| 1. |
|
|
| 2. |
|
|
| 3. |
- Hoxha, A., et al.
(författare)
-
Identification of discrete epitopes of Ro52p200 and association with fetal cardiac conduction system manifestations in a rodent model
- 2016
-
Ingår i: Clinical and Experimental Immunology. - : Wiley-Blackwell. - 0009-9104 .- 1365-2249. ; 186:3, s. 284-291
-
Tidskriftsartikel (refereegranskat)abstract
- Congenital heart block (CHB) is a potentially lethal condition characterized by a third-degree atrioventricular block (AVB). Despite anti-Ro52 antibodies being detected in nearly 90% of mothers of affected children, CHB occurs in only 1-2% of anti-Ro/Sjogrens-syndrome-related antigen A (SSA) autoantibody-positive pregnancies. Maternal antibodies have been suggested to bind molecules crucial to fetal cardiac function; however, it remains unknown whether a single antibody profile associates with CHB or whether several specificities and cross-reactive targets exist. Here, we aimed to define further the reactivity profile of CHB-associated antibodies towards Ro52p200 (amino acid 200-239). We first analysed reactivity of a monoclonal anti-Ro52 antibody shown to induce AVB in rats (7.8C7) and of sera from anti-Ro52p200 antibody-positive mothers of children with CHB towards a panel of modified Ro52p200 peptides, and subsequently evaluated their potential to induce AVB in rats upon transfer during gestation. We observed that CHB maternal sera displayed a homogeneous reactivity profile targeting preferentially the C-terminal part of Ro52p200, in contrast to 7.8C7 that specifically bound the p200 N-terminal end. In particular, amino acid D233 appeared crucial to maternal antibody reactivity towards p200. Despite low to absent reactivity towards rat p200 and different binding profiles towards mutated rat peptides indicating recognition of different epitopes within Ro52p200, immunoglobulin (Ig)G purified from two mothers of children with CHB could induce AVB in rats. Our findings support the hypothesis that several fine antibody specificities and cross-targets may exist and contribute to CHB development in anti-Ro52 antibody-positive pregnancies.
|
|
| 4. |
- Kvarnstrom, M, et al.
(författare)
-
Autoantibodies to the functionally active RING-domain of Ro52/SSA are associated with disease activity in patients with lupus
- 2013
-
Ingår i: Lupus. - : SAGE Publications. - 1477-0962 .- 0961-2033. ; 22:5, s. 477-485
-
Tidskriftsartikel (refereegranskat)abstract
- The Ro52 protein of the Ro/SSA antigen was recently defined as an E3 ligase controlling cytokine production. Autoantibodies from systemic lupus erythematosus (SLE) patients targeting the Ro52-RING domain, containing the E3 ligase activity, have been shown to inhibit the E3 ligase activity of Ro52. The objective of the present study was to investigate correlations between clinical parameters in patients with SLE and levels of Ro/SSA (Ro52 and Ro60) and La/SSB autoantibodies, including autoantibodies directed towards the functional RING and B-box domains of the Ro52 protein. SLE patients ( n = 232) were clinically examined and disease activity indices collected concurrently to blood sampling. The samples were analyzed for immunological parameters including autoantibodies. Ro52 autoantibody levels were associated with more variables than the other analyzed antibodies and were significantly associated with several individual items related to sSS and the diagnosis of sSS itself ( p = 0.004). Other associated variables were high sedimentation rate ( p = 0.0003), levels of immunoglobulins ( p = 0.0003), and an inverse correlation with levels of lymphocytes ( p = 0.003) and leukocytes ( p = 0.01). Antibodies to the RING domain of Ro52, which is the functionally active domain with E3 ligase activity, were significantly correlated with disease activity as measured by the SLAM score. We conclude that autoantibodies against Ro52 and in particular its functional RING domain are important in lupus patients and associated with several clinical and laboratory features of the disease. The impact on disease activity of Ro52-RING specific antibodies was especially noted, and could imply a functional role for these autoantibodies in inhibiting Ro52 activity, which is important for the control of proinflammatory cytokine production, including type 1 interferons.
|
|
| 5. |
- Mohamed, Rana K., et al.
(författare)
-
The Missing C-1-C-5 Cycloaromatization Reaction : Triplet State Antiaromaticity Relief and Self-Terminating Photorelease of Formaldehyde for Synthesis of Fulvenes from Enynes
- 2015
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 137:49, s. 15441-15450
-
Tidskriftsartikel (refereegranskat)abstract
- The last missing example of the four archetypical cycloaromatizations of enediynes and enynes was discovered by combining a twisted alkene excited state with a new self-terminating path for intramolecular conversion of diradicals into closed-shell products. Photoexcitation of aromatic enynes to a twisted alkene triplet state creates a unique stereoelectronic situation, which is facilitated by the relief of excited state antiaromaticity of the benzene ring. This enables the usually unfavorable 5-endo-trig cyclization and merges it with 5-exo-dig closure. The 1,4-diradical product of the C1-C5 cyclization undergoes internal H atom transfer that is coupled with the fragmentation of an exocyclic C-C bond. This sequence provides efficient access to benzofulvenes from enynes and expands the utility of self-terminating aromatizing enyne cascades to photochemical reactions. The key feature of this self-terminating reaction is that, despite the involvement of radical species in the key cyclization step, no external radical sources or quenchers are needed to provide the products. In these cascades, both radical centers are formed transiently and converted to the closed-shell products via intramolecular H-transfer and C-C bond fragmentation. Furthermore, incorporating C-C bond cleavage into the photochemical self-terminating cyclizations of enynes opens a new way for the use of alkenes as alkyne equivalents in organic synthesis.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Asplund, Olof, et al.
(författare)
-
Islet Gene View-a tool to facilitate islet research
- 2022
-
Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 5:12
-
Tidskriftsartikel (refereegranskat)abstract
- Characterization of gene expression in pancreatic islets and its alteration in type 2 diabetes (T2D) are vital in understanding islet function and T2D pathogenesis. We leveraged RNA sequencing and genome-wide genotyping in islets from 188 donors to create the Islet Gene View (IGW) platform to make this information easily accessible to the scientific community. Expression data were related to islet phenotypes, diabetes status, other islet-expressed genes, islet hormone-encoding genes and for expression in insulin target tissues. The IGW web application produces output graphs for a particular gene of interest. In IGW, 284 differentially expressed genes (DEGs) were identified in T2D donor islets compared with controls. Forty percent of DEGs showed cell-type enrichment and a large proportion significantly co-expressed with islet hormone-encoding genes; glucagon (GCG, 56%), amylin (IAPP, 52%), insulin (INS, 44%), and somatostatin (SST, 24%). Inhibition of two DEGs, UNC5D and SERPINE2, impaired glucose-stimulated insulin secretion and impacted cell survival in a human beta-cell model. The exploratory use of IGW could help designing more comprehensive functional follow-up studies and serve to identify therapeutic targets in T2D.
|
|
| 9. |
- Aziz, Emad F., et al.
(författare)
-
Interaction between liquid water and hydroxide revealed by core-hole de-excitation
- 2008
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7209, s. 89-91
-
Tidskriftsartikel (refereegranskat)abstract
- The hydroxide ion plays an important role in many chemical and biochemical processes in aqueous solution(1). But ourmolecular- level understanding of its unusual and fast transport in water, and of the solvation patterns that allow fast transport, is far from complete. One proposal seeks to explain the properties and behaviour of the hydroxide ion by essentially regarding it as a water molecule that is missing a proton(2), and by inferring transport mechanisms and hydration structures from those of the excess proton. A competing proposal invokes instead unique and interchanging hydroxide hydration complexes, particularly the hypercoordinated OH-(H2O)(4) species and tri- coordinated OH-(H2O)(3) that can form a transient hydrogen bond between the H atom of the OH- and a neighbouring water molecule(3-5). Here we report measurements of core- level photoelectron emission and intermolecular Coulombic decay(6-8) for an aqueous hydroxide solution, which show that the hydrated hydroxide ion is capable of transiently donating a hydrogen bond to surrounding watermolecules. In agreement with recent experimental studies of hydroxide solutions(9-12), our finding thus supports the notion that the hydration structure of the hydroxide ion cannot be inferred from that of the hydrated excess proton.
|
|
| 10. |
|
|
| 11. |
- de Vries, Claire E. E., et al.
(författare)
-
Outcomes of the first global multidisciplinary consensus meeting including persons living with obesity to standardize patient-reported outcome measurement in obesity treatment research
- 2022
-
Ingår i: Obesity Reviews. - : John Wiley & Sons. - 1467-7881 .- 1467-789X. ; 23:8
-
Tidskriftsartikel (refereegranskat)abstract
- Quality of life is a key outcome that is not rigorously measured in obesity treatment research due to the lack of standardization of patient-reported outcomes (PROs) and PRO measures (PROMs). The S.Q.O.T. initiative was founded to Standardize Quality of life measurement in Obesity Treatment. A first face-to-face, international, multidisciplinary consensus meeting was conducted to identify the key PROs and preferred PROMs for obesity treatment research. It comprised of 35 people living with obesity (PLWO) and healthcare providers (HCPs). Formal presentations, nominal group techniques, and modified Delphi exercises were used to develop consensus-based recommendations. The following eight PROs were considered important: self-esteem, physical health/functioning, mental/psychological health, social health, eating, stigma, body image, and excess skin. Self-esteem was considered the most important PRO, particularly for PLWO, while physical health was perceived to be the most important among HCPs. For each PRO, one or more PROMs were selected, except for stigma. This consensus meeting was a first step toward standardizing PROs (what to measure) and PROMs (how to measure) in obesity treatment research. It provides an overview of the key PROs and a first selection of the PROMs that can be used to evaluate these PROs.
|
|
| 12. |
- Denisova V, Aleksandra, et al.
(författare)
-
A Computational Investigation of the Substituent Effects on Geometric, Electronic, and Optical Properties of Siloles and 1,4-Disilacyclohexa-2,5-dienes
- 2017
-
Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 22:3
-
Tidskriftsartikel (refereegranskat)abstract
- Thirty two differently substituted siloles 1a–1p and 1,4-disilacyclohexa-2,5-dienes 2a–2p were investigated by quantum chemical calculations using the PBE0 hybrid density functional theory (DFT) method. The substituents included σ-electron donating and withdrawing, as well as π-electron donating and withdrawing groups, and their effects when placed at the Si atom(s) or at the C atoms were examined. Focus was placed on geometries, frontier orbital energies and the energies of the first allowed electronic excitations. We analyzed the variation in energies between the orbitals which correspond to HOMO and LUMO for the two parent species, here represented as ΔεHL, motivated by the fact that the first allowed transitions involve excitation between these orbitals. Even though ΔεHL and the excitation energies are lower for siloles than for 1,4-disilacyclohexa-2,5-dienes the latter display significantly larger variations with substitution. The ΔεHL of the siloles vary within 4.57–5.35 eV (ΔΔεHL = 0.78 eV) while for the 1,4-disilacyclohexa-2,5-dienes the range is 5.49–7.15 eV (ΔΔεHL = 1.66 eV). The excitation energy of the first allowed transitions display a moderate variation for siloles (3.60–4.41 eV) whereas the variation for 1,4-disilacyclohexa-2,5-dienes is nearly doubled (4.69–6.21 eV). Cyclobutadisiloles combine the characteristics of siloles and 1,4-disilacyclohexa-2,5-diene by having even lower excitation energies than siloles yet also extensive variation in excitation energies to substitution of 1,4-disilacyclohexa-2,5-dienes (3.47–4.77 eV, variation of 1.30 eV).
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Ivanchenko, M, et al.
(författare)
-
Natural killer cells and type II interferon in Ro/SSA and La/SSB autoantibody-exposed newborns at risk of congenital heart block
- 2021
-
Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 80:2, s. 194-202
-
Tidskriftsartikel (refereegranskat)abstract
- Congenital heart block (CHB) with immune cell infiltration develops in the fetus after exposure to maternal Ro/La autoantibodies. CHB-related serology has been extensively studied, but reports on immune-cell profiles of anti-Ro/La-exposed neonates are lacking. In the current study, we characterised circulating immune-cell populations in anti-Ro/La+mothers and newborns, and explored potential downstream effects of skewed neonatal cell populations.MethodsIn total, blood from mothers (n=43) and neonates (n=66) was sampled at birth from anti-Ro/La+ (n=36) and control (n=30) pregnancies with or without rheumatic disease and CHB. Flow cytometry, microarrays and ELISA were used for characterising cells and plasma.ResultsSimilar to non-pregnant systemic lupus erythematosus and Sjögren-patients, anti-Ro/La+mothers had altered B-cell subset frequencies, relative T-cell lymphopenia and lower natural killer (NK)-cell frequencies. Surprisingly, their anti-Ro/La exposed neonates presented higher frequencies of CD56dimCD16hiNK cells (p<0.01), but no other cell frequency differences compared with controls. Type I and II interferon (IFN) gene-signatures were revealed in neonates of anti-Ro/La+ pregnancy, and exposure of fetal cardiomyocytes to type I IFN induced upregulation of several NK-cell chemoattractants and activating ligands. Intracellular flow cytometry revealed IFNγ production by NK cells, CD8+and CD4+T cells in anti-Ro/La exposed neonates. IFNγ was also detectable in their plasma.ConclusionOur study demonstrates an increased frequency of NK cells in anti-Ro/La exposed neonates, footprints of type I and II IFN and an upregulation of ligands activating NK cells in fetal cardiac cells after type I IFN exposure. These novel observations demonstrate innate immune activation in neonates of anti-Ro/La+pregnancy, which could contribute to the risk of CHB.
|
|
| 21. |
|
|
| 22. |
- Jonsson Čabrajić, Anna V, 1978-
(författare)
-
Modeling lichen performance in relation to climate : scaling from thalli to landscapes
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lichens can colonize nearly all terrestrial habitats on earth and are functionally important in many ecosystems. Being poikilohydric, their active growth periods are restricted to periods when the thallus is hydrated from atmospheric water sources, such as rain, fog and high relative humidity. Since lichen hydration varies greatly over time lichen growth is therefore more difficult to model compared with, for example vascular plants with more even water supply. I developed two models to predict lichen hydration under field conditions that incorporates the atmospheric water potential (Ψair), derived from air temperature and humidity, only or in combination with species-specific rehydration and desiccation rates. Using Ψair allows the prediction of hydration induced by several water sources. These models were very accurate for epiphytic lichens with a close coupling to atmospheric conditions, but they were less accurate for mat-forming lichens with substantial aerodynamic boundary layers. The hydration model was further developed to include photosynthetic activation for different species, in order to compare their performance under different micro-climatic scenarios. Water balance and activation rate had large effects on lichen activity and were positively related to habitats providing long hydration periods, for example close to streams. To study effects of climate change, a complete model for net carbon gain (photosynthesis minus respiratory losses) was developed for an epiphytic lichen with intricate responses to light, hydration and temperature. Simulation responses in different climate scenarios revealed that projected climate change on a regional scale resulted in varied local scale responses. At the lighter, exposed sites of a forest, the growth responses were positive, but were potentially negative at darker sites with closed canopy. At the local scale, fluctuating hydration, summed irradiance when wet and Chlorophyll a are variables that predict lichen growth. However, at a landscape scale, these variables may be too detailed. We tested this for two terrestrial, mat-forming lichens and developed statistical models for lichen growth in the widest possible climatic gradient in northern Scandinavia, varying in light, temperature and precipitation. Light was the most important factor for high growth at the landscape scale, reaching saturation at a site openness of 40 %, equivalent to a basal tree area of 15 m2 ha -1 in this study. Thereafter, hydration was the next limiting factor, which could be well described by precipitation for one of the species. The simplest predictor was the normal temperature in July, which was negatively correlated with growth. It was apparent that the predictive variables and their power varied at different scales. However, light and hydration are limiting at all scales, particularly by light conditions when lichens are wet. This implies that ensuring that there is sufficient light below the forest canopy is crucial for lichen growth, especially for mat-forming lichens. Hydrophilic lichens may be better preserved in open habitats with long hydration periods. It was shown that models can be powerful and “easy to use” tools to predict lichen responses in various habitats and under different climate scenarios. Models can therefore help to identify suitable habitats with optimal growth conditions, which is very important for the conservation and management of lichens and their habitats.
|
|
| 23. |
- Jonsson Čabrajić, Anna V, et al.
(författare)
-
Modelling hydration and photosystem II activation in relation to in situ rain and humidity patterns : a tool to compare performance of rare an generalist epiphytic lichens
- 2010
-
Ingår i: Plant, Cell and Environment. - : Wiley. - 0140-7791 .- 1365-3040. ; 33, s. 840-850
-
Tidskriftsartikel (refereegranskat)abstract
- A dynamic water and activity model was developed to assess how efficiently lichens can exploit in situ rain and humid air. The capacity to rehydrate and activate photosynthesis [i.e. photosystem II (PSII)] by these water sources was compared among four hydrophilic and one generalist epiphytic lichen. Hydration status, potential (instant activation) and realized (delayed activation) day-light activity were simulated using a model based on species-specific hydration, PSII activation characteristics and in situ water content for Platismatia norvegica in three microclimatic scenarios. The results showed that delayed PSII activation could have profound effects on lichens' ability to exploit environmental water sources. During rain, realized activity was reduced by 19, 34 and 56% compared to simulations assuming instant activation for three hydrophilic lichens in the driest microclimate. During humid air, the reduction was 81% for the most extreme species and scenario, because of slow hydration and low equilibrium water content. Many and brief hydration events may thus hamper species with slow activation and fast desiccation kinetics. No evidence of compensation by a 'water-holding' morphology was observed among studied species. The developed model may provide a tool for identifying suitable habitats for long-term persistence of lichens with physiological constraints.
|
|
| 24. |
- Jorner, Kjell, et al.
(författare)
-
Impact of Ground- and Excited-State Aromaticity on Cyclopentadiene and Silole Excitation Energies and Excited-State Polarities
- 2014
-
Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 20:30, s. 9295-9303
-
Tidskriftsartikel (refereegranskat)abstract
- A new qualitative model for estimating the properties of substituted cyclopentadienes and siloles in their lowest pi pi* excited states is introduced and confirmed through quantum chemical calculations, and then applied to explain earlier reported experimental excitation energies. According to our model, which is based on excited-state aromaticity and antiaromaticity, siloles and cyclopentadienes are cross-hyperconjugated "aromatic chameleons" that adapt their electronic structures to conform to the various aromaticity rules in different electronic states (Huckel's rule in the pi(2) electronic ground state (S-0) and Baird's rule in the lowest pi pi* excited singlet and triplet states (S-1 and T-1)). By using pen-and-paper arguments, one can explain polarity changes upon excitation of substituted cyclopentadienes and siloles, and one can tune their lowest excitation energies by combined considerations of ground-and excited-state aromaticity/antiaromaticity effects. Finally, the "aromatic chameleon" model can be extended to other monocyclic compound classes of potential use in organic electronics, thereby providing a unified view of the S-0, T-1, and S-1 states of a range of different cyclic cross-pi-conjugated and cross-hyperconjugated compound classes.
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- le Roux, Carel W., et al.
(författare)
-
Bariatric Surgery : There Is a Room for Improvement to Reduce Mortality in Patients with Type 2 Diabetes
- 2021
-
Ingår i: Obesity Surgery. - : Springer. - 0960-8923 .- 1708-0428.
-
Tidskriftsartikel (refereegranskat)abstract
- The new Scandinavian Obesity Surgery Registry (SOReg) report may influence current guidelines. Patients without type 2 diabetes (T2DM) prior to bariatric surgery had lower mortality over 6.3 years compared to those with T2DM. Moreover, patients with T2DM who achieved remission within 1 year after surgery had lower mortality than those who did not remit. Finally, there was no threshold at 10 years, but rather a linear relationship between duration of T2DM and glycemic remission. The SOReg report challenges existing recommendations and clinical practice. A case may also be made for patients with T2DM who did not achieve glycemic remission after 1 year to have a combination approach of surgery with medicines rather than surgery alone. Ultimately, the impact of T2DM duration on glycemic remission again suggest that patients with T2DM should have bariatric surgery earlier.
|
|
| 29. |
- Lidén, Marlene, et al.
(författare)
-
Species-specific activation time-lags can explain habitat restrictions in hydrophiclic lichens
- 2010
-
Ingår i: Plant, Cell and Environment. - : Wiley. - 0140-7791 .- 1365-3040. ; 33, s. 851-862
-
Tidskriftsartikel (refereegranskat)abstract
- Photosystem II (PSII) activation after hydration with water or humid air was measured in four hydrophilic and a generalist lichen to test the hypothesis that slow activation might explain habitat restriction in the former group. For the hydrophilic species, activation was after 4 h nearly completed in Lobaria amplissima and Platismatia norvegica, while only c. 50% for Bryoria bicolor and Usnea longissima. The generalist Platismatia glauca was activated instantaneously. The effect of this on lichen field performance was investigated using a dynamic model separating the two water sources rain and humid air. Model simulations were made using the species-specific characteristics and climate data from 12 stream microhabitats. For U. longissima, slow PSII activation could reduce realized photosynthesis by a factor of five. Bryoria bicolor was almost as severely affected, while P. norvegica displayed moderate reductions. Lobaria amplissima displayed longer realized activity periods even in unfavourable microclimates, possibly because of a higher water loss resistance. Both close proximity to streams and presence of turbulent water had a positive impact on realized activity among the slowly activated species, coinciding with observed distribution patterns of hydrophilic species. The results presented here may thus partly explain observed habitat restrictions of rare hydrophilic lichens.
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
- Meisgen, S, et al.
(författare)
-
Auxilin is a novel susceptibility gene for congenital heart block which directly impacts fetal heart function
- 2022
-
Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 81:8, s. 1151-1161
-
Tidskriftsartikel (refereegranskat)abstract
- Neonatal lupus erythematosus (NLE) may develop after transplacental transfer of maternal autoantibodies with cardiac manifestations (congenital heart block, CHB) including atrioventricular block, atrial and ventricular arrhythmias, and cardiomyopathies. The association with anti-Ro/SSA antibodies is well established, but a recurrence rate of only 12%–16% despite persisting maternal autoantibodies suggests that additional factors are required for CHB development. Here, we identify fetal genetic variants conferring risk of CHB and elucidate their effects on cardiac function.MethodsA genome-wide association study was performed in families with at least one case of CHB. Gene expression was analysed by microarrays, RNA sequencing and PCR and protein expression by western blot, immunohistochemistry, immunofluorescence and flow cytometry. Calcium regulation and connectivity were analysed in primary cardiomyocytes and cells induced from pleuripotent stem cells. Fetal heart performance was analysed by Doppler/echocardiography.ResultsWe identified DNAJC6 as a novel fetal susceptibility gene, with decreased cardiac expression of DNAJC6 associated with the disease risk genotype. We further demonstrate that fetal cardiomyocytes deficient in auxilin, the protein encoded by DNAJC6, have abnormal connectivity and Ca2+ homoeostasis in culture, as well as decreased cell surface expression of the Cav1.3 calcium channel. Doppler echocardiography of auxilin-deficient fetal mice revealed cardiac NLE abnormalities in utero, including abnormal heart rhythm with atrial and ventricular ectopias, as well as a prolonged atrioventricular time intervals.ConclusionsOur study identifies auxilin as the first genetic susceptibility factor in NLE modulating cardiac function, opening new avenues for the development of screening and therapeutic strategies in CHB.
|
|
| 33. |
- Nolting, Dirk, et al.
(författare)
-
pH-induced protonation of lysine in aqueous solution causes chemical shifts in X-ray photoelectron spectroscopy.
- 2007
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 129:45, s. 14068-73
-
Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the applicability of X-ray photoelectron spectroscopy to obtain charge- and site-specific electronic structural information of biomolecules in aqueous solution. Changing the pH of an aqueous solution of lysine from basic to acidic results in nitrogen 1s and carbon 1s chemical shifts to higher binding energies. These shifts are associated with the sequential protonation of the two amino groups, which affects both charge state and hydrogen bonding to the surrounding water molecules. The N1s chemical shift is 2.2 eV, and for carbon atoms directly neighboring a nitrogen the shift for C1s is approximately 0.4 eV. The experimental binding energies agree reasonably with our calculated energies of lysine(aq) for different pH values.
|
|
| 34. |
- Nolting, Dirk, et al.
(författare)
-
Pseudoequivalent nitrogen atoms in aqueous imidazole distinguished by chemical shifts in photoelectron spectroscopy.
- 2008
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 130:26, s. 8150-1
-
Tidskriftsartikel (refereegranskat)abstract
- The photoelectron spectra of aqueous imidazole are presented, and the N 1s and C 1s binding energies are assigned aided by density functional theory calculations. The chemical equivalency of the two nitrogens of the cationic form is directly identified by the occurrence of a single N 1s photoelectron peak, which results from the delocalization of the positive charge over the molecule as a consequence of the Cv symmetry of the system. In contrast to NMR measurements, the photoemission process is faster than the rapid proton exchange in the aqueous environment, making the pseudoequivalent nitrogens of the neutral state clearly distinguishable with a N 1s binding energy shift of 1.7 eV.
|
|
| 35. |
- Nääv Ottosson, Jens, et al.
(författare)
-
The effect of traction force on eyelid blood perfusion during closure of defects
- 2024
-
Ingår i: Orbit (London). - 0167-6830. ; , s. 1-7
-
Tidskriftsartikel (refereegranskat)abstract
- PurposeIn oculoplastic surgery the eyelid tissue is frequently stretched in order to repair defects after tumor surgery. However, there is a paucity of research regarding how stretching affects eyelids. The purpose of this study was to gain insight into how traction force affects eyelid stretch as well as tissue perfusion, using a laser-based in vivo monitoring technique.MethodLower-lid pentagonal resections were performed in eight patients and a total of nine eyelids. The medial section of the eyelid was then stretched using a dynamometer up to a force of 2.3 Newtons (N), and eyelid stretching and blood perfusion were continuously measured using laser speckle contrast imaging.ResultsTissue perfusion decreased exponentially when eyelid tissue was stretched, with an initial sharp decline followed by a more gradual reduction. Perfusion approached zero at a force of approximately 2.0 N. The length of the eyelid increased with increasing force up to 1.5 N, after which there was only a very slight increase in length.ConclusionsEyelid tissue seems to respond to traction in a non-linear fashion, where the initial force results in the greatest eyelid stretching and reduction in blood perfusion. The results provide information on the effects of a large force for direct closure of large eyelid defects. Considering how quickly perfusion approaches zero, the high success rate of eyelid reconstruction surgery is likely a testament to the extensive vascularization of the periocular region.
|
|
| 36. |
- Ottosson, L., et al.
(författare)
-
Structurally derived mutations define congenital heart block-related epitopes within the 200-239 amino acid stretch of the Ro52 protein
- 2005
-
Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 61:2, s. 109-118
-
Tidskriftsartikel (refereegranskat)abstract
- Congenital heart block is a passively transferred autoimmune condition, which affects the children of mothers with Ro/SSA autoantibodies. During pregnancy, the antibodies are transported across the placenta and affect the fetus. We have previously demonstrated that antibodies directed to the 200-239 amino acid (aa) stretch of the Ro52 component of the Ro/SSA antigen correlate with the development of congenital heart block. In this report, we investigated the antibody-antigen interaction of this target epitope in detail at a molecular and structural level. Peptides representing aa 200-239 (p200) with structurally derived mutations were synthesized to define the epitopes recognized by two Ro52 human monoclonal antibodies, S3A8 and M4H1, isolated from patient-derived phage display libraries. Analyses by ELISA, circular dichroism and MALDI-TOF-MS demonstrate that the antibody recognition is dependent on a partly a-helical fold within the putative leucine zipper of the 200-239 aa stretch and that the two human anti-p200 monoclonal antibodies, M4H1 and S3A8, recognize different epitopic structures within the p200 peptide. In addition, we investigated the representation of each fine specificity within the sera of mothers with children born with congenital heart block, and in such sera, antibodies of the S3A8 idiotype were more commonly detected and at higher levels than M4H1-like antibodies.
|
|
| 37. |
|
|
| 38. |
- Ottosson, Niklas, et al.
(författare)
-
Molecular Sinkers : X-ray Photoemission and Atomistic Simulations of Benzoic Acid and Benzoate at the Aqueous Solution/Vapor Interface
- 2012
-
Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 116:43, s. 13017-13023
-
Tidskriftsartikel (refereegranskat)abstract
- In this work we, for the first time, provide a detailed microscopic picture of the behavior of benzoic acid at the aqueous solution/vapor interface in its neutral as well as in its dissociated form (benzoate). This is achieved through a combination of highly surface-sensitive X-ray photoelectron spectroscopy experiments and fully atomistic molecular simulations. We show that drastic changes occur in the interface behavior of the neutral acid upon release of the proton. The benzoic acid molecules are found to be strongly adsorbed in the interface layer with the planes of the aromatic rings oriented almost parallel to the water surface. In contrast, in the benzoate form the carboxylate group shows a sinker-like behavior while the aromatic ring acts as a buoy, oriented nearly perpendicular to the surface. Furthermore, a significant fraction of the molecular ions move from the interface layer into the bulk of the solution. We rationalize these findings in terms of the very different hydration properties of benzoic acid's carboxylic group in the two charge states. The molecule has an amphiphilic nature and the deprotonation thus changes the hydrophobic/hydrophilic balance between the nonpolar aromatic and the polar carboxylic parts of the molecule. That, consequently, leads to a pronounced reorientation of the molecule at the interface.
|
|
| 39. |
- Pettersson, Maria, et al.
(författare)
-
Cytogenetically visible inversions are formed by multiple molecular mechanisms
- 2020
-
Ingår i: Human Mutation. - : WILEY. - 1059-7794 .- 1098-1004. ; 41:11, s. 1979-1998
-
Tidskriftsartikel (refereegranskat)abstract
- Cytogenetically detected inversions are generally assumed to be copy number and phenotypically neutral events. While nonallelic homologous recombination is thought to play a major role, recent data suggest the involvement of other molecular mechanisms in inversion formation. Using a combination of short-read whole-genome sequencing (WGS), 10X Genomics Chromium WGS, droplet digital polymerase chain reaction and array comparative genomic hybridization we investigated the genomic structure of 18 large unique cytogenetically detected chromosomal inversions and achieved nucleotide resolution of at least one chromosomal inversion junction for 13/18 (72%). Surprisingly, we observed that seemingly copy number neutral inversions can be accompanied by a copy-number gain of up to 350 kb and local genomic complexities (3/18, 17%). In the resolved inversions, the mutational signatures are consistent with nonhomologous end-joining (8/13, 62%) or microhomology-mediated break-induced replication (5/13, 38%). Our study indicates that short-read 30x coverage WGS can detect a substantial fraction of chromosomal inversions. Moreover, replication-based mechanisms are responsible for approximately 38% of those events leading to a significant proportion of inversions that are actually accompanied by additional copy-number variation potentially contributing to the overall phenotypic presentation of those patients.
|
|
| 40. |
|
|
| 41. |
- Pokapanich, Wandared, et al.
(författare)
-
Ionic charge dependence of ion-solvent ICD time-scale for aqueous ions probed by the core-hole clock
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Auger electron spectroscopy combined with theoretical calculations have been applied to investigate the decay of the Ca 2p core hole of aqueous Ca2+. Localized final states due to Auger-like and de-localized final states due to ICD-like decay processes are identified. By applying the core-hole clock spectroscopy method, the time constant of the ICD-like decay was determined to 24±6 fs for Ca2+. We have compared to ICD-like processes in other aqueous ions, K+, Na+, Mg2+ and Al3+, and observe a variation of the time constants of two orders of magnitude. This large variation is qualitatively explained by differences both internal and external to the ions; different internal decay mechanisms of the ions, as well as external differences in the ion-solute distances and interactions.
|
|
| 42. |
- Pokapanich, Wandared, et al.
(författare)
-
Ionic-Charge Dependence of tie Intermolecular Coulombic Decay Time Scale for Aqueous Ions Probed by the Core-Hole Clock
- 2011
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 133:34, s. 13430-13436
-
Tidskriftsartikel (refereegranskat)abstract
- Auger electron spectroscopy combined with theoretical calculations has been applied to investigate the decay of the Ca 2p core hole of aqueous Ca2+. Beyond the localized two-hole final states on the calcium ion, originating from a normal Auger process, we have further identified the final states delocalized between the calcium ion and its water surroundings and produced by core level intermolecular Coulombic decay (ICD) processes. By applying the core-hole clock method, the time scale of the core level ICD was determined to be 33 +/- 1 fs for the 2p core hole of the aqueous Ca2+. The comparison of this time constant to those associated with the aqueous K+, Na+, Mg2+, and Al3+ ions reveals differences of 1 and up to 2 orders of magnitude. Such large variations in the characteristic time scales of the core level ICD processes is qualitatively explained by different internal decay mechanisms in different ions as well as by different ion solvent distances and interactions.
|
|
| 43. |
- Ramonet, M., et al.
(författare)
-
The fingerprint of the summer 2018 drought in Europe on ground-based atmospheric CO 2 measurements : Atmospheric CO 2 anomaly
- 2020
-
Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 375:1810
-
Tidskriftsartikel (refereegranskat)abstract
- During the summer of 2018, a widespread drought developed over Northern and Central Europe. The increase in temperature and the reduction of soil moisture have influenced carbon dioxide (CO 2) exchange between the atmosphere and terrestrial ecosystems in various ways, such as a reduction of photosynthesis, changes in ecosystem respiration, or allowing more frequent fires. In this study, we characterize the resulting perturbation of the atmospheric CO 2 seasonal cycles. 2018 has a good coverage of European regions affected by drought, allowing the investigation of how ecosystem flux anomalies impacted spatial CO 2 gradients between stations. This density of stations is unprecedented compared to previous drought events in 2003 and 2015, particularly thanks to the deployment of the Integrated Carbon Observation System (ICOS) network of atmospheric greenhouse gas monitoring stations in recent years. Seasonal CO 2 cycles from 48 European stations were available for 2017 and 2018. Earlier data were retrieved for comparison from international databases or national networks. Here, we show that the usual summer minimum in CO 2 due to the surface carbon uptake was reduced by 1.4 ppm in 2018 for the 10 stations located in the area most affected by the temperature anomaly, mostly in Northern Europe. Notwithstanding, the CO 2 transition phases before and after July were slower in 2018 compared to 2017, suggesting an extension of the growing season, with either continued CO 2 uptake by photosynthesis and/or a reduction in respiration driven by the depletion of substrate for respiration inherited from the previous months due to the drought. For stations with sufficiently long time series, the CO 2 anomaly observed in 2018 was compared to previous European droughts in 2003 and 2015. Considering the areas most affected by the temperature anomalies, we found a higher CO 2 anomaly in 2003 (+3 ppm averaged over 4 sites), and a smaller anomaly in 2015 (+1 ppm averaged over 11 sites) compared to 2018. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
|
|
| 44. |
- Ruetz, Tyson, et al.
(författare)
-
Constitutively Active SMAD2/3 Are Broad-Scope Potentiators of Transcription-Factor-Mediated Cellular Reprogramming
- 2017
-
Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909 .- 1875-9777. ; , s. 9-805
-
Tidskriftsartikel (refereegranskat)abstract
- Reprogramming of cellular identity using exogenous expression of transcription factors (TFs) is a powerful and exciting tool for tissue engineering, disease modeling, and regenerative medicine. However, generation of desired cell types using this approach is often plagued by inefficiency, slow conversion, and an inability to produce mature functional cells. Here, we show that expression of constitutively active SMAD2/3 significantly improves the efficiency of induced pluripotent stem cell (iPSC) generation by the Yamanaka factors. Mechanistically, SMAD3 interacts with reprogramming factors and co-activators and co-occupies OCT4 target loci during reprogramming. Unexpectedly, active SMAD2/3 also markedly enhances three other TF-mediated direct reprogramming conversions, from B cells to macrophages, myoblasts to adipocytes, and human fibroblasts to neurons, highlighting broad and general roles for SMAD2/3 as cell-reprogramming potentiators. Our results suggest that co-expression of active SMAD2/3 could enhance multiple types of TF-based cell identity conversion and therefore be a powerful tool for cellular engineering. Ruetz et al. show that constitutively active SMAD2/3 has a surprising ability to boost the efficiency of cell reprogramming both to iPSCs and across lineages and may therefore be a general factor that can enhance transcription-factor-mediated reprogramming in a variety of contexts.
|
|
| 45. |
|
|
| 46. |
- Winter, Bernd, et al.
(författare)
-
Electron dynamics in charge-transfer-to-solvent states of aqueous chloride revealed by Cl- 2p resonant Auger-electron spectroscopy
- 2008
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 130:22, s. 7130-7138
-
Tidskriftsartikel (refereegranskat)abstract
- Charge-transfer-to-solvent (CTTS) excited states of aqueous chloride are studied by a novel experimental approach based on resonant inner-shell photoexcitation, Cl-aq(-) 2p -> e(i), i = 1-4, which denotes a series of excitations to lowest and higher CTTS states. These states are clearly identified through the occurrence of characteristic spectator Auger decays to double Cl 3p valence-hole states, where the CTTS states can be more stabilized as compared to single Cl-aq(-) 2p core excitations and optical valence excitations. Furthermore, we have found for the first time that the CTTS electron e(i) bound by a single Cl 2p hole not only behaves as a spectator e(i) -> e'(i), bound by a double valence-hole state before relaxation of the excited electron (i) itself, but also shows electron dynamics to the relaxed lowest state, e(i) -> e'(1*). This interpretation is supported by ab initio calculations. The key to performing photoelectron and Augerelectron spectroscopy studies from aqueous solutions is the use of a liquid microjet in ultrahigh vacuum in conjunction with synchrotron radiation.
|
|
| 47. |
- Xu, Huiling, et al.
(författare)
-
Pregnancy Weight Gain After Gastric Bypass or Sleeve Gastrectomy
- 2023
-
Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:12
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Pregnancy weight gain may affect the association of bariatric surgery with postsurgery pregnancy outcomes. However, the association of pregnancy weight gain with bariatric surgery is unclear.OBJECTIVE: To compare pregnancy weight gain among women with a history of bariatric surgery vs those without and to investigate whether pregnancy weight gain differs by surgical procedure, surgery-to-conception interval, and/or surgery-to-conception weight loss.DESIGN, SETTING, AND PARTICIPANTS: This nationwide, population-based matched cohort study was conducted in Sweden from 2014 to 2021. Singleton pregnancies with a history of bariatric surgery were propensity score matched (1:1) to pregnancies without such a history according to early-pregnancy body mass index (BMI), prepregnancy diabetes, prepregnancy hypertension, maternal age, smoking status, education level, height, country of birth, and delivery year. In addition, post-gastric bypass pregnancies were matched to post-sleeve gastrectomy pregnancies using the same matching strategy. Data analysis was performed from November 2022 to May 2023. EXPOSURE: History of bariatric surgery.MAIN OUTCOMES AND MEASURES: Pregnancy weight gain was standardized by gestational age into early-pregnancy BMI-specific z scores.RESULTS: This study included 12 776 pregnancies, of which 6388 had a history of bariatric surgery and 6388 were matched controls. The mean (SD) age was 31.6 (4.9) years for the surgery group and 31.4 (5.2) for the matched controls, with an early-pregnancy mean (SD) BMI of 29.4 (5.2) in both groups. Across all early-pregnancy BMI strata, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls. The differences in pregnancy weight gain z score values between the 2 groups were -0.33 (95% CI, -0.43 to -0.23) for normal weight, -0.33 (95% CI, -0.40 to -0.27) for overweight, -0.21 (95% CI, -0.29 to -0.13) for obese class I, -0.16 (95% CI, -0.29 to -0.03) for obese class II, and -0.08 (95% CI, -0.28 to 0.13) for obese class III. Pregnancy weight gain did not differ by surgical procedure. A shorter surgery-to-conception interval (particularly within 1 year) or lower surgery-to-conception weight loss was associated with lower pregnancy weight gain.CONCLUSIONS AND RELEVANCE: In this nationwide matched cohort study, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls with similar early-pregnancy characteristics. Pregnancy weight gain was lower in those with a shorter surgery-to-conception interval or lower surgery-to-conception weight loss, but did not differ by surgical procedure.
|
|
