| 1. |
|
|
| 2. |
|
|
| 3. |
- 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.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Antoniou, A C, et al.
(författare)
-
Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies
- 2005
-
Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 42:7, s. 602-603
-
Tidskriftsartikel (refereegranskat)abstract
- A recent report estimated the breast cancer risks in carriers of the three Ashkenazi founder mutations to be higher than previously published estimates derived from population based studies. In an attempt to confirm this, the breast and ovarian cancer risks associated with the three Ashkenazi founder mutations were estimated using families included in a previous meta-analysis of populatrion based studies. The estimated breast cancer risks for each of the founder BRCA1 and BRCA2 mutations were similar to the corresponding estimates based on all BRCA1 or BRCA2 mutations in the meta-analysis. These estimates appear to be consistent with the observed prevalence of the mutations in the Ashkenazi Jewish population.
|
|
| 21. |
- Brynjolfsson, E. J., et al.
(författare)
-
Black hole thermodynamics and heavy fermion metals
- 2010
-
Ingår i: Journal of High Energy Physics (JHEP). - 1126-6708 .- 1029-8479. ; :8, s. 027-
-
Tidskriftsartikel (refereegranskat)abstract
- Heavy fermion alloys at critical doping typically exhibit non-Fermi-liquid behavior at low temperatures, including a logarithmic or power law rise in the ratio of specific heat to temperature as the temperature is lowered. Anomalous specific heat of this type is also observed in a simple class of gravitational dual models that exhibit anisotropic scaling with dynamical critical exponent z > 1.
|
|
| 22. |
- Brynjolfsson, E. J., et al.
(författare)
-
Holographic models with anisotropic scaling
- 2010
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We consider gravity duals to d+1 dimensional quantum critical points with anisotropic scaling. The primary motivation comes from strongly correlated electron systems in condensed matter theory but the main focus of the present paper is on the gravity models in their own right. Physics at finite temperature and fixed charge density is described in terms of charged black branes. Some exact solutions are known and can be used to obtain a maximally extended spacetime geometry, which has a null curvature singularity inside a single non-degenerate horizon, but generic black brane solutions in the model can only be obtained numerically. Charged matter gives rise to black branes with hair that are dual to the superconducting phase of a holographic superconductor. Our numerical results indicate that holographic superconductors with anisotropic scaling have vanishing zero temperature entropy when the back reaction of the hair on the brane geometry is taken into account.
|
|
| 23. |
- Brynjolfsson, E. J., et al.
(författare)
-
Holographic superconductors with Lifshitz scaling
- 2010
-
Ingår i: Journal of physics. A, Mathematical and theoretical. - : IOP Publishing. - 1751-8113 .- 1751-8121. ; 43:6, s. 065401-
-
Tidskriftsartikel (refereegranskat)abstract
- Black holes in asymptotically Lifshitz spacetime provide a window onto finite temperature effects in strongly coupled Lifshitz models. We add a Maxwell gauge field and charged matter to a recently proposed gravity dual of (2+ 1)-dimensional Lifshitz theory. This gives rise to charged black holes with scalar hair, which correspond to the superconducting phase of holographic superconductors with z > 1 Lifshitz scaling. Along the way we analyze the global geometry of static, asymptotically Lifshitz black holes at the arbitrary critical exponent z > 1. In all known exact solutions there is a null curvature singularity in the black hole region, and, by a general argument, the same applies to generic Lifshitz black holes.
|
|
| 24. |
- Chew, Michelle, et al.
(författare)
-
Soluble CD40L (CD154) is increased in patients with shock.
- 2010
-
Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 59, s. 979-982
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Recent data suggest that soluble CD40L (sCD40L) plays an important role in murine sepsis. The aim of the present study was to determine plasma levels of CD40L in critically ill patients with systemic inflammatory response syndrome (SIRS) and shock, with and without sepsis. DESIGN: A prospective observational one-centre cohort study in a mixed-bed ICU of an university hospital. Fifty-three consecutive patients fulfilling the criteria for SIRS with shock as well as seven age-matched controls were included. ELISA was used to determine sCD40L in the plasma. RESULTS: The level of sCD40L in plasma from healthy controls was 0.18 +/- 0.03 ng/ml. It was found that sCD40L levels were significantly higher in patients with non-septic shock (0.72 +/- 0.18 ng/ml) and septic shock (0.50 +/- 0.1 ng/ml). However, the levels of sCD40L were not different between these two groups of patients, or in those with low and high APACHE scores. CONCLUSION: Our data show that sCD40L is increased in patients with shock from septic and non-septic etiologies. However, further studies are needed to delineate the functional significance of sCD40L in the clinical outcome in shock patients.
|
|
| 25. |
- Clausen, Frederik Banch, et al.
(författare)
-
Recommendation for validation and quality assurance of non-invasive prenatal testing for foetal blood groups and implications for IVD risk classification according to EU regulations
- 2022
-
Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 117:2, s. 157-165
-
Forskningsöversikt (refereegranskat)abstract
- Background and Objectives: Non-invasive assays for predicting foetal blood group status in pregnancy serve as valuable clinical tools in the management of pregnancies at risk of detrimental consequences due to blood group antigen incompatibility. To secure clinical applicability, assays for non-invasive prenatal testing of foetal blood groups need to follow strict rules for validation and quality assurance. Here, we present a multi-national position paper with specific recommendations for validation and quality assurance for such assays and discuss their risk classification according to EU regulations. Materials and Methods: We reviewed the literature covering validation for in-vitro diagnostic (IVD) assays in general and for non-invasive foetal RHD genotyping in particular. Recommendations were based on the result of discussions between co-authors. Results: In relation to Annex VIII of the In-Vitro-Diagnostic Medical Device Regulation 2017/746 of the European Parliament and the Council, assays for non-invasive prenatal testing of foetal blood groups are risk class D devices. In our opinion, screening for targeted anti-D prophylaxis for non-immunized RhD negative women should be placed under risk class C. To ensure high quality of non-invasive foetal blood group assays within and beyond the European Union, we present specific recommendations for validation and quality assurance in terms of analytical detection limit, range and linearity, precision, robustness, pre-analytics and use of controls in routine testing. With respect to immunized women, different requirements for validation and IVD risk classification are discussed. Conclusion: These recommendations should be followed to ensure appropriate assay performance and applicability for clinical use of both commercial and in-house assays.
|
|
| 26. |
- Giangreco Marotta Puletti, Valentina, 1980, et al.
(författare)
-
Friedel oscillations in holographic metals
- 2012
-
Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; 2012:1
-
Tidskriftsartikel (refereegranskat)abstract
- In this article we study the conditions under which holographic metallic states display Friedel oscillations. We focus on systems where the bulk charge density is not hidden behind a black hole horizon. Understanding holographic Friedel oscillations gives a clean way to characterize the boundary system, complementary to probe fermion calculations. We find that fermions in a "hard wall" AdS geometry unambiguously display Friedel oscillations. However, similar oscillations are washed out for electron stars, suggesting a smeared continuum of Fermi surfaces.
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
- 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.
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
- Keränen, Ville, et al.
(författare)
-
Holographic geometries for condensed matter applications
- 2015
-
Ingår i: The 13th Marcel Grossmann Meeting. - : World Scientific. - 9789814612142 ; , s. 902-921
-
Konferensbidrag (refereegranskat)abstract
- Holographic modeling of strongly correlated many-body systems motivates the study of novel spacetime geometries where the scaling behavior of quantum critical systems is encoded into spacetime symmetries. Einstein-Dilaton-Maxwell theory has planar black brane solutions that exhibit Lifshitz scaling and in some cases hyperscaling violation. Entanglement entropy and Wilson loops in the dual field theory are studied by inserting simple geometric probes involving minimal surfaces into the black brane geometry. Coupling to background matter fields leads to interesting low-energy behavior in holographic models, such as U(1) symmetry breaking and emergent Lifshitz scaling.
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- Torkvist, L, et al.
(författare)
-
Heparin protects against skin flap necrosis: relationship to neutrophil recruitment and anti-coagulant activity
- 2004
-
Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 53:1, s. 1-3
-
Tidskriftsartikel (refereegranskat)abstract
- Objective and design: Heparin has been shown to improve survival of surgical skin flaps. However, it is not known whether the protective effect of heparin is related to it's anticoagulative or anti-inflammatory effects. Methods: Surgical flaps were raised in the dorsal skin of Sprague-Dawley rats. Neutrophil recruitment was determined by measuring the tissue content of myeloperoxidase (MPO) and clotting time was estimated by assessment of activated partial thromboplastin time (APTT) in plasma. Results: Administration of heparin (150 U/kg) significantly increased skin flap survival from 44 % in vehicle-treated controls to 91 %. This heparin treatment increased APTT by 4.5 fold. However, administration of 150 U/kg of heparin had no effect on skin flap neutrophil recruitment. In contrast, we found that the polysaccharide fucoidan reduced MPO and also improved skin flap survival. Conclusions: In conclusion, we demonstrate that protective effect of clinically relevant doses of heparin correlates with its' ability to prolong clotting time and not to inhibition of neutrophil accumulation in the healing of skin flaps.
|
|
| 45. |
- Torkvist, L, et al.
(författare)
-
Role of CD18-dependent neutrophil recruitment in skin and intestinal wound healing
- 2001
-
Ingår i: European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes. - : S. Karger AG. - 0014-312X. ; 33:4, s. 249-254
-
Tidskriftsartikel (refereegranskat)abstract
- CD11/CD18 is an important adhesion molecule mediating recruitment of leukocytes, which, in turn, may cause postoperative injury in the skin and gastrointestinal tract. The objective of the present study was to investigate the effects of inhibiting the function of CD18 on surgery-induced dermal and intestinal infiltration of neutrophils and on the healing of surgical skin flaps and colonic anastomosis. A flap in the dorsal skin or an end-to-end colonic anastomosis were created in Sprague-Dawley rats. Skin necrosis and anastomotic breaking strength were analyzed 6 and 3 days after surgery, respectively. Tissue myeloperoxidase (MPO) was used as a marker of neutrophil recruitment. Administration of a monoclonal antibody directed against rat CD18 (WT.3, 2 mg/kg) significantly decreased dermal and anastomotic MPO activity by more than 80%. Passive immunization against CD18 significantly improved flap survival, i.e. the survival was 80% in the anti-CD18 antibody group as compared to 38% in the control group. In contrast, this passive immunization against CD18 had no effect on the reconstitution of the integrity of the colonic anastomosis, i.e. the anastomotic breaking strength was 1.3 ± 0.1 and 1.3 ± 0.3 N in the control and anti-CD18 antibody group, respectively. These findings suggest that specific inhibition of CD18 function and reduced neutrophil recruitment may improve the survival of experimental skin flaps and, thus, may represent a potential target for therapeutic intervention. In contrast, we also found that blocking CD18-dependent neutrophil infiltration in the intestine had no effect on breaking strength of colonic anastomosis. Thus, neutrophils may influence the wound-healing process differently in specific organs and this needs to be considered when applying an anti-inflammatory treatment regime in order to improve tissue healing.
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
