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Fabius, J.

Publications and source records attributed to Fabius, J..

4 recordsLinked to original sources

Mapping memory-guided saccade population receptive fields reveals principles of cortical organization along the human intraparietal sulcus

The intraparietal sulcus is a central hub for motor planning and sensorimotor integration. Its responses are known to support coordinate transformations across reference frames and modalities--for example, eye-position gain fields that convert retinotopic, fovea-centred signals into head-centred representations. In the oculomotor domain, the human intraparietal sulcus is sensitive to eye-movement planning and has been extensively studied using memory-guided saccade paradigms. These classic approaches have revealed topographic organization and contralateral sensitivity for preferred direction in saccade planning and execution. However, such designs provide detailed information about preferred direction; they do not probe tuning width: how narrowly or broadly a given cortical location responds around its preferred direction. At present, it remains unclear whether and how tuning width is organized along the human intraparietal sulcus. Critically, neurophysiological studies in non-human primates do not offer systematic and extensive measurements of tuning width. Moreover, the relationship between tuning width and preferred direction at the population level in human intraparietal cortex is unknown. Here, we address these questions using a forward-modelling approach combined with high-field (7-Tesla) functional MRI. We observe contralateral preference for preferred direction in saccade planning and execution, as well as a novel large-scale organization of preferred saccade tuning width, in vivo, in humans. Highlightssaccade planning and execution tuning width is arranged topographically along human early visual cortex and human intraparietal sulcus; specificity of voxel-level saccade planning and execution decreases along the visual hierarchy; specificity of population-level saccade planning and execution increases along the visual hierarchy; forward modelling applied to memory-guided saccade paradigm outperforms the standard phase-encoding approach;

neuroscience↗

Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant

Emergence of SARS-CoV-2 variants, including the globally successful B.1.1.7 lineage, suggests viral adaptations to host selective pressures resulting in more efficient transmission. Although much effort has focused on Spike adaptation for viral entry and adaptive immune escape, B.1.1.7 mutations outside Spike likely contribute to enhance transmission. Here we used unbiased abundance proteomics, phosphoproteomics, mRNA sequencing and viral replication assays to show that B.1.1.7 isolates more effectively suppress host innate immune responses in airway epithelial cells. We found that B.1.1.7 isolates have dramatically increased subgenomic RNA and protein levels of Orf9b and Orf6, both known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein required for RNA sensing adaptor MAVS activation, and Orf9b binding and activity was regulated via phosphorylation. We conclude that B.1.1.7 has evolved beyond the Spike coding region to more effectively antagonise host innate immune responses through upregulation of specific subgenomic RNA synthesis and increased protein expression of key innate immune antagonists. We propose that more effective innate immune antagonism increases the likelihood of successful B.1.1.7 transmission, and may increase in vivo replication and duration of infection.

microbiology↗

Host-directed therapies against early-lineage SARS-CoV-2 retain efficacy against B.1.1.7 variant

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths worldwide and massive societal and economic burden. Recently, a new variant of SARS-CoV-2, known as B.1.1.7, was first detected in the United Kingdom and is spreading in several other countries, heightening public health concern and raising questions as to the resulting effectiveness of vaccines and therapeutic interventions. We and others previously identified host-directed therapies with antiviral efficacy against SARS-CoV-2 infection. Less prone to the development of therapy resistance, host-directed drugs represent promising therapeutic options to combat emerging viral variants as host genes possess a lower propensity to mutate compared to viral genes. Here, in the first study of the full-length B.1.1.7 variant virus, we find two host-directed drugs, plitidepsin (aplidin; inhibits translation elongation factor eEF1A) and ralimetinib (inhibits p38 MAP kinase cascade), as well as remdesivir, to possess similar antiviral activity against both the early-lineage SARS-CoV-2 and the B.1.1.7 variant, evaluated in both human gastrointestinal and lung epithelial cell lines. We find that plitidepsin is over an order of magnitude more potent than remdesivir against both viruses. These results highlight the importance of continued development of host-directed therapeutics to combat current and future coronavirus variant outbreaks.

microbiology↗

Exploring the interaction between the pupillary light response after exogenous attentional cueing and detection performance

Pupil size changes under different light conditions. Whereas this pupillary light response (PLR) has long been regarded to be influenced by luminance only, recent studies indicated the PLR is also modulated by cognitive factors such as the allocation of spatial attention. This attentional modulation of the PLR has previously been hypothesized to facilitate detection and discrimination of visual information. Here, we replicated the finding that the pupil dilates when a cue is presented at the dark side of a screen and constricts when the cue is presented at the bright side, even when the eyes are fixated at the center. Furthermore, we investigated whether this modulation of the PLR, evoked by exogenous shifts of covert attention, facilitates perception operationalized as detection performance for threshold stimuli. Results showed that a larger pupil was indeed related to increased detection performance, although this effect was restricted to conditions in which both cue and target appeared on a dark surface. Our findings are in line with the notion that pupil dilations improve detectability, whereas pupil constrictions enhance discriminability of small stimuli.

neuroscience↗