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NEURD offers automated proofreading and feature extraction for connectomics
No full textAbstract We are in the era of millimetre-scale electron microscopy volumes collected at nanometre resolution 1,2 . Dense reconstruction of cellular compartments in these electron microscopy volumes has been enabled by recent advances in machine learning 3–6 . Automated segmentation methods produce exceptionally accurate reconstructions of cells, but post hoc proofreading is still required to generate large connectomes that are free of merge and split errors. The elaborate 3D meshes of neurons in these volumes contain detailed morphological information at multiple scales, from the diameter, shape and branching patterns of axons and dendrites, down to the fine-scale structure of dendritic spines. However, extracting these features can require substantial effort to piece together existing tools into custom workflows. Here, building on existing open source software for mesh manipulation, we present Neural Decomposition (NEURD), a software package that decomposes meshed neurons into compact and extensively annotated graph representations. With these feature-rich graphs, we automate a variety of tasks such as state-of-the-art automated proofreading of merge errors, cell classification, spine detection, axonal-dendritic proximities and other annotations. These features enable many downstream analyses of neural morphology and connectivity, making these massive and complex datasets more accessible to neuroscience researchers
Effect of felzartamab on the molecular phenotype of antibody-mediated rejection in kidney transplant biopsies
No full textAbstract A recent randomized controlled trial demonstrated that treatment with anti-CD38 monoclonal antibody felzartamab suppressed antibody-mediated rejection (ABMR) in kidney transplant patients but with recurrence after treatment in some patients. Here we examined the molecular effects of 6 months of felzartamab treatment on biopsies from the trial using genome-wide microarray analysis, comparing pretreatment, end-of-treatment (week 24) and posttreatment (week 52) biopsies from ten patients treated with felzartamab and ten patients in the placebo group. Felzartamab reduced molecular ABMR activity scores in all nine patients with baseline ABMR activity, selectively suppressing interferon gamma-inducible and natural killer cell transcripts, with minimal effect on ABMR stage-related endothelial transcripts. Suppression was often incomplete when ABMR activity was intense, and molecular recurrence was nearly universal by week 52. However, we also found that felzartamab had parenchymal benefits at week 52, slowing the trajectories of molecular injury scores beyond the treatment period, suggesting that suppression of ABMR activity could potentially slow future progression to kidney failure. These data provide preliminary molecular insights into the effects of CD38-directed treatment for ABMR, which have the potential to inform future therapeutic strategies
Comparison of marker-less 2D image-based methods for infant pose estimation
No full textAbstract In this study we compare the performance of available generic- and specialized infant-pose estimators for a video-based automated general movement assessment (GMA), and the choice of viewing angle for optimal recordings, i.e., conventional diagonal view used in GMA vs. top-down view. We used 4500 annotated video-frames from 75 recordings of infant spontaneous motor functions from 4 to 16 weeks. To determine which pose estimation method and camera angle yield the best pose estimation accuracy on infants in a GMA related setting, the error with respect to human annotations and the percentage of correct key-points (PCK) were computed and compared. The results show that the best performing generic model trained on adults, ViTPose, also performs best on infants. We see no improvement from using specific infant-pose estimators over the generic pose estimators on our infant dataset. However, when retraining a generic model on our data, there is a significant improvement in pose estimation accuracy. This indicates limited generalization capabilities of infant-pose estimators to other infant datasets, meaning that one should be careful when choosing infant pose estimators and using them on infant datasets which they were not trained on. The pose estimation accuracy obtained from the top-down view is significantly better than that obtained from the diagonal view (the standard view for GMA). This suggests that a top-down view should be included in recording setups for automated GMA research
Comparative study of small-scale magnetic fields on ξ Boo A using optical and near-infrared spectroscopy
No full textContext. Magnetic field investigations of Sun-like stars, using Zeeman splitting of non-polarised spectra, in the optical and H-band have found significantly different magnetic field strengths for the same stars, the cause of which is currently unknown. Aims. We aim to further investigate this issue by systematically analysing the magnetic field of ξ Boo A, a magnetically active G7 dwarf, using spectral lines at different wavelengths. Methods. We used polarised radiative transfer accounting for the departures from local thermodynamic equilibrium to generate synthetic spectra. To find the magnetic field strengths in the optical, H-band, and K-band, we employed MCMC sampling analysis of high-resolution spectra observed with the spectrographs CRIRES + , ESPaDOnS, NARVAL, and UVES. We also determine the formation depth of different lines by calculating the contribution functions for each line employed in the analysis. Results. We find that the magnetic field strength discrepancy between lines in the optical and H-band persists even when treating the different wavelength regions consistently. In addition, the magnetic measurements derived from the K-band appear to more closely align with the optical. The H-band appears to yield magnetic field strengths ∼0.4 kG with a statistically significant variation while the optical and K-band is stable at ∼0.6 kG for observations spanning about two decades. The contribution functions reveal that the optical lines form at a significantly higher altitude in the photosphere compared to those in the H- and K-band. Conclusions. While we find that the discrepancy remains, the variation of formation depths could indicate that the disagreement between magnetic field measurements obtained at different wavelengths is linked to the variation of the magnetic field along the line of sight and between different structures, such as star spots and faculae, in the stellar photosphere
First experience with a new tool for automatic mapping of fragmented signals in a case report of cardioneuroablation
No full textExpanding our understanding of synucleinopathies: proteinopathy, proteinopenia, and lipidopathy
No full textA possible consequence of the process of protein aggregation in neurodegenerative diseases is the depletion of soluble protein species (proteinopenia), which may, at least in some cases, reduce protein function/activity. This concept, which is often overlooked, may play a role in synucleinopathies such as Parkinson's disease (PD), and dementia with Lewy bodies (DLB), where the protein α‐synuclein (aSyn) is known to accumulate in insoluble inclusions. aSyn is at the crossroads between cellular proteostasis and lipidostasis networks and, therefore, we must be aware of the complexity we face when we try to understand the molecular basis of synucleinopathies. Importantly, aSyn and β‐glucocerebrosidase (GCase), a sphingolipid hydrolase also strongly implicated in PD and DLB, are connected to lipid biology and to protein quality control function. Thus, changes in the normal relationship between these two proteins may shift the balance in the cell and lead to proteinopathy and/or proteinopenia, while also affecting lipidostasis of cells in the brain. Thus, pathological mechanisms that are a consequence of (a) loss‐of‐function, (b) gain‐of‐toxic function, and (c) alterations in lipidostasis need to be carefully analyzed and integrated in our study of the molecular underpinnings of neurodegenerative mechanisms. Here, we highlight implications of the depletion of the soluble form of aSyn, and of GCase, and discuss how state‐of‐the‐art ‘omics technologies’ could be deployed to assist in the clinical assessment of synucleinopathies.Deutsche Forschungsgemeinschaft https://doi.org/10.13039/50110000165
Viruses Facilitate Energy Acquisition Potential by Their Bacterial Hosts in Rhizosphere of Grafted Plants
No full textABSTRACT Viruses alter the ecological and evolutionary trajectories of bacterial host communities. Plant grafting is a technique that integrates two species or varietiies and have consequences on the rhizosphere functioning. The grafting effects on the taxonomic and functional assembly of viruses and their bacterial host in the plant rhizosphere remain largely elusive. Using shotgun metagenome sequencing, we recover a total of 1441 viral operational taxonomic units from the rhizosphere of grafted and ungrafted plants after 8‐year continuous monoculture. In the grafted and ungrafted rhizosphere, the Myoviridae , Zobellviridae and Kyanoviridae emerged as the predominant viral families, collectively representing around 40% of the viral community in each respective environment. Grafting enriched the members in viral family Kyanoviridae , Tectiviridae , Peduoviridae and Suoliviridae , and auxiliary metabolic genes related to pyruvate metabolism and energy acquisition (e.g., gloB , DNMT1 and dcyD ). The virus–bacterial interactions increased the rapid growth potential of bacteria, which explains the strong increase in abundance of specific bacterial hosts (i.e., Chitinophagaceae, Cyclobacteriaceae and Spirosomaceae) in the grafted‐plant rhizosphere. Overall, these results deepen our understanding of microbial community assembly and ecological services from the perspective of virus–host interactions.Summary Statement 1. Grafting increased the abundance rather than the richness of viral auxiliary metabolic genes in the rhizosphere soil. 2. Viruses in the grafted plant rhizosphere increased the ability of their bacterial hosts to obtain energy. 3. Viral hosts in grafted plant rhizosphere have greater potential for rapid growth than those in ungrafted treatment.ABSTRACT Viruses alter the ecological and evolutionary trajectories of bacterial host communities. Plant grafting is a technique that integrates two species or varietiies and have consequences on the rhizosphere functioning. The grafting effects on the taxonomic and functional assembly of viruses and their bacterial host in the plant rhizosphere remain largely elusive. Using shotgun metagenome sequencing, we recover a total of 1441 viral operational taxonomic units from the rhizosphere of grafted and ungrafted plants after 8‐year continuous monoculture. In the grafted and ungrafted rhizosphere, the Myoviridae , Zobellviridae and Kyanoviridae emerged as the predominant viral families, collectively representing around 40% of the viral community in each respective environment. Grafting enriched the members in viral family Kyanoviridae , Tectiviridae , Peduoviridae and Suoliviridae , and auxiliary metabolic genes related to pyruvate metabolism and energy acquisition (e.g., gloB , DNMT1 and dcyD ). The virus–bacterial interactions increased the rapid growth potential of bacteria, which explains the strong increase in abundance of specific bacterial hosts (i.e., Chitinophagaceae, Cyclobacteriaceae and Spirosomaceae) in the grafted‐plant rhizosphere. Overall, these results deepen our understanding of microbial community assembly and ecological services from the perspective of virus–host interactions.Summary Statement 1. Grafting increased the abundance rather than the richness of viral auxiliary metabolic genes in the rhizosphere soil. 2. Viruses in the grafted plant rhizosphere increased the ability of their bacterial hosts to obtain energy. 3. Viral hosts in grafted plant rhizosphere have greater potential for rapid growth than those in ungrafted treatment
Mechanisms of Enhancer-Mediated Gene Activation in the Context of the 3D Genome
No full textPrecise spatiotemporal regulation of gene expression is critical for the development and functioning of complex, multicellular organisms. Enhancers play a fundamental role in the regulation of gene expression, but the molecular underpinnings of enhancer-mediated gene activation remain poorly understood. Many mammalian genes are dependent on the activity of multiple enhancers, which can be separated from their target genes by large genomic distances. Accurate gene regulation therefore relies on specific interactions between enhancers and their target genes in 3D nuclear space. In this review, we discuss recent insights into the mechanisms by which enhancers cooperate to regulate precise and robust gene expression levels. We also review recent progress in our understanding of the molecular drivers of specific 3D interactions between enhancers and their target genes. We conclude by discussing current models of the molecular mechanisms by which enhancers activate gene expression in their 3D chromatin context