Insight
is our reward
Search

NOMIS Insights

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.

Molecular basis of RNA-binding and autoregulation by the cancer-associated splicing factor RBM39

NOMIS Researcher(s)

Published in

September 4, 2023

Pharmacologic depletion of RNA-binding motif 39 (RBM39) using aryl sulfonamides represents a promising anti-cancer therapy but requires high levels of the adaptor protein DCAF15. Consequently, novel approaches to deplete RBM39 in an DCAF15-independent manner are required. Here, we uncover that RBM39 autoregulates via the inclusion of a poison exon into its own pre-mRNA and identify the cis-acting elements that govern this regulation. We also determine the NMR solution structures of RBM39’s tandem RNA recognition motifs (RRM1 and RRM2) bound to their respective RNA targets, revealing how RRM1 recognises RNA stem loops whereas RRM2 binds specifically to single-stranded N(G/U)NUUUG. Our results support a model where RRM2 selects the 3’-splice site of a poison exon and the RRM3 and RS domain stabilise the U2 snRNP at the branchpoint. Our work provides molecular insights into RBM39-dependent 3’-splice site selection and constitutes a solid basis to design alternative anti-cancer therapies. © 2023, Springer Nature Limited.

Research field(s)
Health Sciences

DOI
10.1038/s41467-023-40254-5

Allocative Skill

NOMIS Researcher(s)

Published in

September 1, 2023

Jobs increasingly require good decision-making. Workers are valued not only for how much they can do, but also for their ability to decide what to do. In this paper we develop a theory and measurement paradigm for assessing individual variation in the ability to make good decisions about resource allocation, which we call allocative skill. We begin with a model where agents strategically acquire information about factor productivity under time and effort constraints. Conditional on such constraints, agents’ allocative skill can be defined as the marginal product of their attention. We test our model in a field survey where participants act as managers assigning fictional workers with heterogeneous productivity schedules to job tasks and are paid in proportion to output. Allocative skill strongly predicts full-time labor earnings, even conditional on IQ, numeracy, and education, and the return to allocative skill is greater in decision-intensive occupations.

Research field(s)
Economics

DOI
10.3386/w31674

Horror Vacui: Racial Misalignment, Symbolic Repair, and Imperial Legitimation in German National Socialist Portrait Photography

NOMIS Researcher(s)

Published in

September 1, 2023

Racial purity and supremacy were central to Nazi Germany’s claims to European dominion. At the same time, their very own “racial scientific” research showed that most Germans were “mixed-race.” Given the dissonance between phenotypical aspirations to a Nordic ideal and the reality of a largely nonblond German population, how did the National Socialist regime maintain legitimacy to rule? Anthropologists, bureaucrats, and artists resolved this racial misalignment through horror vacui racialization, an excessive social classification that manifested as a racializing turn inward aimed at Christian Germans. I theorize the role of culture and art in stabilizing race-based rule in authoritarian and colonial contexts through racial repair that realigns desired and actual racial self-understandings. The article shows how an ostensibly biologically essentialist regime strategically used racial relativism in science, politics, and popular culture. I outline the sociological implications of this work for the sociologies of culture, of race and ethnicity, of theories of the state, of empire, and of science and technology studies.

Research field(s)
Sociology

DOI
10.1086/727562

Stress, Intertemporal Choice, and Mitigation Behavior During the COVID-19 Pandemic

NOMIS Researcher(s)

Published in

September 1, 2023

Delayed gratification is an important focus of research, given its potential relationship to forms of behavior, such as savings, susceptibility to addiction, and pro-social behaviors. The COVID-19 pandemic may be one of the most consequential recent examples of this phenomenon, with people’s willingness to delay gratification affecting their willingness to socially distance themselves. COVID-19 also provides a naturalistic context by which to evaluate the ecological validity of delayed gratification. This article outlines four large-scale online experiments (total N =12, 906) where we ask participants to perform Money Earlier or Later (MEL) decisions (e.g., $5 today vs. $10 tomorrow) and to also report stress measures and pandemic mitigation behaviors. We found that stress increases impulsivity and that less stressed and more patient individuals socially distanced more throughout the pandemic. These results help resolve longstanding theoretical debates in the MEL literature as well as provide policymakers with scientific evidence that can help inform response strategies in the future © 2023 American Psychological Association

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

DOI
10.1037/xge0001417

The Work that Work does: How intrinsic and instrumental values are transformed into relational values through active work participation in Swiss community supported agriculture

NOMIS Researcher(s)

Published in

August 31, 2023

Community supported agriculture (CSA) is an alternative food network that aims to enable sustainable and just food production by bringing consumers and producers together. One version of CSA (Solidarische Landwirtschaft in German or Solidarity Agriculture) requires active labour participation of members as part of the subscription price. This paper uses a relational values approach to explore what motivates members to join and participate in solidarity agriculture cooperatives and how the experience of participation changes their values and behaviour. Qualitative interviews were conducted with 21 members of three co-operatives and analysed using a grounded theory approach. Specifically, we applied the Syntax of Environmental Values Framework, developed by Deplazes-Zemp and Chapman. Results show that members typically hold strong intrinsic values regarding fair compensation for farmer’s work and local environmental sustainability and instrumental values regarding food quality and healthy eating. We found that participation and work practices at the cooperative added to and changed values and behaviour through new relational connections to food, farmers and to nature via the agricultural landscape. These findings provide new insight into the ways that relational values can be adopted and more broadly on the relationship between values and behaviour. This paper concludes that values, especially relational values, can form and change through lived experiences. Our results can help guide programs aiming to foster pro-environmental values in a local population by highlighting one possible mechanism to do so. Read the free Plain Language Summary for this article on the Journal blog. © 2023 The Authors. People and Nature published by John Wiley & Sons Ltd on behalf of British Ecological Society.

Research field(s)
Arts & Humanities, Philosophy & Theology, Philosophy

DOI
10.1002/pan3.10531

Leaf metabolic traits reveal hidden dimensions of plant form and function

NOMIS Researcher(s)

Published in

August 30, 2023

The metabolome is the biochemical basis of plant form and function, but we know little about its macroecological variation across the plant kingdom. Here, we used the plant functional trait concept to interpret leaf metabolome variation among 457 tropical and 339 temperate plant species. Distilling metabolite chemistry into five metabolic functional traits reveals that plants vary on two major axes of leaf metabolic specialization—a leaf chemical defense spectrum and an expression of leaf longevity. Axes are similar for tropical and temperate species, with many trait combinations being viable. However, metabolic traits vary orthogonally to life-history strategies described by widely used functional traits. The metabolome thus expands the functional trait concept by providing additional axes of metabolic specialization for examining plant form and function. Copyright © 2023 The Authors,

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

DOI
10.1126/sciadv.adi4029

Paired microbiome and metabolome analyses associate bile acid changes with colorectal cancer progression

NOMIS Researcher(s)

Published in

August 29, 2023

Colorectal cancer (CRC) is driven by genomic alterations in concert with dietary influences, with the gut microbiome implicated as an effector in disease development and progression. While meta-analyses have provided mechanistic insight into patients with CRC, study heterogeneity has limited causal associations. Using multi-omics studies on genetically controlled cohorts of mice, we identify diet as the major driver of microbial and metabolomic differences, with reductions in α diversity and widespread changes in cecal metabolites seen in high-fat diet (HFD)-fed mice. In addition, non-classic amino acid conjugation of the bile acid cholic acid (AA-CA) increased with HFD. We show that AA-CAs impact intestinal stem cell growth and demonstrate that Ileibacterium valens and Ruminococcus gnavus are able to synthesize these AA-CAs. This multi-omics dataset implicates diet-induced shifts in the microbiome and the metabolome in disease progression and has potential utility in future diagnostic and therapeutic developments. © 2023 The Author(s)

Research field(s)
Health Sciences, Microbiology

DOI
10.1016/j.celrep.2023.112997

Acetylcholine and noradrenaline enhance foraging optimality in humans

NOMIS Researcher(s)

Published in

August 28, 2023

Foraging theory prescribes when optimal foragers should leave the current option for more rewarding alternatives. Actual foragers often exploit options longer than prescribed by the theory, but it is unclear how this foraging suboptimality arises. We investigated whether the upregulation of cholinergic, noradrenergic, and dopaminergic systems increases foraging optimality. In a double-blind, between-subject design, participants (N = 160) received placebo, the nicotinic acetylcholine receptor agonist nicotine, a noradrenaline reuptake inhibitor reboxetine, or a preferential dopamine reuptake inhibitor methylphenidate, and played the role of a farmer who collected milk from patches with different yield. Across all groups, participants on average overharvested. While methylphenidate had no effects on this bias, nicotine, and to some extent also reboxetine, significantly reduced deviation from foraging optimality, which resulted in better performance compared to placebo. Concurring with amplified goal-directedness and excluding heuristic explanations, nicotine independently also improved trial initiation and time perception. Our findings elucidate the neurochemical basis of behavioral flexibility and decision optimality and open unique perspectives on psychiatric disorders affecting these functions. Copyright © 2023 the Author(s).

Research field(s)
Health Sciences

DOI
10.1073/pnas.2305596120

CD4+ T cells regulate sickness-induced anorexia and fat wasting during a chronic parasitic infection

NOMIS Researcher(s)

Published in

August 24, 2023

Infections cause catabolism of fat and muscle stores. Traditionally, studies have focused on understanding how the innate immune system contributes to energy stores wasting, while the role of the adaptive immune system remains elusive. In the present study, we examine the role of the adaptive immune response in adipose tissue wasting and cachexia using a murine model of the chronic parasitic infection Trypanosoma brucei, the causative agent of sleeping sickness. We find that the wasting response occurs in two phases, with the first stage involving fat wasting caused by CD4+ T cell-induced anorexia and a second anorexia-independent cachectic stage that is dependent on CD8+ T cells. Fat wasting has no impact on host antibody-mediated resistance defenses or survival, while later-stage muscle wasting contributes to disease-tolerance defenses. Our work reveals a decoupling of adaptive immune-mediated resistance from the catabolic response during infection. © 2023 The Author(s)

Research field(s)
Health Sciences

DOI
10.1016/j.celrep.2023.112814

Effect of apolipoprotein genotype and educational attainment on cognitive function in autosomal dominant Alzheimer’s disease

NOMIS Researcher(s)

Published in

August 23, 2023

Autosomal dominant Alzheimer’s disease (ADAD) is genetically determined, but variability in age of symptom onset suggests additional factors may influence cognitive trajectories. Although apolipoprotein E (APOE) genotype and educational attainment both influence dementia onset in sporadic AD, evidence for these effects in ADAD is limited. To investigate the effects of APOE and educational attainment on age-related cognitive trajectories in ADAD, we analyzed data from 675 Presenilin-1 E280A mutation carriers and 594 non-carriers. Here we show that age-related cognitive decline is accelerated in ADAD mutation carriers who also have an APOE e4 allele compared to those who do not and delayed in mutation carriers who also have an APOE e2 allele compared to those who do not. Educational attainment is protective and moderates the effect of APOE on cognition. Despite ADAD mutation carriers being genetically determined to develop dementia, age-related cognitive decline may be influenced by other genetic and environmental factors. © 2023, Springer Nature Limited.

Research field(s)
Health Sciences

DOI
10.1038/s41467-023-40775-z

Lipid saturation controls nuclear envelope function

NOMIS Researcher(s)

Published in

August 17, 2023

The nuclear envelope (NE) is a spherical double membrane with elastic properties. How NE shape and elasticity are regulated by lipid chemistry is unknown. Here we discover lipid acyl chain unsaturation as essential for NE and nuclear pore complex (NPC) architecture and function. Increased lipid saturation rigidifies the NE and the endoplasmic reticulum into planar, polygonal membranes, which are fracture prone. These membranes exhibit a micron-scale segregation of lipids into ordered and disordered phases, excluding NPCs from the ordered phase. Balanced lipid saturation is required for NPC integrity, pore membrane curvature and nucleocytoplasmic transport. Oxygen deprivation amplifies the impact of saturated lipids, causing NE rigidification and rupture. Conversely, lipid droplets buffer saturated lipids to preserve NE architecture. Our study uncovers a fundamental link between lipid acyl chain structure and the integrity of the cell nucleus with implications for nuclear membrane malfunction in ischaemic tissues. © 2023, The Author(s).

Research field(s)
Natural Sciences

DOI
10.1038/s41556-023-01207-8

Distinct molecular profiles of skull bone marrow in health and neurological disorders

NOMIS Researcher(s)

Published in

August 17, 2023

The bone marrow in the skull is important for shaping immune responses in the brain and meninges, but its molecular makeup among bones and relevance in human diseases remain unclear. Here, we show that the mouse skull has the most distinct transcriptomic profile compared with other bones in states of health and injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals that the skull marrow is the most distinct, with differentially expressed neutrophil-related pathways and a unique synaptic protein signature. 3D imaging demonstrates the structural and cellular details of human skull-meninges connections (SMCs) compared with veins. Last, using translocator protein positron emission tomography (TSPO-PET) imaging, we show that the skull bone marrow reflects inflammatory brain responses with a disease-specific spatial distribution in patients with various neurological disorders. The unique molecular profile and anatomical and functional connections of the skull show its potential as a site for diagnosing, monitoring, and treating brain diseases. © 2023 The Author(s)

Research field(s)
Health Sciences

DOI
10.1016/j.cell.2023.07.009

Orbitofrontal cortex control of striatum leads economic decision-making

NOMIS Researcher(s)

Published in

August 17, 2023

Animals must continually evaluate stimuli in their environment to decide which opportunities to pursue, and in many cases these decisions can be understood in fundamentally economic terms. Although several brain regions have been individually implicated in these processes, the brain-wide mechanisms relating these regions in decision-making are unclear. Using an economic decision-making task adapted for rats, we find that neural activity in both of two connected brain regions, the ventrolateral orbitofrontal cortex (OFC) and the dorsomedial striatum (DMS), was required for economic decision-making. Relevant neural activity in both brain regions was strikingly similar, dominated by the spatial features of the decision-making process. However, the neural encoding of choice direction in OFC preceded that of DMS, and this temporal relationship was strongly correlated with choice accuracy. Furthermore, activity specifically in the OFC projection to the DMS was required for appropriate economic decision-making. These results demonstrate that choice information in the OFC is relayed to the DMS to lead accurate economic decision-making. © 2023, The Author(s).

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

DOI
10.1038/s41593-023-01409-1

Superconductivity from a melted insulator in Josephson junction arrays

NOMIS Researcher(s)

Published in

August 10, 2023

Arrays of Josephson junctions are governed by a competition between superconductivity and repulsive Coulomb interactions, and are expected to exhibit diverging low-temperature resistance when interactions exceed a critical level. Here we report a study of the transport and microwave response of Josephson arrays with interactions exceeding this level. Contrary to expectations, we observe that the array resistance drops dramatically as the temperature is decreased—reminiscent of superconducting behaviour—and then saturates at low temperature. Applying a magnetic field, we eventually observe a transition to a highly resistive regime. These observations can be understood within a theoretical picture that accounts for the effect of thermal fluctuations on the insulating phase. On the basis of the agreement between experiment and theory, we suggest that apparent superconductivity in our Josephson arrays arises from melting the zero-temperature insulator. © 2023, The Author(s).

Research field(s)
Natural Sciences

DOI
10.1038/s41567-023-02161-w

The dark side of the moon: First insights into the microbiome structure and function of one of the last glacier-fed streams in Africa

NOMIS Researcher(s)

Published in

August 9, 2023

The glaciers on Africa’s ‘Mountains of the Moon’ (Rwenzori National Park, Uganda) are predicted to disappear within the next decades owing to climate change. Consequently, the glacier-fed streams (GFSs) that drain them will vanish, along with their resident microbial communities. Despite the relevance of microbial communities for performing ecosystem processes in equatorial GFSs, their ecology remains understudied. Here, we show that the benthic microbiome from the Mt. Stanley GFS is distinct at several levels from other GFSs. Specifically, several novel taxa were present, and usually common groups such as Chrysophytes and Polaromonas exhibited lower relative abundances compared to higher-latitude GFSs, while cyanobacteria and diatoms were more abundant. The rich primary producer community in this GFS likely results from the greater environmental stability of the Afrotropics, and accordingly, heterotrophic processes dominated in the bacterial community. Metagenomics revealed that almost all prokaryotes in the Mt. Stanley GFS are capable of organic carbon oxidation, while greater than 80% have the potential for fermentation and acetate oxidation. Our findings suggest a close coupling between photoautotrophs and other microbes in this GFS, and provide a glimpse into the future for high-latitude GFSs globally where primary production is projected to increase with ongoing glacier shrinkage. © 2023 The Authors.

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

DOI
10.1098/rsos.230329

Female naïve human pluripotent stem cells carry X chromosomes with Xa-like and Xi-like folding conformations

NOMIS Researcher(s)

Published in

August 4, 2023

Three-dimensional (3D) genomics shows immense promise for studying X chromosome inactivation (XCI) by interrogating changes to the X chromosomes’ 3D states. Here, we sought to characterize the 3D state of the X chromosome in naïve and primed human pluripotent stem cells (hPSCs). Using chromatin tracing, we analyzed X chromosome folding conformations in these cells with megabase genomic resolution. X chromosomes in female naïve hPSCs exhibit folding conformations similar to the active X chromosome (Xa) and the inactive X chromosome (Xi) in somatic cells. However, naïve X chromosomes do not exhibit the chromatin compaction typically associated with these somatic X chromosome states. In H7 naïve human embryonic stem cells, XIST accumulation observed on damaged X chromosomes demonstrates the potential for naïve hPSCs to activate XCI-related mechanisms. Overall, our findings provide insight into the X chromosome status of naïve hPSCs with a single-chromosome resolution and are critical in understanding the unique epigenetic regulation in early embryonic cells. Copyright © 2023 The Authors, some rights reserved.

Research field(s)
Health Sciences

DOI
10.1126/sciadv.adf2245

Computation-Limited Bayesian Updating

NOMIS Researcher(s)

Published in

August 1, 2023

Effectively updating one’s beliefs requires sufficient empirical evidence (i.e., data) and the computational capacity to process it. Yet both data and computational resources are limited for human minds. Here, we study the problem of belief updating under limited data and limited computation. Using information theory to characterize constraints on computation, we find that the solution to the resulting optimization problem links the data and computational limitations together: when computational resources are tight, agents may not be able to integrate new empirical evidence. The resource-rational belief updating rule we identify offers a novel interpretation of conservative Bayesian updating.

Research field(s)
Psychology & Cognitive Sciences

Comparing Human Predictions from Expert Advice to On-line Optimization Algorithms

NOMIS Researcher(s)

Published in

August 1, 2023

On-line decision problems – in which a decision is made based on a sequence of past events without knowledge of the future – have been extensively studied in theoretical computer science. A famous example is the Prediction from Expert Advice problem, in which an agent has to make a decision informed by the predictions of a set of experts. An optimal solution to this problem is the Multiplicative Weights Update Method (MWUM). In this paper, we investigate how humans behave in a Prediction from Expert Advice task. We compare MWUM and several other algorithms proposed in the computer science literature against human behavior. We find that MWUM provides the best fit to people’s choices.

Research field(s)
Psychology & Cognitive Sciences

To each their own theory: Exploring the limits of individual differences in decisions under risk

NOMIS Researcher(s)

August 1, 2023

Theories in cognitive science are primarily aimed at explaining human behavior in general, appealing to universal constructs such as perception or attention. When it is considered, modeling of individual differences is typically performed by adapting model parameters. The implicit assumption of this standard approach is that people are relatively similar, employing the same basic cognitive processes in a given problem domain. In this work, we consider a broader evaluation of the way in which people may differ. We evaluate 23 models of risky choice on around 300 individuals, and find that most models—spanning various constructs from heuristic rules and attention to regret and subjective perception—explain the behavior of different subpopulations of individuals. These results may account for part of the difficulty in obtaining a single elegant explanation of behavior in some long-studied domains, and suggest a more serious consideration of individual variability in theory comparisons going forward.

Research field(s)
Psychology & Cognitive Sciences

Delusion-Like Beliefs and Data Quality: Are Classic Cognitive Biases Artifacts of Carelessness?

NOMIS Researcher(s)

Published in

August 1, 2023

There is widespread agreement that delusions in clinical populations and delusion-like beliefs in the general population are, in part, caused by cognitive biases. Much of the evidence comes from two influential tasks: the Beads Task and the Bias Against Disconfirmatory Evidence Task. However, research using these tasks has been hampered by conceptual and empirical inconsistencies. In an online study, we examined relationships between delusion-like beliefs in the general population and cognitive biases associated with these tasks. Our study had four key strengths: A new animated Beads Task designed to reduce task miscomprehension, several data-quality checks to identify careless responders, a large sample (n= 1,002), and a preregistered analysis plan. When analyzing the full sample, our results replicated classic relationships between cognitive biases and delusion-like beliefs. However, when we removed 82 careless participants from the analyses (8.2% of the sample) we found that many of these relationships were severely diminished and, in some cases, eliminated outright. These results suggest that some (but not all) seemingly well-established relationships between cognitive biases and delusion-like beliefs might be artifacts of careless responding. © 2023 American Psychological Association

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

DOI
10.1037/abn0000844

Load More