| 1. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 3. |
- van Rheenen, Wouter, et al.
(författare)
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Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
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| 4. |
- Kurz, Alexander, et al.
(författare)
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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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Ingår i: International psychogeriatrics. - 1041-6102 .- 1741-203X. ; 28:12, s. 2091-2099
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Romanov, Roman A., et al.
(författare)
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Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes
- 2017
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 20:2, s. 176-188
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Tidskriftsartikel (refereegranskat)abstract
- The hypothalamus contains the highest diversity of neurons in the brain. Many of these neurons can co-release neurotransmitters and neuropeptides in a use-dependent manner. Investigators have hitherto relied on candidate protein-based tools to correlate behavioral, endocrine and gender traits with hypothalamic neuron identity. Here we map neuronal identities in the hypothalamus by single-cell RNA sequencing. We distinguished 62 neuronal subtypes producing glutamatergic, dopaminergic or GABAergic markers for synaptic neurotransmission and harboring the ability to engage in task-dependent neurotransmitter switching. We identified dopamine neurons that uniquely coexpress the Onecut3 and Nmur2 genes, and placed these in the periventricular nucleus with many synaptic afferents arising from neuromedin S+ neurons of the suprachiasmatic nucleus. These neuroendocrine dopamine cells may contribute to the dopaminergic inhibition of prolactin secretion diurnally, as their neuromedin S+ inputs originate from neurons expressing Per2 and Per3 and their tyrosine hydroxylase phosphorylation is regulated in a circadian fashion. Overall, our catalog of neuronal subclasses provides new understanding of. hypothalamic organization and function.
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| 6. |
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| 8. |
- Athavale, Rohini, et al.
(författare)
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Robust Solid-Contact Ion Selective Electrodes for High-Resolution In Situ Measurements in Fresh Water Systems
- 2017
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Ingår i: ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS. - : American Chemical Society (ACS). - 2328-8930. ; 4:7, s. 286-291
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Tidskriftsartikel (refereegranskat)abstract
- Biogeochemical processes are often confined to very narrow zones in aquatic systems. Therefore, highly resolved in situ measurements are required to study these processes. Potentiometric solid -contact ion selective electrodes (SC-ISEs) are promising tools for such measurements. SCISEs show good performance in analyses under controlled experimental conditions. Very few sensor designs, however, can sustain the challenges of natural water matrices and external environmental conditions during in situ applications. We fabricated ammonium and pH selective SC-ISEs with functionalized multiwalled carbon nanotubes (f-MWCNT) as a solid contact. Their functionality was tested in the laboratory and applied in situ for vertical profiling in a eutrophic lake. Sensors were insensitive to strong redox changes, high sulfide concentrations, and bright daylight conditions during the application in the lake. In addition, sensors are easily fabricated and exhibit short response times (<10 s). The proposed design of SC-ISEs based on f-MWCNTs is quite suitable for high-resolution in situ profiling of ionic species in fresh water lakes.
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| 9. |
- Borghei, Benny Behbood, 1980-
(författare)
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Incumbent Actors in Sectoral Transformations Towards Sustainability : A sociotechnical study of the European heavy commercial vehicles sector
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Industrial sectors need to be transformed in response to the increasing demands for environmental sustainability as one of the greatest challenges in the modern times. In social science research, extensive efforts have been made over the recent decades to formulate comprehensive theories about transformation of various sectors such as energy, manufacturing, agriculture, food and transportation. Accordingly, ‘sustainability transitions’ have emerged as a research field dedicated to the study of far-reaching sociotechnical transformations.Understanding sectoral transformations and how different actors can get involved in sustainability transitions are in the heart of these efforts. Of particular importance is the involvement of industry incumbents that hold established positions and considerable amounts of knowledge, resources, and technological competence built upon vigorous structures of the existing industrial setup. This in turn calls for more attention to the role of incumbents to actively participate in the transformation of established sectors towards sustainability.However, despite the potentials to get involved in processes of transformative change, incumbents are often neglected in transition theories, and their role is predetermined to resist the change. Incumbents are widely black-boxed as a homogenous group of actors to the extent that they are conceived as a single entity whose predefined role is to act as the guardians of the existing structures and defenders of the status-quo. While there are legitimate concerns about the power of incumbent firms, such one-sided views do not offer an inclusive approach in formulating multi-actor processes for sustainability transitions. Therefore, the purpose of this thesis is to contribute to a more comprehensive theorization on the role of incumbent actors in sectoral transformations. The main research question is formulated as follows: how can incumbents act to facilitate sectoral transformations towards environmental sustainability?In answering this research question, the thesis offers an alternative perspective to the dominant view about incumbents in sustainability transition theories. It challenges prevailing assumptions by providing empirical evidence from the heavy commercial vehicles sector in Europe. The research findings show that incumbents are able to adopt various technological strategies ranging from incremental innovations with highly coordinated actions for reducing emission levels based on the established technologies, to the adoption of radical technological choices for introducing alternative propulsion technologies in the market. In fact, the strong position of incumbents can sometimes enable them to introduce radical innovations in established markets. The research findings also indicate that incumbents can act as learning agents or knowledge repositories to overcome the problem of isolation for new technological innovations by transferring knowledge and technologies over the boundaries of time and space. Moreover, incumbents can facilitate diffusion of radical innovations and ramp up the adoption of new technologies through standardization at the industry level. In addition, incumbents from a range of different sectors have been recognized as integrators for the development of new technological solutions that span over traditional boundaries. Hence, new industrial sectors can emerge through the integration of knowledge and technologies from various established sectors, and incumbents are at the heart of the integration processes due to their knowledge and familiarity of the established sectors.Finally, the theoretical implications from the thesis invite transition scholars to reconsider the role of incumbent actors in sustainability transitions, while the practical implications suggest that policy-makers need to pay more attention to the diversity of technology strategies of incumbent firms and their alignments for sectoral transformations towards sustainability.
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| 10. |
- Brouwer-Brolsma, Elske M., et al.
(författare)
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Combining traditional dietary assessment methods with novel metabolomics techniques: Present efforts by the Food Biomarker Alliance
- 2017
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Ingår i: Proceedings of the Nutrition Society. - 0029-6651 .- 1475-2719. ; 76:4, s. 619-627
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Tidskriftsartikel (refereegranskat)abstract
- FFQ, food diaries and 24 h recall methods represent the most commonly used dietary assessment tools in human studies on nutrition and health, but food intake biomarkers are assumed to provide a more objective reflection of intake. Unfortunately, very few of these biomarkers are sufficiently validated. This review provides an overview of food intake biomarker research and highlights present research efforts of the Joint Programming Initiative 'A Healthy Diet for a Healthy Life' (JPI-HDHL) Food Biomarkers Alliance (FoodBAll). In order to identify novel food intake biomarkers, the focus is on new food metabolomics techniques that allow the quantification of up to thousands of metabolites simultaneously, which may be applied in intervention and observational studies. As biomarkers are often influenced by various other factors than the food under investigation, FoodBAll developed a food intake biomarker quality and validity score aiming to assist the systematic evaluation of novel biomarkers. Moreover, to evaluate the applicability of nutritional biomarkers, studies are presently also focusing on associations between food intake biomarkers and diet-related disease risk. In order to be successful in these metabolomics studies, knowledge about available electronic metabolomics resources is necessary and further developments of these resources are essential. Ultimately, present efforts in this research area aim to advance quality control of traditional dietary assessment methods, advance compliance evaluation in nutritional intervention studies, and increase the significance of observational studies by investigating associations between nutrition and health.
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