University of Dundee

About: University of Dundee is a education organization based out in Dundee, United Kingdom. It is known for research contribution in the topics: Population & Protein kinase A. The organization has 19258 authors who have published 39640 publications receiving 1919433 citations. The organization is also known as: Universitas Dundensis & Dundee University.

Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

Abstract: Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.

Embodied language: A review of the role of the motor system in language comprehension

Abstract: A growing body of research suggests that comprehending verbal descriptions of actions relies on an internal simulation of the described action. To assess this motor resonance account of language comprehension, we first review recent developments in the literature on perception and action, with a view towards language processing. We then examine studies of language processing from an action simulation perspective. We conclude by discussing several criteria that might be helpful with regard to assessing the role of motor resonance during language comprehension.

GSK3 inhibitors: development and therapeutic potential

Abstract: Glycogen synthase kinase-3 (GSK3) was initially identified more than two decades ago as an enzyme involved in the control of glycogen metabolism. In recent years it has been shown to have key roles in regulating a diverse range of cellular functions, which have prompted efforts to develop GSK3 inhibitors as therapeutics. Here, we describe the biology of GSK3 relevant to its potential as a target for diabetes and neurodegenerative diseases, and discuss progress in the development of GSK3 inhibitors.

Beyond Triplet Loss: A Deep Quadruplet Network for Person Re-identification

Abstract: Person re-identification (ReID) is an important task in wide area video surveillance which focuses on identifying people across different cameras. Recently, deep learning networks with a triplet loss become a common framework for person ReID. However, the triplet loss pays main attentions on obtaining correct orders on the training set. It still suffers from a weaker generalization capability from the training set to the testing set, thus resulting in inferior performance. In this paper, we design a quadruplet loss, which can lead to the model output with a larger inter-class variation and a smaller intra-class variation compared to the triplet loss. As a result, our model has a better generalization ability and can achieve a higher performance on the testing set. In particular, a quadruplet deep network using a margin-based online hard negative mining is proposed based on the quadruplet loss for the person ReID. In extensive experiments, the proposed network outperforms most of the state-of-the-art algorithms on representative datasets which clearly demonstrates the effectiveness of our proposed method.

Differential regulation of MAP kinase signalling by dual-specificity protein phosphatases

Abstract: The regulated dephosphorylation of mitogen-activated protein kinases (MAPKs) plays a key role in determining the magnitude and duration of kinase activation and hence the physiological outcome of signalling. In mammalian cells, an important component of this control is mediated by the differential expression and activities of a family of 10 dual-specificity (Thr/Tyr) MAPK phosphatases (MKPs). These enzymes share a common structure in which MAPK substrate recognition is determined by sequences within an amino-terminal non-catalytic domain whereas MAPK binding often leads to a conformational change within the C-terminal catalytic domain resulting in increased enzyme activity. MKPs can either recognize and inactivate a single class of MAP kinase, as in the specific inactivation of extracellular signal regulated kinase (ERK) by the cytoplasmic phosphatase DUSP6/MKP-3 or can regulate more than one MAPK pathway as illustrated by the ability of DUSP1/MKP-1 to dephosphorylate ERK, c-Jun amino-terminal kinase and p38 in the cell nucleus. These properties, coupled with transcriptional regulation of MKP expression in response to stimuli that activate MAPK signalling, suggest a complex negative regulatory network in which individual MAPK activities can be subject to negative feedback control, but also raise the possibility that signalling through multiple MAPK pathways may be integrated at the level of regulation by MKPs.