Steffen Hartel

University of Chile · Facultad de Medicina

Background/Objectives: The accurate quantification of ground-glass opacities (GGOs) and consolidation volumes has prognostic value in COVID-19 patients. Nevertheless, the accurate manual quantification of the corresponding volumes remains a time-consuming task. Deep learning (DL) has demonstrated good performance in the segmentation of normal lung...

Hippocampal neuronal activity generates dendritic and somatic Ca2+ signals, which, depending on stimulus intensity, rapidly propagate to the nucleus and induce the expression of transcription factors and genes with crucial roles in cognitive functions. Soluble amyloid-beta oligomers (AβOs), the main synaptotoxins engaged in the pathogenesis of Alzh...

Hippocampal neuronal activity generates dendritic and somatic Ca2+ signals, which depending on stimulus intensity, rapidly propagate to the nucleus and induce the expression of transcription factors and genes with crucial roles in cognitive functions. Soluble Amyloid-beta Oligomers (AβOs), the main synaptotoxins engaged in the pathogenesis of Alzhe...

Motivation Quantitative descriptions of multi-cellular structures from optical microscopy imaging are prime to understand the variety of three-dimensional (3D) shapes in living organisms. Experimental models of vertebrates, invertebrates and plants, such as zebrafish, killifish, Drosophila or Marchantia, mainly comprise multilayer tissues, and even...

Proteus mirabilis(P. mirabilis) is a common etiological agent of urinary tract infections, particularly those associated with catheterization. P. mirabilis efficiently forms biofilms on different surfaces and shows a multicellular behavior called 'swarming', mediated by flagella. To date, the role of flagella in P. mirabilis biofilm formation has b...

The parapineal organ is a midline-derived epithalamic structure that in zebrafish adopts a left-sided position at embryonic stages to promote the development of left-right asymmetries in the habenular nuclei. Despite extensive knowledge about its embryonic and larval development, it is still unknown whether the parapineal organ and its profuse larv...

In response to brain insults, astrocytes become reactive, promoting protection and tissue repair. However, astroglial reactivity is typical of brain pathologies, including Alzheimer's disease (AD). Considering the heterogeneity of the reac-tive response, the role of astrocytes in the course of different forms of AD has been underestimated. Colombia...

The last decade has shown substantial increasing use of Sperm Chromatin Dispersion tests (SCDt) to evaluate DNA-fragmentation in human sperm. SCDt has been proven advantageous over other techniques. However, the visual evaluation remains a subjective component. The goal of this work was to develop an automated, repeatable and objective image analys...

Upon interaction with immobilized antigens, B cells form an immune synapse where actin remodeling and re-positioning of the microtubule-organizing center (MTOC) together with lysosomes can facilitate antigen extraction. B cells have restricted cytoplasmic space, mainly occupied by a large nucleus, yet the role of nuclear morphology in the formation...

Significance The expression of genes involved in hippocampal synaptic plasticity, learning, and memory requires that Ca ²⁺ signals generated in spines, dendrites, or the soma by neuronal stimulation reach the nucleus. Here, we report that stimulation of hippocampal neurons induces Ca ²⁺ release mediated by RyR2 channels, which contributes to nuclea...

Medical imaging is essential nowadays throughout medical education, research, and care. Accordingly, international efforts have been made to set large-scale image repositories for these purposes. Yet, to date, browsing of large-scale medical image repositories has been troublesome, time-consuming, and generally limited by text search engines. A par...

Salmonella comprises two species and more than 2500 serovars with marked differences in host specificity, and is responsible for a wide spectrum of diseases, ranging from localized gastroenteritis to severe life-threatening invasive disease. The initiation of the host inflammatory response, triggered by many Pathogen-Associated Molecular Patterns (...

Upon interaction with immobilized antigens B cells form an immune synapse, where actin remodeling and re-positioning of the microtubule-organizing center (MTOC) together with lysosomes can facilitate antigen extraction. B cells have restricted cytoplasmic space, mainly occupied by a large nucleus, yet the role of nuclear morphology in the formation...

Neuronal Ca²⁺ signals are fundamental for synaptic transmission and activity-dependent changes in gene expression. Voltage-gated Ca²⁺ channels and N-methyl-d-aspartate receptors play major roles in mediating external Ca²⁺ entry during action potential firing and glutamatergic activity. Additionally, the inositol-1,4,5-trisphosphate receptor (IP3R)...

In response to DNA double-strand breaks (DSB), histone H2AX is phosphorylated around the lesion by a feed forward signal amplification loop, originating γH2AX foci detectable by immunofluorescence and confocal microscopy as elliptical areas of uniform intensity. We exploited the significant increase in resolution (~ × 10) provided by single-molecul...

We study an inverse problem for Light Sheet Fluorescence Microscopy (LSFM), where the density of fluorescent molecules needs to be reconstructed. Our first step is to present a mathematical model to describe the measurements obtained by an optic camera during an LSFM experiment. Two meaningful stages are considered: excitation and fluorescence. We...

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) used to treat mood and anxiety disorders. Chronic treatment with this antidepressant drug is thought to favor functional recovery by promoting structural and molecular changes in several forebrain areas. At the synaptic level, chronic fluoxetine induces an increased size and density of d...

Trypanosoma cruzi calreticulin (TcCalr, formerly known as TcCRT), upon binding to Complement (C) C1 and ficolins, inhibits the classical and lectin pathways and promotes infectivity. This virulence correlates with the expression of TcCalr. The TcCalr C inhibitory capacity was shown in a previous work using a clonal epimastigote cell line from the T...

Imaging spectroscopy integrates conventional imaging and spectroscopy to attain both spatial and spectral information from an object. Processing and analysis of a hypercube can be a hard task. Robust methods for hyperspectral data classification are required, insensitive to imaging deficiencies and high input dimension. Mushrooms have a thin and po...

DCL cells become elongated along the retracting vertices of two EVL cells undergoing fusion in A. nigripinnis (related to Supplementary Fig. 9). Time-lapse movie of confocal microscopy z-stack maximum projections, with an inverted look-up table, of an embryo expressing lifeact-GFP. Images correspond to an embryo animal pole view centred in two EVL...

DCL cells elongate and follow the contractile border of an extruding EVL cell in A. nigripinnis (related to Fig. 4). Time-lapse movie of confocal microscopy z-stack maximum projections, with an inverted look-up table, of an embryo expressing GAP43-EGFP. Images correspond to an embryo animal pole view centred in a single EVL cell undergoing apical e...

DCL cell moving in and out the EVL cell border by means of polarised membrane protrusions in A. nigripinnis (related to Fig. 6f). Time-lapse movie of confocal microscopy z-stack maximum projections, with an inverted look-up table, showing a single DCL cell as it moves in and out the EVL cell border (straight grey line) in an embryo expressing lifea...

Disruption of Rac1 suppresses formation of polarised membrane protrusions and DCL cell migration (related to Fig. 6h). Time-lapse movie of confocal microscopy z-stack maximum projections, with an inverted look-up table, showing the migratory behaviour of two DCL cells at the EVL cell border (black line) in an embryo expressing lifeact-GFP and over-...

DCL cells are able to sense EVL cell borders (related to Supplementary Fig. 6). Time-lapse movie of confocal microscopy z-stack maximum projections, with an inverted look-up table, showing DCL cells migrating at EVL cell borders (straight black lines) in an embryo expressing lifeact-GFP. The image is centred in a DCL cell that shows F-actin brushes...

Effect of mild E-cad knock down in the spatial organisation of DCL cells with respect to EVL cell borders in A. nigripinnis (related to Fig. 10l,m). Time-lapse movie of confocal microscopy z-stack maximum projection, with an inverted look-up table, of an embryo expressing lifeact-GFP and injected at 1-cell stage with a low dose of e-cad morpholino....

Supplementary Figures, Supplementary Table, Supplementary Reference.

Cell movements of the DCL and cell shape changes of the EVL between late blastula and 60% epiboly in A. nigripinnis (related to Fig. 2). Left panel: time-lapse movie of confocal microscopy z-stack maximum projection, with an inverted look-up table, of an embryo expressing lifeact-GFP from an animal pole view. Right panel: corresponding animation af...

DCL cells shift from random to directional migration as they approach the EVL cell border (related to Fig. 7b-g). Time-lapse movie of confocal microscopy z-stack maximum projections, with an inverted look-up table, showing a single DCL cell as it moves in the vicinity of the EVL cell border (straight black lines) in an embryo expressing lifeact-GFP...

Computer simulations recapitulate the dynamics of EVL expansion and DCL spreading from the experiments (related to Fig. 9 and Supplementary Fig. 18). Composite animations from experimental data generated by segmenting the DCL and EVL from time-lapse confocal movies (left panel) and computer simulation of the corresponding period (right panel). Both...

DCL cells follow transient contractions of the EVL cell cortex during events of failed cytokinesis in A. nigripinnis. Time-lapse movie of confocal microscopy z-stack maximum projections, with an inverted look-up table, of an embryo expressing lifeact-GFP. Images correspond to an embryo animal pole view centred in three EVL cells undergoing transien...

Amyloid β peptide oligomers (AβOs), toxic aggregates with pivotal roles in Alzheimer’s disease, trigger persistent and low magnitude Ca2+ signals in neurons. We reported previously that these Ca2+ signals, which arise from Ca2+ entry and subsequent amplification by Ca2+ release through ryanodine receptor (RyR) channels, promote mitochondrial networ...

Background and objective: Infertility is a problem that affects up to 15% of couples worldwide with emotional and physiological implications and semen analysis is the first step in the evaluation of an infertile couple. Indeed the morphology of human sperm cells is considered to be a clinical tool dedicated to the fertility prognosis and serves, ma...

Background and objective: Published algorithms for classification of human sperm heads are based on relatively small image databases that are not open to the public, and thus no direct comparison is available for competing methods. We describe a gold-standard for morphological sperm analysis (SCIAN-MorphoSpermGS), a dataset of sperm head images wi...

Despite the continuous technical advancements around health information standards, a critical component to their widespread adoption involves political agreement between a diverse set of stakeholders. Countries that have addressed this issue have used diverse strategies. In this vision paper we present the path that Chile is taking to establish a n...

Breast cancer is one of the most common cancers in women worldwide. Patient therapy is widely supported by analysis of immunohistochemically (IHC) stained tissue sections. In particular, the analysis of HER2 overexpression by immunohistochemistry helps to determine when patients are suitable to HER2-targeted treatment. Computational HER2 overexpres...

Resumen La Facultad de Medicina de la Universidad de Chile está llevando a cabo un proceso de transformación de la docencia e incorporación de recursos educativos con la finalidad de mejorar los aprendizajes de los estudiantes. En el presente trabajo se comunica el desarrollo, implementación y evaluación de la incorporación de la Microscopía Virtua...

Optical Flow (OF) approaches for motion estimation calculate vector fields for the apparent velocities of objects in image sequences. In 1981 Horn and Schunck (HS) introduced two basic assumptions: 'brightness value constancy' and 'smooth variation' to estimate a smooth OF field over the entire image -global approach-. In parallel, Lucas and Kanade...

Trypanosoma cruzi calreticulin (TcCRT), a 47-kDa chaperone, translocates from the endoplasmic reticulum to the area of flagellum emergence. There, it binds to complement components C1 and mannan-binding lectin (MBL), thus acting as a main virulence factor, and inhibits the classical and lectin pathways. The localization and functions of TcCRT, once...

Semen analysis is the first step in the evaluation of an infertile couple. Within this process, an accurate and objective morphological analysis becomes more critical as it is based on the correct detection and segmentation of human sperm components. In this paper, we present an improved two-stage framework for detection and segmentation of human s...

Exposure to DNA damaging agents triggers phosphorylation of histone variant H2AX (generating γH2AX) in large chromatin regions flanking DNA lesions, allowing their immunodetection as nuclear foci. Even though a predominance of γH2AX foci in euchromatin has been postulated, foci positioning when DNA insult occurs in replicating eu- or heterochromati...

The cholesterol content of the sperm membrane is regulated during both maturation in the epididymis and capacitation in the female tract, two processes required for the spermatozoa to acquire their fertilising ability. Because Niemann-Pick disease, type C2 (NPC2) protein is one of the most abundant components of the epididymal fluid and contains a...

Mounting evidence indicates that iron accumulation impairs brain function. We have reported previously that addition of sub-lethal concentrations of iron to primary hippocampal neurons produces Ca(2) (+) signals and promotes cytoplasmic generation of reactive oxygen species. These Ca(2) (+) signals, which emerge within seconds after iron addition,...

Cell migration is a complex biological process that involves changes in shape and organization at the sub-cellular, cellular, and supra-cellular levels. Individual and collective cell migration can be assessed in vitro and in vivo starting from the flagellar driven movement of single sperm cells or bacteria, bacterial gliding and swarming, and amoe...

Although progress has been made in resolving the genetic pathways that specify neuronal asymmetries in the brain, little is known about genes that mediate the development of structural asymmetries between neurons on left and right. In this study, we identify daam1a as an asymmetric component of the signalling pathways leading to asymmetric morphoge...

The synaptic efficacy of neurons depends on the number of neurotransmitter receptors in the plasma membrane. The availability of these receptors is controlled by their specific intracellular trafficking routes. γ-Aminobutyric acid type B receptors (GABABRs) are heteromeric proteins consisting of GABABR1 and GABABR2 subunits. These receptors are fou...

Introduction: The use of quantitative image processing techniques evolves into a valuable tool for fast and improved interpretation of biomedical images. The validation of algorithm and expert guided definition of appropriate ground truth data are fundamental steps. However, its definition is not unique, actually among experts sometimes there are d...

In Drosophila photoreceptors Ca(2+)-permeable channels TRP and TRPL are the targets of phototransduction, occurring in photosensitive microvilli and mediated by a phospholipase C (PLC) pathway. Using a novel Drosophila brain slice preparation, we studied the distribution and physiological properties of TRP and TRPL in the lamina of the visual syste...

Optical flow approaches calculate vector fields which determine the apparent velocities of objects in time-varying image sequences. They have been analyzed exten-sively in computer science using both natural and synthetic video sequences. In life sciences, there is an increasing need to extract kinetic information from temporal image sequences whic...

Caveolin-1 is known to promote cell migration, and increased caveolin-1 expression is associated with tumor progression and metastasis. In fibroblasts, caveolin-1 polarization and phosphorylation of tyrosine-14 are essential to promote migration. However, the role of caveolin-1 in migration of metastatic cells remains poorly defined. Here, caveolin...

Microtubule-associated protein 1B (MAP1B) is prominently expressed during early stages of neuronal development and it has been implicated in axonal growth and guidance. MAP1B expression is also found in the adult brain, in areas of significant synaptic plasticity. Here, we demonstrate that MAP1B is present in dendritic spines and we describe a decr...

Quantitative characterization of the lateral structure of curved membranes based on fluorescence microscopy requires knowledge of the fluorophore distribution on the surface. We present an image analysis approach for extraction of the fluorophore distribution on a spherical lipid vesicle from confocal imaging stacks. The technique involves projecti...