| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Tobias, Deirdre K, et al.
(författare)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 3. |
- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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| 4. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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| 5. |
- Alenljung, Beatrice, 1971-, et al.
(författare)
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Conveying Emotions by Touch to the Nao Robot : A User Experience Perspective
- 2018
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Ingår i: Multimodal Technologies and Interaction. - : MDPI. - 2414-4088. ; 2:4
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Tidskriftsartikel (refereegranskat)abstract
- Social robots are expected gradually to be used by more and more people in a widerrange of settings, domestic as well as professional. As a consequence, the features and qualityrequirements on human–robot interaction will increase, comprising possibilities to communicateemotions, establishing a positive user experience, e.g., using touch. In this paper, the focus is ondepicting how humans, as the users of robots, experience tactile emotional communication with theNao Robot, as well as identifying aspects affecting the experience and touch behavior. A qualitativeinvestigation was conducted as part of a larger experiment. The major findings consist of 15 differentaspects that vary along one or more dimensions and how those influence the four dimensions ofuser experience that are present in the study, as well as the different parts of touch behavior ofconveying emotions.
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| 6. |
- Alenljung, Beatrice, et al.
(författare)
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User Experience of Conveying Emotions by Touch
- 2017
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Ingår i: Proceedings of the 26th IEEE International Symposium on Robot and Human Interactive Communication (RO-MAN). - : IEEE. - 9781538635179 - 9781538635193 - 9781538635186 ; , s. 1240-1247
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Konferensbidrag (refereegranskat)abstract
- In the present study, 64 users were asked to convey eight distinct emotion to a humanoid Nao robot via touch, and were then asked to evaluate their experiences of performing that task. Large differences between emotions were revealed. Users perceived conveying of positive/pro-social emotions as significantly easier than negative emotions, with love and disgust as the two extremes. When asked whether they would act differently towards a human, compared to the robot, the users’ replies varied. A content analysis of interviews revealed a generally positive user experience (UX) while interacting with the robot, but users also found the task challenging in several ways. Three major themes with impact on the UX emerged; responsiveness, robustness, and trickiness. The results are discussed in relation to a study of human-human affective tactile interaction, with implications for human-robot interaction (HRI) and design of social and affective robotics in particular.
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| 7. |
- Andersson, Lena, et al.
(författare)
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Pancreatic lipase related protein 2, but not classical lipase hydrolyzes galactolipids
- 1996
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002. ; 1302:3, s. 236-240
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Tidskriftsartikel (refereegranskat)abstract
- The pancreatic lipase family contains three subfamilies, the 'classical' lipases and the pancreatic lipase-related proteins 1 (PLRP1) and 2 (PLRP2). Galactolipids are present in membranes of leaves and vegetables and consist of digalactosyldiacylglycerol (DGalDG) monogalactosyldiacylglycerol (MGalDG) and sulfoquinovosyldiacylglycerol (SQDG). These lipids were incubated with PLRP2 from guinea-pig (GPLRP2) and rat (RPLRP2). In the presence of bile salts DGalDG was efficiently hydrolyzed by GPLRP2 and, although less efficiently, by RPLRP2 to digalactosylmonoacylglycerol (DGalMG), free fatty acids and water-soluble galactose-containing compounds. Also, MGalDG and SQDG were hydrolyzed by GPLRP2 and RPLRP2. These data suggest a possible role of PLRP2 in the digestion of dietary galactolipids
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| 8. |
- Andreasson, Rebecca, et al.
(författare)
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Affective Touch in Human-Robot Interaction: Conveying Emotion to the Nao Robot
- 2018
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Ingår i: International Journal of Social Robotics. - : Springer Science and Business Media LLC. - 1875-4791 .- 1875-4805. ; 10:4, s. 473-491
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Tidskriftsartikel (refereegranskat)abstract
- Affective touch has a fundamental role in human development, social bonding, and for providing emotional support in interpersonal relationships. We present, what is to our knowledge, the first HRI study of tactile conveyance of both positive and negative emotions (affective touch) on the Nao robot, and based on an experimental set-up from a study of human-human tactile communication. In the present work, participants conveyed eight emotions to a small humanoid robot via touch. We found that female participants conveyed emotions for a longer time, using more varied interaction and touching more regions on the robot's body, compared to male participants. Several differences between emotions were found such that emotions could be classified by the valence of the emotion conveyed, by combining touch amount and duration. Overall, these results show high agreement with those reported for human-human affective tactile communication and could also have impact on the design and placement of tactile sensors on humanoid robots.
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| 9. |
- Bedford, Lynn, et al.
(författare)
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Depletion of 26S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies
- 2008
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 28:33, s. 8189-98
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Tidskriftsartikel (refereegranskat)abstract
- Ubiquitin-positive intraneuronal inclusions are a consistent feature of the major human neurodegenerative diseases, suggesting that dysfunction of the ubiquitin proteasome system is central to disease etiology. Research using inhibitors of the 20S proteasome to model Parkinson's disease is controversial. We report for the first time that specifically 26S proteasomal dysfunction is sufficient to trigger neurodegenerative disease. Here, we describe novel conditional genetic mouse models using the Cre/loxP system to spatially restrict inactivation of Psmc1 (Rpt2/S4) to neurons of either the substantia nigra or forebrain (e.g., cortex, hippocampus, and striatum). PSMC1 is an essential subunit of the 26S proteasome and Psmc1 conditional knock-out mice display 26S proteasome depletion in targeted neurons, in which the 20S proteasome is not affected. Impairment of specifically ubiquitin-mediated protein degradation caused intraneuronal Lewy-like inclusions and extensive neurodegeneration in the nigrostriatal pathway and forebrain regions. Ubiquitin and alpha-synuclein neuropathology was evident, similar to human Lewy bodies, but interestingly, inclusion bodies contained mitochondria. We support this observation by demonstrating mitochondria in an early form of Lewy body (pale body) from Parkinson's disease patients. The results directly confirm that 26S dysfunction in neurons is involved in the pathology of neurodegenerative disease. The model demonstrates that 26S proteasomes are necessary for normal neuronal homeostasis and that 20S proteasome activity is insufficient for neuronal survival. Finally, we are providing the first reproducible genetic platform for identifying new therapeutic targets to slow or prevent neurodegeneration.
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| 10. |
- Billing, Erik, 1981-, et al.
(författare)
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Finding Your Way from the Bed to the Kitchen: Reenacting and Recombining Sensorimotor Episodes Learned from Human Demonstration
- 2016
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Ingår i: Frontiers in Robotics and Ai. - Lausanne, Switzerland : Frontiers Media SA. - 2296-9144. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Several simulation theories have been proposed as an explanation for how humans and other agents internalize an "inner world" that allows them to simulate interactions with the external real world - prospectively and retrospectively. Such internal simulation of interaction with the environment has been argued to be a key mechanism behind mentalizing and planning. In the present work, we study internal simulations in a robot acting in a simulated human environment. A model of sensory-motor interactions with the environment is generated from human demonstrations and tested on a Robosoft Kompai robot. The model is used as a controller for the robot, reproducing the demonstrated behavior. Information from several different demonstrations is mixed, allowing the robot to produce novel paths through the environment, toward a goal specified by top-down contextual information. The robot model is also used in a covert mode, where the execution of actions is inhibited and perceptions are generated by a forward model. As a result, the robot generates an internal simulation of the sensory-motor interactions with the environment. Similar to the overt mode, the model is able to reproduce the demonstrated behavior as internal simulations. When experiences from several demonstrations are combined with a top-down goal signal, the system produces internal simulations of novel paths through the environment. These results can be understood as the robot imagining an "inner world" generated from previous experience, allowing it to try out different possible futures without executing actions overtly. We found that the success rate in terms of reaching the specified goal was higher during internal simulation, compared to overt action. These results are linked to a reduction in prediction errors generated during covert action. Despite the fact that the model is quite successful in terms of generating covert behavior toward specified goals, internal simulations display different temporal distributions compared to their overt counterparts. Links to human cognition and specifically mental imagery are discussed.
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