| 1. |
- Brenner, David, et al.
(författare)
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Hot-spot KIF5A mutations cause familial ALS
- 2018
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 141, s. 688-697
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Tidskriftsartikel (refereegranskat)abstract
- Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de novo frame-shift mutations in the C-terminal domain of KIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings, together with the observation that many of the disease genes associated with amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular transport, led us to hypothesize that mutations in KIF5A are also a cause of amyotrophic lateral sclerosis. Using whole exome sequencing followed by rare variant analysis of 426 patients with familial amyotrophic lateral sclerosis and 6137 control subjects, we detected an enrichment of KIF5A splice-site mutations in amyotrophic lateral sclerosis (2/426 compared to 0/6137 in controls; P = 4.2 x 10-3), both located in a hot-spot in the C-terminus of the protein and predicted to affect splicing exon 27. We additionally show co-segregation with amyotrophic lateral sclerosis of two canonical splice-site mutations in two families. Investigation of lymphoblast cell lines from patients with KIF5A splice-site mutations revealed the loss of mutant RNA expression and suggested haploinsufficiency as the most probable underlying molecular mechanism. Furthermore, mRNA sequencing of a rare non-synonymous missense mutation (predicting p. Arg1007Gly) located in the C-terminus of the protein shortly upstream of the splice donor of exon 27 revealed defective KIF5A pre-mRNA splicing in respective patient-derived cell lines owing to abrogation of the donor site. Finally, the non-synonymous single nucleotide variant rs113247976 (minor allele frequency = 1.00% in controls, n = 6137), also located in the C-terminal region [p.(Pro986Leu) in exon 26], was significantly enriched in familial amyotrophic lateral sclerosis patients (minor allele frequency = 3.40%; P = 1.28 x 10-7). Our study demonstrates that mutations located specifically in a C-terminal hotspot of KIF5A can cause a classical amyotrophic lateral sclerosis phenotype, and underline the involvement of intracellular transport processes in amyotrophic lateral sclerosis pathogenesis.
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| 2. |
- Fortmann, Jutta, et al.
(författare)
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Demo Hour
- 2015
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Ingår i: Interactions. - 1072-5520. ; 22:1, January + February 2015, s. 6-9
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Tidskriftsartikel (refereegranskat)abstract
- NordiCHI'14 conference attendees got hands-on experience with a number of great new interactive systems. Among the accepted poster, video, and demo submissions, we selected the following four prototypes to illustrate the high-quality design research displayed during the conference, which was held in Helsinki, Finland, October 26--30, 2014.
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| 3. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 4. |
- Matviienko, Andrii, et al.
(författare)
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Deriving design guidelines for ambient light systems
- 2015
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Ingår i: MUM 2015 - Proceedings of the 14th International Conference on Mobile and Ubiquitous Multimedia. - New York, NY, USA : Association for Computing Machinery (ACM). ; , s. 268-277
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Konferensbidrag (refereegranskat)abstract
- Recent interest in the development of ambient light systems has initialized a new research area, where the number of ambient light systems is expected to increase in the next years. To support the development of future ambient light systems, we need clear, explicit, and structured design guidelines. In this paper we present an evaluation of light patterns in a controlled laboratory study with two complementary parts. In the first part, our aim was to reveal and analyze light patterns that encode different types of everyday information. In the second part, we verified the results from the first part by asking another group of participants about their understanding of information encoded with light. Together, our results allowed us to establish light patterns and guidelines for building new ambient light systems and applications in the future.
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| 5. |
- Matviienko, Andrii, et al.
(författare)
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Towards new ambient light systems : A close look at existing encodings of ambient light systems
- 2015
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Ingår i: IxD&A. - : Scuola Iad. - 1826-9745 .- 2283-2998. ; 26:1, s. 10-24
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Tidskriftsartikel (refereegranskat)abstract
- Ambient systems provide information in the periphery of a user's attention. Their aim is to present information as unobtrusively as possible to avoid interrupting primary tasks (e.g. writing or reading). In recent years, light has been used to create ambient systems to display information. Examples of ambient light systems range from simple notification systems such as displaying messages or calendar event reminders, to more complex systems such as focusing on conveying information regarding health activity tracking. However, for ambient light systems, there is a broad design space that lacks guidelines on when to make use of light displays and how to design them. In this paper we provide a systematic overview of existing ambient light systems over four identified information classes derived from 72 existing ambient light systems. The most prominent encoding parameters among the surveyed ambient light systems are color, brightness, and their combination. By analyzing existing ambient light systems, we provide a first step towards developing guidelines for designing future ambient light systems.
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| 6. |
- Müller, Florian, et al.
(författare)
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Towards a conceptual framework for explaining variation in nocturnal departure time of songbird migrants
- 2016
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Ingår i: Movement Ecology. - : Springer Science and Business Media LLC. - 2051-3933. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Most songbird migrants travel between their breeding areas and wintering grounds by a series of nocturnal flights. The exact nocturnal departure time for these flights varies considerably between individuals even of the same species. Although the basic circannual and circadian rhythms of songbirds, their adaptation to migration, and the factors influencing the birds' day-to-day departure decision are reasonably well studied, we do not understand how birds time their departures within the night. These decisions are crucial, because the nocturnal departure time defines the potential flight duration of the migratory night. The distances covered during the nocturnal migratory flights in the course of migration in turn directly affect the overall speed of migration. To understand the factors influencing the arrival of the birds in the breeding/wintering areas, we need to investigate the mechanisms that control nocturnal departure time. Here, we provide the first conceptual framework for explaining the variation commonly observed in this migratory trait. The basic schedule of nocturnal departure is likely regulated by both the circannual and circadian rhythms of the innate migration program. We postulate that the endogenously controlled schedule of nocturnal departures is modified by intrinsic and extrinsic factors. So far there is only correlative evidence that birds with a high fuel load or a considerable increase in fuel load and significant wind (flow) assistance towards their migratory goal depart early within the night. In contrast, birds migrating with little fuel and under unfavorable wind conditions show high variation in their nocturnal departure time. The latter may contain an unknown proportion of nocturnal movements not directly related to migratory flights. Excluding such movements is crucial to clearly identify the main drivers of the variation in nocturnal departure time. In general we assume that the observed variation in the nocturnal departure time is explained by individually different reactions norms of the innate migration program to both intrinsic and extrinsic factors.
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