1. |
- Hop, Paul J., et al.
(author)
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Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
-
In: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
-
Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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2. |
- Dai, Qile, et al.
(author)
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OTTERS: a powerful TWAS framework leveraging summary-level reference data
- 2023
-
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Journal article (peer-reviewed)abstract
- Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies.
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3. |
- Zamora, Juan Carlos, et al.
(author)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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In: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
-
Journal article (peer-reviewed)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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4. |
- Fanelli, Giuseppe, et al.
(author)
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Insulinopathies of the brain? : Genetic overlap between somatic insulin-related and neuropsychiatric disorders
- 2022
-
In: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 12:1
-
Journal article (peer-reviewed)abstract
- The prevalence of somatic insulinopathies, like metabolic syndrome (MetS), obesity, and type 2 diabetes mellitus (T2DM), is higher in Alzheimer's disease (AD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD). Dysregulation of insulin signalling has been implicated in these neuropsychiatric disorders, and shared genetic factors might partly underlie this observed multimorbidity. We investigated the genetic overlap between AD, ASD, and OCD with MetS, obesity, and T2DM by estimating pairwise global genetic correlations using the summary statistics of the largest available genome-wide association studies for these phenotypes. Having tested these hypotheses, other potential brain "insulinopathies" were also explored by estimating the genetic relationship of six additional neuropsychiatric disorders with nine insulin-related diseases/traits. Stratified covariance analyses were then performed to investigate the contribution of insulin-related gene sets. Significant negative genetic correlations were found between OCD and MetS (r(g) = -0.315, p = 3.9 x 10(-8)), OCD and obesity (r(g) = -0.379, p = 3.4 x 10(-5)), and OCD and T2DM (r(g) = -0.172, p = 3 x 10(-4)). Significant genetic correlations with insulin-related phenotypes were also found for anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), major depressive disorder, and schizophrenia (p < 6.17 x 10(-4)). Stratified analyses showed negative genetic covariances between AD, ASD, OCD, ADHD, AN, bipolar disorder, schizophrenia and somatic insulinopathies through gene sets related to insulin signalling and insulin receptor recycling, and positive genetic covariances between AN and T2DM, as well as ADHD and MetS through gene sets related to insulin processing/secretion (p < 2.06 x 10(-4)). Overall, our findings suggest the existence of two dusters of neuropsychiatric disorders, in which the genetics of insulin-related diseases/traits may exert divergent pleiotropic effects. These results represent a starting point for a new research line on "insulinopathies" of the brain.
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5. |
- Günther, Torsten, et al.
(author)
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Population genomics of Mesolithic Scandinavia : Investigating early postglacial migration routes and high-latitude adaptation
- 2018
-
In: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 16:1
-
Journal article (peer-reviewed)abstract
- Scandinavia was one of the last geographic areas in Europe to become habitable for humans after the Last Glacial Maximum (LGM). However, the routes and genetic composition of these postglacial migrants remain unclear. We sequenced the genomes, up to 57x coverage, of seven hunter-gatherers excavated across Scandinavia and dated from 9,500-6,000 years before present (BP). Surprisingly, among the Scandinavian Mesolithic individuals, the genetic data display an east-west genetic gradient that opposes the pattern seen in other parts of Mesolithic Europe. Our results suggest two different early postglacial migrations into Scandinavia: initially from the south, and later, from the northeast. The latter followed the ice-free Norwegian north Atlantic coast, along which novel and advanced pressure-blade stone-tool techniques may have spread. These two groups met and mixed in Scandinavia, creating a genetically diverse population, which shows patterns of genetic adaptation to high latitude environments. These potential adaptations include high frequencies of low pigmentation variants and a gene region associated with physical performance, which shows strong continuity into modern-day northern Europeans.
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6. |
- Kattge, Jens, et al.
(author)
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TRY plant trait database - enhanced coverage and open access
- 2020
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In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
-
Journal article (peer-reviewed)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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7. |
- Kurz, Alexander, et al.
(author)
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RHAPSODY - Internet-based support for caregivers of people with young onset dementia : program design and methods of a pilot study
- 2016
-
In: International psychogeriatrics. - 1041-6102 .- 1741-203X. ; 28:12, s. 2091-2099
-
Journal article (peer-reviewed)abstract
- Background: Young Onset Dementia (YOD), defined by first symptoms of cognitive or behavioral decline occurring before the age of 65 years, is relatively rare compared to dementia of later onset, but it is associated with diagnostic difficulty and heavy burden on affected individuals and their informal carers. Existing health and social care structures rarely meet the needs of YOD patients. Internet-based interventions are a novel format of delivering health-related education, counseling, and support to this vulnerable yet underserved group. Methods: The RHAPSODY (Research to Assess Policies and Strategies for Dementia in the Young) project is a European initiative to improve care for people with YOD by providing an internet-based information and skill-building program for family carers. The e-learning program focuses on managing problem behaviors, dealing with role change, obtaining support, and looking after oneself. It will be evaluated in a pilot study in three countries using a randomized unblinded design with a wait-list control group. Participants will be informal carers of people with dementia in Alzheimer's disease or behavioral-variant Frontotemporal degeneration with an onset before the age of 65 years. The primary outcome will be caregiving self-efficacy after 6 weeks of program use. As secondary outcomes, caregivers' stress and burden, carer health-related quality of life, caring-related knowledge, patient problem behaviors, and user satisfaction will be assessed. Program utilization will be monitored and a health-economic evaluation will also be performed. Conclusions: The RHAPSODY project will add to the evidence on the potential and limitations of a conveniently accessible, user-friendly, and comprehensive internet-based intervention as an alternative for traditional forms of counseling and support in healthcare, aiming to optimize care and support for people with YOD and their informal caregivers.
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8. |
- Andersson, Jonas, 1975-, et al.
(author)
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Estimating Patient Organ Dosewith Computed Tomography: A Review of Present Methodologyand Required DICOM Information : A Joint Report ofAAPM Task Group 246 and the European Federationof Organizations for Medical Physics (EFOMP)
- 2019
-
Reports (peer-reviewed)abstract
- The purpose of this report is (1) to summarize the current state of the art in estimating organ doses from CT examinations and (2) to outline a road map for standardized reporting of essential parameters necessary for estimation of organ doses from CT imaging in the DICOM standard. To address these purposes, the report includes a comprehensive discussion of (1) the various metrics, concepts, and methods that may be used to achieve estimates of patient organ dose and (2) the DICOM standard for CT.This Joint Report of the American Association of Physicists in Medicine (AAPM) Task Group 246 and the European Federation of Organizations for Medical Physics (EFOMP) contains three major sections and an appendix. Section 2 (with additional material in the appendix) provides a review of basic CT dosimetry metrics, their uses and limitations in the context of organ dosimetry, and the DICOM information currently associated with parameters that affect CT dose metrics and, consequently, organ dose estimates. Section 3 provides an overview of present and emerging organ dose estimation methods reported in the literature, e.g., for the lens of the eye, breast tissue, colon, and skin. Finally, the report concludes with section 4, which provides a discussion on the sources and magnitudes of uncertainty for different organ dose estimation methods.Ongoing efforts to facilitate routine standardized estimation of patient organ doses from CT are dependent, in large part, on the availability of the DICOM Radiation Dose Structured Report (RDSR), which provides a host of information pertinent to radiation dose calculations. This report, therefore, includes detailed information on DICOM header content in CT images and how it can be used in organ dose estimation. The RDSR markedly expands the abilities of the clinical medical physicist to estimate doses at the patient, device, and protocol level
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9. |
- Bange, Jan Philipp, et al.
(author)
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Probing electron-hole Coulomb correlations in the exciton landscape of a twisted semiconductor heterostructure
- 2024
-
In: Science advances. - 2375-2548. ; 10:6
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Journal article (peer-reviewed)abstract
- In two-dimensional semiconductors, cooperative and correlated interactions determine the material’s excitonic properties and can even lead to the creation of correlated states of matter. Here, we study the fundamental two-particle correlated exciton state formed by the Coulomb interaction between single-particle holes and electrons. We find that the ultrafast transfer of an exciton’s hole across a type II band-aligned semiconductor heterostructure leads to an unexpected sub-200-femtosecond upshift of the single-particle energy of the electron being photoemitted from the two-particle exciton state. While energy relaxation usually leads to an energetic downshift of the spectroscopic signature, we show that this upshift is a clear fingerprint of the correlated interaction of the electron and hole parts of the exciton. In this way, time-resolved photoelectron spectroscopy is straightforwardly established as a powerful method to access electron-hole correlations and cooperative behavior in quantum materials. Our work highlights this capability and motivates the future study of optically inaccessible correlated excitonic and electronic states of matter.
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10. |
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11. |
- Boen, Rune, et al.
(author)
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Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers
- 2024
-
In: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 95:2, s. 147-160
-
Journal article (peer-reviewed)abstract
- Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
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12. |
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13. |
- Carsten, Hobohm, et al.
(author)
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Land Use Change and the Future of Biodiversity
- 2021
-
In: Perspectives for Biodiversity and Ecosystems. - Cham : Springer. - 2214-2827 .- 2214-2835. - 9783030577094 ; , s. 451-483
-
Book chapter (other academic/artistic)abstract
- This synthesis report is a meta-analysis of perspectives for biodiversity and ecosystems, with a strong focus on human impacts on the environment, and a work order to enable and manage the protection, survival and evolution of all species on Earth. The goal is to protect nature without any further species loss (Zero Extinction). With this report, we assess alarming signals from the environment; determine the needs of threatened biota and the required actions to manage and protect landscapes and ecosystems; and identify some inescapable tendencies, challenges but also possibilities. The story of humans on Earth is at a critical juncture. Human behaviour is inherently dependent on physical and societal relations, including orientation and positioning within the physical environment. There is no single cultural benefit that is independent of provisioning through ecosystem services. Humans are part of the environment, acquire all needs from it and, as such, depend on its integrity and management for life and well-being. Moreover, if human impacts to the environment continue to increase the risk of rebound effects impacting human life and health will increase as well. Whenever a biome, ecosystem, habitat or species is heavily impacted or threatened with irreversible transformation or extinction, prevailing environmental conditions are relevant and should be observed, analysed and remedied as necessary and where possible. Ecology examines the evolutionary, historical and more recent interplay between biological life and the abiotic environment, while the role of social science and the humanities is to question the physical and social landscape, and how and why it should be protected or influenced, e.g. by nature conservation measures under political and economic, ethical and legal considerations. Thus, for all inter-relationships between natural and sociocultural processes, a joint venture in the form of social-ecological thinking is necessary to combine natural sciences and the humanities. With this contribution, we combine ecological knowledge with social science knowledge (s.l.) through the participation of scientists of many different disciplines. We analyse history and current processes to assess risks, threats and possibilities, and call for an array of regulations and measures that can contribute to halting of biodiversity loss and that assist in achieving a sustainable future. Regulations comprise creativity, cultural incentives, social norms, environmental education and economic investments—such as payments for sustainable agriculture, forestry, and fishery; investments in water, soil and air purity; and much clearer and stronger legal restrictions and consequences around waste streams and environmental degradation. Moreover, a gradual change from profit-oriented economies in the short-run to environmentally-sensitive policies that include systematic environmental programmes in the long term might help to decrease pressure on ecosystems and biota. Such economics might also include the real costs of consumerism, including the impacts of particular products on the environment and on human health. The greatest hurdle for the continued existence of many critically endangered species is the impact of widespread anthropogenic-driven change in the usage of water, air and land, and industry intensification in agriculture, aquaculture, forestry, urbanisation, transportation and mining sectors. However, there is not one simple solution to solve these issues. We conclude that many of the current developments have to be adjusted or gradually altered in a step-wise manner, especially with respect to existing sociocultural behaviours. Therefore, various concepts, decisions and measures should be discussed and implemented at all scales from local to supranational and among researchers, practitioners and politicians.
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14. |
- Chen, Tianhui, et al.
(author)
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Distribution and risk of the second discordant primary cancers combined after a specific first primary cancer in German and Swedish cancer registries.
- 2015
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In: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 369:1, s. 152-166
-
Journal article (peer-reviewed)abstract
- We aimed at investigating the distribution and risk of all second discordant primary cancers (SDPCs) after a specific first primary cancer in Germany and Sweden to provide etiological understanding of SDPCs and insight into their incidence rates and recording practices. Among 1,537,004 survivors of first primary cancers in Germany and 588,103 in Sweden, overall 80,162 and 32,544 SDPCs were recorded, respectively. Standardized incidence ratios (SIRs) of all SDPCs were elevated at levels between 1.1 and 2.1 after 23 (out of overall 29) cancers in Germany and at levels between 1.1 and 1.6 after 24 cancers in Sweden, and among them, elevated SIRs were found after 19 cancers in both populations. Decreased SIRs at levels ranging from 0.5 to 0.9 were found for some cancers with poor prognosis in Germany only. We found elevated risk after 19 out of 29 cancers in both countries, suggesting common etiology of SDPCs after most of first cancers and registration similarity. Decreased risks after some fatal cancers were found only in Germany, which may be attributed to reporting practices or missed death data in Germany.
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15. |
- Cohen, Timothy, et al.
(author)
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Continental aridification and the vanishing of Australia's mega-lakes
- 2011
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In: Geology. - 0091-7613 .- 1943-2682. ; 39, s. 167-170
-
Journal article (peer-reviewed)abstract
- The nature of the Australian climate at about the time of rapid megafaunal extinctions and humans arriving in Australia is poorly understood and is an important element in the contentious debate as to whether humans or climate caused the extinctions. Here we present a new paleoshoreline chronology that extends over the past 100 k.y. for Lake Mega-Frome, the coalescence of Lakes Frome, Blanche, Callabonna and Gregory, in the southern latitudes of central Australia. We show that Lake Mega-Frome was connected for the last time to adjacent Lake Eyre at 50–47 ka, forming the largest remaining interconnected system of paleolakes on the Australian continent. The fi nal disconnection and a progressive drop in the level of Lake Mega-Frome represents a major climate shift to aridifi cation that coincided with the arrival of humans and the demise of the megafauna. The supply of moisture to the Australian continent at various times in the Quaternary has commonly been ascribed to an enhanced monsoon. This study, in combination with other paleoclimate data, provides reliable evidence for peri-ods of enhanced tropical and enhanced Southern Ocean sources of water fi lling these lakes at different times during the last full glacial cycle.
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16. |
- Cohen, Tim J., et al.
(author)
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Hydrological transformation coincided with megafaunal extinction in central Australia
- 2015
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In: Geology. - 0091-7613 .- 1943-2682. ; 43:3, s. 195-198
-
Journal article (peer-reviewed)abstract
- Central to the debate over the extinction of many of Australia's last surviving megafauna is the question: Was climate changing significantly when humans arrived and megafauna went extinct? Here we present a new perspective on variations in climate and water resources over the last glacial cycle in arid Australia based on the study of the continent's largest lake basin and its tributaries. By dating paleoshorelines and river deposits in the Lake Eyre basin, we show that major hydrological change caused previously overflowing megalakes to enter a final and catastrophic drying phase at 48 +/- 2 ka just as the giant bird, Genyornis newtoni, went extinct (50-45 ka). The disappearance of Genyornis and other megafauna has been previously attributed to ecosystem collapse coincident with the spread of fire-wielding humans. Our findings suggest a climate-driven hydrological transformation in the critical window of human arrival and megafaunal extinction, and the results call for a re-evaluation of a human-mediated cause for such extinctions in arid Australia.
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17. |
- Cohen, Timothy, et al.
(author)
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Late Quaternary mega-lakes fed by the northern and southern river systems of central Australia : varying moisture sources and increased continental aridity
- 2012
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In: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182 .- 1872-616X. ; 356:Special Issue, s. 89-108
-
Journal article (peer-reviewed)abstract
- Optically stimulated and thermoluminescence ages from relict shorelines, along with accelerator mass spectrometer 14C ages from freshwater molluscs reveal a record of variable moisture sources supplied by northern and southern river systems to Lake Mega-Frome in southern central Australia during the late Quaternary. Additional lacustrine, palynological and terrestrial proxies are used to reconstruct a record that extends back to 105 ka, confirming that Lakes Mega-Frome and Mega-Eyre were joined to create the largest system of palaeolakes on the Australian continent as recently as 50–47 ka. The palaeohydrological record indicates a progressive shift to more arid conditions, with marked drying after 45 ka. Subsequently, Lake Mega-Frome has filled independently at 33–31 ka and at the termination of the Last Glacial Maximum to volumes some 40 times those of today. Further sequentially declining filling episodes (to volumes 25–10 those of today) occurred immediately prior to the Younger Dryas stadial, in the mid Holocene and during the medieval climatic anomaly. Southern hemisphere summer insolation maxima are a poor predictor of palaeolake-filling episodes. An examination of multiple active moisture sources suggests that palaeolake phases were driven independently of insolation and at times by some combination of enhanced Southern Ocean circulation and strengthened tropical moisture sources.
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18. |
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19. |
- Cohen, Timothy, et al.
(author)
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Late Quaternary mega-lakes of central Australia: varying moisture sources and increased continental aridity.
- 2010
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In: <em>EOS Transactions, </em><em>American Geophysical Union</em>, PP31B-1624. San Francisco, USA, Dec. 2010.. - Washington DC : American Geophysical Union.
-
Conference paper (other academic/artistic)abstract
- Optically stimulated (OSL) and thermoluminescence (TL) ages from relict shorelines, along with accelerator mass spectrometer (AMS) 14C ages from freshwater molluscs reveal a record of mega-lake phases over the late Quaternary for Lake Mega-Frome, situated in the arid zone of South Australia. Additional lacustrine, palynological and terrestrial proxies are used to reconstruct a record that extends as far back as 105 ka and demonstrates that Mega-Frome was last joined to the adjacent mega-Eyre at 50 - 47 ka forming the largest palaeolake on the Australian continent. This time interval for hydrological decline coincides with the arrival of humans on the Australian continent and the demise of the mega-fauna. Since then, Mega-Frome has filled independently at 33 - 31 ka (Heinrich event 3) and at the termination of the Last Glacial Maximum (LGM) to depths far in excess of those seen today (up to 15 - 20 times modern lake volumes). Further evidence of subsequent lake-filling episodes is recorded immediately prior to the Younger Dryas, the mid Holocene and during the medieval climatic anomaly. We present evidence for multiple moisture sources over this time period with lake phases being driven by either an enhanced Southern Ocean circulation or an enhanced tropical moisture source or a combination of both. We show however, that southern hemisphere summer insolation maxima (monsoon proxy) is a poor predictor for past palaeo-lake filling episodes. This is the first palaeohydrological record for a large area of southern semi-arid Australia indicating a progressive shift to more arid conditions throughout the last glacial cycle
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20. |
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21. |
- Davies, Stuart J., et al.
(author)
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ForestGEO: Understanding forest diversity and dynamics through a global observatory network
- 2021
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In: Biological Conservation. - : Elsevier BV. - 0006-3207. ; 253
-
Journal article (peer-reviewed)abstract
- ForestGEO is a network of scientists and long-term forest dynamics plots (FDPs) spanning the Earth's major forest types. ForestGEO's mission is to advance understanding of the diversity and dynamics of forests and to strengthen global capacity for forest science research. ForestGEO is unique among forest plot networks in its large-scale plot dimensions, censusing of all stems ≥1 cm in diameter, inclusion of tropical, temperate and boreal forests, and investigation of additional biotic (e.g., arthropods) and abiotic (e.g., soils) drivers, which together provide a holistic view of forest functioning. The 71 FDPs in 27 countries include approximately 7.33 million living trees and about 12,000 species, representing 20% of the world's known tree diversity. With >1300 published papers, ForestGEO researchers have made significant contributions in two fundamental areas: species coexistence and diversity, and ecosystem functioning. Specifically, defining the major biotic and abiotic controls on the distribution and coexistence of species and functional types and on variation in species' demography has led to improved understanding of how the multiple dimensions of forest diversity are structured across space and time and how this diversity relates to the processes controlling the role of forests in the Earth system. Nevertheless, knowledge gaps remain that impede our ability to predict how forest diversity and function will respond to climate change and other stressors. Meeting these global research challenges requires major advances in standardizing taxonomy of tropical species, resolving the main drivers of forest dynamics, and integrating plot-based ground and remote sensing observations to scale up estimates of forest diversity and function, coupled with improved predictive models. However, they cannot be met without greater financial commitment to sustain the long-term research of ForestGEO and other forest plot networks, greatly expanded scientific capacity across the world's forested nations, and increased collaboration and integration among research networks and disciplines addressing forest science.
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22. |
- Diekstra, Frank P., et al.
(author)
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Mapping of Gene Expression Reveals CYP27A1 as a Susceptibility Gene for Sporadic ALS
- 2012
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:4, s. e35333-
-
Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. ALS is considered to be a complex trait and genome-wide association studies (GWAS) have implicated a few susceptibility loci. However, many more causal loci remain to be discovered. Since it has been shown that genetic variants associated with complex traits are more likely to be eQTLs than frequency-matched variants from GWAS platforms, we conducted a two-stage genome-wide screening for eQTLs associated with ALS. In addition, we applied an eQTL analysis to finemap association loci. Expression profiles using peripheral blood of 323 sporadic ALS patients and 413 controls were mapped to genome-wide genotyping data. Subsequently, data from a two-stage GWAS (3,568 patients and 10,163 controls) were used to prioritize eQTLs identified in the first stage (162 ALS, 207 controls). These prioritized eQTLs were carried forward to the second sample with both gene-expression and genotyping data (161 ALS, 206 controls). Replicated eQTL SNPs were then tested for association in the second-stage GWAS data to find SNPs associated with disease, that survived correction for multiple testing. We thus identified twelve cis eQTLs with nominally significant associations in the second-stage GWAS data. Eight SNP-transcript pairs of highest significance (lowest p = 1.27 x 10(-51)) withstood multiple-testing correction in the second stage and modulated CYP27A1 gene expression. Additionally, we show that C9orf72 appears to be the only gene in the 9p21.2 locus that is regulated in cis, showing the potential of this approach in identifying causative genes in association loci in ALS. This study has identified candidate genes for sporadic ALS, most notably CYP27A1. Mutations in CYP27A1 are causal to cerebrotendinous xanthomatosis which can present as a clinical mimic of ALS with progressive upper motor neuron loss, making it a plausible susceptibility gene for ALS.
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23. |
- Eberwein, Jan, et al.
(author)
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Evaluation der Akzeptanz mobiler Lernszenarien auf Basis plattformunabhängiger Webtechnologien.
- 2014
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In: Proceedings der 12ten e-Learning Fachtagung der Informatik (DeLFI 2014). ; , s. 213-220
-
Conference paper (peer-reviewed)abstract
- In den letzten Jahren nahm die Nutzung mobiler Geräte stark zu, wasauch zu einer Verbreitung mobiler Geräte in mobilen Lernszenarien geführt hat.Aufgrund der Heterogenität der am Markt befindlichen mobilen Geräte wird zurSoftwareentwicklung häufig ein plattformunabhängiger Ansatz gewählt. Hierzugibt es im Wesentlichen zwei unterschiedliche Ansätze, die beide aufWebtechnologien basieren. Entweder es werden Applikationen mit spezifischen UIFrameworks für mobile Geräte oder mit responsive Ansätzen, parallel für mobileund stationäre Geräte, entwickelt. Um beide Ansätze vergleichen zu können, stelltdieses Papier eine Evaluation der Akzeptanz mobiler Lernszenarien auf Basisplattformunabhängiger Webtechnologien dar.
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24. |
- Ebrahimi-Fakhari, Darius, et al.
(author)
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Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia
- 2020
-
In: Brain. - OXFORD ENGLAND : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:10, s. 2929-2944
-
Journal article (peer-reviewed)abstract
- Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 +/- 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 +/- 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 +/- 5.1 years, SD) and later tetraplegia (mean age: 16.1 +/- 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 +/- 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 +/- 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.
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25. |
- Ericson, Per G P, 1956-, et al.
(author)
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Inter-generic relationships of the crows, jays, magpies and allied groups (Aves: Corvidae) based on nucleotide sequence data
- 2005
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In: Journal of Avian Biology. - : Wiley. - 0908-8857 .- 1600-048X. ; 36:3, s. 222-234
-
Journal article (peer-reviewed)abstract
- Phylogenetic relationships were studied based on DNA sequences obtained from all recognized genera of the family Corvidae sensu stricto. The aligned data set consists 2589 bp obtained from one mitochondrial and two nuclear genes. Maximum parsimony, maximum-likelihood, and Bayesian inference analyses were used to estimate phylogenetic relationships. The analyses were done for each gene separately, as well as for all genes combined. An analysis of a taxonomically expanded data set of cytochrome b sequences was performed in order to infer the phylogenetic positions of six genera for which nuclear genes could not be obtained. Monophyly of the Corvidae is supported by all analyses, as well as by the occurrence of a deletion of 16 bp in the β-fibrinogen intron in all ingroup taxa. Temnurus and Pyrrhocorax are placed as the sister group to all other corvids, while Cissa and Urocissa appear as the next clade inside them. Further up in the tree, two larger and well-supported clades of genera were recovered by the analyses. One has an entirely New World distribution (the New World jays), while the other includes mostly Eurasian (and one African) taxa. Outside these two major clades are Cyanopica and Perisoreus whose phylogenetic positions could not be determined by the present data. A biogeographic analysis of our data suggests that the Corvidae underwent an initial radiation in Southeast Asia. This is consistent with the observation that almost all basal clades in the phylogenetic tree consist of species adapted to tropical and subtropical forest habitats.
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26. |
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27. |
- Evangelou, Evangelos, et al.
(author)
-
Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
-
Journal article (peer-reviewed)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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28. |
- Fitzsimmons, Kathryn E., et al.
(author)
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Late Quaternary palaeoenvironmental change in the Australian drylands
- 2013
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In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 74, s. 78-96
-
Journal article (peer-reviewed)abstract
- In this paper we synthesise existing palaeoenvironmental data from the arid and semi-arid interior of the Australian continent for the period 40-0 ka. Moisture is the predominant variable controlling environmental change in the arid zone. Landscapes in this region respond more noticeably to changes in precipitation than to temperature. Depending on their location, arid zone records broadly respond to tropical monsoon-influenced climate regimes, the temperate latitude westerly systems, or a combination of both. The timing and extent of relatively arid and humid phases vary across the continent, in particular between the westerly wind-controlled temperate latitudes, and the interior and north which are influenced by tropically sourced precipitation. Relatively humid phases in the Murray-Darling Basin on the semi-arid margins, which were characterised by large rivers most likely fed by snow melt, prevailed from 40 ka to the Last Glacial Maximum (LGM), and from the deglacial to the mid Holocene. By contrast, the Lake Eyre basin in central Australia remained relatively dry throughout the last 40 ka, with lake high stands at lake Frome around 35-30 ka, and parts of the deglacial period and the mid-Holocene. The LGM was characterised by widespread relative aridity and colder conditions, as evidenced by extensive desert dune activity and dust transport, lake level fall, and reduced but episodic fluvial activity. The climate of the deglacial period was spatially divergent. The southern part of the continent experienced a brief humid phase around similar to 17-15 ka, followed by increased dune activity around similar to 14-10 ka. This contrasts with the post-LGM persistence of arid conditions in the north, associated with a lapsed monsoon and reflected in lake level lows and reduced fluvial activity, followed by intensification of the monsoon and increasingly effective precipitation from similar to 14 ka. Palaeoenvironmental change during the Holocene was also spatially variable. The early to mid-Holocene was, however, generally characterised by moderately humid conditions, demonstrated by lake level rise, source-bordering dune activity, and speleothem growth, persisting at different times across the continent. Increasingly arid conditions developed into the late Holocene, particularly in the central arid zone.
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29. |
- Fosse, Erik, et al.
(author)
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Duraflo II coating of cardiopulmonary bypass circuits reduces complement activation, but does not affect the release of granulocyte enzymes : a European multicentre study
- 1997
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In: European Journal of Cardio-Thoracic Surgery. - 1010-7940 .- 1873-734X. ; 11:2, s. 320-327
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: This study was carried out to: (a) compare complement and granulocyte activation during cardiac operations in patients operated with cardiopulmonary bypass coated with heparin by the Duraflo II method, with activation in patients operated with uncoated circuits; and (b) relate complement, and granulocyte activation to selected adverse effects. METHODS: In a multicentre study among Rikshospitalet, Ullevaal Hospital in Norway and Uppsala University Hospital in Sweden, plasma concentrations of the complement activation products C4b/iC4b/C4c (C4bc), C3b/iC3b/C3c (C3bc), the terminal SC5b-9 complement complex (TCC), and the granulocyte proteins myeloperoxidase and lactoferrin were assessed in two groups of patients undergoing aortocoronary bypass. Seventy-six patients underwent surgery operated with circuits coated by the Duraflo II heparin coating and 75 uncoated circuits. The same amount of systemic heparin was administered to all patients. RESULTS: In both groups a significant increase in C4bc was first seen by the end of operation, from 86.7 +/- 12.5 to 273.0 +/- 277.4 nM in controls and from 86.9 +/- 18.5 to 320.2 +/- 190.5 nM in the control group, confirming previous documentation that the classical pathway is not activated during CPB, but as a consequence of protamin administration. The formation of C4bc did not differ significantly between the two groups. In the uncoated group the C3bc concentration increased from 124.0 +/- 15.3 to a maximum of 1176.1 +/- 64.7 nM (P < 0.01) and in the coated group it increased from 129.8 +/- 16.1 to a maximum of 1019.4 +/- 54.9 nM (P < 0.01) during CPB. Summary values but not peak values differed significantly between the groups. In the uncoated group the TCC concentration increased from 0.52 +/- 0.03 to a maximum value of 8.09 +/- 0.57 AU/ml (P < 0.01) while in the coated group the TCC concentration increased from a baseline of 0.53 +/- 0.03 to a peak value of 5.2 +/- 0.24 AU/ml (P <0.01). The difference between the peak values was statistically significant (P = 0.00002). In both groups a significant increase in myeloperoxidase and lactoferrin release was observed by the end of operation. There was no difference in myeloperoxidase or lactoferrin release between the two groups. TCC levels were compared to the occurrence of perioperative infarction, development of lung or renal failure, postoperative bleeding, time on ventilator and days in hospital. Three patients developed perioperative infarction; the peak levels of TCC were significantly higher in these patients than in the 148 patients that did not develop infarction. The reduction in TCC formation in the heparin-coated group was not associated with differences in any of the other clinical parameters. Few adverse effects occurred in the study. The peak values of C3bc were higher in the patients needing inotropic support that in those who did not, the relevance of this finding remains uncertain. CONCLUSION: It is concluded that the Duraflo II heparin coating reduces complement activation, particularly TCC formation, during CPB, but not the release of specific neutrophil granule enzymes. No certain correlation was established between complement and granulocyte activation and clinical outcome.
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30. |
- Gliganic, Luke A., et al.
(author)
-
Late-Holocene climatic variability indicated by three natural archives in arid southern Australia
- 2014
-
In: The Holocene. - : SAGE Publications. - 0959-6836 .- 1477-0911. ; 24:1, s. 104-117
-
Journal article (peer-reviewed)abstract
- Three terrestrial climate proxies are used to investigate the evolution of Holocene palaeoenvironments in southern central Australia, all of which present a coherent record of palaeohydrology. Single-grain optically stimulated luminescence from sediments supplemented by C-14 from charcoal and lacustrine shells was obtained to date shoreline deposits (Lake Callabonna) and the adjacent Mt Chambers Creek alluvial fan. Our findings are complemented by a U/Th-based record of speleothem growth in the Mt Chambers Creek catchment, which we interpret to reflect increased precipitation. Together, these archives shed light on the timing of, and possible sources of water for, Holocene pluvial intervals. We identified several phases of elevated lake levels dated at similar to 5.8-5.2, 4.5, 3.5-2.7 and 1 kyr, most of which correspond to fluvial activity resulting from increased precipitation in the adjacent ranges. The enhanced hydrology during phases of the late Holocene likely increased the reliability of resources for regional human populations during a time of reduced winter rainfall. When considered within the framework of the current understanding of Holocene palaeoclimate in central Australia, our data suggest that the pattern of landscape response was broadly synchronous with larger scale climatic variability and punctuated by pluvial periods greater than today.
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31. |
- Gotthardt, Martin, et al.
(author)
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Detection and quantification of beta cells by PET imaging : why clinical implementation has never been closer
- 2018
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In: Diabetologia. - : SPRINGER. - 0012-186X .- 1432-0428. ; 61:12, s. 2516-2519
-
Journal article (peer-reviewed)abstract
- In this issue of Diabetologia, Alavi and Werner (10.1007/s00125-018-4676-1) criticise the attempts to use positron emission tomography (PET) for in vivo imaging of pancreatic beta cells, which they consider as futile'. In support of this strong statement, they point out the limitations of PET imaging, which they believe render beta cell mass impossible to estimate using this method. In our view, the Alavi and Werner presentation of the technical limitations of PET imaging does not reflect the current state of the art, which leads them to questionable conclusions towards the feasibility of beta cell imaging using this approach. Here, we put forward arguments in favour of continuing the development of innovative technologies enabling in vivo imaging of pancreatic beta cells and concisely present the current state of the art regarding putative technical limitations of PET imaging. Indeed, far from being a futile' effort, we demonstrate that beta cell imaging is now closer than ever to becoming a long-awaited clinical reality.
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32. |
- Hilbert, Kevin, et al.
(author)
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Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.
- 2024
-
In: The American Journal of Psychiatry. - 1535-7228. ; 181:8, s. 728-740
-
Journal article (peer-reviewed)abstract
- Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults).Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis.Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents.Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.
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33. |
- Huang, Lei, et al.
(author)
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Decreasing resection rates for nonmetastatic gastric cancer in Europe and the United States
- 2020
-
In: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 10:6, s. 1-15
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Resection is the cornerstone of curative treatment for many nonmetastatic gastric cancers (GCs), but the population treatment patterns remains largely unknown. This large international population-based study aimed at investigating the treatment patterns and trends for nonmetastatic GC in Europe and the United States and at exploring factors associated with resection.METHODS: Data of patients with microscopically confirmed primary invasive GC without distant metastasis from the national cancer registries of the Netherlands, Belgium, Sweden, Norway, Slovenia, and Estonia and the US Surveillance, Epidemiology, and End Results (SEER)-18 Program were retrieved. Age-standardized treatment rates were computed and trends were evaluated using linear regression. Associations of resection with patient and tumor characteristics were analyzed using multivariable-adjusted log-binomial regression. Analysis was performed in each country respectively without pooling.RESULTS: Together 65 707 nonmetastatic GC patients diagnosed in 2003-2016 were analyzed. Age-standardized resection rates significantly decreased over years in all countries (by 4-24%). In 2013-2014, rates varied greatly from 54 to 75%. Patients with increasing ages, cardia cancers, or cancers invading adjacent structure were significantly less frequently resected. Resection was further associated with sex, performance status, comorbidities, tumor histology, tumor size, hospital type, and hospital volume. Association patterns and strengths varied across countries. After multivariable adjustment, resection rates remained decreasing (prevalence ratio = 0.97-0.995 per year), with decreasing trends consistently seen in various subgroups.CONCLUSIONS: Nonmetastatic GCs were less frequently resected in Europe and the United States in the early 21st century. Resection rates varied greatly across countries and appeared not to be optimal. Various factors associated with resection were revealed. Our findings can help to identify differences and possibly modifiable places in clinical practice and provide important novel references for designing effective population-based GC management strategies. In Europe and the United States, nonmetastatic gastric cancers were less frequently resected in the early 21st century. Resection rates varied greatly across countries and appeared not optimal. Various factors associated with resection were revealed. Our findings identify differences and possibly modifiable places in clinical practice and provide important novel references for designing effective population-based management strategies.
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34. |
- Huhn, Stefanie, et al.
(author)
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Coding variants in NOD-like receptors : An association study on risk and survival of colorectal cancer
- 2018
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:6
-
Journal article (peer-reviewed)abstract
- Nod-like receptors (NLRs) are important innate pattern recognition receptors and regulators of inflammation or play a role during development. We systematically analysed 41 non-synonymous single nucleotide polymorphisms (SNPs) in 21 NLR genes in a Czech discovery cohort of sporadic colorectal cancer (CRC) (1237 cases, 787 controls) for their association with CRC risk and survival. Five SNPs were found to be associated with CRC risk and eight with survival at 5% significance level. In a replication analysis using data of two large genome-wide association studies (GWASs) from Germany (DACHS: 1798 cases and 1810 controls) and Scotland (2210 cases and 9350 controls) the associations found in the Czech discovery set were not confirmed. However, expression analysis in human gut-related tissues and immune cells revealed that the NLRs associated with CRC risk or survival in the discovery set were expressed in primary human colon or rectum cells, CRC tissue and/or cell lines, providing preliminary evidence for a potential involvement of NLRs in general in CRC development and/or progression. Most interesting was the finding that the enigmatic development-related NLRP5 (also known as MATER) was not expressed in normal colon tissue but in colon cancer tissue and cell lines. Future studies may show whether regulatory variants instead of coding variants might affect the expression of NLRs and contribute to CRC risk and survival.
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35. |
- Irisarri, Iker, et al.
(author)
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Unexpected cryptic species among streptophyte algae most distant to land plants
- 2021
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In: Proceedings of the Royal Society of London. Biological Sciences. - : Royal Society. - 0962-8452 .- 1471-2954. ; 288:1963
-
Journal article (peer-reviewed)abstract
- Streptophytes are one of the major groups of the green lineage (Chloroplastida or Viridiplantae). During one billion years of evolution, streptophytes have radiated into an astounding diversity of uni- and multicellular green algae as well as land plants. Most divergent from land plants is a clade formed by Mesostigmatophyceae, Spirotaenia spp. and Chlorokybophyceae. All three lineages are species-poor and the Chlorokybophyceae consist of a single described species, Chlorokybus atmophyticus. In this study, we used phylogenomic analyses to shed light into the diversity within Chlorokybus using a sampling of isolates across its known distribution. We uncovered a consistent deep genetic structure within the Chlorokybus isolates, which prompted us to formally extend the Chlorokybophyceae by describing four new species. Gene expression differences among Chlorokybus species suggest certain constitutive variability that might influence their response to environmental factors. Failure to account for this diversity can hamper comparative genomic studies aiming to understand the evolution of stress response across streptophytes. Our data highlight that future studies on the evolution of plant form and function can tap into an unknown diversity at key deep branches of the streptophytes.
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36. |
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37. |
- Jakubauskas, Dainius, et al.
(author)
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Toward reliable low-density lipoprotein ultrastructure prediction in clinical conditions : A small-angle X-ray scattering study on individuals with normal and high triglyceride serum levels
- 2021
-
In: Nanomedicine. - : Elsevier. - 1549-9634 .- 1549-9642. ; 31, s. 1-13
-
Journal article (peer-reviewed)abstract
- Atherosclerosis is the main killer in the west and therefore a major health challenge today. Total serum cholesterol and lipoprotein concentrations, used as clinical markers, fail to predict the majority of cases, especially between the risk scale extremes, due to the high complexity in lipoprotein structure and composition. In particular, low-density lipoprotein (LDL) plays a key role in atherosclerosis development, with LDL size being a parameter considered for determining the risk for cardiovascular diseases. Determining LDL size and structural parameters is challenging to address experimentally under physiological-like conditions. This article describes the biochemistry and ultrastructure of normolipidemic and hypertriglyceridemic LDL fractions and subfractions using small-angle X-ray scattering. Our results conclude that LDL particles of hypertriglyceridemic compared to healthy individuals 1) have lower LDL core melting temperature, 2) have lower cholesteryl ester ordering in their core, 3) are smaller, rounder and more spherical below melting temperature, and 4) their protein-containing shell is thinner above melting temperature.
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38. |
- Jansen, Barbara, et al.
(author)
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Sinus 64 + blue
- 2014
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Other publication (peer-reviewed)abstract
- Sinus 64 + blue explores a relationship and dialog between sound and light and is a collaborative project carried out by composer and artist Jan Carleklev and textile design researcher Barbara Jansen. It is a practice based research project investigating on the borderline between art and design in order to explore new aesthetics and experiences. In Sinus 64 + blue, sound triggers and creates a dialog with the light embedded in a textile structure. The exhibited artefact uses PMMA optical fibre technology in a woven structure which is activated by light-emitting diodes (LEDs) and uses a digital interface to realize a novel, light-emitting textile expression. Sinus 64 + blue is part of the research for Barbara Jansen`s doctoral thesis which investigates the following research question: What does it mean, if time and change – constant movement – become part of the textile design expression? The research question has been investigated in a number of experiments which explore the visual effects of movement by using light integrated into textile structures as a medium. Thereby, the textile design pattern reveals its composition, not in one moment of time any more, but in fact over time. In this collaborative project, sound has been used as a trigger to activate time-based light patterns, whereby it does not only stimulate patterns of light but in fact initiates a dialog between the two. (Jansen, 2013) Installation The Sinus 64 + blue installation is based on a light-emitting woven structure (1x1 m) in which PMMA optical fibres have been interlaced with paper yarn. The optical fibres are lit by RGB-LEDs (red, green and blue LEDs which are activated through additive colour mixing) and programmed via a digital interface. In the initial experiments, the woven structure was programmed to react to three different basic sound elements, each of which triggered one of the base light colours of the RGB-LEDs, red, green or blue. The dialog between single sine pitches and the three primary colours of light explore elementary aspects of the relationship between sound and light. Sound and light have been stripped down to their most basic elements, i.e. the use of single frequency sound waves (sine pitches) and the three primary colours red, green and blue. Sound element one was created by playing three individual sine waves together. The individual sounds are slightly detuned in relation to each other, but all are close to the center frequency 64 Hz. This approach is causing interference between the three sine waves (The Physics class room, N.D., Infoplease, N.D.). The interference creates unique rhythmic sonic structures, which lay a steady beat as a foundation for the sound-light composition. This sound element triggered blue, pulsating light over the whole textile structure. Sound element two was created through a sequence of sine waves starting at a frequency of 100 Hz and increasing to 440 Hz (playing a scale from lower to higher pitch) before starting over from 100 Hz again. This over and over increasing sound scale activated the red light, floating upwards and upwards the textile structure over and over again. Sound element three was a melodic sequence of single sine waves which covered a range of high and low frequencies. They set off the green light dancing and pulsating over the textile structure. In the continued work towards composing an exhibition piece, sound-light element two and three were further developed. Sound-light element two was altered to play sequences of increasing and decreasing sine pitch scales and the tones of the scales of the pure sine waves were modified to a filtered white noise in order to simulate the sound of wind. The initial colour of the red light was given a richer colour spectrum which shift and fade between red and pink. Sound-light element three, the green colour was made richer and altered by adding some blue to achieve a more subtle nuance of green. Nevertheless, three distinct sound-light patterns create an overall composition by utilizing a more prosperous sound and colour landscape. Let yourself be surprised what happens when one, two or all three of these sound-light elements appear simultaneously during the eight minute long time-based composition.
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39. |
- Jansen, Gunilla Brodda, et al.
(author)
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Differences in symptoms, functioning, and quality of life between women on long-term sick-leave with musculoskeletal pain with and without concomitant depression.
- 2011
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In: Journal of Multidisciplinary Healthcare. - 1178-2390. ; 4, s. 281-292
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: The aim was to describe the differences in symptoms, functioning and quality of life between women on long-term sick-leave due to protracted musculoskeletal pain with and without concomitant depression.DESIGN: Descriptive and comparisons with/without comorbid depression.METHODS: 332 female patients were examined by three specialist physicians in psychiatry, orthopedic surgery, and rehabilitation medicine and assigned to four groups according to the ICD-10 diagnoses: low back/joint disorders (LBJ, n = 150), myalgia (M, n = 43), fibromyalgia (FM, n = 87), or depression without somatic pain diagnosis (DE, n = 52).RESULTS: Patients with somatic pain conditions LBJ, M, or FM showed more activity-related difficulties if concomitant depression was present during the activities 'focusing attention', 'making decisions', and 'undertaking a single task'; and in the domains 'energy level', 'memory functions', 'emotional functions', and 'optimism/pessimism'. Patients with FM and concomitant depression perceived higher pain intensity than patients in group DE. No statistically significant differences in physically related activities were noted between each of the somatic pain conditions with and without coexisting depression. FM patients with coexisting depression reported fewer painful sites on their pain drawings compared with FM-patients without depression. Patients with LBJ or FM and concomitant depression reported lower quality of life in the dimensions vitality, social functioning, emotional role, and mental health. Comorbid depression affected disability and restricted working capacity by reducing mental activity and functioning but not by affecting physical activity problems.CONCLUSION: Women on long-term sick-leave, who have concomitant depression with LBJ or FM, also have more difficulties in focusing attention, making decisions, and carrying out tasks, and with memory functions and optimism/pessimism, as well as reduced quality of life in the dimensions of vitality, social functioning, emotional role, and mental health, than female patients without comorbid depression. As a consequence we suggest further efforts to integrate somatic and psychiatric interventions in the same rehabilitation program.
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40. |
- Jansen, Iris E, et al.
(author)
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Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.
- 2022
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In: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 144:5, s. 821-842
-
Journal article (peer-reviewed)abstract
- Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n=8074; replication n=5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
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41. |
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42. |
- Jansen, Marielle J A, et al.
(author)
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Patient-specific fine-tuning of CNNs for follow-up lesion quantification
- 2020
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In: Journal of Medical Imaging.
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Journal article (peer-reviewed)abstract
- Convolutional neural network (CNN) methods have been proposed to quantify lesions in medical imaging. Commonly more than one imaging examination is available for a patient, but the serial information in these images often remains unused. CNNbased methods have the potential to extract valuable information from previously acquired imaging to better quantify current imaging of the same patient. A pre-trained CNN can be updated with a patient’s previously acquired imaging: patient-specific fine-tuning. In this work, we studied the improvement in performance of lesion quantification methods on MR images after fine-tuning compared to a base CNN. We applied the method to two different approaches: the detection of liver metastases and the segmentation of brain white matter hyperintensities (WMH). The patient-specific fine-tuned CNN has a better performance than the base CNN. For the liver metastases, the median true positive rate increases from 0.67 to 0.85. For the WMH segmentation, the mean Dice similarity coefficient increases from 0.82 to 0.87. In this study we showed that patient-specific fine-tuning has potential to improve the lesion quantification performance of general CNNs by exploiting the patient’s previously acquired imaging
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43. |
- Jansen, Marielle J. A., et al.
(author)
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Patient-specific fine-tuning of convolutional neural networks for follow-up lesion quantification
- 2020
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In: Journal of Medical Imaging. - : SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS. - 2329-4302 .- 2329-4310. ; 7:6
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Journal article (peer-reviewed)abstract
- Purpose: Convolutional neural network (CNN) methods have been proposed to quantify lesions in medical imaging. Commonly, more than one imaging examination is available for a patient, but the serial information in these images often remains unused. CNN-based methods have the potential to extract valuable information from previously acquired imaging to better quantify lesions on current imaging of the same patient.Approach: A pretrained CNN can be updated with a patient's previously acquired imaging: patient-specific fine-tuning (FT). In this work, we studied the improvement in performance of lesion quantification methods on magnetic resonance images after FT compared to a pretrained base CNN. We applied the method to two different approaches: the detection of liver metastases and the segmentation of brain white matter hyperintensities (WMH).Results: The patient-specific fine-tuned CNN has a better performance than the base CNN. For the liver metastases, the median true positive rate increases from 0.67 to 0.85. For the WMH segmentation, the mean Dice similarity coefficient increases from 0.82 to 0.87.Conclusions: We showed that patient-specific FT has the potential to improve the lesion quantification performance of general CNNs by exploiting a patient's previously acquired imaging.
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44. |
- Jansen, Willemijn J, et al.
(author)
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Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
- 2018
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In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
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Journal article (peer-reviewed)abstract
- Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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45. |
- Jansen, Willemijn J, et al.
(author)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Journal article (peer-reviewed)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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46. |
- Jansen, Willemijn J, et al.
(author)
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Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
- 2015
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In: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
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Journal article (peer-reviewed)abstract
- Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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47. |
- Jung, Christian, et al.
(author)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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In: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Journal article (peer-reviewed)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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48. |
- Keizer, Ron J., et al.
(author)
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A model of hypertension and proteinuria in cancer patients treated with the anti-angiogenic drug E7080
- 2010
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In: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Science and Business Media LLC. - 1567-567X .- 1573-8744. ; 37:4, s. 347-363
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Journal article (peer-reviewed)abstract
- Hypertension and proteinuria are commonly observed side-effects for anti-angiogenic drugs targeting the VEGF pathway. In most cases, hypertension can be controlled by prescription of anti-hypertensive (AH) therapy, while proteinuria often requires dose reductions or dose delays. We aimed to construct a pharmacokinetic-pharmacodynamic (PK-PD) model for hypertension and proteinuria following treatment with the experimental VEGF-inhibitor E7080, which would allow optimization of treatment, by assessing the influence of anti-hypertensive medication and dose reduction or dose delays in treating and avoiding toxicity. Data was collected from a phase I study of E7080 (n = 67), an inhibitor of multiple tyrosine kinases, among which VEGF. Blood pressure and urinalysis data were recorded weekly. Modeling was performed in NONMEM, and direct and indirect response PK-PD models were evaluated. A previously developed PK model was used. An indirect response PK-PD model described the increase in BP best, while the probability of developing proteinuria toxicity in response to exposure to E7080, was best described by a Markov transition model. This model may guide clinical interventions and provide treatment recommendations for E7080, and may serve as a template model for other drugs in this class.
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49. |
- Kirchner, Nina, 1972-, et al.
(author)
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Water temperature, mixing, and ice phenology in the arctic-alpine Lake Darfáljávri (Lake Tarfala), northern Sweden
- 2024
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In: Arctic, Antarctic and Alpine research. - : Taylor & Francis. - 1523-0430 .- 1938-4246. ; 56:1
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Journal article (peer-reviewed)abstract
- In the rapidly warming circumpolar Arctic, recent research of lakes has focused on their climatology and ecology but is challenged by sparsity of wintertime data. At the c. 48-m-deep and c. 0.5-km2 large proglacial Darfaljavri (Lake Tarfala), located in an arctic-alpine environment in the Scandinavian Mountains, year-round water temperatures were previously reported for 2016 to 2019. Here, this record is continued for 2019-2020 and 2021-2022, complemented by time-lapse imagery records of the state of the lake surface, as well as degree-day modeling of ice phenology (timing of ice-on and ice-off). Darfaljavri is cryostratified during winter, with interannual variations in the thermocline's thickness and temperature range. The ice season lasts from October to July. Modeled ice-on dates match observed ones reasonably well; however, observed ice-off dates occur much later than modeled ones, likely because of cold impact from Darfaljavri's glacial environment as inferred from a comparison with a close tundra lake. Though new insights into the complex lake mixing and ice phenology are provided, it remains to attribute the characteristics of Darfaljavri's winter stratification to additional potential drivers, such as lake ice thickness, atmospheric heat fluxes, and the water balance of the lake.
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50. |
- Kurz, Alexander, et al.
(author)
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RHAPSODY - Internet-based support for caregivers of people with young onset dementia : program design and methods of a pilot study
- 2016
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In: International Psychogeriatrics. - : Cambridge University Press. - 1041-6102 .- 1741-203X. ; 28:12, s. 2091-2099
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Journal article (peer-reviewed)abstract
- Background: Young Onset Dementia (YOD), defined by first symptoms of cognitive or behavioral decline occurring before the age of 65 years, is relatively rare compared to dementia of later onset, but it is associated with diagnostic difficulty and heavy burden on affected individuals and their informal carers. Existing health and social care structures rarely meet the needs of YOD patients. Internet-based interventions are a novel format of delivering health-related education, counseling, and support to this vulnerable yet underserved group. Methods: The RHAPSODY (Research to Assess Policies and Strategies for Dementia in the Young) project is a European initiative to improve care for people with YOD by providing an internet-based information and skill-building program for family carers. The e-learning program focuses on managing problem behaviors, dealing with role change, obtaining support, and looking after oneself. It will be evaluated in a pilot study in three countries using a randomized unblinded designwith a wait-list control group. Participants will be informal carers of people with dementia in Alzheimer's disease or behavioral-variant Frontotemporal degeneration with an onset before the age of 65 years. The primary outcome will be caregiving self-efficacy after 6 weeks of program use. As secondary outcomes, caregivers' stress and burden, carer health-related quality of life, caring-related knowledge, patient problem behaviors, and user satisfaction will be assessed. Program utilization will be monitored and a health-economic evaluation will also be performed. Conclusions: The RHAPSODY project will add to the evidence on the potential and limitations of a conveniently accessible, user-friendly, and comprehensive internet-based intervention as an alternative for traditional forms of counseling and support in healthcare, aiming to optimize care and support for people with YOD and their informal caregivers.
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