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Publications in Health Sciences by NOMIS researchers

Genetic determinants of survival in progressive supranuclear palsy: a genome-wide association study

NOMIS Researcher(s)

Published in

February 1, 2021

Background: The genetic basis of variation in the progression of primary tauopathies has not been determined. We aimed to identify genetic determinants of survival in progressive supranuclear palsy (PSP). Methods: In stage one of this two stage genome-wide association study (GWAS), we included individuals with PSP, diagnosed according to pathological and clinical criteria, from two separate cohorts: the 2011 PSP GWAS cohort, from brain banks based at the Mayo Clinic (Jacksonville, FL, USA) and in Munich (Germany), and the University College London PSP cohort, from brain banks and the PROSPECT study, a UK-wide longitudinal study of patients with atypical parkinsonian syndromes. Individuals were included if they had clinical data available on sex, age at motor symptom onset, disease duration (from motor symptom onset to death or to the date of censoring, Dec 1, 2019, if individuals were alive), and PSP phenotype (with reference to the 2017 Movement Disorder Society criteria). Genotype data were used to do a survival GWAS using a Cox proportional hazards model. In stage two, data from additional individuals from the Mayo Clinic brain bank, which were obtained after the 2011 PSP GWAS, were used for a pooled analysis. We assessed the expression quantitative trait loci (eQTL) profile of variants that passed genome-wide significance in our GWAS using the Functional Mapping and Annotation of GWAS platform, and did colocalisation analyses using the eQTLGen and PsychENCODE datasets. Findings: Data were collected and analysed between Aug 1, 2016, and Feb 1, 2020. Data were available for 1001 individuals of white European ancestry with PSP in stage one. We found a genome-wide significant association with survival at chromosome 12 (lead single nucleotide polymorphism rs2242367, p=7·5 × 10−10, hazard ratio 1·42 [95% CI 1·22–1·67]). rs2242367 was associated with survival in the individuals added in stage two (n=238; p=0·049, 1·22 [1·00–1·48]) and in the pooled analysis of both stages (n=1239; p=1·3 × 10−10, 1·37 [1·25–1·51]). An eQTL database screen revealed that rs2242367 is associated with increased expression of LRRK2 and two long intergenic non-coding RNAs (lncRNAs), LINC02555 and AC079630.4, in whole blood. Although we did not detect a colocalisation signal for LRRK2, analysis of the PSP survival signal and eQTLs for LINC02555 in the eQTLGen blood dataset revealed a posterior probability of hypothesis 4 of 0·77, suggesting colocalisation due to a single shared causal variant. Interpretation: Genetic variation at the LRRK2 locus was associated with survival in PSP. The mechanism of this association might be through a lncRNA-regulated effect on LRRK2 expression because LINC02555 has previously been shown to regulate LRRK2 expression. LRRK2 has been associated with sporadic and familial forms of Parkinson’s disease, and our finding suggests a genetic overlap with PSP. Further functional studies will be important to assess the potential of LRRK2 modulation as a disease-modifying therapy for PSP and related tauopathies. Funding: PSP Association, CBD Solutions, Medical Research Council (UK).

Research field(s)
Health Sciences, Clinical Medicine, Neurology & Neurosurgery

DOI
10.1016/S1474-4422(20)30394-X

Developmental mechanisms underlying circuit wiring: Novel insights and challenges ahead

NOMIS Researcher(s)

Published in

February 1, 2021

Synaptic connectivity within neural circuits is characterized by high degrees of cellular and subcellular specificity. This precision arises from the combined action of several classes of molecular cues, transmembrane receptors, secreted cues and extracellular matrix components, coordinating transitions between axon guidance, dendrite patterning, axon branching and synapse specificity. We focus this review on recent insights into some of the molecular and cellular mechanisms controlling these transitions and present the results of large-scale efforts and technological developments aimed at mapping neural connectivity at single cell resolution in the mouse cortex as a mammalian model organism. Finally, we outline some of the technical and conceptual challenges lying ahead as the field is starting to explore one of the most challenging problems in neuroscience: the molecular and cellular logic underlying the emergence of the connectome characterizing specific circuits within the central nervous system of mammals.

Research field(s)
Health Sciences, Clinical Medicine, Neurology & Neurosurgery

DOI
10.1016/j.conb.2020.12.013

Neural divergence and convergence for attention to and detection of interoceptive and somatosensory stimuli

NOMIS Researcher(s)

Published in

February 1, 2021

Body awareness is constructed by signals originating from within and outside the body. How do these apparently divergent signals converge? We developed a signal detection task to study the neural convergence and divergence of interoceptive and somatosensory signals. Participants focused on either cardiac or tactile events and reported their presence or absence. Beyond some evidence of divergence, we observed a robust overlap in the pattern of activation evoked across both conditions in frontal areas including the insular cortex, as well as parietal and occipital areas, and for both attention and detection of these signals. Psycho-physiological interaction analysis revealed that right insular cortex connectivity was modulated by the conscious detection of cardiac compared to somatosensory sensations, with greater connectivity to occipito-parietal regions when attending to cardiac signals. Our findings speak in favour of the inherent convergence of bodily-related signals and move beyond the apparent antagonism between exteroception and interoception.

Research field(s)
Health Sciences, Psychology & Cognitive Sciences, Experimental Psychology

DOI
10.1016/j.cortex.2020.11.019

A neuronal blood marker is associated with mortality in old age

NOMIS Researcher(s)

Published in

February 1, 2021

Neurofilament light chain (NfL) has emerged as a promising blood biomarker for the progression of various neurological diseases. NfL is a structural protein of nerve cells, and elevated NfL levels in blood are thought to mirror damage to the nervous system. We find that plasma NfL levels increase in humans with age (n = 122; 21–107 years of age) and correlate with changes in other plasma proteins linked to neural pathways. In centenarians (n = 135), plasma NfL levels are associated with mortality equally or better than previously described multi-item scales of cognitive or physical functioning, and this observation was replicated in an independent cohort of nonagenarians (n = 180). Plasma NfL levels also increase in aging mice (n = 114; 2–30 months of age), and dietary restriction, a paradigm that extends lifespan in mice, attenuates the age-related increase in plasma NfL levels. These observations suggest a contribution of nervous system functional deterioration to late-life mortality.

Research field(s)
Health Sciences, Biomedical Research, Developmental Biology

DOI
10.1038/s43587-021-00028-4

Manipulation of single neural stem cells and neurons in brain slices using robotic microinjection

NOMIS Researcher(s)

Published in

January 1, 2021

A central question in developmental neurobiology is how neural stem and progenitor cells form the brain. To answer this question, one needs to label, manipulate, and follow single cells in the brain tissue with high resolution over time. This task is extremely challenging due to the complexity of tissues in the brain. We have recently developed a robot, that guide a microinjection needle into brain tissue upon utilizing images acquired from a microscope to deliver femtoliter volumes of solution into single cells. The robotic operation increases resulting an overall yield that is an order of magnitude greater than manual microinjection and allows for precise labeling and flexible manipulation of single cells in living tissue. With this, one can microinject hundreds of cells within a single organotypic slice. This article demonstrates the use of the microinjection robot for automated microinjection of neural progenitor cells and neurons in the brain tissue slices. More broadly, it can be used on any epithelial tissue featuring a surface that can be reached by the pipette. Once set up, the microinjection robot can execute 15 or more microinjections per minute. The microinjection robot because of its throughput and versality will make microinjection a broadly straightforward high-performance cell manipulation technique to be used in bioengineering, biotechnology, and biophysics for performing single-cell analyses in organotypic brain slices.

Research field(s)
Health Sciences, Clinical Medicine, Neurology & Neurosurgery

DOI
10.3791/61599

Cortical thickness across the lifespan in a Colombian cohort with autosomal-dominant Alzheimer’s disease: A cross-sectional study

NOMIS Researcher(s)

Published in

January 1, 2021

Introduction: Cortical thinning is a marker of neurodegeneration in Alzheimer’s disease (AD). We investigated the age-related trajectory of cortical thickness across the lifespan (9-59 years) in a Colombian kindred with autosomal dominant AD (ADAD). Methods: Two hundred eleven participants (105 presenilin-1 [PSEN1] E280A mutation carriers, 16 with cognitive impairment; 106 non-carriers) underwent magnetic resonance imaging. A piecewise linear regression identified change-points in the age-related trajectory of cortical thickness in carriers and non-carriers. Results: Unimpaired carriers exhibited elevated cortical thickness compared to non-carriers, and thickness more negatively correlated with age and cognition in carriers relative to non-carriers. We found increased cortical thickness in child carriers, after which thickness steadied compared to non-carriers prior to a rapid reduction in the decade leading up to the expected age at cognitive impairment in carriers. Discussion: Findings suggest that cortical thickness may fluctuate across the ADAD lifespan, from early-life increased thickness to atrophy proximal to clinical onset.

Research field(s)
Health Sciences, Clinical Medicine, Neurology & Neurosurgery

DOI
10.1002/dad2.12233

PET evidence of preclinical cerebellar amyloid plaque deposition in autosomal dominant Alzheimer’s disease-causing Presenilin-1 E280A mutation carriers

NOMIS Researcher(s)

Published in

January 1, 2021

Background: In contrast to sporadic Alzheimer’s disease, autosomal dominant Alzheimer’s disease (ADAD) is associated with greater neuropathological evidence of cerebellar amyloid plaque (Aβ) deposition. In this study, we used positron emission tomography (PET) measurements of fibrillar Aβ burden to characterize the presence and age at onset of cerebellar Aβ deposition in cognitively unimpaired (CU) Presenilin-1 (PSEN1) E280A mutation carriers from the world’s largest extended family with ADAD. Methods: 18F florbetapir and 11C Pittsburgh compound B (PiB) PET data from two independent studies – API ADAD Colombia Trial (NCT01998841) and Colombia-Boston (COLBOS) longitudinal biomarker study were included. The tracers were selected independently by the respective sponsors prior to the start of each study and used exclusively throughout. Template-based cerebellar Aβ-SUVR (standard-uptake value ratios) using a known-to-be-spared pons reference region (cerebellar SUVR_pons), to a) compare 28–56-year-old CU carriers and non-carriers; b) estimate the age at which cerebellar SUVR_pons began to differ significantly in carrier and non-carrier groups; and c) characterize in carriers associations with age, cortical SUVR_pons, delayed recall memory, and API ADAD composite score. Results: Florbetapir and PiB cerebellar SUVR_pons were significantly higher in carriers than non-carriers (p < 0.0001). Cerebellar SUVR_pons began to distinguish carriers from non-carriers at age 34, 10 years before the carriers’ estimated age at mild cognitive impairment onset. Florbetapir and PiB cerebellar SUVR_pons in carriers were positively correlated with age (r = 0.44 & 0.69, p < 0.001), cortical SUVR_pons (r = 0.55 & 0.69, p < 0.001), and negatively correlated with delayed recall memory (r = −0.21 & −0.50, p < 0.05, unadjusted for cortical SUVR_pons) and API ADAD composite (r = −0.25, p < 0.01, unadjusted for cortical SUVR_pons in florbetapir API ADAD cohort). Conclusion: This PET study provides evidence of cerebellar Aβ plaque deposition in CU carriers starting about a decade before the clinical onset of ADAD. Additional studies are needed to clarify the impact of using a cerebellar versus pons reference region on the power to detect and track ADAD changes, even in preclinical stages of this disorder.

Research field(s)
Health Sciences, Clinical Medicine, Neurology & Neurosurgery

DOI
10.1016/j.nicl.2021.102749

Muscleblind acts as a modifier of FUS toxicity by modulating stress granule dynamics and SMN localization

NOMIS Researcher(s)

Published in

January 1, 2021

Mutations in fused in sarcoma (FUS) lead to amyotrophic lateral sclerosis (ALS) with varying ages of onset, progression and severity. This suggests that unknown genetic factors contribute to disease pathogenesis. Here we show the identification of muscleblind as a novel modifier of FUS-mediated neurodegeneration in vivo. Muscleblind regulates cytoplasmic mislocalization of mutant FUS and subsequent accumulation in stress granules, dendritic morphology and toxicity in mammalian neuronal and human iPSC-derived neurons. Interestingly, genetic modulation of endogenous muscleblind was sufficient to restore survival motor neuron (SMN) protein localization in neurons expressing pathogenic mutations in FUS, suggesting a potential mode of suppression of FUS toxicity. Upregulation of SMN suppressed FUS toxicity in Drosophila and primary cortical neurons, indicating a link between FUS and SMN. Our data provide in vivo evidence that muscleblind is a dominant modifier of FUS-mediated neurodegeneration by regulating FUS-mediated ALS pathogenesis.

Research field(s)
Health Sciences, Clinical Medicine, Neurology & Neurosurgery

DOI
10.1038/s41467-019-13383-z

FUS-dependent liquid-liquid phase separation is important for DNA repair initiation

NOMIS Researcher(s)

Published in

January 1, 2021

RNA-binding proteins (RBPs) are emerging as important effectors of the cellular DNA damage response (DDR). The RBP FUS is implicated in RNA metabolism and DNA repair, and it undergoes reversible liquid-liquid phase separation (LLPS) in vitro. Here, we demonstrate that FUS-dependent LLPS is necessary for the initiation of the DDR. Using laser microirradiation in FUS-knockout cells, we show that FUS is required for the recruitment to DNA damage sites of the DDR factors KU80, NBS1, and 53BP1 and of SFPQ, another RBP implicated in the DDR. The relocation of KU80, NBS1, and SFPQ is similarly impaired by LLPS inhibitors, or LLPS-deficient FUS variants. We also show that LLPS is necessary for efficient γH2AX foci formation. Finally, using superresolution structured illumination microscopy, we demonstrate that the absence of FUS impairs the proper arrangement of γH2AX nanofoci into higher-order clusters. These findings demonstrate the early requirement for FUS-dependent LLPS in the activation of the DDR and the proper assembly of DSB repair complexes.

Research field(s)
Health Sciences, Biomedical Research, Developmental Biology

DOI
10.1083/JCB.202008030

Emotion matters: Different psychophysiological responses to expressive and non-expressive full-body movements

NOMIS Researcher(s)

Published in

January 1, 2021

We explore dance video clip stimuli as a means to test human observers’ accuracy in detecting genuine emotional expressivity in full-body movements. Stimuli of every-day-type full-body expressions of emotions usually use culturally very recognizable actions (e.g. fist shaking for anger, etc). However, expressive dance movement stimuli can be created to contain fully abstract movements. The expressivity results from subtle variations in the body movements of the expressor, and emotions cannot be recognised by observers via particular actions (e.g. fist shaking, etc). Forty-one participants watched and rated 24 pairs of short dance videos –from a published normalised dance stimuli library– in randomised order (N = 48). Of each carefully matched pair, one version of the full-body movement sequence had been danced to be emotionally genuinely expressive (clip a), while the other version of the same sequence (clip b) had been danced –while technically correct– without any emotional expressivity. Participants rated (i) expressivity (to test their accuracy; block 1), and (ii) how much they liked each movement (an implicit measure to test their emotional response (“liking”); block 2). Participants rated clips that were intended to be expressive as more expressive (part 1: expressivity ratings), and liked those expressive clips more than the non-expressive clips (part 2: liking ratings). Besides, their galvanic skin response differed, depending on the category of clips they were watching (expressive vs. non-expressive), and this relationship was modulated by interceptive accuracy and arts experience. Results are discussed in relation to the Body Precision Hypothesis and the Hypothesis of Constructed Emotion.

Research field(s)
Health Sciences, Psychology & Cognitive Sciences, Experimental Psychology

DOI
10.1016/j.actpsy.2020.103215

Asynchronous, contagious and digital aging

NOMIS Researcher(s)

Published in

January 1, 2021

Organismal aging is often characterized as a steady, monotonic decline of organ and tissue function. However, recent studies indicate spatial and temporal variations of aging rates across the lifespan. We consider these variations from the perspective of underlying cellular changes. Cells in certain tissues may age earlier and produce signals that accelerate the aging of other cells, locally or distantly, acting as drivers for organismal aging and leading to a lack of synchronous aging between tissues. As cells adopt new homeostatic states, cellular aging can be viewed, at least in part, as a quantal process we refer to as digital aging. Analog declines of tissue function with age may be the sum of underlying digital events. Cellular aging, digital or otherwise, is not uniform across time or space within organisms or between organisms of the same species. Advanced systems-level and single-cell methodologies will refine our understanding of cell and tissue aging, and how these processes integrate to produce the complexities of individual, organismal aging.

Research field(s)
Health Sciences, Biomedical Research, Developmental Biology

DOI
10.1038/s43587-020-00015-1

Impact of tspo receptor polymorphism on [18 f]ge-180 binding in healthy brain and pseudo-reference regions of neurooncological and neurodegenerative disorders

NOMIS Researcher(s)

Published in

January 1, 2021

TSPO-PET tracers are sensitive to a single-nucleotide polymorphism (rs6971-SNP), resulting in low-, medium-and high-affinity binders (LABs, MABs and HABS), but the clinical relevance of [18 F]GE-180 is still unclear. We evaluated the impact of rs6971-SNP on in vivo [18 F]GE-180 binding in a healthy brain and in pseudo-reference tissue in neuro-oncological and neurodegenerative diseases. Standardized uptake values (SUVs) of [18 F]GE-180-PET were assessed using a manually drawn region of interest in the frontoparietal and cerebellar hemispheres. The SUVs were compared between the LABs, MABs and HABs in control, glioma, four-repeat tauopathy (4RT) and Alzheimer’s disease (AD) subjects. Second, the SUVs were compared between the patients and controls within their rs6971-subgroups. After excluding patients with prior therapy, 24 LABs (7 control, 5 glioma, 6 4RT and 6 AD) were analyzed. Age-and sex-matched MABs (n = 38) and HABs (n = 50) were selected. The LABs had lower frontoparietal and cerebellar SUVs when compared with the MABs and HABs, but no significant difference was observed between the MABs and HABs. Within each rs6971 group, no SUV difference between the patients and controls was detected in the pseudo-reference tissues. The rs6971-SNP affects [18 F]GE-180 quantification, revealing lower binding in the LABs when compared to the MABs and HABs. The frontoparietal and cerebellar ROIs were successfully validated as pseudo-reference regions.

Research field(s)
Health Sciences, Biomedical Research, Microbiology

DOI
10.3390/life11060484

Using machine learning tools to investigate factors associated with trends in ‘no-shows’ in outpatient appointments

NOMIS Researcher(s)

Published in

January 1, 2021

Missed appointments are estimated to cost the UK National Health Service (NHS) approximately £1 billion annually. Research that leads to a fuller understanding of the types of factors influencing spatial and temporal patterns of these so-called “Did-Not-Attends” (DNAs) is therefore timely. This research articulates the results of a study that uses machine learning approaches to investigate whether these factors are consistent across a range of medical specialities. A predictive model was used to determine the risk-increasing and risk-mitigating factors associated with missing appointments, which were then used to assign a risk score to patients on an appointment-by-appointment basis for each speciality. Results show that the best predictors of DNAs include the patient’s age, appointment history, and the deprivation rank of their area of residence. Findings have been analysed at both a geographical and medical speciality level, and the factors associated with DNAs have been shown to differ in terms of both importance and association. This research has demonstrated how machine learning techniques have real value in informing future intervention policies related to DNAs that can help reduce the burden on the NHS and improve patient care and well-being.

Research field(s)
Health Sciences, Public Health & Health Services, Public Health

DOI
10.1016/j.healthplace.2020.102496

A distinction concerning vision-for-action and affordance perception

NOMIS Researcher(s)

Published in

January 1, 2021

In this paper, I offer a discussion concerning the conceptual connection between the notion of vision-for-action and the one of affordance perception. I first analyze the notion of vision-for-action. I then analyze a notion usually coupled with it: the notion of affordance perception, the main insights behind which are guiding several current neuroscientific enterprises and the related philosophical speculations. Then, I argue that we should not couple these two notions with a light heart: though these two processes can be, from a theoretical point of view, related, we should be careful in inferring the actual and effective occurrence of the latter in the presence of the former. This will be done by carrying out a conceptual analysis of the experimental evidence coming from the ‘Two Visual Systems Model’, which is the main reference in the literature on affordance perception and vision-for-action. My point has strong philosophical implications for our view concerning the best interpretation of how vision-for-action really works, and the specific relation it actually entertains with affordance perception.

Research field(s)
Health Sciences, Psychology & Cognitive Sciences, Experimental Psychology

DOI
10.1016/j.concog.2020.103028

A Molecular Calcium Integrator Reveals a Striatal Cell Type Driving Aversion

NOMIS Researcher(s)

Published in

December 23, 2020

The ability to record transient cellular events in the DNA or RNA of cells would enable precise, large-scale analysis, selection, and reprogramming of heterogeneous cell populations. Here, we report a molecular technology for stable genetic tagging of cells that exhibit activity-related increases in intracellular calcium concentration (FLiCRE). We used FLiCRE to transcriptionally label activated neural ensembles in the nucleus accumbens of the mouse brain during brief stimulation of aversive inputs. Using single-cell RNA sequencing, we detected FLiCRE transcripts among the endogenous transcriptome, providing simultaneous readout of both cell-type and calcium activation history. We identified a cell type in the nucleus accumbens activated downstream of long-range excitatory projections. Taking advantage of FLiCRE’s modular design, we expressed an optogenetic channel selectively in this cell type and showed that direct recruitment of this otherwise genetically inaccessible population elicits behavioral aversion. The specificity and minute resolution of FLiCRE enables molecularly informed characterization, manipulation, and reprogramming of activated cellular ensembles.

Research field(s)
Health Sciences, Biomedical Research, Developmental Biology

DOI
10.1016/j.cell.2020.11.015

Nuclear Import Receptors Directly Bind to Arginine-Rich Dipeptide Repeat Proteins and Suppress Their Pathological Interactions

NOMIS Researcher(s)

Published in

December 22, 2020

Hutten et al. show that arginine-rich dipeptide repeat proteins (DPRs) associated with the neurodegenerative diseases ALS and FTD bind directly to importins, promote their condensation, and interfere with importin function. Elevated importin levels can shield arginine-rich DPRs and suppress DPR-induced phase separation of TDP-43 and RNA.

Research field(s)
Health Sciences, Biomedical Research, Developmental Biology

DOI
10.1016/j.celrep.2020.108538

Interoceptive Awareness Is Negatively Related to the Exteroceptive Manipulation of Bodily Self-Location

NOMIS Researcher(s)

Published in

December 4, 2020

The perception of being located within one’s body (i.e., bodily self-location) is an essential feature of everyday self-experience. However, by manipulating exteroceptive input, healthy participants can easily be induced to perceive themselves as being spatially dislocated from their physical bodies. It has previously been suggested that interoception, i.e., the processing of inner physiological signals, contributes to the stability of body representations; however, this relationship has not previously been tested for different dimensions of interoception and bodily self-location. In the present study, using an advanced automatized setup, we systematically manipulated participants’ perspective of their own body (first- vs third-person perspective) as well as the synchrony of visuotactile stimulation (synchronous vs asynchronous). The malleability of bodily self-location was assessed using a questionnaire targeting in-body and out-of-body experiences. Participants also performed a heartbeat discrimination task to assess their interoceptive accuracy (behavioral performance), interoceptive sensibility (confidence in their interoceptive abilities), and interoceptive awareness (meta-cognitive representation of interoceptive signals). Bodily self-location was significantly influenced by perspective, with third-person perspective being associated with stronger out-of-body experiences compared to first-person perspective. Furthermore, there was a significant perspective × stimulation interaction, with subsequent analyses showing that participants reported out-of-body experiences particularly under third-person perspective combined with synchronous visuotactile stimulation. Correlation and regression analyses revealed that meta-cognitive interoceptive awareness was specifically and negatively related to the exteroceptively mediated malleability of body experiences. These results indicate that the perception of the self being located within one’s body relies on the interaction of exteroceptive input and higher-order interoceptive abilities. This has implications for theoretical considerations about the bodily self in health as well as for the understanding of disturbed bodily self-processing in clinical contexts.

Research field(s)
Health Sciences, Psychology & Cognitive Sciences, Experimental Psychology

DOI
10.3389/fpsyg.2020.562016

Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair

NOMIS Researcher(s)

Published in

December 1, 2020

Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification.

Research field(s)
Health Sciences, Biomedical Research, Developmental Biology

DOI
10.1038/s41467-020-15845-1

Coordinating attention requires coordinated senses

NOMIS Researcher(s)

Published in

December 1, 2020

From playing basketball to ordering at a food counter, we frequently and effortlessly coordinate our attention with others towards a common focus: we look at the ball, or point at a piece of cake. This non-verbal coordination of attention plays a fundamental role in our social lives: it ensures that we refer to the same object, develop a shared language, understand each other’s mental states, and coordinate our actions. Models of joint attention generally attribute this accomplishment to gaze coordination. But are visual attentional mechanisms sufficient to achieve joint attention, in all cases? Besides cases where visual information is missing, we show how combining it with other senses can be helpful, and even necessary to certain uses of joint attention. We explain the two ways in which non-visual cues contribute to joint attention: either as enhancers, when they complement gaze and pointing gestures in order to coordinate joint attention on visible objects, or as modality pointers, when joint attention needs to be shifted away from the whole object to one of its properties, say weight or texture. This multisensory approach to joint attention has important implications for social robotics, clinical diagnostics, pedagogy and theoretical debates on the construction of a shared world.

Research field(s)
Health Sciences, Psychology & Cognitive Sciences, Experimental Psychology

DOI
10.3758/s13423-020-01766-z

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