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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.

Systematic review and analysis of human proteomics aging studies unveils a novel proteomic aging clock and identifies key processes that change with age

NOMIS Researcher(s)

Published in

July 1, 2020

The development of clinical interventions that significantly improve human healthspan requires robust markers of biological age as well as thoughtful therapeutic targets. To promote these goals, we performed a systematic review and analysis of human aging and proteomics studies. The systematic review includes 36 different proteomics analyses, each of which identified proteins that significantly changed with age. We discovered 1,128 proteins that had been reported by at least two or more analyses and 32 proteins that had been reported by five or more analyses. Each of these 32 proteins has known connections relevant to aging and age-related disease. GDF15, for example, extends both lifespan and healthspan when overexpressed in mice and is additionally required for the anti-diabetic drug metformin to exert beneficial effects on body weight and energy balance. Bioinformatic enrichment analyses of our 1,128 commonly identified proteins heavily implicated processes relevant to inflammation, the extracellular matrix, and gene regulation. We additionally propose a novel proteomic aging clock comprised of proteins that were reported to change with age in plasma in three or more different studies. Using a large patient cohort comprised of 3,301 subjects (aged 18–76 years), we demonstrate that this clock is able to accurately predict human age.

Research field(s)
Health Sciences, Public Health & Health Services, Gerontology

DOI
10.1016/j.arr.2020.101070

Prion infection, transmission, and cytopathology modeled in a low-biohazard human cell line

NOMIS Researcher(s)

Published in

June 30, 2020

Transmission of prion infectivity to susceptible murine cell lines has simplified prion titration assays and has greatly reduced the need for animal experimentation. However, murine cell models suffer from technical and biological constraints. Human cell lines might be more useful, but they are much more biohazardous and are often poorly infectible. Here, we describe the human clonal cell line hovS, which lacks the human PRNP gene and expresses instead the ovine PRNP VRQ allele. HovS cells were highly susceptible to the PG127 strain of sheep-derived murine prions, reaching up to 90% infected cells in any given culture and were maintained in a continuous infected state for at least 14 passages. Infected hovS cells produced proteinase K–resistant prion protein (PrPSc), pelletable PrP aggregates, and bona fide infectious prions capable of infecting further generations of naïve hovS cells and mice expressing the VRQ allelic variant of ovine PrPC. Infection in hovS led to prominent cytopathic vacuolation akin to the spongiform changes observed in individuals suffering from prion diseases. In addition to expanding the toolbox for prion research to human experimental genetics, the hovS cell line provides a human-derived system that does not require human prions. Hence, the manipulation of scrapie-infected hovS cells may present fewer biosafety hazards than that of genuine human prions.

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

DOI
10.26508/LSA.202000814

Cryo-Electron Tomography Reveals the Complex Ultrastructural Organization of Multicellular Filamentous Chloroflexota (Chloroflexi) Bacteria

NOMIS Researcher(s)

Published in

June 26, 2020

The cell biology of Chloroflexota is poorly studied. We applied cryo-focused ion beam milling and cryo-electron tomography to study the ultrastructural organization of thermophilic Roseiflexus castenholzii and Chloroflexus aggregans, and mesophilic “Ca. Viridilinea mediisalina.” These species represent the three main lineages within a group of multicellular filamentous anoxygenic phototrophic Chloroflexota bacteria belonging to the Chloroflexales order. We found surprising structural complexity in the Chloroflexales. As with filamentous cyanobacteria, cells of C. aggregans and “Ca. Viridilinea mediisalina” share the outer membrane-like layers of their intricate multilayer cell envelope. Additionally, cells of R. castenholzii and “Ca. Viridilinea mediisalina” are connected by septal channels that resemble cyanobacterial septal junctions. All three strains possess long pili anchored close to cell-to-cell junctions, a morphological feature comparable to that observed in cyanobacteria. The cytoplasm of the Chloroflexales bacteria is crowded with intracellular organelles such as different types of storage granules, membrane vesicles, chlorosomes, gas vesicles, chemoreceptor-like arrays, and cytoplasmic filaments. We observed a higher level of complexity in the mesophilic strain compared to the thermophilic strains with regards to the composition of intracellular bodies and the organization of the cell envelope. The ultrastructural details that we describe in these Chloroflexales bacteria will motivate further cell biological studies, given that the function and evolution of the many discovered morphological traits remain enigmatic in this diverse and widespread bacterial group.

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

DOI
10.3389/fmicb.2020.01373

In vivo activation of a conserved microRNA program induces mammalian heart regeneration

NOMIS Researcher(s)

Published in

June 26, 2020

Heart failure is a leading cause of mortality and morbidity in the developed world, partly because mammals lack the ability to regenerate heart tissue. Whether this is due to evolutionary loss of regenerative mechanisms present in other organisms or to an inability to activate such mechanisms is currently unclear. Here we decipher mechanisms underlying heart regeneration in adult zebrafish and show that the molecular regulators of this response are conserved in mammals. We identified miR-99/100 and Let-7a/c and their protein targets smarca5 and fntb as critical regulators of cardiomyocyte dedifferentiation and heart regeneration in zebrafish. Although human and murine adult cardiomyocytes fail to elicit an endogenous regenerative response after myocardial infarction, we show that in vivo manipulation of this molecular machinery in mice results in cardiomyocyte dedifferentiation and improved heart functionality after injury. These data provide a proof of concept for identifying and activating conserved molecular programs to regenerate the damaged heart.

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

DOI
10.1016/j.stem.2014.10.003

Reversing a model of Parkinson’s disease with in situ converted nigral neurons

NOMIS Researcher(s)

Published in

June 25, 2020

Parkinson’s disease is characterized by loss of dopamine neurons in the substantia nigra1. Similar to other major neurodegenerative disorders, there are no disease-modifying treatments for Parkinson’s disease. While most treatment strategies aim to prevent neuronal loss or protect vulnerable neuronal circuits, a potential alternative is to replace lost neurons to reconstruct disrupted circuits2. Here we report an efficient one-step conversion of isolated mouse and human astrocytes to functional neurons by depleting the RNA-binding protein PTB (also known as PTBP1). Applying this approach to the mouse brain, we demonstrate progressive conversion of astrocytes to new neurons that innervate into and repopulate endogenous neural circuits. Astrocytes from different brain regions are converted to different neuronal subtypes. Using a chemically induced model of Parkinson’s disease in mouse, we show conversion of midbrain astrocytes to dopaminergic neurons, which provide axons to reconstruct the nigrostriatal circuit. Notably, re-innervation of striatum is accompanied by restoration of dopamine levels and rescue of motor deficits. A similar reversal of disease phenotype is also accomplished by converting astrocytes to neurons using antisense oligonucleotides to transiently suppress PTB. These findings identify a potentially powerful and clinically feasible approach to treating neurodegeneration by replacing lost neurons.

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

DOI
10.1038/s41586-020-2388-4

Information arms race explains plant-herbivore chemical communication in ecological communities

NOMIS Researcher(s)

Published in

June 19, 2020

Plants emit an extraordinary diversity of chemicals that provide information about their identity and mediate their interactions with insects. However, most studies of this have focused on a few model species in controlled environments, limiting our capacity to understand plant-insect chemical communication in ecological communities. Here, by integrating information theory with ecological and evolutionary theories, we show that a stable information structure of plant volatile organic compounds (VOCs) can emerge from a conflicting information process between plants and herbivores. We corroborate this information “arms race” theory with field data recording plant-VOC associations and plant-herbivore interactions in a tropical dry forest. We reveal that plant VOC redundancy and herbivore specialization can be explained by a conflicting information transfer. Information-based communication approaches can increase our understanding of species interactions across trophic levels.

Research field(s)
Natural Sciences, Biology, Ecology

DOI
10.1126/science.aba2965

Nuclear Periphery Takes Center Stage: The Role of Nuclear Pore Complexes in Cell Identity and Aging

NOMIS Researcher(s)

Published in

June 17, 2020

In recent years, the nuclear pore complex (NPC) has emerged as a key player in genome regulation and cellular homeostasis. New discoveries have revealed that the NPC has multiple cellular functions besides mediating the molecular exchange between the nucleus and the cytoplasm. In this review, we discuss non-transport aspects of the NPC focusing on the NPC-genome interaction, the extreme longevity of the NPC proteins, and NPC dysfunction in age-related diseases. The examples summarized herein demonstrate that the NPC, which first evolved to enable the biochemical communication between the nucleus and the cytoplasm, now doubles as the gatekeeper of cellular identity and aging. Cho and Hetzer discuss recent studies that have established the nuclear pore complex as a key regulator of transcription control of cell identity genes and have linked its functional decline to premature, physiological, and pathological aging.

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

DOI
10.1016/j.neuron.2020.05.031

Plasma neurofilament light chain in the presenilin 1 E280A autosomal dominant Alzheimer’s disease kindred: a cross-sectional and longitudinal cohort study

NOMIS Researcher(s)

Published in

June 1, 2020

Background: Neurofilament light chain (NfL) is a promising biomarker of active axonal injury and neuronal degeneration. We aimed to characterise cross-sectional and longitudinal plasma NfL measurements and determine the age at which NfL concentrations begin to differentiate between carriers of the presenilin 1 (PSEN1) E280A (Glu280Ala) mutation and age-matched non-carriers from the Colombian autosomal dominant Alzheimer’s disease kindred. Methods: In this cross-sectional and longitudinal cohort study, members of the familial Alzheimer’s disease Colombian kindred aged 8–75 years with no other neurological or health conditions were recruited from the Alzheimer’s Prevention Initiative Registry at the University of Antioquia (Medellín, Colombia) between Aug 1, 1995, and Dec 15, 2018. We used a single molecule array immunoassay and log-transformed data to examine the relationship between plasma NfL concentrations and age, and establish the earliest age at which NfL concentrations begin to diverge between mutation carriers and non-carriers. Findings: We enrolled a cohort of 1070 PSEN1 E280A mutation carriers and 1074 non-carriers with baseline assessments; of these participants, longitudinal measures (with a mean follow-up of 6 years) were available for 242 mutation carriers and 262 non-carriers. Plasma NfL measurements increased with age in both groups (p<0·0001), and began to differentiate carriers from non-carriers when aged 22 years (22 years before the estimated median age at mild cognitive impairment onset of 44 years), although the ability of plasma NfL to discriminate between carriers and non-carriers only reached high sensitivity close to the age of clinical onset. Interpretation: Our findings further support the promise of plasma NfL as a biomarker of active neurodegeneration in the detection and tracking of Alzheimer's disease and the evaluation of disease-modifying therapies. Funding: National Institute on Aging, National Institute of Neurological Disorders and Stroke, Banner Alzheimer's Foundation, COLCIENCIAS, the Torsten Söderberg Foundation, the Swedish Research Council, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, and the Swedish state under the ALF-agreement.

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

DOI
10.1016/S1474-4422(20)30137-X

Copathology in Progressive Supranuclear Palsy: Does It Matter?

NOMIS Researcher(s)

Published in

June 1, 2020

Background: The influence of concomitant brain pathologies on the progression rate in PSP is unclear. Objectives: To analyze the frequency and severity of copathologies and their impact on the progression in PSP. Methods: We analyzed clinic-pathological features of 101 PSP patients. Diagnoses and stages of copathologies were established according to standardized criteria, including Alzheimer’s disease–related pathology, argyrophilic grains, Lewy-related pathology, transactive response DNA-binding protein 43 pathology, fused in sarcoma pathology, cerebral amyloid angiopathy, and small vessel disease. Demographic data and major clinical milestones (frequency and latency to onset) were extracted from patients’ files. Results: Only 8% of 101 patients presented with pure PSP pathology without any copathology. Alzheimer’s disease–related pathology was the most frequent (84%), followed by argyrophilic grains (58%), both occurring as single copathology or in combination with other proteinopathies or cerebrovascular disease. Lewy-related and transactive response DNA-binding protein 43 copathology occurred rarely (8% and 6%, respectively). Fused in sarcoma–positive cases were not found. While being common, copathology was mostly mild in severity, with the exception of frequently widespread argyrophilic grains. Small vessel disease was also frequent (65%). Cerebral amyloid angiopathy occurred only in the presence of Alzheimer’s disease–related changes (25%). The copathologies did not have major impact on prevalence and time frame of major disease milestones. Conclusions: In PSP, concomitant neurodegenerative proteinopathies or cerebrovascular diseases are frequent, but generally mild in severity. Our data confirmed that four repeat tau is still the most relevant target for PSP, whereas the impact of copathologies on progression rate appears to be of less importance. This is relevant information for the development of disease-modifying therapies. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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

DOI
10.1002/mds.28011

Genome-wide transcriptomics identifies an early preclinical signature of prion infection

NOMIS Researcher(s)

Published in

June 1, 2020

The clinical course of prion diseases is accurately predictable despite long latency periods, suggesting that prion pathogenesis is driven by precisely timed molecular events. We constructed a searchable genome-wide atlas of mRNA abundance and splicing alterations during the course of disease in prion-inoculated mice. Prion infection induced PrP-dependent transient changes in mRNA abundance and processing already at eight weeks post inoculation, well ahead of any neuropathological and clinical signs. In contrast, microglia-enriched genes displayed an increase simultaneous with the appearance of clinical signs, whereas neuronal-enriched transcripts remained unchanged until the very terminal stage of disease. This suggests that glial pathophysiology, rather than neuronal demise, could be the final driver of disease. The administration of young plasma attenuated the occurrence of early mRNA abundance alterations and delayed signs in the terminal phase of the disease. The early onset of prion-induced molecular changes might thus point to novel biomarkers and potential interventional targets.

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

DOI
10.1371/journal.ppat.1008653

Do Trompe l’oeils Look Right When Viewed from the Wrong Place?

NOMIS Researcher(s)

Published in

June 1, 2020

Picture perception and ordinary perception of real objects differ in several respects. Two of their main differences are: (1) Depicted objects are not perceived as present and (2) We cannot perceive significant spatial shifts as we move with respect to them. Some special illusory pictures escape these visual effects obtained in usual picture perception. First, trompe l’oeil paintings violate (1): the depicted object looks, even momentarily, like a present object. Second, anamorphic paintings violate (2): they lead to appreciate spatial shifts resulting from movement. However, anamorphic paintings do not violate (1): they are still perceived as clearly pictorial, that is, nonpresent. What about the relation between trompe l’oeil paintings and (2)? Do trompe l’oeils allow us to perceive spatial shifts? Nobody has ever focused on this aspect of trompe l’oeil perception. I offer the first speculation about this question. I suggest that, if we follow our most recent theories in philosophy and vision science about the mechanisms of picture perception, then, the only plausible answer, in line with phenomenological intuitions, is that, differently from nonillusory, usual picture perception, and similarly to ordinary perception, trompe l’oeil perception does allow us to perceive spatial shifts resulting from movement. I also discuss the philosophical implications of this claim.

Research field(s)
Arts & Humanities, Visual & Performing Arts, Art Practice, History & Theory

DOI
10.1111/jaac.12750

Do you hear what I see? An audio-visual paradigm to assess emotional egocentricity bias

NOMIS Researcher(s)

Published in

May 18, 2020

We often use our own emotions to understand other people’s emotions. However, emotional egocentric biases (EEB), namely the tendency to use one’s own emotional state when relating to others’ emotions, may hinder this process, especially when emotions are incongruent. We capitalised on the classic EEB task to develop a new version that is easier to implement and control. Unlike the original EEB task that relies on a combination of private (e.g. touch) and public (e.g. vision) sensory information, our EEB task (AV-EEB) used audio-visual stimuli to evoke congruent/incongruent emotions in participants. Auditory and visual signals are both public, in that they can be shared among individuals, and make the task easier to implement and control. We provide lab-based and online validations of the AV-EEB, and demonstrate a positive relationship between EEB and social negative potency. This new, easily implemented version of the EEB task can accelerate the investigation of egocentricity biases in several research areas.

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

DOI
10.1080/02699931.2019.1683516

Human spinal motor neurons are particularly vulnerable to cerebrospinal fluid of amyotrophic lateral sclerosis patients

NOMIS Researcher(s)

Published in

May 2, 2020

Amyotrophic lateral sclerosis (ALS) is the most common and devastating motor neuron (MN) disease. Its pathophysiological cascade is still enigmatic. More than 90% of ALS patients suffer from sporadic ALS, which makes it specifically demanding to generate appropriate model systems. One interesting aspect considering the seeding, spreading and further disease development of ALS is the cerebrospinal fluid (CSF). We therefore asked whether CSF from sporadic ALS patients is capable of causing disease typical changes in human patient-derived spinal MN cultures and thus could represent a novel model system for sporadic ALS. By using induced pluripotent stem cell (iPSC)-derived MNs from healthy controls and monogenetic forms of ALS we could demonstrate a harmful effect of ALS-CSF on healthy donor-derived human MNs. Golgi fragmentation—a typical finding in lower organism models and human postmortem tissue—was induced solely by addition of ALS-CSF, but not control-CSF. No other neurodegenerative hallmarks—including pathological protein aggregation—were found, underpinning Golgi fragmentation as early event in the neurodegenerative cascade. Of note, these changes occurred predominantly in MNs, the cell type primarily affected in ALS. We thus present a novel way to model early features of sporadic ALS.

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

DOI
10.3390/ijms21103564

Collective communication and behaviour in response to uncertain ‘Danger’ in network experiments

NOMIS Researcher(s)

Published in

May 1, 2020

In emergencies, social coordination is especially challenging. People connected with each other may respond better or worse to an uncertain danger than isolated individuals. We performed experiments involving a novel scenario simulating an unpredictable situation faced by a group in which 2480 subjects in 108 groups had to both communicate information and decide whether to ‘evacuate’. We manipulated the permissible sorts of interpersonal communication and varied group topology and size. Compared to groups of isolated individuals, we find that communication networks suppress necessary evacuations because of the spontaneous and diffuse emergence of false reassurance; yet, communication networks also restrain unnecessary evacuations in situations without disasters. At the individual level, subjects have thresholds for responding to social information that are sensitive to the negativity, but not the actual accuracy, of the signals being transmitted. Social networks can function poorly as pathways for inconvenient truths that people would rather ignore.

Research field(s)
Natural Sciences, Mathematics & Statistics, Applied Mathematics

DOI
10.1098/rspa.2019.0685

CRISPR off-target detection with DISCOVER-seq

NOMIS Researcher(s)

Published in

May 1, 2020

DISCOVER-seq (discovery of in situ Cas off-targets and verification by sequencing) is a broadly applicable approach for unbiased CRISPR–Cas off-target identification in cells and tissues. It leverages the recruitment of DNA repair factors to double-strand breaks (DSBs) after genome editing with CRISPR nucleases. Here, we describe a detailed experimental protocol and analysis pipeline with which to perform DISCOVER-seq. The principle of this method is to track the precise recruitment of MRE11 to DSBs by chromatin immunoprecipitation followed by next-generation sequencing. A customized open-source bioinformatics pipeline, BLENDER (blunt end finder), then identifies off-target sequences genome wide. DISCOVER-seq is capable of finding and measuring off-targets in primary cells and in situ. The two main advantages of DISCOVER-seq are (i) low false-positive rates because DNA repair enzyme binding is required for genome edits to occur and (ii) its applicability to a wide variety of systems, including patient-derived cells and animal models. The whole protocol, including the analysis, can be completed within 2 weeks.

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

DOI
10.1038/s41596-020-0309-5

A CRISPR view on autophagy

NOMIS Researcher(s)

Published in

May 1, 2020

Autophagy is a fundamental pathway for the degradation of cytoplasmic content in response to pleiotropic extracellular and intracellular stimuli. Recent advances in the autophagy field have demonstrated that different organelles can also be specifically targeted for autophagy with broad implications on cellular and organismal health. This opens new dimensions in the autophagy field and more unanswered questions on the rationale and underlying mechanisms to degrade different organelles. Functional genomics via clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-based screening has gained popularity in the autophagy field to understand the common and unique factors that are implicated in the signaling, recognition, and execution of different cargo-specific autophagies. We focus on recent applications of CRISPR-based screens in the autophagy field, their discoveries, and the future directions of autophagy screens.

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

DOI
10.1016/j.tcb.2022.04.006

Microwave quantum illumination using a digital receiver

NOMIS Researcher(s)

Published in

May 1, 2020

Quantum illumination uses entangled signal-idler photon pairs to boost the detection efficiency of low-reflectivity objects in environments with bright thermal noise. Its advantage is particularly evident at low signal powers, a promising feature for applications such as noninvasive biomedical scanning or low-power short-range radar. Here, we experimentally investigate the concept of quantum illumination at microwave frequencies. We generate entangled fields to illuminate a room-temperature object at a distance of 1 m in a free-space detection setup. We implement a digital phase-conjugate receiver based on linear quadrature measurements that outperforms a symmetric classical noise radar in the same conditions, despite the entanglement-breaking signal path. Starting from experimental data, we also simulate the case of perfect idler photon number detection, which results in a quantum advantage compared with the relative classical benchmark. Our results highlight the opportunities and challenges in the way toward a first room-temperature application of microwave quantum circuits.

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

DOI
10.1126/sciadv.abb0451

Disease-modifying strategies in primary tauopathies

NOMIS Researcher(s)

Published in

May 1, 2020

Tauopathies are neurodegenerative brain diseases that are characterized by the formation of intraneuronal inclusions containing the microtubule-associated protein tau. This major hallmark defines tau pathology which is predominant in primary tauopathies, while in secondary forms additional driving forces are involved. In the course of the disease, different brain areas degenerate and lead to severe defects of language, behavior and movement. Although neuropathologically heterogeneous, primary tauopathies share a common feature, which is the generation of abnormal tau species that aggregate and progress into filamentous deposits in neurons. Mechanisms that are involved in this disease-related process offer a broad range of targets for disease-modifying therapeutics. The present review provides an up-to-date overview of currently known targets in primary tauopathies and their possible therapeutic modulation. It is structured into four major targets, the post-translational modifications of tau and tau aggregation, protein homeostasis, disease propagation, and tau genetics. Chances, as well as obstacles in the development of effective therapies are highlighted. Some therapeutic strategies, e.g., passive or active immunization, have already reached clinical development, raising hopes for affected patients. Other concepts, e.g., distinct modulators of proteostasis, are at the ready to be developed into promising future therapies. This article is part of the special issue entitled ‘The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders’.

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

DOI
10.1016/j.neuropharm.2019.107842

Nature and People in the Andes, East African Mountains, European Alps, and Hindu Kush Himalaya: Current Research and Future Directions

NOMIS Researcher(s)

Published in

May 1, 2020

Mountains are facing growing environmental, social, and economic challenges. Accordingly, effective policies and management approaches are needed to safeguard their inhabitants, their ecosystems, their biodiversity, and the livelihoods they support. The formulation and implementation of such policies and approaches requires a thorough understanding of, and extensive knowledge about, the interactions between nature and people particular to mountain social-ecological systems. Here, we applied the conceptual framework of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services to assess and compare the contents of 631 abstracts on the interactions among biodiversity, ecosystem services, human wellbeing, and drivers of change, and formulate a set of research recommendations. Our comparative assessment of literature pertained to the Andes, the East African mountains, the European Alps, and the Hindu Kush Himalaya. It revealed interesting differences between mountain systems, in particular in the relative importance given in the literature to individual drivers of change and to the ecosystem services delivered along elevational gradients. Based on our analysis and with reference to alternative conceptual frameworks of mountain social-ecological systems, we propose future research directions and options. In particular, we recommend improving biodiversity information, generating spatially explicit knowledge on ecosystem services, integrating knowledge and action along elevational gradients, generating knowledge on interacting effects of global change drivers, delivering knowledge that is relevant for transformative action toward sustainable mountain development, and using comprehensive concepts and codesigned approaches to effectively address knowledge gaps.

Research field(s)
Natural Sciences, Biology, Ecology

DOI
10.1659/MRD-JOURNAL-D-19-00075.1

Transcriptional and Functional Changes of the Human Microvasculature during Physiological Aging and Alzheimer Disease

NOMIS Researcher(s)

Published in

May 1, 2020

Aging of the circulatory system correlates with the pathogenesis of a large spectrum of diseases. However, it is largely unknown which factors drive the age-dependent or pathological decline of the vasculature and how vascular defects relate to tissue aging. The goal of the study is to design a multianalytical approach to identify how the cellular microenvironment (i.e., fibroblasts) and serum from healthy donors of different ages or Alzheimer disease (AD) patients can modulate the functionality of organ-specific vascular endothelial cells (VECs). Long-living human microvascular networks embedding VECs and fibroblasts from skin biopsies are generated. RNA-seq, secretome analyses, and microfluidic assays demonstrate that fibroblasts from young donors restore the functionality of aged endothelial cells, an effect also achieved by serum from young donors. New biomarkers of vascular aging are validated in human biopsies and it is shown that young serum induces angiopoietin-like-4, which can restore compromised vascular barriers. This strategy is then employed to characterize transcriptional/functional changes induced on the blood–brain barrier by AD serum, demonstrating the importance of PTP4A3 in the regulation of permeability. Features of vascular degeneration during aging and AD are recapitulated, and a tool to identify novel biomarkers that can be exploited to develop future therapeutics modulating vascular function is established.

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

DOI
10.1002/adbi.202000044

The Biology of Physiological Health

NOMIS Researcher(s)

Published in

April 16, 2020

In this Perspective, Janelle Ayres argues for a paradigm shift in how we think about “health,” toward viewing it as an active process involving mechanisms distinct from those of disease.

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

DOI
10.1016/j.cell.2020.03.036

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