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Stevenson, N.

Publications and source records attributed to Stevenson, N..

11 recordsLinked to original sources

Pheromones induce visuomotor arousal in jumping spiders

Perception in one sensory modality can be influenced by stimulation in another modality. Such cross-modal effects may arise from multiple underlying processes. For example, animals may be primed by exposure to a cue in one sensory modality and attend to congruent cues in a separate modality. In contrast, input from one sensory modality may result in a general increase in arousal, which in turn influences behavior. Jumping spiders (Salticidae) are famously visual animals but they also respond to pheromones. Here, we test whether pheromones influence visual attention in Phidippus jumping spiders and, if so, whether we see evidence of priming to relevant stimuli or simply an increase in arousal. In Experiment 1, male spiders exposed to female pheromones increased their movements in an arena, a sign of physiological arousal associated with mate searching, whereas females decreased their movements in response to male pheromones. In Experiment 2, freely moving male spiders exposed to female pheromones were more likely to detect and court an image of a female. In Experiment 3, male spiders were shown a series of images of conspecifics, crickets, and abstract shapes as we visualized the gaze direction of their principal eyes using a specialized eyetracker. When pheromones were present, retinal movement markedly increased, but this effect did not differ by stimulus category. Spiders showed greater retinal movement during presentations of crickets and front-facing female conspecifics than during presentations of side-view male conspecifics, regardless of pheromone exposure. In Experiment 4, spiders were shown an array of stimuli, but spiders did not preferentially look at a conspecific stimulus with pheromone exposure. In a second iteration of Experiment 4 with male spiders tested in both control and pheromone conditions, however, pheromone-exposed males looked longer at a front-facing female than at an abstract shape. In Experiment 5, spiders were presented with a salient image of a conspecific of the opposite sex. With pheromone exposure, males were more likely to divert their gaze away from the initial stimulus to an oval distractor, while females were less likely to divert their gaze than controls, mirroring sex-specific shifts in activity from Experiment 1. Increased male movement may enhance encounters, whereas reduced female movement may facilitate being found and evaluating male displays. While we found only limited evidence that spiders were primed to direct their attention toward congruent stimuli, our results show pheromones influence vision, specifically by affecting the spiders' propensity to move their bodies and eyes.

animal behavior and cognition↗

Distinct roles for TANGO1S domains in maintaining ER-Golgi architecture

The endoplasmic reticulum (ER)-Golgi interface is a dynamic trafficking hub maintained in part by TANGO1, a scaffolding protein that coordinates proteins and membranes at ER exit sites (ERES). TANGO1 has two isoforms: TANGO1L, which has a lumenal SH3 domain, and TANGO1S, which lacks this domain but retains the transmembrane and cytoplasmic coiled coil (CC), TEER, and PRD domains common to both forms. We showed previously that loss of both isoforms disrupts ER - Golgi organization more severely than TANGO1L loss alone, indicating TANGO1S is functional and can compensate. Here we dissect the role of each TANGO1 cytoplasmic domain in maintaining secretory pathway organisation by expressing TANGO1S domain-deletion mutants in TANGO1L-/S- knockout cells. We show that TANGO1 loss causes cis-Golgi vesiculation that cannot be rescued by TANGO1S. TANGO1S re-expression also failed to rescue COPII and Sec16 recruitment in this cell line. Meanwhile, the TEER domain is essential for the organisation of the ER, and the TEER, CC2 and PRD domain are required for a defined ERGIC. This study represents an advance towards a domain-level resolution of TANGO1S function.

cell biology↗

Joint models reveal human subcortical underpinnings of choice and learning behaviour

Decision making and learning processes together enable adaptive goal-oriented behaviour. Animal studies demonstrated the importance of subcortical regions in these cognitive processes, but the human subcortical contributions remain poorly characterised. Here, we study choice and learning processes in the human subcor-tex, using a tailored ultra-high field 7 T fMRI imaging protocol combined with joint models. Joint models provide unbiased estimates of brain-behaviour rela-tions by simultaneously including behavioural and neural data at the participant and group level. Results demonstrate relations between subcortical regions and the adjustment of decision urgency. Value-related BOLD differences were found with opposite BOLD polarity in different parts of the striatum. Multiple sub-cortical regions showed BOLD signatures of reward prediction error processing, but contrary to expectations, these did not include the dopaminergic midbrain. Combined, this study characterises the human subcortical contributions to choice and learning, and demonstrates the feasibility and value of joint modelling in facilitating our understanding of brain-behaviour relationships.

neuroscience↗

Golgins support extracellular matrix secretion by collectively maintaining the Golgi structure-function relationship

The secretion of extracellular matrix (ECM) proteins is vital to the maintenance of tissue health. One major control point of this process is the Golgi apparatus, whose dysfunction causes numerous connective tissue disorders. Golgi function is tightly linked to its structure, which is maintained by the cytoskeleton and Golgi organising proteins. We sought to investigate the role of two of these organising proteins, the golgins GMAP210 and Golgin-160, in ECM secretion. We found that loss of either protein had distinct impacts on Golgi organisation. GMAP210 loss caused cisternal fragmentation and dilation, alongside the accumulation of tubulovesicular structures. Meanwhile, Golgin-160 knockout lead to Golgi fragmentation and vesicle build-up. Nonetheless, loss of each protein had a similar impact on ECM secretion and glycosaminoglycan synthesis. We therefore propose that golgins are collectively required to create the correct physical-chemical space to support efficient ECM protein secretion and modification. This is the first time that Golgin-160 has been shown to be required for ECM secretion. SummaryIn this study, Thompson et al demonstrate that two cis-Golgi golgins, GMAP210 and Golgin-160, have distinct, non-redundant roles in maintaining Golgi organisation and that both are required to support the efficient secretion, assembly, and modification of extracellular matrix proteins.

cell biology↗

The canonical stopping network: Revisiting the role of the subcortex in response inhibition

This study investigates the functional network underlying response inhibition in the human brain, particularly the role of the basal ganglia in successful action cancellation. Functional magnetic resonance imaging (fMRI) approaches have frequently used the stop-signal task (SST) to examine this network. We merge five such datasets, using a novel aggregatory method allowing the unification of raw fMRI data across sites. This meta-analysis, along with other recent aggregatory fMRI studies, does not find evidence for the innervation of the hyperdirect or indirect cortico-basal-ganglia pathways in successful response inhibition. What we do find, is large subcortical activity profiles for failed stop trials. We discuss possible explanations for the mismatch of findings between the fMRI results presented here and results from other research modalities that have implicated nodes of the basal ganglia in successful inhibition. We also highlight the substantial effect smoothing can have on the conclusions drawn from task-specific GLMs. First and foremost, this study presents a proof of concept for meta-analytical methods that enable the merging of extensive, unprocessed or unreduced datasets. It demonstrates the significant potential that open-access data sharing can offer to the research community. With an increasing number of datasets being shared publicly, researchers will have the ability to conduct meta-analyses on more than just summary data.

neuroscience↗

Clinical mutations in WDR34 lead to diverse impacts on the assembly and function of dynein-2

The primary cilium is a sensory organelle, receiving signals from the external environment and relaying them into the cell. Mutations in proteins required for transport in the primary cilium result in ciliopathies, a group of genetic disorders that commonly lead to the malformation of organs such as the kidney, liver and eyes and skeletal dysplasias. Motor proteins dynein-2 and kinesin-2 mediate retrograde and anterograde transport respectively in the cilium. WDR34, a dynein-2 intermediate chain, is required for the maintenance of cilia function. Here, we investigated WDR34 mutations identified in Jeune syndrome, short-rib polydactyly syndrome or asphyxiating thoracic dysplasia patients. There is a poor correlation between genotype and phenotype in these cases making diagnosis and treatment highly complex. We set out to define the biological impacts on cilia formation and function of WDR34 mutations by stably expressing the mutant proteins in WDR34 knockout cells. WDR34 mutations led to different spectrums of phenotypes. Quantitative proteomics demonstrated changes in dynein-2 assembly, whereas initiation and extension of the axoneme, IFT-B protein localization, transition zone (TZ) integrity, and Hedgehog signalling were also affected. Summary statementDisease-associated mutations in WDR34 are found to have diverse impacts on ciliogenesis and cilia function following stable expression in a WDR34 knockout cell model.

cell biology↗

Automated detection of artefacts in neonatal EEG with residual neural networks

Background and ObjectiveTo develop a computational algorithm that detects and identifies different artefact types in neonatal electroencephalography (EEG) signals. MethodsAs part of a larger algorithm, we trained a Residual Deep Neural Network on expert human annotations of EEG recordings from 79 term infants recorded in a neonatal intensive care unit (112 h of 18-channel recording). The network was trained using 10 fold cross validation in Matlab. Artefact types included: device interference, EMG, movement, electrode pop, and non-cortical biological rhythms. Performance was assessed by prediction statistics and further validated on a separate independent dataset of 13 term infants (143 h of 3-channel recording). EEG pre-processing steps, and other post-processing steps such as averaging probability over a temporal window, were also included in the algorithm. ResultsThe Residual Deep Neural Network showed high accuracy (95%) when distinguishing periods of clean, artefact-free EEG from any kind of artefact, with a median accuracy for individual patient of 91% (IQR: 81%-96%). The accuracy in identifying the five different types of artefacts ranged from 57%-92%, with electrode pop being the hardest to detect and EMG being the easiest. This reflected the proportion of artefact available in the training dataset. Misclassification as clean was low for each artefact type, ranging from 1%-11%. The detection accuracy was lower on the validation set (87%). We used the algorithm to show that EEG channels located near the vertex were the least susceptible to artefact. ConclusionArtefacts can be accurately and reliably identified in the neonatal EEG using a deep learning algorithm. Artefact detection algorithms can provide continuous bedside quality assessment and support EEG review by clinicians or analysis algorithms. HighlightsO_LIWe applied a Residual Deep Neural Network as part of an artefact detection algorithm in neonatal electroencephalograms. C_LIO_LIThe algorithm shows high accuracy in identifying artefactual data in general and for specific artefact types. C_LIO_LIEEG channels near the top of the head are less prone to artefact. C_LI

neuroscience↗

Giantin is required for 1 intracellular N-terminal processing of type I procollagen

Knockout of the golgin giantin leads to skeletal and craniofacial defects driven by poorly studied changes in glycosylation and extracellular matrix deposition. Here, we sought to determine how giantin impacts the production of healthy bone tissue by focussing on the main protein component of the osteoid, type I collagen. Giantin mutant zebrafish accumulate multiple spontaneous fractures in their caudal fin, suggesting their bones may be more brittle. Inducing new experimental fractures revealed defects in the mineralisation of newly deposited collagen as well as diminished procollagen reporter expression in mutant fish. Analysis of giantin knockout cells expressing a GFP-tagged procollagen showed that procollagen trafficking is independent of giantin. However, our data show that intracellular N-propeptide processing of pro-1(I) is defective in the absence of giantin. These data demonstrate a conserved role for giantin in collagen biosynthesis and extracellular matrix assembly. Our work also provides evidence of a giantin-dependent pathway for intracellular procollagen processing.

cell biology↗

ER-to-Golgi trafficking of procollagen in the absence of large carriers.

Secretion and assembly of collagen is fundamental to the function of the extracellular matrix. Defects in the assembly of a collagen matrix lead to pathologies including fibrosis and osteogenesis imperfecta. Owing to the size of fibril-forming procollagen molecules it is assumed that they are transported from the endoplasmic reticulum to the Golgi in specialised large COPII-dependent carriers. Here, analysing endogenous procollagen and a new engineered GFP-tagged form, we show that transport to the Golgi occurs in the absence of large carriers. Large GFP-positive structures are observed occasionally but these are non-dynamic, are not COPII-positive, and label with markers of the ER. We propose a \"short-loop\" model of COPII-dependent ER-to-Golgi traffic that, while consistent with models of ERGIC-dependent expansion of COPII carriers, does not invoke long-range trafficking of large vesicular structures. Our findings provide an important insight into the process of procollagen trafficking and reveal a short-loop pathway from the ER to the Golgi, without the use of large carriers.\n\nSummaryTrafficking of procollagen is essential for normal cell function. Here, imaging of GFP-tagged type I procollagen reveals that it is transported from the endoplasmic reticulum to the Golgi, without the use of large carriers.

cell biology↗

Regulator of calcineurin-2 is a ciliary protein with a role in cilia length control.

Almost every cell in the human body extends a primary cilium. Defective cilia function leads to a set of disorders known as ciliopathies characterised by debilitating developmental defects affecting many tissues. Here we report a new role for regulator of calcineurin 2, RCAN2, in primary cilia function. It localises to centrioles and the basal body and is required to maintain normal cilia length. RCAN2 was identified as the most strongly upregulated gene from a comparative RNAseq analysis of cells in which expression of the Golgi matrix protein giantin had been abolished by gene editing. In contrast to previous work where we showed that depletion of giantin by RNAi results in defects in ciliogenesis and in cilia length control, giantin knockout cells generate normal cilia on serum withdrawal. Furthermore, giantin knockout zebrafish show increased expression of RCAN2. Importantly, suppression of RCAN2 expression in giantin knockout cells results in the same defects in cilia length control seen on RNAi of giantin itself. Together these data define RCAN2 as a regulator of cilia function that can compensate for loss of giantin function.

cell biology↗

Giantin Knockout Models Reveal The Capacity Of The Golgi To Regulate Its Biochemistry By Controlling Glycosyltransferase Expression

The Golgi is the cellular hub for complex glycosylation, controlling accurate processing of complex proteoglycans, receptors, ligands, and glycolipids. Its structure and organisation is dependent on golgins, which tether cisternal membranes and incoming transport vesicles. Here we show that knockout of the largest golgin, giantin, leads to substantial changes in gene expression despite only limited effects on Golgi structure. Notably, 22 Golgi-resident glycosyltransferases, but not glycan processing enzymes or the ER glycosylation machinery, are differentially expressed following giantin ablation. This includes near-complete loss-of-function of GALNT3 in both mammalian cell and zebrafish models. Giantin knockout zebrafish exhibit hyperostosis and ectopic calcium deposits, recapitulating phenotypes of hyperphosphatemic familial tumoral calcinosis, a disease caused by mutations in GALNT3. These data reveal a new feature of Golgi homeostasis, the ability to regulate glycosyltransferase expression to generate a functional proteoglycome.\n\nSummary statementKnockout of giantin in a genome-engineered cell line and zebrafish models reveals the capacity of the Golgi to control its own biochemistry through changes in gene expression.

cell biology↗