| 1. |
- Hibar, Derrek P., et al.
(author)
-
Novel genetic loci associated with hippocampal volume
- 2017
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Journal article (peer-reviewed)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
|
|
| 2. |
- Ademuyiwa, Adesoji O., et al.
(author)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
|
|
| 3. |
|
|
| 4. |
- Sønderby, Ida E., et al.
(author)
-
1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
-
In: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
-
Journal article (peer-reviewed)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
|
|
| 5. |
- Taylor, M. J., et al.
(author)
-
Isospin symmetry in the odd-odd mirror nuclei (44)V/(44)Sc
- 2011
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 84:6
-
Journal article (peer-reviewed)abstract
- Excited states in the N = Z - 2 nucleus (44)V have been observed for the first time. The states have been identified through particle-gamma-gamma coincidence relationships and comparison with analog states in themirror nucleus (44)Sc. Mirror energy differences have been extracted and compared to state-of-the-art shell-model calculations which include charge-symmetry-breaking forces. Observed decay pattern asymmetries between the mirror pair are discussed in terms of core excitations, electromagnetic spin-orbit effects and isospin mixing.
|
|
| 6. |
- van der Meer, Dennis, et al.
(author)
-
Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
-
In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
-
Journal article (peer-reviewed)abstract
- Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
|
|
| 7. |
- Brodin, N., et al.
(author)
-
Coaching patients with early rheumatoid arthritis to healthy physical activity : A multicenter, randomized, controlled study
- 2008
-
In: Arthritis and Rheumatism. - Hoboken, NJ : Wiley. - 0004-3591 .- 1529-0131. ; 59:3, s. 325-331
-
Journal article (peer-reviewed)abstract
- Objective. To investigate the effect of a 1-year coaching program for healthy physical activity on perceived health status, body function, and activity limitation in patients with early rheumatoid arthritis. Methods. A total of 228 patients (169 women, 59 men, mean age 55 years, mean time since diagnosis 21 months) were randomized to 2 groups after assessments with the EuroQol visual analog scale (VAS), Grippit, Timed-Stands Test, Escola Paulista de Medicina Range of Motion scale, walking in a figure-of-8, a visual analog scale for pain, the Health Assessment Questionnaire disability index, a self-reported physical activity questionnaire, and the Disease Activity Score in 28 joints. All patients were regularly seen by rheumatologists and underwent rehabilitation as prescribed. Those in the intervention group were further individually coached by a physical therapist to reach or maintain healthy physical activity (=30 minutes, moderately intensive activity, most days of the week). Results. The retention rates after 1 year were 82% in the intervention group and 85% in the control group. The percentages of individuals in the intervention and control groups fulfilling the requirements for healthy physical activity were similar before (47% versus 51%, P > 0.05) and after (54% versus 44%, P > 0.05) the intervention. Analyses of outcome variables indicated improvements in the intervention group over the control group in the EuroQol VAS (P = 0.025) and muscle strength (Timed-Stands Test, P = 0.000) (Grippit, P = 0.003), but not in any other variables assessed. Conclusion. A 1-year coaching program for healthy physical activity resulted in improved perceived health status and muscle strength, but the mechanisms remain unclear, as self-reported physical activity at healthy level did not change. © 2008, American College of Rheumatology.
|
|
| 8. |
- Doornenbal, P., et al.
(author)
-
RISING: Gamma‐ray Spectroscopy with Radioactive Beams at GSI
- 2007
-
In: AIP Conference Proceedings. - : AIP. - 0094-243X. - 9780735413283 ; 891, s. 99-107
-
Conference paper (peer-reviewed)abstract
- The Rare Isotope Spectroscopic INvestigation at GSI (RISING) project is a major pan‐European collaboration. Its physics aims are the studies of exotic nuclear matter with abnormal proton‐to‐neutron ratios compared with naturally occurring isotopes. RISING combines the FRagment Separator (FRS) which allows relativistic energies and projectile fragmentation reactions with EUROBALL Ge Cluster detectors for γ spectroscopic research. The RISING setup can be used in two different configurations. Either the nuclei of interest are investigated after being stopped or the heavy ions hit a secondary target at relativistic energies and the thereby occurring excitations are studied. For the latter case, MINIBALL Ge detectors and the HECTOR array are used in addition. Example achievements of the Fast Beam setup are presented and compared to various shell model calculations, while for the Stopped Beam setup initial results are shown.
|
|
| 9. |
- Hildebrandt, Franziska, 1994-, et al.
(author)
-
Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the mouse liver
- 2021
-
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- Reconstruction of heterogeneity through single cell transcriptional profiling has greatly advanced our understanding of the spatial liver transcriptome in recent years. However, global transcriptional differences across lobular units remain elusive in physical space. Here, we apply Spatial Transcriptomics to perform transcriptomic analysis across sectioned liver tissue. We confirm that the heterogeneity in this complex tissue is predominantly determined by lobular zonation. By introducing novel computational approaches, we enable transcriptional gradient measurements between tissue structures, including several lobules in a variety of orientations. Further, our data suggests the presence of previously transcriptionally uncharacterized structures within liver tissue, contributing to the overall spatial heterogeneity of the organ. This study demonstrates how comprehensive spatial transcriptomic technologies can be used to delineate extensive spatial gene expression patterns in the liver, indicating its future impact for studies of liver function, development and regeneration as well as its potential in pre-clinical and clinical pathology. Global transcriptional differences across lobular units in the liver remain unknown. Here the authors perform spatial transcriptomics of liver tissue to delineate transcriptional differences in physical space, confirm lobular zonation along transcriptional gradients and suggest the presence of previously uncharacterized structures within liver tissue.
|
|
| 10. |
- McPhearson, Timon, et al.
(author)
-
A social-ecological-technological systems framework for urban ecosystem services
- 2022
-
In: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 5:5, s. 505-518
-
Journal article (peer-reviewed)abstract
- As rates of urbanization and climatic change soar, decision-makers are increasingly challenged to provide innovative solutions that simultaneously address climate change impacts and risks and inclusively ensure quality of life for urban residents. Cities have turned to nature-based solutions to help address these challenges. Nature-based solutions, through the provision of ecosystem services, can yield numerous benefits for people and address multiple challenges simultaneously. Yet, efforts to mainstream nature-based solutions are impaired by the complexity of the interacting social, ecological, and technological dimensions of urban systems. This complexity must be understood and managed to ensure ecosystem-service provisioning is effective, equitable, and resilient. Here, we provide a social-ecological-technological system (SETS) framework that builds on decades of urban ecosystem services research to better understand four core challenges associated with urban nature-based solutions: multi-functionality, systemic valuation, scale mismatch of ecosystem services, and inequity and injustice. The framework illustrates the importance of coordinating natural, technological, and socio-economic systems when designing, planning, and managing urban nature-based solutions to enable optimal social-ecological outcomes.
|
|
| 11. |
- Rudolph, Dirk, et al.
(author)
-
Isospin and Deformation Studies in the Odd-odd N = Z Nucleus 54Co
- 2010
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 82:5
-
Journal article (peer-reviewed)abstract
- High-spin states in the odd-odd N = Z nucleus Co-54 have been investigated by the fusion-evaporation reaction Si-28(S-32,1 alpha 1p1n)Co-54. Gamma-ray information gathered with the Ge detector array Gammasphere was correlated with evaporated particles detected in the charged particle detector system Microball and a 1 pi neutron detector array. A significantly extended excitation scheme of Co-54 is presented, which includes a candidate for the isospin T = 1, 6(+) state of the 1f(7/2)(-2) multiplet. The results are compared to large-scale shell-model calculations in the fp shell. Effective interactions with and without isospin-breaking terms have been used to probe isospin symmetry and isospin mixing. A quest for deformed high-spin rotational cascades proved negative. This feature is discussed by means of cranking calculations.
|
|
| 12. |
- Sonderby, Ida E., et al.
(author)
-
Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
-
In: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
-
Journal article (peer-reviewed)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
|
|
| 13. |
- Taylor, M. J., et al.
(author)
-
First Gamma-Ray Spectroscopy and Isospin Symmetry Study of the N = Z-2 Nucleus V-44
- 2010
-
In: Modern Physics Letters A. - 0217-7323. ; 25:21-23, s. 2028-2029
-
Conference paper (peer-reviewed)abstract
- Excited states in the T-z = -1 nucleus V-44 have been observed for the first time. The states have been identified through recoil-gamma-gamma coincidences and comparison with analogue states in the mirror nucleus Sc-44. Mirror energy differences have been extracted and compared to state-of-the-art fp shell-model calculations which include charge symmetry breaking forces.
|
|
| 14. |
- Andersson, Emma K., et al.
(author)
-
Modulation of Curli Assembly and Pellicle Biofilm Formation by Chemical and Protein Chaperones
- 2013
-
In: Chemistry and Biology. - : Elsevier. - 1074-5521 .- 1879-1301. ; 20:10, s. 1245-1254
-
Journal article (peer-reviewed)abstract
- Enteric bacteria assemble functional amyloid fibers, curli, on their surfaces that share structural and biochemical properties with disease-associated amyloids. Here, we test rationally designed 2-pyridone compounds for their ability to alter amyloid formation of the major curli subunit CsgA. We identified several compounds that discourage CsgA amyloid formation and several compounds that accelerate CsgA amyloid formation. The ability of inhibitor compounds to stop growing CsgA fibers was compared to the same property of the CsgA chaperone, CsgE. CsgE blocked CsgA amyloid assembly and arrested polymerization when added to actively polymerizing fibers. Additionally, CsgE and the 2-pyridone inhibitors prevented biofilm formation by Escherichia coli at the air-liquid interface of a static culture. We demonstrate that curli amyloid assembly and curli-dependent biofilm formation can be modulated not only by protein chaperones, but also by "chemical chaperones."
|
|
| 15. |
- Andersson, Lise-Lotte, et al.
(author)
-
Extensive Gamma-ray Spectroscopy of Normally and Superdeformed Structures in 61Cu
- 2008
-
In: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 36:3, s. 251-278
-
Journal article (peer-reviewed)abstract
- A largely extended experimental knowledge of the Cu-61(29)32 nucleus has been obtained from three experiments. Excited states in Cu-61 were produced via the fusion-evaporation reaction Si-28(Ar-36, 3p)Cu-61. In addition to the Ge array GAMMASPHERE, neutron and charged-particle detectors placed around the target position were used for high-performance particle spectroscopy. The constructed level scheme includes more than 160 energy levels and 320 gamma-ray transitions belonging to both normally deformed as well as superdeformed rotational structures. The multipolarities have been determined for the gamma-ray transitions and as a result spin-parity assignments are given for nearly all energy levels. Experimental results in the normally deformed region are compared with predictions from large-scale shell model calculations. The collective structures are compared with results from cranked Nilsson-Strutinsky calculations. The results reveal the need to modify the standard Nilsson parameters in the mass A similar to 60 region.
|
|
| 16. |
|
|
| 17. |
- Banijamali, Elnaz, et al.
(author)
-
RNA:RNA interaction in ternary complexes resolved by chemical probing
- 2022
-
In: RNA. - : Cold Spring Harbor Laboratory Press (CSHL). - 1355-8382 .- 1469-9001. ; 29:3, s. 317-329
-
Journal article (peer-reviewed)abstract
- RNA regulation can be performed by a second targeting RNA molecule, such as in the microRNA regulation mechanism. Selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) probes the structure of RNA molecules and can resolve RNA:protein interactions, but RNA:RNA interactions have not yet been addressed with this technique. Here, we apply SHAPE to investigate RNA-mediated binding processes in RNA:RNA and RNA:RNA-RBP complexes. We use RNA:RNA binding by SHAPE (RABS) to investigate microRNA-34a (miR-34a) binding its mRNA target, the silent information regulator 1 (mSIRT1), both with and without the Argonaute protein, constituting the RNA-induced silencing complex (RISC). We show that the seed of the mRNA target must be bound to the microRNA loaded into RISC to enable further binding of the compensatory region by RISC, while the naked miR-34a is able to bind the compensatory region without seed interaction. The method presented here provides complementary structural evidence for the commonly performed luciferase-assay-based evaluation of microRNA binding-site efficiency and specificity on the mRNA target site and could therefore be used in conjunction with it. The method can be applied to any nucleic acid-mediated RNA- or RBP-binding process, such as splicing, antisense RNA binding, or regulation by RISC, providing important insight into the targeted RNA structure.
|
|
| 18. |
- Bonagas, Nadilly, et al.
(author)
-
Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
-
In: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
-
Journal article (peer-reviewed)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
|
|
| 19. |
- Chorell, Erik, et al.
(author)
-
Bacterial Chaperones CsgE and CsgC Differentially Modulate Human α-Synuclein Amyloid Formation via Transient Contacts.
- 2015
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 10:10, s. e0140194-
-
Journal article (peer-reviewed)abstract
- Amyloid formation is historically associated with cytotoxicity, but many organisms produce functional amyloid fibers (e.g., curli) as a normal part of cell biology. Two E. coli genes in the curli operon encode the chaperone-like proteins CsgC and CsgE that both can reduce in vitro amyloid formation by CsgA. CsgC was also found to arrest amyloid formation of the human amyloidogenic protein α-synuclein, which is involved in Parkinson's disease. Here, we report that the inhibitory effects of CsgC arise due to transient interactions that promote the formation of spherical α-synuclein oligomers. We find that CsgE also modulates α-synuclein amyloid formation through transient contacts but, in contrast to CsgC, CsgE accelerates α-synuclein amyloid formation. Our results demonstrate the significance of transient protein interactions in amyloid regulation and emphasize that the same protein may inhibit one type of amyloid while accelerating another.
|
|
| 20. |
- Creed, Irena F., et al.
(author)
-
Global change-driven effects on dissolved organic matter composition : Implications for food webs of northern lakes
- 2018
-
In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 24:8, s. 3692-3714
-
Research review (peer-reviewed)abstract
- Northern ecosystems are experiencing some of the most dramatic impacts of global change on Earth. Rising temperatures, hydrological intensification, changes in atmospheric acid deposition and associated acidification recovery, and changes in vegetative cover are resulting in fundamental changes in terrestrial-aquatic biogeochemical linkages. The effects of global change are readily observed in alterations in the supply of dissolved organic matter (DOM)-the messenger between terrestrial and lake ecosystems-with potentially profound effects on the structure and function of lakes. Northern terrestrial ecosystems contain substantial stores of organic matter and filter or funnel DOM, affecting the timing and magnitude of DOM delivery to surface waters. This terrestrial DOM is processed in streams, rivers, and lakes, ultimately shifting its composition, stoichiometry, and bioavailability. Here, we explore the potential consequences of these global change-driven effects for lake food webs at northern latitudes. Notably, we provide evidence that increased allochthonous DOM supply to lakes is overwhelming increased autochthonous DOM supply that potentially results from earlier ice-out and a longer growing season. Furthermore, we assess the potential implications of this shift for the nutritional quality of autotrophs in terms of their stoichiometry, fatty acid composition, toxin production, and methylmercury concentration, and therefore, contaminant transfer through the food web. We conclude that global change in northern regions leads not only to reduced primary productivity but also to nutritionally poorer lake food webs, with discernible consequences for the trophic web to fish and humans.
|
|
| 21. |
- Gonzalez-Ortiz, Fernando, et al.
(author)
-
Association of Serum Brain-Derived Tau With Clinical Outcome and Longitudinal Change in Patients With Severe Traumatic Brain Injury.
- 2023
-
In: JAMA network open. - 2574-3805. ; 6:7
-
Journal article (peer-reviewed)abstract
- Blood-based measurements of total tau (T-tau) are commonly used to examine neuronal injury in patients with traumatic brain injury (TBI), but current assays do not differentiate between brain-derived tau (BD-tau) and tau produced in peripheral tissues. A novel assay for BD-tau has recently been reported that selectively quantifies nonphosphorylated tau of central nervous system origin in blood samples.To examine the association of serum BD-tau with clinical outcomes in patients with severe TBI (sTBI) and its longitudinal changes over 1 year.This prospective cohort study was conducted at the neurointensive unit at the Sahlgrenska University Hospital, Gothenburg, Sweden, between September 1, 2006, and July 1, 2015. The study included 39 patients with sTBI followed up for up to 1 year. Statistical analysis was performed between October and November 2021.Serum BD-tau, T-tau, phosphorylated tau231 (p-tau231), and neurofilament light chain (NfL) measured on days 0, 7, and 365 after injury.Associations of serum biomarkers with clinical outcome and longitudinal change in sTBI. Severity of sTBI was evaluated using the Glasgow Coma Scale at hospital admission, while clinical outcome was assessed with the Glasgow Outcome Scale (GOS) at 1-year follow-up. Participants were classified as having a favorable outcome (GOS score, 4-5) or unfavorable outcome (GOS score, 1-3).Among the 39 patients (median age at admission, 36 years [IQR, 22-54 years]; 26 men [66.7%]) in the study on day 0, the mean (SD) serum BD-tau level was higher among patients with unfavorable outcomes vs those with favorable outcomes (191.4 [190.8] pg/mL vs 75.6 [60.3] pg/mL; mean difference, 115.9 pg/mL [95% CI, 25.7-206.1 pg/mL]), while the other markers had smaller between-group mean differences (serum T-tau, 60.3 pg/mL [95% CI, -22.0 to 142.7 pg/mL]; serum p-tau231, 8.3 pg/mL [95% CI, -6.4 to 23.0 pg/mL]; serum NfL, -5.4 pg/mL [95% CI, -99.0 to 88.3 pg/mL]). Similar results were recorded on day 7. Longitudinally, baseline serum BD-tau concentrations showed slower decreases in the whole cohort (42.2% on day 7 [from 138.6 to 80.1 pg/mL] and 93.0% on day 365 [from 138.6 to 9.7 pg/mL]) compared with serum T-tau (81.5% on day 7 [from 57.3 to 10.6 pg/mL] and 99.0% on day 365 [from 57.3 to 0.6 pg/mL]) and p-tau231 (92.5% on day 7 [from 20.1 to 1.5 pg/mL] and 95.0% on day 365 [from 20.1 to 1.0 pg/mL]). These results did not change when considering clinical outcome, where T-tau decreased twice as fast as BD-tau in both groups. Similar results were obtained for p-tau231. Furthermore, the biomarker levels on day 365 were lower, compared with day 7, for BD-tau but not T-tau or p-tau231. Serum NfL had a different trajectory to the tau biomarkers, with levels increasing by 255.9% on day 7 compared with day 0 (from 86.8 to 308.9 pg/mL) but decreasing by 97.0% by day 365 vs day 7 (from 308.9 to 9.2 pg/mL).This study suggests that serum BD-tau, T-tau, and p-tau231 have differential associations with clinical outcome and 1-year longitudinal change in patients with sTBI. Serum BD-tau demonstrated utility as a biomarker to monitor outcomes in sTBI and can provide valuable information regarding acute neuronal damage.
|
|
| 22. |
|
|
| 23. |
- Hoischen, Robert, et al.
(author)
-
Isomeric Mirror States as Probes for Effective Charges in the Lower pf Shell
- 2011
-
In: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 38:3
-
Journal article (peer-reviewed)abstract
- Following the fragmentation of a 550 MeV u(-1)primary beam of Ni-58, time-and energy-correlated gamma decays from isomeric states in neutron-deficient nuclei in the 1f(7/2) shell have been identified using the GSI fragment separator in combination with the RISING Ge-detector array. The results on isomers in the mirror pairs Ti-43(22)21-Sc-43(21)22 (I-pi = 3/2(+) and 19/2(-)), Cr-45(24)21-Sc-45(21)24 (I-pi = 3/2(+)) and V-45(23)22-Ti-45(22)23 (I-pi = 3/2(-)) are discussed in the framework of large scale pf and sdpf shell-model calculations, the former in conjunction with isospin symmetry breaking effects with emphasis on effective charges.
|
|
| 24. |
- Johansson, Emma, et al.
(author)
-
Prompt Proton Decay and Deformed Bands in 56Ni
- 2008
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 77:6
-
Journal article (peer-reviewed)abstract
- High-spin states in the doubly magic N=Z nucleus Ni-56 have been investigated with three fusion-evaporation reaction experiments. New gamma-ray transitions are added, and a confirmation of a previously suggested prompt proton decay from a rotational band in Ni-56 into the ground state of Co-55 is presented. The rotational bands in Ni-56 are discussed within the framework of cranked Nilsson-Strutinsky calculations.
|
|
| 25. |
- Johansson, Emma, et al.
(author)
-
Prompt Proton Decay in the Vicinity of 56Ni
- 2007
-
In: Proton Emitting Nuclei and Related Topics. - : AIP. - 1551-7616 .- 0094-243X. ; 961, s. 41-46
-
Conference paper (peer-reviewed)abstract
- A new decay mode, the so called prompt proton decay, was discovered in 1998. It has since proven to be an important decay mechanism for several neutron deficient nuclei in the A similar to 60 region. To measure with high accuracy the energies and angular distributions of these protons, a state-of-the-art charged particle detector - LuWuSiA - was developed. It was first utilized during a fusion-evaporation reaction experiment performed at Argonne National Laboratory, U.S.A. In this contribution, the characteristics of the prompt proton decay are discussed along with the special features of LuWuSiA as well as a revisit to the prompt proton decay in Cu-58.
|
|
| 26. |
- Johansson, Emma, et al.
(author)
-
Thorough Gamma-ray and Particle Decay Investigations of 58Ni
- 2009
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 80:1
-
Journal article (peer-reviewed)abstract
- The combined data from three fusion-evaporation reaction experiments have been utilized to investigate the semi-magic nucleus Ni-58(28)30. To detect gamma rays in coincidence with evaporated particles, the Ge-detector array Gammasphere was used in conjunction with the charged-particle detectors Microball and LuWuSiA (the Lund Washington University Silicon Array), and a neutron detector array. The results yield a significantly extended level scheme of Ni-58 comprising some 340 gamma-ray transitions and include a total of at least 14 discrete particle decays into excited states of the daughter nuclei Fe-54 and Co-57. The level scheme is compared with large-scale shell-model calculations and cranked Nilsson-Strutinsky calculations.
|
|
| 27. |
- Kumar Anand, Sumit, et al.
(author)
-
Inhibition of MAP4K4 signaling initiates metabolic reprogramming to protect hepatocytes from lipotoxic damage
- 2022
-
In: Journal of Lipid Research. - : Elsevier BV. - 0022-2275. ; 63:7
-
Journal article (peer-reviewed)abstract
- The primary hepatic consequence of obesity is non-alcoholic fatty liver disease (NAFLD), affecting about 25% of the global adult population. Non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD characterized by liver lipid accumulation, inflammation, and hepatocyte ballooning, with a different degree of hepatic fibrosis. In the light of rapidly increasing prevalence of NAFLD and NASH, there is an urgent need for improved understanding of the molecular pathogenesis of these diseases. The aim of this study was to decipher the possible role of STE20-type kinase MAP4K4 in the regulation of he-patocellular lipotoxicity and susceptibility to NAFLD. We found that MAP4K4 mRNA expression in human liver biopsies was positively correlated with key hallmarks of NAFLD (i.e., liver steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis). We also found that the silencing of MAP4K4 suppressed lipid deposition in human he-patocytes by stimulating beta-oxidation and tri-acylglycerol secretion, while attenuating fatty acid influx and lipid synthesis. Furthermore, down -regulation of MAP4K4 markedly reduced the glycolysis rate and lowered incidences of oxidative/ endoplasmic reticulum stress. In parallel, we observed suppressed JNK and ERK and increased AKT phosphorylation in MAP4K4-deficient hep-atocytes. Together, these results provide the first experimental evidence supporting the potential involvement of STE20-type kinase MAP4K4 as a component of the hepatocellular lipotoxic milieu promoting NAFLD susceptibility.
|
|
| 28. |
- Mattsson, Charlotte L, et al.
(author)
-
Differential involvement of caveolin-1 in brown adipocyte signaling : impaired beta3-adrenergic, but unaffected LPA, PDGF and EGF receptor signaling.
- 2010
-
In: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 1878-2434. ; 1803:8, s. 983-9
-
Journal article (peer-reviewed)abstract
- Caveolae and caveolin have been implicated as being involved in the signal transduction of many receptors, including the EGF, PDGF, LPA and beta3-adrenergic receptors. To investigate the role of caveolin-1 (Cav1) in these signaling pathways in brown adipose tissue, primary brown adipocyte cultures from Cav1-ablated mice and wild-type mice were investigated. In pre-adipocytes, Cav1-ablation affected neither the G-protein coupled LPA receptor signaling to Erk1/2, nor the receptor tyrosine kinases PDGF- or EGF-receptor signaling to Erk1/2. Mature primary Cav1-/- brown adipocytes accumulated lipids and expressed aP2 to the same extent as did wild-type cells. However, the cAMP levels induced by the beta3-adrenergic receptor agonist CL316,243 were lower in the Cav1-/- cultures, with an unchanged EC50 for CL316,243. Also the response to the direct adenylyl cyclase agonist forskolin was reduced. Thus, in brown adipocytes, Cav1 is apparently required for an intact response to adenylyl cyclase-linked agonists/activators, whereas other signaling pathways examined function without Cav1
|
|
| 29. |
|
|
| 30. |
- Pietri, S., et al.
(author)
-
First Results from the Stopped Beam Isomer RISING Campaign at GSI
- 2007
-
In: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 38:4, s. 1255-1264
-
Journal article (peer-reviewed)abstract
- The first results from a series of experiments focused on the study of the internal structure of nuclei at the extremes of N:Z ratio using isomer spectroscopy are reported. These experiments represent the first of the Stopped Beam section of the Rare Isotopes Investigations at GSI (RISING) project. Exotic nuclei were synthesized using relativistic projectile fragmentation of similar to 500 -> 1000 MeV/u beams of Ag-107, Pb-208, Xe-136 and Ni-58, or fission of 750 MeV/u U-238 provided by the SIS synchrotron at GSI. A detailed description of the RISING stopped beam set up is given, together with a report of the performance of the associated gamma-ray spectrometer array. Selected results of the first experimental campaign are presented together with a discussion on the use of isomeric spectroscopy to study GeV range nuclear fragmentation. Details on future research plans of this collaboration are also outlined.
|
|
| 31. |
|
|
| 32. |
- Rudolph, Dirk, et al.
(author)
-
Evidence for an Isomeric 3/2- State in 53Co
- 2008
-
In: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 36:2, s. 131-138
-
Journal article (peer-reviewed)abstract
- The fragmentation of a 550MeV/u primary beam of Ni-58 on a Be-9 target has been used to measure time-and energy-correlated gamma decays following the implantation of event-by-event discriminated secondary fragments into a Be-9 stopper plate. A new isomeric gamma decay with T-1/2 = 14(6 4) ns and E-gamma = 646.2(2) keV is observed and attributed to the decay of the yrast 3/2-state in Co-53(27)26. This short-lived isomeric state has been populated by means of nuclear reactions during the stopping process of the secondary fragments. The experimental findings are discussed in the framework of large-scale spherical shell model calculations in conjunction with isospin symmetry-breaking residual interactions for the A = 53, Tz = +/- 1/2 mirror nuclei Co-53 and Fe-53.
|
|
| 33. |
- Rudolph, Dirk, et al.
(author)
-
Exciting Isomers from the First Stopped-beam RISING Campaign
- 2007
-
In: The European Physical Journal. Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 150, s. 173-176
-
Journal article (peer-reviewed)abstract
- First results are reported from a major new initiative of experiments, which focus on nuclear structure studies at extreme isospin values by means of isomer spectroscopy. The experiments represent the first part of the so-called stopped-beam campaign within the Rare ISotope INvestigations at GSI (RISING) project. Time-correlated gamma decays from individually identified nuclear species have been measured, allowing the clean identification of isomeric decays in a wide range of exotic nuclei both at the proton drip-line and in heavy, neutron-rich systems. An overview of the experimental technique will be given, together with the performance of the new germanium detector array and future research plans for the collaboration.
|
|
| 34. |
- Rudolph, Dirk, et al.
(author)
-
Isospin Symmetry and Proton Decay: Identification of the 10+ Isomer in 54Ni
- 2008
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 78:2
-
Journal article (peer-reviewed)abstract
- The gamma decays from an isomeric 10+ state at 6457 keV in the nucleus 54Ni have been identified using the GSI fragment separator in conjunction with the RISING Ge-detector array. The state is interpreted as the isobaric analog of the 6527-keV 10+ isomer in 54Fe. The results are discussed in terms of isospin-dependent shell-model calculations. Clear evidence is presented for a discrete l = 5 proton decay branch into the first excited 9/2- state of the daughter 53Co. This decay is the first of its kind observed following projectile fragmentation reactions.
|
|
| 35. |
- Smith, Shawn R., et al.
(author)
-
Ship-based contributions to global ocean, weather, and climate observing systems
- 2019
-
In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
-
Research review (peer-reviewed)abstract
- © 2019 Smith, Alory, Andersson, Asher, Baker, Berry, Drushka, Figurskey, Freeman, Holthus, Jickells, Kleta, Kent, Kolodziejczyk, Kramp, Loh, Poli, Schuster, Steventon, Swart, Tarasova, Petit De La Villéon and Vinogradova Shiffer. The role ships play in atmospheric, oceanic, and biogeochemical observations is described with a focus on measurements made within 100 m of the ocean surface. Ships include merchant and research vessels, cruise liners and ferries, fishing vessels, coast guard, military, and other government-operated ships, yachts, and a growing fleet of automated surface vessels. The present capabilities of ships to measure essential climate/ocean variables and the requirements from a broad community to address operational, commercial, and scientific needs are described. Following the guidance from the OceanObs'19 organizing committee, the authors provide a vision to expand observations needed from ships to understand and forecast the exchanges across the ocean-atmosphere interface. The vision addresses (1) recruiting vessels to improve both spatial and temporal sampling, (2) conducting multi-variate sampling on ships, (3) raising technology readiness levels of automated shipboard sensors and ship-to-shore data communications, (4) advancing quality evaluation of observations, and (5) developing a unified data management approach for observations and metadata that meets the needs of a diverse user community. Recommendations are made focusing on integrating private and autonomous vessels into the observing system, investing in sensor and communications technology development, developing an integrated data management structure that includes all types of ships, and moving towards a quality evaluation process that will result in a subset of ships being defined as mobile reference ships that will support climate studies. We envision a future where commercial, research, and privately-owned vessels are making multivariate observations using a combination of automated and human-observed measurements. All data and metadata will be documented, tracked, evaluated, distributed, and archived to benefit users of marine data. This vision looks at ships as a holistic network, not a set of disparate commercial, research, and/or third-party activities working in isolation, to bring these communities together for the mutual benefit of all.
|
|
| 36. |
- Torres, D. A., et al.
(author)
-
Deformations and Magnetic Rotations in the 60Ni Nucleus
- 2008
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 78:5
-
Journal article (peer-reviewed)abstract
- Data from three experiments using the heavy-ion fusion evaporation-reaction Ar-36+Si-28 have been combined to study high-spin states in the residual nucleus Ni-60, which is populated via the evaporation of four protons from the compound nucleus Ge-64. The GAMMASPHERE array was used for all the experiments in conjunction with a 4 pi charged-particle detector arrays (MICROBALL, LUWUSIA) and neutron detectors (NEUTRON SHELL) to allow for the detection of. rays in coincidence with the evaporated particles. An extended Ni-60 level scheme is presented, comprising more than 270 gamma-ray transitions and 110 excited states. Their spins and parities have been assigned via directional correlations of gamma rays emitted from oriented states. Spherical shell-model calculations in the fp-shell characterize some of the low-spin states, while the experimental results of the rotational bands are analyzed with configuration-dependent cranked Nilsson-Strutinsky calculations.
|
|
| 37. |
|
|
| 38. |
- Xia, Ying, et al.
(author)
-
Silencing of STE20-type kinase TAOK1 confers protection against hepatocellular lipotoxicity through metabolic rewiring
- 2023
-
In: Hepatology communications.. - : Ovid Technologies (Wolters Kluwer Health). - 2471-254X. ; 7:4
-
Journal article (peer-reviewed)abstract
- Background: NAFLD has become the leading cause of chronic liver disease worldwide afflicting about one quarter of the adult population. NASH is a severe subtype of NAFLD, which in addition to hepatic steatosis connotes liver inflammation and hepatocyte ballooning. In light of the exponentially increasing prevalence of NAFLD, it is imperative to gain a better understanding of its molecular pathogenesis. The aim of this study was to examine the potential role of STE20-type kinase TAOK1 -a hepatocellular lipid droplet-associated protein-in the regulation of liver lipotoxicity and NAFLD etiology. Methods: The correlation between TAOK1 mRNA expression in liver biopsies and the severity of NAFLD was evaluated in a cohort of 62 participants. Immunofluorescence microscopy was applied to describe the subcellular localization of TAOK1 in human and mouse hepatocytes. Metabolic reprogramming and oxidative/endoplasmic reticulum stress were investigated in immortalized human hepatocytes, where TAOK1 was overexpressed or silenced by small interfering RNA, using functional assays, immunofluorescence microscopy, and colorimetric analysis. Migration, invasion, and epithelial-mesenchymal transition were examined in TAOK1-deficient human hepatoma-derived cells. Alterations in hepatocellular metabolic and pro-oncogenic signaling pathways were assessed by immunoblotting. Results: We observed a positive correlation between the TAOK1 mRNA abundance in human liver biopsies and key hallmarks of NAFLD (i.e., hepatic steatosis, inflammation, and ballooning). Furthermore, we found that TAOK1 protein fully colocalized with intracellular lipid droplets in human and mouse hepatocytes. The silencing of TAOK1 alleviated lipotoxicity in cultured human hepatocytes by accelerating lipid catabolism (mitochondrial beta-oxidation and triacylglycerol secretion), suppressing lipid anabolism (fatty acid influx and lipogenesis), and mitigating oxidative/endoplasmic reticulum stress, and the opposite changes were detected in TAOK1-overexpressing cells. We also found decreased proliferative, migratory, and invasive capacity, as well as lower epithelial-mesenchymal transition in TAOK1-deficient human hepatoma-derived cells. Mechanistic studies revealed that TAOK1 knockdown inhibited ERK and JNK activation and repressed acetyl-CoA carboxylase (ACC) protein abundance in human hepatocytes. Conclusions: Together, we provide the first experimental evidence supporting the role of hepatic lipid droplet-decorating kinase TAOK1 in NAFLD development through mediating fatty acid partitioning between anabolic and catabolic pathways, regulating oxidative/endoplasmic reticulum stress, and modulating metabolic and pro-oncogenic signaling.
|
|
