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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.

If you please, draw me a neuron — linking evolutionary tinkering with human neuron evolution

NOMIS Researcher(s)

Published in

October 1, 2024

Animal speciation often involves novel behavioral features that rely on nervous system evolution. Human-specific brain features have been proposed to underlie specialized cognitive functions and to be linked, at least in part, to the evolution of synapses, neurons, and circuits of the cerebral cortex. Here, we review recent results showing that, while the human cortex is composed of a repertoire of cells that appears to be largely similar to the one found in other mammals, human cortical neurons do display specialized features at many levels, from gene expression to intrinsic physiological properties. The molecular mechanisms underlying human species-specific neuronal features remain largely unknown but implicate hominid-specific gene duplicates that encode novel molecular modifiers of neuronal function. The identification of human-specific genetic modifiers of neuronal function brings novel insights on brain evolution and function and, could also provide new insights on human species-specific vulnerabilities to brain disorders.

Research field(s)
Genetics & Heredity, Evolutionary Biology

DOI
10.1016/j.gde.2024.102260

Bayes in the age of intelligent machines

NOMIS Researcher(s)

Published in

September 21, 2024

The success of methods based on artificial neural networks in creating intelligent machines seems like it might pose a challenge to explanations of human cognition in terms of Bayesian inference. We argue that this is not the case and that these systems in fact offer new opportunities for Bayesian modeling. Specifically, we argue that artificial neural networks and Bayesian models of cognition lie at different levels of analysis and are complementary modeling approaches, together offering a way to understand human cognition that spans these levels. We also argue that the same perspective can be applied to intelligent machines, in which a Bayesian approach may be uniquely valuable in understanding the behavior of large, opaque artificial neural networks that are trained on proprietary data.

Research field(s)
Artificial Intelligence & Image Processing, Psychology & Cognitive Sciences

DOI
10.1177/09637214241262329

Gradients of Deposition and In Situ Production Drive Global Glacier Organic Matter Composition

NOMIS Researcher(s)

Published in

September 19, 2024

Runoff from rapidly melting mountain glaciers is a dominant source of riverine organic carbon in many high-latitude and high-elevation regions. Glacier dissolved organic carbon is highly bioavailable, and its composition likely reflects internal (e.g., autotrophic production) and external (i.e., atmospheric deposition) sources. However, the balance of these sources across Earth’s glaciers is poorly understood, despite implications for the mineralization and assimilation of glacier organic carbon within recipient ecosystems. We assessed the molecular-level composition of dissolved organic matter from 136 mountain glacier outflows from 11 regions covering six continents using ultrahigh resolution 21 T mass spectrometry. We found substantial diversity in organic matter composition with coherent and predictable (80% accuracy) regional patterns. Employing stable and radiocarbon isotopic analyses, we demonstrate that these patterns are inherently linked to atmospheric deposition and in situ production. In remote regions like Greenland and New Zealand, the glacier organic matter pool appears to be dominated by in situ production. However, downwind of industrial centers (e.g., Alaska and Nepal), fossil fuel combustion byproducts likely underpin organic matter composition, resulting in older and more aromatic material being exported downstream. These findings highlight that the glacier carbon cycle is spatially distinct, with ramifications for predicting the dynamics and fate of glacier organic carbon concurrent with continued retreat and anthropogenic perturbation.

Research field(s)
Conservation Biology, Biology

DOI
10.1029/2024GB008212

New insights to be gained from a Virtual Ecosystem

NOMIS Researcher(s)

Published in

September 16, 2024

The myriad interactions among individual plants, animals, microbes and their abiotic environment generate emergent phenomena that will determine the future of life on Earth. Here, we argue that holistic ecosystem models – incorporating key biological domains and feedbacks between biotic and abiotic processes and capable of predicting emergent phenomena – are required if we are to understand the functioning of complex, terrestrial ecosystems in a rapidly changing planet. We argue that holistic ecosystem models will provide a framework for integrating the many approaches used to study ecosystems, including biodiversity science, population and community ecology, soil science, biogeochemistry, hydrology and climate science. Holistic models will provide new insights into the nature and importance of feedbacks that cut across scales of space and time, and that connect ecosystem domains such as microbes with animals or above with below ground. They will allow us to critically examine the origins and maintenance of ecosystem stability, resilience and sustainability through the lens of systems theory, and provide a much-needed boost for conservation and the management of natural environments. We outline our approach to developing a holistic ecosystem model – the Virtual Ecosystem – and argue that while the construction of such complex models is obviously ambitious, it is both feasible and necessary.

Research field(s)
Conservation Biology, Ecology, Environmental Sciences

DOI
10.1016/j.ecolmodel.2024.110866

Visual Pleasures? Wehrmacht Vernacular Trophy Photographs and the Female Other in Nazi-Occupied Europe

NOMIS Researcher(s)

Published in

September 9, 2024

Innumerable historical snapshots from World War II depict German soldiers visually celebrating their victories over an enemy or conquered population. Trophy photographs of German soldiers serve as one valuable heuristic tool to probe German visual cultures and military performances of the self. Indulging in common pictorial tropes that include fixating on female bodies, they have largely been ignored by Holocaust scholars who tend to concentrate on photographs of violence and their evidentiary value. This article places German images of wartime courtship and sexual conquest in dialogue within a broader spectrum of images depicting encounters with women in Nazi-occupied Europe. Photographs of hookups and flirtation with the female vanquished population enable us to embed Nazi warfare and the Holocaust not only in the larger context of conquest and exploitation, but also the cultural and affective mindset of combatants. Delving into the multifaceted histories of these images allows one to deconstruct the violence that lurks beneath the esthetically ‘benign’ visibility and to question the ambivalent affective power of the hyper-violent photographs. In the aggregate, images of violence, humiliation, and non-injurious sexual desire expose a range of behaviors and further shine a light on the ways in which mass violence and genocide are embedded in photographs. The article investigates different motives and ways in which German soldiers visually and physically conquered foreign women and how they ogled and photographically appropriated them. By scrutinizing body language, gestures, facial expressions, and poses the article peels back different layers of the camera’s gaze and of the depicted German soldiers and female subjects, while simultaneously scrutinizing the intersection of sexuality and violence, where desire, spectacle, and esthetics converge into visual pleasure.

Research field(s)
History

DOI
10.1080/25785648.2024.2385160

Digital solutions in paediatric sepsis: current state, challenges, and opportunities to improve care around the world

NOMIS Researcher(s)

Published in

September 1, 2024
The digitisation of health care is offering the promise of transforming the management of paediatric sepsis, which is a major source of morbidity and mortality in children worldwide. Digital technology is already making an impact in paediatric sepsis, but is almost exclusively benefiting patients in high-resource health-care settings. However, digital tools can be highly scalable and cost-effective, and—with the right planning—have the potential to reduce global health disparities. Novel digital solutions, from wearable devices and mobile apps, to electronic health record-embedded decision support tools, have an unprecedented opportunity to transform paediatric sepsis research and care. In this Series paper, we describe the current state of digital solutions in paediatric sepsis around the world, the advances in digital technology that are enabling the development of novel applications, and the potential effect of advances in artificial intelligence in paediatric sepsis research and clinical care.

Research field(s)
Pediatrics

DOI
10.1016/S2589-7500(24)00141-9

Quality improvement programmes in paediatric sepsis from a global perspective

NOMIS Researcher(s)

Published in

September 1, 2024

Sepsis is a major contributor to poor child health outcomes around the world. The high morbidity, mortality, and societal cost associated with paediatric sepsis render it a global health priority, as summarised in Paper 1 of this Series. Sepsis is characterised by a dysregulated host response to infection that manifests as organ failure, and children are uniquely susceptible to sepsis, as discussed in Paper 2. The focus of this third Series paper is quality improvement in paediatric sepsis. The 2017 WHO resolution on sepsis outlined key aims to reduce the burden of sepsis. As of 2024, only a small number of countries have implemented systematic, paediatric-focused quality improvement programmes to raise sepsis awareness, enhance recognition of sepsis, promote timely treatment, and provide long-term support for paediatric sepsis survivors. We examine programme successes and systematic barriers to quality improvement targeting paediatric sepsis. We highlight the need for programme design to consider the entire patient journey, starting with prevention, caregiver awareness, recognition at home, education of the health-care workforce, development of health-care systems, and establishment of long-term family and survivor support extending beyond the intensive care unit. Building on lessons learnt from existing quality improvement programmes, we outline implementation strategies and measures to enable benchmarking. Ultimately, quality improvement on a global scale can only be accelerated through a global learning platform focusing on paediatric sepsis.

This is the third in a Series of four papers on paediatric sepsis (Paper 4 appears in The Lancet Digital Health). All papers in the Series are available at thelancet.com/series/paediatric-sepsis

Research field(s)
Pediatrics

DOI
10.1016/S2352-4642(24)00142-1

Susceptibility to childhood sepsis, contemporary management, and future directions

NOMIS Researcher(s)

Published in

September 1, 2024

Sepsis disproportionally affects children across all health-care settings and is one of the leading causes of morbidity and mortality in neonatal and paediatric age groups. As shown in the first paper in this Series, the age-specific incidence of sepsis is highest during the first years of life, before approaching adult incidence rates during adolescence. In the second paper in this Series, we focus on the unique susceptibility of paediatric patients to sepsis and how the underlying dysregulated host response relates to developmental aspects of children’s immune system, genetic, perinatal, and environmental factors, and comorbidities and socioeconomic determinants of health, which often differ between children and adults. State-of-the-art clinical management of paediatric sepsis is organised around three treatment pillars—diagnosis, early resuscitation, and titration of advanced care—and we examine available treatment guidelines and the limitations of their supporting evidence. Serious evidence gaps remain in key areas of paediatric sepsis care, especially surrounding recognition, common interventions, and survivor support, and to this end we offer a research roadmap for the next decade that could accelerate targeted diagnostics and personalised use of immunomodulation. However, improving outcomes for children with sepsis relies fundamentally on systematic quality improvement in both recognition and treatment, which is the theme of the third paper in this Series. Digital health, as shown in the fourth and final paper of this Series, holds promising potential in breaking down the barriers that hinder progress in paediatric sepsis care and, ultimately, global child health.

This is the second in a Series of four papers on paediatric sepsis (Paper 4 appears in The Lancet Digital Health). All papers in the Series are available at thelancet.com/series/paediatric-sepsis

Research field(s)
Pediatrics

DOI
10.1016/S2352-4642(24)00141-X

The burden and contemporary epidemiology of sepsis in children

NOMIS Researcher(s)

Published in

September 1, 2024

Sepsis is a dysregulated host response to infection that leads to life-threatening organ dysfunction. Half of the 50 million people affected by sepsis globally every year are neonates and children younger than 19 years. This burden on the paediatric population translates into a disproportionate impact on global child health in terms of years of life lost, morbidity, and lost opportunities for children to reach their developmental potential. This Series on paediatric sepsis presents the current state of diagnosis and treatment of sepsis in children, and maps the challenges in alleviating the burden on children, their families, and society. Drawing on diverse experience and multidisciplinary expertise, we offer a roadmap to improving outcomes for children with sepsis. This first paper of the Series is a narrative review of the burden of paediatric sepsis from low-income to high-income settings. Advances towards improved operationalisation of paediatric sepsis across all age groups have facilitated more standardised assessment of the Global Burden of Disease estimates of the impact of sepsis on child health, and these estimates are expected to gain further precision with the roll out of the new Phoenix criteria for sepsis. Sepsis remains one of the leading causes of childhood morbidity and mortality, with immense direct and indirect societal costs. Although substantial regional differences persist in relation to incidence, microbiological epidemiology, and outcomes, these cannot be explained by differences in income level alone. Recent insights into post-discharge sequelae after paediatric sepsis, ranging from late mortality and persistent neurodevelopmental impairment to reduced health-related quality of life, show how common post-sepsis syndrome is in children. Targeting sepsis as a key contributor to poor health outcomes in children is therefore an essential component of efforts to meet the Sustainable Development Goals.

This is the first in a Series of four papers on paediatric sepsis (Paper 4 appears in The Lancet Digital Health). All papers in the Series are available at thelancet.com/series/paediatric-sepsis

Research field(s)
Pediatrics

DOI
10.1016/S2352-4642(24)00140-8

Docking a flexible basket onto the core of the nuclear pore complex

NOMIS Researcher(s)

Published in

August 13, 2024

The nuclear basket attaches to the nucleoplasmic side of the nuclear pore complex (NPC), coupling transcription to mRNA quality control and export. The basket expands the functional repertoire of a subset of NPCs in Saccharomyces cerevisiae by drawing a unique RNA/protein interactome. Yet, how the basket docks onto the NPC core remains unknown. By integrating AlphaFold-based interaction screens, electron microscopy and membrane-templated reconstitution, we uncovered a membrane-anchored tripartite junction between basket and NPC core. The basket subunit Nup60 harbours three adjacent short linear motifs, which connect Mlp1, a parallel homodimer consisting of coiled-coil segments interrupted by flexible hinges, and the Nup85 subunit of the Y-complex. We reconstituted the Y-complex•Nup60•Mlp1 assembly on a synthetic membrane and validated the protein interfaces in vivo. Here we explain how a short linear motif-based protein junction can substantially reshape NPC structure and function, advancing our understanding of compositional and conformational NPC heterogeneity.

Research field(s)
Biochemistry & Molecular Biology, Biology

DOI
10.1038/s41556-024-01484-x

Removal of TREX1 activity enhances CRISPR–Cas9-mediated homologous recombination

NOMIS Researcher(s)

Published in

August 12, 2024

CRISPR–Cas9-mediated homology-directed repair (HDR) can introduce desired mutations at targeted genomic sites, but achieving high efficiencies is a major hurdle in many cell types, including cells deficient in DNA repair activity. In this study, we used genome-wide screening in Fanconi anemia patient lymphoblastic cell lines to uncover suppressors of CRISPR–Cas9-mediated HDR. We found that a single exonuclease, TREX1, reduces HDR efficiency when the repair template is a single-stranded or linearized double-stranded DNA. TREX1 expression serves as a biomarker for CRISPR–Cas9-mediated HDR in that the high TREX1 expression present in many different cell types (such as U2OS, Jurkat, MDA-MB-231 and primary T cells as well as hematopoietic stem and progenitor cells) predicts poor HDR. Here we demonstrate rescue of HDR efficiency (ranging from two-fold to eight-fold improvement) either by TREX1 knockout or by the use of single-stranded DNA templates chemically protected from TREX1 activity. Our data explain why some cell types are easier to edit than others and indicate routes for increasing CRISPR–Cas9-mediated HDR in TREX1-expressing contexts.

Research field(s)
Biochemistry & Molecular Biology, Genetics & Heredity

DOI
10.1038/s41587-024-02356-3

An audacious approach to conservation

NOMIS Researcher(s)

Published in

August 8, 2024

New digital and sensor technology provides a huge opportunity to revolutionise conservation, but we lack a plan for deploying the technologies effectively. I argue that environmental research should be concentrated at a small number of ‘super-sites’ and that the concentrated knowledge from super-sites should be used to develop holistic ecosystem models. These, in turn, should be morphed into digital twin ecosystems by live connecting them with automated environmental monitoring programmes. Data-driven simulations can then help select pathways to achieve locally determined conservation goals, and digital twins could revise and adapt those decisions in real-time. This technology-heavy vision for ‘smart conservation’ provides a map toward a future defined by more flexible, more responsive, and more efficient management of natural environments.

Research field(s)
Conservation Biology, Ecology, Environmental Sciences

DOI
10.1016/j.tree.2024.07.003

A gate tunable transmon qubit in planar Ge

NOMIS Researcher(s)

Published in

July 30, 2024

Gate-tunable transmons (gatemons) employing semiconductor Josephson junctions have recently emerged as building blocks for hybrid quantum circuits. In this study, we present a gatemon fabricated in planar Germanium. We induce superconductivity in a two-dimensional hole gas by evaporating aluminum atop a thin spacer, which separates the superconductor from the Ge quantum well. The Josephson junction is then integrated into an Xmon circuit and capacitively coupled to a transmission line resonator. We showcase the qubit tunability in a broad frequency range with resonator and two-tone spectroscopy. Time-domain characterizations reveal energy relaxation and coherence times up to 75 ns. Our results, combined with the recent advances in the spin qubit field, pave the way towards novel hybrid and protected qubits in a group IV, CMOS-compatible material.

Research field(s)
Josephson Junctions, Qubits

DOI
10.1038/s41467-024-50763-6

The peripheral interior and people as infrastructure: adopting the sewer system for passage

NOMIS Researcher(s)

Published in

July 29, 2024

During the Warsaw Uprising of 1944, soldiers and civilians used the city’s sewer system to move from place to place and to pass objects and information. Although many who entered the underground did not survive its conditions, the adoption of the sewer as a passage for people did save thousands of lives. Drawing on technical materials and testimonies of the survivors, the article examines this appropriation of the sewer system, concentrating on the way it functioned. It explicates how the reliance of the sewer’s adoption on the engagement of people turned them and their bodies into infrastructure, and how it led to augmenting the ontology of the sewer. The article offers a new interpretation of the Warsaw sewer appropriation and enriches the conceptual framework by bridging infrastructural notions with the periphery-centre concepts. Moreover, it advances research on ‘periphery’ by, firstly, counteracting the underrepresented and peripheral status of Eastern Europe in architectural history and, secondly, validating infrastructural spaces and broadening the scope of spaces included as interiors frequented by people. The paper also contributes to scholarship on spaces experienced largely through non-visual sensory modalities, an understudied area of architectural history due to the discipline’s rootedness in the domain of sight.

Research field(s)
Architecture

DOI
10.1080/13602365.2024.2370284

CCAR1 promotes DNA repair via alternative splicing

NOMIS Researcher(s)

Published in

July 25, 2024

DNA repair is directly performed by hundreds of core factors and indirectly regulated by thousands of others. We massively expanded a CRISPR inhibition and Cas9-editing screening system to discover factors indirectly modulating homology-directed repair (HDR) in the context of ∼18,000 individual gene knockdowns. We focused on CCAR1, a poorly understood gene that we found the depletion of reduced both HDR and interstrand crosslink repair, phenocopying the loss of the Fanconi anemia pathway. CCAR1 loss abrogated FANCA protein without substantial reduction in the level of its mRNA or that of other FA genes. We instead found that CCAR1 prevents inclusion of a poison exon in FANCA. Transcriptomic analysis revealed that the CCAR1 splicing modulatory activity is not limited to FANCA, and it instead regulates widespread changes in alternative splicing that would damage coding sequences in mouse and human cells. CCAR1 therefore has an unanticipated function as a splicing fidelity factor.

Research field(s)
Genetics & Heredity, Biomedical Research

DOI
10.1016/j.molcel.2024.06.011

Learning from aggregated opinion

NOMIS Researcher(s)

Published in

July 24, 2024

The capacity to leverage information from others’ opinions is a hallmark of human cognition. Consequently, past research has investigated how we learn from others’ testimony. Yet a distinct form of social information—aggregated opinion—increasingly guides our judgments and decisions. We investigated how people learn from such information by conducting three experiments with participants recruited online within the United States (N = 886) comparing the predictions of three computational models: a Bayesian solution to this problem that can be implemented by a simple strategy for combining proportions with prior beliefs, and two alternatives from epistemology and economics. Across all studies, we found the strongest concordance between participants’ judgments and the predictions of the Bayesian model, though some participants’ judgments were better captured by alternative strategies. These findings lay the groundwork for future research and show that people draw systematic inferences from aggregated opinion, often in line with a Bayesian solution.

Research field(s)
Artificial Intelligence & Image Processing, Psychology & Cognitive Sciences

DOI
10.1177/09567976241251741

Thresholds for adding degraded tropical forest to the conservation estate

NOMIS Researcher(s)

Published in

July 17, 2024

Logged and disturbed forests are often viewed as degraded and depauperate environments compared with primary forest. However, they are dynamic ecosystems1 that provide refugia for large amounts of biodiversity2,3, so we cannot afford to underestimate their conservation value4. Here we present empirically defined thresholds for categorizing the conservation value of logged forests, using one of the most comprehensive assessments of taxon responses to habitat degradation in any tropical forest environment. We analysed the impact of logging intensity on the individual occurrence patterns of 1,681 taxa belonging to 86 taxonomic orders and 126 functional groups in Sabah, Malaysia. Our results demonstrate the existence of two conservation-relevant thresholds. First, lightly logged forests (<29% biomass removal) retain high conservation value and a largely intact functional composition, and are therefore likely to recover their pre-logging values if allowed to undergo natural regeneration. Second, the most extreme impacts occur in heavily degraded forests with more than two-thirds (>68%) of their biomass removed, and these are likely to require more expensive measures to recover their biodiversity value. Overall, our data confirm that primary forests are irreplaceable5, but they also reinforce the message that logged forests retain considerable conservation value that should not be overlooked.

Research field(s)
Conservation Biology, Forestry, Ecology, Environmental Sciences

DOI
10.1038/s41586-024-07657-w

Moving beyond stewardship to partnership with nature: how Swiss alpine farmers’ relationships to nature and relational values are co-constituted

NOMIS Researcher(s)

Published in

July 15, 2024

Ecologically considerate use of nature (including agriculture) has often been associated with ‘stewardship’ as a human-nature relationship which involves human care, responsibility and accountability and is thus more sustainable than the alternative human-nature relationship of manager of nature. We show that the consideration of nature in agriculture can go further than stewardship by presenting data from qualitative interviews with Swiss Alpine farmers indicating that many of them view their relationship with nature as a form of partnership. Drawing on literature of human-nature partnership, we characterize this relationship by 1) bidirectionality – a give and take between nature and humans–, 2) the understanding of nature as a subject rather than an object and 3) interaction with nature that consists of collaboration rather than giving commands. The mountain farmers expressed all of these features in their farming practices and descriptions of their role in nature. A few farmers even saw their role as subordinates to nature, for which we introduced the new human-nature relationship category of “apprenticeship”. We further suggest that the partnership relation between humans and nature in many respects shares key features with relational values, for instance in its non-centric nature and in its emphasis of the combination of benefits for people with care for nature. In that sense, we aim at combining different accounts of inclusive, non-dichotomous and context-sensitive dealings with nature and we suggest that this combination is applicable also to contexts beyond agriculture.

Research field(s)
Philosophy

DOI
10.1080/26395916.2024.2374757

Deep 3D histology powered by tissue clearing, omics and AI

NOMIS Researcher(s)

Published in

July 12, 2024

To comprehensively understand tissue and organism physiology and pathophysiology, it is essential to create complete three-dimensional (3D) cellular maps. These maps require structural data, such as the 3D configuration and positioning of tissues and cells, and molecular data on the constitution of each cell, spanning from the DNA sequence to protein expression. While single-cell transcriptomics is illuminating the cellular and molecular diversity across species and tissues, the 3D spatial context of these molecular data is often overlooked. Here, I discuss emerging 3D tissue histology techniques that add the missing third spatial dimension to biomedical research. Through innovations in tissue-clearing chemistry, labeling and volumetric imaging that enhance 3D reconstructions and their synergy with molecular techniques, these technologies will provide detailed blueprints of entire organs or organisms at the cellular level. Machine learning, especially deep learning, will be essential for extracting meaningful insights from the vast data. Further development of integrated structural, molecular and computational methods will unlock the full potential of next-generation 3D histology.

Research field(s)
Biochemistry & Molecular Biology, Chemistry

DOI
10.1038/s41592-024-02327-1

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