Insight
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Publications in Natural Sciences by NOMIS researchers

NOMIS Researcher(s)

Published in

July 10, 2024

The emergence of single nucleus RNA sequencing (snRNA-seq) offers to revolutionize the study of Alzheimer’s disease (AD). Integration with complementary multiomics data such as genetics, proteomics and clinical data provides powerful opportunities to link cell subpopulations and molecular networks with a broader disease-relevant context. We report snRNA-seq profiles from superior frontal gyrus samples from 101 well characterized subjects from the Banner Brain and Body Donation Program in combination with whole genome sequences. We report findings that link common AD risk variants with CR1 expression in oligodendrocytes as well as alterations in hematological parameters. We observed an AD-associated CD83(+) microglial subtype with unique molecular networks and which is associated with immunoglobulin IgG4 production in the transverse colon. Our major observations were replicated in two additional, independent snRNA-seq data sets. These findings illustrate the power of multi-tissue molecular profiling to contextualize snRNA-seq brain transcriptomics and reveal disease biology.

Research field(s)
Genetics & Heredity, Biology

NOMIS Researcher(s)

Published in

June 20, 2024

Gamete formation and subsequent offspring development often involve extended phases of suspended cellular development or even dormancy. How cells adapt to recover and resume growth remains poorly understood. Here, we visualized budding yeast cells undergoing meiosis by cryo-electron tomography (cryoET) and discovered elaborate filamentous assemblies decorating the nucleus, cytoplasm, and mitochondria. To determine filament composition, we developed a “filament identification” (FilamentID) workflow that combines multiscale cryoET/cryo-electron microscopy (cryoEM) analyses of partially lysed cells or organelles. FilamentID identified the mitochondrial filaments as being composed of the conserved aldehyde dehydrogenase Ald4ALDH2 and the nucleoplasmic/cytoplasmic filaments as consisting of acetyl-coenzyme A (CoA) synthetase Acs1ACSS2. Structural characterization further revealed the mechanism underlying polymerization and enabled us to genetically perturb filament formation. Acs1 polymerization facilitates the recovery of chronologically aged spores and, more generally, the cell cycle re-entry of starved cells. FilamentID is broadly applicable to characterize filaments of unknown identity in diverse cellular contexts.

Research field(s)
Microbiology, Biology

NOMIS Researcher(s)

Published in

June 20, 2024

Sexually reproducing eukaryotes employ a developmentally regulated cell division program—meiosis—to generate haploid gametes from diploid germ cells. To understand how gametes arise, we generated a proteomic census encompassing the entire meiotic program of budding yeast. We found that concerted waves of protein expression and phosphorylation modify nearly all cellular pathways to support meiotic entry, meiotic progression, and gamete morphogenesis. Leveraging this comprehensive resource, we pinpointed dynamic changes in mitochondrial components and showed that phosphorylation of the FoF1-ATP synthase complex is required for efficient gametogenesis. Furthermore, using cryoET as an orthogonal approach to visualize mitochondria, we uncovered highly ordered filament arrays of Ald4ALDH2, a conserved aldehyde dehydrogenase that is highly expressed and phosphorylated during meiosis. Notably, phosphorylation-resistant mutants failed to accumulate filaments, suggesting that phosphorylation regulates context-specific Ald4ALDH2 polymerization. Overall, this proteomic census constitutes a broad resource to guide the exploration of the unique sequence of events underpinning gametogenesis.

Research field(s)
Biology

A key feature of many developmental systems is their ability to self-organize spatial patterns of functionally distinct cell fates. To ensure proper biological function, such patterns must be established reproducibly, by controlling and even harnessing intrinsic and extrinsic fluctuations. While the relevant molecular processes are increasingly well understood, we lack a principled framework to quantify the performance of such stochastic self-organizing systems. To that end, we introduce an information-theoretic measure for self-organized fate specification during embryonic development. We show that the proposed measure assesses the total information content of fate patterns and decomposes it into interpretable contributions corresponding to the positional and correlational information. By optimizing the proposed measure, our framework provides a normative theory for developmental circuits, which we demonstrate on lateral inhibition, cell type proportioning, and reaction–diffusion models of self-organization. This paves a way toward a classification of developmental systems based on a common information-theoretic language, thereby organizing the zoo of implicated chemical and mechanical signaling processes.

Research field(s)
Biology

NOMIS Researcher(s)

Published in

May 13, 2024

Retrospective lineage reconstruction of humans predicts that dramatic clonal imbalances in the body can be traced to the 2-cell stage embryo. However, whether and how such clonal asymmetries arise in the embryo is unclear. Here, we performed prospective lineage tracing of human embryos using live imaging, non-invasive cell labeling, and computational predictions to determine the contribution of each 2-cell stage blastomere to the epiblast (body), hypoblast (yolk sac), and trophectoderm (placenta). We show that the majority of epiblast cells originate from only one blastomere of the 2-cell stage embryo. We observe that only one to three cells become internalized at the 8-to-16-cell stage transition. Moreover, these internalized cells are more frequently derived from the first cell to divide at the 2-cell stage. We propose that cell division dynamics and a cell internalization bottleneck in the early embryo establish asymmetry in the clonal composition of the future human body.

Research field(s)
Biology

NOMIS Researcher(s)

Published in

April 4, 2024

Genomic DNA that resides in the nuclei of mammalian neurons can be as old as the organism itself. The life span of nuclear RNAs, which are critical for proper chromatin architecture and transcription regulation, has not been determined in adult tissues. In this work, we identified and characterized nuclear RNAs that do not turn over for at least 2 years in a subset of postnatally born cells in the mouse brain. These long-lived RNAs were stably retained in nuclei in a neural cell type–specific manner and were required for the maintenance of heterochromatin. Thus, the life span of neural cells may depend on both the molecular longevity of DNA for the storage of genetic information and also the extreme stability of RNA for the functional organization of chromatin.

Research field(s)
Genetics & Heredity, Biology

NOMIS Researcher(s)

Published in

March 1, 2024

Most cryospheric ecosystems are energy limited. How their energetics will respond to climate change remains largely unknown. This is particularly true for glacier-fed streams, which interface with the cryosphere and initiate some of Earth’s largest river systems. Here, by studying resource stoichiometry and microbial energetics in 154 glacier-fed streams sampled by the Vanishing Glaciers project across Earth’s major mountain ranges, we show that these ecosystems and their benthic microbiome are overall carbon and phosphorus limited. Threshold elemental ratios and low carbon use efficiencies (median: 0.15) modelled from extracellular enzymatic activities corroborate resource limitation in agreement with maintenance metabolism of benthic microorganisms. Space-for-time substitution analyses suggest that glacier shrinkage will stimulate benthic primary production in glacier-fed streams, thereby relieving microbial metabolism from carbon limitation. Concomitantly, we find that increasing streamwater temperature will probably stimulate microbial growth (temperature sensitivity: 0.62 eV). Consequently, elevated microbial demands for phosphorus, but diminishing inputs from subglacial sources, may intensify phosphorus limitation as glaciers shrink. Our study thus unveils a ‘green transition’ towards autotrophy in the world’s glacier-fed streams, entailing shifts in the energetics of their microorganisms.

Research field(s)
Ecology, Environmental Sciences

NOMIS Researcher(s)

Published in

February 19, 2024

Earth’s surface is deficient in available forms of many elements considered limiting for prebiotic chemistry. In contrast, many extraterrestrial rocky objects are rich in these same elements. Limiting prebiotic ingredients may, therefore, have been delivered by exogenous material; however, the mechanisms by which exogeneous material may be reliably and non-destructively supplied to a planetary surface remains unclear. Today, the flux of extraterrestrial matter to Earth is dominated by fine-grained cosmic dust. Although this material is rarely discussed in a prebiotic context due to its delivery over a large surface area, concentrated cosmic dust deposits are known to form on Earth today due to the action of sedimentary processes. Here we combine empirical constraints on dust sedimentation with dynamical simulations of dust formation and planetary accretion to show that localized sedimentary deposits of cosmic dust could have accumulated in arid environments on early Earth, in particular glacial settings that today produce cryoconite sediments. Our results challenge the widely held assumption that cosmic dust is incapable of fertilizing prebiotic chemistry. Cosmic dust deposits may have plausibly formed on early Earth and acted to fertilize prebiotic chemistry.

Research field(s)
Earth & Environmental Sciences, Physics & Astronomy

NOMIS Researcher(s)

November 16, 2023

Biological conservation practices and approaches take many forms. Conservation projects do not only differ in their aims and methods, but also concerning their conceptual and normative background assumptions and their underlying motivations and objectives. We draw on philosophical distinctions from the ethics of conservation to explain variances of different positions on conservation projects along six dimensions: (1) conservation ideals, (2) intervention intuitions, (3) the moral considerability of nonhuman beings, (4) environmental values, (5) views on nature and (6) human roles in nature. The result is a map of the moral landscape of biological conservation, on which these six dimensions are layered. This map functions as a heuristic tool to understand conceptual and normative foundations of specific conservation projects, which we will illustrate with four paradigmatic examples: the Pisavaara Strict Nature Reserve, Predator Free New Zealand, the Oostvaardersplassen Nature Reserve and the Great Green Wall Project. With this map as a heuristic tool, we aim to conceptually illuminate disagreement and clarify misunderstandings between representatives of different environmental protection strategies and to show that the same project can be supported (or criticised) on different grounds.

Research field(s)
Biology, Environmental Sciences

NOMIS Researcher(s)

October 20, 2023

State-of-the-art transmon qubits rely on large capacitors, which systematically improve their coherence due to reduced surface-loss participation. However, this approach increases both the footprint and the parasitic cross-coupling and is ultimately limited by radiation losses – a potential roadblock for scaling up quantum processors to millions of qubits. In this work we present transmon qubits with sizes as low as 36×39μm2 with ≳100-nm-wide vacuum-gap capacitors that are micromachined from commercial silicon-on-insulator wafers and shadow evaporated with aluminum. We achieve a vacuum participation ratio up to 99.6% in an in-plane design that is compatible with standard coplanar circuits. Qubit relaxation-time measurements for small gaps with high zero-point electric field variance of up to 22 V/m reveal a double exponential decay indicating comparably strong qubit interaction with long-lived two-level systems. The exceptionally high selectivity of up to 20 dB to the superconductor-vacuum interface allows us to precisely back out the sub-single-photon dielectric loss tangent of aluminum oxide previously exposed to ambient conditions. In terms of future scaling potential, we achieve a ratio of qubit quality factor to a footprint area equal to 20μm-2, which is comparable with the highest T1 devices relying on larger geometries, a value that could improve substantially for lower surface-loss superconductors. © 2023 American Physical Society.

Research field(s)
Natural Sciences, Quantum, Josephson Junctions, Microwave, Qubits

NOMIS Researcher(s)

Published in

October 14, 2023

Remote sensing of vegetation by spectroscopy is increasingly used to characterize trait distributions in plant communities. How leaves interact with electromagnetic radiation is determined by their structure and contents of pigments, water, and abundant dry matter constituents like lignins, phenolics, and proteins. High-resolution (“hyperspectral”) spectroscopy can characterize trait variation at finer scales, and may help to reveal underlying genetic variation—information important for assessing the potential of populations to adapt to global change. Here, we use a set of 360 inbred genotypes of the wild coyote tobacco Nicotiana attenuata: wild accessions, recombinant inbred lines (RILs), and transgenic lines (TLs) with targeted changes to gene expression, to dissect genetic versus non-genetic influences on variation in leaf spectra across three experiments. We calculated leaf reflectance from hand-held field spectroradiometer measurements covering visible to short-wave infrared wavelengths of electromagnetic radiation (400–2500 nm) using a standard radiation source and backgrounds, resulting in a small and quantifiable measurement uncertainty. Plants were grown in more controlled (glasshouse) or more natural (field) environments, and leaves were measured both on- and off-plant with the measurement set-up thus also in more to less controlled environmental conditions. Entire spectra varied across genotypes and environments. We found that the greatest variance in leaf reflectance was explained by between-experiment and non-genetic between-sample differences, with subtler and more specific variation distinguishing groups of genotypes. The visible spectral region was most variable, distinguishing experimental settings as well as groups of genotypes within experiments, whereas parts of the short-wave infrared may vary more specifically with genotype. Overall, more genetically variable plant populations also showed more varied leaf spectra. We highlight key considerations for the application of field spectroscopy to assess genetic variation in plant populations. © 2023, BioMed Central Ltd., part of Springer Nature.

Research field(s)
Natural Sciences, Biology, Plant Biology & Botany

NOMIS Researcher(s)

Published in

August 30, 2023

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

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

NOMIS Researcher(s)

Published in

August 17, 2023

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

Research field(s)
Natural Sciences

NOMIS Researcher(s)

Published in

August 10, 2023

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

Research field(s)
Natural Sciences

NOMIS Researcher(s)

Published in

August 9, 2023

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

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

NOMIS Researcher(s)

Published in

July 20, 2023

Non-membrane-bound biomolecular condensates have been proposed to represent an important mode of subcellular organization in diverse biological settings. However, the fundamental principles governing the spatial organization and dynamics of condensates at the atomistic level remain unclear. The Saccharomyces cerevisiae Lge1 protein is required for histone H2B ubiquitination and its N-terminal intrinsically disordered fragment (Lge11-80) undergoes robust phase separation. This study connects single-and multi-chain all-atom molecular dynamics simulations of Lge11-80 with the in vitro behavior of Lge11-80 condensates. Analysis of modeled protein-protein interactions elucidates the key determinants of Lge11-80 condensate formation and links configurational entropy, valency, and compactness of proteins inside the condensates. A newly derived analytical formalism, related to colloid fractal cluster formation, describes condensate architecture across length scales as a function of protein valency and compactness. In particular, the formalism provides an atomisti-cally resolved model of Lge11-80 condensates on the scale of hundreds of nanometers starting from individual protein conformers captured in simulations. The simulation-derived fractal dimensions of condensates of Lge11-80 and its mutants agree with their in vitro morphologies. The presented framework enables a multiscale description of biomolecular condensates and embeds their study in a wider context of colloid self-organization. © Polyansky, Gallego et al.

Research field(s)
Natural Sciences

NOMIS Researcher(s)

Published in

July 5, 2023

Currently available quantum processors are dominated by noise, which severely limits their applicability and motivates the search for new physical qubit encodings. In this work, we introduce the inductively shunted transmon, a weakly flux-tunable superconducting qubit that offers charge offset protection for all levels and a 20-fold reduction in flux dispersion compared to the state-of-the-art resulting in a constant coherence over a full flux quantum. The parabolic confinement provided by the inductive shunt as well as the linearity of the geometric superinductor facilitates a high-power readout that resolves quantum jumps with a fidelity and QND-ness of >90% and without the need for a Josephson parametric amplifier. Moreover, the device reveals quantum tunneling physics between the two prepared fluxon ground states with a measured average decay time of up to 3.5 h. In the future, fast time-domain control of the transition matrix elements could offer a new path forward to also achieve full qubit control in the decay-protected fluxon basis. © 2023, The Author(s).

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

NOMIS Researcher(s)

Published in

June 14, 2023

We study ab initio approaches for calculating x-ray Thomson scattering spectra from density functional theory molecular dynamics simulations based on a modified Chihara formula that expresses the inelastic contribution in terms of the dielectric function. We study the electronic dynamic structure factor computed from the Mermin dielectric function using an ab initio electron-ion collision frequency in comparison to computations using a linear-response time-dependent density functional theory (LR-TDDFT) framework for hydrogen and beryllium and investigate the dispersion of free-free and bound-free contributions to the scattering signal. A separate treatment of these contributions, where only the free-free part follows the Mermin dispersion, shows good agreement with LR-TDDFT results for ambient-density beryllium, but breaks down for highly compressed matter where the bound states become pressure ionized. LR-TDDFT is used to reanalyze x-ray Thomson scattering experiments on beryllium demonstrating strong deviations from the plasma conditions inferred with traditional analytic models at small scattering angles. © 2023 American Physical Society.

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

NOMIS Researcher(s)

Published in

May 29, 2023

Under high pressures and temperatures, molecular systems with substantial polarization charges, such as ammonia and water, are predicted to form superionic phases and dense fluid states with dissociating molecules and high electrical conductivity. This behaviour potentially plays a role in explaining the origin of the multipolar magnetic fields of Uranus and Neptune, whose mantles are thought to result from a mixture of H2O, NH3 and CH4 ices. Determining the stability domain, melting curve and electrical conductivity of these superionic phases is therefore crucial for modelling planetary interiors and dynamos. Here we report the melting curve of superionic ammonia up to 300 GPa from laser-driven shock compression of pre-compressed samples and atomistic calculations. We show that ammonia melts at lower temperatures than water above 100 GPa and that fluid ammonia’s electrical conductivity exceeds that of water at conditions predicted by hot, super-adiabatic models for Uranus and Neptune, and enhances the conductivity in their fluid water-rich dynamo layers. © 2023, The Author(s), under exclusive licence to Springer Nature Limited.

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

NOMIS Researcher(s)

Published in

May 24, 2023

The ability to control the direction of scattered light is crucial to provide flexibility and scalability for a wide range of on-chip applications, such as integrated photonics, quantum information processing, and nonlinear optics. Tunable directionality can be achieved by applying external magnetic fields that modify optical selection rules, by using nonlinear effects, or interactions with vibrations. However, these approaches are less suitable to control microwave photon propagation inside integrated superconducting quantum devices. Here, we demonstrate on-demand tunable directional scattering based on two periodically modulated transmon qubits coupled to a transmission line at a fixed distance. By changing the relative phase between the modulation tones, we realize unidirectional forward or backward photon scattering. Such an in-situ switchable mirror represents a versatile tool for intra- and inter-chip microwave photonic processors. In the future, a lattice of qubits can be used to realize topological circuits that exhibit strong nonreciprocity or chirality. © 2023, The Author(s).

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

NOMIS Researcher(s)

May 16, 2023

Aim: Globally distributed plant trait data are increasingly used to understand relationships between biodiversity and ecosystem processes. However, global trait databases are sparse because they are compiled from many, mostly small databases. This sparsity in both trait space completeness and geographical distribution limits the potential for both multivariate and global analyses. Thus, ‘gap-filling’ approaches are often used to impute missing trait data. Recent methods, like Bayesian hierarchical probabilistic matrix factorization (BHPMF), can impute large and sparse data sets using side information. We investigate whether BHPMF imputation leads to biases in trait space and identify aspects influencing bias to provide guidance for its usage. Innovation: We use a fully observed trait data set from which entries are randomly removed, along with extensive but sparse additional data. We use BHPMF for imputation and evaluate bias by: (1) accuracy (residuals, RMSE, trait means), (2) correlations (bi- and multivariate) and (3) taxonomic and functional clustering (valuewise, uni- and multivariate). BHPMF preserves general patterns of trait distributions but induces taxonomic clustering. Data set–external trait data had little effect on induced taxonomic clustering and stabilized trait–trait correlations. Main Conclusions: Our study extends the criteria for the evaluation of gap-filling beyond RMSE, providing insight into statistical data structure and allowing better informed use of imputed trait data, with improved practice for imputation. We expect our findings to be valuable beyond applications in plant ecology, for any study using hierarchical side information for imputation. © 2023 The Authors. Global Ecology and Biogeography published by John Wiley & Sons Ltd.

Research field(s)
Natural Sciences, Biology, Ecology