Los contratos sobre el buque en Derecho Español. Análisis práctico

Prólogo / José Luis Gabaldón García (pp. 9-13). -- Introducción (pp. 15-18). -- El contrato de construcción naval: aspectos prácticos / Gonzalo Alvar Ezquerra (pp. 19-37). -- El contrato de compraventa / Carlos López-Quiroga, Luz Martínez de Azcoitia y José Sánchez-Fayos Martín-Peña (pp. 39-58). -- El contrato de arrendamiento de buque / Rodolfo González Lebrero (pp. 59-75). -- El contrato de fletamento por tiempo / José María Alcántara González (pp. 77-102). -- El contrato de fletamento por viaje: contenido obligacional / Juan Pablo Rodríguez Delgado (pp. 103-144). -- El contrato de transporte marítimo en régimen de conocimiento de embarque / Javier del Corte (pp. 145-186). -- Los documentos de transporte / Carlos Llorente (pp. 187-205). -- Contratos de utilización del buque para fines distintos del transporte de mercancías / José Manuel G. Pellicer (pp. 207-221). -- El contrato de arrendamiento náutico / León von Ondarza (pp. 223-244). -- El contrato de pasaje marítimo / Hannah de Bustos, Antonio Quirós de Sas y Julio López Quiroga (pp. 245-260). -- Los contratos de gestión naval para la dotación del buque / Bernardo Ruiz Lima (pp. 261-279). -- El contrato de gestión naval / Víctor Mata Garrido (pp. 281-302). -- El contrato de consignación de buques /Jesús Barbadillo Eyzaguirre (pp. 303-323). -- El contrato de manipulación portuaria / Carlos Pérez (pp. 325-338). -- El contrato de practicaje / Alicia Velasco Nates (pp. 339-356). -- Los contratos de mediación en la explotación del buque / Carmen Codes Cid y Martín Prieto Sulleiro (pp. 357-372). -- El contrato de remolque / Ana Sánchez Horneros (pp. 373- 392). -- El contrato de remolque / Jaime de Castro (pp. 393-412). -- El contrato de salvamento / Luis Souto (pp. 413-430). -- El contrato de remoción de restos / Verónica Meana (pp. 431-446). -- El contrato de clasificación del buque / Jaime Rodrigo de Larrucea (pp. 447-463). -- El seguro de casco y máquina / Carlos Cerdá Donat y Diego de San Simón Palacios (pp. 465-491). -- Los clubes de protección e indemnización (P&I) / Miguel Caballero (pp. 493-504). -- El seguro de protección e indemnización (P&I) / Jaime Albors (pp. 505-524). -- El seguro del acreedor hipotecario / Luis F. Gómez de Mariaca Fernández (pp. 525-540)

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Repair of Rat Mandibular Bone Defects by Alveolar Osteoblasts in a Novel Plasma-Derived Albumin Scaffold

9 páginas, 6 figuras, 1 tabla.-- et al.Repair of bone deficiencies in the craniofacial skeleton remains a difficult clinical problem. The aim of this study was to evaluate a novel albumin scaffold seeded with human alveolar osteoblasts and implanted into experimental mandibular defects. An experimental solid protein scaffold was prepared with human plasmatic albumin crossed with a glutaraldehyde-type agent. Microstructure of scaffold and mechanical properties were examined using scanning electron microscopy and a stress-controlled rheometer. Bilateral critical mandibular defects were created in eight immunodeficient rats. Defects of the right side of the mandibles received the cell–scaffold construct in all animals. All left mandibular defects were left untreated as blank controls. Sections of the defects were collected at 5, 8, and 11 weeks postsurgery and processed for histological and immunohistochemical observation, computed tomography examination, and computed tomography digital analysis. Histologically, bone formation was observed in both groups at 5 weeks postsurgery, and the engineered bone became more mature after 8 and 11 weeks, which was similar to normal bone. The origin of bone-forming cells within the defects and the localization of implanted human osteoblasts were confirmed by human vimentin expression. No bone formation could be observed at any control defect. Bone density after 8 weeks was significantly higher than that of the 5-week group (p = 0.02), and significant differences were also observed between 8 and 11 weeks (p < 0.01). The results indicate the clinical feasibility of albumin scaffold loaded with human alveolar cells and that it can be used as a good alternative for bone regeneration.This study was supported by the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III (PI070174).Peer reviewe

UPR pathway contributes to the underlying depressive-like phenotype in a mouse model overexpressing human ¿-synuclein

Trabajo presentado en el ECNP Workshop for Early Career Scientists in Europe, celebrado en Niza (Francia) del 16 al 19 de marzo de 202

Sex differences, endoplasmic reticulum stress and ketamine effect in mouse model overexpressing human ¿-synuclein in serotonin neurons

Trabajo presentado en el 35th ECNP Congress, celebrado en Viena (Austria), del 15 al 18 de octubre de 202

Sex differences in mouse model overexpressing human ¿-Synuclein in serotonin neurons: endoplasmic reticulum stress and ketamine effect

Trabajo presentado en el XII Simposi de Neurobiologia, Societat Catalana de Biologia, celebrado en Barcelona (España), los días 7 y 8 de junio de 202

Sex differences in behavioral phenotype and markers of the unfolded protein response (UPR) pathway in a mouse model overexpressing human ¿-synuclein

Trabajo presentado en el congreso del FENS (Federation of European Neuroscience Societies), celebrado en Paris (France) del 9 al 13 de julio de 202

Mithramycin delivery systems to develop effective therapies in sarcomas

Sarcomas comprise a group of aggressive malignancies with very little treatment options beyond standard chemotherapy. Reposition of approved drugs represents an attractive approach to identify effective therapeutic compounds. One example is mithramycin (MTM), a natural antibiotic which has demonstrated a strong antitumour activity in several tumour types, including sarcomas. However, its widespread use in the clinic was limited by its poor toxicity profile. Results In order to improve the therapeutic index of MTM, we have loaded MTM into newly developed nanocarrier formulations. First, polylactide (PLA) polymeric nanoparticles (NPs) were generated by nanoprecipitation. Also, liposomes (LIP) were prepared by ethanol injection and evaporation solvent method. Finally, MTM-loaded hydrogels (HG) were obtained by passive loading using a urea derivative non-peptidic hydrogelator. MTM-loaded NPs and LIP display optimal hydrodynamic radii between 80 and 105 nm with a very low polydispersity index (PdI) and encapsulation efficiencies (EE) of 92 and 30%, respectively. All formulations show a high stability and different release rates ranging from a fast release in HG (100% after 30 min) to more sustained release from NPs (100% after 24 h) and LIP (40% after 48 h). In vitro assays confirmed that all assayed MTM formulations retain the cytotoxic, anti-invasive and anti-stemness potential of free MTM in models of myxoid liposarcoma, undifferentiated pleomorphic sarcoma and chondrosarcoma. In addition, whole genome transcriptomic analysis evidenced the ability of MTM, both free and encapsulated, to act as a multi-repressor of several tumour-promoting pathways at once. Importantly, the treatment of mice bearing sarcoma xenografts showed that encapsulated MTM exhibited enhanced therapeutic effects and was better tolerated than free MTM. Conclusions Overall, these novel formulations may represent an efficient and safer MTM-delivering alternative for sarcoma treatment.Peer ReviewedPostprint (published version

Abrogation of stemness in osteosarcoma by the mithramycin analog EC-8042 is mediated by its ability to inhibit NOTCH-1 signaling

Osteosarcomas are frequently associated to a poor prognosis and a modest response to current treatments. EC-8042 is a well-tolerated mithramycin analog that has demonstrated an efficient ability to eliminate tumor cells, including cancer stem cell subpopulations (CSC), in sarcomas. In transcriptomic and protein expression analyses, we identified NOTCH1 signaling as one of the main pro-stemness pathways repressed by EC-8042 in osteosarcomas. Overexpression of NOTCH-1 resulted in a reduced anti-tumor effect of EC-8042 in CSC-enriched 3D tumorspheres cultures. On the other hand, the depletion of the NOTCH-1 downstream target HES-1 was able to enhance the action of EC-8042 on CSCs. Moreover, HES1 depleted cells failed to recover after treatment withdrawal and showed reduced tumor growth potential in vivo. In contrast, mice xenografted with NOTCH1-overexpressing cells responded worse than parental cells to EC-8042. Finally, we found that active NOTCH1 levels in sarcoma patients was associated to advanced disease and lower survival. Overall, these data highlight the relevant role that NOTCH1 signaling plays in mediating stemness in osteosarcoma. Moreover, we demonstrate that EC-8042 is powerful inhibitor of NOTCH signaling and that the anti-CSC activity of this mithramycin analog highly rely on its ability to repress this pathway.This work was supported by the Agencia Estatal de Investigación (AEI) [MICINN/Fondo Europeo de Desarrollo Regional (FEDER) (grant PID2019–106666RB-I00 to R.R.) and ISC III/FEDER (Consorcio CIBERONC - CB16/12/00390)] and the Plan de Ciencia Tecnología e Innovación del Principado de Asturias/FEDER [grant IDI/2021/000027 and Severo Ochoa predoctoral fellowships BP-17–108 to O.E., BP‐ 20–046 to B.G. and BP-21–084 to DM]

Selective Knockdown of TASK3 Potassium Channel in Monoamine Neurons: a New Therapeutic Approach for Depression

Current pharmacological treatments for major depressive disorder (MDD) are severely compromised by both slow action and limited efficacy. RNAi strategies have been used to evoke antidepressant-like effects faster than classical drugs. Using small interfering RNA (siRNA), we herein show that TASK3 potassium channel knockdown in monoamine neurons induces antidepressant-like responses in mice. TASK3-siRNAs were conjugated to cell-specific ligands, sertraline (Ser) or reboxetine (Reb), to promote their selective accumulation in serotonin (5-HT) and norepinephrine (NE) neurons, respectively, after intranasal delivery. Following neuronal internalization of conjugated TASK3-siRNAs, reduced TASK3 mRNA and protein levels were found in the brainstem 5-HT and NE cell groups. Moreover, Ser-TASK3-siRNA induced robust antidepressant-like behaviors, enhanced the hippocampal plasticity, and potentiated the fluoxetine-induced increase on extracellular 5-HT. Similar responses, yet of lower magnitude, were detected for Reb-TASK3-siRNA. These findings provide substantial support for TASK3 as a potential target, and RNAi-based strategies as a novel therapeutic approach to treat MDD.This work was supported by the following grants: SAF2015-68346-P (F.A.); SAF2013-48586-R (J.M.); SAF2016-75797-R (A.B.); Retos-Colaboración Subprograms RTC-2014-2812-1 and RTC-2015-3309-1 (A.B.); Ministry of Economy and Competitiveness (MINECO)—European Regional Development Fund (ERDF), UE; PI13/01390, Instituto de Salud Carlos III co-financed by ERDF (A.B.); IT616-13 Basque Government—ERDF (J.M.); 20003 NARSAD Independent Investigator (A.B.); and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). CERCA Programme/Generalitat de Catalunya is also acknowledged. M.N.F. and A.F-C. are recipients of a fellowship from the Spanish Ministry of Education, Culture and Sport.Peer reviewe