| 1. |
- Aad, G, et al.
(author)
-
- 2015
-
swepub:Mat__t
|
|
| 2. |
- Kanai, M, et al.
(author)
-
- 2023
-
swepub:Mat__t
|
|
| 3. |
- Forouzanfar, Mohammad H, et al.
(author)
-
Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
- 2015
-
In: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
|
|
| 4. |
- 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.
|
|
| 5. |
- Wain, Louise V., et al.
(author)
-
Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
- 2017
-
In: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
-
Journal article (peer-reviewed)abstract
- Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
|
|
| 6. |
|
|
| 7. |
- Kattge, Jens, et al.
(author)
-
TRY plant trait database - enhanced coverage and open access
- 2020
-
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.
|
|
| 8. |
- Webb, Thomas R., et al.
(author)
-
Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease
- 2017
-
In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 69:7, s. 823-836
-
Journal article (peer-reviewed)abstract
- BACKGROUND Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.OBJECTIVES This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.METHODS In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.RESULTS We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 x 10(-4) with a range of other diseases/traits.CONCLUSIONS We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
|
|
| 9. |
- Scott, Robert A., et al.
(author)
-
Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:9, s. 991-1005
-
Journal article (peer-reviewed)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
|
|
| 10. |
- Crous, Pedro W., et al.
(author)
-
Fungal Planet description sheets: 1383–1435
- 2022
-
In: Persoonia: Molecular Phylogeny and Evolution of Fungi. - : Naturalis Biodiversity Center. - 0031-5850 .- 1878-9080. ; 48, s. 261-371
-
Journal article (peer-reviewed)abstract
- Novel species of fungi described in this study include those from various countries as follows: Australia, Agaricus albofoetidus, Agaricus aureoelephanti and Agaricus parviumbrus on soil, Fusarium ramsdenii from stem cankers of Araucaria cunninghamii, Keissleriella sporoboli from stem of Sporobolus natalensis, Leptosphaerulina queenslandica and Pestalotiopsis chiaroscuro from leaves of Sporobolus natalensis, Serendipita petricolae as endophyte from roots of Eriochilus petricola, Stagonospora tauntonensis from stem of Sporobolus natalensis, Teratosphaeria carnegiei from leaves of Eucalyptus grandis × E. camaldulensis and Wongia ficherai from roots of Eragrostis curvula. Canada, Lulworthia fundyensis from intertidal wood and Newbrunswickomyces abietophilus (incl. Newbrunswickomyces gen. nov.) on buds of Abies balsamea. Czech Republic, Geosmithia funiculosa from a bark beetle gallery on Ulmus minor and Neoherpotrichiella juglandicola (incl. Neoherpotrichiella gen. nov.) from wood of Juglans regia. France, Aspergillus rouenensis and Neoacrodontium gallica (incl. Neoacrodontium gen. nov.) from bore dust of Xestobium rufovillosum feeding on Quercus wood, Endoradiciella communis (incl. Endoradiciella gen. nov.) endophytic in roots of Microthlaspi perfoliatum and Entoloma simulans on soil. India, Amanita konajensis on soil and Keithomyces indicus from soil. Israel, Microascus rothbergiorum from Stylophora pistillata. Italy, Calonarius ligusticus on soil. Netherlands, Appendopyricularia juncicola (incl. Appendopyricularia gen. nov.), Eriospora juncicola and Tetraploa juncicola on dead culms of Juncus effusus, Gonatophragmium physciae on Physcia caesia and Paracosmospora physciae (incl. Paracosmospora gen. nov.) on Physcia tenella, Myrmecridium phragmitigenum on dead culm of Phragmites australis, Neochalara lolae on stems of Pteridium aquilinum, Niesslia nieuwwulvenica on dead culm of undetermined Poaceae, Nothodevriesia narthecii (incl. Nothodevriesia gen. nov.) on dead leaves of Narthecium ossifragum and Parastenospora pini (incl. Parastenospora gen. nov.) on dead twigs of Pinus sylvestris. Norway, Verticillium bjoernoeyanum from sand grains attached to a piece of driftwood on a sandy beach. Portugal, Collybiopsis cimrmanii on the base of living Quercus ilex and amongst dead leaves of Laurus and herbs. South Africa, Paraproliferophorum hyphaenes (incl. Paraproliferophorum gen. nov.) on living leaves of Hyphaene sp. and Saccothecium widdringtoniae on twigs of Widdringtonia wallichii. Spain, Cortinarius dryosalor on soil, Cyphellophora endoradicis endophytic in roots of Microthlaspi perfoliatum, Geoglossum laurisilvae on soil, Leptographium gemmatum from fluvial sediments, Physalacria auricularioides from a dead twig of Castanea sativa, Terfezia bertae and Tuber davidlopezii in soil. Sweden, Alpova larskersii, Inocybe alpestris and Inocybe boreogodeyi on soil. Thailand, Russula banwatchanensis, Russula purpureoviridis and Russula lilacina on soil. Ukraine, Nectriella adonidis on overwintered stems of Adonis vernalis. USA, Microcyclus jacquiniae from living leaves of Jacquinia keyensis and Penicillium neoherquei from a minute mushroom sporocarp. Morphological and culture characteristics are supported by DNA barcodes.
|
|
| 11. |
- Cohen, T. J., et al.
(author)
-
A pluvial episode identified in arid Australia during the Medieval Climatic Anomaly
- 2012
-
In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 56, s. 167-171
-
Journal article (peer-reviewed)abstract
- Optically stimulated luminescence (OSL) ages from a relict shoreline on Lake Callabonna record a major pluvial episode in southern central Australia between 1050 70 and 1100 60 Common Era (CE), within the Medieval Climatic Anomaly (MCA). During this pluvial interval Lake Callabonna filled to 10e12 times the volume of the largest historical filling (1974) and reached maximum depths of 4e5 m, compared to the 0.5e1.0 m achieved today. Until now there has been no direct evidence for the MCA in the arid interior of Australia. A multi-proxy, analogue-based atmospheric circulation reconstruction indicates that the pluvial episode was associated with an anomalous meridional atmospheric circulation pattern over the Southern extratropics, with high sea-level pressure ridges in the central Indian Ocean and Tasman Sea, and a trough extending from the Southern Ocean into central Australia. A major decline in the mobility of the Australian aboriginal hunter-gatherer coincides with this MCA period, in southern central Australia.
|
|
| 12. |
- Hop, Paul J., et al.
(author)
-
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.
|
|
| 13. |
- Jansen, John D., et al.
(author)
-
Lowland river responses to intraplate tectonism and climate forcing quantified with luminescence and cosmogenic Be-10
- 2013
-
In: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X .- 1385-013X. ; 366, s. 49-58
-
Journal article (peer-reviewed)abstract
- Intraplate tectonism has produced large-scale folding that steers regional drainage systems, such as the 1600 km-long Cooper Ck, en route to Australia's continental depocentre at Lake Eyre. We apply cosmogenic Be-10 exposure dating in bedrock, and luminescence dating in sediment, to quantify the erosional and depositional response of Cooper Ck where it incises the rising Innamincka Dome. The detachment of bedrock joint-blocks during extreme floods governs the minimum rate of incision (17.4 +/- 6.5 mm/ky) estimated using a numerical model of episodic erosion calibrated with our 10Be measurements. The last big-flood phase occurred no earlier than similar to 112-121 ka. Upstream of the Innamincka Dome long-term rates of alluvial deposition, partly reflecting synclinal-basin subsidence, are estimated from 47 luminescence dates in sediments accumulated since similar to 270 ka. Sequestration of sediment in subsiding basins such as these may account for the lack of Quaternary accumulation in Lake Eyre, and moreover suggests that notions of a single primary depocentre at base-level may poorly represent lowland, arid-zone rivers. Over the period similar to 75-55 ka Cooper Ck changed from a bedload-dominant, laterally-active meandering river to a muddy anabranching channel network up to 60 km wide. We propose that this shift in river pattern was a product of base-level rise linked with the slowly deforming syncline-anticline structure, coupled with a climate-forced reduction in discharge. The uniform valley slope along this subsiding alluvial and rising bedrock system represents an adjustment between the relative rates of deformation and the ability of greatly enhanced flows at times during the Quaternary to incise the rising anticline. Hence, tectonic and climate controls are balanced in the long term.
|
|
| 14. |
- Jansen, Willemijn J, et al.
(author)
-
Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
-
In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
-
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.
|
|
| 15. |
- Prudencio, Mercedes, et al.
(author)
-
Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3
- 2020
-
In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 12:566
-
Journal article (peer-reviewed)abstract
- Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (ATXN3), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials. Here, we developed an immunoassay that readily detects polyQ ATXN3 proteins in human biological fluids and discriminates patients with SCA3 from healthy controls and individuals with other ataxias. We show that polyQ ATXN3 serves as a marker of target engagement in human fibroblasts, which may bode well for its use in clinical trials. Last, we identified a single-nucleotide polymorphism that strongly associates with the expanded allele, thus providing an exciting drug target to abrogate detrimental events initiated by mutant ATXN3. Gene-silencing strategies for several repeat diseases are well under way, and our results are expected to improve clinical trial preparedness for SCA3 therapies.
|
|
| 16. |
- Jansen, John D., et al.
(author)
-
Inner gorges cut by subglacial meltwater during Fennoscandian ice sheet decay
- 2014
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3815-
-
Journal article (peer-reviewed)abstract
- The century-long debate over the origins of inner gorges that were repeatedly covered by Quaternary glaciers hinges upon whether the gorges are fluvial forms eroded by subaerial rivers, or subglacial forms cut beneath ice. Here we apply cosmogenic nuclide exposure dating to seven inner gorges along similar to 500 km of the former Fennoscandian ice sheet margin in combination with a new deglaciation map. We show that the timing of exposure matches the advent of ice-free conditions, strongly suggesting that gorges were cut by channelized subglacial meltwater while simultaneously being shielded from cosmic rays by overlying ice. Given the exceptional hydraulic efficiency required for meltwater channels to erode bedrock and evacuate debris, we deduce that inner gorges are the product of ice sheets undergoing intense surface melting. The lack of postglacial river erosion in our seven gorges implicates subglacial meltwater as a key driver of valley deepening on the Baltic Shield over multiple glacial cycles.
|
|
| 17. |
- Jansen, Willemijn J, et al.
(author)
-
Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
- 2018
-
In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
-
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.
|
|
| 18. |
- Jansen, Willemijn J, et al.
(author)
-
Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
- 2015
-
In: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
-
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.
|
|
| 19. |
- Jung, Christian, et al.
(author)
-
A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
-
In: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
-
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.
|
|
| 20. |
- Lagou, Vasiliki, et al.
(author)
-
Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
-
In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
|
|
| 21. |
- Le Guen, Yann, et al.
(author)
-
Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
- 2023
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 120:36
-
Journal article (peer-reviewed)abstract
- Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
|
|
| 22. |
- Mattsson, Niklas, et al.
(author)
-
Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimers disease
- 2018
-
In: Alzheimer's & Dementia. - : ELSEVIER SCIENCE INC. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
-
Journal article (peer-reviewed)abstract
- Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimers disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P amp;lt;.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimers Association. Published by Elsevier Inc. All rights reserved.
|
|
| 23. |
- Mattsson, Niklas, et al.
(author)
-
Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
- 2018
-
In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
-
Journal article (peer-reviewed)abstract
- Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P <.05) but not in Aβ+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
|
|
| 24. |
- Reeves, Jessica M., et al.
(author)
-
Palaeoenvironmental change in tropical Australasia over the last 30,000 years - a synthesis by the OZ-INTIMATE group
- 2013
-
In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 74, s. 97-114
-
Journal article (peer-reviewed)abstract
- The tropics are the major source of heat and moisture for the Australasian region. Determining the tropics' response over time to changes in climate forcing mechanisms, such as summer insolation, and the effects of relative sea level on exposed continental shelves during the Last Glacial period, is an ongoing process of re-evaluation. We present a synthesis of climate proxy data from tropical Australasia spanning the last 30,000 years that incorporates deep sea core, coral, speleothem, pollen, charcoal and terrestrial sedimentary records. Today, seasonal variability is governed largely by the annual migration of the inter-tropical convergence zone (ITCZ), influencing this region most strongly during the austral summer. However, the position of the ITCZ has varied through time. Towards the end of Marine Isotope Stage (MIS) 3, conditions were far wetter throughout the region, becoming drier first in the south. Universally cooler land and sea-surface temperature (SST) were characteristic of the Last Glacial Maximum, with drier conditions than previously, although episodic wet periods are noted in the fluvial records of northern Australia. The deglacial period saw warming first in the Coral Sea and then the Indonesian seas, with a pause in this trend around the time of the Antarctic Cold Reversal (c. 14.5 ka), coincident with the flooding of the Sunda Shelf. Wetter conditions occurred first in Indonesia around 17 ka and northern Australia after 14 ka. The early Holocene saw a peak in marine SST to the northwest and northeast of Australia. Modern vegetation was first established on Indonesia, then progressively south and eastward to NE Australia. Flores and the Atherton Tablelands show a dry period around 11.6 ka, steadily becoming wetter through the early Holocene. The mid-late Holocene was punctuated by millennial-scale variability, associated with the El Nino-Southern Oscillation; this is evident in the marine, coral, speleothem and pollen records of the region.
|
|
| 25. |
- Windhorst, Rogier A., et al.
(author)
-
JWST PEARLS. Prime extragalactic areas for reionization and lensing science : project overview and first results
- 2023
-
In: Astronomical Journal. - : Institute of Physics (IOP). - 0004-6256 .- 1538-3881. ; 165:1
-
Journal article (peer-reviewed)abstract
- We give an overview and describe the rationale, methods, and first results from NIRCam images of the JWST “Prime Extragalactic Areas for Reionization and Lensing Science” (PEARLS) project. PEARLS uses up to eight NIRCam filters to survey several prime extragalactic survey areas: two fields at the North Ecliptic Pole (NEP); seven gravitationally lensing clusters; two high redshift protoclusters; and the iconic backlit VV 191 galaxy system to map its dust attenuation. PEARLS also includes NIRISS spectra for one of the NEP fields and NIRSpec spectra of two high-redshift quasars. The main goal of PEARLS is to study the epoch of galaxy assembly, active galactic nucleus (AGN) growth, and First Light. Five fields—the JWST NEP Time-Domain Field (TDF), IRAC Dark Field, and three lensing clusters—will be observed in up to four epochs over a year. The cadence and sensitivity of the imaging data are ideally suited to find faint variable objects such as weak AGN, high-redshift supernovae, and cluster caustic transits. Both NEP fields have sightlines through our Galaxy, providing significant numbers of very faint brown dwarfs whose proper motions can be studied. Observations from the first spoke in the NEP TDF are public. This paper presents our first PEARLS observations, their NIRCam data reduction and analysis, our first object catalogs, the 0.9–4.5 μm galaxy counts and Integrated Galaxy Light. We assess the JWST sky brightness in 13 NIRCam filters, yielding our first constraints to diffuse light at 0.9–4.5 μm. PEARLS is designed to be of lasting benefit to the community.
|
|
| 26. |
- Carling, Paul, et al.
(author)
-
Multichannel rivers : their definition and classification
- 2014
-
In: Earth Surface Processes and Landforms. - : Wiley. - 0197-9337 .- 1096-9837. ; 39:1, s. 26-37
-
Journal article (peer-reviewed)abstract
- The etymology and historic usage of such terms as anabranch', anastamose' and braided' within river science are reviewed. Despite several decades of modern research to define river channel typologies inclusive of single channels and multiple channel networks, typologies remain ill-conditioned and consequently ill-defined. Conventionally employed quantitative planform characteristics of river networks possibly cannot be used alone to define channel types, yet the planform remains a central part of all modern classification schemes, supplemented by sedimentological and other qualitative channel characteristics. Planform characteristics largely have been defined using non-standardized metrics describing individual network components, such as link lengths, braiding intensity and bifurcation angles, which often fail to separate visually-different networks of channels. We find that existing typologies remain pragmatically utilitarian rather than fundamentally physics-based and too often fail to discriminate between two distinctive and important processes integral to new channel initiation and flow-splitting: (i) in-channel bar accretion, and (ii) channel avulsion and floodplain excision. It is suggested that, first, if channel planform is to remain central to river typologies, then more rigorous quantitative approaches to the analysis of extended integral channel networks at extended reach scales (rather than network components) are required to correctly determine whether visually-different' channel patterns can be discriminated consistently; and, second, if such visually-different styles do in fact differ in their governing processes of formation and maintenance. A significant question is why do so many seemingly equilibrium network geometries possess a large number of anabranches in excess of predictions from theoretical considerations? The key research frontier with respect to initiating and maintaining multichannel networks remains the understanding and discrimination of accretionary-bar flow splitting versus avulsive processes. Existing and new knowledge on flow splitting processes needs to be better integrated into channel typologies.
|
|
| 27. |
- Castillo, Miguel, et al.
(author)
-
Knickpoint retreat and transient bedrock channel morphology triggered by base-level fall in small bedrock river catchments : The case of the Isle of Jura, Scotland
- 2013
-
In: Geomorphology. - : Elsevier BV. - 0169-555X .- 1872-695X. ; 180, s. 1-9
-
Journal article (peer-reviewed)abstract
- A sudden drop in river base-level can trigger a knickpoint that propagates throughout the fluvial network causing a transient state in the landscape. Knickpoint retreat has been confirmed in large fluvial settings (drainage areas > 100 km(2)) and field data suggest that the same applies to the case of small bedrock river catchments (drainage areas < 100 km(2)). Nevertheless, knickpoint recession on resistant lithologies with structure that potentially affects the retreat rate needs to be confirmed with field-based data. Moreover, it remains unclear whether small bedrock rivers can absorb base-level fall via knickpoint retreat. Here we evaluate the response of small bedrock rivers to base-level fall on the isle of Jura in western Scotland (UK), where rivers incise into dipping quartzite. The mapping of raised beach deposits and strath terraces, and the analysis of stream long profiles, were used to identify knickpoints that had been triggered by base-level fall. Our results indicate that the distance of knickpoint retreat scales to the drainage area in a power law function irrespective of structural setting. On the other hand, local channel slope and basin size influence the vertical distribution of knickpoints. As well, at low drainage areas (similar to 4 km(2)) rivers are unable to absorb the full amount of base-level fall and channel reach morphology downstream of the knickpoint tends towards convexity. The results obtained here confirm that knickpoint retreat is mostly controlled by stream discharge, as has been observed for other transient landscapes. Local controls, reflecting basin size and channel slope, have an effect on the vertical distribution of knickpoints; such controls are also related to the ability of rivers to absorb the base-level fall.
|
|
| 28. |
- Cohen, Tim J., et al.
(author)
-
Hydrological transformation coincided with megafaunal extinction in central Australia
- 2015
-
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.
|
|
| 29. |
- Croke, Jacky, et al.
(author)
-
A 100 ka record of fluvial activity in the Fitzroy River Basin, tropical northeastern Australia
- 2011
-
In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 30:13-14, s. 1681-1695
-
Journal article (peer-reviewed)abstract
- This study reports the nature and timing of Quaternary fluvial activity in the Fitzroy River basin, which drains a diverse 143,000 km(2) area in northeastern Queensland, before discharging into the Great Barrier Reef Marine Park. The catchment consists of an extensive array of channel and floodplain types that we show have undergone large-scale fluvial adjustment in-channel planform, geometry and sinuosity. Optically stimulated luminescence (OSL) dating of quartz sediments from fifteen (3-18 m) floodplain cores throughout the basin indicates several discrete phases of active bedload activity: at similar to 105-85 ka in Marine Isotope Stage (MIS) 5, at similar to 50-40 ka (MIS 3), and at similar to 30-10 ka (MIS 3/2). The overall timing of late Quaternary fluvial activity correlates well with previous accounts from across Australia with rivers being primarily active during interstadials. Fluvial activity, however, does not appear to have been synchronous throughout the basin's major sub-catchments. Fluvial activity throughout MIS 2 (i.e. across the Last Glacial Maximum) in the meandering channels of the Fitzroy correlates well with regional data in tropical northeastern Queensland, and casts new light on the river response to reduced rainfall and vegetation cover suggested by regional palaeoclimate indicators. Moreover, the absence of a strong Holocene signal is at odds with previous accounts from elsewhere throughout Australia. The latitudinal position of the Fitzroy across the Tropic of Capricorn places this catchment at a key location for elucidating the main hydrological drivers of Quaternary fluvial activity in northeastern Australia, and especially for determining tropical moisture sources feeding into the headwaters of Cooper Creek, a major river system of the continental interior.
|
|
| 30. |
- Fang, Jun, et al.
(author)
-
Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148
- 2017
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Journal article (peer-reviewed)abstract
- Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.
|
|
| 31. |
- 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.
|
|
| 32. |
- Jansen, John D., et al.
(author)
-
Does decreasing paraglacial sediment supply slow knickpoint retreat?
- 2011
-
In: Geology. - 0091-7613 .- 1943-2682. ; 39:6, s. 543-546
-
Journal article (peer-reviewed)abstract
- In four rivers in western Scotland for which there is a well-constrained record of relative base-level fall, the rate of postglacial bedrock erosion is quantified by measuring the concentration of in situ cosmogenic (10)Be on strath terraces downstream of headward-retreating knickpoints. Along-channel gradients in (10)Be exposure age show two distinct trends: upstream younging and constant age, which we interpret as diagnostic of knickpoint retreat and diffusive transport-limited incision, respectively. We show that bedrock channel incision and regional formation of strath terraces began shortly after deglaciation (ca. 11.5 ka), and that knickpoint retreat rates peaked in the early to mid-Holocene. Erosion rates have since decreased by two orders of magnitude, converging in the late Holocene to low rates independent of stream power per unit channel area. We infer this regional slowing in postglacial knickpoint retreat to be the result of the depletion of paraglacial sediment supply over the Holocene, leading to a deficiency in tools for bedrock erosion. Our results imply that episodes of major fluvial erosion may be in tune with glacial cycles, and that sediment depletion following glacial-interglacial transitions may be an important cause of bedrock erosion rate variations in rivers draining glaciated landscapes.
|
|
| 33. |
- Jiroušek, Martin, et al.
(author)
-
Classification of European bog vegetation of the Oxycocco‐Sphagnetea class
- 2022
-
In: Applied Vegetation Science. - : Wiley. - 1402-2001 .- 1654-109X. ; 25:1, s. 1-19
-
Journal article (peer-reviewed)abstract
- Aims: Classification of European bog vegetation (Oxycocco- Sphagnetea class); iden -tification of diagnostic species for the class and vegetation subgroups (orders and alliances); development of an expert system for automatic classification of vegetation plots; and production of distribution maps of the Oxycocco- Sphagnetea class and its alliances.Location: Europe.Methods: A data set of vegetation- plot records was compiled to include various bog types over most of the European continent. An unsupervised classification (beta- flexible linkage method, Sørensen distance measure) and detrended correspondenceanalysis (DCA) ordination were applied. Formal definitions of syntaxa based on spe -cies presence and covers, and respecting the results of the unsupervised classifica-tion, were developed and included in a classification expert system.Results: The Oxycocco- Sphagnetea class, its two orders (Sphagno- Ericetalia tetralicisand Sphagnetalia medii) and seven compositionally distinct alliances were formally de -fined. In addition to the syntaxa included in EuroVegChecklist, three new alliances were distinguished: Rubo chamaemori- Dicranion elongati (subarctic polygon and palsa mires); Erico mackaianae- Sphagnion papillosi (blanket bogs of the northwestern IberianPeninsula); and Sphagno baltici- Trichophorion cespitosi (boreal bog lawns). The latter alliance is newly described in this article.Conclusions: This first pan- European formalized classification of European bog veg -etation partially followed the system presented in EuroVegChecklist, but suggested three additional alliances. One covers palsa and polygon mires, one covers Iberian bogs with endemics and one fills the syntaxonomical gap for lawn microhabitats in boreal bogs. A classification expert system has been developed, which allows assign -ment of vegetation plots to the types described.
|
|
| 34. |
- Margold, Martin, et al.
(author)
-
Extensive glaciation in Transbaikalia, Siberia, at the Last Glacial Maximum
- 2016
-
In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 132, s. 161-174
-
Journal article (peer-reviewed)abstract
- Successively smaller glacial extents have been proposed for continental Eurasia during the stadials of the last glacial period leading up to the Last Glacial Maximum (LGM). At the same time the large mountainous region east of Lake Baikal, Transbaikalia, has remained unexplored in terms of glacial chronology despite clear geomorphological evidence of substantial past glaciations. We have applied cosmogenic Be-10 exposure dating and optically stimulated luminescence to establish the first quantitative glacial chronology for this region. Based on eighteen exposure ages from five moraine complexes, we propose that large mountain ice fields existed in the Kodar and Udokan mountains during Oxygen Isotope Stage 2, commensurate with the global LGM. These ice fields fed valley glaciers (>100 km in length) reaching down to the Chara Depression between the Kodar and Udokan mountains and to the valley of the Vitim River northwest of the Kodar Mountains. Two of the investigated moraines date to the Late Glacial, but indications of incomplete exposure among some of the sampled boulders obscure the specific details of the post-LGM glacial history. In addition to the LGM ice fields in the highest mountains of Transbaikalia, we report geomorphological evidence of a much more extensive, ice-cap type glaciation at a time that is yet to be firmly resolved.
|
|
| 35. |
- Margold, Martin, et al.
(author)
-
Repeated megafloods from glacial Lake Vitim, Siberia, to the Arctic Ocean over the past 60,000 years
- 2018
-
In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 187, s. 41-61
-
Journal article (peer-reviewed)abstract
- Cataclysmic outburst floods transformed landscapes and caused abrupt climate change during the last deglaciation. Whether such events have also characterized previous deglaciations is not known. Arctic marine cores hint at megafloods prior to Oxygen Isotope Stage (OIS) 2, but the overprint of successive glaciations means that geomorphological traces of ancient floods remain scarce in Eurasia and North America. Here we present the first well-constrained terrestrial megaflood record to be linked with Arctic archives. Based on cosmogenic-nuclide exposure dating and optically stimulated luminescence dating applied to glacial-lake sediments, a 300-m deep bedrock spillway, and giant eddy-bars > 200-m high, we reconstruct a history of cataclysmic outburst floods from glacial Lake Vitim, Siberia, to the Arctic Ocean over the past 60,000-years. Three megafloods have reflected the rhythm of Eurasian glaciations, leaving traces that stretch more than 3500 km to the Lena Delta. The first flood was coincident with deglaciation from OIS-4 and the largest meltwater spike in Arctic marine-cores within the past 100,000 years (isotope-event 3.31 at 55.5 ka). The second flood marked the lead up to the local Last Glacial Maximum, and the third flood occurred during the last deglaciation. This final 3000 km(3) megaflood stands as one of the largest freshwater floods ever documented, with peak discharge of 4.0-6.5 million m(3)s(-1), mean flow depths of 120-150 m, and average flow velocities up to 21 ms(-1)
|
|
| 36. |
- Nørgaard, Jesper, et al.
(author)
-
Absence of Large-Scale Ice Masses in Central Northeast Siberia During the Late Pleistocene
- 2023
-
In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 50:10
-
Journal article (peer-reviewed)abstract
- Ongoing speculation regarding the existence of large Late Pleistocene ice masses in Northeast Eurasia reflects the dearth of age constraints on glaciations across this vast region. Here, we report the first dates from the central part of Northeast Siberia, consisting of 22 cosmogenic 10Be exposure ages from boulders deriving from a sequence of three moraines in the Chersky Range. The dated moraine sequence indicates progressive contraction of maximum glacier extent from Marine Isotope Stage 6 to the Last Glacial Maximum, while the remotely-sensed mapping indicates an older, more expansive glaciation in the region yet undated. Our results show that Late Pleistocene glaciations were limited to the highlands, and Northeast Siberia did not host a large, coalescent ice sheet during the Last Glacial Maximum or Marine Isotope Stage 6.
|
|
| 37. |
- Raval, Aparna, et al.
(author)
-
Downregulation of death-associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia
- 2007
-
In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 129:5, s. 879-890
-
Journal article (peer-reviewed)abstract
- The heritability of B cell chronic lymphocytic leukemia (CLL) is relatively high; however, no predisposing mutation has been convincingly identified. We show that loss or reduced expression of death-associated protein kinase 1 (DAPK1) underlies cases of heritable predisposition to CLL and the majority of sporadic CLL. Epigenetic silencing of DAPK1 by promoter methylation occurs in almost all sporadic CLL cases. Furthermore, we defined a disease haplotype, which segregates with the CLL phenotype in a large family. DAPK1 expression of the CLL allele is downregulated by 75% in germline cells due to increased HOXB7 binding. In the blood cells from affected family members, promoter methylation results in additional loss of DAPK1 expression. Thus, reduced expression of DAPK1 can result from germline predisposition, as well as epigenetic or somatic events causing or contributing to the CLL phenotype.
|
|
| 38. |
- Reeves, Jessica M., et al.
(author)
-
Climate variability over the last 35,000 years recorded in marine and terrestrial archives in the Australian region : an OZ-INTIMATE compilation
- 2013
-
In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 74, s. 21-34
-
Journal article (peer-reviewed)abstract
- The Australian region spans some 600 of latitude and 500 of longitude and displays considerable regional climate variability both today and during the Late Quaternary. A synthesis of marine and terrestrial climate records, combining findings from the Southern Ocean, temperate, tropical and arid zones, identifies a complex response of climate proxies to a background of changing boundary conditions over the last 35,000 years. Climate drivers include the seasonal timing of insolation, greenhouse gas content of the atmosphere, sea level rise and ocean and atmospheric circulation changes. Our compilation finds few climatic events that could be used to construct a climate event stratigraphy for the entire region, limiting the usefulness of this approach. Instead we have taken a spatial approach, looking to discern the patterns of change across the continent. The data identify the clearest and most synchronous climatic response at the time of the Last Glacial Maximum (LGM) (21 +/- 3 ka), with unambiguous cooling recorded in the ocean, and evidence of glaciation in the highlands of tropical New Guinea, southeast Australia and Tasmania. Many terrestrial records suggest drier conditions, but with the timing of inferred snowmelt, and changes to the rainfall/runoff relationships, driving higher river discharge at the LGM. In contrast, the deglaciation is a time of considerable south-east to north-west variation across the region. Warming was underway in all regions by 17 ka. Post-glacial sea level rise and its associated regional impacts have played an important role in determining the magnitude and timing of climate response in the north-west of the continent in contrast to the southern latitudes. No evidence for cooling during the Younger Dryas chronozone is evident in the region, but the Antarctic cold reversal clearly occurs south of Australia. The Holocene period is a time of considerable climate variability associated with an intense monsoon in the tropics early in the Holocene, giving way to a weakened monsoon and an increasingly El Nino-dominated ENSO to the present. The influence of ENSO is evident throughout the southeast of Australia, but not the southwest. This climate history provides a template from which to assess the regionality of climate events across Australia and make comparisons beyond our region.
|
|
| 39. |
- Scharf, Taryn E., et al.
(author)
-
Strong rocks sustain ancient postorogenic topography in southern Africa
- 2013
-
In: Geology. - 0091-7613 .- 1943-2682. ; 41:3, s. 331-334
-
Journal article (peer-reviewed)abstract
- The Cape Mountains of southern Africa exhibit an alpine-like topography in conjunction with some of the lowest denudation rates in the world. This presents an exception to the often-cited coupling of topography and denudation rates and suggests that steep slopes alone are not sufficient to incite the high denudation rates with which they are commonly associated. Within the Cape Mountains, slope angles are often in excess of 30 degrees and relief frequently exceeds 1 km, yet Be-10-based catchment-averaged denudation rates vary between 2.32 +/- 0.29 m/m.y. and 7.95 +/- 0.90 m/m.y. We attribute the maintenance of rugged topography and suppression of denudation rates primarily to the presence of physically robust and chemically inert quartzites that constitute the backbone of the mountains. Be-10-based bedrock denudation rates on the interfluves of the mountains vary between 1.98 +/- 0.23 m/m.y. and 4.61 +/- 0.53 m/m.y. The close agreement between the rates of catchment-averaged and interfluve denudation indicates topography in steady state. These low denudation rates, in conjunction with the suggestion of geomorphic stability, are in agreement with the low denudation rates (<20 m/m.y.) estimated for southern Africa during the late Cenozoic by means of cosmogenic nuclide, thermochronology, and offshore sedimentation analyses. Accumulatively, these data suggest that the coastal hinterland of the subcontinent may have experienced relative tectonic stability throughout the Cenozoic.
|
|
| 40. |
- Stroeven, Arjen P., et al.
(author)
-
Deglaciation of Fennoscandia
- 2016
-
In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 147:SI, s. 91-121
-
Journal article (peer-reviewed)abstract
- To provide a new reconstruction of the deglaciation of the Fennoscandian Ice Sheet, in the form of calendar-year time-slices, which are particularly useful for ice sheet modelling, we have compiled and synthesized published geomorphological data for eskers, ice-marginal formations, lineations, marginal meltwater channels, striae, ice-dammed lakes, and geochronological data from radiocarbon, varve, optically-stimulated luminescence, and cosmogenic nuclide dating. This is summarized as a deglaciation map of the Fennoscandian Ice Sheet with isochrons marking every 1000 years between 22 and 13 cal kyr BP and every hundred years between 11.6 and final ice decay after 9.7 cal kyr BP. Deglaciation patterns vary across the Fennoscandian Ice Sheet domain, reflecting differences in climatic and geomorphic settings as well as ice sheet basal thermal conditions and terrestrial versus marine margins. For example, the ice sheet margin in the high-precipitation coastal setting of the western sector responded sensitively to climatic variations leaving a detailed record of prominent moraines and other ice-marginal deposits in many fjords and coastal valleys. Retreat rates across the southern sector differed between slow retreat of the terrestrial margin in western and southern Sweden and rapid retreat of the calving ice margin in the Baltic Basin. Our reconstruction is consistent with much of the published research. However, the synthesis of a large amount of existing and new data support refined reconstructions in some areas. For example, the LGM extent of the ice sheet in northwestern Russia was located far east and it occurred at a later time than the rest of the ice sheet, at around 17-15 cal kyr BP. We also propose a slightly different chronology of moraine formation over southern Sweden based on improved correlations of moraine segments using new LiDAR data and tying the timing of moraine formation to Greenland ice core cold stages. Retreat rates vary by as much as an order of magnitude in different sectors of the ice sheet, with the lowest rates on the high-elevation and maritime Norwegian margin. Retreat rates compared to the climatic information provided by the Greenland ice core record show a general correspondence between retreat rate and climatic forcing, although a close match between retreat rate and climate is unlikely because of other controls, such as topography and marine versus terrestrial margins. Overall, the time slice reconstructions of Fennoscandian Ice Sheet deglaciation from 22 to 9.7 cal kyr BP provide an important dataset for understanding the contexts that underpin spatial and temporal patterns in retreat of the Fennoscandian Ice Sheet, and are an important resource for testing and refining ice sheet models.
|
|
| 41. |
|
|
| 42. |
- van Karnebeek, Clara D. M., et al.
(author)
-
CIAO1 and MMS19 de fi ciency : A lethal neurodegenerative phenotype caused by cytosolic Fe-S cluster protein assembly disorders
- 2024
-
In: Genetics in Medicine. - : Elsevier. - 1098-3600 .- 1530-0366. ; 26:6
-
Journal article (peer-reviewed)abstract
- Purpose: The functionality of many cellular proteins depends on cofactors; yet, they have only been implicated in a minority of Mendelian diseases. Here, we describe the first 2 inherited disorders of the cytosolic iron-sulfur protein assembly system.Methods: Genetic testing via genome sequencing was applied to identify the underlying disease cause in 3 patients with microcephaly, congenital brain malformations, progressive developmental and neurologic impairments, recurrent infections, and a fatal outcome. Studies in patient-derived skin fibroblasts and zebrafish models were performed to investigate the biochemical and cellular consequences.Results: Metabolic analysis showed elevated uracil and thymine levels in body fluids but no pathogenic variants in DPYD, encoding dihydropyrimidine dehydrogenase. Genome sequencing identified compound heterozygosity in 2 patients for missense variants in CIAO1, encoding cytosolic iron-sulfur assembly component 1, and homozygosity for an in-frame 3-nucleotide deletion in MMS19, encoding the MMS19 homolog, cytosolic iron-sulfur assembly component, in the third patient. Profound alterations in the proteome, metabolome, and lipidome were observed in patient-derived fibroblasts. We confirmed the detrimental effect of deficiencies in CIAO1 and MMS19 in zebrafish models.Conclusion: A general failure of cytosolic and nuclear iron-sulfur protein maturation caused pleiotropic effects. The critical function of the cytosolic iron-sulfur protein assembly machinery for antiviral host defense may well explain the recurrent severe infections occurring in our patients. (c) 2024 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
|
|
