| 1. |
- Abelev, Betty, et al.
(författare)
-
Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
-
Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
-
Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
|
|
| 2. |
- Abelev, Betty, et al.
(författare)
-
Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
-
Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
-
Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
|
|
| 3. |
- Abelev, Betty, et al.
(författare)
-
Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
-
Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
-
Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
|
|
| 4. |
- Beal, Jacob, et al.
(författare)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
|
|
| 5. |
- Colvill, Emma, et al.
(författare)
-
A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy : A multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking
- 2016
-
Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 119:1, s. 159-165
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion. Methods and materials Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for γ-tests recorded. Results For all lung traces all measurement sets show improved dose accuracy with a mean 2%/2 mm γ-fail rate of 1.6% with adaptation and 15.2% without adaptation (p < 0.001). For all prostate the mean 2%/2 mm γ-fail rate was 1.4% with adaptation and 17.3% without adaptation (p < 0.001). The difference between the four systems was small with an average 2%/2 mm γ-fail rate of <3% for all systems with adaptation for lung and prostate. Conclusions The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods.
|
|
| 6. |
|
|
| 7. |
- Hudson, Lawrence N, et al.
(författare)
-
The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
-
Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
-
Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
|
|
| 8. |
|
|
| 9. |
- Alpkvist, Helena, et al.
(författare)
-
Clinical and Microbiological Factors Associated with High Nasopharyngeal Pneumococcal Density in Patients with Pneumococcal Pneumonia
- 2015
-
Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 10:10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to study if certain clinical and/or microbiological factors are associated with a high nasopharyngeal (NP) density of Streptococcus pneumoniae in pneumococcal pneumonia. In addition, we aimed to study if a high NP pneumococcal density could be useful to detect severe pneumococcal pneumonia.Methods: Adult patients hospitalized for radiologically confirmed community-acquired pneumonia were included in a prospective study. NP aspirates were collected at admission and were subjected to quantitative PCR for pneumococcal DNA (Spn9802 DNA). Patients were considered to have pneumococcal etiology if S. pneumoniae was detected in blood culture and/ or culture of respiratory secretions and/or urinary antigen test.Results: Of 166 included patients, 68 patients had pneumococcal DNA detected in NP aspirate. Pneumococcal etiology was noted in 57 patients (84%) with positive and 8 patients (8.2%) with negative test for pneumococcal DNA (p<0.0001). The median NP pneumococcal density of DNA positive patients with pneumococcal etiology was 6.83 log(10) DNA copies/mL (range 1.79-9.50). In a multivariate analysis of patients with pneumococcal etiology, a high pneumococcal density was independently associated with severe pneumonia (Pneumonia Severity Index risk class IV-V), symptom duration >= 2 days prior to admission, and a medium/high serum immunoglobulin titer against the patient's own pneumococcal serotype. NP pneumococcal density was not associated with sex, age, smoking, co-morbidity, viral co-infection, pneumococcal serotype, or bacteremia. Severe pneumococcal pneumonia was noted in 28 study patients. When we studied the performance of PCR with different DNA cut-off levels for detection of severe pneumococcal pneumonia, we found sensitivities of 54-82% and positive predictive values of 37-56%, indicating suboptimal performance.Conclusions: Pneumonia severity, symptom duration similar to 2 days, and a medium/high serum immunoglobulin titer against the patient's own serotype were independently associated with a high NP pneumococcal density. NP pneumococcal density has limited value for detection of severe pneumococcal pneumonia.
|
|
| 10. |
|
|
| 11. |
- Athlin, Simon, 1971-, et al.
(författare)
-
Association between serotype-specific antibody response and serotype characteristics in patients with pneumococcal pneumonia, with special reference to degree of encapsulation and invasive potential
- 2014
-
Ingår i: Clinical and Vaccine Immunology. - : American Society for Microbiology. - 1556-6811 .- 1556-679X. ; 21:11, s. 1541-1549
-
Tidskriftsartikel (refereegranskat)abstract
- We studied the immunoglobulin (Ig) response to causative serotype-specific capsular polysaccharides in adult pneumococcal pneumonia patients. The serotypes were grouped according to their degree of encapsulation and invasive potential. Seventy patients with pneumococcal pneumonia, 20 of whom were bacteremic, were prospectively studied. All pneumococcal isolates from the patients were serotyped, and the Ig titers to the homologous serotype were determined in acute- and convalescent-phase sera using a serotype-specific enzyme-linked immunosorbent assay. The Ig titers were lower in bacteremic cases than in nonbacteremic cases (P < 0.042). The Ig titer ratio (convalescent/acute titer) was ≥2 in 33 patients, 1 to 1.99 in 20 patients, and <1 in 17 patients. Patients ≥65 years old had a lower median Ig titer ratio than did younger patients (P < 0.031). The patients with serotypes with a thin capsule (1, 4, 7F, 9N, 9V, and 14) and medium/high invasive potential (1, 4, 7F, 9N, 9V, 14, and 18C) had higher Ig titer ratios than did patients with serotypes with a thick capsule (3, 6B, 11A, 18C, 19A, 19F, and 23F) and low invasive potential (3, 6B, 19A, 19F, and 23F) (P < 0.05 for both comparisons after adjustment for age). Ig titer ratios of <1 were predominantly noted in patients with serotypes with a thick capsule. In 8 patients with pneumococcal DNA detected in plasma, the three patients with the highest DNA load had the lowest Ig titer ratios. In conclusion, a high antibody response was associated with serotypes with a thin capsule and medium/high invasive potential, although a low antibody response was associated with serotypes with a thick capsule and a high pneumococcal plasma load.
|
|
| 12. |
- Broadaway, K Alaine, et al.
(författare)
-
Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
-
Ingår i: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
-
Tidskriftsartikel (refereegranskat)abstract
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
|
|
| 13. |
- Burman, Robert, et al.
(författare)
-
Cyclotide proteins and precursors from the genus Gloeospermum : filling a blank spot in the cyclotide map of Violaceae
- 2010
-
Ingår i: Phytochemistry. - : Elsevier BV. - 0031-9422 .- 1873-3700. ; 71:1, s. 13-20
-
Tidskriftsartikel (refereegranskat)abstract
- Cyclotides are disulfide-rich plant proteins that are exceptional in their cyclic structure; their N and C termini are joined by a peptide bond, forming a continuous circular backbone, which is reinforced by three interlocked disulfide bonds. Cyclotides have been found mainly in the coffee (Rubiaceae) and violet (Violaceae) plant families. Within the Violaceae, cyclotides seem to be widely distributed, but the cyclotide complements of the vast majority of Violaceae species have not yet been explored. This study provides insight into cyclotide occurrence, diversity and biosynthesis in the Violaceae, by identifying mature cyclotide proteins, their precursors and enzymes putatively involved in their biosynthesis in the tribe Rinoreeae and the genus Gloeospermum. Twelve cyclotides from two Panamanian species, Gloeospermum pauciflorum Hekking and Gloeospermum blakeanum (Standl.) Hekking (designated Glopa A-E and Globa A-G, respectively) were characterised through cDNA screening and protein isolation. Screening of cDNA for the oxidative folding enzymes protein-disulfide isomerase (PDI) and thioredoxin (TRX) resulted in positive hits in both species. These enzymes have demonstrated roles in oxidative folding of cyclotides in Rubiaceae, and results presented here indicate that Violaceae plants have evolved similar mechanisms of cyclotide biosynthesis. We also describe PDI and TRX sequences from a third cyclotide-expressing Violaceae species, Viola biflora L., which further support this hypothesis.
|
|
| 14. |
|
|
| 15. |
- Chapman, Henry N, et al.
(författare)
-
Femtosecond X-ray protein nanocrystallography.
- 2011
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 470:7332, s. 73-7
-
Tidskriftsartikel (refereegranskat)abstract
- X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (∼200nm to 2μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.
|
|
| 16. |
- Giannakopoulos, Panteleimon, et al.
(författare)
-
Alzheimer resemblance atrophy index, BrainAGE, and normal pressure hydrocephalus score in the prediction of subtle cognitive decline : added value compared to existing MR imaging markers.
- 2022
-
Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 32:11, s. 7833-7842
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Established visual brain MRI markers for dementia include hippocampal atrophy (mesio-temporal atrophy MTA), white matter lesions (Fazekas score), and number of cerebral microbleeds (CMBs). We assessed whether novel quantitative, artificial intelligence (AI)-based volumetric scores provide additional value in predicting subsequent cognitive decline in elderly controls.METHODS: A prospective study including 80 individuals (46 females, mean age 73.4 ± 3.5 years). 3T MR imaging was performed at baseline. Extensive neuropsychological assessment was performed at baseline and at 4.5-year follow-up. AI-based volumetric scores were derived from 3DT1: Alzheimer Disease Resemblance Atrophy Index (AD-RAI), Brain Age Gap Estimate (BrainAGE), and normal pressure hydrocephalus (NPH) index. Analyses included regression models between cognitive scores and imaging markers.RESULTS: AD-RAI score at baseline was associated with Corsi (visuospatial memory) decline (10.6% of cognitive variability in multiple regression models). After inclusion of MTA, CMB, and Fazekas scores simultaneously, the AD-RAI score remained as the sole valid predictor of the cognitive outcome explaining 16.7% of its variability. Its percentage reached 21.4% when amyloid positivity was considered an additional explanatory factor. BrainAGE score was associated with Trail Making B (executive functions) decrease (8.5% of cognitive variability). Among the conventional MRI markers, only the Fazekas score at baseline was positively related to the cognitive outcome (8.7% of cognitive variability). The addition of the BrainAGE score as an independent variable significantly increased the percentage of cognitive variability explained by the regression model (from 8.7 to 14%). The addition of amyloid positivity led to a further increase in this percentage reaching 21.8%.CONCLUSIONS: The AI-based AD-RAI index and BrainAGE scores have limited but significant added value in predicting the subsequent cognitive decline in elderly controls when compared to the established visual MRI markers of brain aging, notably MTA, Fazekas score, and number of CMBs.KEY POINTS: • AD-RAI score at baseline was associated with Corsi score (visuospatial memory) decline. • BrainAGE score was associated with Trail Making B (executive functions) decrease. • AD-RAI index and BrainAGE scores have limited but significant added value in predicting the subsequent cognitive decline in elderly controls when compared to the established visual MRI markers of brain aging, notably MTA, Fazekas score, and number of CMBs.
|
|
| 17. |
|
|
| 18. |
- Graham, Ian, et al.
(författare)
-
European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
- 2007
-
Ingår i: European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. - : Oxford University Press (OUP). - 1741-8267. ; 14 Suppl 2
-
Tidskriftsartikel (refereegranskat)abstract
- Other experts who contributed to parts of the guidelines: Edmond Walma, Tony Fitzgerald, Marie Therese Cooney, Alexandra Dudina European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG): Alec Vahanian (Chairperson), John Camm, Raffaele De Caterina, Veronica Dean, Kenneth Dickstein, Christian Funck-Brentano, Gerasimos Filippatos, Irene Hellemans, Steen Dalby Kristensen, Keith McGregor, Udo Sechtem, Sigmund Silber, Michal Tendera, Petr Widimsky, Jose Luis Zamorano Document reviewers: Irene Hellemans (CPG Review Co-ordinator), Attila Altiner, Enzo Bonora, Paul N. Durrington, Robert Fagard, Simona Giampaoli, Harry Hemingway, Jan Hakansson, Sverre Erik Kjeldsen, Mogens Lytken Larsen, Giuseppe Mancia, Athanasios J. Manolis, Kristina Orth-Gomer, Terje Pedersen, Mike Rayner, Lars Ryden, Mario Sammut, Neil Schneiderman, Anton F. Stalenhoef, Lale Tokgözoglu, Olov Wiklund, Antonis Zampelas
|
|
| 19. |
- Herrmann, Inga, et al.
(författare)
-
Hydraulic conductivity of fly ash : sewage sludge mixes for use in landfill cover liners
- 2009
-
Ingår i: Water Research. - : Elsevier BV. - 0043-1354 .- 1879-2448. ; 43:14, s. 3541-3547
-
Tidskriftsartikel (refereegranskat)abstract
- Secondary materials could help meeting the increasing demand of landfill cover liner materials. In this study, the effect of compaction energy, water content, ash ratio, freezing, drying and biological activity on the hydraulic conductivity of two fly ash - sewage sludge mixes was investigated using a 27-1 fractional factorial design. The aim was to identify the factors that influence hydraulic conductivity, to quantify their effects and to assess how a sufficiently low hydraulic conductivity can be achieved. The factors compaction energy and drying, as well as the factor interactions material×ash ratio and ash ratio×compaction energy affected hydraulic conductivity significantly (α = 0.05). Freezing on 5 freeze-thaw cycles did not affect hydraulic conductivity. Water content affected hydraulic conductivity only initially. The hydraulic conductivity data were modelled using multiple linear regression. The derived models were reliable as indicated by R2adjusted values between 0.75 and 0.86. Independent on the ash ratio and the material, hydraulic conductivity was predicted to be between 1.7 × 10-11 m s-1 and 8.9 × 10-10 m s-1 if the compaction energy was 2.4 J cm-3, the ash ratio between 20 and 75 % and drying did not occur. Thus, the investigated materials met the limit value for non-hazardous waste landfills of 10-9 m s-1.
|
|
| 20. |
- Karlsson, Elin, et al.
(författare)
-
Disordered Regions Flanking the Binding Interface Modulate Affinity between CBP and NCOA
- 2022
-
Ingår i: Journal of Molecular Biology. - : Elsevier. - 0022-2836 .- 1089-8638. ; 434:13
-
Tidskriftsartikel (refereegranskat)abstract
- Recognition motifs that mediate protein-protein interactions are usually embedded within longer intrinsically disordered regions. While binding interfaces involving the recognition motif in such interactions are well studied, less is known about the role of disordered regions flanking the motifs. The interaction between the transcriptional co-activators NCOA3 (ACTR) and CBP is mediated by coupled binding and folding of the two domains CID and NCBD. Here, we used circular dichroism and kinetics to directly quantify the contribution of the adjacent flanking regions of CID to its interaction with NCBD. Using N-and C terminal combinatorial variants we found that the flanking regions promote binding in an additive fashion while retaining a large degree of disorder in the complex. Experiments at different ionic strengths demonstrated that the increase in affinity is not mediated by electrostatic interactions from the flanking regions. Instead, site-directed mutagenesis and molecular dynamics simulations suggest that binding is promoted by short-lived non-specific hydrophobic contacts between the flanking regions and NCBD. Our findings are consistent with highly frustrated interactions outside of the canonical binding interface resulting in a slightly energetically favorable fuzzy binding. Modulation of affinity via flanking regions could represent a general mechanism for functional regulation by intrinsically disordered protein regions.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
|
|
| 21. |
- Klint, Markus, et al.
(författare)
-
High-resolution genotyping of Chlamydia trachomatis strains by multilocus sequence analysis
- 2007
-
Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 45:5, s. 1410-1414
-
Tidskriftsartikel (refereegranskat)abstract
- Genotyping of Chlamydia trachomatis is limited by the low sequence variation in the genome, and no adequatemethod is available for analysis of the spread of chlamydial infections in the community. We have developeda multilocus sequence typing (MLST) system based on five target regions and compared it with analysis ofompA, the single gene most extensively used for genotyping. Sequence determination of 16 reference strains,comprising all major serotypes, serotypes A to L3, showed that the number of genetic variants in the fiveseparate target regions ranged from 8 to 16. The genetic variation in 47 clinical C. trachomatis isolates ofrepresentative serotypes (14 serotype D, 12 serotype E, 11 serotype G, and 10 serotype K strains) was analyzed;and the MLST system detected 32 variants, whereas 12 variants were detected by using ompA analysis.Specimens of the predominant serotype, serotype E, were differentiated into seven genotypes by MLST but intoonly two by ompA analysis. The MLST system was applied to C. trachomatis specimens from a population ofmen who have sex with men and was able to differentiate 10 specimens of one predominant ompA genotype Gvariant into four distinct MLST variants. To conclude, our MLST system can be used to discriminate C.trachomatis strains and can be applied to high-resolution molecular epidemiology.
|
|
| 22. |
- Lodder, Paul, et al.
(författare)
-
Type D Personality as a Risk Factor for Adverse Outcome in Patients With Cardiovascular Disease : An Individual Patient-Data Meta-analysis
- 2023
-
Ingår i: Psychosomatic Medicine. - : Lippincott Williams & Wilkins. - 0033-3174 .- 1534-7796. ; 85:2, s. 188-202
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveType D personality, a joint tendency toward negative affectivity and social inhibition, has been linked to adverse events in patients with heart disease, although with inconsistent findings. Here, we apply an individual patient-data meta-analysis to data from 19 prospective cohort studies (N = 11,151) to investigate the prediction of adverse outcomes by type D personality in patients with acquired cardiovascular disease.MethodFor each outcome (all-cause mortality, cardiac mortality, myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, major adverse cardiac event, any adverse event), we estimated type D's prognostic influence and the moderation by age, sex, and disease type.ResultsIn patients with cardiovascular disease, evidence for a type D effect in terms of the Bayes factor (BF) was strong for major adverse cardiac event (BF = 42.5; odds ratio [OR] = 1.14) and any adverse event (BF = 129.4; OR = 1.15). Evidence for the null hypothesis was found for all-cause mortality (BF = 45.9; OR = 1.03), cardiac mortality (BF = 23.7; OR = 0.99), and myocardial infarction (BF = 16.9; OR = 1.12), suggesting that type D had no effect on these outcomes. This evidence was similar in the subset of patients with coronary artery disease (CAD), but inconclusive for patients with heart failure (HF). Positive effects were found for negative affectivity on cardiac and all-cause mortality, with the latter being more pronounced in male than female patients.ConclusionAcross 19 prospective cohort studies, type D predicts adverse events in patients with CAD, whereas evidence in patients with HF was inconclusive. In both patients with CAD and HF, we found evidence for a null effect of type D on cardiac and all-cause mortality.
|
|
| 23. |
- Manzoni, Stefano, et al.
(författare)
-
Reviews and syntheses : Carbon use efficiency from organisms to ecosystems - definitions, theories, and empirical evidence
- 2018
-
Ingår i: Biogeosciences. - : COPERNICUS GESELLSCHAFT MBH. - 1726-4170 .- 1726-4189. ; 15:19, s. 5929-5949
-
Forskningsöversikt (refereegranskat)abstract
- The cycling of carbon (C) between the Earth surface and the atmosphere is controlled by biological and abiotic processes that regulate C storage in biogeochemical compartments and release to the atmosphere. This partitioning is quantified using various forms of C-use efficiency (CUE) - the ratio of C remaining in a system to C entering that system. Biological CUE is the fraction of C taken up allocated to biosynthesis. In soils and sediments, C storage depends also on abiotic processes, so the term C-storage efficiency (CSE) can be used. Here we first review and reconcile CUE and CSE definitions proposed for autotrophic and heterotrophic organisms and communities, food webs, whole ecosystems and watersheds, and soils and sediments using a common mathematical framework. Second, we identify general CUE patterns; for example, the actual CUE increases with improving growth conditions, and apparent CUE decreases with increasing turnover. We then synthesize > 5000CUE estimates showing that CUE decreases with increasing biological and ecological organization - from uni-cellular to multicellular organisms and from individuals to ecosystems. We conclude that CUE is an emergent property of coupled biological-abiotic systems, and it should be regarded as a flexible and scale-dependent index of the capacity of a given system to effectively retain C.
|
|
| 24. |
- Meitzner, Rico, et al.
(författare)
-
Impact of P3HT materials properties and layer architecture on OPV device stability
- 2019
-
Ingår i: Solar Energy Materials and Solar Cells. - : Elsevier BV. - 0927-0248. ; 202
-
Tidskriftsartikel (refereegranskat)abstract
- We report a cooperative study conducted between different laboratories to investigate organic solar cell degradation with respect to P3HT material properties and different solar cell architectures. Various batches of P3HT were collected from different suppliers reflecting commercial availability as well as properties variability. Among the materials properties explicitly considered were the molar mass, dispersity, regio-regularity, impurities by trace metals and intrinsic doping evaluated from radical concentrations. Each of the participating laboratories contributing test devices applied their own layer stack, i.e. their own device architecture and layout. This variation was appreciated as another parameter for evaluation. Even though a large amount of devices failed due to extrinsic degradation effects, indeed, some materials properties were found to be more important than others for obtaining long lifetimes and high stability of P3HT-based polymer solar cells.
|
|
| 25. |
- Peng, X., et al.
(författare)
-
Photodissociation of particulate nitrate as a source of daytime tropospheric Cl2
- 2022
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Chlorine atoms (Cl) are highly reactive and can strongly influence the abundances of climate and air quality-relevant trace gases. Despite extensive research on molecular chlorine (Cl2), a Cl precursor, in the polar atmosphere, its sources in other regions are still poorly understood. Here we report the daytime Cl2 concentrations of up to 1 ppbv observed in a coastal area of Hong Kong, revealing a large daytime source of Cl2 (2.7 pptv s−1 at noon). Field and laboratory experiments indicate that photodissociation of particulate nitrate by sunlight under acidic conditions (pH < 3.0) can activate chloride and account for the observed daytime Cl2 production. The high Cl2 concentrations significantly increased atmospheric oxidation. Given the ubiquitous existence of chloride, nitrate, and acidic aerosols, we propose that nitrate photolysis is a significant daytime chlorine source globally. This so far unaccounted for source of chlorine can have substantial impacts on atmospheric chemistry. © 2022, The Author(s).
|
|
| 26. |
- Quintel, Michael, et al.
(författare)
-
An increase of abdominal pressure increases pulmonary edema in oleic acid-induced lung injury.
- 2004
-
Ingår i: American journal of respiratory and critical care medicine. - 1073-449X. ; 169:4, s. 534-41
-
Tidskriftsartikel (refereegranskat)abstract
- Increased abdominal pressure is common in intensive care unit patients. To investigate its impact on respiration and hemodynamics we applied intraabdominal pressure (aIAP) of 0 and 20 cm H(2)O (pneumoperitoneum) in seven pigs. The whole-lung computed tomography scan and a complete set of respiratory and hemodynamics variables were recorded both in healthy lung and after oleic acid (OA) injury. In healthy lung, aIAP 20 cm H(2)O significantly lowered the gas content, leaving the tissue content unchanged. In OA-injured lung at aIAP 0 cm H(2)O, the gas content significantly decreased compared with healthy lung. The excess tissue mass (edema) amounted to 30 +/- 24% of the original tissue weight (455 +/- 80 g). The edema was primarily distributed in the base regions and was not gravity dependent. Heart volume, central venous, pulmonary artery, wedge, and systemic arterial pressures significantly increased. At aIAP 20 cm H(2)O in OA-injured lung, the central venous and pulmonary artery pressures further increased. The gas content further decreased, and the excess tissue mass rose up to 103 +/- 37% (tissue weight 905 +/- 134 g), with homogeneous distribution along the cephalocaudal and sternovertebral axis. We conclude that in OA-injured lung, the increase of IAP increases the amount of edema.
|
|
| 27. |
|
|
| 28. |
- Reutter, Heiko, et al.
(författare)
-
Genome-wide association study and mouse expression data identify a highly conserved 32kb intergenic region between WNT3 and WNT9b as possible susceptibility locus for isolated classic exstrophy of the bladder.
- 2014
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:20, s. 5536-5544
-
Tidskriftsartikel (refereegranskat)abstract
- Bladder Exstrophy-Epispadias Complex (BEEC), the severe end of the uro-rectal malformation spectrum, has a profound impact on continence as well as sexual and renal functions. It is widely accepted that for the majority of cases the genetic basis appears to be multifactorial. Here, we report the first study which utilizes genome-wide association methods to analyze a cohort comprising patients presenting the most common BEEC form, classic bladder exstrophy (CBE), to identify common variation associated with risk for isolated CBE. We employed discovery and follow-up samples comprising 218/865 cases/controls and 78 trios in total, all of European descent. Our discovery sample identified a marker near SALL1, showing genome-wide significant association with CBE. However, analyses performed on follow-up samples did not add further support to these findings. We were also able to identify an association with CBE across our study samples (discovery: P=8.88 x 10(-5); follow-up: P=0.0025; combined: 1.09 x 10(-6)) in a highly conserved 32kb intergenic region containing regulatory elements between WNT3 and WNT9B. Subsequent analyses in mice revealed expression for both genes in the genital region during stages relevant to the development of CBE in humans. Unfortunately, we were not able to replicate the suggestive signal for WNT3 and WNT9B in a sample that was enriched for non-CBE BEEC cases (P=0.51). Our suggestive findings support the hypothesis that larger samples are warranted to identify association of common variation with CBE.
|
|
| 29. |
- Rylander, Christian, 1960, et al.
(författare)
-
Uneven distribution of ventilation in acute respiratory distress syndrome
- 2005
-
Ingår i: Crit Care. ; 9:2
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of this study was to assess the volume of gas being poorly ventilated or non-ventilated within the lungs of patients treated with mechanical ventilation and suffering from acute respiratory distress syndrome (ARDS). METHODS: A prospective, descriptive study was performed of 25 sedated and paralysed ARDS patients, mechanically ventilated with a positive end-expiratory pressure (PEEP) of 5 cmH2O in a multidisciplinary intensive care unit of a tertiary university hospital. The volume of poorly ventilated or non-ventilated gas was assumed to correspond to a difference between the ventilated gas volume, determined as the end-expiratory lung volume by rebreathing of sulphur hexafluoride (EELVSF6), and the total gas volume, calculated from computed tomography images in the end-expiratory position (EELVCT). The methods used were validated by similar measurements in 20 healthy subjects in whom no poorly ventilated or non-ventilated gas is expected to be found. RESULTS: EELVSF6 was 66% of EELVCT, corresponding to a mean difference of 0.71 litre. EELVSF6 and EELVCT were significantly correlated (r2 = 0.72; P < 0.001). In the healthy subjects, the two methods yielded almost identical results. CONCLUSION: About one-third of the total pulmonary gas volume seems poorly ventilated or non-ventilated in sedated and paralysed ARDS patients when mechanically ventilated with a PEEP of 5 cmH2O. Uneven distribution of ventilation due to airway closure and/or obstruction is likely to be involved.
|
|
| 30. |
- Schafmayer, Clemens, et al.
(författare)
-
Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms
- 2019
-
Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 68:5, s. 854-865
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. Design Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. Results We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p< 0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3x10-10 and 0.002 (OR allelic = 1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). Conclusion I n silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.
|
|
| 31. |
- Seibert, M. Marvin, et al.
(författare)
-
Single mimivirus particles intercepted and imaged with an X-ray laser
- 2011
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 470:7332, s. 78-81
-
Tidskriftsartikel (refereegranskat)abstract
- X-ray lasers offer new capabilities in understanding the structure of biological systems, complex materials and matter under extreme conditions(1-4). Very short and extremely bright, coherent X-ray pulses can be used to outrun key damage processes and obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma(1). The continuous diffraction pattern of non-crystalline objects permits oversampling and direct phase retrieval(2). Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a noncrystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source(5). Calculations indicate that the energy deposited into the virus by the pulse heated the particle to over 100,000 K after the pulse had left the sample. The reconstructed exit wavefront (image) yielded 32-nm full-period resolution in a single exposure and showed no measurable damage. The reconstruction indicates inhomogeneous arrangement of dense material inside the virion. We expect that significantly higher resolutions will be achieved in such experiments with shorter and brighter photon pulses focused to a smaller area. The resolution in such experiments can be further extended for samples available in multiple identical copies.
|
|
| 32. |
- Smid, Joost H., et al.
(författare)
-
Rise and fall of the new variant of Chlamydia trachomatis in Sweden : mathematical modelling study
- 2020
-
Ingår i: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 96:5, s. 375-379
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: A new variant of Chlamydia trachomatis (nvCT) was discovered in Sweden in 2006. The nvCT has a plasmid deletion, which escaped detection by two nucleic acid amplification tests (Abbott-Roche, AR), which were used in 14 of 21 Swedish counties. The objectives of this study were to assess when and where nvCT emerged in Sweden, the proportion of nvCT in each county and the role of a potential fitness difference between nvCT and co-circulating wild-type strains (wtCT).METHODS: We used a compartmental mathematical model describing the spatial and temporal spread of nvCT and wtCT. We parameterised the model using sexual behaviour data and Swedish spatial and demographic data. We used Bayesian inference to fit the model to surveillance data about reported diagnoses of chlamydia infection in each county and data from four counties that assessed the proportion of nvCT in multiple years.RESULTS: Model results indicated that nvCT emerged in central Sweden (Dalarna, Gävleborg, Västernorrland), reaching a proportion of 1% of prevalent CT infections in late 2002 or early 2003. The diagnostic selective advantage enabled rapid spread of nvCT in the presence of high treatment rates. After detection, the proportion of nvCT decreased from 30%-70% in AR counties and 5%-20% in counties that Becton Dickinson tests, to around 5% in 2015 in all counties. The decrease in nvCT was consistent with an estimated fitness cost of around 5% in transmissibility or 17% reduction in infectious duration.CONCLUSIONS: We reconstructed the course of a natural experiment in which a mutant strain of C. trachomatis spread across Sweden. Our modelling study provides support, for the first time, of a reduced transmissibility or infectious duration of nvCT. This mathematical model improved our understanding of the first nvCT epidemic in Sweden and can be adapted to investigate the impact of future diagnostic escape mutants.
|
|
| 33. |
- Stephens, Lucas, et al.
(författare)
-
Archaeological assessment reveals Earth’s early transformation through land use
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 365:6456, s. 897-902
-
Tidskriftsartikel (refereegranskat)abstract
- Humans began to leave lasting impacts on Earth’s surface starting 10,000 to 8000 years ago. Through a synthetic collaboration with archaeologists around the globe, Stephens et al. compiled a comprehensive picture of the trajectory of human land use worldwide during the Holocene (see the Perspective by Roberts). Hunter-gatherers, farmers, and pastoralists transformed the face of Earth earlier and to a greater extent than has been widely appreciated, a transformation that was essentially global by 3000 years before the present.Science, this issue p. 897; see also p. 865Environmentally transformative human use of land accelerated with the emergence of agriculture, but the extent, trajectory, and implications of these early changes are not well understood. An empirical global assessment of land use from 10,000 years before the present (yr B.P.) to 1850 CE reveals a planet largely transformed by hunter-gatherers, farmers, and pastoralists by 3000 years ago, considerably earlier than the dates in the land-use reconstructions commonly used by Earth scientists. Synthesis of knowledge contributed by more than 250 archaeologists highlighted gaps in archaeological expertise and data quality, which peaked for 2000 yr B.P. and in traditionally studied and wealthier regions. Archaeological reconstruction of global land-use history illuminates the deep roots of Earth’s transformation and challenges the emerging Anthropocene paradigm that large-scale anthropogenic global environmental change is mostly a recent phenomenon.
|
|
| 34. |
- Stolle, Christian, et al.
(författare)
-
The MILAN Campaign : Studying Diel Light Effects on the Air–Sea Interface
- 2020
-
Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 101:2, s. E146-E166
-
Tidskriftsartikel (refereegranskat)abstract
- The sea surface microlayer (SML) at the air–sea interface is <1 mm thick, but it is physically, chemically, and biologically distinct from the underlying water and the atmosphere above. Wind-driven turbulence and solar radiation are important drivers of SML physical and biogeochemical properties. Given that the SML is involved in all air–sea exchanges of mass and energy, its response to solar radiation, especially in relation to how it regulates the air–sea exchange of climate-relevant gases and aerosols, is surprisingly poorly characterized. MILAN (Sea Surface Microlayer at Night) was an international, multidisciplinary campaign designed to specifically address this issue. In spring 2017, we deployed diverse sampling platforms (research vessels, radio-controlled catamaran, free-drifting buoy) to study full diel cycles in the coastal North Sea SML and in underlying water, and installed a land-based aerosol sampler. We also carried out concurrent ex situ experiments using several microsensors, a laboratory gas exchange tank, a solar simulator, and a sea spray simulation chamber. In this paper we outline the diversity of approaches employed and some initial results obtained during MILAN. Our observations of diel SML variability show, for example, an influence of (i) changing solar radiation on the quantity and quality of organic material and (ii) diel changes in wind intensity primarily forcing air–sea CO2 exchange. Thus, MILAN underlines the value and the need of multidiciplinary campaigns for integrating SML complexity into the context of air–sea interaction.
|
|
| 35. |
- Triesch, Nadja, et al.
(författare)
-
Sea Spray Aerosol Chamber Study on Selective Transfer and Enrichment of Free and Combined Amino Acids
- 2021
-
Ingår i: ACS Earth and Space Chemistry. - : American Chemical Society (ACS). - 2472-3452. ; 5:6, s. 1564-1574
-
Tidskriftsartikel (refereegranskat)abstract
- Free (FAAs) and combined amino acids (CAAs) were investigated on size-resolved samples of nascent sea spray aerosol (SSA) particles generated during controlled laboratory experiments. Compared to seawater, the amino acids were strongly enriched on the SSA particles. The enrichment factors (EFaer) on submicron SSA particles (EFaer Sigma(FAA): 2.5 x 10(6) and EFaer Sigma CAA: 7.9 x 10(5)) were 1-2 orders of magnitude higher than on supermicron ones (EFaerSFAA: 1.0 x 105 and EFaer Sigma(CAA): 7.3 x 10(4)) and continuously increased toward smaller SSA particles. Molecular-level analysis showed that the more polar the FAAs, the more they are enriched on the SSA particles (especially FAAs with polar acid side chains, e.g., aspartic acid: EFaer of 5.8 x 10(6)). Comparison of the amino acids present on nascent SSA with those present on ambient marine aerosol particles revealed a higher complexity of the amino acids of the nascent SSA, suggesting that atmospheric processes likely reduce the amino acid diversity. In addition, our results highlight that although almost all the amino acids studied are transferred to the atmosphere via bubble bursting under controlled conditions, two amino acids, gamma-aminobutyric acid (GABA) and glycine likely have additional sources to the atmosphere. GABA is likely formed on ambient marine submicron aerosol particles to a large extent (35-47% of Sigma FAA). Glycine likely originates from long-range transport processes or photochemical reactions, as discussed in the literature; however, our results highlight the potential for a direct oceanic source via bubble bursting (similar to 20% of Sigma FAA). Overall, bubble-bursting-derived total amino acids made up 11-18% of the mass of dissolved organic carbon on the submicron SSA particles.
|
|
| 36. |
- Träger, Chantal, et al.
(författare)
-
Evolution from the Prokaryotic to the Higher Plant Chloroplast Signal Recognition Particle: The Signal Recognition Particle RNA Is Conserved in Plastids of a Wide Range of Photosynthetic Organisms
- 2012
-
Ingår i: The Plant Cell. - : Oxford University Press (OUP). - 1040-4651 .- 1532-298X. ; 24:12, s. 4819-4836
-
Tidskriftsartikel (refereegranskat)abstract
- The protein targeting signal recognition particle (SRP) pathway in chloroplasts of higher plants has undergone dramatic evolutionary changes. It disposed of its RNA, which is an essential SRP component in bacteria, and uses a unique chloroplast-specific protein cpSRP43. Nevertheless, homologs of the conserved SRP54 and the SRP receptor, FtsY, are present in higher plant chloroplasts. In this study, we analyzed the phylogenetic distribution of SRP components in photosynthetic organisms to elucidate the evolution of the SRP system. We identified conserved plastid SRP RNAs within all nonspermatophyte land plant lineages and in all chlorophyte branches. Furthermore, we show the simultaneous presence of cpSRP43 in these organisms. The function of this novel SRP system was biochemically and structurally characterized in the moss Physcomitrella patens. We show that P. patens chloroplast SRP (cpSRP) RNA binds cpSRP54 but has lost the ability to significantly stimulate the GTPase cycle of SRP54 and FtsY. Furthermore, the crystal structure at 1.8-Å resolution and the nucleotide specificity of P. patens cpFtsY was determined and compared with bacterial FtsY and higher plant chloroplast FtsY. Our data lead to the view that the P. patens cpSRP system occupies an intermediate position in the evolution from bacterial-type SRP to higher plant-type cpSRP system.
|
|
| 37. |
- Tsolaki, Elena, et al.
(författare)
-
Multiscale multimodal characterization and simulation of structural alterations in failed bioprosthetic heart valves
- 2023
-
Ingår i: Acta Biomaterialia. - 1878-7568 .- 1742-7061. ; 169, s. 138-154
-
Tidskriftsartikel (refereegranskat)abstract
- Calcific degeneration is the most frequent type of heart valve failure, with rising incidence due to the ageing population. The gold standard treatment to date is valve replacement. Unfortunately, calcification oftentimes re-occurs in bioprosthetic substitutes, with the governing processes remaining poorly understood. Here, we present a multiscale, multimodal analysis of disturbances and extensive mineralisation of the collagen network in failed bioprosthetic bovine pericardium valve explants with full histoanatomical context. In addition to highly abundant mineralized collagen fibres and fibrils, calcified micron-sized particles previously discovered in native valves were also prevalent on the aortic as well as the ventricular surface of bioprosthetic valves. The two mineral types (fibres and particles) were detectable even in early-stage mineralisation, prior to any macroscopic calcification. Based on multiscale multimodal characterisation and high-fidelity simulations, we demonstrate that mineral occurrence coincides with regions exposed to high haemodynamic and biomechanical indicators. These insights obtained by multiscale analysis of failed bioprosthetic valves serve as groundwork for the evidence-based development of more durable alternatives. Statement of significance: Bioprosthetic valve calcification is a well-known clinically significant phenomenon, leading to valve failure. The nanoanalytical characterisation of bioprosthetic valves gives insights into the highly abundant, extensive calcification and disorganization of the collagen network and the presence of calcium phosphate particles previously reported in native cardiovascular tissues. While the collagen matrix mineralisation can be primarily attributed to a combination of chemical and mechanical alterations, the calcified particles are likely of host cellular origin. This work presents a straightforward route to mineral identification and characterization at high resolution and sensitivity, and with full histoanatomical context and correlation to hemodynamic and biomechanical indicators, hence providing design cues for improved bioprosthetic valve alternatives.
|
|
| 38. |
- van Bergen, Jan E. A. M., et al.
(författare)
-
Where to go to in chlamydia control? : From infection control towards infectious disease control
- 2021
-
Ingår i: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 97:7, s. 501-506
-
Forskningsöversikt (refereegranskat)abstract
- Objectives: The clinical and public health relevance of widespread case finding by testing for asymptomatic chlamydia infections is under debate. We wanted to explore future directions for chlamydia control and generate insights that might guide for evidence-based strategies. In particular, we wanted to know the extent to which we should pursue testing for asymptomatic infections at both genital and extragenital sites.Methods: We synthesised findings from published literature and from discussions among national and international chlamydia experts during an invitational workshop. We described changing perceptions in chlamydia control to inform the development of recommendations for future avenues for chlamydia control in the Netherlands.Results: Despite implementing a range of interventions to control chlamydia, there is no practice-based evidence that population prevalence can be reduced by screening programmes or widespread opportunistic testing. There is limited evidence about the beneficial effect of testing on pelvic inflammatory disease prevention. The risk of tubal factor infertility resulting from chlamydia infection is low and evidence on the preventable fraction remains uncertain. Overdiagnosis and overtreatment with antibiotics for self-limiting and non-viable infections have contributed to antimicrobial resistance in other pathogens and may affect oral, anal and genital microbiota. These changing insights could affect the outcome of previous cost-effectiveness analysis.Conclusion: The balance between benefits and harms of widespread testing to detect asymptomatic chlamydia infections is changing. The opinion of our expert group deviates from the existing paradigm of 'test and treat' and suggests that future strategies should reduce, rather than expand, the role of widespread testing for asymptomatic chlamydia infections.
|
|
| 39. |
- Williamson, Alice, et al.
(författare)
-
Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
-
Tidskriftsartikel (refereegranskat)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
|
|
| 40. |
- Witjes, J. Alfred, et al.
(författare)
-
EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees
- 2020
-
Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 77:2, s. 223-250
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
|
|
| 41. |
- Zewinger, Stephen, et al.
(författare)
-
Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease : a molecular and genetic association study
- 2017
-
Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:7, s. 534-543
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear.Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts.Findings: The median follow-up was 9.9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1.44, 95% CI 1.14-1.83) and the presence of either LPA SNP (1.88, 1.40-2.53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0.95, 0.81-1.11 and either LPA SNP 1.10, 0.92-1.31) or cardiovascular mortality (0.99, 0.81-1.2 and 1.13, 0.90-1.40, respectively) or in the validation studies.Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established.
|
|
