat)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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| 42. |
- Leion, Felicia, et al.
(författare)
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Estimating glomerular filtration rate (GFR) in children. The average between a cystatin C- and a creatinine-based equation improves estimation of GFR in both children and adults and enables diagnosing Shrunken Pore Syndrome.
- 2017
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 77:5, s. 338-344
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Tidskriftsartikel (refereegranskat)abstract
- Estimating glomerular filtration rate (GFR) in adults by using the average of values obtained by a cystatin C- (eGFRcystatin C) and a creatinine-based (eGFRcreatinine) equation shows at least the same diagnostic performance as GFR estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparison of eGFRcystatin C and eGFRcreatinine plays a pivotal role in the diagnosis of Shrunken Pore Syndrome, where low eGFRcystatin C compared to eGFRcreatinine has been associated with higher mortality in adults. The present study was undertaken to elucidate if this concept can also be applied in children. Using iohexol and inulin clearance as gold standard in 702 children, we studied the diagnostic performance of 10 creatinine-based, 5 cystatin C-based and 3 combined cystatin C-creatinine eGFR equations and compared them to the result of the average of 9 pairs of a eGFRcystatin C and a eGFRcreatinine estimate. While creatinine-based GFR estimations are unsuitable in children unless calibrated in a pediatric or mixed pediatric-adult population, cystatin C-based estimations in general performed well in children. The average of a suitable creatinine-based and a cystatin C-based equation generally displayed a better diagnostic performance than estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparing eGFRcystatin and eGFRcreatinine may help identify pediatric patients with Shrunken Pore Syndrome.
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| 44. |
- Ljung, Rickard, et al.
(författare)
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Association between SARS-CoV-2 vaccination and healthcare contacts for menstrual disturbance and bleeding in women before and after menopause: nationwide, register based cohort study.
- 2023
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Ingår i: BMJ (Clinical research ed.). - : BMJ Publishing Group Ltd. - 0959-535X .- 1756-1833 .- 0959-8146. ; 381
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the risks of any menstrual disturbance and bleeding following SARS-CoV-2 vaccination in women who are premenopausal or postmenopausal.A nationwide, register based cohort study.All inpatient and specialised outpatient care in Sweden from 27 December 2020 to 28 February 2022. A subset covering primary care for 40% of the Swedish female population was also included.2946448 Swedish women aged 12-74 years were included. Pregnant women, women living in nursing homes, and women with history of any menstruation or bleeding disorders, breast cancer, cancer of female genital organs, or who underwent a hysterectomy between 1 January 2015 and 26 December 2020 were excluded.SARS-CoV-2 vaccination, by vaccine product (BNT162b2, mRNA-1273, or ChAdOx1 nCoV-19 (AZD1222)) and dose (unvaccinated and first, second, and third dose) over two time windows (one to seven days, considered the control period, and 8-90 days).Healthcare contact (admission to hospital or visit) for menstrual disturbance or bleeding before or after menopause (diagnosed with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes N91, N92, N93, N95).2580007 (87.6%) of 2946448 women received at least one SARS-CoV-2 vaccination and 1652472 (64.0%) 2580007 of vaccinated women received three doses before the end of follow-up. The highest risks for bleeding in women who were postmenopausal were observed after the third dose, in the one to seven days risk window (hazard ratio 1.28 (95% confidence interval 1.01 to 1.62)) and in the 8-90 days risk window (1.25 (1.04 to 1.50)). The impact of adjustment for covariates was modest. Risk of postmenopausal bleeding suggested a 23-33% increased risk after 8-90 days with BNT162b2 and mRNA-1273 after the third dose, but the association with ChAdOx1 nCoV-19 was less clear. For menstrual disturbance or bleeding in women who were premenopausal, adjustment for covariates almost completely removed the weak associations noted in the crude analyses.Weak and inconsistent associations were observed between SARS-CoV-2 vaccination and healthcare contacts for bleeding in women who are postmenopausal, and even less evidence was recorded of an association for menstrual disturbance or bleeding in women who were premenopausal. These findings do not provide substantial support for a causal association between SARS-CoV-2 vaccination and healthcare contacts related to menstrual or bleeding disorders.
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| 45. |
- López Durán, Verónica, 1987-
(författare)
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Chemical Modification of Cellulose Fibres and Fibrils for Design of New Materials
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Due to the growing interest in biobased materials in today’s society, where the need for a cyclic economy is obvious, there has been a huge increase in the interest for using cellulose due to its excellent mechanical and chemical properties. However, the properties of cellulose have to be modified and improved in order to satisfy advanced material applications where the cellulose properties can be tuned to fit the properties of other components in composite mixtures. This thesis explores the heterogeneous chemical modification of cellulose for improved material properties of cellulose-based materials and the use of cellulose fibres and fibrils in novel applications.In the first part of the work described in this thesis, a fundamental study was performed to clarify how the chemical composition and the fibre/fibril structure of the cellulose following chemical modification affect the material properties. The second part of the work was aimed at exploring the potential for using the chemically modified fibres/fibrils in novel material applications. Lignocellulosic fibres with different chemical compositions were modified by periodate oxidation and borohydride reduction, and it was found that the most important factor was the amount of holocellulose present in the fibres, since lignin-rich fibres were less reactive and less responsive to the treatments. Despite the lower reactivity of lignin-rich fibres, it was however possible to improve their mechanical properties and to achieve a significant increase in the compressive strength of papers prepared from modified unbleached kraft fibres.The chemical modifications were then expanded to nine different molecular structures and two different degrees of modification. Fibres modified at low degrees of modification were used to prepare handsheets, followed by mechanical and physical characterization. Highly modified fibres were also used to prepare cellulose nanofibrils (CNFs). It was found that the properties of handsheets and films prepared from modified fibres/fibrils are highly dependent on the chemical structure of the modified cellulose and, as an example, the ductility was greatly improved by converting secondary alcohols to primary alcohols. A detailed analysis of the modified fibres and fibrils also showed that, due to the heterogeneous chemical reaction used, the modified fibrils had a core-shell structure with a shell of modified cellulose with a lower crystalline order surrounding a core of crystalline cellulose. The results also showed that the chemical structure of the modified shell dramatically affects the interaction with moisture. Materials from fibrils containing covalent crosslinks have shown to be less sensitive to moisture at the cost of being more brittle. In a different application, modified CNFs were used as paper strength additives. Three differently modified CNFs were used: carboxymethylated CNFs, periodate-oxidised carboxymethylated CNFs and dopamine-grafted carboxymethylated CNFs. The properties of these CNFs were compared with that of a microfibrillated cellulose from unbleached kraft fibres. In general, a great improvement in the dry mechanical properties of handsheets was observed with the addition of the periodate-oxidised oxidised and dopamine-grafted modified fibrils, whereas only the periodate-oxidised carboxymethylated CNFs improved the wet strength.Finally, it was found that the chemically modified fibres could be used to prepare a novel low-density material with good mechanical strength, both wet and dry, and excellent shape recovery capacity in the wet state after mechanical compression. The fibre networks were produced by solvent exchange from water to acetone followed by air drying at room temperature. The properties of the fibre networks could also fairly easily be tuned in terms of porosity, density and strength.
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| 46. |
- López Durán, Verónica, et al.
(författare)
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Chemical modification of cellulose-rich fibres to clarify the influence of the chemical structure on the physical and mechanical properties of cellulose fibres and thereof made sheets
- 2018
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Ingår i: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 182, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Despite the different chemical approaches used earlier to increase the ductility of fibre-based materials, it has not been possible to link the chemical modification to their mechanical performance. In this study, cellulose fibres have been modified by periodate oxidation, alone or followed either by borohydride reduction, reductive amination or chlorite oxidation. In addition, TEMPO oxidation, and TEMPO oxidation in combination with periodate oxidation and further reduction with sodium borohydride have also been studied. The objective was to gain understanding of the influence of different functional groups on the mechanical and structural properties of handsheets made from the modified fibres. It was found that the modifications studied improved the tensile strength of the fibres to different extents, but that only periodate oxidation followed by borohydride reduction provided more ductile fibre materials. Changes in density, water-holding capacity and mechanical performance were also quantified and all are dependent on the functional group introduced.
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| 47. |
- López Durán, Veronica, 1987-, et al.
(författare)
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Effect of Chemical Functionality on the Mechanical and Barrier Performance of Nanocellulose Films
- 2018
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Ingår i: ACS APPLIED NANO MATERIALS. - : AMER CHEMICAL SOC. - 2574-0970. ; 1:4, s. 1959-1967
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Tidskriftsartikel (refereegranskat)abstract
- In the present work, we have partially modified fibrils chemically to eate a shell of derivatized cellulose that surrounds the crystalline re of native cellulose. Through the different modifications, we aimed creating a toolbox to enable the properties of CNF materials and terials containing CNFs to be tuned to meet specific material demands. total, nine different chemical modifications using different ueous-based procedures were used as chemical pretreatments before CNF oduction through homogenization. Eight of these modifications included riodate oxidation with an average of 27% of the anhydroglucose units the cellulose chain being cleaved into dialdehydes. The presence of dehydes then facilitated a conversion to other functional groups.
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| 48. |
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