Data-driven cell tracking and segmentation methods in biomedical imaging require diverse and information-rich training data. In cases where the number of training samples is limited, synthetic computer-generated data sets can be used to improve these methods. This requires the synthesis of cell shapes as well as corresponding microscopy images using generative models. To synthesize realistic living cell shapes, the shape representation used by the generative model should be able to accurately represent fine details and changes in topology, which are common in cells. These requirements are not met by 3D voxel masks, which are restricted in resolution, and polygon meshes, which do not easily model processes like cell growth and mitosis. In this work, we propose to represent living cell shapes as level sets of signed distance functions (SDFs) which are estimated by neural networks. We optimize a fully-connected neural network to provide an implicit representation of the SDF value at any point in a 3D+time domain, conditioned on a learned latent code that is disentangled from the rotation of the cell shape. We demonstrate the effectiveness of this approach on cells that exhibit rapid deformations (Platynereis dumerilii), cells that grow and divide (C. elegans), and cells that have growing and branching filopodial protrusions (A549 human lung carcinoma cells). A quantitative evaluation using shape features and Dice similarity coefficients of real and synthetic cell shapes shows that our model can generate topologically plausible complex cell shapes in 3D+time with high similarity to real living cell shapes. Finally, we show how microscopy images of living cells that correspond to our generated cell shapes can be synthesized using an image-to-image model.

• MeSH
• Caenorhabditis elegans * MeSH
• lidé MeSH
• mitóza MeSH
• nádory plic * MeSH
• neuronové sítě MeSH
• počítačové zpracování obrazu metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Recognition memory is the ability to recognize previously encountered objects. Even this relatively simple, yet extremely fast, ability requires the coordinated activity of large-scale brain networks. However, little is known about the sub-second dynamics of these networks. The majority of current studies into large-scale network dynamics is primarily based on imaging techniques suffering from either poor temporal or spatial resolution. We investigated the dynamics of large-scale functional brain networks underlying recognition memory at the millisecond scale. Specifically, we analyzed dynamic effective connectivity from intracranial electroencephalography while epileptic subjects (n = 18) performed a fast visual recognition memory task. Our data-driven investigation using Granger causality and the analysis of communities with the Louvain algorithm spotlighted a dynamic interplay of two large-scale networks associated with successful recognition. The first network involved the right visual ventral stream and bilateral frontal regions. It was characterized by early, predominantly bottom-up information flow peaking at 115 ms. It was followed by the involvement of another network with predominantly top-down connectivity peaking at 220 ms, mainly in the left anterior hemisphere. The transition between these two networks was associated with changes in network topology, evolving from a more segregated to a more integrated state. These results highlight that distinct large-scale brain networks involved in visual recognition memory unfold early and quickly, within the first 300 ms after stimulus onset. Our study extends the current understanding of the rapid network changes during rapid cognitive processes.

• MeSH
• čelní lalok MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku * metody   MeSH
• mozek * diagnostické zobrazování   MeSH
• paměť MeSH
• rozpoznávání (psychologie) MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Tapeworms of the order Caryophyllidea are the earliest diverging 'true' tapeworms (Eucestoda) and parasitise cypriniform and siluriform fishes almost exclusively. They are typified by a monozoic (non-proglottised) body plan, which is a characteristic shared with early diverging 'cestodarians' Gyrocotylidea and Amphilinidea. Here we present the most comprehensive multi-gene molecular phylogeny of this group, to date. Specimens of 63 species from 32 genera (~50% and ~75% of known species and genus diversity, respectively) were gathered during an intense and targeted 15-year collecting effort. Phylogenetic reconstructions provide high nodal support for three major lineages, which only partly correspond to currently recognised families. The three well-supported clades were as follows: Clade A was in an unsupported position at the base of the tree and was almost exclusively comprised of parasites of catfishes (Siluriformes) from the Afrotropical and Indomalayan regions, including the type genus of the Lytocestidae (Lytocestus). Clade B formed the sister group to the remaining taxa (Clade C) and was composed of species that parasitise cyprinids and loaches (Cypriniformes: Cyprinoidei and Cobitoidei) from the Palaearctic Region. This clade included the type genus of the Caryophyllaeidae (Caryophyllaeus). Clade C comprised Nearctic species from suckers and minnows (Cypriniformes: Catostomidae and Cyprinoidei), which were previously accommodated in two families, i.e. Capingentidae and Caryophyllaeidae. This clade included the type genus of the Capingentidae (Capingens). In addition to Clades A-C, Balanotaenia bancrofti from the monotypic Balanotaeniidae, which parasitises plotosid catfishes in Australia, and Lytocestoides tanganyikae, which parasitises African cichlids, formed a poorly supported clade at the base of the tree. Whereas morphological characteristics traditionally used to differentiate caryophyllidean families do not characterise molecular lineages, host association and biogeographical distribution play a key role in the circumscription of the three well-supported clades revealed by molecular data. Thus, the taxonomic rearrangement proposed herein was guided by the molecular clades. The names of all four extant families were preserved and family affinity was determined by topological clustering with the type genera of the families. The family diagnoses of the Lytocestidae, Caryophyllaeidae and Capingentidae are amended. Biogeographic patterns are indicative of separate Gondwanan and Laurasian radiations having taken place. Regarding the Gondwanan radiation in the Siluriformes, the topology in Clade A indicates an Asian origin with a subsequent African colonisation. Concerning Laurasia, separate radiations appear to have taken place in the Cypriniformes in the temperate zones of North America and Eurasia. Complete absence of caryophyllideans in the Neotropical Region, where numerous catfishes occur, may be due to the Gondwanan radiation having taken place after the continental separation of Africa and South America.

• MeSH
• Cestoda * genetika   MeSH
• Cyprinidae * MeSH
• fylogeneze MeSH
• lidé MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Austrálie MeSH
• Severní Amerika MeSH

DNA double-strand breaks (DSBs), known as the most severe damage in chromatin, were induced in breast cancer cells and normal skin fibroblasts by 2 Gy ionizing photon radiation. In response to DSB induction, phosphorylation of the histone variant H2AX to γH2AX was observed in the form of foci visualized by specific antibodies. By means of super-resolution single-molecule localization microscopy (SMLM), it has been recently shown in a first article about these data that these foci can be separated into clusters of about the same size (diameter ~400 nm). The number of clusters increased with the dose applied and decreased with the repair time. It has also been shown that during the repair period, antibody-labeled MRE11 clusters of about half of the γH2AX cluster diameter were formed inside several γH2AX clusters. MRE11 is part of the MRE11-RAD50-NBS1 (MRN) complex, which is known as a DNA strand resection and broken-end bridging component in homologous recombination repair (HRR) and alternative non-homologous end joining (a-NHEJ). This article is a follow-up of the former ones applying novel procedures of mathematics (topology) and similarity measurements on the data set: to obtain a measure for cluster shape and shape similarities, topological quantifications employing persistent homology were calculated and compared. In addition, based on our findings that γH2AX clusters associated with heterochromatin show a high degree of similarity independently of dose and repair time, these earlier published topological analyses and similarity calculations comparing repair foci within individual cells were extended by topological data averaging (2nd-generation heatmaps) over all cells analyzed at a given repair time point; thereby, the two dimensions (0 and 1) expressed by components and holes were studied separately. Finally, these mean value heatmaps were averaged, in addition. For γH2AX clusters, in both normal fibroblast and MCF-7 cancer cell lines, an increased similarity was found at early time points (up to 60 min) after irradiation for both components and holes of clusters. In contrast, for MRE11, the peak in similarity was found at later time points (2 h up to 48 h) after irradiation. In general, the normal fibroblasts showed quicker phosphorylation of H2AX and recruitment of MRE11 to γH2AX clusters compared to breast cancer cells and a shorter time interval of increased similarity for γH2AX clusters. γH2AX foci and randomly distributed MRE11 molecules naturally occurring in non-irradiated control cells did not show any significant topological similarity.

• Publikační typ
• časopisecké články MeSH

The degree of response to subthalamic nucleus deep brain stimulation (STN-DBS) is individual and hardly predictable. We hypothesized that DBS-related changes in cortical network organization are related to the clinical effect. Network analysis based on graph theory was used to evaluate the high-density electroencephalography (HDEEG) recorded during a visual three-stimuli paradigm in 32 Parkinson's disease (PD) patients treated by STN-DBS in stimulation "off" and "on" states. Preprocessed scalp data were reconstructed into the source space and correlated to the behavioral parameters. In the majority of patients (n = 26), STN-DBS did not lead to changes in global network organization in large-scale brain networks. In a subgroup of suboptimal responders (n = 6), identified according to reaction times (RT) and clinical parameters (lower Unified Parkinson's Disease Rating Scale [UPDRS] score improvement after DBS and worse performance in memory tests), decreased global connectivity in the 1-8 Hz frequency range and regional node strength in frontal areas were detected. The important role of the supplementary motor area for the optimal DBS response was demonstrated by the increased node strength and eigenvector centrality in good responders. This response was missing in the suboptimal responders. Cortical topologic architecture is modified by the response to STN-DBS leading to a dysfunction of the large-scale networks in suboptimal responders.

• MeSH
• elektroencefalografie MeSH
• hluboká mozková stimulace * MeSH
• hodnocení výsledků zdravotní péče MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozková kůra patofyziologie   MeSH
• nervová síť patofyziologie   MeSH
• nucleus subthalamicus patofyziologie   MeSH
• Parkinsonova nemoc patofyziologie   terapie   MeSH
• psychomotorický výkon fyziologie   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Developing sensitive and reliable methods to distinguish normal and abnormal brain states is a key neuroscientific challenge. Topological Data Analysis, despite its relative novelty, already generated many promising applications, including in neuroscience. We conjecture its prominent tool of persistent homology may benefit from going beyond analysing structural and functional connectivity to effective connectivity graphs capturing the direct causal interactions or information flows. Therefore, we assess the potential of persistent homology to directed brain network analysis by testing its discriminatory power in two distinctive examples of disease-related brain connectivity alterations: epilepsy and schizophrenia. We estimate connectivity from functional magnetic resonance imaging and electrophysiology data, employ Persistent Homology and quantify its ability to distinguish healthy from diseased brain states by applying a support vector machine to features quantifying persistent homology structure. We show how this novel approach compares to classification using standard undirected approaches and original connectivity matrices. In the schizophrenia classification, topological data analysis generally performs close to random, while classifications from raw connectivity perform substantially better; potentially due to topographical, rather than topological, specificity of the differences. In the easier task of seizure discrimination from scalp electroencephalography data, classification based on persistent homology features generally reached comparable performance to using raw connectivity, albeit with typically smaller accuracies obtained for the directed (effective) connectivity compared to the undirected (functional) connectivity. Specific applications for topological data analysis may open when direct comparison of connectivity matrices is unsuitable - such as for intracranial electrophysiology with individual number and location of measurements. While standard homology performed overall better than directed homology, this could be due to notorious technical problems of accurate effective connectivity estimation.

• MeSH
• elektroencefalografie MeSH
• epilepsie diagnostické zobrazování   patofyziologie   MeSH
• konektom * MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku MeSH
• modely neurologické * MeSH
• mozek diagnostické zobrazování   patofyziologie   MeSH
• nervová síť diagnostické zobrazování   patofyziologie   MeSH
• schizofrenie diagnostické zobrazování   patofyziologie   MeSH
• záchvaty diagnostické zobrazování   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

While brain imaging tools like functional magnetic resonance imaging (fMRI) afford measurements of whole-brain activity, it remains unclear how best to interpret patterns found amid the data's apparent self-organization. To clarify how patterns of brain activity support brain function, one might identify metric spaces that optimally distinguish brain states across experimentally defined conditions. Therefore, the present study considers the relative capacities of several metric spaces to disambiguate experimentally defined brain states. One fundamental metric space interprets fMRI data topographically, that is, as the vector of amplitudes of a multivariate signal, changing with time. Another perspective compares the brain's functional connectivity, that is, the similarity matrix computed between signals from different brain regions. More recently, metric spaces that consider the data's topology have become available. Such methods treat data as a sample drawn from an abstract geometric object. To recover the structure of that object, topological data analysis detects features that are invariant under continuous deformations (such as coordinate rotation and nodal misalignment). Moreover, the methods explicitly consider features that persist across multiple geometric scales. While, certainly, there are strengths and weaknesses of each brain dynamics metric space, wefind that those that track topological features optimally distinguish experimentally defined brain states.

• Publikační typ
• časopisecké články MeSH

Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene in 13q12.2 are among the most common driver events in acute leukemia, leading to increased cell proliferation and survival through activation of the phosphatidylinositol 3-kinase/AKT-, RAS/MAPK-, and STAT5-signaling pathways. In this study, we examine the pathogenetic impact of somatic hemizygous 13q12.2 microdeletions in B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) using 5 different patient cohorts (in total including 1418 cases). The 13q12.2 deletions occur immediately 5' of FLT3 and involve the PAN3 locus. By detailed analysis of the 13q12.2 segment, we show that the deletions lead to loss of a topologically associating domain border and an enhancer of FLT3. This results in increased cis interactions between the FLT3 promoter and another enhancer located distally to the deletion breakpoints, with subsequent allele-specific upregulation of FLT3 expression, expected to lead to ligand-independent activation of the receptor and downstream signaling. The 13q12.2 deletions are highly enriched in the high-hyperdiploid BCP ALL subtype (frequency 3.9% vs 0.5% in other BCP ALL) and in cases that subsequently relapsed. Taken together, our study describes a novel mechanism of FLT3 involvement in leukemogenesis by upregulation via chromatin remodeling and enhancer hijacking. These data further emphasize the role of FLT3 as a driver gene in BCP ALL.

• MeSH
• akutní lymfatická leukemie genetika   MeSH
• buněčné linie MeSH
• chromozomální delece MeSH
• chromozomální poruchy komplikace   genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• kohortové studie MeSH
• lidé MeSH
• lidské chromozomy, pár 13 genetika   MeSH
• mikročipová analýza MeSH
• regulace genové exprese u leukemie MeSH
• restrukturace chromatinu genetika   fyziologie   MeSH
• sekvenování celého genomu MeSH
• sekvenování transkriptomu MeSH
• tyrosinkinasa 3 podobná fms genetika   MeSH
• upregulace genetika   MeSH
• variabilita počtu kopií segmentů DNA genetika   MeSH
• zesilovače transkripce genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The domestic cat (Felis catus) is an important companion animal and is used as a large animal model for human disease. However, the comprehensive study of adaptive immunity in this species is hampered by the lack of data on lymphocyte antigen receptor genes and usage. The objectives of this study were to annotate the feline T cell receptor (TR) loci and to characterize the expressed repertoire in lymphoid organs of normal cats using high-throughput sequencing. RESULTS: The Felis catus TRG locus contains 30 genes: 12 TRGV, 12 TRGJ and 6 TRGC, the TRB locus contains 48 genes: 33 TRBV, 2 TRBD, 11 TRBJ, 2 TRBC, the TRD locus contains 19 genes: 11 TRDV, 2 TRDD, 5 TRDJ, 1 TRDC, and the TRA locus contains 127 genes: 62 TRAV, 64 TRAJ, 1 TRAC. Functional feline V genes form monophyletic clades with their orthologs, and clustering of multimember subgroups frequently occurs in V genes located at the 5' end of TR loci. Recombination signal (RS) sequences of the heptamer and nonamer of functional V and J genes are highly conserved. Analysis of the TRG expressed repertoire showed preferential intra-cassette over inter-cassette rearrangements and dominant usage of the TRGV2-1 and TRGJ1-2 genes. The usage of TRBV genes showed minor bias but TRBJ genes of the second J-C-cluster were more commonly rearranged than TRBJ genes of the first cluster. The TRA/TRD V genes almost exclusively rearranged to J genes within their locus. The TRAV/TRAJ gene usage was relatively balanced while the TRD repertoire was dominated by TRDJ3. CONCLUSIONS: This is the first description of all TR loci in the cat. The genomic organization of feline TR loci was similar to that of previously described jawed vertebrates (gnathostomata) and is compatible with the birth-and-death model of evolution. The large-scale characterization of feline TR genes provides comprehensive baseline data on immune repertoires in healthy cats and will facilitate the development of improved reagents for the diagnosis of lymphoproliferative diseases in cats. In addition, these data might benefit studies using cats as a large animal model for human disease.

• MeSH
• adaptivní imunita genetika   MeSH
• fylogeneze MeSH
• genetické lokusy genetika   MeSH
• genomika metody   MeSH
• kočky genetika   imunologie   MeSH
• lidé MeSH
• lymfoidní tkáň metabolismus   MeSH
• receptory antigenů T-buněk klasifikace   genetika   MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• zvířata MeSH
• Check Tag
• kočky genetika   imunologie   MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Naive use of molecular data may lead to ambiguous conclusions, especially within the context of "cryptic" species. Here, we integrated molecular and morphometric data to evaluate phylogenetic relationships in the widespread terrestrial micro-snail genus, Euconulus. We analyzed mitochondrial (16S + COII) and nuclear (ITS1 + ITS2) sequence across 94 populations from Europe, Asia and North America within the nominate species E. alderi, E. fulvus and E. polygyratus, and used the southeastern USA E. chersinus, E. dentatus, and E. trochulus as comparative outgroups. Phylogeny was reconstructed using four different reconstruction methods to identify robust, well-supported topological features. We then performed discriminant analysis on shell measurements between these genetically-identified species-level clades. These analyses provided evidence for a biologically valid North American "cryptic" species within E. alderi. However, while highly supported polyphyletic structure was also observed within E. fulvus, disagreement in placement of individuals between mtDNA and nDNA clades, lack of morphological differences, and presence of potential hybrids imply that these lineages do not rise to the threshold as biologically valid cryptic species, and rather appear to simply represent a complex of geographically structured populations within a single species. These results caution that entering into a cryptic species hypothesis should not be undertaken lightly, and should be optimally supported along multiple lines of evidence. Generally, post-hoc analyses of macro-scale features should be conducted to attempt identification of previously ignored diagnostic traits. If such traits cannot be found, i.e. in the case of potentially "fully cryptic" species, additional criteria should be met to propound a cryptic species hypothesis, including the agreement in tree topology among both mtDNA and nDNA, and little (or no) evidence of hybridization based on a critical analysis of sequence chromatograms. Even when the above conditions are satisfied, it only implies that the cryptic species hypothesis is plausible, but should optimally be subjected to further careful examination.

• MeSH
• analýza hlavních komponent MeSH
• buněčné jádro genetika   MeSH
• fylogeneze MeSH
• hlemýždi klasifikace   genetika   MeSH
• pravděpodobnostní funkce MeSH
• respirační komplex IV klasifikace   genetika   MeSH
• RNA ribozomální 16S klasifikace   genetika   MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA MeSH
• sekvenční seřazení MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH