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Publications in Health Sciences by NOMIS researchers

‘So Help Me God’? Does oath swearing in courtroom scenarios impact trial outcomes?

NOMIS Researcher(s)

Published in

April 3, 2023

In countries such as Britain and the US, court witnesses must declare they will provide truthful evidence and are often compelled to publicly choose between religious (“oath”) and secular (“affirmation”) versions of this declaration. Might defendants who opt to swear an oath enjoy more favourable outcomes than those who choose to affirm? Two preliminary, pre-registered survey studies using minimal vignettes (Study 1, N = 443; Study 2, N = 913) indicated that people associate choice of the oath with credible testimony; and that participants, especially religious participants, discriminate against defendants who affirm. In a third, Registered Report study (Study 3, N = 1821), we used a more elaborate audiovisual mock trial paradigm to better estimate the real-world influence of declaration choice. Participants were asked to render a verdict for a defendant who either swore or affirmed, and were themselves required to swear or affirm that they would try the defendant in good faith. Overall, the defendant was not considered guiltier when affirming rather than swearing, nor did mock-juror belief in God moderate this effect. However, jurors who themselves swore an oath did discriminate against the affirming defendant. Exploratory analyses suggest this effect may be driven by authoritarianism, perhaps because high-authoritarian jurors consider the oath the traditional (and therefore correct) declaration to choose. We discuss the real-world implications of these findings and conclude the religious oath is an antiquated legal ritual that needs reform. © 2023 The Authors. British Journal of Psychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.

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

DOI
10.1111/bjop.12651

Protocol to determine antibody affinity and concentration in complex solutions using microfluidic antibody affinity profiling

NOMIS Researcher(s)

Published in

March 17, 2023

Conventional methods of measuring affinity are limited by artificial immobilization, large sample volumes, and homogeneous solutions. This protocol describes microfluidic antibody affinity profiling on complex human samples in solution to obtain a fingerprint reflecting both affinity and active concentration of the target protein. To illustrate the protocol, we analyze the antibody response in SARS-CoV-2 omicron-naïve samples against different SARS-CoV-2 variants of concern. However, the protocol and the technology are amenable to a broad spectrum of biomedical questions. For complete details on the use and execution of this protocol, please refer to Emmenegger et al. (2022),1 Schneider et al. (2022),2 and Fiedler et al. (2022).3 © 2023 The Author(s)

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

DOI
10.1016/j.xpro.2023.102095

Cytoplasmic contractile injection systems mediate cell death in Streptomyces

NOMIS Researcher(s)

Published in

March 9, 2023

Contractile injection systems (CIS) are bacteriophage tail-like structures that mediate bacterial cell–cell interactions. While CIS are highly abundant across diverse bacterial phyla, representative gene clusters in Gram-positive organisms remain poorly studied. Here we characterize a CIS in the Gram-positive multicellular model organism Streptomyces coelicolor and show that, in contrast to most other CIS, S. coelicolor CIS (CISSc) mediate cell death in response to stress and impact cellular development. CISSc are expressed in the cytoplasm of vegetative hyphae and are not released into the medium. Our cryo-electron microscopy structure enabled the engineering of non-contractile and fluorescently tagged CISSc assemblies. Cryo-electron tomography showed that CISSc contraction is linked to reduced cellular integrity. Fluorescence light microscopy furthermore revealed that functional CISSc mediate cell death upon encountering different types of stress. The absence of functional CISSc had an impact on hyphal differentiation and secondary metabolite production. Finally, we identified three putative effector proteins, which when absent, phenocopied other CISSc mutants. Our results provide new functional insights into CIS in Gram-positive organisms and a framework for studying novel intracellular roles, including regulated cell death and life-cycle progression in multicellular bacteria. © 2023, The Author(s).

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

DOI
10.1038/s41564-023-01341-x

Delusions as Epistemic Hypervigilance

NOMIS Researcher(s)

Published in

March 8, 2023

Delusions are distressing and disabling symptoms of various clinical disorders. Delusions are associated with an aberrant and apparently contradictory treatment of evidence, characterized by both excessive credulity (adopting unusual beliefs on minimal evidence) and excessive rigidity (holding steadfast to these beliefs in the face of strong counterevidence). Here we attempt to make sense of this contradiction by considering the literature on epistemic vigilance. Although there is little evolutionary advantage to scrutinizing the evidence our senses provide, it pays to be vigilant toward ostensive evidence—information communicated by others. This asymmetry is generally adaptive, but in deluded individuals the scales tip too far in the direction of the sensory and perceptual, producing an apparently paradoxical combination of credulity (with respect to one’s own perception) and skepticism (with respect to the testimony of others). © The Author(s) 2023.

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

DOI
10.1177/09637214221128320

Functional dissection of two amino acid substitutions unique to the human FOXP2 protein

NOMIS Researcher(s)

Published in

March 6, 2023

The transcription factor forkhead box P2 (FOXP2) is involved in the development of language and speech in humans. Two amino acid substitutions (T303N, N325S) occurred in the human FOXP2 after the divergence from the chimpanzee lineage. It has previously been shown that when they are introduced into the FOXP2 protein of mice they alter striatal synaptic plasticity by increasing long-term depression in medium spiny neurons. Here we introduce each of these amino acid substitutions individually into mice and analyze their effects in the striatum. We find that long-term depression in medium spiny neurons is increased in mice carrying only the T303N substitution to the same extent as in mice carrying both amino acid substitutions. In contrast, the N325S substitution has no discernable effects. © 2023, The Author(s).

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

DOI
10.1038/s41598-023-30663-3

Cardiogenic control of affective behavioural state

NOMIS Researcher(s)

Published in

March 1, 2023

Emotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of the heart1–3. However, whether an increased heart rate might itself induce anxiety or fear responses is unclear3–8. Physiological theories of emotion, proposed over a century ago, have considered that in general, there could be an important and even dominant flow of information from the body to the brain9. Here, to formally test this idea, we developed a noninvasive optogenetic pacemaker for precise, cell-type-specific control of cardiac rhythms of up to 900 beats per minute in freely moving mice, enabled by a wearable micro-LED harness and the systemic viral delivery of a potent pump-like channelrhodopsin. We found that optically evoked tachycardia potently enhanced anxiety-like behaviour, but crucially only in risky contexts, indicating that both central (brain) and peripheral (body) processes may be involved in the development of emotional states. To identify potential mechanisms, we used whole-brain activity screening and electrophysiology to find brain regions that were activated by imposed cardiac rhythms. We identified the posterior insular cortex as a potential mediator of bottom-up cardiac interoceptive processing, and found that optogenetic inhibition of this brain region attenuated the anxiety-like behaviour that was induced by optical cardiac pacing. Together, these findings reveal that cells of both the body and the brain must be considered together to understand the origins of emotional or affective states. More broadly, our results define a generalizable approach for noninvasive, temporally precise functional investigations of joint organism-wide interactions among targeted cells during behaviour. © 2023, The Author(s).

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

DOI
10.1038/s41586-023-05748-8

Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region

NOMIS Researcher(s)

Published in

February 17, 2023

Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72′250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae. © 2023 The Authors

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

DOI
10.1016/j.isci.2023.105928

Does decision confidence reflect effort?

NOMIS Researcher(s)

Published in

February 16, 2023

Goal directed behaviour requires transformation of sensory input to decision, and then to output action. How the sensory input is accumulated to form the decision has been extensively studied, however, the influence of output action on decision making has been largely dismissed. Although the recent emerging view postulates the reciprocal interaction between action and decision, still little is known about how the parameters of an action modulates the decision. In this study, we focused on the physical effort which necessarily entails with action. We tested if the physical effort during the deliberation period of the perceptual decision, not the effort required after deciding a particular option, can impact on the process of forming the decision. Here, we set up an experimental situation where investing effort is necessary for the initiation of the task, but importantly, is orthogonal to success in task performance. The study was pre-registered to test the hypothesis that the increased effort will decrease the metacognitive accuracy of decision, without affecting the decision accuracy. Participants judged the direction of a random-dot motion stimuli, while holding and maintaining the position of a robotic manipulandum with their right hand. In the key experimental condition, the manipulandum produced force to move away from its position, requiring the participants to resist the force while accumulating the sensory evidence for the decision. The decision was reported by a key-press using the left-hand. We found no evidence that such incidental (i.e., non-instrumental) effort may influence the subsequent decision process and most importantly decision confidence. The possible reason for this result and the future direction of the research are discussed. © 2023 Hagura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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

DOI
10.1371/journal.pone.0278617

Developmental mechanisms underlying the evolution of human cortical circuits

NOMIS Researcher(s)

Published in

February 15, 2023

The brain of modern humans has evolved remarkable computational abilities that enable higher cognitive functions. These capacities are tightly linked to an increase in the size and connectivity of the cerebral cortex, which is thought to have resulted from evolutionary changes in the mechanisms of cortical development. Convergent progress in evolutionary genomics, developmental biology and neuroscience has recently enabled the identification of genomic changes that act as human-specific modifiers of cortical development. These modifiers influence most aspects of corticogenesis, from the timing and complexity of cortical neurogenesis to synaptogenesis and the assembly of cortical circuits. Mutations of human-specific genetic modifiers of corticogenesis have started to be linked to neurodevelopmental disorders, providing evidence for their physiological relevance and suggesting potential relationships between the evolution of the human brain and its sensitivity to specific diseases. © 2023, Springer Nature Limited.

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

DOI
10.1038/s41583-023-00675-z

Systematic estimation of biological age of in vitro cell culture systems by an age-associated marker panel

NOMIS Researcher(s)

Published in

February 15, 2023

Aging is a process that affects almost all multicellular organisms and since our population ages with increasing prevalence of age-related diseases, it is important to study basic processes involved in aging. Many studies have been published so far using different and often single age markers to estimate the biological age of organisms or different cell culture systems. However, comparability of studies is often hampered by the lack of a uniform panel of age markers. Consequently, we here suggest an easy-to-use biomarker-based panel of classical age markers to estimate the biological age of cell culture systems that can be used in standard cell culture laboratories. This panel is shown to be sensitive in a variety of aging conditions. We used primary human skin fibroblasts of different donor ages and additionally induced either replicative senescence or artificial aging by progerin overexpression. Using this panel, highest biological age was found for artificial aging by progerin overexpression. Our data display that aging varies depending on cell line and aging model and even from individual to individual showing the need for comprehensive analyses. Copyright © 2023 Hartmann, Herling, Hartmann, Köckritz, Fuellen, Walter and Hermann.

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

DOI
10.3389/fragi.2023.1129107

Quantitative proteomic landscapes of primary and recurrent glioblastoma reveal a protumorigeneic role for FBXO2-dependent glioma-microenvironment interactions

NOMIS Researcher(s)

Published in

February 14, 2023

Background: Recent efforts have described the evolution of glioblastoma from initial diagnosis to post-treatment recurrence on a genomic and transcriptomic level. However, the evolution of the proteomic landscape is largely unknown.

Methods: Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was used to characterize the quantitative proteomes of two independent cohorts of paired newly diagnosed and recurrent glioblastomas. Recurrence-associated proteins were validated using immunohistochemistry and further studied in human glioma cell lines, orthotopic xenograft models, and human organotypic brain slice cultures. External spatial transcriptomic, single-cell, and bulk RNA sequencing data were analyzed to gain mechanistic insights.

Results: Although overall proteomic changes were heterogeneous across patients, we identified BCAS1, INF2, and FBXO2 as consistently upregulated proteins at recurrence and validated these using immunohistochemistry. Knockout of FBXO2 in human glioma cells conferred a strong survival benefit in orthotopic xenograft mouse models and reduced invasive growth in organotypic brain slice cultures. In glioblastoma patient samples, FBXO2 expression was enriched in the tumor infiltration zone and FBXO2-positive cancer cells were associated with synaptic signaling processes.

Conclusions: These findings demonstrate a potential role of FBXO2-dependent glioma-microenvironment interactions to promote tumor growth. Furthermore, the published datasets provide a valuable resource for further studies.

Research field(s)
Oncology & Carcinogenesis

DOI
10.1093/neuonc/noac169

RNA binding protein DDX5 restricts RORγt+Tregsuppressor function to promote intestine inflammation

NOMIS Researcher(s)

Published in

February 1, 2023

Retinoid-related orphan receptor (RAR) gamma (RORγt)-expressing regulatory T cells (RORγt+ Tregs) play pivotal roles in preventing T cell hyperactivation and maintaining tissue homeostasis, in part by secreting the anti-inflammation cytokine interleukin-10 (IL-10). Here, we report that hypoxia-induced factor 1α (HIF1α) is the master transcription factor for Il10 in RORγt+ Tregs. This critical anti-inflammatory pathway is negatively regulated by an RNA binding protein DEAD box helicase 5 (DDX5). As a transcriptional corepressor, DDX5 restricts the expression of HIF1α and its downstream target gene Il10 in RORγt+ Tregs. T cell-specific Ddx5 knockout (DDX5ΔT) mice have augmented RORγt+ Treg suppressor activities and are better protected from intestinal inflammation. Genetic ablation or pharmacologic inhibition of HIF1α restores enteropathy susceptibility in DDX5ΔT mice. The DDX5-HIF1α- IL-10 pathway is conserved in mice and humans. These findings reveal potential therapeutic targets for intestinal inflammatory diseases. Copyright © 2023 The Authors.

Research field(s)
Health Sciences

DOI
10.1126/sciadv.add6165

FUS ALS neurons activate major stress pathways and reduce translation as an early protective mechanism against neurodegeneration

NOMIS Researcher(s)

Published in

January 24, 2023

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder causing progressive loss of motor neurons. Mutations in Fused in sarcoma (FUS) leading to its cytoplasmic mislocalization cause a subset of ALS. Under stress, mutant FUS localizes to stress granules (SGs)—cytoplasmic condensates composed of RNA and various proteins. Aberrant dynamics of SGs is linked to the pathology of ALS. Here, using motor neurons (MNs) derived from human induced pluripotent stem cells, we show that, in mutant FUS, MN dynamics of SGs is disturbed. Additionally, heat-shock response (HSR) and integrated stress response (ISR) involved in the regulation of SGs are upregulated in mutant MNs. HSR activation correlates with the amount of cytoplasmic FUS mislocalization. While inhibition of SG formation, translation, or ISR does not influence survival of FUS ALS neurons, proteotoxicity that cannot be compensated with the activation of stress pathways is the main driver of neurodegeneration in early FUS ALS. © 2023 The Author(s)

Research field(s)
Health Sciences

DOI
10.1016/j.celrep.2023.112025

Glacier-Fed Stream Biofilms Harbor Diverse Resistomes and Biosynthetic Gene Clusters

NOMIS Researcher(s)

Published in

January 23, 2023

Antimicrobial resistance (AMR) is a universal phenomenon the origins of which lay in natural ecological interactions such as competition within niches, within and between micro- to higher-order organisms. To study these phenomena, it is crucial to examine the origins of AMR in pristine environments, i.e., limited anthropogenic influences. In this context, epilithic biofilms residing in glacier-fed streams (GFSs) are an excellent model system to study diverse, intra- and inter-domain, ecological crosstalk. We assessed the resistomes of epilithic biofilms from GFSs across the Southern Alps (New Zealand) and the Caucasus (Russia) and observed that both bacteria and eukaryotes encoded twenty-nine distinct AMR categories. Of these, beta-lactam, aminoglycoside, and multidrug resistance were both abundant and taxonomically distributed in most of the bacterial and eukaryotic phyla. AMR-encoding phyla included Bacteroidota and Proteobacteria among the bacteria, alongside Ochrophyta (algae) among the eukaryotes. Additionally, biosynthetic gene clusters (BGCs) involved in the production of antibacterial compounds were identified across all phyla in the epilithic biofilms. Furthermore, we found that several bacterial genera (Flavobacterium, Polaromonas, Superphylum Patescibacteria) encode both atimicrobial resistance genes (ARGs) and BGCs within close proximity of each other, demonstrating their capacity to simultaneously influence and compete within the microbial community. Our findings help unravel how naturally occurring BGCs and AMR contribute to the epilithic biofilms mode of life in GFSs. Additionally, we report that eukaryotes may serve as AMR reservoirs owing to their potential for encoding ARGs. Importantly, these observations may be generalizable and potentially extended to other environments that may be more or less impacted by human activity. IMPORTANCE Antimicrobial resistance is an omnipresent phenomenon in the anthropogenically influenced ecosystems. However, its role in shaping microbial community dynamics in pristine environments is relatively unknown. Using metagenomics, we report the presence of antimicrobial resistance genes and their associated pathways in epilithic biofilms within glacier-fed streams. Importantly, we observe biosynthetic gene clusters associated with antimicrobial resistance in both pro- and eukaryotes in these biofilms. Understanding the role of resistance in the context of this pristine environment and complex biodiversity may shed light on previously uncharacterized mechanisms of cross-domain interactions. Copyright © 2023 Busi et al.

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

DOI
10.1128/spectrum.04069-22

All-optical physiology resolves a synaptic basis for behavioral timescale plasticity

NOMIS Researcher(s)

Published in

January 19, 2023

Learning has been associated with modifications of synaptic and circuit properties, but the precise changes storing information in mammals have remained largely unclear. We combined genetically targeted voltage imaging with targeted optogenetic activation and silencing of pre- and post-synaptic neurons to study the mechanisms underlying hippocampal behavioral timescale plasticity. In mice navigating a virtual-reality environment, targeted optogenetic activation of individual CA1 cells at specific places induced stable representations of these places in the targeted cells. Optical elicitation, recording, and modulation of synaptic transmission in behaving mice revealed that activity in presynaptic CA2/3 cells was required for the induction of plasticity in CA1 and, furthermore, that during induction of these place fields in single CA1 cells, synaptic input from CA2/3 onto these same cells was potentiated. These results reveal synaptic implementation of hippocampal behavioral timescale plasticity and define a methodology to resolve synaptic plasticity during learning and memory in behaving mammals. © 2022 The Author(s)

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

DOI
10.1016/j.cell.2022.12.035

Evolutionary diversification of methanotrophic ANME-1 archaea and their expansive virome

NOMIS Researcher(s)

Published in

January 19, 2023

‘Candidatus Methanophagales’ (ANME-1) is an order-level clade of archaea responsible for anaerobic methane oxidation in deep-sea sediments. The diversity, ecology and evolution of ANME-1 remain poorly understood. In this study, we use metagenomics on deep-sea hydrothermal samples to expand ANME-1 diversity and uncover the effect of virus–host dynamics. Phylogenetic analyses reveal a deep-branching, thermophilic family, ‘Candidatus Methanospirareceae’, closely related to short-chain alkane oxidizers. Global phylogeny and near-complete genomes show that hydrogen metabolism within ANME-1 is an ancient trait that was vertically inherited but differentially lost during lineage diversification. Metagenomics also uncovered 16 undescribed virus families so far exclusively targeting ANME-1 archaea, showing unique structural and replicative signatures. The expansive ANME-1 virome contains a metabolic gene repertoire that can influence host ecology and evolution through virus-mediated gene displacement. Our results suggest an evolutionary continuum between anaerobic methane and short-chain alkane oxidizers and underscore the effects of viruses on the dynamics and evolution of methane-driven ecosystems. © 2023, The Author(s).

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

DOI
10.1038/s41564-022-01297-4

Whole-brain microscopy reveals distinct temporal and spatial efficacy of anti-Aβ therapies

NOMIS Researcher(s)

Published in

January 11, 2023

Many efforts targeting amyloid-β (Aβ) plaques for the treatment of Alzheimer’s Disease thus far have resulted in failures during clinical trials. Regional and temporal heterogeneity of efficacy and dependence on plaque maturity may have contributed to these disappointing outcomes. In this study, we mapped the regional and temporal specificity of various anti-Aβ treatments through high-resolution light-sheet imaging of electrophoretically cleared brains. We assessed the effect on amyloid plaque formation and growth in Thy1-APP/PS1 mice subjected to β-secretase inhibitors, polythiophenes, or anti-Aβ antibodies. Each treatment showed unique spatiotemporal Aβ clearance, with polythiophenes emerging as a potent anti-Aβ compound. Furthermore, aligning with a spatial-transcriptomic atlas revealed transcripts that correlate with the efficacy of each Aβ therapy. As observed in this study, there is a striking dependence of specific treatments on the location and maturity of Aβ plaques. This may also contribute to the clinical trial failures of Aβ-therapies, suggesting that combinatorial regimens may be significantly more effective in clearing amyloid deposition. © 2022 The Authors. Published under the terms of the CC BY 4.0 license.

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

DOI
10.15252/emmm.202216789

Plasma p-tau217 predicts in vivo brain pathology and cognition in autosomal dominant Alzheimer’s disease

NOMIS Researcher(s)

Published in

December 26, 2022

Introduction: Plasma-measured tau phosphorylated at threonine 217 (p-tau217) is a potential non-invasive biomarker of Alzheimer’s disease (AD). We investigated whether plasma p-tau217 predicts subsequent cognition and positron emission tomography (PET) markers of pathology in autosomal dominant AD. Methods: We analyzed baseline levels of plasma p-tau217 and its associations with amyloid PET, tau PET, and word list delayed recall measured 7.61 years later in non-demented age- and education-matched presenilin-1 E280A carriers (n = 24) and non-carrier (n = 20) family members. Results: Carriers had higher plasma p-tau217 levels than non-carriers. Baseline plasma p-tau217 was associated with subsequent amyloid and tau PET pathology levels and cognitive function. Discussion: Our findings suggest that plasma p-tau217 predicts subsequent brain pathological burden and memory performance in presenilin-1 E280A carriers. These results provide support for plasma p-tau217 as a minimally invasive diagnostic and prognostic biomarker for AD, with potential utility in clinical practice and trials. Highlights: Non-demented presenilin-1 E280A carriers have higher plasma tau phosphorylated at threonine 217 (p-tau217) than do age-matched non-carriers. Higher baseline p-tau217 is associated with greater future amyloid positron emission tomography (PET) pathology burden. Higher baseline p-tau217 is associated with greater future tau PET pathology burden. Higher baseline p-tau217 is associated with worse future memory performance. © 2022 the Alzheimer’s Association.

Research field(s)
Health Sciences, Clinical Medicine, Immunology

DOI
10.1002/alz.12906

Spatial proteomics in three-dimensional intact specimens

NOMIS Researcher(s)

Published in

December 22, 2022

Spatial molecular profiling of complex tissues is essential to investigate cellular function in physiological and pathological states. However, methods for molecular analysis of large biological specimens imaged in 3D are lacking. Here, we present DISCO-MS, a technology that combines whole-organ/whole-organism clearing and imaging, deep-learning-based image analysis, robotic tissue extraction, and ultra-high-sensitivity mass spectrometry. DISCO-MS yielded proteome data indistinguishable from uncleared samples in both rodent and human tissues. We used DISCO-MS to investigate microglia activation along axonal tracts after brain injury and characterized early- and late-stage individual amyloid-beta plaques in a mouse model of Alzheimer’s disease. DISCO-bot robotic sample extraction enabled us to study the regional heterogeneity of immune cells in intact mouse bodies and aortic plaques in a complete human heart. DISCO-MS enables unbiased proteome analysis of preclinical and clinical tissues after unbiased imaging of entire specimens in 3D, identifying diagnostic and therapeutic opportunities for complex diseases. Video abstract: [Figure presented]

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

DOI
10.1016/j.cell.2022.11.021

On the realness of people who do not exist: The social processing of artificial faces

NOMIS Researcher(s)

Published in

December 22, 2022

Today more than ever, we are asked to evaluate the realness, truthfulness and trustworthiness of our social world. Here, we focus on how people evaluate realistic-looking faces of non-existing people generated by generative adversarial networks (GANs). GANs are increasingly used in marketing, journalism, social media, and political propaganda. In three studies, we investigated if and how participants can distinguish between GAN and REAL faces and the social consequences of their exposure to artificial faces. GAN faces were more likely to be perceived as real than REAL faces, a pattern partly explained by intrinsic stimulus characteristics. Moreover, participants’ realness judgments influenced their behavior because they displayed increased social conformity toward faces perceived as real, independently of their actual realness. Lastly, knowledge about the presence of GAN faces eroded social trust. Our findings point to potentially far-reaching consequences for the pervasive use of GAN faces in a culture powered by images at unprecedented levels.

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

DOI
10.1016/j.isci.2022.105441

Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment

NOMIS Researcher(s)

Published in

December 22, 2022

Cerebrospinal fluid (CSF) contains a tightly regulated immune system. However, knowledge is lacking about how CSF immunity is altered with aging or neurodegenerative disease. Here, we performed single-cell RNA sequencing on CSF from 45 cognitively normal subjects ranging from 54 to 82 years old. We uncovered an upregulation of lipid transport genes in monocytes with age. We then compared this cohort with 14 cognitively impaired subjects. In cognitively impaired subjects, downregulation of lipid transport genes in monocytes occurred concomitantly with altered cytokine signaling to CD8 T cells. Clonal CD8 T effector memory cells upregulated C-X-C motif chemokine receptor 6 (CXCR6) in cognitively impaired subjects. The CXCR6 ligand, C-X-C motif chemokine ligand 16 (CXCL16), was elevated in the CSF of cognitively impaired subjects, suggesting CXCL16-CXCR6 signaling as a mechanism for antigen-specific T cell entry into the brain. Cumulatively, these results reveal cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment.

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

DOI
10.1016/j.cell.2022.11.019

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