Showing papers by "University of Göttingen published in 2021"

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19.

Abstract: The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS is likely. By various means, we demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Furthermore, we describe the morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and present evidence of SARS-CoV-2 neurotropism. SARS-CoV-2 can enter the nervous system by crossing the neural-mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings. Subsequently, SARS-CoV-2 appears to follow neuroanatomical structures, penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.

Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Abstract: Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Mechanism of SARS-CoV-2 polymerase stalling by remdesivir.

Abstract: Remdesivir is the only FDA-approved drug for the treatment of COVID-19 patients. The active form of remdesivir acts as a nucleoside analog and inhibits the RNA-dependent RNA polymerase (RdRp) of coronaviruses including SARS-CoV-2. Remdesivir is incorporated by the RdRp into the growing RNA product and allows for addition of three more nucleotides before RNA synthesis stalls. Here we use synthetic RNA chemistry, biochemistry and cryo-electron microscopy to establish the molecular mechanism of remdesivir-induced RdRp stalling. We show that addition of the fourth nucleotide following remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation. This translocation barrier causes retention of the RNA 3'-nucleotide in the substrate-binding site of the RdRp and interferes with entry of the next nucleoside triphosphate, thereby stalling RdRp. In the structure of the remdesivir-stalled state, the 3'-nucleotide of the RNA product is matched and located with the template base in the active center, and this may impair proofreading by the viral 3'-exonuclease. These mechanistic insights should facilitate the quest for improved antivirals that target coronavirus replication.

Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis.

Abstract: Molnupiravir is an orally available antiviral drug candidate currently in phase III trials for the treatment of patients with COVID-19. Molnupiravir increases the frequency of viral RNA mutations and impairs SARS-CoV-2 replication in animal models and in humans. Here, we establish the molecular mechanisms underlying molnupiravir-induced RNA mutagenesis by the viral RNA-dependent RNA polymerase (RdRp). Biochemical assays show that the RdRp uses the active form of molnupiravir, β-D-N4-hydroxycytidine (NHC) triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RdRp uses the resulting RNA as a template, NHC directs incorporation of either G or A, leading to mutated RNA products. Structural analysis of RdRp-RNA complexes that contain mutagenesis products shows that NHC can form stable base pairs with either G or A in the RdRp active center, explaining how the polymerase escapes proofreading and synthesizes mutated RNA. This two-step mutagenesis mechanism probably applies to various viral polymerases and can explain the broad-spectrum antiviral activity of molnupiravir.

Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination.

Abstract: Currently approved viral vector-based and mRNA-based vaccine approaches against coronavirus disease 2019 (COVID-19) consider only homologous prime-boost vaccination. After reports of thromboembolic events, several European governments recommended using AstraZeneca's ChAdOx1-nCov-19 (ChAd) only in individuals older than 60 years, leaving millions of already ChAd-primed individuals with the decision to receive either a second shot of ChAd or a heterologous boost with mRNA-based vaccines. However, such combinations have not been tested so far. We used Hannover Medical School's COVID-19 Contact Study cohort of healthcare professionals to monitor ChAd-primed immune responses before and 3 weeks after booster with ChAd (n = 32) or BioNTech/Pfizer's BNT162b2 (n = 55). Although both vaccines boosted prime-induced immunity, BNT162b2 induced significantly higher frequencies of spike-specific CD4+ and CD8+ T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and P.1 variants of concern of severe acute respiratory syndrome coronavirus 2.

Falling living standards during the COVID-19 crisis: Quantitative evidence from nine developing countries.

Abstract: Despite numerous journalistic accounts, systematic quantitative evidence on economic conditions during the ongoing COVID-19 pandemic remains scarce for most low- and middle-income countries, partly due to limitations of official economic statistics in environments with large informal sectors and subsistence agriculture. We assemble evidence from over 30,000 respondents in 16 original household surveys from nine countries in Africa (Burkina Faso, Ghana, Kenya, Rwanda, Sierra Leone), Asia (Bangladesh, Nepal, Philippines), and Latin America (Colombia). We document declines in employment and income in all settings beginning March 2020. The share of households experiencing an income drop ranges from 8 to 87% (median, 68%). Household coping strategies and government assistance were insufficient to sustain precrisis living standards, resulting in widespread food insecurity and dire economic conditions even 3 months into the crisis. We discuss promising policy responses and speculate about the risk of persistent adverse effects, especially among children and other vulnerable groups.

Recent Progress on Nanocellulose Aerogels: Preparation, Modification, Composite Fabrication, Applications

Abstract: The rapid development of modern industry and excessive consumption of petroleum-based polymers have triggered a double crisis presenting a shortage of nonrenewable resources and environmental pollution However, this has provided an opportunity to stimulate researchers to harness native biobased materials for novel advanced materials and applications Nanocellulose-based aerogels, using abundant and sustainable cellulose as raw material, present a third-generation of aerogels that combine traditional aerogels with high porosity and large specific surface area, as well as the excellent properties of cellulose itself Currently, nanocellulose aerogels provide a highly attention-catching platform for a wide range of functional applications in various fields, eg, adsorption, separation, energy storage, thermal insulation, electromagnetic interference shielding, and biomedical applications Here, the preparation methods, modification strategies, composite fabrications, and further applications of nanocellulose aerogels are summarized, with additional discussions regarding the prospects and potential challenges in future development

Finite-temperature transport in one-dimensional quantum lattice models

Abstract: Over the last decade impressive progress has been made in the theoretical understanding of transport properties of clean, one-dimensional quantum lattice systems. Many physically relevant models in one dimension are Bethe-ansatz integrable, including the anisotropic spin-1/2 Heisenberg (also called the spin-1/2 XXZ chain) and the Fermi-Hubbard model. Nevertheless, practical computations of correlation functions and transport coefficients pose hard problems from both the conceptual and technical points of view. Only because of recent progress in the theory of integrable systems, on the one hand, and the development of numerical methods, on the other hand, has it become possible to compute their finite-temperature and nonequilibrium transport properties quantitatively. Owing to the discovery of a novel class of quasilocal conserved quantities, there is now a qualitative understanding of the origin of ballistic finite-temperature transport, and even diffusive or superdiffusive subleading corrections, in integrable lattice models. The current understanding of transport in one-dimensional lattice models, in particular, in the paradigmatic example of the spin-1/2 XXZ and Fermi-Hubbard models, is reviewed, as well as state-of-the-art theoretical methods, including both analytical and computational approaches. Among other novel techniques, matrix-product-state-based simulation methods, dynamical typicality, and, in particular, generalized hydrodynamics are covered. The close and fruitful connection between theoretical models and recent experiments is discussed, with examples given from the realms of both quantum magnets and ultracold quantum gases in optical lattices.

Late-stage C-H functionalization offers new opportunities in drug discovery

Abstract: Over the past decade, the landscape of molecular synthesis has gained major impetus by the introduction of late-stage functionalization (LSF) methodologies. C–H functionalization approaches, particularly, set the stage for new retrosynthetic disconnections, while leading to improvements in resource economy. A variety of innovative techniques have been successfully applied to the C–H diversification of pharmaceuticals, and these key developments have enabled medicinal chemists to integrate LSF strategies in their drug discovery programmes. This Review highlights the significant advances achieved in the late-stage C–H functionalization of drugs and drug-like compounds, and showcases how the implementation of these modern strategies allows increased efficiency in the drug discovery process. Representative examples are examined and classified by mechanistic patterns involving directed or innate C–H functionalization, as well as emerging reaction manifolds, such as electrosynthesis and biocatalysis, among others. Structurally complex bioactive entities beyond small molecules are also covered, including diversification in the new modalities sphere. The challenges and limitations of current LSF methods are critically assessed, and avenues for future improvements of this rapidly expanding field are discussed. We, hereby, aim to provide a toolbox for chemists in academia as well as industrial practitioners, and introduce guiding principles for the application of LSF strategies to access new molecules of interest. Late-stage C–H functionalization of complex molecules has emerged as a powerful tool in drug discovery. This Review classifies significant examples by reaction manifold and assesses the benefits and challenges of each approach. Avenues for future improvements of this fast-expanding field are proposed.

Root traits as drivers of plant and ecosystem functioning: current understanding, pitfalls and future research needs

Abstract: The effects of plants on the biosphere, atmosphere and geosphere are key determinants of terrestrial ecosystem functioning. However, despite substantial progress made regarding plant belowground components, we are still only beginning to explore the complex relationships between root traits and functions. Drawing on the literature in plant physiology, ecophysiology, ecology, agronomy and soil science, we reviewed 24 aspects of plant and ecosystem functioning and their relationships with a number of root system traits, including aspects of architecture, physiology, morphology, anatomy, chemistry, biomechanics and biotic interactions. Based on this assessment, we critically evaluated the current strengths and gaps in our knowledge, and identify future research challenges in the field of root ecology. Most importantly, we found that belowground traits with the broadest importance in plant and ecosystem functioning are not those most commonly measured. Also, the estimation of trait relative importance for functioning requires us to consider a more comprehensive range of functionally relevant traits from a diverse range of species, across environments and over time series. We also advocate that establishing causal hierarchical links among root traits will provide a hypothesis-based framework to identify the most parsimonious sets of traits with the strongest links on functions, and to link genotypes to plant and ecosystem functioning.

ERS clinical practice guidelines on treatment of sarcoidosis

Abstract: Background The major reasons to treat sarcoidosis are to lower the morbidity and mortality risk or to improve quality of life (QoL). The indication for treatment varies depending on which manifestation is the cause of symptoms: lungs, heart, brain, skin, or other manifestations. While glucocorticoids (GC) remain the first choice for initial treatment of symptomatic disease, prolonged use is associated with significant toxicity. GC-sparing alternatives are available. The presented treatment guideline aims to provide guidance to physicians treating the very heterogenous sarcoidosis manifestations. Materials and Methods A European Respiratory Society Task Force (TF) committee composed of clinicians, methodologists, and patients with experience in sarcoidosis developed recommendations based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology. The committee developed eight PICO (Patients, Intervention, Comparison, Outcomes) questions and these were used to make specific evidence-based recommendations. Results The TF committee delivered twelve recommendations for seven PICOs. These included treatment of pulmonary, cutaneous, cardiac, and neurologic disease as well as fatigue. One PICO question regarding small fiber neuropathy had insufficient evidence to support a recommendation. In addition to the recommendations, the committee provided information on how they use alternative treatments, when there was insufficient evidence to support a recommendation. Conclusions There are many treatments available to treat sarcoidosis. Given the diverse nature of the disease, treatment decisions require an assessment of organ involvement, risk for significant morbidity, and impact on QoL of the disease and treatment. Message An evidence based guideline for treatment of sarcoidosis is presented. The panel used the GRADE approach and specific recommendations are made. A major factor in treating patients is the risk of loss of organ function or impairment of quality of life.

Organic Electrochemistry: Molecular Syntheses with Potential.

Abstract: Efficient and selective molecular syntheses are paramount to inter alia biomolecular chemistry and material sciences as well as for practitioners in chemical, agrochemical, and pharmaceutical industries. Organic electrosynthesis has undergone a considerable renaissance and has thus in recent years emerged as an increasingly viable platform for the sustainable molecular assembly. In stark contrast to early strategies by innate reactivity, electrochemistry was recently merged with modern concepts of organic synthesis, such as transition-metal-catalyzed transformations for inter alia C-H functionalization and asymmetric catalysis. Herein, we highlight the unique potential of organic electrosynthesis for sustainable synthesis and catalysis, showcasing key aspects of exceptional selectivities, the synergism with photocatalysis, or dual electrocatalysis, and novel mechanisms in metallaelectrocatalysis until February of 2021.

Four Generations of High-Dimensional Neural Network Potentials.

Abstract: Since their introduction about 25 years ago, machine learning (ML) potentials have become an important tool in the field of atomistic simulations After the initial decade, in which neural networks were successfully used to construct potentials for rather small molecular systems, the development of high-dimensional neural network potentials (HDNNPs) in 2007 opened the way for the application of ML potentials in simulations of large systems containing thousands of atoms To date, many other types of ML potentials have been proposed continuously increasing the range of problems that can be studied In this review, the methodology of the family of HDNNPs including new recent developments will be discussed using a classification scheme into four generations of potentials, which is also applicable to many other types of ML potentials The first generation is formed by early neural network potentials designed for low-dimensional systems High-dimensional neural network potentials established the second generation and are based on three key steps: first, the expression of the total energy as a sum of environment-dependent atomic energy contributions; second, the description of the atomic environments by atom-centered symmetry functions as descriptors fulfilling the requirements of rotational, translational, and permutation invariance; and third, the iterative construction of the reference electronic structure data sets by active learning In third-generation HDNNPs, in addition, long-range interactions are included employing environment-dependent partial charges expressed by atomic neural networks In fourth-generation HDNNPs, which are just emerging, in addition, nonlocal phenomena such as long-range charge transfer can be included The applicability and remaining limitations of HDNNPs are discussed along with an outlook at possible future developments

How biochar works, and when it doesn't: A review of mechanisms controlling soil and plant responses to biochar

Abstract: We synthesized 20 years of research to explain the interrelated processes that determine soil and plant responses to biochar. The properties of biochar and its effects within agricultural ecosystems largely depend on feedstock and pyrolysis conditions. We describe three stages of reactions of biochar in soil: dissolution (1–3 weeks); reactive surface development (1–6 months); and aging (beyond 6 months). As biochar ages, it is incorporated into soil aggregates, protecting the biochar carbon and promoting the stabilization of rhizodeposits and microbial products. Biochar carbon persists in soil for hundreds to thousands of years. By increasing pH, porosity, and water availability, biochars can create favorable conditions for root development and microbial functions. Biochars can catalyze biotic and abiotic reactions, particularly in the rhizosphere, that increase nutrient supply and uptake by plants, reduce phytotoxins, stimulate plant development, and increase resilience to disease and environmental stressors. Meta-analyses found that, on average, biochars increase P availability by a factor of 4.6; decrease plant tissue concentration of heavy metals by 17%–39%; build soil organic carbon through negative priming by 3.8% (range −21% to +20%); and reduce non-CO2 greenhouse gas emissions from soil by 12%–50%. Meta-analyses show average crop yield increases of 10%–42% with biochar addition, with greatest increases in low-nutrient P-sorbing acidic soils (common in the tropics), and in sandy soils in drylands due to increase in nutrient retention and water holding capacity. Studies report a wide range of plant responses to biochars due to the diversity of biochars and contexts in which biochars have been applied. Crop yields increase strongly if site-specific soil constraints and nutrient and water limitations are mitigated by appropriate biochar formulations. Biochars can be tailored to address site constraints through feedstock selection, by modifying pyrolysis conditions, through pre- or post-production treatments, or co-application with organic or mineral fertilizers. We demonstrate how, when used wisely, biochar mitigates climate change and supports food security and the circular economy.

C–H activation

Abstract: Transition metal-catalysed C–H activation has emerged as an increasingly powerful platform for molecular syntheses, enabling applications to natural product syntheses, late-stage modification, pharmaceutical industries and material sciences, among others. This Primer summarizes representative best practices for the experimental set-up and data deposition for C–H activation, as well as discussing key developments including recent advances in asymmetric, photoinduced and electrocatalytic C–H activation. Likewise, strategies for applications of C–H activation towards the assembly of structurally complex (bio)polymers and drugs in academia and industry are discussed. In addition, current limitations in C–H activation and possible approaches for overcoming these shortcomings are reviewed. This Primer provides an overview of the best practices for C–H activation as well as key advances in asymmetric, photoinduced and electrocatalytic-mediated catalysis for this synthetic platform. An overview of how C–H activation facilitates the synthesis of molecules such as structurally complex (bio)polymers and drugs is provided along with the current challenges and priorities for the next decade.

The microplastisphere: biodegradable microplastics addition alters soil microbial community structure and function

Abstract: Plastics accumulating in the environment, especially microplastics (defined as particles

Advanced Nanocellulose-Based Composites for Flexible Functional Energy Storage Devices.

Abstract: With the increasing demand for wearable electronics (such as smartwatch equipment, wearable health monitoring systems, and human-robot interface units), flexible energy storage systems with eco-friendly, low-cost, multifunctional characteristics, and high electrochemical performances are imperative to be constructed. Nanocellulose with sustainable natural abundance, superb properties, and unique structures has emerged as a promising nanomaterial, which shows significant potential for fabricating functional energy storage systems. This review is intended to provide novel perspectives on the combination of nanocellulose with other electrochemical materials to design and fabricate nanocellulose-based flexible composites for advanced energy storage devices. First, the unique structural characteristics and properties of nanocellulose are briefly introduced. Second, the structure-property-application relationships of these composites are addressed to optimize their performances from the perspective of processing technologies and micro/nano-interface structure. Next, the recent specific applications of nanocellulose-based composites, ranging from flexible lithium-ion batteries and electrochemical supercapacitors to emerging electrochemical energy storage devices, such as lithium-sulfur batteries, sodium-ion batteries, and zinc-ion batteries, are comprehensively discussed. Finally, the current challenges and future developments in nanocellulose-based composites for the next generation of flexible energy storage systems are proposed.

Beyond organic farming - harnessing biodiversity-friendly landscapes.

Abstract: We challenge the widespread appraisal that organic farming is the fundamental alternative to conventional farming for harnessing biodiversity in agricultural landscapes. Certification of organic production is largely restricted to banning synthetic agrochemicals, resulting in limited benefits for biodiversity but high yield losses despite ongoing intensification and specialisation. In contrast, successful agricultural measures to enhance biodiversity include diversifying cropland and reducing field size, which can multiply biodiversity while sustaining high yields in both conventional and organic systems. Achieving a landscape-level mosaic of natural habitat patches and fine-grained cropland diversification in both conventional and organic agriculture is key for promoting large-scale biodiversity. This needs to be urgently acknowledged by policy makers for an agricultural paradigm shift.

Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase Gα oxidation.

Abstract: Aims Sodium-glucose-cotransporter-2 inhibitors showed favourable cardiovascular outcomes, but the underlying mechanisms are still elusive. This study investigated the mechanisms of empagliflozin in human and murine heart failure with preserved ejection fraction (HFpEF). Methods and results The acute mechanisms of empagliflozin were investigated in human myocardium from patients with HFpEF and murine ZDF obese rats, which were treated in vivo. As shown with immunoblots and ELISA, empagliflozin significantly suppressed increased levels of ICAM-1, VCAM-1, TNF-α, and IL-6 in human and murine HFpEF myocardium and attenuated pathological oxidative parameters (H2O2, 3-nitrotyrosine, GSH, lipid peroxide) in both cardiomyocyte cytosol and mitochondria in addition to improved endothelial vasorelaxation. In HFpEF, we found higher oxidative stress-dependent activation of eNOS leading to PKGIα oxidation. Interestingly, immunofluorescence imaging and electron microscopy revealed that oxidized PKG1α in HFpEF appeared as dimers/polymers localized to the outer-membrane of the cardiomyocyte. Empagliflozin reduced oxidative stress/eNOS-dependent PKGIα oxidation and polymerization resulting in a higher fraction of PKGIα monomers, which translocated back to the cytosol. Consequently, diminished NO levels, sGC activity, cGMP concentration, and PKGIα activity in HFpEF increased upon empagliflozin leading to improved phosphorylation of myofilament proteins. In skinned HFpEF cardiomyocytes, empagliflozin improved cardiomyocyte stiffness in an anti-oxidative/PKGIα-dependent manner. Monovariate linear regression analysis confirmed the correlation of oxidative stress and PKGIα polymerization with increased cardiomyocyte stiffness and diastolic dysfunction of the HFpEF patients. Conclusion Empagliflozin reduces inflammatory and oxidative stress in HFpEF and thereby improves the NO-sGC-cGMP-cascade and PKGIα activity via reduced PKGIα oxidation and polymerization leading to less pathological cardiomyocyte stiffness.

Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress- and aging-related diseases.

Abstract: Adaptogens comprise a category of herbal medicinal and nutritional products promoting adaptability, resilience, and survival of living organisms in stress. The aim of this review was to summarize the growing knowledge about common adaptogenic plants used in various traditional medical systems (TMS) and conventional medicine and to provide a modern rationale for their use in the treatment of stress-induced and aging-related disorders. Adaptogens have pharmacologically pleiotropic effects on the neuroendocrine-immune system, which explain their traditional use for the treatment of a wide range of conditions. They exhibit a biphasic dose-effect response: at low doses they function as mild stress-mimetics, which activate the adaptive stress-response signaling pathways to cope with severe stress. That is in line with their traditional use for preventing premature aging and to maintain good health and vitality. However, the potential of adaptogens remains poorly explored. Treatment of stress and aging-related diseases require novel approaches. Some combinations of adaptogenic plants provide unique effects due to their synergistic interactions in organisms not obtainable by any ingredient independently. Further progress in this field needs to focus on discovering new combinations of adaptogens based on traditional medical concepts. Robust and rigorous approaches including network pharmacology and systems pharmacology could help in analyzing potential synergistic effects and, more broadly, future uses of adaptogens. In conclusion, the evolution of the adaptogenic concept has led back to basics of TMS and a new level of understanding of holistic approach. It provides a rationale for their use in stress-induced and aging-related diseases.

Plant flavones enrich rhizosphere Oxalobacteraceae to improve maize performance under nitrogen deprivation

Abstract: Beneficial interactions between plant roots and rhizosphere microorganisms are pivotal for plant fitness. Nevertheless, the molecular mechanisms controlling the feedback between root architecture and microbial community structure remain elusive in maize. Here, we demonstrate that transcriptomic gradients along the longitudinal root axis associate with specific shifts in rhizosphere microbial diversity. Moreover, we have established that root-derived flavones predominantly promote the enrichment of bacteria of the taxa Oxalobacteraceae in the rhizosphere, which in turn promote maize growth and nitrogen acquisition. Genetic experiments demonstrate that LRT1-mediated lateral root development coordinates the interactions of the root system with flavone-dependent Oxalobacteraceae under nitrogen deprivation. In summary, these experiments reveal the genetic basis of the reciprocal interactions between root architecture and the composition and diversity of specific microbial taxa in the rhizosphere resulting in improved plant performance. These findings may open new avenues towards the breeding of high-yielding and nutrient-efficient crops by exploiting their interaction with beneficial soil microorganisms.