| 1. |
|
|
| 2. |
|
|
| 3. |
- Bellenguez, C, et al.
(författare)
-
New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
-
Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
|
|
| 4. |
- Aalbers, J., et al.
(författare)
-
A next-generation liquid xenon observatory for dark matter and neutrino physics
- 2023
-
Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 50:1
-
Forskningsöversikt (refereegranskat)abstract
- The nature of dark matter and properties of neutrinos are among the most pressing issues in contemporary particle physics. The dual-phase xenon time-projection chamber is the leading technology to cover the available parameter space for weakly interacting massive particles, while featuring extensive sensitivity to many alternative dark matter candidates. These detectors can also study neutrinos through neutrinoless double-beta decay and through a variety of astrophysical sources. A next-generation xenon-based detector will therefore be a true multi-purpose observatory to significantly advance particle physics, nuclear physics, astrophysics, solar physics, and cosmology. This review article presents the science cases for such a detector.
|
|
| 5. |
- Weyhenmeyer, Gesa A., Professor, et al.
(författare)
-
Global Lake Health in the Anthropocene : Societal Implications and Treatment Strategies
- 2024
-
Ingår i: Earth's Future. - : American Geophysical Union (AGU). - 2328-4277. ; 12:4
-
Forskningsöversikt (refereegranskat)abstract
- The world's 1.4 million lakes (>= 10 ha) provide many ecosystem services that are essential for human well-being; however, only if their health status is good. Here, we reviewed common lake health issues and classified them using a simple human health-based approach to outline that lakes are living systems that are in need of oxygen, clean water and a balanced energy and nutrient supply. The main reason for adopting some of the human health terminology for the lake health classification is to increase the awareness and understanding of global lake health issues. We show that lakes are exposed to various anthropogenic stressors which can result in many lake health issues, ranging from thermal, circulatory, respiratory, nutritional and metabolic issues to infections and poisoning. Of particular concern for human well-being is the widespread lake drying, which is a severe circulatory issue with many cascading effects on lake health. We estimated that similar to 115,000 lakes evaporate twice as much water as they gain from direct precipitation, making them vulnerable to potential drying if inflowing waters follow the drying trend, putting more than 153 million people at risk who live in close vicinity to those lakes. Where lake health issues remain untreated, essential ecosystem services will decline or even vanish, posing a threat to the well-being of millions of people. We recommend coordinated multisectoral and multidisciplinary prevention and treatment strategies, which need to include a follow-up of the progress and an assessment of the resilience of lakes to intensifying threats. Priority should be given to implementing sewage water treatment, mitigating climate change, counteracting introductions of non-native species to lakes and decreasing uncontrolled anthropogenic releases of chemicals into the hydro-, bio-, and atmosphere. Lakes around the world come in an array of sizes, shapes and colors, each telling a unique story of geological history and environmental importance. When lakes are healthy they contribute to the achievement of the global sustainable development goals by providing many important ecosystem services. Lakes are, however, not always healthy. Here, it is shown that lakes can suffer from a large variety of health issues, ranging from thermal, circulatory, respiratory, nutritional and metabolic issues to infections and poisoning. Without improved treatment strategies, many of the health issues may become chronic, affecting millions of people who are dependent on the ecosystem services from the lakes. To prevent and cure lakes from critical health conditions, strategies that are similar to those used in human healthcare should be applied: intervention and preventative actions before health problems occur, regular screening and early identification of lake health issues, and remediation and mitigation efforts at an appropriate scale, spanning from local to global. Anthropogenic stressors can cause lake health issues that range from thermal, circulatory, respiratory, nutritional and metabolic issues to infections and poisoning Lake health varies geographically, with the highest risk of critical conditions occurring in densely populated low-income countries There is an urgent need to follow-up the progress of treatments and to make adjustments whenever needed
|
|
| 6. |
- Malzbender, K., et al.
(författare)
-
Validation, Deployment, and Real-World Implementation of a Modular Toolbox for Alzheimer’s Disease Detection and Dementia Risk Reduction: The AD-RIDDLE Project
- 2024
-
Ingår i: Journal of Prevention of Alzheimer's Disease. - 2274-5807 .- 2426-0266. ; 11:2, s. 329-338
-
Tidskriftsartikel (refereegranskat)abstract
- The Real-World Implementation, Deployment, and Validation of Early Detection Tools and Lifestyle Enhancement (AD-RIDDLE) project, recently launched with the support of the EU Innovative Health Initiative (IHI) public-private partnership and UK Research and Innovation (UKRI), aims to develop, test, and deploy a modular toolbox platform that can reduce existing barriers to the timely detection, and therapeutic approaches in Alzheimer’s disease (AD), thus accelerating AD innovation. By focusing on health system and health worker practices, AD-RIDDLE seeks to improve and smooth AD management at and between each key step of the clinical pathway and across the disease continuum, from at-risk asymptomatic stages to early symptomatic ones. This includes innovation and improvement in AD awareness, risk reduction and prevention, detection, diagnosis, and intervention. The 24 partners in the AD-RIDDLE interdisciplinary consortium will develop and test the AD-RIDDLE toolbox platform and its components individually and in combination in six European countries. Expected results from this cross-sectoral research collaboration include tools for earlier detection and accurate diagnosis; validated, novel digital cognitive and blood-based biomarkers; and improved access to individualized preventative interventions (including multimodal interventions and symptomatic/disease-modifying therapies) across diverse populations, within the framework of precision medicine. Overall, AD-RIDDLE toolbox platform will advance management of AD, improving outcomes for patients and their families, and reducing costs.
|
|
| 7. |
- Vermunt, L., et al.
(författare)
-
Prescreening for European Prevention of Alzheimer Dementia (EPAD) trial-ready cohort: impact of AD risk factors and recruitment settings
- 2020
-
Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Recruitment is often a bottleneck in secondary prevention trials in Alzheimer disease (AD). Furthermore, screen-failure rates in these trials are typically high due to relatively low prevalence of AD pathology in individuals without dementia, especially among cognitively unimpaired. Prescreening on AD risk factors may facilitate recruitment, but the efficiency will depend on how these factors link to participation rates and AD pathology. We investigated whether common AD-related factors predict trial-ready cohort participation and amyloid status across different prescreen settings. Methods We monitored the prescreening in four cohorts linked to the European Prevention of Alzheimer Dementia (EPAD) Registry (n = 16,877; mean +/- SD age = 64 +/- 8 years). These included a clinical cohort, a research in-person cohort, a research online cohort, and a population-based cohort. Individuals were asked to participate in the EPAD longitudinal cohort study (EPAD-LCS), which serves as a trial-ready cohort for secondary prevention trials. Amyloid positivity was measured in cerebrospinal fluid as part of the EPAD-LCS assessment. We calculated participation rates and numbers needed to prescreen (NNPS) per participant that was amyloid-positive. We tested if age, sex, education level, APOE status, family history for dementia, memory complaints or memory scores, previously collected in these cohorts, could predict participation and amyloid status. Results A total of 2595 participants were contacted for participation in the EPAD-LCS. Participation rates varied by setting between 3 and 59%. The NNPS were 6.9 (clinical cohort), 7.5 (research in-person cohort), 8.4 (research online cohort), and 88.5 (population-based cohort). Participation in the EPAD-LCS (n = 413 (16%)) was associated with lower age (odds ratio (OR) age = 0.97 [0.95-0.99]), high education (OR = 1.64 [1.23-2.17]), male sex (OR = 1.56 [1.19-2.04]), and positive family history of dementia (OR = 1.66 [1.19-2.31]). Among participants in the EPAD-LCS, amyloid positivity (33%) was associated with higher age (OR = 1.06 [1.02-1.10]) and APOE e4 allele carriership (OR = 2.99 [1.81-4.94]). These results were similar across prescreen settings. Conclusions Numbers needed to prescreen varied greatly between settings. Understanding how common AD risk factors link to study participation and amyloid positivity is informative for recruitment strategy of studies on secondary prevention of AD.
|
|
| 8. |
- Horne, C. R., et al.
(författare)
-
Mechanism of NanR gene repression and allosteric induction of bacterial sialic acid metabolism
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Bacteria respond to environmental changes by inducing transcription of some genes and repressing others. Sialic acids, which coat human cell surfaces, are a nutrient source for pathogenic and commensal bacteria. The Escherichia coli GntR-type transcriptional repressor, NanR, regulates sialic acid metabolism, but the mechanism is unclear. Here, we demonstrate that three NanR dimers bind a (GGTATA)(3)-repeat operator cooperatively and with high affinity. Single-particle cryo-electron microscopy structures reveal the DNA-binding domain is reorganized to engage DNA, while three dimers assemble in close proximity across the (GGTATA)(3)-repeat operator. Such an interaction allows cooperative protein-protein interactions between NanR dimers via their N-terminal extensions. The effector, N-acetylneuraminate, binds NanR and attenuates the NanR-DNA interaction. The crystal structure of NanR in complex with N-acetylneuraminate reveals a domain rearrangement upon N-acetylneuraminate binding to lock NanR in a conformation that weakens DNA binding. Our data provide a molecular basis for the regulation of bacterial sialic acid metabolism. The GntR superfamily is one of the largest families of transcription factors in prokaryotes. Here the authors combine biophysical analysis and structural biology to dissect the mechanism by which NanR - a GntR-family regulator - binds to its promoter to repress the transcription of genes necessary for sialic acid metabolism.
|
|
| 9. |
- Nava, Veronica, et al.
(författare)
-
Plastic debris in lakes and reservoirs
- 2023
-
Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 619:7969, s. 317-322
-
Tidskriftsartikel (refereegranskat)abstract
- Plastic debris is thought to be widespread in freshwater ecosystems globally(1). However, a lack of comprehensive and comparable data makes rigorous assessment of its distribution challenging(2,3). Here we present a standardized cross-national survey that assesses the abundance and type of plastic debris (>250 mu m) in freshwater ecosystems. We sample surface waters of 38 lakes and reservoirs, distributed across gradients of geographical position and limnological attributes, with the aim to identify factors associated with an increased observation of plastics. We find plastic debris in all studied lakes and reservoirs, suggesting that these ecosystems play a key role in the plastic-pollution cycle. Our results indicate that two types of lakes are particularly vulnerable to plastic contamination: lakes and reservoirs in densely populated and urbanized areas and large lakes and reservoirs with elevated deposition areas, long water-retention times and high levels of anthropogenic influence. Plastic concentrations vary widely among lakes; in the most polluted, concentrations reach or even exceed those reported in the subtropical oceanic gyres, marine areas collecting large amounts of debris(4). Our findings highlight the importance of including lakes and reservoirs when addressing plastic pollution, in the context of pollution management and for the continued provision of lake ecosystem services.
|
|
| 10. |
- Reinl, Kaitlin L., et al.
(författare)
-
Cyanobacterial blooms in oligotrophic lakes : Shifting the high-nutrient paradigm
- 2021
-
Ingår i: Freshwater Biology. - : John Wiley & Sons. - 0046-5070 .- 1365-2427. ; 66:9, s. 1846-1859
-
Tidskriftsartikel (refereegranskat)abstract
- Freshwater cyanobacterial blooms have become ubiquitous, posing major threats to ecological and public health. Decades of research have focused on understanding drivers of these blooms with a primary focus on eutrophic systems; however, cyanobacterial blooms also occur in oligotrophic systems, but have received far less attention, resulting in a gap in our understanding of cyanobacterial blooms overall. In this review, we explore evidence of cyanobacterial blooms in oligotrophic freshwater systems and provide explanations for those occurrences. We show that through their unique physiological adaptations, cyanobacteria are able to thrive under a wide range of environmental conditions, including low-nutrient waterbodies. We contend that to fully understand cyanobacterial blooms, and thereby mitigate and manage them, we must expand our inquiries to consider systems along the trophic gradient, and not solely focus on eutrophic systems, thus shifting the high-nutrient paradigm to a trophic-gradient paradigm.
|
|
