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Progress Report12685125/04/2022 7:46:48https://web.unican.es/ibbtec/es-es/Lists/Events/AllItems.aspxFalse652022-05-24T22:00:00Z Los Progress Reports del IBBTEC son un ciclo de seminarios de investigación en el que presentan el estado actual de sus proyectos los jóvenes investigadores del IBBTEC y del IDIVAL. Las sesiones se celebran semanalmente en las instalaciones del IBBTEC –aunque durante actualmente, debido a las restricciones sanitarias, se realizan de forma semipresencial, por lo que pueden seguirse online–, y se imparten en inglés.&#160;<div><br></div><div> El ciclo está coordinado por el investigador del IBBTEC Ramón Merino.</div>SeminarioMagdalena Foltman y Daniel MolinaIBBTEC17_Event
The Rho guanosine nucleotide exchange factors Vav2 and Vav3 modulate epidermal stem cell function14272812/05/2022 10:08:02https://web.unican.es/ibbtec/es-es/Lists/Papers/AllItems.aspxFalse405<img alt="" src="/ibbtec/PublishingImages/Journals/Oncogene%2019.png" width="301" style="BORDER&#58;0px solid;" />2022-05-08T22:00:00Z<h3>​Abstract<br></h3><div><br></div><div>It is known that Rho GTPases control different aspects of the biology of skin stem cells (SSCs). However, little information is available on the role of their upstream regulators under normal and tumorigenic conditions in this process. To address this issue, we have used here mouse models in which the activity of guanosine nucleotide exchange factors of the Vav subfamily has been manipulated using both gain- and loss-of-function strategies. These experiments indicate that Vav2 and Vav3 regulate the number, functional status, and responsiveness of hair follicle bulge stem cells. This is linked to gene expression programs related to the reinforcement of the identity and the quiescent state of normal SSCs. By contrast, in the case of cancer stem cells, they promote transcriptomal programs associated with the identity, activation state, and cytoskeletal remodeling. These results underscore the role of these Rho exchange factors in the regulation of normal and tumor epidermal stem cells.<br></div>Lorenzo-Martín LF, Menacho-Márquez M, Fernández-Parejo N, Rodríguez-Fdez S, Pascual G, Abad A, Crespo P, Dosil M, Benitah SA, Bustelo XRIBBTEC17_Paper
Seminario de Doctorado12684825/04/2022 7:43:16https://web.unican.es/ibbtec/es-es/Lists/Events/AllItems.aspxFalse622022-05-03T22:00:00ZSeminarioJúlia SenserrichIBBTEC17_Event
Molecular Signaling Mechanisms for the Antidepressant Effects of NLX-101, a Selective Cortical 5-HT 1A Receptor Biased Agonist13042006/05/2022 12:00:06https://web.unican.es/ibbtec/es-es/Lists/Papers/AllItems.aspxFalse403<img alt="" src="/ibbtec/PublishingImages/Journals/big_cover-pharmaceuticals-v15-i3.jpg" width="282" style="BORDER&#58;0px solid;" />2022-04-14T22:00:00Z<h3>​Abstract<br></h3><div><br></div><div><br></div><div>Depression is the most prevalent of the mental illnesses and serotonin (5-hydroxytryptamine, 5-HT) is considered to be the major neurotransmitter involved in its etiology and treatment. In this context, 5-HT1A receptors have attracted interest as targets for therapeutic intervention. Notably the activation of presynaptic 5-HT1A autoreceptors delays antidepressant effects whereas the stimulation of postsynaptic 5-HT1A heteroreceptors is needed for an antidepressant action. NLX-101 (also known as F15599) is a selective biased agonist which exhibits preferred activation of cortical over brain stem 5-HT1A receptors. Here, we used behavioral, neurochemical and molecular methods to examine the antidepressant-like effects in rats of a single dose of NLX-101 (0.16 mg/kg, i.p.). NLX-101 reduced immobility in the forced swim test when measured 30 min but not 24 h after drug administration. NLX-101 increased extracellular concentrations of glutamate and dopamine in the medial prefrontal cortex, but no changes were detected in the efflux of noradrenaline or 5-HT. NLX-101 also produced an increase in the activation of pmTOR, pERK1/2 and pAkt, and the expression of PSD95 and GluA1, which may contribute to its rapid antidepressant action.<br></div>Cabanu S, Pilar-Cuéllar F, Zubakina P, Florensa-Zanuy E, Senserrich J, Newman-Tancredi A, Adell A.IBBTEC17_Paper
Analysis of laccase-like enzymes secreted by fungi isolated from a cave in northern Spain13093029/04/2022 7:48:42https://web.unican.es/ibbtec/es-es/Lists/Papers/AllItems.aspxFalse401<img alt="" src="/ibbtec/PublishingImages/Journals/mbo31282-gra-0001-m.jpeg" style="BORDER&#58;0px solid;" />2022-04-10T22:00:00Z<h3>​Abstract</h3><div><br></div><div>Laccases belong to a family of multicopper enzymes able to oxidize a broad spectrum of organic compounds. Despite the well-known property of laccases to carry out bleaching and degradation of industrial dyes and polyphenolic compounds, their industrial use is often limited by the high cost, low efficiency, or instability of these enzymes. To look for new microorganisms which produce laccases that are potentially suitable for industrial applications, we have isolated several fungal strains from a cave in northern Spain. Their phenotypic analysis on agar plates supplemented with ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) disclosed two laccase-positive strains. Further genotyping revealed that they belonged to the Gliomastix murorum and Conidiobolus thromboides species. The secretion of G. murorum and C. thromboides laccase-like enzymes was then confirmed by zymography. Further identification of these polypeptides by mass-spectroscopy revealed the nature of the laccases and made it possible to predict their functional domains and other features. In addition, plate assays revealed that the laccases secreted by both G. murorum and C. thromboides were capable of degrading industrial dyes (Congo Red, Indigo, and Eriochrome Black T). Homology modeling and substrate docking predicted the putative structure of the currently uncrystallized G. murorum enzyme as well as its amino acid residues potentially involved in interactions with these dyes. In summary, new biochemical and structural insights into decolorization mediated by G. murorum laccase as well as identification of laccase-like oxidase in C. thromboides point to a promising future for these enzymes in biotechnology.<br></div>Fernández-Remacha D, González-Riancho C, Lastra Osua M, González Arce A, Montánchez I, García-Lobo JM, Estrada-Tejedor R, Kaberdin VR.IBBTEC17_Paper
Isolation and phenotypic and genomic characterization of Tetragenococcus spp. from two Spanish traditional blue-veined cheeses made of raw milk13093229/04/2022 8:15:57https://web.unican.es/ibbtec/es-es/Lists/Papers/AllItems.aspxFalse402<img alt="" src="/ibbtec/PublishingImages/Journals/IJFM2022.jpeg" width="375" style="BORDER&#58;0px solid;" />2022-04-07T22:00:00Z<h3>​Abstract<br></h3><p><br></p><div>High throughput sequencing has recently revealed the presence of Tetragenococcus-related DNA sequences in dairy environments such as brine and cheeses. In the present work, a selective medium was developed to isolate Tetragenococcus spp. from two ripened, traditional, Spanish, blue-veined cheese varieties made from raw milk. The strains recovered belonged to either Tetragenococcus koreensis or Tetragenococcus halophilus species. Twenty of these isolates (15 of T. koreensis and 5 of T. halophilus) were then subjected to a battery of phenotypic and genetic tests, and six strains (4 T. koreensis and 2 T. halophilus) to genome sequencing. Wide genetic and phenotypic diversity was noted. All strains grew poorly in milk, producing small quantities of lactic and acetic acids. Most strains used lactose as a carbon source and ferment milk citrate. In agreement, genome analysis detected in the genome of the six strains analyzed gene clusters harboring several lactose/galactose-related genes and genes encoding citrate metabolic enzymes (permease, citrate lyase, and oxaloacetate decarboxylase). Most of the tested strains were resistant to erythromycin and clindamycin, and a few to other antimicrobial agents, but neither known mutations nor acquired genes conferring resistance to antibiotics were identified in their genomes. Neither were genes coding for pathogenicity or virulence factors detected. Decarboxylase-encoding genes involved in biogenic amine production were not identified, in keeping with the strains' negative biogenic amine-producer phenotype. Genome comparison revealed vast arrays of genes (similar in number to those described in other lactic acid bacteria) coding for components of proteolytic and lipolytic systems. Tetragenococcus strains showing desirable traits plus the absence of detrimental features might be exploitable in the form of secondary, adjunct or ripening cultures to ensure the typical bouquet of traditional blue-veined cheeses is obtained, or to diversify the final flavor in other varieties.<br></div>Rodríguez J, González-Guerra A, Vázquez L, Fernández-López R, Flórez AB, de la Cruz F, Mayo B.IBBTEC17_Paper
Stromal oncostatin M cytokine promotes breast cancer progression by reprogramming the tumor microenvironmentStromal oncostatin M cytokine promotes breast cancer progression by reprogramming the tumor microenvironment14173720/05/2022 10:14:34https://web.unican.es/ibbtec/es-es/Lists/Papers/AllItems.aspxFalse406<img alt="" src="/ibbtec/es-es/PublishingImages/Journals/JCI-132-7.jpeg" style="BORDER&#58;0px solid;" />2022-03-31T22:00:00Z<p><span style="color&#58;#262626;font-family&#58;&quot;segoe ui semilight&quot;, &quot;segoe ui&quot;, segoe, tahoma, helvetica, arial, sans-serif;font-size&#58;1.15em;">Abstract</span><br></p><div><br></div><div>The tumor microenvironment (TME) is reprogrammed by cancer cells and participates in all stages of tumor progression. The contribution of stromal cells to the reprogramming of the TME is not well understood. Here, we provide evidence of the role of the cytokine oncostatin M (OSM) as central node for multicellular interactions between immune and nonimmune stromal cells and the epithelial cancer cell compartment. OSM receptor (OSMR) deletion in a multistage breast cancer model halted tumor progression. We ascribed causality to the stromal function of the OSM axis by demonstrating reduced tumor burden of syngeneic tumors implanted in mice lacking OSMR. Single-cell and bioinformatic analysis of murine and human breast tumors revealed that OSM expression was restricted to myeloid cells, whereas OSMR was detected predominantly in fibroblasts and, to a lower extent, cancer cells. Myeloid-derived OSM reprogrammed fibroblasts to a more contractile and tumorigenic phenotype and elicited the secretion of VEGF and proinflammatory chemokines CXCL1 and CXCL16, leading to increased myeloid cell recruitment. Collectively, our data support the notion that the stromal OSM/OSMR axis reprograms the immune and nonimmune microenvironment and plays a key role in breast cancer progression.<br></div>Araujo AM, Abaurrea A, Azcoaga P et al.IBBTEC17_Paper
Prácticas de verano en el IBBTEC12042021/03/2022 7:22:58https://web.unican.es/ibbtec/es-es/Lists/News/AllItems.aspxFalse65<img alt="" src="/ibbtec/noticias/PublishingImages/Practicas.jpeg" style="BORDER&#58;0px solid;" />2022-03-15T23:00:00Z<p>​<span style="font-family&#58;calibri;font-size&#58;14px;text-align&#58;justify;">El Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC) convoca 2 ayudas para el desarrollo de prácticas de verano en sus laboratorios de investigación desde el 15 de julio al 15 de septiembre de 2022.</span></p><p style="text-align&#58;justify;"><span class="ms-rteFontFace-5" style="font-size&#58;14px;"><br></span></p><p style="text-align&#58;justify;"><span class="ms-rteFontFace-5" style="font-size&#58;14px;"><a href="/unidades/coie/Documents/IBBITEC/Bases%20ayudas%20verano%20IBBITEC%202022.pdf"><img class="ms-asset-icon ms-rtePosition-4" src="/_layouts/15/images/icpdf.png" alt="" style="margin&#58;5px;" />Bases convocatoria 2022&#160;· IBBTEC.pdf</a><br></span></p><p style="text-align&#58;justify;"><br></p><p style="text-align&#58;justify;"><span class="ms-rteFontFace-5" style="font-size&#58;14px;"></span><span style="font-size&#58;14px;font-family&#58;calibri;">Los candidatos deberán acreditar estar matriculados en un Grado (con al menos el 50% de los créditos totales superados) o Máster de alguna disciplina biomédica (biología, biotecnología, biomedicina, farmacia, medicina o similares) durante todo el periodo de prácticas. En cualquiera de los casos se requiere una nota media mínima de 8 sobre 10 en el expediente académico.</span></p><div><p class="subtitle" style="margin-top&#58;1.5em;margin-bottom&#58;1.5em;box-sizing&#58;border-box;padding&#58;5px 5px 0px;border&#58;0px;font-size&#58;14px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;text-align&#58;justify;background-color&#58;#ffffff;"><span class="ms-rteFontFace-5"><span style="box-sizing&#58;border-box;margin&#58;0px;padding&#58;0px;border&#58;0px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;font-weight&#58;700 !important;">Duración y número de las ayudas&#58;</span><br style="box-sizing&#58;border-box;"></span></p><ul style="box-sizing&#58;border-box;margin&#58;0px;padding&#58;0px 0px 0px 40px;border&#58;0px;font-size&#58;14px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;font-family&#58;roboto, tahoma, sans-serif;text-align&#58;justify;background-color&#58;#ffffff;"><li style="box-sizing&#58;border-box;margin&#58;0px;padding&#58;0px;border&#58;0px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;text-align&#58;justify;"><span class="ms-rteFontFace-5">Son financiables 3&#160;ayudas durante el año 2022</span></li><li style="box-sizing&#58;border-box;margin&#58;0px;padding&#58;0px;border&#58;0px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;text-align&#58;justify;"><span class="ms-rteFontFace-5">La duración de cada ayuda será de&#160;<span aria-hidden="true"></span>ocho semanas seguidas durante los meses de julio, agosto y septiembre<span aria-hidden="true"></span></span></li><li style="box-sizing&#58;border-box;margin&#58;0px;padding&#58;0px;border&#58;0px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;text-align&#58;justify;"><span class="ms-rteFontFace-5">Los estudiantes seleccionados por la comisión de evaluación recibirán una ayuda de&#160;</span><span class="ms-rteFontFace-5" style="box-sizing&#58;border-box;margin&#58;0px;padding&#58;0px;border&#58;0px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;font-weight&#58;700 !important;">1500 €</span><span class="ms-rteFontFace-5">&#160;total por el conjunto de los dos meses</span><br></li></ul><div style="text-align&#58;justify;"><font face="Calibri"><span style="font-size&#58;14px;"><br></span></font></div><div style="text-align&#58;justify;"><font face="Calibri"><span style="font-size&#58;14px;"><br></span></font></div><div style="text-align&#58;justify;"><span class="ms-rteFontFace-5" style="box-sizing&#58;border-box;margin&#58;0px;padding&#58;0px;border&#58;0px;font-size&#58;14px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;background-color&#58;#ffffff;font-weight&#58;700 !important;">Documentación requerida&#58;</span></div><div style="text-align&#58;justify;"><font face="Calibri"><span style="font-size&#58;14px;"><strong><br></strong></span></font><span class="ms-rteFontFace-5" style="box-sizing&#58;border-box;margin&#58;0px;padding&#58;0px;border&#58;0px;font-size&#58;14px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;background-color&#58;#ffffff;font-weight&#58;700 !important;"></span><span class="ms-rteFontFace-5" style="font-size&#58;14px;background-color&#58;#ffffff;"></span><ul style="box-sizing&#58;border-box;margin&#58;0px;padding&#58;0px 0px 0px 40px;border&#58;0px;font-size&#58;14px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;background-color&#58;#ffffff;"><li style="box-sizing&#58;border-box;margin&#58;0px;padding&#58;0px;border&#58;0px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;text-align&#58;justify;"><span class="ms-rteFontFace-5">Certificación académica de los años cursados de Educación Superior</span></li><li style="box-sizing&#58;border-box;margin&#58;0px;padding&#58;0px;border&#58;0px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;text-align&#58;justify;"><span class="ms-rteFontFace-5">Curriculum Vitae del solicitante</span></li><li style="box-sizing&#58;border-box;margin&#58;0px;padding&#58;0px;border&#58;0px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;text-align&#58;justify;"><span class="ms-rteFontFace-5">Pueden presentarse cartas de presentación que actúen de aval</span></li><li style="box-sizing&#58;border-box;margin&#58;0px;padding&#58;0px;border&#58;0px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;text-align&#58;justify;"><span class="ms-rteFontFace-5">Carta de motivación que incluya posibles prioridades de investigación según los intereses del candidato. Las principales líneas de investigación del IBBTEC pueden consultarse en nuestra página web&#58;&#160;</span><a href="http&#58;//www.unican.es/ibbtec/" style="color&#58;#195b5f;box-sizing&#58;border-box;margin&#58;0px;padding&#58;0px;border&#58;0px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;transition&#58;all 0.2s ease-in-out 0s, color 0.2s ease-in-out 0s;cursor&#58;pointer;"><span class="ms-rteFontFace-5">http&#58;//www.unican.es/ibbtec/</span></a></li></ul><p style="box-sizing&#58;border-box;padding&#58;0px;border&#58;0px;font-size&#58;14px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;background-color&#58;#ffffff;"></p><p style="box-sizing&#58;border-box;padding&#58;0px;border&#58;0px;font-size&#58;14px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;background-color&#58;#ffffff;"><span class="ms-rteFontFace-5">La documentación deberá enviarse a través del formulario de participación del COIE (<span aria-hidden="true"></span><a href="https&#58;//bit.ly/3MPv0zj">https&#58;//bit.ly/3MPv0zj</a><span aria-hidden="true"></span></span><span class="ms-rteFontFace-5">) antes del&#160;</span><span class="ms-rteFontFace-5" style="box-sizing&#58;border-box;margin&#58;0px;padding&#58;0px;border&#58;0px;vertical-align&#58;baseline;outline&#58;0px;min-width&#58;auto;font-weight&#58;700 !important;">29 de abril a las 13&#58;00h</span><span class="ms-rteFontFace-5">. La comunicación de las resoluciones se realizará la segunda semana de mayo de 2022.</span></p></div></div>IBBTEC17_News
PP2A-Cdc55 phosphatase regulates actomyosin ring contraction and septum formation during cytokinesis5134607/03/2022 7:53:185https://web.unican.es/ibbtec/es-es/Lists/Papers/AllItems.aspxFalse3952022-02-28T23:00:00Z<h3>​Abstract</h3><div><br></div><div>Eukaryotic cells divide and separate all their components after chromosome segregation by a process called cytokinesis to complete cell division. Cytokinesis is highly regulated by the recruitment of the components to the division site and through post-translational modifications such as phosphorylations. The budding yeast mitotic kinases Cdc28-Clb2, Cdc5, and Dbf2-Mob1 phosphorylate several cytokinetic proteins contributing to the regulation of cytokinesis. The PP2A-Cdc55 phosphatase regulates mitosis counteracting Cdk1- and Cdc5-dependent phosphorylation. This prompted us to propose that PP2A-Cdc55 could also be counteracting the mitotic kinases during cytokinesis. Here we show that in the absence of Cdc55, AMR contraction and the primary septum formation occur asymmetrically to one side of the bud neck supporting a role for PP2A-Cdc55 in cytokinesis regulation. In addition, by in vivo and in vitro assays, we show that PP2A-Cdc55 dephosphorylates the chitin synthase II (Chs2 in budding yeast) a component of the Ingression Progression Complexes (IPCs) involved in cytokinesis. Interestingly, the non-phosphorylable version of Chs2 rescues the asymmetric AMR contraction and the defective septa formation observed in cdc55∆ mutant cells. Therefore, timely dephosphorylation of the Chs2 by PP2A-Cdc55 is crucial for proper actomyosin ring contraction. These findings reveal a new mechanism of cytokinesis regulation by the PP2A-Cdc55 phosphatase and extend our knowledge of the involvement of multiple phosphatases during cytokinesis.<br></div>Yolanda Moyano-Rodríguez, David Vaquero, Odena Vilalta-Castany, Magdalena Foltman, Alberto Sanchez-Diaz & Ethel QueraltIBBTEC17_Paper
Combination of Resminostat with Ruxolitinib Exerts Antitumor Effects in the Chick Embryo Chorioallantoic Membrane Model for Cutaneous T Cell Lymphoma13042206/05/2022 12:07:57https://web.unican.es/ibbtec/es-es/Lists/Papers/AllItems.aspxFalse404<img alt="" src="/ibbtec/PublishingImages/Journals/big_cover-cancers-v14-i4.png" style="BORDER&#58;0px solid;" />2022-02-19T23:00:00Z<h3>​Abstract<br></h3><p><br></p><p>The combination of Resminostat (HDACi) and Ruxolitinib (JAKi) exerted cytotoxic effects and inhibited proliferation of CTCL cell lines (MyLa, SeAx) in previously published work. A xenograft tumor formation was produced by implanting the MyLa or SeAx cells on top of the chick embryo chorioallantoic membrane (CAM). The CAM assay protocol was developed to monitor the metastatic properties of CTCL cells and the effects of Resminostat and/or Ruxolitinib in vivo. In the spontaneous CAM assays, Resminostat and Ruxolitinib treatment inhibited the cell proliferation (p &lt; 0.001) of MyLa and SeAx, and induced cell apoptosis (p &lt; 0.005, p &lt; 0.001, respectively). Although monotherapies reduced the size of primary tumors in the metastasis CAM assay, the drug combination exhibited a significant inhibition of primary tumor size (p &lt; 0.0001). Furthermore, the combined treatment inhibited the intravasation of MyLa (p &lt; 0.005) and SeAx cells (p &lt; 0.0001) in the organs, as well as their extravasation to the liver (p &lt; 0.0001) and lung (p &lt; 0.0001). The drug combination also exerted a stronger inhibitory effect in migration (p &lt; 0.0001) rather in invasion (p &lt; 0.005) of both MyLa and SeAx cells. It further reduced p-p38, p-ERK, p-AKT, and p-STAT in MyLa cells, while it decreased p-ERK and p-STAT in SeAx cells in CAM tumors. Our data demonstrated that the CAM assay could be employed as a preclinical in vivo model in CTCL for pharmacological testing. In agreement with previous in vitro data, the combination of Resminostat and Ruxolitinib was shown to exert antitumor effects in CTCL in vivo.<br></p>Karagianni F, Piperi C, Casar B, de la Fuente-Vivas D, García-Gómez R, Lampadaki K, Pappa V, Papadavid E.IBBTEC17_Paper