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| 2. |
- Davies, G., et al.
(författare)
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Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
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| 3. |
- Abbott, Benjamin W., et al.
(författare)
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Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire : an expert assessment
- 2016
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%-85% of permafrost carbon release can still be avoided if human emissions are actively reduced.
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| 4. |
- Hesslow, Thomas, et al.
(författare)
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Internet-delivered psychodynamic psychotherapy in the treatment of social anxiety disorder
- 2015
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Ingår i: Abstracts from the 7th Swedish Congress on internet interventions (SWEsrii). - Linköping : Linköping University Press. ; , s. 12-12
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Social anxiety disorder is one of the most common mental health disorders. Effective treatments exist, but limited access and high costs causes many sufferers to remain untreated. As not all patients accept the CBTmodel of psychopathology, alternative treatments are desirable. We conducted two studies to help establish the efficacy of a psychodynamic model of guided self-help (IPDT). In the first study (N=72) participants were randomized to either ten weeks of IPDT or a waiting list control condition. Mixed-effects models revealed a significant difference at post-treatment in favor of the treatment condition on the primary outcome measure, LSAS-SR, with a large effect size. Rates of remission were comparable to recent face-to-face trials, and improvements were maintained at 6- and 12-month follow-ups. The second study was a pilot preference study where the control group in study 1 chose either IPDT (N=23) or ICBT (N=13). Both treatments led to moderate improvements. Notably, both groups suffered an exacerbation of interpersonal symptoms at 6-month follow-up. In summary, the results suggest that IPDT is effective in the treatment of social anxiety, with effect sizes in the same range as ICBT and face-to-face psychotherapy.
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| 5. |
- Steinz, Maarten M, et al.
(författare)
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Oxidative hotspots on actin promote skeletal muscle weakness in rheumatoid arthritis
- 2019
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Ingår i: JCI Insight. - : American Society for Clinical Investigation (ASCI). - 2379-3708 .- 2324-7703 .- 2325-4556. ; 4:9
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Tidskriftsartikel (refereegranskat)abstract
- Skeletal muscle weakness in patients suffering from rheumatoid arthritis (RA) adds to their impaired working abilities and reduced quality of life. However, little molecular insight is available on muscle weakness associated with RA. Oxidative stress has been implicated in the disease pathogenesis of RA. Here, we show that oxidative posttranslational modifications of the contractile machinery targeted to actin result in impaired actin polymerization and reduced force production. Using mass spectrometry, we identified the actin residues targeted by oxidative 3-nitrotyrosine (3-NT) or malondialdehyde (MDA) adduct modifications in weakened skeletal muscle from mice with arthritis and patients afflicted by RA. The residues were primarily located in 3 distinct regions positioned at matching surface areas of the skeletal muscle actin molecule from arthritic mice and patients with RA. Moreover, molecular dynamics simulations revealed that these areas, here coined "hotspots," are important for the stability of the actin molecule and its capacity to generate filaments and interact with myosin. Together, these data demonstrate how oxidative modifications on actin promote muscle weakness in RA patients and may provide novel leads for targeted therapeutic treatment to improve muscle function.
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| 6. |
- Biver, N., et al.
(författare)
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Isotopic ratios of H, C, N, O, and S in comets C/2012 F6 (Lemmon) and C/2014 Q2 (Lovejoy)
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 589, s. Art. no. A78-
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Tidskriftsartikel (refereegranskat)abstract
- The apparition of bright comets C/2012 F6 (Lemmon) and C/2014 Q2 (Lovejoy) in March-April 2013 and January 2015, combined with the improved observational capabilities of submillimeter facilities, offered an opportunity to carry out sensitive compositional and isotopic studies of the volatiles in their coma. We observed comet Lovejoy with the IRAM 30 m telescope between 13 and 26 January 2015, and with the Odin submillimeter space observatory on 29 January-3 February 2015. We detected 22 molecules and several isotopologues. The (H2O)-O-16 and (H2O)-O-18 production rates measured with Odin follow a periodic pattern with a period of 0.94 days and an amplitude of similar to 25%. The inferred isotope ratios in comet Lovejoy are O-16/O-18 = 499 +/- 24 and D/H = 1.4 +/- 0.4 x 10(-4) in water, S-32/S-34 = 24.7 +/- 3.5 in CS, all compatible with terrestrial values. The ratio C-12/C-13 = 109 +/- 14 in HCN is marginally higher than terrestrial and N-14/N-15 = 145 +/- 12 in HCN is half the Earth ratio. Several upper limits for D/H or C-12/C-13 in other molecules are reported. From our observation of HDO in comet C/2014 Q2 (Lovejoy), we report the first D/H ratio in an Oort Cloud comet that is not larger than the terrestrial value. On the other hand, the observation of the same HDO line in the other Oort-cloud comet, C/2012 F6 (Lemmon), suggests a D/H value four times higher. Given the previous measurements of D/H in cometary water, this illustrates that a diversity in the D/H ratio and in the chemical composition, is present even within the same dynamical group of comets, suggesting that current dynamical groups contain comets formed at very different places or times in the early solar system.
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| 7. |
- Filippov, Stanislav, et al.
(författare)
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Analysis of Dihydrogen Bonding in Ammonium Borohydride
- 2019
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 123:47, s. 28631-28639
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Tidskriftsartikel (refereegranskat)abstract
- The structural and vibrational properties of ammonium borohydride, NH4BH4, have been examined by first-principles density functional theory (DFT) calculations and inelastic neutron scattering (INS). The H disordered crystal structure of NH4BH4 is composed of the tetrahedral complex ions NH4+ and BH4-, which are arranged as in the fcc NaCl structure and linked by intermolecular dihydrogen bonding. Upon cooling, the INS spectra revealed a structural transition between 45 and 40 K. The reversible transition occurs upon heating between 46 and 49 K. In the low-temperature form reorientational dynamics are frozen. The libration modes for BH4- and NH4+ are near 300 and 200 cm(-1), respectively. Upon entering the fcc high-temperature form, NH4+ ions attain fast reorientational dynamics, as indicated in the disappearance of the NH4+ libration band, whereas BH4- ions become significantly mobile only at temperatures above 100 K. The vibrational behavior of BH4- ions in NH4BH4 compares well to the heavier alkali metal borohydrides, NaBH4-CsBH4. DFT calculations revealed a nondirectional nature of the dihydrogen bonding in NH4BH4 with only weak tendency for long-range order. Different rotational configurations of complex ions appear quasi-degenerate, which is reminiscent of glasses.
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| 8. |
- Gliga, Anda R., et al.
(författare)
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RNA-sequencing reveals long-term effects of silver nanoparticles on human lung cells
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Despite a considerable focus on the adverse effects of silver nanoparticles (AgNPs) in recent years, studies on the potential long-term effects of AgNPs are scarce. The aim of this study was to explore the effects of AgNPs following repeated low-dose, long-term exposure of human bronchial epithelial cells. To this end, the human BEAS-2B cell line was exposed to 1 mu g/mL AgNPs (10 nm) for 6 weeks followed by RNA-sequencing (RNA-Seq) as well as genome-wide DNA methylation analysis. The transcriptomics analysis showed that a substantial number of genes (1717) were differentially expressed following AgNP exposure whereas only marginal effects on DNA methylation were observed. Downstream analysis of the transcriptomics data identified several affected pathways including the 'fibrosis' and 'epithelial-mesenchymal transition' (EMT) pathway. Subsequently, functional validation studies were performed using AgNPs of two different sizes (10 nm and 75 nm). Both NPs increased collagen deposition, indicative of fibrosis, and induced EMT, as evidenced by an increased invasion index, anchorage independent cell growth, as well as cadherin switching. In conclusion, using a combination of RNA-Seq and functional assays, our study revealed that repeated low-dose, long-term exposure of human BEAS-2B cells to AgNPs is pro-fibrotic, induces EMT and cell transformation.
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| 9. |
- Lundin, Erik J, et al.
(författare)
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Is the subarctic landscape still a carbon sink? : Evidence from a detailed catchment balance
- 2016
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 43:5, s. 1988-1995
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Tidskriftsartikel (refereegranskat)abstract
- Climate warming raises the question whether high-latitude landscape still function as net carbon (C) sinks. By compiling an integrated C balance for an intensely studied subarctic catchment, we show that this catchment's C balance is not likely to be a strong current sink of C, a commonly held assumption. In fact, it is more plausible (71% probability) that the studied catchment functions as a C source (-1120gCm(-2)yr(-1)). Analyses of individual fluxes indicate that soil and aquatic C losses offset C sequestering in other landscape components (e.g., peatlands and aboveground forest biomass). Our results stress the importance of fully integrated catchment C balance estimates and highlight the importance of upland soils and their interaction with the aquatic network for the catchment C balance.
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| 10. |
- Nejedla, Michaela, et al.
(författare)
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A Fluorophore Fusion Construct of Human Profilin I with Non-Compromised Poly(L-Proline) Binding Capacity Suitable for Imaging
- 2017
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 429:7, s. 964-976
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Tidskriftsartikel (refereegranskat)abstract
- Profilin is vital for actin organisation in eukaryotic cells. It controls actin filament formation by binding monomeric actin and numerous proteins involved in polarised actin assembly. Important for the latter is the interaction surface formed by the N- and C-terminal helices, which pack close to each other on one side of the molecule at a distance from the actin site and mediate binding to poly-proline sequences present in many of the targeted proteins. Via these interactions, profilin contributes to the spatiotemporal control of actin filament growth. Studies of profilin dynamics in living cells by imaging techniques have been hampered by problems to generate fusion constructs with fluorophore proteins without negatively impacting on its poly-proline binding. With the object to circumvent this problem, we have generated an internal fusion of profilin with the green fluorescent variant citrine, here referred to as citrine profilin. The characterisation of citrine profilin (CIT-Pfn) demonstrates that it has full capacity to interact with poly-proline and also binds phosphatidylinositol lipids and actin, albeit with 10 times reduced affinity for the latter. Imaging of living cells expressing CIT-Pfn showed a distribution of the fusion protein similar to endogenous profilin. Furthermore, CIT-Pfn rescued the phenotypes observed after the Crispr/Cas9 knockout of the profilin 1 gene, including the lost migratory capacity characterising the knockout cells. Based on this, we conclude that the CIT-Pfn construct will be useful as a tool for displaying profilin localisation in living cells and obtaining information on its dynamic organisation under different conditions and activations of the actin microfilament and microtubule systems.
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