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Conclusiones 2023 del Comité Europeo de Derecho Sociales: los incumplimientos de la Carta Social Europea por parte de España
Francisco Giner de los Ríos y las trayectorias del liberalismo social español
In Francisco Giner de los Ríos (Ronda, 1839-Madrid, 1919), like other progressive liberal authors such as J. Dewey, Hobhouse and the first Laski, and within the same specific current of the Spanish krausist Adolfo Posada, education is one of the pillars of democracy, since the aim is to form men ("persons" we would say in today's inclusive language) with decision-making capacity; to form free citizens. The education of the citizen in and for democracy is a constant in the theory of democracy and has been linked to it as an existential condition for public debate to take place in society and in the decision-making process in democratic societies, debate being a dynamic moment that precedes the decision in the framework of a deliberative policy and participatory policy of all individuals (giving them a voice) through different pluralist mechanisms created in civil society.
From his Krausist "ideal of humanity" he thought that law - and the aspiration towards social justice that accompanies it - was embedded in the heart of social development: his social-democratic organicism was also social evolutionism. Consequently, social progress is a living law, which, however, needed to be driven by appropriate reforms. Through this social organicism, the most restless Krausist intellectuals would end up linking organic social liberalism with non-authoritarian state interventionism. This intervention should correct the social and economic dysfunctionalities of industrial modernization (the "social question").
The ideas of Francisco Giner de los Ríos and their implementation through institutional and socio-political actions have been a determining factor in the development of culture and social and pedagogical thought in Spain, with great repercussions in Latin America.En Francisco Giner de los Ríos (Ronda, 1839-Madrid, 1919), al igual que otros autores liberales progresistas como es el caso J. Dewey, Hobhouse y el primer Laski, y dentro de la misma corriente específica del krausista español Adolfo Posada, la educación es uno de los pilares de la democracia, pues de lo que se trata es de formar hombres (“personas” diríamos en el lenguaje inclusivo de hoy) con capacidad de decisión; de formar ciudadanos libres. La educación del ciudadano en y para la democracia es una constante de la teoría de la democracia y se le ha vinculado como una condición existencial para que se puede producir un debate público en la sociedad y en el proceso de toma de decisiones en las sociedades democráticas, siendo el debate un momento dinámico que precede a la decisión en el marco de una política deliberativa y de la política participativa de todos los individuos (dándoles voz) a través de distintos mecanismos pluralistas creados en la sociedad civil.
Desde su “ideal de la humanidad” krausista pensaba que el Derecho –y la aspiración hacia la justicia social que la acompaña- estaba incrustado en el corazón del desarrollo social: su organicismo democrático-social era también evolucionismo social. En consecuencia, el progreso social es una ley vida, que, sin embargo, necesitaba ser impulsada a través de las reformas adecuadas. A través de ese organicismo social los intelectuales krausistas más inquietos acabarían vinculando el liberalismo social orgánico con el intervencionismo estatal no autoritario. Esa intervención debería ser correctora de las disfuncionalidades sociales y económicas de la modernización industrial (la “cuestión social”).
Las ideas de Francisco Giner de los Ríos y su puesta en práctica a través de acciones institucionales y sociopolíticas han sido un factor determinante en el desarrollo de la cultura y del pensamiento social y pedagógico en España, con una gran repercusión en Latinoamérica.
 
La producción vitivinícola en la ciudad altomedieval de Olèrdola y su término castral (Penedès, Barcelona)
The civitas Olerdola was an active border town between the 10th and 11th centuries during the expansion of the county of Barcelona towards the South, to Tarragona and the Ebro River. Archaeological research in recent years within the framework of the ECLOC project (2014-2017, 2018-2021 and 2022-2025, funded by Generalitat de Catalunya) has identified productive areas and numerous wineries located within the fortified enclosure and in the suburbs, highlighting the importance of wine production. The economic weight of vineyard and viticulture in the city and in its terminus castralis or castral territory was already well known through purchases, donations and wills recorded in written sources.La civitas Olerdola fue una ciudad de frontera activa entre los siglos X y XI, durante la fase de expansión del condado de Barcelona hacia Tarragona y el Ebro. La investigación arqueológica de los últimos años en el marco del proyecto ECLOC (2014-2017, 2018-2021 y 2022-2025, financiado por la Generalitat de Catalunya), ha permitido identificar espacios productivos y, entre ellos, numerosos lagares ubicados tanto dentro del recinto fortificado como en el suburbio, poniendo de manifiesto la importancia de la producción vitivinícola. El peso de la viticultura en la economía de la ciudad y su terminus castralis era ya bien conocida a través de las compras, donaciones y testamentos recogidos en las fuentes escritas
Monasterios y Almunias de Córdoba. El control productivo de la periferia urbana en época tardoantigua y omeya
This work explores the extension of peri-urban agricultural sectors in Córdoba, particularly those that were irrigated, from the Late Antique period to the Umayyad period. Historiography has defined a late antique Córdoba surrounded by basilicas, highlightingprimarily its religious role, but often overlooking its residential and productive functions as Christian estates or monasteries. However, both textual and archaeological evidence demonstrate that such spaces had great economic importance. After the Islamic conquest, a good portion of these peri-urban areas gradually came under the control of the Umayyad elites, who developed an extensive network of almunias around the city, largely based on patterns established previously by late antique estates.Este trabajo explora la prolongación de sectores agrícolas periurbanos en Córdoba, particularmente aquellos irrigados, desde época tardoantigua hasta el período omeya. La historiografía ha definido una Córdoba tardoantigua rodeada de basílicas, resaltando fundamentalmente su papel religioso, pero obviando a menudo sus funciones residenciales y productivas en tanto fincas cristianas o monasterios. No obstante, tanto la evidencia textual como arqueológica demuestran que tales espacios tenían una gran importancia económica. Después de la conquista islámica, buena parte de estas áreas periurbanas pasaron gradualmente a estar bajo el control de las élites omeyas, que desarrollaron una extensa red de almunias alrededor de la ciudad, partiendo en gran medida de patrones establecidos previamente por las fincas tardoantiguas
Phosphorylation-mediated regulation of the gamma tubulin complex.
Motivation: Microtubules perform vital functions such as chromosome segregation, nuclear positioning, vesicular transport and determination of cell polarity and morphogenesis. The gamma tubulin complex is an essential element responsible for microtubule nucleation and is highly conserved from yeast to human and the core of the complex is basically composed of three esential proteins (Alp4/GCP2, Alp6/GCP3 and Gtb1/GTB). Its function is subject to a multiple regulation processes both temporally and spatially, and phosphorilation is one of the main postranslational modifications to regulate protein function. The fission yeast Schizosaccharomyces pombe is a potent model for studying microtubules (MT) nucleation because of its simple MT cytoskeleton, genetic tractability, limited number of regulators, and amenability to assays of individual nucleation events. In this work, we use S. pombe to determine the role of different putative phosphorylation sites to understand the regulation of this complex in different stages of the cell cycle.
Methods: In our laboratory, a collection of mutants of Alp4 and Alp6 genes was generated. These mutants consisted of the modification of the phosphorylation sites described in massive phosphoproteomes. Usind directed mutagenesis we generated non-phosphorylatable and phosphomimetic alleles (changins Serines to Alanine or Aspartic acid residues respectively. In this project, a phenotypic analysis of the different mutants from this collection has been performed using different approaches such as spot tests, western blots, fluorescence microscopy with live cells, and genetic interaction analysis techniques.
Results: We found that different mutants display phenotypic differences under the conditions analysed. The most representative phenotypes are related to delayed and aberrant mitotic spindle formation, no mitotic spindle formation and the appearance of stress granules at high temperatures. This establishes a connection between the phosphorylation state of Alp4 and Alp6 with microtubule formation, and its implication in the biology of microtubules in the cell.
Conclusions: Our data suggest that phosphorylation of components of the gamma tubulin complex is involved in the regulation of microtubule nucleation in different stages of the cell cycle and cell phisiology. This shed light in new molecular mechanisms not been previously described
Mechanoregulatory feedback loops in tissue morphogenesis: Functional analysis of genes and cis-regulator elements modulated by mechanical stress.
Gastrulation is a key process in embryonic development, necessary for the formation of the trilaminar embryonic disc. This is the differentiation and redistribution of blastula cells to form the three embryonic layers that will give rise to different functional tissues (ectoderm, mesoderm and endoderm). This reorganization occurs through highly coordinated movements of specific groups of cells in which the entire embryo is involved.
The teleost medaka (Oryzias latipes) has been chosen as experimental animal model. In this species the gastrulation occurs simultaneously with the epibolia process. During this, the cells migrate from the animal pole to the vegetal pole leading to the formation of the embryonic axis, fundamental for the establishment of the vertebrate body plan. Little is known about the morphogenetic processes that occur during epiboly. However, the importance of some elements has been described for this process, as is the case of the members of the Yap family. These proteins are transcriptional regulators that receive signals and mechanical stimuli from the medium and integrate them together with genetic signals. This is necessary for cells to migrate correctly towards the midline of the embryo. If these signals are deregulated, gastrulation may not be properly developed which could even have lethal effects.
To learn more about the role of Yap in gastrulation, we will study the involvement of Yap downstream genes (Afap12, Akap12b, Efs, Glis2b, MarcksL1A/B, Rock2b, Synaptopodin and Ved) in the process of cytoskeletal reorganization, cell adhesion and interaction with the extracellular matrix. For this, the CRISPR-Cas9 system is used to generate knockout mutants of each gene. This genome editing mechanism is a tool adapted from a natural adaptive immune defense system of bacteria and archaea. This tool consists of two components: the sgRNAs, short fragments that match the target sequences of the genome, and the Cas9 endonuclease which cause a double-stranded DNA break in the same place. Afterwards, the cell repairs the affected area of the DNA, causing permanent modifications in the genome.
To perform data analysis we use the STATA statistical software. The preliminary data show special results in the study of Afap12, MarcksL1, Ved and Rock2b. In these cases, there seems to be a difference in the epiboly progress between controls and knockouts
Feasibility of a Klebsiella pneumoniae vaccine: a proposal for a first-in-human trial and future challenges.
Klebsiella pneumoniae is an opportunistic bacteria causing 650.000 deaths worldwideassociated with antibiotic-resistance. K. pneumoniae causes a variety of infections, includinglower-respiratory, urinary-tract, abdominal, thoracic infections, and sepsis, which can leadrapidly to death due to the high level of antibiotic-resistance. The most vulnerable populationsare elderly people with chronic conditions and neonates1.The World-Health Organization and other international agencies are calling for thedevelopment of solutions alternative to antibiotics to combat the rising incidence of diseasecaused by K. pneumoniae worldwide. One type of the sought solutions are vaccines for risingimmunity able to contain the evolution of the infections to invasive disease in the vulnerablepopulation2. One of the vaccines under development is K-vax, a chimeric inactivated whole cellbacterial vaccine developed by Vaxdyn, currently in preclinical stage.Testing vaccines in human trials is a challenge due to the complexity in selecting the trialdesign and the trial population. One decisive step in the development of K-Vax is to design itsfuture clinical study. In this work, we have reviewed the state of the art regarding clinical trialsof vaccines with similarities to K-Vax. The designs have been crossed with available preclinicaldata to define the potential variables of the clinical trial.Thus, using both preclinical data and a database created through an exhaustive searching andanalysis of 34 studies with similar characteristics, our work led to the proposal of a feasible firstin human trial for K-Vax. In particular, after evaluating different scenarios, the most suitablestudy would include a group of at least 90 human volunteers, that could provide safety data toshow the lack of reactogenicity and immunogenicity data to establish a correlation of protectionand test strain coverage of the adjuvanted vaccine. We consider including a sentinel groupfirst, and the whole trial would be carried out in a randomized way, using placebo, doubleblinding, and with a dose escalation scheme, where 2 or 3 doses would be tested.In this work, we have also discussed how the information from the first in human trial couldlead to the design of feasible efficacy trials in subsequent clinical stages to overcome thebarriers for marketing the vaccine3 to prevent disease by K. pneumoniae and fulfill the currenturgent need
Autoinflammatory and immunodeficiency due to loss of function mutation in ELF4.
Background: Inborn errors of immunity (IEI) are defined as monogenetic germline defects characterized by increasedsusceptibility to infections, immune diseases, allergies, and cancers. Recently, a new condition called "deficiency inELF4, X-linked" (DEX) has been identified as a disease of immune dysregulation [1]. DEX patients commonly manifestsymptoms such as fevers, along with various inflammatory manifestations that primarily affect the gastrointestinaltract, as well as notable involvement of the skin [2, 3]. Despite the identification of the condition and the involvementof the ELF4 gene, the specific biological processes and mechanisms by which DEX and ELF4 function results in theobserved symptoms are not completely understood. In addition, a personalized therapy is needed due to thecomplexity of the disease.Objective: Here, we aim to explore the link between ELF4 deficiency and the pro-inflammatory state resulting in theclinical manifestations of these patients. We also pursue to evaluate the ex vivo effects of JAK inhibition.Methods: Using flow cytometry, RT-qPCR and ELISA techniques, the levels of STAT1 and pSTAT1 were examined inIFN stimulated cells obtained from ELF4 deficient, STAT1 GOF patients and healthy controls. By using nCounterFLEX (NanoString) platform and Luminex assay, we quantified expression levels of IFN-response genes and serumcytokine levels.Results: ELF4 deficient and STAT1 GOF patients presented similar phenotype characterized by increased STAT1 andpSTAT1 levels in response to INFa and IFNg. STAT1-downstream gene expression and CXCL10 secretion wereelevated compare to healthy controls. Ex vivo treatment with Ruxolitinib (JAK1/2 inhibitor) reduced STAT1phosphorylation in ELF4 and STAT1 GOF patient cells.Conclusion: These results have improved the comprehension of ELF4 role in autoinflammatory syndromes. However,further investigations are required in order to fully understand the impact of ELF4 deficiency in immunedysregulation and the potential targeted therapies that could benefit those patients including JAK inhibitors
Functional metagenomic for the identification of new lignocellulose-degrading enzymes.
Motivation: Due to the necessity of mitigation of climate change we are facing nowadays, new economic and industrial approaches are needed to be developed. Enzymatic biotechnology has demonstrated to be an efficient tool to reach a more sustainable economic system, allowing to discover enzymatic activities with industrial interest. Nevertheless, there are some limitations on the already discovered enzymes when applied industrially due to the extreme conditions they have to bear, such as high temperatures or pH. Functional metagenomic permits accessing to the genomic information of the vast microbial diversity of a specific ecosystem without the need of prior cultivation of microorganisms and to reveal new and more efficient enzymatic activities without knowing its gene sequence (1). In this project, we focus on the identification of new enzymes for developing a biocatalyst for lignocellulosic revalorization and plastic degradation. For this purpose, we are using specialised vectors and bacterial strains and several metagenomic libraries previously constructed (2, 3). Moreover, we are constructing a new metagenomic library from a compost pile of agro-industrial waste, that must be enriched in lignocellulose and plastic degrading microorganisms.Methods: The methodology applied screening of enzymatic activities consists of conjugating the metagenomic library to E. coli MPO554Nal or MPO554Nal/pMPO1077 strains. Plasmid pMPO1077 contains an inducible autolysis system to facilitate phenotype detection of extracellular enzymes (2). For exoglycanase activity screening, the metagenomic library was transferred to E. coli MPO554Nal and positive clones were selected in M9 agar plates with Avicel as carbon source. For screening of endoglucanase activity, the metagenomic library was transferred to E. coli MPO554Nal/pMPO1077, transconjugants were plated on LB agar plates with 0.7% CMC, and after colonies grew, lysis was induced with anhydrotetracycline (2). After confirmation of positive clones phenotypes, we analyse enzymatic restriction patterns in order to select only different clones for posterior sequencing analysis.Results: To date we have 248 candidates for endoglucanase and 223 for exoglucanase activity from screening of a metagenomic library obtained from the soil of Los Alcornocales natural park (Cádiz). Identification of the genes responsible for each activity will be done by the metagenomic plasmid sequencing and comparation with previuos reported data
Entoleuca sp. as a tool for decreasing the pathogenicity of almond wood fungi.
Motivation: The almond crop has a high socio-economic importance in Spain. The intensification of its management, aimed at increasing productivity, coupled with the current climate change scenario is increasing the incidence of canker diseases in almond. Botryosphaeria dieback is a fungal disease that is increasingly threatening almond and other woody crops worldwide [1]. The causal agents are fungi of the Botryosphaeriaceae family, being Neofusicoccum parvum one of the most virulent species. The limitations in the use of chemical fungicides, due to their impact on humans, animals and the environment, prompted me to investigate biological control strategies for protecting almond fields. The objective of this project was to explore the fungus Entoleuca sp. as a new biological control agent against fungi of the Botryosphaeriaceae family.Methods: Pathogenicity tests were carried out on excised almond shoots to test the aggressivity of five isolates of N. parvum. To evaluate the antagonistic effect of Entoleuca sp. against this pathogenic species, inhibitory assays, involving the growth of Entoleuca sp. on cellophane membranes, were conducted including a collection of 30 Entoleuca sp. and two N. parvum isolates (NpALM2 and F085). In addition, in vitro dual confrontations experiments were carried out in which the percentage of inhibition of the mycelial growth of N. parvum was measured 15 days after the dual confrontation. In this experiment, it was also observed whether the Entoleuca sp. isolates exhibited the capacity to inhibit the growth of N. parvum or if they displayed overgrowth upon them [2].Results: All N. parvum isolates tested produced necrotic lesions on inoculated excised almond shoots. NpALM2 and F085 isolates were the most virulent. Among the 30 Entoleuca sp. isolates evaluated, six (E302-9, E450-9, E471-14, E472-9, E473-2 and E474-11) were selected for exhibiting the best control of N. parvum by inhibiting their mycelial growth around 50%. All the selected Entoleuca sp. isolates controlled better N. parvum F085 than NpALM2 isolate.Conclusions: Entoleuca sp. is a potential biological control agent against the fungus N. parvum pathogenic to almond. The mode of action could be to inhibit the growth of the pathogenic fungus or to overgrowth it. Further experiments should be carried out to evaluate the antagonist of the selected Entoleuca sp. isolates in planta