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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.

Functional dissection of two amino acid substitutions unique to the human FOXP2 protein

NOMIS Researcher(s)

Published in

March 6, 2023

The transcription factor forkhead box P2 (FOXP2) is involved in the development of language and speech in humans. Two amino acid substitutions (T303N, N325S) occurred in the human FOXP2 after the divergence from the chimpanzee lineage. It has previously been shown that when they are introduced into the FOXP2 protein of mice they alter striatal synaptic plasticity by increasing long-term depression in medium spiny neurons. Here we introduce each of these amino acid substitutions individually into mice and analyze their effects in the striatum. We find that long-term depression in medium spiny neurons is increased in mice carrying only the T303N substitution to the same extent as in mice carrying both amino acid substitutions. In contrast, the N325S substitution has no discernable effects. © 2023, The Author(s).

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

DOI
10.1038/s41598-023-30663-3

Cardiogenic control of affective behavioural state

NOMIS Researcher(s)

Published in

March 1, 2023

Emotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of the heart1–3. However, whether an increased heart rate might itself induce anxiety or fear responses is unclear3–8. Physiological theories of emotion, proposed over a century ago, have considered that in general, there could be an important and even dominant flow of information from the body to the brain9. Here, to formally test this idea, we developed a noninvasive optogenetic pacemaker for precise, cell-type-specific control of cardiac rhythms of up to 900 beats per minute in freely moving mice, enabled by a wearable micro-LED harness and the systemic viral delivery of a potent pump-like channelrhodopsin. We found that optically evoked tachycardia potently enhanced anxiety-like behaviour, but crucially only in risky contexts, indicating that both central (brain) and peripheral (body) processes may be involved in the development of emotional states. To identify potential mechanisms, we used whole-brain activity screening and electrophysiology to find brain regions that were activated by imposed cardiac rhythms. We identified the posterior insular cortex as a potential mediator of bottom-up cardiac interoceptive processing, and found that optogenetic inhibition of this brain region attenuated the anxiety-like behaviour that was induced by optical cardiac pacing. Together, these findings reveal that cells of both the body and the brain must be considered together to understand the origins of emotional or affective states. More broadly, our results define a generalizable approach for noninvasive, temporally precise functional investigations of joint organism-wide interactions among targeted cells during behaviour. © 2023, The Author(s).

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

DOI
10.1038/s41586-023-05748-8

Thermodynamics of diamond formation from hydrocarbon mixtures in planets

NOMIS Researcher(s)

Published in

February 27, 2023

Hydrocarbon mixtures are extremely abundant in the Universe, and diamond formation from them can play a crucial role in shaping the interior structure and evolution of planets. With first-principles accuracy, we first estimate the melting line of diamond, and then reveal the nature of chemical bonding in hydrocarbons at extreme conditions. We finally establish the pressure-temperature phase boundary where it is thermodynamically possible for diamond to form from hydrocarbon mixtures with different atomic fractions of carbon. Notably, here we show a depletion zone at pressures above 200 GPa and temperatures below 3000 K-3500 K where diamond formation is thermodynamically favorable regardless of the carbon atomic fraction, due to a phase separation mechanism. The cooler condition of the interior of Neptune compared to Uranus means that the former is much more likely to contain the depletion zone. Our findings can help explain the dichotomy of the two ice giants manifested by the low luminosity of Uranus, and lead to a better understanding of (exo-)planetary formation and evolution. © 2023, The Author(s).

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

DOI
10.1038/s41467-023-36841-1

Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region

NOMIS Researcher(s)

Published in

February 17, 2023

Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72′250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae. © 2023 The Authors

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

DOI
10.1016/j.isci.2023.105928

Does decision confidence reflect effort?

NOMIS Researcher(s)

Published in

February 16, 2023

Goal directed behaviour requires transformation of sensory input to decision, and then to output action. How the sensory input is accumulated to form the decision has been extensively studied, however, the influence of output action on decision making has been largely dismissed. Although the recent emerging view postulates the reciprocal interaction between action and decision, still little is known about how the parameters of an action modulates the decision. In this study, we focused on the physical effort which necessarily entails with action. We tested if the physical effort during the deliberation period of the perceptual decision, not the effort required after deciding a particular option, can impact on the process of forming the decision. Here, we set up an experimental situation where investing effort is necessary for the initiation of the task, but importantly, is orthogonal to success in task performance. The study was pre-registered to test the hypothesis that the increased effort will decrease the metacognitive accuracy of decision, without affecting the decision accuracy. Participants judged the direction of a random-dot motion stimuli, while holding and maintaining the position of a robotic manipulandum with their right hand. In the key experimental condition, the manipulandum produced force to move away from its position, requiring the participants to resist the force while accumulating the sensory evidence for the decision. The decision was reported by a key-press using the left-hand. We found no evidence that such incidental (i.e., non-instrumental) effort may influence the subsequent decision process and most importantly decision confidence. The possible reason for this result and the future direction of the research are discussed. © 2023 Hagura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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

DOI
10.1371/journal.pone.0278617

Developmental mechanisms underlying the evolution of human cortical circuits

NOMIS Researcher(s)

Published in

February 15, 2023

The brain of modern humans has evolved remarkable computational abilities that enable higher cognitive functions. These capacities are tightly linked to an increase in the size and connectivity of the cerebral cortex, which is thought to have resulted from evolutionary changes in the mechanisms of cortical development. Convergent progress in evolutionary genomics, developmental biology and neuroscience has recently enabled the identification of genomic changes that act as human-specific modifiers of cortical development. These modifiers influence most aspects of corticogenesis, from the timing and complexity of cortical neurogenesis to synaptogenesis and the assembly of cortical circuits. Mutations of human-specific genetic modifiers of corticogenesis have started to be linked to neurodevelopmental disorders, providing evidence for their physiological relevance and suggesting potential relationships between the evolution of the human brain and its sensitivity to specific diseases. © 2023, Springer Nature Limited.

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

DOI
10.1038/s41583-023-00675-z

Systematic estimation of biological age of in vitro cell culture systems by an age-associated marker panel

NOMIS Researcher(s)

Published in

February 15, 2023

Aging is a process that affects almost all multicellular organisms and since our population ages with increasing prevalence of age-related diseases, it is important to study basic processes involved in aging. Many studies have been published so far using different and often single age markers to estimate the biological age of organisms or different cell culture systems. However, comparability of studies is often hampered by the lack of a uniform panel of age markers. Consequently, we here suggest an easy-to-use biomarker-based panel of classical age markers to estimate the biological age of cell culture systems that can be used in standard cell culture laboratories. This panel is shown to be sensitive in a variety of aging conditions. We used primary human skin fibroblasts of different donor ages and additionally induced either replicative senescence or artificial aging by progerin overexpression. Using this panel, highest biological age was found for artificial aging by progerin overexpression. Our data display that aging varies depending on cell line and aging model and even from individual to individual showing the need for comprehensive analyses. Copyright © 2023 Hartmann, Herling, Hartmann, Köckritz, Fuellen, Walter and Hermann.

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

DOI
10.3389/fragi.2023.1129107

Quantitative proteomic landscapes of primary and recurrent glioblastoma reveal a protumorigeneic role for FBXO2-dependent glioma-microenvironment interactions

NOMIS Researcher(s)

Published in

February 14, 2023

Background: Recent efforts have described the evolution of glioblastoma from initial diagnosis to post-treatment recurrence on a genomic and transcriptomic level. However, the evolution of the proteomic landscape is largely unknown.

Methods: Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was used to characterize the quantitative proteomes of two independent cohorts of paired newly diagnosed and recurrent glioblastomas. Recurrence-associated proteins were validated using immunohistochemistry and further studied in human glioma cell lines, orthotopic xenograft models, and human organotypic brain slice cultures. External spatial transcriptomic, single-cell, and bulk RNA sequencing data were analyzed to gain mechanistic insights.

Results: Although overall proteomic changes were heterogeneous across patients, we identified BCAS1, INF2, and FBXO2 as consistently upregulated proteins at recurrence and validated these using immunohistochemistry. Knockout of FBXO2 in human glioma cells conferred a strong survival benefit in orthotopic xenograft mouse models and reduced invasive growth in organotypic brain slice cultures. In glioblastoma patient samples, FBXO2 expression was enriched in the tumor infiltration zone and FBXO2-positive cancer cells were associated with synaptic signaling processes.

Conclusions: These findings demonstrate a potential role of FBXO2-dependent glioma-microenvironment interactions to promote tumor growth. Furthermore, the published datasets provide a valuable resource for further studies.

Research field(s)
Oncology & Carcinogenesis

DOI
10.1093/neuonc/noac169

RNA binding protein DDX5 restricts RORγt+Tregsuppressor function to promote intestine inflammation

NOMIS Researcher(s)

Published in

February 1, 2023

Retinoid-related orphan receptor (RAR) gamma (RORγt)-expressing regulatory T cells (RORγt+ Tregs) play pivotal roles in preventing T cell hyperactivation and maintaining tissue homeostasis, in part by secreting the anti-inflammation cytokine interleukin-10 (IL-10). Here, we report that hypoxia-induced factor 1α (HIF1α) is the master transcription factor for Il10 in RORγt+ Tregs. This critical anti-inflammatory pathway is negatively regulated by an RNA binding protein DEAD box helicase 5 (DDX5). As a transcriptional corepressor, DDX5 restricts the expression of HIF1α and its downstream target gene Il10 in RORγt+ Tregs. T cell-specific Ddx5 knockout (DDX5ΔT) mice have augmented RORγt+ Treg suppressor activities and are better protected from intestinal inflammation. Genetic ablation or pharmacologic inhibition of HIF1α restores enteropathy susceptibility in DDX5ΔT mice. The DDX5-HIF1α- IL-10 pathway is conserved in mice and humans. These findings reveal potential therapeutic targets for intestinal inflammatory diseases. Copyright © 2023 The Authors.

Research field(s)
Health Sciences

DOI
10.1126/sciadv.add6165

Whole-mouse clearing and imaging at the cellular level with vDISCO

NOMIS Researcher(s)

Published in

January 25, 2023

Homeostatic and pathological phenomena often affect multiple organs across the whole organism. Tissue clearing methods, together with recent advances in microscopy, have made holistic examinations of biological samples feasible. Here, we report the detailed protocol for nanobody(VHH)-boosted 3D imaging of solvent-cleared organs (vDISCO), a pressure-driven, nanobody-based whole-body immunolabeling and clearing method that renders whole mice transparent in 3 weeks, consistently enhancing the signal of fluorescent proteins, stabilizing them for years. This allows the reliable detection and quantification of fluorescent signal in intact rodents enabling the analysis of an entire body at cellular resolution. Here, we show the high versatility of vDISCO applied to boost the fluorescence signal of genetically expressed reporters and clear multiple dissected organs and tissues, as well as how to image processed samples using multiple fluorescence microscopy systems. The entire protocol is accessible to laboratories with limited expertise in tissue clearing. In addition to its applications in obtaining a whole-mouse neuronal projection map, detecting single-cell metastases in whole mice and identifying previously undescribed anatomical structures, we further show the visualization of the entire mouse lymphatic system, the application for virus tracing and the visualization of all pericytes in the brain. Taken together, our vDISCO pipeline allows systematic and comprehensive studies of cellular phenomena and connectivity in whole bodies. © 2023, Springer Nature Limited.

Research field(s)
Applied Sciences, Enabling & Strategic Technologies, Bioinformatics

DOI
10.1038/s41596-022-00788-2

Beyond Intrinsic and Instrumental: Third-Category Value in Environmental Ethics and Environmental Policy

NOMIS Researcher(s)

Published in

January 24, 2023

Values have always tended to play a central role in discourse on the environment, a tendency which is currently particularly evident in the biodiversity context. Traditionally, arguments about the environment have invoked instrumental value to highlight the necessity or utility of a healthy environment for people and intrinsic value to emphasize the importance of protecting nature for its own sake. More recently, this value dichotomy has been challenged, and the notion of a third value category – relational value – has been introduced into the political and social conservation discussion. In the field of environmental philosophy, the idea of a third category of environmental value already has a longer tradition. This article describes and compares several philosophical accounts of third-category environmental value to contribute to a better characterization of relational value and thus to a better understanding of the role this type of value can play in environmental discourse and policy.

Research field(s)
Philosophy

DOI
10.1080/21550085.2023.2166341

FUS ALS neurons activate major stress pathways and reduce translation as an early protective mechanism against neurodegeneration

NOMIS Researcher(s)

Published in

January 24, 2023

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder causing progressive loss of motor neurons. Mutations in Fused in sarcoma (FUS) leading to its cytoplasmic mislocalization cause a subset of ALS. Under stress, mutant FUS localizes to stress granules (SGs)—cytoplasmic condensates composed of RNA and various proteins. Aberrant dynamics of SGs is linked to the pathology of ALS. Here, using motor neurons (MNs) derived from human induced pluripotent stem cells, we show that, in mutant FUS, MN dynamics of SGs is disturbed. Additionally, heat-shock response (HSR) and integrated stress response (ISR) involved in the regulation of SGs are upregulated in mutant MNs. HSR activation correlates with the amount of cytoplasmic FUS mislocalization. While inhibition of SG formation, translation, or ISR does not influence survival of FUS ALS neurons, proteotoxicity that cannot be compensated with the activation of stress pathways is the main driver of neurodegeneration in early FUS ALS. © 2023 The Author(s)

Research field(s)
Health Sciences

DOI
10.1016/j.celrep.2023.112025

Glacier-Fed Stream Biofilms Harbor Diverse Resistomes and Biosynthetic Gene Clusters

NOMIS Researcher(s)

Published in

January 23, 2023

Antimicrobial resistance (AMR) is a universal phenomenon the origins of which lay in natural ecological interactions such as competition within niches, within and between micro- to higher-order organisms. To study these phenomena, it is crucial to examine the origins of AMR in pristine environments, i.e., limited anthropogenic influences. In this context, epilithic biofilms residing in glacier-fed streams (GFSs) are an excellent model system to study diverse, intra- and inter-domain, ecological crosstalk. We assessed the resistomes of epilithic biofilms from GFSs across the Southern Alps (New Zealand) and the Caucasus (Russia) and observed that both bacteria and eukaryotes encoded twenty-nine distinct AMR categories. Of these, beta-lactam, aminoglycoside, and multidrug resistance were both abundant and taxonomically distributed in most of the bacterial and eukaryotic phyla. AMR-encoding phyla included Bacteroidota and Proteobacteria among the bacteria, alongside Ochrophyta (algae) among the eukaryotes. Additionally, biosynthetic gene clusters (BGCs) involved in the production of antibacterial compounds were identified across all phyla in the epilithic biofilms. Furthermore, we found that several bacterial genera (Flavobacterium, Polaromonas, Superphylum Patescibacteria) encode both atimicrobial resistance genes (ARGs) and BGCs within close proximity of each other, demonstrating their capacity to simultaneously influence and compete within the microbial community. Our findings help unravel how naturally occurring BGCs and AMR contribute to the epilithic biofilms mode of life in GFSs. Additionally, we report that eukaryotes may serve as AMR reservoirs owing to their potential for encoding ARGs. Importantly, these observations may be generalizable and potentially extended to other environments that may be more or less impacted by human activity. IMPORTANCE Antimicrobial resistance is an omnipresent phenomenon in the anthropogenically influenced ecosystems. However, its role in shaping microbial community dynamics in pristine environments is relatively unknown. Using metagenomics, we report the presence of antimicrobial resistance genes and their associated pathways in epilithic biofilms within glacier-fed streams. Importantly, we observe biosynthetic gene clusters associated with antimicrobial resistance in both pro- and eukaryotes in these biofilms. Understanding the role of resistance in the context of this pristine environment and complex biodiversity may shed light on previously uncharacterized mechanisms of cross-domain interactions. Copyright © 2023 Busi et al.

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

DOI
10.1128/spectrum.04069-22

All-optical physiology resolves a synaptic basis for behavioral timescale plasticity

NOMIS Researcher(s)

Published in

January 19, 2023

Learning has been associated with modifications of synaptic and circuit properties, but the precise changes storing information in mammals have remained largely unclear. We combined genetically targeted voltage imaging with targeted optogenetic activation and silencing of pre- and post-synaptic neurons to study the mechanisms underlying hippocampal behavioral timescale plasticity. In mice navigating a virtual-reality environment, targeted optogenetic activation of individual CA1 cells at specific places induced stable representations of these places in the targeted cells. Optical elicitation, recording, and modulation of synaptic transmission in behaving mice revealed that activity in presynaptic CA2/3 cells was required for the induction of plasticity in CA1 and, furthermore, that during induction of these place fields in single CA1 cells, synaptic input from CA2/3 onto these same cells was potentiated. These results reveal synaptic implementation of hippocampal behavioral timescale plasticity and define a methodology to resolve synaptic plasticity during learning and memory in behaving mammals. © 2022 The Author(s)

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

DOI
10.1016/j.cell.2022.12.035

Evolutionary diversification of methanotrophic ANME-1 archaea and their expansive virome

NOMIS Researcher(s)

Published in

January 19, 2023

‘Candidatus Methanophagales’ (ANME-1) is an order-level clade of archaea responsible for anaerobic methane oxidation in deep-sea sediments. The diversity, ecology and evolution of ANME-1 remain poorly understood. In this study, we use metagenomics on deep-sea hydrothermal samples to expand ANME-1 diversity and uncover the effect of virus–host dynamics. Phylogenetic analyses reveal a deep-branching, thermophilic family, ‘Candidatus Methanospirareceae’, closely related to short-chain alkane oxidizers. Global phylogeny and near-complete genomes show that hydrogen metabolism within ANME-1 is an ancient trait that was vertically inherited but differentially lost during lineage diversification. Metagenomics also uncovered 16 undescribed virus families so far exclusively targeting ANME-1 archaea, showing unique structural and replicative signatures. The expansive ANME-1 virome contains a metabolic gene repertoire that can influence host ecology and evolution through virus-mediated gene displacement. Our results suggest an evolutionary continuum between anaerobic methane and short-chain alkane oxidizers and underscore the effects of viruses on the dynamics and evolution of methane-driven ecosystems. © 2023, The Author(s).

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

DOI
10.1038/s41564-022-01297-4

River ecosystem metabolism and carbon biogeochemistry in a changing world

NOMIS Researcher(s)

Published in

January 18, 2023

River networks represent the largest biogeochemical nexus between the continents, ocean and atmosphere. Our current understanding of the role of rivers in the global carbon cycle remains limited, which makes it difficult to predict how global change may alter the timing and spatial distribution of riverine carbon sequestration and greenhouse gas emissions. Here we review the state of river ecosystem metabolism research and synthesize the current best available estimates of river ecosystem metabolism. We quantify the organic and inorganic carbon flux from land to global rivers and show that their net ecosystem production and carbon dioxide emissions shift the organic to inorganic carbon balance en route from land to the coastal ocean. Furthermore, we discuss how global change may affect river ecosystem metabolism and related carbon fluxes and identify research directions that can help to develop better predictions of the effects of global change on riverine ecosystem processes. We argue that a global river observing system will play a key role in understanding river networks and their future evolution in the context of the global carbon budget. © 2023, Springer Nature Limited.

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

DOI
10.1038/s41586-022-05500-8

Non-pyrogenic highly pure magnetosomes for efficient hyperthermia treatment of prostate cancer

NOMIS Researcher(s)

Published in

January 12, 2023

We report the fabrication of highly pure magnetosomes that are synthesized by magnetotactic bacteria (MTB) using pharmaceutically compatible growth media, i.e., without compounds of animal origin (yeast extracts), carcinogenic, mutagenic, or toxic for reproduction (CMR) products, and other heavy metals than iron. To enable magnetosome medical applications, these growth media are reduced and amended compared with media commonly used to grow these bacteria. Furthermore, magnetosomes are made non-pyrogenic by being extracted from these micro-organisms and heated above 400 °C to remove and denature bacterial organic material and produce inorganic magnetosome minerals. To be stabilized, these minerals are further coated with citric acid to yield M-CA, leading to fully reconstructed chains of magnetosomes. The heating properties and anti-tumor activity of highly pure M-CA are then studied by bringing M-CA into contact with PC3-Luc tumor cells and by exposing such assembly to an alternating magnetic field (AMF) of 42 mT and 195 kHz during 30 min. While in the absence of AMF, M-CA are observed to be non-cytotoxic, they result in a 35% decrease in cell viability following AMF application. The treatment efficacy can be associated with a specific absorption rate (SAR) value of M-CA, which is relatively high in cellular environment, i.e., SARcell = 253 ± 11 W/gFe, while being lower than the M-CA SAR value measured in water, i.e., SARwater = 1025 ± 194 W/gFe, highlighting that a reduction in the Brownian contribution to the SAR value in cellular environment does not prevent efficient tumor cell destruction with these nanoparticles. Key points: • Highly pure magnetosomes were produced in pharmaceutically compatible growth media • Non-pyrogenic and stable magnetosomes were prepared for human injection • Magnetosomes efficiently destroyed prostate tumor cells in magnetic hyperthermia © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Research field(s)
Applied Sciences, Enabling & Strategic Technologies, Biotechnology

DOI
10.1007/s00253-022-12247-9

Whole-brain microscopy reveals distinct temporal and spatial efficacy of anti-Aβ therapies

NOMIS Researcher(s)

Published in

January 11, 2023

Many efforts targeting amyloid-β (Aβ) plaques for the treatment of Alzheimer’s Disease thus far have resulted in failures during clinical trials. Regional and temporal heterogeneity of efficacy and dependence on plaque maturity may have contributed to these disappointing outcomes. In this study, we mapped the regional and temporal specificity of various anti-Aβ treatments through high-resolution light-sheet imaging of electrophoretically cleared brains. We assessed the effect on amyloid plaque formation and growth in Thy1-APP/PS1 mice subjected to β-secretase inhibitors, polythiophenes, or anti-Aβ antibodies. Each treatment showed unique spatiotemporal Aβ clearance, with polythiophenes emerging as a potent anti-Aβ compound. Furthermore, aligning with a spatial-transcriptomic atlas revealed transcripts that correlate with the efficacy of each Aβ therapy. As observed in this study, there is a striking dependence of specific treatments on the location and maturity of Aβ plaques. This may also contribute to the clinical trial failures of Aβ-therapies, suggesting that combinatorial regimens may be significantly more effective in clearing amyloid deposition. © 2022 The Authors. Published under the terms of the CC BY 4.0 license.

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

DOI
10.15252/emmm.202216789

New approaches to epidemic modeling on networks

NOMIS Researcher(s)

Published in

January 10, 2023

In this article, we develop two independent and new approaches to model epidemic spread in a network. Contrary to the most studied models, those developed here allow for contacts with different probabilities of transmitting the disease (transmissibilities). We then examine each of these models using some mean field type approximations. The first model looks at the late-stage effects of an epidemic outbreak and allows for the computation of the probability that a given vertex was infected. This computation is based on a mean field approximation and only depends on the number of contacts and their transmissibilities. This approach shares many similarities with percolation models in networks. The second model we develop is a dynamic model which we analyze using a mean field approximation which highly reduces the dimensionality of the system. In particular, the original system which individually analyses each vertex of the network is reduced to one with as many equations as different transmissibilities. Perhaps the greatest contribution of this article is the observation that, in both these models, the existence and size of an epidemic outbreak are linked to the properties of a matrix which we call the R-matrix. This is a generalization of the basic reproduction number which more precisely characterizes the main routes of infection. © 2023, The Author(s).

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

DOI
10.1038/s41598-022-19827-9

Tropical forests post-logging are a persistent net carbon source to the atmosphere

NOMIS Researcher(s)

Published in

January 9, 2023

Logged and structurally degraded tropical forests are fast becoming one of the most prevalent land-use types throughout the tropics and are routinely assumed to be a net carbon sink because they experience rapid rates of tree regrowth. Yet this assumption is based on forest biomass inventories that record carbon stock recovery but fail to account for the simultaneous losses of carbon from soil and necromass. Here, we used forest plots and an eddy covariance tower to quantify and partition net ecosystem CO2 exchange in Malaysian Borneo, a region that is a hot spot for deforestation and forest degradation. Our data represent the complete carbon budget for tropical forests measured throughout a logging event and subsequent recovery and found that they constitute a substantial and persistent net carbon source. Consistent with existing literature, our study showed a significantly greater woody biomass gain across moderately and heavily logged forests compared with unlogged forests, but this was counteracted by much larger carbon losses from soil organic matter and deadwood in logged forests. We estimate an average carbon source of 1.75 ± 0.94 Mg C ha−1 yr−1 within moderately logged plots and 5.23 ± 1.23 Mg C ha−1 yr−1 in unsustainably logged and severely degraded plots, with emissions continuing at these rates for at least one-decade post-logging. Our data directly contradict the default assumption that recovering logged and degraded tropical forests are net carbon sinks, implying the amount of carbon being sequestered across the world’s tropical forests may be considerably lower than currently estimated. Copyright © 2023 the Author(s).

Research field(s)
Natural Sciences, Biology, Ecology

DOI
10.1073/pnas.2214462120

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