| 191. |
- Nounu, Aayah, et al.
(författare)
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Salicylic Acid and Risk of Colorectal Cancer : A Two-Sample Mendelian Randomization Study
- 2021
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Salicylic acid (SA) has observationally been shown to decrease colorectal cancer (CRC) risk. Aspirin (acetylsalicylic acid, that rapidly deacetylates to SA) is an effective primary and secondary chemopreventive agent. Through a Mendelian randomization (MR) approach, we aimed to address whether levels of SA affected CRC risk, stratifying by aspirin use. A two-sample MR analysis was performed using GWAS summary statistics of SA (INTERVAL and EPIC-Norfolk, N = 14,149) and CRC (CCFR, CORECT, GECCO and UK Biobank, 55,168 cases and 65,160 controls). The DACHS study (4410 cases and 3441 controls) was used for replication and stratification of aspirin-use. SNPs proxying SA were selected via three methods: (1) functional SNPs that influence the activity of aspirin-metabolising enzymes; (2) pathway SNPs present in enzymes' coding regions; and (3) genome-wide significant SNPs. We found no association between functional SNPs and SA levels. The pathway and genome-wide SNPs showed no association between SA and CRC risk (OR: 1.03, 95% CI: 0.84-1.27 and OR: 1.08, 95% CI: 0.86-1.34, respectively). Results remained unchanged upon aspirin use stratification. We found little evidence to suggest that an SD increase in genetically predicted SA protects against CRC risk in the general population and upon stratification by aspirin use.
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| 192. |
- Nystedt, Björn, et al.
(författare)
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The Norway spruce genome sequence and conifer genome evolution
- 2013
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 497:7451, s. 579-584
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Tidskriftsartikel (refereegranskat)abstract
- Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.
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| 193. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Inducible Wnt16 inactivation: WNT16 regulates cortical bone thickness in adult mice.
- 2018
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Ingår i: The Journal of endocrinology. - 1479-6805. ; 237:2, s. 113-122
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Tidskriftsartikel (refereegranskat)abstract
- Substantial progress has been made in the therapeutic reduction of vertebral fracture risk in patients with osteoporosis, but non-vertebral fracture risk has been improved only marginally. Human genetic studies demonstrate that the WNT16 locus is a major determinant of cortical bone thickness and non-vertebral fracture risk and mouse models with life-long Wnt16 inactivation revealed that WNT16 is a key regulator of cortical thickness. These studies, however, could not exclude that the effect of Wnt16 inactivation on cortical thickness might be caused by early developmental and/or growth effects. To determine the effect of WNT16 specifically on adult cortical bone homeostasis, Wnt16 was conditionally ablated in young adult and old mice through tamoxifen-inducible Cre-mediated recombination using CAG-Cre-ER; Wnt16flox/flox (Cre-Wnt16flox/flox) mice. First, 10-week-old Cre-Wnt16flox/flox and Wnt16flox/flox littermate control mice were treated with tamoxifen. Four weeks later, Wnt16 mRNA levels in cortical bone were reduced and cortical thickness in femur was decreased in Cre-Wnt16flox/flox mice compared to Wnt16flox/flox mice. Then, inactivation of Wnt16 in 47-week-old mice (evaluated four weeks later) resulted in a reduction of Wnt16 mRNA levels, cortical thickness and cortical bone strength with no effect on trabecular bone volume fraction. Mechanistic studies demonstrated that the reduced cortical bone thickness was caused by a combination of increased bone resorption and reduced periosteal bone formation. In conclusion, WNT16 is a crucial regulator of cortical bone thickness in young adult and old mice. We propose that new treatment strategies targeting the adult regulation of WNT16 might be useful to reduce fracture risk at cortical bone sites.
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| 194. |
- Olafsen, Tove, et al.
(författare)
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Protein targeting constructs in alpha therapy.
- 2011
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Ingår i: Current radiopharmaceuticals. - : Bentham Science Publishers Ltd.. - 1874-4729 .- 1874-4710. ; 4:3, s. 197-213
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Tidskriftsartikel (refereegranskat)abstract
- The progress in the field of targeted α-particle therapy (TAT) has to a great extent been enhanced by developments in both recombinant DNA technology and radionuclide labeling chemistry. Advances in genomics and proteomics have promoted an increase in the identification of novel targets and molecules that can define different diseases, such as cancer. In radioimmunotherapy (RIT), the primary goal is to improve delivery to and therapeutic efficacy of the cancer cells, whilst minimizing toxicity. Different approaches have been investigated to achieve this, such as reducing the size of the carrier, pretargeting, multidosing, locoregional administration and using a cocktail of radiolabeled monoclonal antibodies for targeting multiple antigens simultaneously. Some of these approaches have been encouraging, but translation of TAT into the clinic has been slow, in part because of the limited availability and the short physical half-lives of some of the available α-particle emitters. The clinical studies carried out to date have been promising, although many challenges remain in order to make TAT safe and economically feasible. In this paper a number of different targeting constructs used hitherto that may be promising carriers for TAT in the future are presented and discussed. The constructs include enzymatic cleaved antibody fragments (Fab and F(ab˙)2 fragments); genetically engineered antibody fragments (scFv monomer, dimer (i.e. diabody) and tetramer, CH2 domain deleted antibody fragments); other protein targeting constructs such as affibodies and peptides as well as liposomal delivery.
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| 195. |
- O'Seaghdha, Conall M., et al.
(författare)
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Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations
- 2013
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:9, s. e1003796-
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Tidskriftsartikel (refereegranskat)abstract
- Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in <= 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.
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| 196. |
- Ostaszewski, Marek, et al.
(författare)
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COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms
- 2021
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Ingår i: Molecular Systems Biology. - : John Wiley & Sons. - 1744-4292 .- 1744-4292. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.
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| 197. |
- Pan, Linfeng, et al.
(författare)
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High carrier mobility along the [111] orientation in Cu2O photoelectrodes
- 2024
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 628:8009, s. 765-770
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Tidskriftsartikel (refereegranskat)abstract
- Solar fuels offer a promising approach to provide sustainable fuels by harnessing sunlight1,2. Following a decade of advancement, Cu2O photocathodes are capable of delivering a performance comparable to that of photoelectrodes with established photovoltaic materials3,4,5. However, considerable bulk charge carrier recombination that is poorly understood still limits further advances in performance6. Here we demonstrate performance of Cu2O photocathodes beyond the state-of-the-art by exploiting a new conceptual understanding of carrier recombination and transport in single-crystal Cu2O thin films. Using ambient liquid-phase epitaxy, we present a new method to grow single-crystal Cu2O samples with three crystal orientations. Broadband femtosecond transient reflection spectroscopy measurements were used to quantify anisotropic optoelectronic properties, through which the carrier mobility along the [111] direction was found to be an order of magnitude higher than those along other orientations. Driven by these findings, we developed a polycrystalline Cu2O photocathode with an extraordinarily pure (111) orientation and (111) terminating facets using a simple and low-cost method, which delivers 7 mA cm−2 current density (more than 70% improvement compared to that of state-of-the-art electrodeposited devices) at 0.5 V versus a reversible hydrogen electrode under air mass 1.5 G illumination, and stable operation over at least 120 h.
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| 198. |
- Pang, Cheng, et al.
(författare)
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Software-Defined Decentralized Domestic Wastewater Treatment : 1st Milestone
- 2020
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Ingår i: Proceedings. - : IEEE. ; , s. 3841-3846
-
Konferensbidrag (refereegranskat)abstract
- Water scarcity has been intensified globally due to the rapid growth of economic and population. Wastewater treatment and recycling is one of the most feasible strategies for meeting the ever-increasing water usage. However, conventional centralized wastewater treatment plants are being stretched to their limits with the emerging urban structures. To mitigate this situation, this paper proposes a decentralized treatment solution for domestic wastewater leveraging the recent advancements in instrumentation, automation, and information technologies. In particular, a 60-ton adjustable secondary wastewater treatment facility has been designed as a foundation, upon which in-situ monitoring, software-centric automation system, and industrial edge-cloud computing platform have been deployed to form a holistic solution. The resultant facility has been consecutively and successfully operating onsite to date.
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| 199. |
- Papadimitriou, Nikos, et al.
(författare)
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Physical activity and risks of breast and colorectal cancer : a Mendelian randomisation analysis
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value=0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value=0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers. Physical activity has been linked to lower risks of colorectal and breast cancer. Here, the authors present a Mendelian randomisation analysis supporting a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer.
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| 200. |
- Paulraj, Thomas, et al.
(författare)
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Porous Cellulose Nanofiber-Based Microcapsules for Biomolecular Sensing
- 2018
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 10:48, s. 41146-41154
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Tidskriftsartikel (refereegranskat)abstract
- Cellulose nanofibers (CNFs) have recently attracted a lot of attention in sensing because of their multifunctional character and properties such as renewability, nontoxicity, biodegradability, printability, and optical transparency in addition to unique physicochemical, barrier, and mechanical properties. However, the focus has exclusively been devoted toward developing two-dimensional sensing platforms in the form of nanopaper or nanocellulose-based hydrogels. To improve the flexibility and sensing performance in situ, for example, to detect biomarkers in vivo for early disease diagnostics, more advanced CNF-based structures are needed. Here, we developed porous and hollow, yet robust, CNF-based microcapsules using only the primary plant cell wall components, CNF, pectin, and xyloglucan, to assemble the capsule wall. The fluorescein isothiocyanate-labeled dextrans with M-w of 70 and 2000 kDa could enter the hollow capsules at a rate of 0.13 +/- 0.04 and 0.014 +/- 0.009 s(-1), respectively. This property is very attractive because it minimizes the influence of mass transport through the capsule wall on the response time. As a proof of concept, glucose oxidase (GOx) enzyme was loaded (and cross-linked) in the microcapsule interior with an encapsulation efficiency of 68 +/- 2%. The GOx-loaded microcapsules were immobilized on a variety of surfaces (here, inside a flow channel, on a carbon-coated sensor or a graphite rod) and glucose concentrations up to 10 mM could successfully be measured. The present concept offers new opportunities in the development of simple, more efficient, and disposable nanocellulose-based analytical devices for several sensing applications including environmental monitoring, healthcare, and diagnostics.
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