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.

Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis

Abstract: We previously reported that Parkinson’s disease (PD) kinase LRRK2 phosphorylates a subset of Rab GTPases on a conserved residue in their switch-II domains (Steger et al., 2016) (PMID: 26824392). Here, we systematically analyzed the Rab protein family and found 14 of them (Rab3A/B/C/D, Rab5A/B/C, Rab8A/B, Rab10, Rab12, Rab29, Rab35 and Rab43) to be specifically phosphorylated by LRRK2, with evidence for endogenous phosphorylation for ten of them (Rab3A/B/C/D, Rab8A/B, Rab10, Rab12, Rab35 and Rab43). Affinity enrichment mass spectrometry revealed that the primary ciliogenesis regulator, RILPL1 specifically interacts with the LRRK2-phosphorylated forms of Rab8A and Rab10, whereas RILPL2 binds to phosphorylated Rab8A, Rab10, and Rab12. Induction of primary cilia formation by serum starvation led to a two-fold reduction in ciliogenesis in fibroblasts derived from pathogenic LRRK2-R1441G knock-in mice. These results implicate LRRK2 in primary ciliogenesis and suggest that Rab-mediated protein transport and/or signaling defects at cilia may contribute to LRRK2-dependent pathologies.

Synaptosomes possess an exocytotic pool of glutamate

Abstract: There is increasing evidence that L-glutamate is a major excitatory neurotransmitter in the central nervous system1,2. Immunocytochemical studies indicate that glutamate within nerve terminals may be concentrated in vesicles3 and glutamate-accumulating vesicles have recently been isolated4. Exocytotic release of glutamate from synaptosomes (isolated nerve terminals) has not been convincingly demonstrated, however, and remains highly controversial5–7. In order to study the kinetics of release of endogenous L-glutamate from guinea pig cerebral cortical synaptosomes we have devised a continuous enzymatic assay. This has enabled us to identify a pool, equivalent to 15–20% of the total synaptosomal glutamate, which is capable of rapid Ca2+-dependent exocytotic release.

On the cognitive link between space and number: a meta-analysis of the SNARC effect

Abstract: An association of numbers and space (SNARC effect) has been examined in an ever growing literature. In the present quantitative meta-analysis, 46 studies with a total of 106 experiments and 2,206 participants were examined. Deeper number magnitude processing determined by task, stimulus and participants characteristics was associated with a stronger SNARC effect. In magnitude classification tasks the SNARC effect assumed consistently a categorical shape. Furthermore, the SNARC effect was found to increase with age from childhood to elderly age. No specific difference in the size of the SNARC effect was observed due to the explicit use of imagery strategies that could not be explained by increased reaction times. In general, these results corroborate the predictions by the dual-route model of the SNARC effect regarding the activation of number magnitude representation and suggest that automaticity may play a role in the development of the association of numbers and space across the lifespan. Key words: SNARC, mental number line, aging, imagery, meta-analysis In 1993, Dehaene, Bossini, and Giraux showed that small numbers (e.g., 0 or 1) were associated with faster left hand responses, and larger numbers (e.g., 8 or 9) with faster right hand responses (Figure 1A). This result held for single- (Experiment 1) as well as two-digit numbers (Experiment 2) and was not affected by whether participants were left-hand dominant (Experiment 5), or crossed their hands on the response buttons (Experiment 6). The effect did, however, depend on the relative magnitude of numbers in the stimulus set (Experiment 3) and was reduced in participants with right-to-left reading habits (Experiment 7). A similar spatial association was absent for letters (Experiment 4) but present when participants categorized number words (Experiments 8 and 9). Dehaene et al. (1993) concluded that numbers are systematically associated with space, and that this association reflects the orientation of a "mental number line". Specifically, the authors proposed that "...the representation of number magnitude is automatically accessed during parity judgment of Arabic digits. This representation may be linked to a mental number line [...], because it bears a natural and seemingly irrepressible correspondence with the natural left - right coordinates of external space. " (p. 394). Recently, Proctor and Cho (2006) proposed an alternative explanation for the SNARC effect based on polarity correspondence that contests the necessity of assuming the existence of a mental number line. The polarity correspondence account is a general theory of compatibility effects and does not require a spatially oriented mental number line to explain the SNARC effect. Proctor and Cho (2006) argue that the polarity assigned to each stimulus and response depends on the relative saliency of their dimensions. Instead of perceptual or conceptual similarity, the polarity categorization suffices to produce the mapping of stimuli onto responses. This account is based on the activation of positive or negative polarities for different dimensions and is applicable not only to the SNARC effect but also to non-numerical experimental set-ups. When the same polarity ("+" or "-") is assigned to different dimensions of the experimental set-up (e.g., stimuli and responses), they become associated. When applied to the domain of numerical processing, both "right" and "large" have polarity "+" while both "left" and "small" have polarity "-". When the polarities of stimulus and response overlap, a link is established regardless of perceptual, spatial or conceptual overlap, improving performance. Although the polarity correspondence account offers a parsimonious explanation for the SNARC effect in speeded binary classification tasks, some new evidence from cognitive neuropsychology lends support to the existence and relevance of a mental number line for the formation of spatial numerical associations (Zorzi et al. …

A molecular mechanical force field for the conformational analysis of oligosaccharides: comparison of theoretical and crystal structures of Man alpha 1-3Man beta 1-4GlcNAc.

Abstract: A molecular mechanical force field is described for the conformational analysis of oligosaccharides. This force field has been derived by the addition of new parameters to the AMBER force field and is compatible with simulations of proteins. This new parametrization is assessed by comparison of the theoretically predicted conformations of Man alpha 1-3Man beta 1-4GlcNAc with the corresponding crystal structure. Molecular dynamics simulation data are presented for this structure both in vacuo and with the explicit inclusion of water molecules. While the former demonstrate significant torsional oscillations about glycosidic linkages at physiological temperature, in the latter these oscillations are highly damped due to the stabilizing influence of a "cage" of solvent-solvent and solvent-solute hydrogen bonds.