| 1. |
- Thompson, B.A., et al.
(författare)
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Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:2, s. 107-115
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Tidskriftsartikel (refereegranskat)abstract
- The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.
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| 2. |
- Horikoshi, Momoko, et al.
(författare)
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New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
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Tidskriftsartikel (refereegranskat)abstract
- Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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| 3. |
- Hasan, A, et al.
(författare)
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World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia : Part 1: Update 2012 on the acute treatment of schizophrenia and the management of treatment resistance.
- 2012
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Ingår i: The World Journal of Biological Psychiatry. - : Informa UK Limited. - 1562-2975 .- 1814-1412. ; 13:5, s. 318-378
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Tidskriftsartikel (refereegranskat)abstract
- These updated guidelines are based on a first edition of the World Federation of Societies of Biological Psychiatry Guidelines for Biological Treatment of Schizophrenia published in 2005. For this 2012 revision, all available publications pertaining to the biological treatment of schizophrenia were reviewed systematically to allow for an evidence-based update. These guidelines provide evidence-based practice recommendations that are clinically and scientifically meaningful and these guidelines are intended to be used by all physicians diagnosing and treating people suffering from schizophrenia. Based on the first version of these guidelines, a systematic review of the MEDLINE/PUBMED database and the Cochrane Library, in addition to data extraction from national treatment guidelines, has been performed for this update. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into six levels of evidence (A–F; Bandelow et al. 2008b, World J Biol Psychiatry 9:242). This first part of the updated guidelines covers the general descriptions of antipsychotics and their side effects, the biological treatment of acute schizophrenia and the management of treatment-resistant schizophrenia.
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| 4. |
- Knudsen, Endre, et al.
(författare)
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Challenging claims in the study of migratory birds and climate change.
- 2011
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Ingår i: Biological Reviews. - 1469-185X. ; 86, s. 928-946
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Tidskriftsartikel (refereegranskat)abstract
- Recent shifts in phenology in response to climate change are well established but often poorly understood. Many animals integrate climate change across a spatially and temporally dispersed annual life cycle, and effects are modulated by ecological interactions, evolutionary change and endogenous control mechanisms. Here we assess and discuss key statements emerging from the rapidly developing study of changing spring phenology in migratory birds. These well-studied organisms have been instrumental for understanding climate-change effects, but research is developing rapidly and there is a need to attack the big issues rather than risking affirmative science. Although we agree poorly on the support for most claims, agreement regarding the knowledge basis enables consensus regarding broad patterns and likely causes. Empirical data needed for disentangling mechanisms are still scarce, and consequences at a population level and on community composition remain unclear. With increasing knowledge, the overall support ('consensus view') for a claim increased and between-researcher variability in support ('expert opinions') decreased, indicating the importance of assessing and communicating the knowledge basis. A proper integration across biological disciplines seems essential for the field's transition from affirming patterns to understanding mechanisms and making robust predictions regarding future consequences of shifting phenologies.
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| 5. |
- Willerslev, E, et al.
(författare)
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Fifty thousand years of arctic vegetation change and megafauna diet
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 506:7486, s. 47-47
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Tidskriftsartikel (refereegranskat)abstract
- Although it is generally agreed that the Arctic flora is among the youngest and least diverse on Earth, the processes that shaped it are poorly understood. Here we present 50 thousand years (kyr) of Arctic vegetation history, derived from the first large-scale ancient DNA metabarcoding study of circumpolar plant diversity. For this interval we also explore nematode diversity as a proxy for modelling vegetation cover and soil quality, and diets of herbivorous megafaunal mammals, many of which became extinct around 10 kyr bp (before present). For much of the period investigated, Arctic vegetation consisted of dry steppe-tundra dominated by forbs (non-graminoid herbaceous vascular plants). During the Last Glacial Maximum (25–15 kyr bp), diversity declined markedly, although forbs remained dominant. Much changed after 10 kyr bp, with the appearance of moist tundra dominated by woody plants and graminoids. Our analyses indicate that both graminoids and forbs would have featured in megafaunal diets. As such, our findings question the predominance of a Late Quaternary graminoid-dominated Arctic mammoth steppe.
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| 6. |
- Arnold, L.J., et al.
(författare)
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Paper II - Dirt, dates and DNA: OSL and radiocarbon chronologies of perennially-frozen sediments in Siberia, and their implications for sedimentary ancient DNA studies
- 2011
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Ingår i: Boreas. - : Wiley. - 1502-3885 .- 0300-9483. ; 40:3, s. 417-445
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in UndeterminedThe sedimentary ancient DNA (sedaDNA) technique offers a potentially invaluable means of investigating species evolution and extinction dynamics in high-latitude environments. An implicit assumption of the sedaDNA approach is that the extracted DNA is autochthonous with the host deposit and that it has not been physically transported from older source deposits or reworked within the sedimentary profile by postdepositional mixing. In this paper we investigate whether these fundamental conditions are upheld at seven perennially frozen wetland sites across the Taimyr Peninsula and coastal lowlands of north-central Siberia. Optically stimulated luminescence (OSL) and radiocarbon (C-14) dating are used to constrain the ages of both the inorganic and organic fractions of perennially frozen deposits from which sedaDNA of extinct and extant species have been recovered. OSL and C-14 age/depth profiles, as well as single-grain equivalent dose (De) distribution characteristics, are used to assess the stratigraphic integrity of these sedaDNA sequences by (i) identifying the presence of primary or reworked organic and inorganic material, and (ii) examining the types of depositional and postdepositional processes that have affected specific sedimentary facies. The results of this study demonstrate that even though DNA preservation and stratigraphic integrity are commonly superior in perennially frozen settings, this does not, in itself, guarantee the suitability of the sedaDNA approach. The combined OSL and C-14 chronologies reveal that certain perennially frozen sites may be poorly suited for sedaDNA analysis, and that careful site selection is paramount to ensuring the accuracy of any sedaDNA study - particularly for 'latest appearance date' estimates of extinct taxa.
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| 7. |
- Browse, John A., et al.
(författare)
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Respiration and Lipid Metabolism
- 2014. - 6th ed.
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Ingår i: Plant Physiology and Development. - 9781605352558 - 9781605354354 ; , s. 317-352
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Bokkapitel (refereegranskat)
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| 8. |
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| 9. |
- Lemcke, S., et al.
(författare)
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Nerve conduction velocity is regulated by the inositol polyphosphate-4-phosphatase II gene
- 2014
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 184:9, s. 2420-2429
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Tidskriftsartikel (refereegranskat)abstract
- Impairment of nerve conduction is common in neurodegenerative and neuroinflammatory diseases such as multiple sclerosis (MS), and measurement of evoked potentials (visual, motor, or sensory) has been widely used for diagnosis and recently also as a prognostic marker for MS. We used a classical genetic approach to identify novel genes controlling nerve conduction. First, we used quantitative trait mapping in F2 progeny of B10/SJL mice to identify EAE31, a locus controlling latency of motor evoked potentials (MEPs) and clinical onset of experimental autoimmune encephalomyelitis. Then, by combining congenic mapping, in silico haplotype analyses, and comparative genomics we identified inositol polyphosphate-4-phosphatase, type II (Inpp4b) as the quantitative trait gene for EAE31. Sequence variants of Inpp4b (C/A, exon 13; A/C, exon 14) were identified as differing among multiple mouse strains and correlated with individual cortical MEP latency differences. To evaluate the functional relevance of the amino acid exchanges at positions S474R and H548P, we generated transgenic mice carrying the longer-latency allele (Inpp4b(474R/548P)) in the C57BL/6J background. Inpp4b(474R/548P) mice exhibited significantly longer cortical MEP latencies (4.5 +/- 0.22 ms versus 3.7 +/- 0.13 ms; P = 1.04 x 10(-9)), indicating that INPP4B regulates nerve conduction velocity. An association of an INPP4B polymorphism (rs13102150) with MS was observed in German and Spanish MS cohorts (3676 controls and 911 cases) (P = 8.8 x 10(-3)).
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| 10. |
- Marzal, Alfonso, et al.
(författare)
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Diversity, Loss, and Gain of Malaria Parasites in a Globally Invasive Bird.
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- Invasive species can displace natives, and thus identifying the traits that make aliens successful is crucial for predicting and preventing biodiversity loss. Pathogens may play an important role in the invasive process, facilitating colonization of their hosts in new continents and islands. According to the Novel Weapon Hypothesis, colonizers may out-compete local native species by bringing with them novel pathogens to which native species are not adapted. In contrast, the Enemy Release Hypothesis suggests that flourishing colonizers are successful because they have left their pathogens behind. To assess the role of avian malaria and related haemosporidian parasites in the global spread of a common invasive bird, we examined the prevalence and genetic diversity of haemosporidian parasites (order Haemosporida, genera Plasmodium and Haemoproteus) infecting house sparrows (Passer domesticus). We sampled house sparrows (N = 1820) from 58 locations on 6 continents. All the samples were tested using PCR-based methods; blood films from the PCR-positive birds were examined microscopically to identify parasite species. The results show that haemosporidian parasites in the house sparrows' native range are replaced by species from local host-generalist parasite fauna in the alien environments of North and South America. Furthermore, sparrows in colonized regions displayed a lower diversity and prevalence of parasite infections. Because the house sparrow lost its native parasites when colonizing the American continents, the release from these natural enemies may have facilitated its invasion in the last two centuries. Our findings therefore reject the Novel Weapon Hypothesis and are concordant with the Enemy Release Hypothesis.
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