PROYECTOS

@article{nokey,

title = {Análisis adaptativo de trayectorias sinusoidales altamente heterogéneas. },

author = {Pablo Grisanti, Bettera Marcat, Eduardo Pulgar, Veronica Marconi.},

url = {https://anales.fisica.org.ar/index.php/analesafa/article/view/2404},

year  = {2023},

date = {2023-12-28},

urldate = {2023-12-28},

journal = {Anales AFA},

volume = {34},

issue = {4},

abstract = {El estudio de la dinámica de espermatozoides tiene distintas aplicaciones en la medicina reproductiva, así como en la acuicultura o industria pecuaria. Con la motivación de lograr un análisis más objetivo y automático de la movilidad poblacional, se desarrolló un software que permite medir parámetros de movimiento representativos de la dinámica espermática a partir de sus trayectorias, como la velocidad media, amplitud y frecuencia de cabeceo. El mismo utiliza un sólo parámetro de ajuste, una ventana temporal inicial para promediar, la cual es optimizada recursivamente para cada célula. Aplicando el mismo a espermatozoides acuáticos seguidos a 400 fps, demuestra ser robusto y adaptable a poblaciones con alta heterogeneidad en sus parámetros de movilidad.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {VolumePeeler: a novel FIJI plugin for geometric tissue peeling to improve visualization and quantification of 3D image stacks.},

author = {Marilyn Gatica, Carlos F. Navarro, Alejandro Lavado, German Reig, Eduardo Pulgar, Paula Llanos, Steffen Härtel, Andrea Ravasio, Cristina Bertocchi, Miguel L. Concha, Mauricio Cerda.},

url = {https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-023-05403-z},

doi = {10.1186/s12859-023-05403-z},

year  = {2023},

date = {2023-07-12},

urldate = {2023-07-12},

journal = {BMC Bioinformatics},

volume = {24},

issue = {1},

abstract = {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 if microscopes can reach the needed depth, their geometry hinders the selection and subsequent analysis of the optical volumes of interest. Computational tools to "peel" tissues by removing specific layers and reducing 3D volume into planar images, can critically improve visualization and analysis.

Results: We developed VolumePeeler, a versatile FIJI plugin for virtual 3D "peeling" of image stacks. The plugin implements spherical and spline surface projections. We applied VolumePeeler to perform peeling in 3D images of spherical embryos, as well as non-spherical tissue layers. The produced images improve the 3D volume visualization and enable analysis and quantification of geometrically challenging microscopy datasets.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Mutation in protein disulfide isomerase A3 causes neurodevelopmental defects by disturbing endoplasmic reticulum proteostasis.},

author = {Danilo Bilches Medinas, Sajid Malik, Esra Yıldız-Bölükbaşı, Janina Borgonovo, Mirva J Saaranen, Hery Urra, Eduardo Pulgar, Muhammad Afzal, Darwin Contreras, Madison T Wright, Felipe Bodaleo, Gabriel Quiroz, Pablo Rozas, Sara Mumtaz, Rodrigo Díaz, Carlos Rozas, Felipe Cabral-Miranda, Ricardo Piña, Vicente Valenzuela, Ozgun Uyan, Christopher Reardon, Ute Woehlbier, Robert H Brown, Miguel Sena-Esteves, Christian Gonzalez-Billault, Bernardo Morales, Lars Plate, Lloyd W Ruddock, Miguel L Concha, Claudio Hetz, Aslıhan Tolun.},

url = {https://www.embopress.org/doi/full/10.15252/embj.2020105531},

doi = {10.15252/embj.2020105531},

year  = {2021},

date = {2021-12-14},

urldate = {2021-12-14},

journal = {The EMBO Journal},

volume = {14},

number = {e105531},

issue = {2},

abstract = {Recessive gene mutations underlie many developmental disorders and often lead to disabling neurological problems. Here, we report identification of a homozygous c.170G>A (p.Cys57Tyr or C57Y) mutation in the gene coding for protein disulfide isomerase A3 (PDIA3, also known as ERp57), an enzyme that catalyzes formation of disulfide bonds in the endoplasmic reticulum, to be associated with syndromic intellectual disability. Experiments in zebrafish embryos show that PDIA3C57Y expression is pathogenic and causes developmental defects such as axonal disorganization as well as skeletal abnormalities. Expression of PDIA3C57Y in the mouse hippocampus results in impaired synaptic plasticity and memory consolidation. Proteomic and functional analyses reveal that PDIA3C57Y expression leads to dysregulation of cell adhesion and actin cytoskeleton dynamics, associated with altered integrin biogenesis and reduced neuritogenesis. Biochemical studies show that PDIA3C57Y has decreased catalytic activity and forms disulfide-crosslinked aggregates that abnormally interact with chaperones in the endoplasmic reticulum. Thus, rare disease gene variant can provide insight into how perturbations of neuronal proteostasis can affect the function of the nervous system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism.},

author = {Eduardo Pulgar, Cornelia Schwayer, Néstor Guerrero, Loreto López, Susana Márquez, Steffen Härtel, Rodrigo Soto, Carl-Philipp Heisenberg, Miguel L Concha.},

url = {https://elifesciences.org/articles/66483},

doi = {10.7554/eLife.66483},

year  = {2021},

date = {2021-08-27},

urldate = {2021-08-27},

journal = {Elife},

number = {10:e66483},

abstract = {The developmental strategies used by progenitor cells to allow a safe journey from their induction place towards the site of terminal differentiation are still poorly understood. Here, we uncovered a mechanism of progenitor cell allocation that stems from an incomplete process of epithelial delamination that allows progenitors to coordinate their movement with adjacent extra-embryonic tissues. Progenitors of the zebrafish laterality organ originate from the superficial epithelial enveloping layer by an apical constriction process of cell delamination. During this process, progenitors retain long-lasting apical contacts that enable the epithelial layer to pull a subset of progenitors on their way to the vegetal pole. The remaining delaminated cells follow the movement of apically attached progenitors by a protrusion-dependent cell-cell contact mechanism, avoiding sequestration by the adjacent endoderm, ensuring their collective fate and allocation at the site of differentiation. Thus, we reveal that incomplete delamination serves as a cellular platform for coordinated tissue movements during development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {KCTD5, a novel TRPM4-regulatory protein required for cell migration as a new predictor for breast cancer prognosis.},

author = {José Rivas, Nicolás Díaz, Ian Silva, Danna Morales, Boris Lavanderos, Alhejandra Álvarez, María Paz Saldías, Eduardo Pulgar, Pablo Cruz, Diego Maureira, Guillermo Flores, Alicia Colombo, Constanza Blanco, Héctor R. Contreras, Fabián Jaña, Ivan Gallegos, Miguel L. Concha, Ariela Vergara-Jaque, Horacio Poblete, Wendy González, Diego Varela, James S. Trimmer, Mónica Cáceres, Oscar Cerda},

url = {https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.201901195RRR},

doi = {10.1096/fj.201901195RRR},

year  = {2020},

date = {2020-04-17},

urldate = {2020-04-17},

journal = {The FASEB Journal},

volume = {34},

issue = {6},

pages = {7847-7865},

abstract = {Transient receptor potential melastatin 4 (TRPM4) is a Ca2+-activated nonselective cationic channel that regulates cell migration and contractility. Increased TRPM4 expression has been related to pathologies, in which cytoskeletal rearrangement and cell migration are altered, such as metastatic cancer. Here, we identify the K+ channel tetramerization domain 5 (KCTD5) protein, a putative adaptor of cullin3 E3 ubiquitin ligase, as a novel TRPM4-interacting protein. We demonstrate that KCTD5 is a positive regulator of TRPM4 activity by enhancing its Ca2+ sensitivity. We show that through its effects on TRPM4 that KCTD5 promotes cell migration and contractility. Finally, we observed that both TRPM4 and KCTD5 expression are increased in distinct patterns in different classes of breast cancer tumor samples. Together, these data support that TRPM4 activity can be regulated through expression levels of either TRPM4 or KCTD5, not only contributing to increased understanding of the molecular mechanisms involved on the regulation of these important ion channels, but also providing information that could inform treatments based on targeting these distinct molecules that define TRPM4 activity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {IRE1α governs cytoskeleton remodelling and cell migration through a direct interaction with filamin A.},

author = {Hery Urra, Daniel R Henriquez, José Cánovas, David Villarroel-Campos, Amado Carreras-Sureda, Eduardo Pulgar, Emiliano Molina 4 6, Younis M Hazari, Celia M Limia, Sebastián Alvarez-Rojas, Ricardo Figueroa, Rene L Vidal, Diego A Rodriguez, Claudia A Rivera, Felipe A Court, Andrés Couve, Ling Qi, Eric Chevet, Ryoko Akai, Takao Iwawaki, Miguel L Concha, Álvaro Glavic, Christian Gonzalez-Billault, Claudio Hetz.},

url = {https://www.nature.com/articles/s41556-018-0141-0},

doi = {10.1038/s41556-018-0141-0},

year  = {2018},

date = {2018-07-16},

urldate = {2018-07-16},

journal = {Nature Cell Biology},

volume = {20},

issue = {8},

pages = {942-953},

abstract = {Maintenance of endoplasmic reticulum (ER) proteostasis is controlled by a signalling network known as the unfolded protein response (UPR). Here, we identified filamin A as a major binding partner of the ER stress transducer IRE1α. Filamin A is an actin crosslinking factor involved in cytoskeleton remodelling. We show that IRE1α controls actin cytoskeleton dynamics and affects cell migration upstream of filamin A. The regulation of cytoskeleton dynamics by IRE1α is independent of its canonical role as a UPR mediator, serving instead as a scaffold that recruits and regulates filamin A. Targeting IRE1α expression in mice affected normal brain development, generating a phenotype resembling periventricular heterotopia, a disease linked to the loss of function of filamin A. IRE1α also modulated cell movement and cytoskeleton dynamics in fly and zebrafish models. This study unveils an unanticipated biological function of IRE1α in cell migration, whereby filamin A operates as an interphase between the UPR and the actin cytoskeleton.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Cell migration: from tissue culture to embryos.},

author = {Germán Reig, Eduardo Pulgar, Miguel L. Concha.},

url = {https://journals.biologists.com/dev/article/141/10/1999/45986/Cell-migration-from-tissue-culture-to-embryos},

year  = {2014},

date = {2014-03-15},

urldate = {2014-03-15},

journal = {Development},

volume = {141},

issue = {100},

abstract = {Cell migration is a fundamental process that occurs during embryo development. Classic studies using in vitro culture systems have been instrumental in dissecting the principles of cell motility and highlighting how cells make use of topographical features of the substrate, cell-cell contacts, and chemical and physical environmental signals to direct their locomotion. Here, we review the guidance principles of in vitro cell locomotion and examine how they control directed cell migration in vivo during development. We focus on developmental examples in which individual guidance mechanisms have been clearly dissected, and for which the interactions among guidance cues have been explored. We also discuss how the migratory behaviours elicited by guidance mechanisms generate the stereotypical patterns of migration that shape tissues in the developing embryo.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Computational methods for analysis of dynamic events in cell migration.},

author = {V Castañeda, M Cerda, F Santibáñez, J Jara, E Pulgar, K Palma, C G Lemus, M Osorio-Reich, M L Concha, S Härtel.},

url = {https://www.eurekaselect.com/article/58824},

doi = {10.2174/1566524014666140128113952},

year  = {2013},

date = {2013-09-27},

urldate = {2013-09-27},

journal = {Current Molecular Medicine},

volume = {14},

issue = {2},

pages = {291-307},

abstract = {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 amoeboid movement to the orchestrated movement of collective cell migration. One key technology to access migration phenomena is the combination of optical microscopy with image processing algorithms. This approach resolves simple motion estimation (e.g. preferred direction of migrating cells or path characteristics), but can also reveal more complex descriptors (e.g. protrusions or cellular deformations). In order to ensure an accurate quantification, the phenomena under study, their complexity, and the required level of description need to be addressed by an adequate experimental setup and processing pipeline. Here, we review typical workflows for processing starting with image acquisition, restoration (noise and artifact removal, signal enhancement), registration, analysis (object detection, segmentation and characterization) and interpretation (high level understanding). Image processing approaches for quantitative description of cell migration in 2- and 3-dimensional image series, including registration, segmentation, shape and topology description, tracking and motion fields are presented. We discuss advantages, limitations and suitability for different approaches and levels of description.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Vitamin C and oxidative stress in the seminiferous epithelium.},

author = {Constanza Angulo, Rodrigo Maldonado, Eduardo Pulgar, Héctor Mancilla, Alex Córdova, Franz Villarroel, Maite A Castro, Ilona I Concha.},

url = {https://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602011000200009&lng=en&nrm=iso&tlng=en},

doi = {http://dx.doi.org/10.4067/S0716-97602011000200009 },

year  = {2011},

date = {2011-03-16},

urldate = {2011-03-16},

journal = {Biological Research},

volume = {144},

issue = {2},

pages = {169-80},

abstract = {In this article, we focus on the fundamental role of vitamin C transporters for the normal delivery of vitamin C to germ cells in the adluminal compartment of seminiferous tubules. We argue that the redox status within spermatozoa or in semen is partly responsible for the etiology of infertility. In this context, antioxidant defence plays a critical role in male fertility. Vitamin C, a micronutrient required for a wide variety of metabolic functions, has long been associated with male reproduction. Two systems for vitamin C transport have been described in mammals. Facilitative hexose transporters (GLUTs), with 14 known isoforms to date, GLUT1-GLUT14, transport the oxidized form of vitamin C (dehydroascorbic acid) into the cells. Sodium ascorbic acid co-transporters (SVCTs), SVCT1 and SVCT2 transport the reduced form of vitamin C (ascorbic acid). Sertoli cells control germ cell proliferation and differentiation through cell-cell communication and form the blood-testis barrier. Because the blood-testis barrier limits direct access of molecules from the plasma into the adluminal compartment of the seminiferous tubule, one important question is the method by which germ cells obtain vitamin C. Some interesting results have thrown light on this matter. Expression of SVCT2 and some isoforms of GLUT transporters in the testis have previously been described. Our group has demonstrated that Sertoli cells express functionally active vitamin C transporters. Kinetic characteristics were described for both transport systems (SVCT and GLUT systems). Sertoli cells are able to transport both forms of vitamin C. These findings are extremely relevant, because Sertoli cells may control the amount of vitamin C in the adluminal compartment, as well as regulating the availability of this metabolite throughout spermatogenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Planar cell polarity signalling regulates cell adhesion properties in progenitors of the zebrafish laterality organ.},

author = {Pablo Oteiza 1, Mathias Köppen, Michael Krieg, Eduardo Pulgar, Cecilia Farias, Cristina Melo, Stephan Preibisch, Daniel Müller, Masazumi Tada, Steffen Hartel, Carl-Philipp Heisenberg, Miguel L Concha},

url = {https://journals.biologists.com/dev/article/137/20/3459/43944/Planar-cell-polarity-signalling-regulates-cell},

doi = {10.1242/dev.049981},

year  = {2010},

date = {2010-10-15},

urldate = {2010-10-15},

journal = {Development},

volume = {137},

issue = {20},

pages = {3459-68},

abstract = {Organ formation requires the precise assembly of progenitor cells into a functional multicellular structure. Mechanical forces probably participate in this process but how they influence organ morphogenesis is still unclear. Here, we show that Wnt11- and Prickle1a-mediated planar cell polarity (PCP) signalling coordinates the formation of the zebrafish ciliated laterality organ (Kupffer's vesicle) by regulating adhesion properties between organ progenitor cells (the dorsal forerunner cells, DFCs). Combined inhibition of Wnt11 and Prickle1a reduces DFC cell-cell adhesion and impairs their compaction and arrangement during vesicle lumen formation. This leads to the formation of a mis-shapen vesicle with small fragmented lumina and shortened cilia, resulting in severely impaired organ function and, as a consequence, randomised laterality of both molecular and visceral asymmetries. Our results reveal a novel role for PCP-dependent cell adhesion in coordinating the supracellular organisation of progenitor cells during vertebrate laterality organ formation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}