| 1. |
- Ng, M Y M, et al.
(author)
-
Meta-analysis of 32 genome-wide linkage studies of schizophrenia
- 2009
-
In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 14:8, s. 774-785
-
Journal article (peer-reviewed)abstract
- A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P(SR)) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.
|
|
| 2. |
- Sigmundsson, F., et al.
(author)
-
Segmented lateral dyke growth in a rifting event at Bardarbunga volcanic system, Iceland
- 2015
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 517:7533
-
Journal article (peer-reviewed)abstract
- Crust at many divergent plate boundaries forms primarily by the injection of vertical sheet-like dykes, some tens of kilometres long(1). Previous models of rifting events indicate either lateral dyke growth away from a feeding source, with propagation rates decreasing as the dyke lengthens(2-4), or magma flowing vertically into dykes from an underlying source(5,6), with the role of topography on the evolution of lateral dykes not clear. Here we show how a recent segmented dyke intrusion in the Bardarbunga volcanic system grew laterally for more than 45 kilometres at a variable rate, with topography influencing the direction of propagation. Barriers at the ends of each segment were overcome by the build-up of pressure in the dyke end; then a new segment formed and dyke lengthening temporarily peaked. The dyke evolution, which occurred primarily over 14 days, was revealed by propagating seismicity, ground deformation mapped by Global Positioning System(GPS), interferometric analysis of satellite radar images (InSAR), and graben formation. The strike of the dyke segments varies from an initially radial direction away from the Bardarbunga caldera, towards alignment with that expected from regional stress at the distal end. A model minimizing the combined strain and gravitational potential energy explains the propagation path. Dyke opening and seismicity focused at the most distal segment at any given time, and were simultaneous with magma source deflation and slow collapse at the Bardarbunga caldera, accompanied by a series of magnitude M > 5 earthquakes. Dyke growth was slowed down by an effusive fissure eruption near the end of the dyke. Lateral dyke growth with segment barrier breaking by pressure build-up in the dyke distal end explains how focused upwelling of magma under central volcanoes is effectively redistributed over long distances to create new upper crust at divergent plate boundaries.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Auriac, A., et al.
(author)
-
Iceland rising : Solid Earth response to ice retreat inferred from satellite radar interferometry and visocelastic modeling
- 2013
-
In: Journal of Geophysical Research. - : American Geophysical Union (AGU). - 0148-0227 .- 2156-2202 .- 2169-9313 .- 2169-9356. ; 118:4, s. 1331-1344
-
Journal article (peer-reviewed)abstract
- A broad uplift occurs in Iceland in response to the retreat of ice caps, which began circa 1890. Until now, this deformation signal has been measured primarily using GPS at points some distance away from the ice caps. Here, for the first time we use satellite radar interferometry (interferometric synthetic aperture radar) to constrain uplift of the ground all the way up to the edge of the largest ice cap, Vatnajokull. This allows for improved constraints on the Earth rheology, both the thickness of the uppermost Earth layer that responds only in an elastic manner and the viscosity below it. The interferometric synthetic aperture radar velocities indicate a maximum displacement rate of 24 +/- 4 and 31 +/- 4 mm/yr at the edge of Vatnajokull, during 1995-2002 and 2004-2009, respectively. The fastest rates occur at outlet glaciers of low elevation where ice retreat is high. We compare the observations with glacial isostatic adjustment models that include the deglaciation history of the Icelandic ice caps since 1890 and two Earth layers. Using a Bayesian approach, we derived probability density functions for the average Earth model parameters for three satellite tracks. Based on our assumptions, the three best fit models give elastic thicknesses in the range of 15-40 km, and viscosities ranging from 4-10x1018 Pa s.
|
|
| 9. |
- Hareni, Niyaz, et al.
(author)
-
Back pain is also improved by lumbar disc herniation surgery
- 2021
-
In: Acta Orthopaedica. - : Taylor & Francis. - 1745-3674 .- 1745-3682. ; 92:1, s. 4-8
-
Journal article (peer-reviewed)abstract
- Background and purpose: Indication for lumbar disc herniation (LDH) surgery is usually to relieve sciatica. We evaluated whether back pain also decreases after LDH surgery.Patients and methods: In the Swedish register for spinal surgery (SweSpine) we identified 14,097 patients aged 20-64 years, with pre- and postoperative data, who in 2000-2016 had LDH surgery. We calculated 1-year improvement on numeric rating scale (rating 0-10) in back pain (Nback) and leg pain (Nleg) and by negative binomial regression relative risk (RR) for gaining improvement exceeding minimum clinically important difference (MCID).Results: Nleg was preoperatively (mean [SD]) 6.7 (2.5) and Nback was 4.7 (2.9) (p < 0.001). Surgery reduced Nleg by mean 4.5 (95% CI 4.5-4.6) and Nback by 2.2 (CI 2.1-2.2). Mean reduction in Nleg) was 67% and in Nback 47% (p < 0.001). Among patients with preoperative pain ≥ MCID (that is, patients with significant baseline pain and with a theoretical possibility to improve above MCID), the proportion who reached improvement ≥ MCID was 79% in Nleg and 60% in Nback. RR for gaining improvement ≥ MCID in smokers compared with non-smokers was for Nleg 0.9 (CI 0.8-0.9) and -Nback 0.9 (CI 0.8-0.9), and in patients with preoperative duration of back pain 0-3 months compared with > 24 months for Nleg 1.3 (CI 1.2-1.5) and for Nback 1.4 (CI 1.2-1.5).Interpretation: LDH surgery improves leg pain more than back pain; nevertheless, 60% of the patients with significant back pain improved ≥ MCID. Smoking and long duration of pain is associated with inferior recovery in both Nleg and Nback.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Klaile, E, et al.
(author)
-
The CEACAM1 N-terminal Ig domain mediates cis- and trans-binding and is essential for allosteric rearrangements of CEACAM1 microclusters
- 2009
-
In: The Journal of cell biology. - : Rockefeller University Press. - 1540-8140 .- 0021-9525. ; 187:4, s. 553-567
-
Journal article (peer-reviewed)abstract
- Cell adhesion molecules (CAMs) sense the extracellular microenvironment and transmit signals to the intracellular compartment. In this investigation, we addressed the mechanism of signal generation by ectodomains of single-pass transmembrane homophilic CAMs. We analyzed the structure and homophilic interactions of carcinoembryonic antigen (CEA)–related CAM 1 (CEACAM1), which regulates cell proliferation, apoptosis, motility, morphogenesis, and microbial responses. Soluble and membrane-attached CEACAM1 ectodomains were investigated by surface plasmon resonance–based biosensor analysis, molecular electron tomography, and chemical cross-linking. The CEACAM1 ectodomain, which is composed of four glycosylated immunoglobulin-like (Ig) domains, is highly flexible and participates in both antiparallel (trans) and parallel (cis) homophilic binding. Membrane-attached CEACAM1 ectodomains form microclusters in which all four Ig domains participate. Trans-binding between the N-terminal Ig domains increases formation of CEACAM1 cis-dimers and changes CEACAM1 interactions within the microclusters. These data suggest that CEACAM1 transmembrane signaling is initiated by adhesion-regulated changes of cis-interactions that are transmitted to the inner phase of the plasma membrane.
|
|
| 13. |
- Lindahl, E, et al.
(author)
-
Cellular internalization of proinsulin C-peptide
- 2007
-
In: Cellular and molecular life sciences : CMLS. - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 64:4, s. 479-486
-
Journal article (peer-reviewed)
|
|
| 14. |
- Llona-Minguez, Sabin, et al.
(author)
-
Discovery of the First Potent and Selective Inhibitors of Human dCTP Pyrophosphatase 1
- 2016
-
In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 59:3, s. 1140-1148
-
Journal article (peer-reviewed)abstract
- The dCTPase pyrophosphatase 1 (dCTPase) regulates the intracellular nucleotide pool through hydrolytic degradation of canonical and noncanonical nucleotide triphosphates (dNTPs). dCTPase is highly expressed in multiple carcinomas and is associated with cancer cell sternness. Here we report on the development of the first potent and selective dCTPase inhibitors that enhance the cytotoxic effect of cytidine analogues in leukemia cells. Boronate 30 displays a promising in vitro ADME profile, including plasma and mouse microsomal half-lives, aqueous solubility, cell permeability and CYP inhibition, deeming it a suitable compound for in vivo studies.
|
|
| 15. |
- Loras, H., et al.
(author)
-
Individual differences in timing of discrete and continuous movements : a dimensional approach
- 2014
-
In: Psychological Research. - : Springer. - 0340-0727 .- 1430-2772. ; 78:2, s. 289-299
-
Journal article (peer-reviewed)abstract
- This study investigated aspects of individual differences in timing of continuous and discontinuous movements to different pacing signals (auditory or visual), pacing intervals (500, 650, 800, 950 ms), and across effectors (dominant versus non-dominant hand). Correlation and principal component analysis demonstrated that a single statistical dimension accounted for up to 60 % of the explained variance in discontinuous tasks and 25 % of the variance in continuous tasks, when applied to performance obtained from tasks conducted with different effectors and at different pacing rates. Correlation analysis of factor scores representing effector and rate independent task performances showed that timing of discrete or continuous movements can be associated with modality independent mechanisms. Timing variability from discrete and continuous trials was not significantly correlated. This study goes beyond previous correlational work on individual differences in discrete and continuous movements, demonstrating that individual differences in discrete (event-based) or continuous (emergent) motor timing tasks can be modeled as distinctive statistical components with dissimilar capability to capture effector, rate, and modality independent variance.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Sigmundsson, F., et al.
(author)
-
Intrusion triggering of the 2010 Eyjafjallajökull explosive eruption
- 2010
-
In: Nature. ; 468:7322, s. 426-430
-
Journal article (peer-reviewed)abstract
- Gradual inflation of magma chambers often precedes eruptions at highly active volcanoes. During such eruptions, rapid deflation occurs as magma flows out and pressure is reduced1–3. Less is known about the deformation style at moderately active volcanoes, such as Eyjafjallajo¨kull, Iceland, where an explosive summit eruption of trachyandesite beginning on 14 April 2010 caused exceptional disruption to air traffic, closing airspace over much of Europe for days. This eruption was preceded by an effusive flank eruption of basalt from 20 March to 12 April 2010. The 2010 eruptions are the culmination of 18 years of intermittent volcanic unrest4–9. Here we show that deformation associated with the eruptions was unusual because it did not relate to pressure changes within a single magma chamber. Deformation was rapid before the first eruption (.5mm per day after 4 March), but negligible during it. Lack of distinct co-eruptive deflation indicates that the net volume of magma drained from shallow depth during this eruption was small; rather, magma flowed from considerable depth. Before the eruption, a 0.05km3 magmatic intrusion grew over a period of three months, in a temporally and spatially complex manner, as revealed by GPS (Global Positioning System) geodetic measurements and interferometric analysis of satellite radar images. The second eruption occurred within the ice-capped caldera of the volcano, with explosivity amplified by magma–ice interaction. Gradual contraction of a source, distinct from the pre-eruptive inflation sources, is evident from geodetic data. Eyjafjallajo¨kull’s behaviour can be attributed to its off-rift setting with a ‘cold’ subsurface structure and limited magma at shallow depth, as may be typical for moderately active volcanoes. Clear signs of volcanic unrest signals over years to weeks may indicate reawakening of such volcanoes, whereas immediate short-term eruption precursors may be subtle and difficult to detect.
|
|
| 20. |
- Sigmundsson, Kristmundur, et al.
(author)
-
Culturing functional pancreatic islets on α5-laminins and curative transplantation to diabetic mice.
- 2018
-
In: Matrix Biology. - : Elsevier BV. - 0945-053X .- 1569-1802. ; 70, s. 5-19
-
Journal article (peer-reviewed)abstract
- The efficacy of islet transplantation for diabetes treatment suffers from lack of cadaver-derived islets, islet necrosis and long transfer times prior to transplantation. Here, we developed a method for culturing mouse and human islets in vitro on α5-laminins, which are natural components of islet basement membranes. Adhering islets spread to form layers of 1-3 cells in thickness and remained normoxic and functional for at least 7 days in culture. In contrast, spherical islets kept in suspension developed hypoxia and central necrosis within 16 h. Transplantation of 110-150 mouse islets cultured on α5-laminin-coated polydimethylsiloxane membranes for 3-7 days normalized blood glucose already within 3 days in mice with streptozotocin-induced diabetes. RNA-sequencing of isolated and cultured mouse islets provided further evidence for the adhesion and spreading achieved with α5-laminin. Our results suggest that use of such in vitro expanded islets may significantly enhance the efficacy of islet transplantation treatment for diabetes.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Strömqvist, Fredrik, et al.
(author)
-
Incidental durotomy in degenerative lumbar spine surgery – a register study of 64,431 operations
- 2019
-
In: Spine Journal. - : Elsevier BV. - 1529-9430 .- 1878-1632. ; 19:4, s. 624-630
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Incidental durotomy (ID) is one of the most common intraoperative complications seen in spine surgery. Conflicting evidence has been presented regarding whether or not outcomes are affected by the presence of an ID. PURPOSE: To evaluate whether outcomes following degenerative spine surgery are affected by ID and the incidence of ID with different diagnoses and different surgical procedures. MATERIALS: By using SweSpine, the national Swedish Spine Surgery Register, preoperative, surgical and postoperative 1-year follow-up data were obtained for 64,431 surgeries. All patients were surgically treated due to lumbar spinal stenosis (LSS) without or with concomitant degenerative spondylolisthesis (DS) or lumbar disc herniation (LDH) between 2000 and 2015. Gender, age, smoking habits, walking distance, consumption of analgesics, back and leg pain (Visual Analogue Scale [VAS]), quality of life (EuroQol [EQ5D] and Short Form 36 [SF-36]), and disability (Oswestry Disability Index [ODI]) were recorded. RESULTS: Overall, incidence of ID during the study period was 5.0%. For the LDH, LSS, and DS subgroups, it was 2.8%, 6.5%, and 6.5%, respectively. Laminectomy was associated with a higher incidence of ID than discectomy (p<.001). ID was more common in all three subgroups if the patient had previously been subjected to spine surgery and with increasing age of the patients (p<.001). LDH patients with an ID reported a higher degree of residual leg pain, inferior mental quality of life (SF-36 MCS), and higher disability (ODI) than LDH patients without ID (all p<.001) 1-year after surgery. LSS patients with an ID reported inferior SF-36 MCS (p<.001) and DS patients with an ID had inferior SF-36 MCS and higher ODI compared to patients with the same diagnosis but without an ID (p<.001). However, these numerical differences are well below references for MCID, for all three subgroups. ID was associated with a higher frequency of patients being dissatisfied with the surgical outcome at 1-year follow-up. In patients who did not improve in back and leg pain following surgery (delta-value), ID was less common than in patients reporting improved back and leg pain from before as compared to following surgery. CONCLUSIONS: The overall occurrence of ID in the present study was 5%, with higher figures in LSS and DS and lower figures in LDH. Higher age of the patient and previous surgery were associated with higher frequencies of ID. The outcome at 1 year following surgery was not affected to a clinically relevant extent when an ID was obtained. However, ID was associated with a higher degree of patient dissatisfaction and a longer hospital length of stay.
|
|
| 25. |
|
|
