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Research is the vital expression of humankind’s most important qualities: curiosity and imagination.

Explorers, inventors, pioneers—dedicated researchers on the frontiers of science and the humanities.

Insight, when it comes, changes everything.

Publications

The NOMIS community of researchers and partners is instrumental in driving interdisciplinary collaboration, generating insights and ultimately advancing our understanding of the world. A key component of these efforts is knowledge sharing. Comprising a unique offering of engaging scientific lectures, insightful films about our awardees’ research, and a comprehensive publication database, NOMIS Insights are designed to facilitate the sharing of knowledge. They showcase the groundbreaking findings and innovative perspectives born from NOMIS-supported research endeavors, embodying our dedication to enabling scientific progress.

Our NOMIS Insight database provides a comprehensive source of all publications resulting from NOMIS-supported research projects.

PHGDH preserves one-carbon cycle to confer metabolic plasticity in chemoresistant gastric cancer during nutrient stress

NOMIS Researcher(s)

Published in

May 16, 2023

Molecular classification of gastric cancer (GC) identified a subgroup of patients showing chemoresistance and poor prognosis, termed SEM (Stem-like/Epithelial-to-mesenchymal transition/Mesenchymal) type in this study. Here, we show that SEM-type GC exhibits a distinct metabolic profile characterized by high glutaminase (GLS) levels. Unexpectedly, SEM-type GC cells are resistant to glutaminolysis inhibition. We show that under glutamine starvation, SEM-type GC cells up-regulate the 3 phosphoglycerate dehydrogenase (PHGDH)-mediated mitochondrial folate cycle pathway to produce NADPH as a reactive oxygen species scavenger for survival. This metabolic plasticity is associated with globally open chromatin structure in SEM-type GC cells, with ATF4/CEBPB identified as transcriptional drivers of the PHGDH-driven salvage pathway. Single-nucleus transcriptome analysis of patient-derived SEM-type GC organoids revealed intratumoral heterogeneity, with stemness-high subpopulations displaying high GLS expression, a resistance to GLS inhibition, and ATF4/CEBPB activation. Notably, coinhibition of GLS and PHGDH successfully eliminated stemness-high cancer cells. Together, these results provide insight into the metabolic plasticity of aggressive GC cells and suggest a treatment strategy for chemoresistant GC patients. Copyright © 2023 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).

Research field(s)
Health Sciences, Biomedical Research, Biochemistry & Molecular Biology

DOI
10.1073/pnas.2217826120

Imputing missing data in plant traits: A guide to improve gap-filling

NOMIS Researcher(s)

Published in

May 16, 2023

Aim: Globally distributed plant trait data are increasingly used to understand relationships between biodiversity and ecosystem processes. However, global trait databases are sparse because they are compiled from many, mostly small databases. This sparsity in both trait space completeness and geographical distribution limits the potential for both multivariate and global analyses. Thus, ‘gap-filling’ approaches are often used to impute missing trait data. Recent methods, like Bayesian hierarchical probabilistic matrix factorization (BHPMF), can impute large and sparse data sets using side information. We investigate whether BHPMF imputation leads to biases in trait space and identify aspects influencing bias to provide guidance for its usage. Innovation: We use a fully observed trait data set from which entries are randomly removed, along with extensive but sparse additional data. We use BHPMF for imputation and evaluate bias by: (1) accuracy (residuals, RMSE, trait means), (2) correlations (bi- and multivariate) and (3) taxonomic and functional clustering (valuewise, uni- and multivariate). BHPMF preserves general patterns of trait distributions but induces taxonomic clustering. Data set–external trait data had little effect on induced taxonomic clustering and stabilized trait–trait correlations. Main Conclusions: Our study extends the criteria for the evaluation of gap-filling beyond RMSE, providing insight into statistical data structure and allowing better informed use of imputed trait data, with improved practice for imputation. We expect our findings to be valuable beyond applications in plant ecology, for any study using hierarchical side information for imputation. © 2023 The Authors. Global Ecology and Biogeography published by John Wiley & Sons Ltd.

Research field(s)
Natural Sciences, Biology, Ecology

DOI
10.1111/geb.13695

Disulfide bond in SUN2 regulates dynamic remodeling of LINC complexes at the nuclear envelope

NOMIS Researcher(s)

Published in

May 15, 2023

The LINC complex tethers the cell nucleus to the cytoskeleton to regulate mechanical forces during cell migration, differentiation, and various diseases. The function of LINC complexes relies on the interaction between highly conserved SUN and KASH proteins that form higher-order assemblies capable of load bearing. These structural details have emerged from in vitro assembled LINC complexes; however, the principles of in vivo assembly remain obscure. Here, we report a conformation-specific SUN2 antibody as a tool to visualize LINC complex dynamics in situ. Using imaging, biochemical, and cellular methods, we find that conserved cysteines in SUN2 undergo KASH-dependent inter- and intramolecular disulfide bond rearrangements. Disruption of the SUN2 terminal disulfide bond compromises SUN2 localization, turnover, LINC complex assembly in addition to cytoskeletal organization and cell migration. Moreover, using pharmacological and genetic perturbations, we identify components of the ER lumen as SUN2 cysteines redox state regulators. Overall, we provide evidence for SUN2 disulfide bond rearrangement as a physiologically relevant structural modification that regulates LINC complex functions. © 2023 Sharma and Hetzer.

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

DOI
10.26508/lsa.202302031

Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man

NOMIS Researcher(s)

Published in

May 15, 2023

We characterized the world’s second case with ascertained extreme resilience to autosomal dominant Alzheimer’s disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact until 67 years of age despite carrying a PSEN1-E280A mutation. Like the APOECh carrier, he had extremely elevated amyloid plaque burden and limited entorhinal Tau tangle burden. He did not carry the APOECh variant but was heterozygous for a rare variant in RELN (H3447R, termed COLBOS after the Colombia–Boston biomarker research study), a ligand that like apolipoprotein E binds to the VLDLr and APOEr2 receptors. RELN-COLBOS is a gain-of-function variant showing stronger ability to activate its canonical protein target Dab1 and reduce human Tau phosphorylation in a knockin mouse. A genetic variant in a case protected from ADAD suggests a role for RELN signaling in resilience to dementia. © 2023, The Author(s).

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

DOI
10.1038/s41591-023-02318-3

Live Cell Imaging of ATP Levels Reveals Metabolic Compartmentalization within Motoneurons and Early Metabolic Changes in FUS ALS Motoneurons

NOMIS Researcher(s)

Published in

May 9, 2023

Motoneurons are one of the most energy-demanding cell types and a primary target in Amyotrophic lateral sclerosis (ALS), a debilitating and lethal neurodegenerative disorder without currently available effective treatments. Disruption of mitochondrial ultrastructure, transport, and metabolism is a commonly reported phenotype in ALS models and can critically affect survival and the proper function of motor neurons. However, how changes in metabolic rates contribute to ALS progression is not fully understood yet. Here, we utilize hiPCS-derived motoneuron cultures and live imaging quantitative techniques to evaluate metabolic rates in fused in sarcoma (FUS)-ALS model cells. We show that differentiation and maturation of motoneurons are accompanied by an overall upregulation of mitochondrial components and a significant increase in metabolic rates that correspond to their high energy-demanding state. Detailed compartment-specific live measurements using a fluorescent ATP sensor and FLIM imaging show significantly lower levels of ATP in the somas of cells carrying FUS-ALS mutations. These changes lead to the increased vulnerability of diseased motoneurons to further metabolic challenges with mitochondrial inhibitors and could be due to the disruption of mitochondrial inner membrane integrity and an increase in its proton leakage. Furthermore, our measurements demonstrate heterogeneity between axonal and somatic compartments, with lower relative levels of ATP in axons. Our observations strongly support the hypothesis that mutated FUS impacts the metabolic states of motoneurons and makes them more susceptible to further neurodegenerative mechanisms. © 2023 by the authors.

Research field(s)
Health Sciences, Biomedical Research, Biochemistry & Molecular Biology

DOI
10.3390/cells12101352

A Tropical Cocktail of Organic Matter Sources: Variability in Supraglacial and Glacier Outflow Dissolved Organic Matter Composition and Age Across the Ecuadorian Andes

NOMIS Researcher(s)

Published in

May 9, 2023

The biogeochemistry of rapidly retreating Andean glaciers is poorly understood, and Ecuadorian glacier dissolved organic matter (DOM) composition is unknown. This study examined molecular composition and carbon isotopes of DOM from supraglacial and outflow streams (n = 5 and 14, respectively) across five ice capped volcanoes in Ecuador. Compositional metrics were paired with streamwater isotope analyses (δ18O) to assess if outflow DOM composition was associated with regional precipitation gradients and thus an atmospheric origin of glacier DOM. Ecuadorian glacier outflows exported ancient, biolabile dissolved organic carbon (DOC), and DOM contained a high relative abundance (RA) of aliphatic and peptide-like compounds (≥27%RA). Outflows were consistently more depleted in Δ14C-DOC (i.e., older) compared to supraglacial streams (mean −195.2 and −61.3‰ respectively), perhaps due to integration of spatially heterogenous and variably aged DOM pools across the supraglacial environment, or incorporation of aged subglacial OM as runoff was routed to the outflow. Across Ecuador, Δ14C-DOC enrichment was associated with decreased aromaticity of DOM, due to increased contributions of organic matter (OM) from microbial processes or atmospheric deposition of recently fixed and subsequently degraded OM (e.g., biomass burning byproducts). There was a regional gradient between glacier outflow DOM composition and streamwater δ18O, suggesting covariation between regional precipitation gradients and the DOM exported from glacier outflows. Ultimately, this highlights that atmospheric deposition may exert a control on glacier outflow DOM composition, suggesting regional air circulation patterns and precipitation sources in part determine the origins and quality of OM exported from glacier environments. © 2023. American Geophysical Union. All Rights Reserved.

Research field(s)
Natural Sciences, Earth & Environmental Sciences, Meteorology & Atmospheric Sciences

DOI
10.1029/2022JG007188

The large GTPase Sey1/atlastin mediates lipid droplet-and FadL-dependent intracellular fatty acid metabolism of Legionella pneumophila

NOMIS Researcher(s)

Published in

May 9, 2023

The amoeba-resistant bacterium Legionella pneumophila causes Legionnaires’ disease and employs a type IV secretion system (T4SS) to replicate in the unique, ER-associated Legionella-containing vacuole (LCV). The large fusion GTPase Sey1/atlastin is implicated in ER dynamics, ER-de-rived lipid droplet (LD) formation, and LCV maturation. Here, we employ cryo-electron tomography, confocal microscopy, proteomics, and isotopologue profiling to analyze LCV-LD interactions in the genetically tractable amoeba Dictyostelium discoideum. Dually fluorescence-labeled D. discoideum producing LCV and LD markers revealed that Sey1 as well as the L. pneumophila T4SS and the Ran GTPase activator LegG1 promote LCV-LD interactions. In vitro reconstitution using purified LCVs and LDs from parental or Δsey1 mutant D. discoideum indicated that Sey1 and GTP promote this process. Sey1 and the L. pneumophila fatty acid transporter FadL were implicated in palmi-tate catabolism and palmitate-dependent intracellular growth. Taken together, our results reveal that Sey1 and LegG1 mediate LD-and FadL-dependent fatty acid metabolism of intracellular L. pneumophila. © Hüsler et al.

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

DOI
10.7554/eLife.85142

Explanations in the wild

NOMIS Researcher(s)

Published in

May 3, 2023

Why do some explanations strike people as highly satisfying while others, seemingly equally accurate, satisfy them less? We asked laypeople to generate and rate thousands of open-ended explanations in response to ‘Why?’ questions spanning multiple domains, and analyzed the properties of these explanations to discover (1) what kinds of features are associated with greater explanation quality; (2) whether people can tell how good their explanations are; and (3) which cognitive traits predict the ability to generate good explanations. Our results support a pluralistic view of explanation, where satisfaction is best predicted by either functional or mechanistic content. Respondents were better able to judge how accurate their explanations were than how satisfying they were to others. Insight problem solving ability was the cognitive ability most strongly associated with the generation of satisfying explanations. © 2023 Elsevier B.V.

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

DOI
10.1016/j.cognition.2023.105464

Ordinary citizens are more severe towards verbal than nonverbal hate-motivated incidents with identical consequences

NOMIS Researcher(s)

Published in

May 2, 2023

Do we judge hate incidents similarly when they are performed using words or bodily actions? Hate speech incidents are rarely reported by bystanders, and whether or how much they should be punished remains a matter of legal, theoretical and social disagreement. In a pre-registered study (N = 1309), participants read about verbal and nonverbal attacks stemming from identical hateful intent, which created the same consequences for the victims. We asked them how much punishment the perpetrator should receive, how likely they would be to denounce such an incident and how much harm they judged the victim suffered. The results contradicted our pre-registered hypotheses and the predictions of dual moral theories, which hold that intention and harmful consequences are the sole psychological determinants of punishment. Instead, participants consistently rated verbal hate attacks as more deserving of punishment, denunciation and being more harmful to the victim than nonverbal attacks. This difference is explained by the concept of action aversion, suggesting that lay observers have different intrinsic associations with interactions involving words compared to bodily actions, regardless of consequences. This explanation has implications for social psychology, moral theories, and legislative efforts to sanction hate speech, which are considered. Protocol registration: The Stage 1 protocol for this Registered Report was accepted in principle on 29/06/2022. The protocol, as accepted by the journal, can be found at: https://doi.org/10.17605/OSF.IO/Z86TV . © 2023, The Author(s).

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

DOI
10.1038/s41598-023-33892-8

Semisynthetic LC3 Probes for Autophagy Pathways Reveal a Noncanonical LC3 Interacting Region Motif Crucial for the Enzymatic Activity of Human ATG3

NOMIS Researcher(s)

Published in

April 27, 2023

Macroautophagy is one of two major degradation systems in eukaryotic cells. Regulation and control of autophagy are often achieved through the presence of short peptide sequences called LC3 interacting regions (LIR) in autophagy-involved proteins. Using a combination of new protein-derived activity-based probes prepared from recombinant LC3 proteins, along with protein modeling and X-ray crystallography of the ATG3-LIR peptide complex, we identified a noncanonical LIR motif in the human E2 enzyme responsible for LC3 lipidation, ATG3. The LIR motif is present in the flexible region of ATG3 and adopts an uncommon β-sheet structure binding to the backside of LC3. We show that the β-sheet conformation is crucial for its interaction with LC3 and used this insight to design synthetic macrocyclic peptide-binders to ATG3. CRISPR-enabled in cellulo studies provide evidence that LIRATG3is required for LC3 lipidation and ATG3∼LC3 thioester formation. Removal of LIRATG3negatively impacts the rate of thioester transfer from ATG7 to ATG3. © 2023 American Chemical Society. All rights reserved.

Research field(s)
Health Sciences, Chemistry, Organic Chemistry

DOI
10.1021/acscentsci.3c00009

Ab initio calculation of the reflectivity of molecular fluids under shock compression

NOMIS Researcher(s)

Published in

April 13, 2023

We calculate reflectivities of dynamically compressed water, water-ethanol mixtures, and ammonia at infrared and optical wavelengths with density functional theory and molecular dynamics simulations. The influence of the exchange-correlation functional on the results is examined in detail. Our findings indicate that the consistent use of the HSE hybrid functional reproduces experimental results much better than the commonly used PBE functional. The HSE functional offers not only a more accurate description of the electronic band gap but also shifts the onset of molecular dissociation in the molecular dynamics simulations to significantly higher pressures. We also highlight the importance of using accurate reference standards in reflectivity experiments and reanalyze infrared and optical reflectivity data from recent experiments. Thus, our combined theoretical and experimental work explains and resolves lingering discrepancies between calculations and measurements for the investigated molecular substances under shock compression. © 2023 American Physical Society.

Research field(s)
Natural Sciences

DOI
10.1103/PhysRevB.107.134109

Precise modulation of transcription factor levels identifies features underlying dosage sensitivity

NOMIS Researcher(s)

Published in

April 6, 2023

Transcriptional regulation exhibits extensive robustness, but human genetics indicates sensitivity to transcription factor (TF) dosage. Reconciling such observations requires quantitative studies of TF dosage effects at trait-relevant ranges, largely lacking so far. TFs play central roles in both normal-range and disease-associated variation in craniofacial morphology; we therefore developed an approach to precisely modulate TF levels in human facial progenitor cells and applied it to SOX9, a TF associated with craniofacial variation and disease (Pierre Robin sequence (PRS)). Most SOX9-dependent regulatory elements (REs) are buffered against small decreases in SOX9 dosage, but REs directly and primarily regulated by SOX9 show heightened sensitivity to SOX9 dosage; these RE responses partially predict gene expression responses. Sensitive REs and genes preferentially affect functional chondrogenesis and PRS-like craniofacial shape variation. We propose that such REs and genes underlie the sensitivity of specific phenotypes to TF dosage, while buffering of other genes leads to robust, nonlinear dosage-to-phenotype relationships. © 2023, The Author(s).

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

DOI
10.1038/s41588-023-01366-2

Generation of ventralized human thalamic organoids with thalamic reticular nucleus

NOMIS Researcher(s)

Published in

April 4, 2023

Human brain organoids provide unique platforms for modeling several aspects of human brain development and pathology. However, current brain organoid systems mostly lack the resolution to recapitulate the development of finer brain structures with subregional identity, including functionally distinct nuclei in the thalamus. Here, we report a method for converting human embryonic stem cells (hESCs) into ventral thalamic organoids (vThOs) with transcriptionally diverse nuclei identities. Notably, single-cell RNA sequencing revealed previously unachieved thalamic patterning with a thalamic reticular nucleus (TRN) signature, a GABAergic nucleus located in the ventral thalamus. Using vThOs, we explored the functions of TRN-specific, disease-associated genes patched domain containing 1 (PTCHD1) and receptor tyrosine-protein kinase (ERBB4) during human thalamic development. Perturbations in PTCHD1 or ERBB4 impaired neuronal functions in vThOs, albeit not affecting the overall thalamic lineage development. Together, vThOs present an experimental model for understanding nuclei-specific development and pathology in the thalamus of the human brain. © 2023 Elsevier Inc.

Research field(s)
Health Sciences

DOI
10.1016/j.stem.2023.03.007

Algorithmic Nudging: The Need for an Interdisciplinary Oversight

NOMIS Researcher(s)

Published in

April 3, 2023

Nudge is a popular public policy tool that harnesses well-known biases in human judgement to subtly guide people’s decisions, often to improve their choices or to achieve some socially desirable outcome. Thanks to recent developments in artificial intelligence (AI) methods new possibilities emerge of how and when our decisions can be nudged. On the one hand, algorithmically personalized nudges have the potential to vastly improve human daily lives. On the other hand, blindly outsourcing the development and implementation of nudges to “black box” AI systems means that the ultimate reasons for why such nudges work, that is, the underlying human cognitive processes that they harness, will often be unknown. In this paper, we unpack this concern by considering a series of examples and case studies that demonstrate how AI systems can learn to harness biases in human judgment to reach a specified goal. Drawing on an analogy in a philosophical debate concerning the methodology of economics, we call for the need of an interdisciplinary oversight of AI systems that are tasked and deployed to nudge human behaviours. © 2023, The Author(s).

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

DOI
10.1007/s11245-023-09907-4

‘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

The Transition to Agriculture

NOMIS Researcher(s)

March 31, 2023

A review of ideas about the spread of agriculture from the Near East into Europe introduces a bioarchaeological investigation of the question. Strontium isotope analysis is used to make an important point about the transition to agriculture, rather large datasets are available from two areas where the transition to agriculture is well defined and where there are a substantial number of burials—in the Danube Gorges between Serbia and Romania and in Southern Scandinavia. This paper will discuss each area separately prior to a more general synthesis of the results. The moral of the story has to do with mobility and sedentism.

Research field(s)
Archaeology

DOI
10.1007/978-3-031-25722-3_6

Curvature induces active velocity waves in rotating spherical tissues

NOMIS Researcher(s)

Published in

March 24, 2023

The multicellular organization of diverse systems, including embryos, intestines, and tumors relies on coordinated cell migration in curved environments. In these settings, cells establish supracellular patterns of motion, including collective rotation and invasion. While such collective modes have been studied extensively in flat systems, the consequences of geometrical and topological constraints on collective migration in curved systems are largely unknown. Here, we discover a collective mode of cell migration in rotating spherical tissues manifesting as a propagating single-wavelength velocity wave. This wave is accompanied by an apparently incompressible supracellular flow pattern featuring topological defects as dictated by the spherical topology. Using a minimal active particle model, we reveal that this collective mode arises from the effect of curvature on the active flocking behavior of a cell layer confined to a spherical surface. Our results thus identify curvature-induced velocity waves as a mode of collective cell migration, impacting the dynamical organization of 3D curved tissues. © 2023, The Author(s).

Research field(s)
Natural Sciences, Physics & Astronomy, Fluids & Plasmas

DOI
10.1038/s41467-023-37054-2

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

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