| 1. |
- Ades, M., et al.
(författare)
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Global Climate : in State of the climate in 2019
- 2020
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 101:8, s. S17-S127
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Ades, M., et al.
(författare)
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GLOBAL CLIMATE
- 2020
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Ingår i: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007 .- 1520-0477. ; 101:8
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Johnston, Jennifer J., et al.
(författare)
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Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations
- 2010
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 31:10, s. 1142-1154
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Tidskriftsartikel (refereegranskat)abstract
- A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here. This includes 19 probands (12 mutations) who fulfilled clinical criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6 mutations) with features of PHS or GCPS and oral-facial- digital syndrome, and 5 probands (1 mutation) with nonsyndromic polydactyly. These data support previously identified genotype-phenotype correlations and demonstrate a more variable degree of severity than previously recognized. The finding of GLI3 mutations in patients with features of oral-facial-digital syndrome supports the observation that GLI3 interacts with cilia. We conclude that the phenotypic spectrum of GLI3 mutations is broader than that encompassed by the clinical diagnostic criteria, but the genotype-phenotype correlation persists. Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria. Hum Mutat 31:1142-1154, 2010. (C) 2010 Wiley-Liss, Inc.
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| 4. |
- Flodell, Sara, et al.
(författare)
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Solution structure of the apical stem-loop of the human hepatitis B virus encapsidation signal.
- 2006
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 34:16, s. 4449-4457
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis B virus (HBV) replication is initiated by HBV RT binding to the highly conserved encapsidation signal, epsilon, at the 5' end of the RNA pregenome. Epsilon contains an apical stem-loop, whose residues are either totally conserved or show rare non-disruptive mutations. Here we present the structure of the apical stem-loop based on NOE, RDC and (1)H chemical shift NMR data. The (1)H chemical shifts proved to be crucial to define the loop conformation. The loop sequence 5'-CUGUGC-3' folds into a UGU triloop with a CG closing base pair and a bulged out C and hence forms a pseudo-triloop, a proposed protein recognition motif. In the UGU loop conformations most consistent with experimental data, the guanine nucleobase is located on the minor groove face and the two uracil bases on the major groove face. The underlying helix is disrupted by a conserved non-paired U bulge. This U bulge adopts multiple conformations, with the nucleobase being located either in the major groove or partially intercalated in the helix from the minor groove side, and bends the helical stem. The pseudo-triloop motif, together with the U bulge, may represent important anchor points for the initial recognition of epsilon by the viral RT.
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| 5. |
- Khalili, Bita, et al.
(författare)
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Associations between common genetic variants and income provide insights about the socioeconomic health gradient
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We conducted a genome-wide association study (GWAS) on income among individuals of European descent and leveraged the results to investigate the socio-economic health gradient (N=668,288). We found 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes. Our GWAS-derived polygenic index captures 1 - 4% of income variance, with only one-fourth attributed to direct genetic effects. A phenome-wide association study using this polygenic index showed reduced risks for a broad spectrum of diseases, including hypertension, obesity, type 2 diabetes, coronary atherosclerosis, depression, asthma, and back pain. The income factor showed a substantial genetic correlation (0.92, s.e. = .006) with educational attainment (EA). Accounting for EA's genetic overlap with income revealed that the remaining genetic signal for higher income related to better mental health but reduced physical health benefits and increased participation in risky behaviours such as drinking and smoking.
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| 6. |
- Kidd, Sue, et al.
(författare)
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Marine Spatial Planning and sustainability : Examining the roles of integration - Scale, policies, stakeholders and knowledge
- 2020
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Ingår i: Ocean and Coastal Management. - : Elsevier. - 0964-5691 .- 1873-524X. ; 191
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Tidskriftsartikel (refereegranskat)abstract
- Marine Spatial Planning (MSP) has been heralded as the key means of achieving a more integrated approach to marine use across sectors and spatial scales. Achieving greater integration and coherence in MSP governance arrangements is seen as a way to resolve current problems of marine governance (such as fragmentation) and address future resource demands in a sustainable way. However, there is a lack of clarity and consensus in practice regarding sustainability in MSP, both in terms of MSP governance practices and sustainable resource use. For example, how are we to treat the environment in MSP? Should we conceive the environment as just another sector with interests to be negotiated, or as the very boundary condition that limits possibilities for maritime activities and developments? How do we integrate diverse views on this in MSP decision-making? This is but one example of an integration challenge in MSP important for sustainability. There are numerous others. Integration is intimately connected to the ability of MSP to deliver sustainable marine resource use at various levels and scales. The roles of integration are diverse and interconnected, including those that affect social-ecological integration or land-sea interaction, but also aspects of good governance and social sustainability. The latter include inter-sectoral decisionmaking, stakeholder engagement, cross-border interaction and knowledge pluralism. How integration is exercised in these procedural aspects of MSP is likely to substantively affect outcomes both in terms of sustainable blue growth or the ability to deliver an ecosystem-based approach. Integration as a policy and analytical problem to be addressed has also been discussed elsewhere – most saliently in the fields of sustainable development, ICZM, environmental policy integration, planning theory and socio-ecological systems. While there has been some work on integration in MSP, additional insight is needed: to better empirically ground the roles of integration in MSP, to understand the multidimensionality and interdependencies of integration dimensions and to unpack what ‘balance’ might mean for understanding and pursuing sustainability in different MSP contexts. In response, this special issue aims to explore the roles, problems and opportunities of various types of integration in relation to MSP's sustainability ambitions.
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| 7. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Reference measurement procedures for Alzheimer's disease cerebrospinal fluid biomarkers: definitions and approaches with focus on amyloid β42.
- 2012
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Ingår i: Biomarkers in medicine. - : Future Medicine Ltd. - 1752-0371 .- 1752-0363. ; 6:4, s. 409-17
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in clinical settings, research and drug trials. However, their broad-scale use on different technology platforms is hampered by the lack of standardization at the level of sample handling, determination of concentrations of analytes and the absence of well-defined performance criteria for in vitro diagnostic or companion diagnostic assays, which influences the apparent concentration of the analytes measured and the subsequent interpretation of the data. There is a need for harmonization of CSF AD biomarker assays that can reliably, across centers, quantitate CSF biomarkers with high analytical precision, selectivity and stability over long time periods. In this position paper, we discuss reference procedures for the measurement of CSF AD biomarkers, especially amyloid β42 and tau. We describe possible technical approaches, focusing on a selected reaction monitoring mass spectrometry assay as a candidate reference method for quantification of CSF amyloid β42.
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| 8. |
- Mattsson, Niklas, 1979, et al.
(författare)
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The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.
- 2011
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.
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| 9. |
- Sun, Dianxing, et al.
(författare)
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Quantitative assessment of the antiviral potencies of 21 shRNA vectors targeting conserved, including structured, hepatitis B virus sites
- 2010
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Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278. ; 52:6, s. 817-826
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: RNA interference (RNAi) may offer new treatment options for chronic hepatitis B. Replicating via an RNA intermediate, hepatitis B virus (HBV) is known to be principally vulnerable to RNAi. However, beyond delivery, the relevant issues of potential off-target effects, target site conservation in circulating HBV strains, and efficacy of RNAi itself have not systematically been addressed, nor can the different existing data be quantitatively compared. The aim of this study was to provide such information. Methods: To focus on the intracellular RNAi process itself and minimise other variables affecting overall RNAi efficacy, we used a robust co-transfection system to quantitatively assess the relative potencies of 21 small-hairpin (sh) RNA vectors, targeting conserved sites throughout the HBV genome, against viral RNAs, proteins, nucleocapsids, and secreted virions under standardised conditions. Results: The approach enabled a distinct efficacy ranking, with the six most potent shRNAs achieving >= 95% reductions in virion formation, sequence-specifically and without detectable interferon induction, yet by differentially affecting different steps. Efficacy correlated poorly with predictions and was not principally abolished by target structure. Sequence comparisons suggest that truly conserved, RNAi-targetable sequences comprise less than 500 nucleotides of the circulating HBV genomes. Conclusions: The HBV genome can harbour only a finite number of optimal target sites, but current predictions are poorly suited to constrain the number of possible candidates. However, the small size of the highly conserved sequence space suggests experimental identification as a viable option. (c) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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| 10. |
- Zody, Michael C., et al.
(författare)
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Evolutionary toggling of the MAPT 17q21.31 inversion region
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 40:9, s. 1076-83
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Tidskriftsartikel (refereegranskat)abstract
- Using comparative sequencing approaches, we investigated the evolutionary history of the European-enriched 17q21.31 MAPT inversion polymorphism. We present a detailed, BAC-based sequence assembly of the inverted human H2 haplotype and compare it to the sequence structure and genetic variation of the corresponding 1.5-Mb region for the noninverted H1 human haplotype and that of chimpanzee and orangutan. We found that inversion of the MAPT region is similarly polymorphic in other great ape species, and we present evidence that the inversions occurred independently in chimpanzees and humans. In humans, the inversion breakpoints correspond to core duplications with the LRRC37 gene family. Our analysis favors the H2 configuration and sequence haplotype as the likely great ape and human ancestral state, with inversion recurrences during primate evolution. We show that the H2 architecture has evolved more extensive sequence homology, perhaps explaining its tendency to undergo microdeletion associated with mental retardation in European populations.
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