Insight
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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.

NOMIS Researcher(s)

January 1, 2022

Predictions pose unique problems. Experts regularly get them wrong, and collective solutions (such as prediction markets and super-forecaster schemes) do better but remain selective and costly. Contrary to the idea that face-to-face discussion hinders collective intelligence, social deliberation improves the resolution of general knowledge problems, with four consensually agreed answers outperforming the aggregate knowledge of 5,000 nondeliberating individuals. Could discussion help predict the future in an efficient, cheap, and inclusive way? We show that smaller groups of lay individuals, when organized, come up with better predictions than those they provide alone. Deliberation and consensus made individual predictions significantly more accurate. Aggregating as few as two consensual predictions did better than classical “wisdom of crowds” aggregation of 100 individual ones. Against the view that discussion can impair decision-making, our results demonstrate that collective intelligence of small groups and consensus-seeking improves accuracy about yet unknown facts, opening the avenue for efficient, inclusive, and inexpensive group forecasting solutions.

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

NOMIS Researcher(s)

Published in

January 1, 2022

Anthropologists increasingly turn to design research for inspiration. Yet work in design anthropology is frequently cut off from ethnographic research. To some extent this is intentional, given concerns that ethnographic methods have failed to keep pace with a rapidly changing world. But anthropologists should not have to choose between ethnography and design research. This article examines the author’s participation in an industrial think tank in which anthropologists and engineers collaborated to address the environmental impacts of mining. This included discussion of unrecognized sources of pollution at mining sites and rising penalties for environmental damage. The members of the think tank also developed designs for new technology intended to reduce the exposure of artisanal gold miners to mercury and its release into the atmosphere, facilitate the recycling of electronic waste in developing countries, and reduce the catastrophic risks posed by tailings dams. Our collaborations point to the value of combining ethnography and design research in new ways.

Research field(s)
Arts & Humanities, Historical Studies, Anthropology

NOMIS Researcher(s)

Published in

January 1, 2022

Quantitative measurements of physical parameters become increasingly important for understanding biological processes. Brillouin microscopy (BM) has recently emerged as one technique providing the 3D distribution of viscoelastic properties inside biological samples — so far relying on the implicit assumption that refractive index (RI) and density can be neglected. Here, we present a novel method (FOB microscopy) combining BM with optical diffraction tomography and epi-fluorescence imaging for explicitly measuring the Brillouin shift, RI and absolute density with specificity to fluorescently labeled structures. We show that neglecting the RI and density might lead to erroneous conclusions. Investigating the nucleoplasm of wild-type HeLa cells, we find that it has lower density but higher longitudinal modulus than the cytoplasm. Thus, the longitudinal modulus is not merely sensitive to the water content of the sample — a postulate vividly discussed in the field. We demonstrate the further utility of FOB on various biological systems including adipocytes and intracellular membraneless compartments. FOB microscopy can provide unexpected scientific discoveries and shed quantitative light on processes such as phase separation and transition inside living cells.

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

NOMIS Researcher(s)

January 1, 2022

Region specific brain organoids are brain organoids derived by patterning protocols using extrinsic signals as opposed to cerebral organoids obtained by self-patterning. The main focus of this review is to discuss various region-specific brain organoids developed so far and their application in modeling neurodevelopmental disease. We first discuss the principles of neural axis formation by series of growth factors, such as SHH, WNT, BMP signalings, that are critical to generate various region-specific brain organoids. Then we discuss various neurodevelopmental disorders modeled so far with these region-specific brain organoids, and findings made on mechanism and treatment options for neurodevelopmental disorders (NDD)

Research field(s)
Applied Sciences, Engineering, Biomedical Engineering

NOMIS Researcher(s)

Published in

January 1, 2022

Objectives: To identify the clinical characteristics of the subgroup of benign progressive supranuclear palsy with particularly long disease duration; to define neuropathological determinants underlying variability in disease duration in progressive supranuclear palsy. Methods: Clinical and pathological features were compared among 186 autopsy-confirmed cases with progressive supranuclear palsy with ≥10 years and shorter survival times. Results: The 45 cases (24.2%) had a disease duration of ≥10 years. The absence of ocular motor abnormalities within the first 3 years from disease onset was the only significant independent clinical predictor of longer survival. Histopathologically, the neurodegeneration parameters in each survival group were paralleled anatomically by the distribution of neuronal cytoplasmic inclusions, whereas the tufted astrocytes displayed anatomically an opposite severity pattern. Most interestingly, we found significantly less coiled bodies in those who survive longer, in contrast to patients with less favorable course. Interpretation: A considerable proportion of patients had a more ”benign” disease course with ≥10 years survival. They had a distinct pattern and evolution of core symptoms compared to patients with short survival. The inverted anatomical patterns of astrocytic tau distribution suggest distinct implications of these cell types in trans-cellular propagation. The tempo of disease progression appeared to be determined mostly by oligodendroglial tau, where the high degree of oligodendroglial tau pathology might affect neuronal integrity and function on top of neuronal tau pathology. The relative contribution of glial tau should be further explored in cellular and animal models. ANN NEUROL 2022.

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

NOMIS Researcher(s)

Published in

January 1, 2022

Tatos Cartozian was naturalized in Portland, Oregon in May 1923, a decision that was immediately challenged on racial grounds. This article follows the Cartozian family – from their sitting for an Ottoman expatriation portrait to exit the Ottoman empire in 1906 to their deft use of advertising and portrait photography in the United States in order to rethink the politics of visibility and legal belonging. As several Asian groups were deemed ineligible for citizenship on account of not being ”white,” the very grounds on which ”whiteness” was to be determined – whether scientific expertise or assumed common knowledge – was continually shifting. In order to become US citizens the Cartozians had to exit the category of “Asiatic” and join the ranks of the unmarked citizenry in the United States. Counterintuitively, they managed to do so while advertising their family business frequently and boldly as ”America’s Largest Oriental Rug Organization.”.

Research field(s)
Arts & Humanities, Communication & Textual Studies, Communication & Media Studies

NOMIS Researcher(s)

January 1, 2022

Halorhodospira halophila, one of the most-xerophilic halophiles, inhabits biophysically stressful and energetically expensive, salt-saturated alkaline brines. Here, we report an additional stress factor that is biotic: a diminutive Candidate-Phyla-Radiation bacterium, that we named ‘Ca. Absconditicoccus praedator’ M39-6, which predates H. halophila M39-5, an obligately photosynthetic, anaerobic purple-sulfur bacterium. We cultivated this association (isolated from the hypersaline alkaline Lake Hotontyn Nur, Mongolia) and characterized their biology. ‘Ca. Absconditicoccus praedator’ is the first stably cultivated species from the candidate class-level lineage Gracilibacteria (order-level lineage Absconditabacterales). Its closed-and-curated genome lacks genes for the glycolytic, pentose phosphate- and Entner–Doudoroff pathways which would generate energy/reducing equivalents and produce central carbon currencies. Therefore, ‘Ca. Absconditicoccus praedator’ is dependent on host-derived building blocks for nucleic acid-, protein-, and peptidoglycan synthesis. It shares traits with (the uncultured) ‘Ca. Vampirococcus lugosii’, which is also of the Gracilibacteria lineage. These are obligate parasitic lifestyle, feeding on photosynthetic anoxygenic Gammaproteobacteria, and absorption of host cytoplasm. Commonalities in their genomic composition and structure suggest that the entire Absconditabacterales lineage consists of predatory species which act to cull the populations of their respective host bacteria. Cultivation of vampire : host associations can shed light on unresolved aspects of their metabolism and ecosystem dynamics at life-limiting extremes.

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

NOMIS Researcher(s)

January 1, 2022

Introduction: The Alzheimer’s Prevention Initiative Autosomal-Dominant Alzheimer’s Disease (API ADAD) Trial evaluated the anti-oligomeric amyloid beta (Aβ) antibody therapy crenezumab in cognitively unimpaired members of the Colombian presenilin 1 (PSEN1) E280A kindred. We report availability, methods employed to protect confidentiality and anonymity of participants, and process for requesting and accessing baseline data. Methods: We developed mechanisms to share baseline data from the API ADAD Trial in consultation with experts and other groups sharing data from Alzheimer’s disease (AD) prevention trials, balancing the need to protect anonymity and trial integrity with making data broadly available to accelerate progress in the field. We pressure-tested deliberate and inadvertent potential threats under specific assumptions, employed a system to suppress or mask both direct and indirect identifying variables, limited and firewalled data managers, and put forth specific principles requisite to receive data. Results: Baseline demographic, PSEN1 E280A and apolipoprotein E genotypes, florbetapir and fluorodeoxyglucose positron emission tomography, magnetic resonance imaging, clinical, and cognitive data can now be requested by interested researchers. Discussion: Baseline data are publicly available; treatment data and biological samples, including baseline and treatment-related blood-based biomarker data will become available in accordance with our original trial agreement and subsequently developed Collaboration for Alzheimer’s Prevention principles. Sharing of these data will allow exploration of important questions including the differential effects of initiating an investigational AD prevention therapy both before as well as after measurable Aβ plaque deposition.

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

NOMIS Researcher(s)

January 1, 2022

Plant functional traits can predict community assembly and ecosystem functioning and are thus widely used in global models of vegetation dynamics and land–climate feedbacks. Still, we lack a global understanding of how land and climate affect plant traits. A previous global analysis of six traits observed two main axes of variation: (1) size variation at the organ and plant level and (2) leaf economics balancing leaf persistence against plant growth potential. The orthogonality of these two axes suggests they are differently influenced by environmental drivers. We find that these axes persist in a global dataset of 17 traits across more than 20,000 species. We find a dominant joint effect of climate and soil on trait variation. Additional independent climate effects are also observed across most traits, whereas independent soil effects are almost exclusively observed for economics traits. Variation in size traits correlates well with a latitudinal gradient related to water or energy limitation. In contrast, variation in economics traits is better explained by interactions of climate with soil fertility. These findings have the potential to improve our understanding of biodiversity patterns and our predictions of climate change impacts on biogeochemical cycles.

Research field(s)
Natural Sciences, Biology, Evolutionary Biology

NOMIS Researcher(s)

Published in

January 1, 2022

Objective: People are highly attuned to fairness, with people willingly suffering personal costs to prevent others benefitting from unfair acts. Are fairness judgments influenced by group alignments? A new theory posits that we favor ingroups and denigrate members of rival outgroups when our personal identity is fused to a group. Although the mPFC has been separately implicated in group membership and fairness processing, it is unclear whether group alignments affect medial prefrontal cortex (mPFC) activity in response to fairness. Here, we examine the contribution of different regions of the mPFC to processing from ingroup and outgroup members and test whether its response differs depending on how fused we are to an ingroup. Methods: Subjects performed rounds of the Ultimatum Game, being offered fair or unfair divisions of money from supporters of the same soccer team (ingroup), the fiercest rival (outgroup) or neutral individuals whilst undergoing functional Magnetic Resonance Imaging (fMRI). Results: Strikingly, people willingly suffered personal costs to prevent outgroup members benefitting from both unfair and fair offers. Activity across dorsal and ventral (VMPFC) portions of the mPFC reflected an interaction between fairness and group membership. VMPFC activity in particular was consistent with it coding one’s fusion to a group, with the fairness by group membership interaction correlating with the extent that the responder’s identity was fused to the ingroup. Conclusions: The influence of fusion on social behavior therefore seems to be linked to processing in the VMPFC.

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

NOMIS Researcher(s)

Published in

December 17, 2021

Competition for social influence is a major force shaping societies, from baboons guiding their troop in different directions, to politicians competing for voters, to influencers competing for attention on social media. Social influence is invariably a competitive exercise with multiple influencers competing for it. We study which strategy maximizes social influence under competition. Applying game theory to a scenario where two advisers compete for the attention of a client, we find that the rational solution for advisers is to communicate truthfully when favored by the client, but to lie when ignored. Across seven pre-registered studies, testing 802 participants, such a strategic adviser consistently outcompeted an honest adviser. Strategic dishonesty outperformed truth-telling in swaying individual voters, the majority vote in anonymously voting groups, and the consensus vote in communicating groups. Our findings help explain the success of political movements that thrive on disinformation, and vocal underdog politicians with no credible program.

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

Published in

December 16, 2021

Physical exercise is generally beneficial to all aspects of human and animal health, slowing cognitive ageing and neurodegeneration1. The cognitive benefits of physical exercise are tied to an increased plasticity and reduced inflammation within the hippocampus2–4, yet little is known about the factors and mechanisms that mediate these effects. Here we show that ‘runner plasma’, collected from voluntarily running mice and infused into sedentary mice, reduces baseline neuroinflammatory gene expression and experimentally induced brain inflammation. Plasma proteomic analysis revealed a concerted increase in complement cascade inhibitors including clusterin (CLU). Intravenously injected CLU binds to brain endothelial cells and reduces neuroinflammatory gene expression in a mouse model of acute brain inflammation and a mouse model of Alzheimer’s disease. Patients with cognitive impairment who participated in structured exercise for 6 months had higher plasma levels of CLU. These findings demonstrate the existence of anti-inflammatory exercise factors that are transferrable, target the cerebrovasculature and benefit the brain, and are present in humans who engage in exercise.

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

NOMIS Researcher(s)

Published in

December 1, 2021

Alzheimer’s disease is an incurable neurodegenerative disorder in which neuroinflammation has a critical function1. However, little is known about the contribution of the adaptive immune response in Alzheimer’s disease2. Here, using integrated analyses of multiple cohorts, we identify peripheral and central adaptive immune changes in Alzheimer’s disease. First, we performed mass cytometry of peripheral blood mononuclear cells and discovered an immune signature of Alzheimer’s disease that consists of increased numbers of CD8+ T effector memory CD45RA+ (TEMRA) cells. In a second cohort, we found that CD8+ TEMRA cells were negatively associated with cognition. Furthermore, single-cell RNA sequencing revealed that T cell receptor (TCR) signalling was enhanced in these cells. Notably, by using several strategies of single-cell TCR sequencing in a third cohort, we discovered clonally expanded CD8+ TEMRA cells in the cerebrospinal fluid of patients with Alzheimer’s disease. Finally, we used machine learning, cloning and peptide screens to demonstrate the specificity of clonally expanded TCRs in the cerebrospinal fluid of patients with Alzheimer’s disease to two separate Epstein–Barr virus antigens. These results reveal an adaptive immune response in the blood and cerebrospinal fluid in Alzheimer’s disease and provide evidence of clonal, antigen-experienced T cells patrolling the intrathecal space of brains affected by age-related neurodegeneration.

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

NOMIS Researcher(s)

Published in

December 1, 2021

At the heart of social cognition is our ability to distinguish between self and other and correctly attribute mental and affective states to their origin. Emotional egocentricity bias (EEB) reflects the tendency to use one’s own emotional state when relating to others. Although interoception underpins our emotional experience, little is known about its role on how we affectively relate to others. Here, we assessed how cardiac interoceptive impact, manipulated by presenting affective stimuli across different phases of the cardiac cycle coupled with trait-like levels of interoceptive accuracy, modulate the EEB. Individuals with higher interoceptive accuracy displayed an increased EEB when the other’s emotional state was presented at the point of maximum interoceptive impact (i.e., at systole), whereas the reverse was observed for individuals with lower interoceptive accuracy. These findings show how interoceptive activity provides the physiological context within which we process other’s emotional states in parallel to ours.

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

NOMIS Researcher(s)

December 1, 2021

Background: Neuroimaging studies of autosomal dominant Alzheimer’s disease (ADAD) enable characterization of the trajectories of cerebral amyloid-β (Aβ) and tau accumulation in the decades prior to clinical symptom onset. Longitudinal rates of regional tau accumulation measured with positron emission tomography (PET) and their relationship with other biomarker and cognitive changes remain to be fully characterized in ADAD. Methods: Fourteen ADAD mutation carriers (Presenilin-1 E280A) and 15 age-matched non-carriers from the Colombian kindred underwent 2–3 sessions of Aβ (11C-Pittsburgh compound B) and tau (18F-flortaucipir) PET, structural magnetic resonance imaging, and neuropsychological evaluation over a 2–4-year follow-up period. Annualized rates of change for imaging and cognitive variables were compared between carriers and non-carriers, and relationships among baseline measurements and rates of change were assessed within carriers. Results: Longitudinal measurements were consistent with a sequence of ADAD-related changes beginning with Aβ accumulation (16 years prior to expected symptom onset, EYO), followed by entorhinal cortex (EC) tau (9 EYO), neocortical tau (6 EYO), hippocampal atrophy (6 EYO), and cognitive decline (4 EYO). Rates of tau accumulation among carriers were most rapid in parietal neocortex (~ 9%/year). EC tau PET signal at baseline was a significant predictor of subsequent neocortical tau accumulation and cognitive decline within carriers. Conclusions: Our results are consistent with the sequence of biological changes in ADAD implied by cross-sectional studies and highlight the importance of EC tau as an early biomarker and a potential link between Aβ burden and neocortical tau accumulation in ADAD.

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

NOMIS Researcher(s)

Published in

December 1, 2021

Septins are cytoskeletal proteins that assemble into hetero-oligomeric complexes and sense micron-scale membrane curvature. During infection with Shigella flexneri, an invasive enteropathogen, septins restrict actin tail formation by entrapping bacteria in cage-like structures. Here, we reconstitute septin cages in vitro using purified recombinant septin complexes (SEPT2-SEPT6-SEPT7), and study how these recognize bacterial cells and assemble on their surface. We show that septin complexes recognize the pole of growing Shigella cells. An amphipathic helix domain in human SEPT6 enables septins to sense positively curved membranes and entrap bacterial cells. Shigella strains lacking lipopolysaccharide components are more efficiently entrapped in septin cages. Finally, cryo-electron tomography of in vitro cages reveals how septins assemble as filaments on the bacterial cell surface.

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

NOMIS Researcher(s)

Published in

December 1, 2021

Dopaminergic (DA) cell death in Parkinson’s disease (PD) is associated with the gradual appearance of neuronal protein aggregates termed Lewy bodies (LBs) that are comprised of vesicular membrane structures and dysmorphic organelles in conjunction with the protein alpha-Synuclein (α-Syn). Although the exact mechanism of neuronal aggregate formation and death remains elusive, recent research suggests α-Syn-mediated alterations in the lysosomal degradation of aggregated proteins and organelles – a process termed autophagy. Here, we used a combination of molecular biology and immunochemistry to investigate the effect of α-Syn on autophagy turnover in cultured human DA neurons and in human post-mortem brain tissue. We found α-Syn overexpression to reduce autophagy turnover by compromising the fusion of autophagosomes with lysosomes, thus leading to a decrease in the formation of autolysosomes. In accord with a compensatory increase in the plasma membrane fusion of autophagosomes, α-Syn enhanced the number of extracellular vesicles (EV) and the abundance of autophagy-associated proteins in these EVs. Mechanistically, α-Syn decreased the abundance of the v-SNARE protein SNAP29, a member of the SNARE complex mediating autophagolysosome fusion. In line, SNAP29 knockdown mimicked the effect of α-Syn on autophagy whereas SNAP29 co-expression reversed the α-Syn-induced changes on autophagy turnover and EV release and ameliorated DA neuronal cell death. In accord with our results from cultured neurons, we found a stage-dependent reduction of SNAP29 in SNc DA neurons from human post-mortem brain tissue of Lewy body pathology (LBP) cases. In summary, our results thus demonstrate a previously unknown effect of α-Syn on intracellular autophagy-associated SNARE proteins and, as a consequence, a reduced autolysosome fusion. As such, our findings will therefore support the investigation of autophagy-associated pathological changes in PD

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

NOMIS Researcher(s)

Published in

December 1, 2021

In everyday life, people sometimes find themselves making decisions on behalf of others, taking risks on another’s behalf, accepting the responsibility for these choices and possibly suffering regret for what they could have done differently. Previous research has extensively studied how people deal with risk when making decisions for others or when being observed by others. Here, we asked whether making decisions for present others is affected by regret avoidance. We studied value-based decision making under uncertainty, manipulating both whether decisions benefited the participant or a partner (beneficiary effect) and whether the partner watched the participant’s choices (audience effect) and their factual and counterfactual outcomes. Computational behavioural analysis revealed that participants were less mindful of regret (and more strongly driven by bigger risks) when choosing for others vs for themselves. Conversely, they chose more conservatively (regarding both regret and risk) when being watched vs alone. The effects of beneficiary and audience on anticipated regret counteracted each other, suggesting that participants’ financial and reputational interests impacted the feeling of regret independently.

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

NOMIS Researcher(s)

Published in

December 1, 2021

According to the received view in the philosophical literature on pictorial perception, when perceiving an object in a picture, we perceive both the picture’s surface and the depicted object, but the surface is only unconsciously represented. Furthermore, it is suggested, such unconscious representation does not need attention. This poses a crucial problem, as empirical research on visual attention shows that there can hardly be any visual representation, conscious or unconscious, without attention. Secondly, according to such a received view, when looking at a picture aesthetically, one both consciously represents and visually attends to both the depicted object and the picture’s surface simultaneously. Thus, contra the empirical research on attention, only conscious visual representations are coupled, by such current view, with attention. And this clearly poses a second problem, as this philosophical account is not in tune with what vision science tells us about the functioning of our visual system. Furthermore, this raises another crucial problem, namely, that of explaining why aesthetic experience of pictures does not feel odd or conflicting, since, as previously noted in the philosophical literature, and contra the received view, if we are simultaneously consciously perceiving both the picture’s surface and the depicted object, there seems to be two things, at the same time, in the foreground of one’s visual consciousness. But, if so, as suggested, this would lead to a conflicting spatial visual experience. This paper offers a new description of the role of visual attention in picture perception, which explains the difference between the usual and the aesthetic way of perceiving a depicted object, without facing the problems reported above. A crucial role in our new account is played by the notion of unconscious attention, the distinction between focal and distributed, as well as top-down and bottom-up visual attention and the relationship between visual attention and visual consciousness. The paper, thus, offers the first theory concerning the exercise of visual attention in pictorial perception that is both philosophically rigorous and empirically reliable.

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