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| 2. |
- Al Adwani, Salma, et al.
(författare)
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Citrullination Alters the Antibacterial and Anti-Inflammatory Functions of the Host Defense Peptide Canine Cathelicidin K9CATH In Vitro
- 2021
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 207:3, s. 974-984
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Tidskriftsartikel (refereegranskat)abstract
- K9CATH is the sole cathelicidin in canines (dogs) and exhibits broad antimicrobial activity against both Gram-positive and Gram-negative bacteria. K9CATH also modulates inflammatory responses and binds to LPS. These activities depend on the secondary structure and a net-positive charge of the peptide. Peptidylarginine deiminases (PAD) convert cationic peptidyl arginine to neutral citrulline. Thus, we hypothesized that citrullination is a biologically relevant modification of the peptide that would reduce the antibacterial and LPS-binding activities of K9CATH. Recombinant PAD2 and PAD4 citrullinated K9CATH to various extents and circular dichroism spectroscopy revealed that both native and citrullinated K9CATH exhibited similar α-helical secondary structures. Notably, citrullination of K9CATH reduced its bactericidal activity, abolished its ability to permeabilize the membrane of Gram-negative bacteria and reduced the hemolytic capacity. Electron microscopy showed that citrullinated K9CATH did not cause any morphological changes of Gram-negative bacteria, whereas the native peptide caused clear alterations of membrane integrity, concordant with a rapid bactericidal effect. Finally, citrullination of K9CATH impaired its capacity to inhibit LPS-mediated release of proinflammatory molecules from mouse and canine macrophages. In conclusion, citrullination attenuates the antibacterial and the LPS-binding properties of K9CATH, demonstrating the importance of a net positive charge for antibacterial lysis of bacteria and LPS-binding effects and suggests that citrullination is a means to regulate cathelicidin activities.
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| 3. |
- Al-Adwani, S, et al.
(författare)
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Studies on citrullinated LL-37: detection in human airways, antibacterial effects and biophysical properties
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 2376-
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Tidskriftsartikel (refereegranskat)abstract
- Arginine residues of the antimicrobial peptide LL-37 can be citrullinated by peptidyl arginine deiminases, which reduce the positive charge of the peptide. Notably, citrullinated LL-37 has not yet been detected in human samples. In addition, functional and biophysical properties of citrullinated LL-37 are not fully explored. The aim of this study was to detect citrullinated LL-37 in human bronchoalveolar lavage (BAL) fluid and to determine antibacterial and biophysical properties of citrullinated LL-37. BAL fluid was obtained from healthy human volunteers after intra-bronchial exposure to lipopolysaccharide. Synthetic peptides were used for bacterial killing assays, transmission electron microscopy, isothermal titration calorimetry, mass-spectrometry and circular dichroism. Using targeted proteomics, we were able to detect both native and citrullinated LL-37 in BAL fluid. The citrullinated peptide did not kill Escherichia coli nor lysed human red blood cells. Both peptides had similar α-helical secondary structures but citrullinated LL-37 was more stable at higher temperatures, as shown by circular dichroism. In conclusion, citrullinated LL-37 is present in the human airways and citrullination impaired bacterial killing, indicating that a net positive charge is important for antibacterial and membrane lysing effects. It is possible that citrullination serves as a homeostatic regulator of AMP-function by alteration of key functions.
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| 4. |
- Bergman, Astrid, et al.
(författare)
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Analytical traffic models for roundabouts with pedestrian crossings
- 2011
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Ingår i: Procedia - Social and Behavioral Sciences. - : Elsevier BV. - 1877-0428. ; 16, s. 697-708
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Tidskriftsartikel (refereegranskat)abstract
- Roundabouts have become a more common type of intersection in Sweden over the last 30 years. In order to evaluate the roundabout level-of-service both analytical models and simulation models are being used. Analytical traffic models for intersections, such as the Swedish capacity model Capcal, has difficulties estimating the level-of-service of a roundabout if there are pedestrians and cyclists at crossings located close to the roundabout. It is well known that a crossing located after a roundabout exit can cause an up-stream blocking effect that affects the performance of the roundabout. But how the upstream blocking effect depends on the different flows of vehicles and pedestrians is not known. In this paper an existing analytical model by Rodegerdts and Blackwelder has been investigated and compared to simulations in VISSIM and measurements from Swedish roundabouts. The purpose of this investigation is to examine if the model by Rodegerdts and Blackwelder is suitable for implementing into existing analytical models such as Capcal. The results show that the model by Rodegerdts and Blackwelder can estimate if a capacity loss will occur, but the magnitude of this loss is more difficult to evaluate. The conclusion and recommendation is that the model by Rodegerdts and Blackwelder should be implemented into the Swedish capacity model Capcal. The model by Rodegerdts and Blackwelder is to be used as a warning system if the results in Capcal are too uncertain to use for analysis of the roundabout performance.
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| 6. |
- Bergman, Penny, 1982, et al.
(författare)
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Perceptual validation of auralized heavy-duty vehicles
- 2015
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Ingår i: Euronoise 2015. ; , s. 769-774
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Konferensbidrag (refereegranskat)abstract
- Auralization is a valuable tool when evaluating the effect of traffic noise on people. The present study focuses on the validation of auralization of heavy-duty vehicles with a diesel engine. To capture the characteristics of the diesel engine a granular approach has been used. The granular approach has proven to be successful in a previous validation test examining two microphone positions around a still-standing truck. In the present study a granular approach was used to achieve pass-by noise at an artificial listening position alongside a Volvo truck (experiment 1) and pass-by noise inside an apartment (experiment 2). The aim of experiment 1 was to determine the number of interpolated sets of grains needed, in order to create a perceptually valid auralized signal. The results were used in the auralization of pass-by noise in an apartment in experiment 2. 20 and 15 participants respectively rated original recordings and auralized signals on four different attributes: realism, annoyance, and emotional response measured by valence and arousal. The results of both experiments suggest that auralizations of heavy-duty vehicles are successful and usable. It further indicates that what distinguish the auralized signals from the original recordings is mostly the arousal responses.
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| 7. |
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"Det universella och det individuella" : Festskrift till Eva Hættner Aurelius
- 2013
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- ”Det universella och det individuella” ger en inblick i det samtida litteraturvetenskapliga forskningsfältet. Ett trettiotal forskare medverkar i denna antologi vars innehåll spänner från det andliga till det sekulära, från medeltiden till det moderna, från det teoretiska till det biografiska och från det lokala till det globala. Perspektiven är svenska och nordiska så väl som internationella. Boken är en festskrift till Eva Hættner Aurelius, professor i litteraturvetenskap vid Lunds universitet. Skribenterna kommer från Sverige, Danmark och Tyskland där de under åren haft Eva Hættner Aurelius som inspirerande kollega, lärare, handledare och vän, och bidragen ansluter till frågor som hon under sin långa forskargärning har lyft fram: litteratur- och ämneshistoria, kvinnolitteraturhistoria, självbiografiskt skrivande.
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| 11. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 12. |
- Linder, Astrid, et al.
(författare)
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Evaluation of the BioRID P3 and the Hybrid III in pendulum impacts to the back : a comparison to human subject test data
- 2000
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Ingår i: Annual proceedings / Association for the Advancement of Automotive Medicine. Association for the Advancement of Automotive Medicine. - : Association for the Advancement of Automotive Medicine. - 1540-0360. ; 44, s. 283-297
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Tidskriftsartikel (refereegranskat)abstract
- The BioRID P3 (Biofidelic Rear Impact Dummy) and the Hybrid III were evaluated in pendulum impacts to the back and compared to data from previous cadaver tests. The test setup impacting seated cadavers was reproduced with a pendulum impacting seated dummies at the level of T6 (6th thoracic vertebra). The pendulum mass was 23 kg and the impact velocity 4.6 m/s. The results showed that the BioRID P3 was more biofidelic than the Hybrid III in terms of the peak responses and the temporal window of the head and head relative to T1 horizontal, vertical, and angular displacement. This study is an evaluation of both the BioRID P3 and the Hybrid III against a recently available set of human subject data. The study meets the need for validation of the BioRID P3 at a higher impact severity than has been previously accomplished.
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| 13. |
- Marinova, Zoya, et al.
(författare)
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Translocation of dynorphin neuropeptides across the plasma membrane. A putative mechanism of signal transmission.
- 2005
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 280:28
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Tidskriftsartikel (refereegranskat)abstract
- Several peptides, including penetratin and Tat, are known to translocate across the plasma membrane. Dynorphin opioid peptides are similar to cell-penetrating peptides in a high content of basic and hydrophobic amino acid residues. We demonstrate that dynorphin A and big dynorphin, consisting of dynorphins A and B, can penetrate into neurons and non-neuronal cells using confocal fluorescence microscopy/immunolabeling. The peptide distribution was characterized by cytoplasmic labeling with minimal signal in the cell nucleus and on the plasma membrane. Translocated peptides were associated with the endoplasmic reticulum but not with the Golgi apparatus or clathrin-coated endocytotic vesicles. Rapid entry of dynorphin A into the cytoplasm of live cells was revealed by fluorescence correlation spectroscopy. The translocation potential of dynorphin A was comparable with that of transportan-10, a prototypical cell-penetrating peptide. A central big dynorphin fragment, which retains all basic amino acids, and dynorphin B did not enter the cells. The latter two peptides interacted with negatively charged phospholipid vesicles similarly to big dynorphin and dynorphin A, suggesting that interactions of these peptides with phospholipids in the plasma membrane are not impaired. Translocation was not mediated via opioid receptors. The potential of dynorphins to penetrate into cells correlates with their ability to induce non-opioid effects in animals. Translocation across the plasma membrane may represent a previously unknown mechanism by which dynorphins can signal information to the cell interior.
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| 14. |
- Matuozzo, Daniela, et al.
(författare)
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Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.
- 2023
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Ingår i: Genome medicine. - 1756-994X. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in~80% of cases.We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1×10-4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1×10-4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4×10-3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7×10-8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68×10-5).Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60years old.
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| 15. |
- Mylrea-Foley, Bronacha, et al.
(författare)
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Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise : the TRUFFLE 2 randomised trial protocol
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (>= 4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire.Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy.
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| 18. |
- Stenström, Johan, et al.
(författare)
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Textens roll i operan
- 2013
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Ingår i: "Det universella och det individuella". Festskrift till Eva Hættner Aurelius. - 9789170611315 ; , s. 195-201
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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