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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.

Part-Time Bayesians: Incentives and Behavioral Heterogeneity in Belief Updating

NOMIS Researcher(s)

Published in

January 4, 2023

Decisions in management and finance rely on information that often includes win-lose feedback (e.g., gains and losses, success and failure). Simple reinforcement then suggests to blindly repeat choices if they led to success in the past and change them otherwise, which might conflict with Bayesian updating of beliefs. We use finite mixture models and hidden Markov models, adapted from machine learning, to uncover behavioral heterogeneity in the reliance on difference behavioral rules across and within individuals in a belief-updating experiment. Most decision makers rely both on Bayesian updating and reinforcement. Paradoxically, an increase in incentives increases the reliance on reinforcement because the win-lose cues become more salient.

DOI
10.1287/mnsc.2022.4584

Social Metacognition Drives Willingness to Commit

NOMIS Researcher(s)

Published in

January 1, 2023

Showing or telling others that we are committed to cooperate with them can boost social cooperation. But what makes us willing to signal our cooperativeness, when it is costly to do so? In two experiments,we tested the hypothesis that agents engage in social commitments if their subjective confidence in predicting the interaction partner’s behavior is low. In Experiment 1 (preregistered), 48 participants played a prisoner’s dilemma game where they could signal their intentions to their co-player by enduring a monetary cost. As hypothesized, low confidence in one’s prediction of the co-player’s intentions was associated with a higher willingness to engage in costly commitment. In Experiment 2 (31 participants), we replicate these findings and moreover provide causal evidence that experimentally lowering the predictability of others’ actions (and thereby confidence in these predictions) motivates commitment decisions. Finally, across both experiments, we show that participants possess and demonstrate metacognitive access to the accuracy of their mentalizing processes. Taken together, our findings shed light on the importance of confidence representations and metacognitive processes in social interactions © 2023 American Psychological Association

Research field(s)
Applied Sciences, Information & Communication Technologies, Artificial Intelligence & Image Processing

DOI
10.1037/xge0001419

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

NOMIS Researcher(s)

Published in

December 26, 2022

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

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

DOI
10.1002/alz.12906

Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment

NOMIS Researcher(s)

Published in

December 22, 2022

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

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

DOI
10.1016/j.cell.2022.11.019

Spatial proteomics in three-dimensional intact specimens

NOMIS Researcher(s)

Published in

December 22, 2022

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

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

DOI
10.1016/j.cell.2022.11.021

Logged tropical forests have amplified and diverse ecosystem energetics

NOMIS Researcher(s)

Published in

December 22, 2022

Old-growth tropical forests are widely recognized as being immensely important for their biodiversity and high biomass1. Conversely, logged tropical forests are usually characterized as degraded ecosystems2. However, whether logging results in a degradation in ecosystem functions is less clear: shifts in the strength and resilience of key ecosystem processes in large suites of species have rarely been assessed in an ecologically integrated and quantitative framework. Here we adopt an ecosystem energetics lens to gain new insight into the impacts of tropical forest disturbance on a key integrative aspect of ecological function: food pathways and community structure of birds and mammals. We focus on a gradient spanning old-growth and logged forests and oil palm plantations in Borneo. In logged forest there is a 2.5-fold increase in total resource consumption by both birds and mammals compared to that in old-growth forests, probably driven by greater resource accessibility and vegetation palatability. Most principal energetic pathways maintain high species diversity and redundancy, implying maintained resilience. Conversion of logged forest into oil palm plantation results in the collapse of most energetic pathways. Far from being degraded ecosystems, even heavily logged forests can be vibrant and diverse ecosystems with enhanced levels of ecological function.

Research field(s)
Natural Sciences, Biology, Ecology

DOI
10.1038/s41586-022-05523-1

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

NOMIS Researcher(s)

Published in

December 22, 2022

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

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

DOI
10.1016/j.isci.2022.105441

Beyond playing 20 questions with nature: Integrative experiment design in the social and behavioral sciences

NOMIS Researcher(s)

Published in

December 21, 2022

The dominant paradigm of experiments in the social and behavioral sciences views an experiment as a test of a theory, where the theory is assumed to generalize beyond the experiment’s specific conditions. According to this view, which Alan Newell once characterized as “playing twenty questions with nature,” theory is advanced one experiment at a time, and the integration of disparate findings is assumed to happen via the scientific publishing process. In this article, we argue that the process of integration is at best inefficient, and at worst it does not, in fact, occur. We further show that the challenge of integration cannot be adequately addressed by recently proposed reforms that focus on the reliability and replicability of individual findings, nor simply by conducting more or larger experiments. Rather, the problem arises from the imprecise nature of social and behavioral theories and, consequently, a lack of commensurability across experiments conducted under different conditions. Therefore, researchers must fundamentally rethink how they design experiments and how the experiments relate to theory. We specifically describe an alternative framework, integrative experiment design, which intrinsically promotes commensurability and continuous integration of knowledge. In this paradigm, researchers explicitly map the design space of possible experiments associated with a given research question, embracing many potentially relevant theories rather than focusing on just one. Researchers then iteratively generate theories and test them with experiments explicitly sampled from the design space, allowing results to be integrated across experiments. Given recent methodological and technological developments, we conclude that this approach is feasible and would generate more-reliable, more-cumulative empirical and theoretical knowledge than the current paradigm – and with far greater efficiency.

Research field(s)
Experimental Psychology, Social Sciences

DOI
10.1017/S0140525X22002874

Actin cytoskeleton and complex cell architecture in an Asgard archaeon

NOMIS Researcher(s)

Published in

December 21, 2022

Asgard archaea are considered to be the closest known relatives of eukaryotes. Their genomes contain hundreds of eukaryotic signature proteins (ESPs), which inspired hypotheses on the evolution of the eukaryotic cell1–3. A role of ESPs in the formation of an elaborate cytoskeleton and complex cellular structures has been postulated4–6, but never visualized. Here we describe a highly enriched culture of ‘Candidatus Lokiarchaeum ossiferum’, a member of the Asgard phylum, which thrives anaerobically at 20 °C on organic carbon sources. It divides every 7–14 days, reaches cell densities of up to 5 × 107 cells per ml and has a significantly larger genome compared with the single previously cultivated Asgard strain7. ESPs represent 5% of its protein-coding genes, including four actin homologues. We imaged the enrichment culture using cryo-electron tomography, identifying ‘Ca. L. ossiferum’ cells on the basis of characteristic expansion segments of their ribosomes. Cells exhibited coccoid cell bodies and a network of branched protrusions with frequent constrictions. The cell envelope consists of a single membrane and complex surface structures. A long-range cytoskeleton extends throughout the cell bodies, protrusions and constrictions. The twisted double-stranded architecture of the filaments is consistent with F-actin. Immunostaining indicates that the filaments comprise Lokiactin—one of the most highly conserved ESPs in Asgard archaea. We propose that a complex actin-based cytoskeleton predated the emergence of the first eukaryotes and was a crucial feature in the evolution of the Asgard phylum by scaffolding elaborate cellular structures. © 2022, The Author(s).

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

DOI
10.1038/s41586-022-05550-y

FXR mediates ILC-intrinsic responses to intestinal inflammation

NOMIS Researcher(s)

Published in

December 20, 2022

The pleiotropic actions of the Farnesoid X Receptor (FXR) are required for gut health, and reciprocally, reduced intestinal FXR signaling is seen in inflammatory bowel diseases (IBDs). Here, we show that activation of FXR selectively in the intestine is protective in inflammation-driven models of IBD. Prophylactic activation of FXR restored homeostatic levels of pro-inflammatory cytokines, most notably IL17. Importantly, these changes were attributed to FXR regulation of innate lymphoid cells (ILCs), with both the inflammation-driven increases in ILCs, and ILC3s in particular, and the induction of Il17a and Il17f in ILC3s blocked by FXR activation. Moreover, a population of ILC precursor-like cells increased with treatment, implicating FXR in the maturation/ differentiation of ILC precursors. These findings identify FXR as an intrinsic regulator of intestinal ILCs and a potential therapeutic target in inflammatory intestinal diseases.

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

DOI
10.1073/pnas.2213041119

Adaptable toolbox to characterize Alzheimer’s disease pathology in mouse models

NOMIS Researcher(s)

Published in

December 16, 2022

Here, we describe a highly adaptable toolbox for characterizing and analyzing molecular and histopathological changes in Alzheimer’s disease (AD) mouse models. We detail optimized and streamlined approaches from sample preparation to image analysis to facilitate reproducible analyses. We also describe the extraction and measurement of the soluble Aβ level by sandwich ELISA in the cortex and hippocampus of AD mouse models before and after plaque deposition. Finally, we outline the steps for image quantification and analysis using Imaris and ImageJ. For complete details on the use and execution of this protocol, please refer to Huang et al. (2021).1

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

DOI
10.1016/j.xpro.2022.101891

Majorana-like Coulomb spectroscopy in the absence of zero-bias peaks

NOMIS Researcher(s)

Published in

December 15, 2022

Hybrid semiconductor–superconductor devices hold great promise for realizing topological quantum computing with Majorana zero modes1–5. However, multiple claims of Majorana detection, based on either tunnelling6–10 or Coulomb blockade (CB) spectroscopy11,12, remain disputed. Here we devise an experimental protocol that allows us to perform both types of measurement on the same hybrid island by adjusting its charging energy via tunable junctions to the normal leads. This method reduces ambiguities of Majorana detections by checking the consistency between CB spectroscopy and zero-bias peaks in non-blockaded transport. Specifically, we observe junction-dependent, even–odd modulated, single-electron CB peaks in InAs/Al hybrid nanowires without concomitant low-bias peaks in tunnelling spectroscopy. We provide a theoretical interpretation of the experimental observations in terms of low-energy, longitudinally confined island states rather than overlapping Majorana modes. Our results highlight the importance of combined measurements on the same device for the identification of topological Majorana zero modes.

Research field(s)
Natural Sciences, Physics & Astronomy, Applied Physics

DOI
10.1038/s41586-022-05382-w

LATE-NC staging in routine neuropathologic diagnosis: an update

NOMIS Researcher(s)

Published in

December 13, 2022

An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer’s disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience. © 2022, The Author(s).

Research field(s)
Health Sciences

DOI
10.1007/s00401-022-02524-2

A novel synthesis of two decades of microsatellite studies on European beech reveals decreasing genetic diversity from glacial refugia

NOMIS Researcher(s)

Published in

December 12, 2022

Genetic diversity influences the evolutionary potential of forest trees under changing environmental conditions, thus indirectly the ecosystem services that forests provide. European beech (Fagus sylvatica L.) is a dominant European forest tree species that increasingly suffers from climate change-related die-back. Here, we conducted a systematic literature review of neutral genetic diversity in European beech and created a meta-data set of expected heterozygosity (He) from all past studies providing nuclear microsatellite data. We propose a novel approach, based on population genetic theory and a min–max scaling to make past studies comparable. Using a new microsatellite data set with unprecedented geographic coverage and various re-sampling schemes to mimic common sampling biases, we show the potential and limitations of the scaling approach. The scaled meta-dataset reveals the expected trend of decreasing genetic diversity from glacial refugia across the species range and also supports the hypothesis that different lineages met and admixed north of the European mountain ranges. As a result, we present a map of genetic diversity across the range of European beech which could help to identify seed source populations harboring greater diversity and guide sampling strategies for future genome-wide and functional investigations of genetic variation. Our approach illustrates how to combine information from several nuclear microsatellite data sets to describe patterns of genetic diversity extending beyond the geographic scale or mean number of loci used in each individual study, and thus is a proof-of-concept for synthesizing knowledge from existing studies also in other species. © 2022, The Author(s).

Research field(s)
Natural Sciences

DOI
10.1007/s11295-022-01577-4

An Axiomatic Characterization of Bayesian Updating

NOMIS Researcher(s)

Published in

December 9, 2022

We provide an axiomatic characterization of Bayesian updating, viewed as a mapping from prior beliefs and new information to posteriors, which is disentangled from any reference to preferences. Bayesian updating is characterized by Non-Innovativeness (events considered impossible in the prior remain impossible in the posterior), Dropping (events contradicted by new evidence are considered impossible in the posterior), and Proportionality (for other events, the posterior simply rescales the prior’s probabilities proportionally). The result clarifies the differences between the normative Bayesian benchmark, alternative models, and actual human behavior.

Research field(s)
Economics

DOI
10.1016/j.jmateco.2022.102799

The sound of swearing: Are there universal patterns in profanity?

NOMIS Researcher(s)

Published in

December 6, 2022

Why do swear words sound the way they do? Swear words are often thought to have sounds that render them especially fit for purpose, facilitating the expression of emotion and attitude. To date, however, there has been no systematic cross-linguistic investigation of phonetic patterns in profanity. In an initial, pilot study we explored statistical regularities in the sounds of swear words across a range of typologically distant languages. The best candidate for a cross-linguistic phonemic pattern in profanity was the absence of approximants (sonorous sounds like l, r, w and y). In Study 1, native speakers of various languages (Arabic, Chinese, Finnish, French, German, Spanish; N = 215) judged foreign words less likely to be swear words if they contained an approximant. In Study 2 we found that sanitized versions of English swear words – like darn instead of damn – contain significantly more approximants than the original swear words. Our findings reveal that not all sounds are equally suitable for profanity, and demonstrate that sound symbolism – wherein certain sounds are intrinsically associated with certain meanings – is more pervasive than has previously been appreciated, extending beyond denoting single concepts to serving pragmatic functions.

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

DOI
10.3758/s13423-022-02202-0

Methods to investigate intrathecal adaptive immunity in neurodegeneration

NOMIS Researcher(s)

Published in

December 1, 2022

Background: Cerebrospinal fluid (CSF) provides basic mechanical and immunological protection to the brain. Historically, analysis of CSF has focused on protein changes, yet recent studies have shed light on cellular alterations. Evidence now exists for involvement of intrathecal T cells in the pathobiology of neurodegenerative diseases. However, a standardized method for long-term preservation of CSF immune cells is lacking. Further, the functional role of CSF T cells and their cognate antigens in neurodegenerative diseases are largely unknown. Results: We present a method for long-term cryopreservation of CSF immune cells for downstream single cell RNA and T cell receptor sequencing (scRNA-TCRseq) analysis. We observe preservation of CSF immune cells, consisting primarily of memory CD4+ and CD8+ T cells. We then utilize unbiased bioinformatics approaches to quantify and visualize TCR sequence similarity within and between disease groups. By this method, we identify clusters of disease-associated, antigen-specific TCRs from clonally expanded CSF T cells of patients with neurodegenerative diseases. Conclusions: Here, we provide a standardized approach for long-term storage of CSF immune cells. Additionally, we present unbiased bioinformatic approaches that will facilitate the discovery of target antigens of clonally expanded T cells in neurodegenerative diseases. These novel methods will help improve our understanding of adaptive immunity in the central nervous system.

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

DOI
10.1186/s13024-021-00423-w

The Self in the Mind’s Eye: Revealing How We Truly See Ourselves Through Reverse Correlation

NOMIS Researcher(s)

Published in

December 1, 2022

Is there a way to visually depict the image people “see” of themselves in their minds’ eyes? And if so, what can these mental images tell us about ourselves? We used a computational reverse-correlation technique to explore individuals’ mental “self-portraits” of their faces and body shapes in an unbiased, data-driven way (total N = 116 adults). Self-portraits were similar to individuals’ real faces but, importantly, also contained clues to each person’s self-reported personality traits, which were reliably detected by external observers. Furthermore, people with higher social self-esteem produced more true-to-life self-portraits. Unlike face portraits, body portraits had negligible relationships with individuals’ actual body shape, but as with faces, they were influenced by people’s beliefs and emotions. We show how psychological beliefs and attitudes about oneself bias the perceptual representation of one’s appearance and provide a unique window into the internal mental self-representation—findings that have important implications for mental health and visual culture.

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

DOI
10.1177/09567976211018618

A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects

NOMIS Researcher(s)

Published in

December 1, 2022

Background: The Colombian population, as well as those in other Latin American regions, arose from a recent tri-continental admixture among Native Americans, Spanish invaders, and enslaved Africans, all of whom passed through a population bottleneck due to widespread infectious diseases that left small isolated local settlements. As a result, the current population reflects multiple founder effects derived from diverse ancestries. Methods: We characterized the role of admixture and founder effects on the origination of the mutational landscape that led to neurodegenerative disorders under these historical circumstances. Genomes from 900 Colombian individuals with Alzheimer’s disease (AD) [n = 376], frontotemporal lobar degeneration-motor neuron disease continuum (FTLD-MND) [n = 197], early-onset dementia not otherwise specified (EOD) [n = 73], and healthy participants [n = 254] were analyzed. We examined their global and local ancestry proportions and screened this cohort for deleterious variants in disease-causing and risk-conferring genes. Results: We identified 21 pathogenic variants in AD-FTLD related genes, and PSEN1 harbored the majority (11 pathogenic variants). Variants were identified from all three continental ancestries. TREM2 heterozygous and homozygous variants were the most common among AD risk genes (102 carriers), a point of interest because the disease risk conferred by these variants differed according to ancestry. Several gene variants that have a known association with MND in European populations had FTLD phenotypes on a Native American haplotype. Consistent with founder effects, identity by descent among carriers of the same variant was frequent. Conclusions: Colombian demography with multiple mini-bottlenecks probably enhanced the detection of founder events and left a proportionally higher frequency of rare variants derived from the ancestral populations. These findings demonstrate the role of genomically defined ancestry in phenotypic disease expression, a phenotypic range of different rare mutations in the same gene, and further emphasize the importance of inclusiveness in genetic studies.

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

DOI
10.1186/s13073-022-01035-9

Deep residual inception encoder-decoder network for amyloid PET harmonization

NOMIS Researcher(s)

Published in

December 1, 2022

Introduction: Multiple positron emission tomography (PET) tracers are available for amyloid imaging, posing a significant challenge to consensus interpretation and quantitative analysis. We accordingly developed and validated a deep learning model as a harmonization strategy. Method: A Residual Inception Encoder-Decoder Neural Network was developed to harmonize images between amyloid PET image pairs made with Pittsburgh Compound-B and florbetapir tracers. The model was trained using a dataset with 92 subjects with 10-fold cross validation and its generalizability was further examined using an independent external dataset of 46 subjects. Results: Significantly stronger between-tracer correlations (P <.001) were observed after harmonization for both global amyloid burden indices and voxel-wise measurements in the training cohort and the external testing cohort. Discussion: We proposed and validated a novel encoder-decoder based deep model to harmonize amyloid PET imaging data from different tracers. Further investigation is ongoing to improve the model and apply to additional tracers.

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

DOI
10.1002/alz.12564

SepN is a septal junction component required for gated cell–cell communication in the filamentous cyanobacterium Nostoc

NOMIS Researcher(s)

Published in

December 1, 2022

Multicellular organisms require controlled intercellular communication for their survival. Strains of the filamentous cyanobacterium Nostoc regulate cell–cell communication between sister cells via a conformational change in septal junctions. These multi-protein cell junctions consist of a septum spanning tube with a membrane-embedded plug at both ends, and a cap covering the plug on the cytoplasmic side. The identities of septal junction components are unknown, with exception of the protein FraD. Here, we identify and characterize a FraD-interacting protein, SepN, as the second component of septal junctions in Nostoc. We use cryo-electron tomography of cryo-focused ion beam-thinned cyanobacterial filaments to show that septal junctions in a sepN mutant lack a plug module and display an aberrant cap. The sepN mutant exhibits highly reduced cell–cell communication rates, as shown by fluorescence recovery after photobleaching experiments. Furthermore, the mutant is unable to gate molecule exchange through septal junctions and displays reduced filament survival after stress. Our data demonstrate the importance of controlling molecular diffusion between cells to ensure the survival of a multicellular organism.

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

DOI
10.1038/s41467-022-34946-7

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