Volatile compounds are usually associated with an appearance/presence in the atmosphere. Recent advances, however, indicated that the soil is a huge reservoir and source of biogenic volatile organic ...compounds (bVOCs), which are formed from decomposing litter and dead organic material or are synthesized by underground living organism or organs and tissues of plants. This review summarizes the scarce available data on the exchange of VOCs between soil and atmosphere and the features of the soil and particle structure allowing diffusion of volatiles in the soil, which is the prerequisite for biological VOC‐based interactions. In fact, soil may function either as a sink or as a source of bVOCs. Soil VOC emissions to the atmosphere are often 1–2 (0–3) orders of magnitude lower than those from aboveground vegetation. Microorganisms and the plant root system are the major sources for bVOCs. The current methodology to detect belowground volatiles is described as well as the metabolic capabilities resulting in the wealth of microbial and root VOC emissions. Furthermore, VOC profiles are discussed as non‐destructive fingerprints for the detection of organisms. In the last chapter, belowground volatile‐based bi‐ and multi‐trophic interactions between microorganisms, plants and invertebrates in the soil are discussed.
Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. Various studies exist about the molecular mechanisms of viral infection. However, such information is ...spread across many publications and it is very time-consuming to integrate, and exploit. We develop CoVex, an interactive online platform for SARS-CoV-2 host interactome exploration and drug (target) identification. CoVex integrates virus-human protein interactions, human protein-protein interactions, and drug-target interactions. It allows visual exploration of the virus-host interactome and implements systems medicine algorithms for network-based prediction of drug candidates. Thus, CoVex is a resource to understand molecular mechanisms of pathogenicity and to prioritize candidate therapeutics. We investigate recent hypotheses on a systems biology level to explore mechanistic virus life cycle drivers, and to extract drug repurposing candidates. CoVex renders COVID-19 drug research systems-medicine-ready by giving the scientific community direct access to network medicine algorithms. It is available at https://exbio.wzw.tum.de/covex/.
We present the AIMe registry, a community-driven reporting platform for AI in biomedicine. It aims to enhance the accessibility, reproducibility and usability of biomedical AI models, and allows ...future revisions by the community.
Aggregating transcriptomics data across hospitals can increase sensitivity and robustness of differential expression analyses, yielding deeper clinical insights. As data exchange is often restricted ...by privacy legislation, meta-analyses are frequently employed to pool local results. However, the accuracy might drop if class labels are inhomogeneously distributed among cohorts. Flimma ( https://exbio.wzw.tum.de/flimma/ ) addresses this issue by implementing the state-of-the-art workflow limma voom in a federated manner, i.e., patient data never leaves its source site. Flimma results are identical to those generated by limma voom on aggregated datasets even in imbalanced scenarios where meta-analysis approaches fail.
The emission of volatiles is a common, but mostly neglected, ability of bacteria that is important for inter‐ and intraspecific interactions. Currently, limited information is available on how the ...bacterial volatile (mVOC) signal is integrated into a plant's life at the physiological, transcriptional and metabolic level. Previous results provided evidence for volatile‐dependent regulation of WRKY18, a pathogen‐responsive transcription factor of Arabidopsis thaliana in co‐culture with two rhizobacteria, Serratia plymuthica HRO‐C48 and Stenotrophomonas maltophilia R3089.
Dual cultures of these bacteria and A. thaliana; application of the common mVOC 2‐phenyl‐ethanol; extraction of metabolites of A. thaliana after exposure to bacterial volatiles; and analysis of the metabolomes (GC‐TOF/MS) were carried out.
The prominent microbial aromatic compound 2‐phenyl‐ethanol, emitted by both bacteria, negatively affects growth of A. thaliana wild type, whereas WRKY18 T‐DNA insertion mutants were significantly more tolerant than wild‐type seedlings. This paper also demonstrates for the first time the impact of the rhizobacterial volatiles on the metabolome of A. thaliana. Upon mVOC exposure the plants rearrange their metabolism by accumulation of e.g. amino acids and TCA intermediates that potentially allow plants to cope with and survive this stress.
Our findings illustrate the high degree of complexity of metabolic rearrangements underlying the interactions of bacterial volatile elicitors and resulting plant responses. Furthermore, the impact of the volatile 2‐phenyl‐ethanol as a signal in the WRKY18‐dependent pathway highlights this compound as an important molecular player.
SEE ZEKERIDOU AND LENNON DOI101093/AWW213 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently discovered autoimmune syndrome associated ...with psychosis, dyskinesias, and seizures. Little is known about the cerebrospinal fluid autoantibody repertoire. Antibodies against the NR1 subunit of the NMDAR are thought to be pathogenic; however, direct proof is lacking as previous experiments could not distinguish the contribution of further anti-neuronal antibodies. Using single cell cloning of full-length immunoglobulin heavy and light chain genes, we generated a panel of recombinant monoclonal NR1 antibodies from cerebrospinal fluid memory B cells and antibody secreting cells of NMDAR encephalitis patients. Cells typically carried somatically mutated immunoglobulin genes and had undergone class-switching to immunoglobulin G, clonally expanded cells carried identical somatic hypermutation patterns. A fraction of NR1 antibodies were non-mutated, thus resembling 'naturally occurring antibodies' and indicating that tolerance induction against NMDAR was incomplete and somatic hypermutation not essential for functional antibodies. However, only a small percentage of cerebrospinal fluid-derived antibodies reacted against NR1. Instead, nearly all further antibodies bound specifically to diverse brain-expressed epitopes including neuronal surfaces, suggesting that a broad repertoire of antibody-secreting cells enrich in the central nervous system during encephalitis. Our functional data using primary hippocampal neurons indicate that human cerebrospinal fluid-derived monoclonal NR1 antibodies alone are sufficient to cause neuronal surface receptor downregulation and subsequent impairment of NMDAR-mediated currents, thus providing ultimate proof of antibody pathogenicity. The observed formation of immunological memory might be relevant for clinical relapses.
Machine learning and artificial intelligence have shown promising results in many areas and are driven by the increasing amount of available data. However, these data are often distributed across ...different institutions and cannot be easily shared owing to strict privacy regulations. Federated learning (FL) allows the training of distributed machine learning models without sharing sensitive data. In addition, the implementation is time-consuming and requires advanced programming skills and complex technical infrastructures.
Various tools and frameworks have been developed to simplify the development of FL algorithms and provide the necessary technical infrastructure. Although there are many high-quality frameworks, most focus only on a single application case or method. To our knowledge, there are no generic frameworks, meaning that the existing solutions are restricted to a particular type of algorithm or application field. Furthermore, most of these frameworks provide an application programming interface that needs programming knowledge. There is no collection of ready-to-use FL algorithms that are extendable and allow users (eg, researchers) without programming knowledge to apply FL. A central FL platform for both FL algorithm developers and users does not exist. This study aimed to address this gap and make FL available to everyone by developing FeatureCloud, an all-in-one platform for FL in biomedicine and beyond.
The FeatureCloud platform consists of 3 main components: a global frontend, a global backend, and a local controller. Our platform uses a Docker to separate the local acting components of the platform from the sensitive data systems. We evaluated our platform using 4 different algorithms on 5 data sets for both accuracy and runtime.
FeatureCloud removes the complexity of distributed systems for developers and end users by providing a comprehensive platform for executing multi-institutional FL analyses and implementing FL algorithms. Through its integrated artificial intelligence store, federated algorithms can easily be published and reused by the community. To secure sensitive raw data, FeatureCloud supports privacy-enhancing technologies to secure the shared local models and assures high standards in data privacy to comply with the strict General Data Protection Regulation. Our evaluation shows that applications developed in FeatureCloud can produce highly similar results compared with centralized approaches and scale well for an increasing number of participating sites.
FeatureCloud provides a ready-to-use platform that integrates the development and execution of FL algorithms while reducing the complexity to a minimum and removing the hurdles of federated infrastructure. Thus, we believe that it has the potential to greatly increase the accessibility of privacy-preserving and distributed data analyses in biomedicine and beyond.
Recently, the transcription factor AP-2ɛ was shown to be a regulator of hypertrophy in cartilage and to be differentially expressed in osteoarthritis (OA). However, the only known target gene of ...AP-2ɛ up to date is
integrin alpha10. To better characterize the function of AP-2ɛ in cartilage we screened for additional target genes.
Promoter analysis, ChIP-assays and electrophoretic mobility shift assay were used to characterize the regulation of a new AP-2ɛ target gene in detail.
In this study, we determined the chemokine CXCL1, already known to be important in osteoarthritis (OA), as a new target gene of AP-2ɛ. We could confirm that CXCL1 is expressed in chondrocytes and significantly over-expressed in OA-chondrocytes. Transient transfection of chondrocytes with an AP-2ɛ expression construct led to a significant increase of the CXCL1 mRNA level in these cells. We identified three potential AP-2 binding sites within the
CXCL1 promoter and performed luciferase assays, indicating that an AP-2 binding motif (AP-2.2) ranging from position −135 to −144
bp relative to the translation start is responsive to AP-2ɛ. This result was further addressed by site-directed mutagenesis demonstrating that activation of the
CXCL1 promoter by AP-2ɛ is exclusively dependent on AP-2.2. Chromatin immunoprecipitation and electromobility shift assays confirmed the direct binding of AP-2ɛ to the
CXCL1 promoter in OA-chondrocytes at this site.
These findings revealed
CXCL1 as a novel target gene of AP-2ɛ in chondrocytes and support the important role of AP-2ɛ in cartilage.
Objective
Maternal autoantibodies are a risk factor for impaired brain development in offspring. Antibodies (ABs) against the NR1 (GluN1) subunit of the N‐methyl‐d‐aspartate receptor (NMDAR) are ...among the most frequently diagnosed anti‐neuronal surface ABs, yet little is known about effects on fetal development during pregnancy.
Methods
We established a murine model of in utero exposure to human recombinant NR1 and isotype‐matched nonreactive control ABs. Pregnant C57BL/6J mice were intraperitoneally injected on embryonic days 13 and 17 each with 240μg of human monoclonal ABs. Offspring were investigated for acute and chronic effects on NMDAR function, brain development, and behavior.
Results
Transferred NR1 ABs enriched in the fetus and bound to synaptic structures in the fetal brain. Density of NMDAR was considerably reduced (up to −49.2%) and electrophysiological properties were altered, reflected by decreased amplitudes of spontaneous excitatory postsynaptic currents in young neonates (−34.4%). NR1 AB‐treated animals displayed increased early postnatal mortality (+27.2%), impaired neurodevelopmental reflexes, altered blood pH, and reduced bodyweight. During adolescence and adulthood, animals showed hyperactivity (+27.8% median activity over 14 days), lower anxiety, and impaired sensorimotor gating. NR1 ABs caused long‐lasting neuropathological effects also in aged mice (10 months), such as reduced volumes of cerebellum, midbrain, and brainstem.
Interpretation
The data collectively support a model in which asymptomatic mothers can harbor low‐level pathogenic human NR1 ABs that are diaplacentally transferred, causing neurotoxic effects on neonatal development. Thus, AB‐mediated network changes may represent a potentially treatable neurodevelopmental congenital brain disorder contributing to lifelong neuropsychiatric morbidity in affected children. ANN NEUROL 2019;86:656–670
During vertebrate embryogenesis, vascular endothelial cells (ECs) and primitive erythrocytes become specified within close proximity in the posterior lateral plate mesoderm (LPM) from a common ...progenitor. However, the signaling cascades regulating the specification into either lineage remain largely elusive. Here, we analyze the contribution of β-catenin dependent Wnt signaling to EC and erythrocyte specification during zebrafish embryogenesis.
We generated novel β-catenin dependent Wnt signaling reporters which, by using destabilized fluorophores (Venus-Pest, dGFP), specifically allow us to detect Wnt signaling responses in narrow time windows as well as in spatially restricted domains, defined by Cre recombinase expression (Tg(axin2BAC:Venus-Pest)mu288; Tg(14TCF:loxP-STOP-loxP-dGFP)mu202). We therefore can detect β-catenin dependent Wnt signaling activity in a subset of the Fli1a-positive progenitor population. Additionally, we show that mesodermal Wnt3a-mediated signaling via the transcription factor Lef1 positively regulates EC specification (defined by kdrl expression) at the expense of primitive erythrocyte specification (defined by gata1 expression) in zebrafish embryos.
Using mesoderm derived from human embryonic stem cells, we identified the same principle of Wnt signaling dependent EC specification in conjunction with auto-upregulation of LEF1.
Our data indicate a novel role of β-catenin dependent Wnt signaling in regulating EC specification during vasculogenesis.
•Wnt3a promotes angioblast specification at the expense of primitive erythropoiesis.•In zebrafish and hESC culture Wnt mediated progenitor specification occurs via Lef1.•Generation of novel zebrafish Wnt signaling reporter with destabilized fluorophores in vivo.
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