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| 2. |
- Akbari, Parsa, et al.
(författare)
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Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 373:6550
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale human exome sequencing can identify rare protein-coding variants with a large impact on complex traits such as body adiposity. We sequenced the exomes of 645,626 individuals from the United Kingdom, the United States, and Mexico and estimated associations of rare coding variants with body mass index (BMI). We identified 16 genes with an exome-wide significant association with BMI, including those encoding five brain-expressed G protein-coupled receptors (CALCR, MC4R, GIPR, GPR151, and GPR75). Protein-truncating variants in GPR75 were observed in ∼4/10,000 sequenced individuals and were associated with 1.8 kilograms per square meter lower BMI and 54% lower odds of obesity in the heterozygous state. Knock out of Gpr75 in mice resulted in resistance to weight gain and improved glycemic control in a high-fat diet model. Inhibition of GPR75 may provide a therapeutic strategy for obesity.
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| 3. |
- Verweij, Niek, et al.
(författare)
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Germline Mutations in CIDEB and Protection against Liver Disease
- 2022
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 387:4, s. 332-344
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Exome sequencing in hundreds of thousands of persons may enable the identification of rare protein-coding genetic variants associated with protection from human diseases like liver cirrhosis, providing a strategy for the discovery of new therapeutic targets. METHODS We performed a multistage exome sequencing and genetic association analysis to identify genes in which rare protein-coding variants were associated with liver phenotypes. We conducted in vitro experiments to further characterize associations. RESULTS The multistage analysis involved 542,904 persons with available data on liver aminotransferase levels, 24,944 patients with various types of liver disease, and 490,636 controls without liver disease. We found that rare coding variants in APOB, ABCB4, SLC30A10, and TM6SF2 were associated with increased aminotransferase levels and an increased risk of liver disease. We also found that variants in CIDEB, which encodes a structural protein found in hepatic lipid droplets, had a protective effect. The burden of rare predicted loss-of-function variants plus missense variants in CIDEB (combined carrier frequency, 0.7%) was associated with decreased alanine aminotransferase levels (beta per allele, -1.24 U per liter; 95% confidence interval [CI], -1.66 to -0.83; P=4.8×10-9) and with 33% lower odds of liver disease of any cause (odds ratio per allele, 0.67; 95% CI, 0.57 to 0.79; P=9.9×10-7). Rare coding variants in CIDEB were associated with a decreased risk of liver disease across different underlying causes and different degrees of severity, including cirrhosis of any cause (odds ratio per allele, 0.50; 95% CI, 0.36 to 0.70). Among 3599 patients who had undergone bariatric surgery, rare coding variants in CIDEB were associated with a decreased nonalcoholic fatty liver disease activity score (beta per allele in score units, -0.98; 95% CI, -1.54 to -0.41 [scores range from 0 to 8, with higher scores indicating more severe disease]). In human hepatoma cell lines challenged with oleate, CIDEB small interfering RNA knockdown prevented the buildup of large lipid droplets. CONCLUSIONS Rare germline mutations in CIDEB conferred substantial protection from liver disease.
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| 5. |
- Fonollosa, J., et al.
(författare)
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Biologically inspired computation for chemical sensing
- 2011
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Ingår i: Procedia Comput. Sci.. - : Elsevier BV. ; , s. 226-227
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Konferensbidrag (refereegranskat)abstract
- In this paper, we present how the achievements related to NEUROCHEM project (FP7, Bio-ICT, Grant number 216916) have increased the understanding of the olfactory system and helped to develop novel computing architectures and models for chemical sensing. We present the developed computational models of the olfactory pathway of vertebrates and insects to capture the mechanisms that underlie their chemical information processing abilities. To mimic the biological olfactory epithelium a large scale chemical sensor array has been developed.We also present a robot that demonstrates the chemical search task as a direct application of the computing paradigms extracted.
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| 7. |
- Marco, S., et al.
(författare)
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A biomimetic approach to machine olfaction, featuring a very large-scale chemical sensor array and embedded neuro-bio-inspired computation
- 2014
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Ingår i: Microsystem Technologies. - : Springer Science and Business Media LLC. - 0946-7076 .- 1432-1858. ; 20:4-5, s. 729-742
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Tidskriftsartikel (refereegranskat)abstract
- Biological olfaction outperforms chemical instrumentation in specificity, response time, detection limit, coding capacity, time stability, robustness, size, power consumption, and portability. This biological function provides outstanding performance due, in a large extent, to the unique architecture of the olfactory pathway, which combines a high degree of redundancy and efficient combinatorial coding, with unmatched chemical information processing mechanisms. The last decade has seen important advances in the understanding of the computational primitives underlying the functioning of the olfactory system. The EU-funded Project NEUROCHEM (Bio-ICT-FET- 216916) developed novel computing paradigms and biologically motivated artefacts for chemical sensing, taking its inspiration from the biological olfactory pathway. To demonstrate this approach, a biomimetic demonstrator has been built that features a very large-scale sensor array (65,536 elements) using conducting polymer technology which mimics the olfactory receptor neuron layer. It implements derived computational neuroscience algorithms in an embedded system that interfaces the chemical sensors and processes their signals in real-time. This embedded system integrates abstracted computational models of the main anatomic building blocks in the olfactory pathway: the olfactory bulb, and olfactory cortex in vertebrates (respectively, antennal lobe and mushroom bodies in the insect). For implementation in the embedded processor, an abstraction phase has been carried out in which their processing capabilities are captured by algorithmic solutions implemented in software. Finally, the algorithmic models are tested in mixed chemical plumes with an odour robot having navigation capabilities.
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| 8. |
- Marco, S., et al.
(författare)
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Biologically inspired large scale chemical sensor arrays and embedded data processing
- 2013
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Ingår i: Smart Sensors, Actuators, And Mems VI. - : SPIE - International Society for Optical Engineering. - 9780819495600 ; , s. 876303-
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Konferensbidrag (refereegranskat)abstract
- Biological olfaction outperforms chemical instrumentation in specificity, response time, detection limit, coding capacity, time stability, robustness, size, power consumption, and portability. This biological function provides outstanding performance due, to a large extent, to the unique architecture of the olfactory pathway, which combines a high degree of redundancy, an efficient combinatorial coding along with unmatched chemical information processing mechanisms. The last decade has witnessed important advances in the understanding of the computational primitives underlying the functioning of the olfactory system. EU Funded Project NEUROCHEM (Bio-ICT-FET- 216916) has developed novel computing paradigms and biologically motivated artefacts for chemical sensing taking inspiration from the biological olfactory pathway. To demonstrate this approach, a biomimetic demonstrator has been built featuring a large scale sensor array (65K elements) in conducting polymer technology mimicking the olfactory receptor neuron layer, and abstracted biomimetic algorithms have been implemented in an embedded system that interfaces the chemical sensors. The embedded system integrates computational models of the main anatomic building blocks in the olfactory pathway: The olfactory bulb, and olfactory cortex in vertebrates (alternatively, antennal lobe and mushroom bodies in the insect). For implementation in the embedded processor an abstraction phase has been carried out in which their processing capabilities are captured by algorithmic solutions. Finally, the algorithmic models are tested with an odour robot with navigation capabilities in mixed chemical plumes.
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| 9. |
- Persaud, Shanta J., et al.
(författare)
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Pseudoislets as primary islet replacements for research Report on a symposium at King's College London, London UK
- 2010
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Ingår i: Islets. - : Informa UK Limited. - 1938-2014 .- 1938-2022. ; 2:4, s. 236-239
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Laboratory-based research aimed at understanding processes regulating insulin secretion and mechanisms underlying beta-cell dysfunction and loss in diabetes often makes use of rodents, as these processes are in many respects similar between rats/mice and humans. Indeed, a rough calculation suggests that islets have been isolated from as many as 150,000 rodents to generate the data contained within papers published in 2009 and the first four months of 2010. Rodent use for islet isolation has been mitigated, to a certain extent, by the availability of a variety of insulin-secreting cell lines that are used by researchers world-wide. However, when maintained as monolayers the cell lines do not replicate the robust, sustained secretory responses of primary islets which limits their usefulness as islet surrogates. On the other hand, there have been several reports that configuration of MIN6 beta-cells, derived from a mouse insulinoma, as three-dimensional cell clusters termed 'pseudoislets' largely recapitulates the function of primary islet beta-cells. The Diabetes Research Group at King's College London has been using the MIN6 pseudoislet model for over a decade and they hosted a symposium on "Pseudoislets as primary islet replacements for research", which was funded by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), in London on 15(th) and 16(th) April 2010. This small, focused meeting was conceived as an opportunity to consolidate information on experiences of working with pseudoislets between different UK labs, and to introduce the theory and practice of pseudoislet culture to laboratories working with islets and/or beta-cell lines but who do not currently use pseudoislets. This short review summarizes the background to the development of the cell line-derived pseudoislet model, the key messages arising from the symposium and emerging themes for future pseudoislet research.
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| 10. |
- Rangelow, I. W., et al.
(författare)
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Piezoresistive and self-actuated 128-cantilever arrays for nanotechnology applications
- 2007
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Ingår i: Microelectronic Engineering. - : Elsevier BV. - 0167-9317 .- 1873-5568. ; 84:5-8, s. 1260-1264
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Tidskriftsartikel (refereegranskat)abstract
- A major limitation for future nanotechnology, particularly for bottom-up manufacturing is the non-availability of 2-dimensional massively parallel probe arrays. Scanning proximity probes are uniquely powerful tools for analysis, manipulation and bottom-up synthesis: they are capable of addressing and engineering surfaces at the atomic level and are the key to unlocking the full potential of Nanotechnology. Generic massively parallel intelligent cantilever-probe platforms is demonstrated through a number of existing and ground-breaking techniques. A packaged VLSI NEMS-chip (Very Large Scale Integrated Nano Electro Mechanical System) incorporating 128 proximal probes, fully addressable with control and readout interconnects and advanced software will be presented.
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