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[ES] El proyecto trata el desarrollo de un nuevo modelo habitacional entendido como un organismo con vida propia que apuesta por la autosuficiencia y proporciona al habitante el poder de la acción individual. Se trata de una comunidad transitoria localizada en el periurbano este del barrio de Benimaclet, en Valencia, cuyo eje motor es la recuperación de la huerta, ahondando en sus valores productivo, paisajístico y natural. Las viviendas, reciclables y sostenibles, acogerán a personas en riesgo de exclusión social por lo que la comunidad será un punto de confluencia de diferentes culturas e ideologías. Además, se dará cabida a usos auxiliares vinculados a la acción social, educación y relaciones interpersonales., [EN] The project deals with the development of a new housing model understood as a living organism base on the self-sufficiency and the power of individual action. It is a transitory community located in the eastern peri-urban neighborhood of Benimaclet, in Valencia, whose driving force is the recovery of the vegetable garden, delving into its productive, landscape and natural values. The homes, recyclable and sustainable, will welcome people at risk of social exclusion so the community will be a point of confluence of different cultures and ideologies. In addition, the community will develop auxiliary uses about social action, education and interpersonal relationships.

Vertebrate Hox genes are critical for the establishment of structures during the development of the main body axis. Subsequently, they play important roles either in organizing secondary axial structures such as the appendages, or during homeostasis in postnatal stages and adulthood. Here, we set up to analyze their elusive function in the ectodermal compartment, using the mouse limb bud as a model. We report that the HoxC gene cluster was co-opted to be transcribed in the distal limb ectoderm, where it is activated following the rule of temporal colinearity. These ectodermal cells subsequently produce various keratinized organs such as nails or claws. Accordingly, deletion of the HoxC cluster led to mice lacking nails (anonychia), a condition stronger than the previously reported loss of function of Hoxc13, which is the causative gene of the ectodermal dysplasia 9 (ECTD9) in human patients. We further identified two mammalian-specific ectodermal enhancers located upstream of the HoxC gene cluster, which together regulate Hoxc gene expression in the hair and nail ectodermal organs. Deletion of these regulatory elements alone or in combination revealed a strong quantitative component in the regulation of Hoxc genes in the ectoderm, suggesting that these two enhancers may have evolved along with the mammalian taxon to provide the level of HOXC proteins necessary for the full development of hair and nail.

John Francis Fallon, a widely respected developmental biologist, revered teacher and mentor, distinguished colleague, critical yet constructive editor, inspiring leader, devoted family man, and dear friend passed away on February 11, 2020. John was born in Boston, Massachusetts, on March 21, 1938, and he grew up in Massachusetts, Indiana, and California. He attended high school at Roosevelt Military Academy (named in honor of Theodore Roosevelt) in Aledo, Illinois, and he attended college at Marquette University in Milwaukee, Wisconsin, where he majored in philosophy and biology. At Marquette, John met two people who would shape his life: Elaine (nee Degnan), his wife for 57 years and the mother of his three children; and Professor John W. Saunders, Jr., who would determine John's future career choice by instilling in him a passion for scientific discovery, especially in the field of developmental biology. After receiving a PhD under Saunders' tutelage, John served 2 years in the US Army Service Corps before being recruited as an Assistant Professor to the University of Wisconsin, Madison, where he progressively advanced through the ranks. He remained at the University of Wisconsin throughout his career, with his retirement on December 31, 2009, being celebrated on April 15, 2010, with the John Fallon Symposium held in Madison in his honor.

Classical tissue recombination experiments performed in the chick embryo provide evidence that signals operating during early limb development specify the position and identity of feathers. Here, we show that Sonic hedgehog (Shh) signalling in the embryonic chick wing bud specifies positional information required for the formation of adult flight feathers in a defined spatial and temporal sequence that reflects their different identities. We also reveal that Shh signalling is interpreted into specific patterns of Sim1 and Zic transcription factor expression, providing evidence of a putative gene regulatory network operating in flight feather patterning. Our data suggest that flight feather specification involved the co-option of the pre-existing digit patterning mechanism and therefore uncovers an embryonic process that played a fundamental step in the evolution of avian flight.

In the tetrapod limb, the digits (fingers or toes) are the elements most subject to morphological diversification in response to functional adaptations. However, despite their functional importance, the mechanisms controlling digit morphology remain poorly understood. Here we have focused on understanding the special morphology of the thumb (digit 1), the acquisition of which was an important adaptation of the human hand. To this end, we have studied the limbs of the Hoxa13 mouse mutant that specifically fail to form digit 1. We show that, consistent with the role of Hoxa13 in Hoxd transcriptional regulation, the expression of Hoxd13 in Hoxa13 mutant limbs does not extend into the presumptive digit 1 territory, which is therefore devoid of distal Hox transcripts, a circumstance that can explain its agenesis. The loss of Hoxd13 expression, exclusively in digit 1 territory, correlates with increased Gli3 repressor activity, a Hoxd negative regulator, resulting from increased Gli3 transcription that, in turn, is due to the release from the negative modulation exerted by Hox13 paralogs on Gli3 regulatory sequences. Our results indicate that Hoxa13 acts hierarchically to initiate the formation of digit 1 by reducing Gli3 transcription and by enabling expansion of the 5′Hoxd second expression phase, thereby establishing anterior−posterior asymmetry in the handplate. Our work uncovers a mutual antagonism between Gli3 and Hox13 paralogs that has important implications for Hox and Gli3 gene regulation in the context of development and evolution.

Desde el Vicerrectorado de Innovación y Empresa de la UPCT y el Centro de Orientación e Información de Empleo, se dio a conocer las múltiples posibilidades laborales que tienen las titulaciones que se imparten, de la mano de profesionales del sector, estudiantes titulados y profesores de los Centros. El acto estaba dirigido a futuros estudiantes universitarios, padres, orientadores de IES y cualquier persona interesada. Estudiantes preuniversitarios y sus familiares llenaron el salón de actos del edificio Cajamar en Murcia para conocer las titulaciones técnicas de la Universidad Politécnica de Cartagena y sus salidas profesionales de la mano de profesores, exalumnos que describieron su trayectoria laboral y empresas que emplean a egresados de la UPCT.

[EN] Phototoxic effects of 6,8 dihalogenated quinolones confers to this type of molecules a potential property as photochemotherapeutic agents. Two photodehalogenation processes seem to be involved in the remarkable photoinduced cellular damage. In this context, a new 6,8 dihalogenated quinolone 1 (1-methyl-6,8-difluoro-4-oxo-7-aminodimethy1-1,4-dihydroquinoline-3-carboxylic acid) was synthesized looking for improving the phototoxic properties of fluoroquinolones (FQ) and to determine the role of the photodegradation pathways in the FQ phototoxicity. With this purpose, fluorescence emissions, laser flash photolysis experiments and photodegradation studies were performed with compound 1 using 1-ethyl-6,8-difluoro-4-oxo-7-aminodimethy1-1,4-dihidroquinoline-3-carboxylic acid (2) and lomefloxacin (LFX) as reference compounds. The shortening of alkyl chain of the N(1) of the quinolone ring revealed a lifetime increase of the reactive aryl cation generated from photolysis of the three FQ and a significant reduction of the FQ photodegradation quantum yield. The fact that these differences were smaller when the same study was done using a hydrogen donor solvent (ethanol-aqueous buffer, 50/50 v/v) evidenced the highest ability of the reactive intermediate arising from 1 to produce intermolecular alkylations. These results were correlated with in vitro 3T3 NRU phototoxicity test. Thus, when PhotoIrritation-Factor (PIF) was determined for 1, 2 and LFX using cytotoxicity profiles of BALB/c 3T3 fibroblasts treated with each compound in the presence and absence of UVA light, a PIF more higher than 30 was obtained for 1 while the values for 2 and LFX were only higher than 8 and 10, respectively. Thereby, the present study illustrates an approach to modulate the photosensitizing properties of FQ with the purpose to improve the chemotherapeutic properties of antitumor quinolones. Moreover, the results obtained in this study also evidence that the key pathway responsible for the phot

[EN] Cholesterol (Ch) is an integral part of cell membrane, where it is prone to oxidation. In humans, oxidation of Ch is commonly linked to various pathologies like Alzheimer's disease, atherosclerosis, and even cancer, which proceed via mechanisms involving enzymatic and free radical pathways. The latter begin with hydrogen abstraction (HA) from Ch by a reactive free radical. It has been established that the most efficient HA from Ch occurs at C7, although HA from C4 by peroxyl radicals has recently been observed. Conversely, HA from Ch positions other than the thermodynamically preferred C7 or C4 has never been reported. We have designed a Ch derivative where a benzophenone moiety is linked to C7 by a covalent bond. This mirrors a specific orientation of Ch within a confined environment. Product analysis and time-resolved spectroscopic studies reveal an unprecedented HA from C15, which is a thermodynamically unfavorable position. This indicates that a specific topology of reactants is crucial for the reactivity of Ch. The relative orientation of the reactants can also be relevant in biological membranes, where Ch, polyunsaturated fatty acids, and numerous oxidizing species are confined in highly restricted and anisotropic environments.

[ES] Objetivos del proyecto: -Dotar a los equipos tácticos que operan sobre el terreno realizando actividades de influencia y obtención de información de zona, de unos procedimientos operativos con los que obtengan el mayor rendimiento en el desarrollo y desempeño de sus responsabilidades dentro del cumplimiento de su misión. -Implementar los procedimientos ya establecidos con métodos que confieran una mayor calidad a los productos generados por los equipos tácticos (TPT) así como a sus esfuerzos de difusión. -Proporcionar al Mando una herramienta de calidad que transfiera mayores garantías en el proceso de toma de decisiones minimizando riesgos.

During limb development, the Lmx1b homeodomain transcription factor is restricted to dorsal mesenchyme and is required for distal dorsalization. Lmx1b also contributes to kidney, eye and cerebellar development. Haploinsufficiency of the human LMX1B genes causes Nail-Patella Syndrome (NPS) characterized by nail dysplasia, absent or hypoplastic patellae, eye abnormalities, and progressive kidney disease. In the functional Lmx1b knockout mouse, transcription of the mutant Lmx1b mRNA in the limb is reduced, indicating a role for Lmx1b in an auto-amplifying feedback loop. Previous Lmx1b-targeted ChIP-seq data identified two Lmx1b-associated regulatory modules (LARM1/2) bound by Lmx1b. Herein, we demonstrate that LARM1/2 activity overlaps Lmx1b expression in the dorsal limb mesoderm and is dependent on conserved Lmx1b binding sites for activity. We also demonstrate interaction between the LARM enhancers and the Lmx1b promoter. In addition, we performed a targeted CRISPR-Cas excision of the LARM1/2 region in mice; loss of LARM1/2 reduced the expression of Lmx1b in normal mice and generated a phenotype with nearly symmetrical ventral-ventral distal limbs. LARM1/2 loss was limb-specific and did not affect any other Lmx1b-related organs. We extended our investigation to humans with an NPS phenotype that lacked a variation within the LMX1B coding sequence. In two families with a limb-restricted phenotype, loss-of-function variations in the LARM region were identified. These data indicate that the limb-specific expression of Lmx1b is amplified through an auto-regulatory loop involving LARM1/2. Furthermore, disruption of LARM1/2 function can cause isolated limb malformations in mice and human NPS.

The flight feathers of the wing are unique amongst feather types in possessing bilateral asymmetry and forming ligamentous connections to the ulna and digits, features which are important for their function in bird flight. Classical tissue recombination experiments have suggested a role for signals acting in the early chick limb bud in specifying the position and identity of feathers. In this study we show the Sonic Hedgehog is a key signal which provides a positional information gradient necessary for the production of adult flight feathers. We reveal that Shh signalling specifies the identity of feathers in a defined sequence that closely mirrors the order in which it specifies the anterior to posterior pattern of digits. In addition, we use RNA-sequencing to understand how Shh signalling acting early in the limb bud is required for the activation of a molecular programme for flight feathers much later in development. We identify a number of genes, including Sim1 and Zic1, whose expression is spatially and temporally associated with the flight feather domain. Our results unexpectedly reveal polarising region-derived Sonic Hedgehog as an important molecular player in flight feather development. We suggest that a key transition in the evolution of flight feathers and flight itself may have been the co-option of the pre-existing digit patterning mechanism to patterning of feathers on the integument of the wing.

Water pollution by wastewater containing dyes is an environmental issue that can be mitigated by the use of advanced oxidation processes (AOP). Pulsed light (PL) is an emerging food processing technology that uses eco-friendly lamps and can potentially be adapted as light source of an UV-based AOP. In the present work, a PL/H 2 O 2 process was tested for the decolourization of two azo dyes, and a pulsed light/H 2 O 2 /ferrioxalate process was tested for the decolourization of one azo dye. The efficiency of the PL/H 2 O 2 process in a batch reactor under different parametric values: dye concentration, pH, H 2 O 2 and salt doses was followed by spectrophotometry and fitted to first-order kinetics; and several degradation products were detected. In the PL/H 2 O 2 process, decolourization rates increased at low dye concentrations and high H 2 O 2 doses, were pH-dependent and were inhibited by the addition of NaCl, Na 2 SO 3 or Na 2 CO 3. More than 50% decolouration was achieved with the PL/H 2 O 2 process for both dyes after applying 54 J/cm 2 (25 light pulses). The PL/H 2 O 2 /ferrioxalate process achieved >95% decolouration for Methyl orange when applying 21 J/cm 2 (10 pulses); that level of energy can be supplied by PL commercial systems in nine and four seconds respectively. No known toxic degradation products were detected. Results show that a PL/H 2 O 2 process has potential to be used for the efficient degradation of dyes from wastewater. Furthermore, the efficacy of this process can be improved by the use of ferrioxalate. PL technology could become an alternative light source to contribute to decrease the environmental impact of wastewater produced by the dyeing industry. © 2019

[EN] In this work, the attention is focused on UVA-photosensitized reactions triggered by a DNA chromophore-containing lesion, namely 5-formyluracil. This is a major oxidatively generated lesion that exhibits an enhanced light absorption in the UVB-UVA region. The mechanistic study combining photochemical and photobiological techniques shows that irradiation of S-formyluracil leads to a triplet excited state capable of sensitizing formation of cyclobutane pyrimidine dimers in DNA via a triplet-triplet energy transfer. This demonstrates for the first time that oxidatively generated DNA damage can behave as an intrinsic sensitizer and result in an important extension of the active fraction of the solar spectrum with photocarcinogenic potential. Overall, this raises the question of an aggravated photomutagenicity of the 5-formyluracil lesion.

[EN] Diclofenac (DCF) can cause adverse reactions such as gastrointestinal, renal and cardiovascular disorders; therefore, topical administration may be an attractive alternative to the management of local pain in order to avoid these side effects. However, previous studies have shown that DCF, in combination with sunlight, displays capability to induce photosensitivity disorders. In humans, DCF is biotransformed into hydroxylated metabolites at positions 4¿ and 5 (4¿OH-DCF and 5OH-DCF), and this chemical change produces non negligible alterations of the drug chromophore, resulting in a significant modification of its light-absorbing properties. In the present work, 5OH-DCF exhibited higher photo(geno)toxic potential than the parent drug, as shown by several in vitro assays (3T3 NRU phototoxicity, DNA ssb gel electrophoresis and COMET), whereas 4¿OH-DCF did not display significant photo(geno)toxicity. This could be associated, at least partially with their more efficient UV-light absorption by 5OH-DCF metabolite and with a higher photoreactivity. Interestingly, most of the cellular DNA damage photosensitized by DCF and 5OH-DCF was repaired by the cells after several hours, although this effect was not complete in the case of 5OH-DCF.

La parcela desde el principio se planteó subdividida en dos partes con vistas a resolver la relación barrio-paseo: la antigua Calle del Castell de Pop que ahora se convertía en calle peatonal, quedaría cubierta y albergaría el mercado temporal, en el resto de días de la semana funcionaría como paseo cubierto que conectaría con el parque oeste. La antigua parcela del cine de verano albergaría el mercado. Se dividió el sistema en dos grandes grupos: puestos de carnes y pescados, a los que se dotará de una circulación de dirección única, formando un pasillo donde la introducción de luz natural será controlada y desde el cual se tendrá acceso perpendicularmente a las otras partes del mercado; y puestos de frutas y verduras, que no requieren de un control tan exhaustivo del ambiente permitiendo un contacto más directo con el exterior y conformando un sistema de circulaciones más diverso y menos controlado.

En la actualidad son numerosos los estudios que demuestran los beneficios de la actividad física en el rendimiento cognitivo. Entre los procesos incluidos en el rendimiento cognitivo o función ejecutiva se destacan tres componentes fundamentales en el aprendizaje y en el éxito académico: control inhibitorio, memoria de trabajo y flexibilidad cognitiva. En la misma línea, encontramos cada vez más propuestas educativas que incluyen la inteligencia emocional como un factor relevante en el éxito académico y en la formación integral de las personas. Integrando ambos componentes, función ejecutiva e inteligencia emocional, la presente propuesta de intervención educativa tiene como objetivo incrementar el control inhibitorio motriz en niños de Educación Infantil a través del recurso metodológico del cuento motor, con el objetivo de influir sobre el rendimiento académico aumentando la atención, la memoria de trabajo y la inhibición

The distal part of the tetrapod limb, the autopod, is characterized by the presence of digits. The digits display a wide diversity of shapes and number reflecting selection pressure for functional adaptation. Despite extensive study, the different aspects of digit patterning, as well as the factors and mechanisms involved are not completely understood. Here, we review the evidence implicating Hox proteins in digit patterning and the interaction between Hox genes and the Sonic hedgehog/Gli3 pathway, the other major regulator of digit number and identity. Currently, it is well accepted that a self-organizing Turing-type mechanism underlies digit patterning, this being understood as the establishment of an iterative arrangement of digit/interdigit in the hand plate. We also discuss the involvement of 5’ Hox genes in regulating digit spacing in the digital plate and therefore the number of digits formed in this self-organizing system.

The longstanding view of how proliferative outgrowth terminates following the patterning phase of limb development involves the breakdown of reciprocal extrinsic signalling between the distal mesenchyme and the overlying epithelium (e-m signalling). However, by grafting distal mesenchyme cells from late stage chick wing buds to the epithelial environment of younger wing buds, we show that this mechanism is not required. RNA sequencing reveals that distal mesenchyme cells complete proliferative outgrowth by an intrinsic cell cycle timer in the presence of e-m signalling. In this process, e-m signalling is required permissively to allow the intrinsic cell cycle timer to run its course. We provide evidence that a temporal switch from BMP antagonism to BMP signalling controls the intrinsic cell cycle timer during limb outgrowth. Our findings have general implications for other patterning systems in which extrinsic signals and intrinsic timers are integrated.

The Stockholm Convention (SC) on Persistent Organic Pollutants (POPs) calls for the Parties’ effectiveness evaluation of those measures taken to meet the reduction and eventual elimination of POPs from the environment. With that goal, air concentrations of different POP families have been measured uninterruptedly since 2008 under the Spanish Monitoring Program (SMP) by means of passive air sampling. This work focuses on data for polybrominated diphenyl ethers (PBDEs) determined in a total of 321 samples collected seasonally each year in 5 urban and 7 background sites. Neither significant temporal trends nor significant seasonal variations for total PBDE air burdens were detected. In contrast, significant variations were found among PBDE congeners. Those related to the octa-PBDE formulation significantly decreased in the study period. However, PBDEs related to the penta-formulation showed steady concentrations while PBDE-209, the congener found at the greatest levels, showed increasing or steady levels in most sampling sites. Seasonal variations were also markedly different among congeners. Concentrations of the lightest PBDEs (tri- to penta-substituted) were highly influenced by ambient temperature (T), showing maximum values in summer probably due to higher volatilization rates compared to those of heavier PBDEs. Contrarily, no clear seasonal trends were found for hexa- to deca-PBDEs, which were negatively related to precipitation; thereby, indicating an efficient atmospheric wash out by wet deposition episodes. Regarding spatial patterns, overall significant greater PBDE levels were found in cities compared to background areas, pointing out the role of highly populated areas as sources for these pollutants in Spain. Yet and especially in the case of PBDE-209, our results suggested the presence of significant unknown sources of PBDEs in some background sites. Further monitoring efforts are needed to assess potential unknown sources in the sampling network as well a

Time series (2008–2015) of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) in ambient air from the Spanish Monitoring Program were analyzed. A total of 321 samples were collected seasonally each year in 5 urban and 7 background sites by means of passive air sampling. Air concentrations were higher at urban than background sites (urban vs. background concentration ranges): PCDD/Fs (26.9–1010 vs. 20.0–357 fg/m), non-ortho PCBs (0.113–3.14 vs. 0.042–2.00 pg/m) and mono-ortho PCBs (0.644–41.3 vs. 0.500–32.8 pg/m). Results showed significant decreases from 2009 for non-ortho PCBs and PCDD/Fs as well as for WHO-TEQs. These declines were sharper, and sometimes only significant, in urban places resulting in converging levels at urban and background sites for these pollutants at the end of the study period. In contrast, mono-ortho PCBs did not show any significant variation but a steady flat temporal behavior in their concentrations, suggesting the existence of different sources between mono-ortho and non-ortho PCBs. Seasonality was observed for air burdens of all these POPs. PCDD/Fs were mostly measured at higher concentrations in colder than in hot seasons, and the opposite was true for dl-PCBs. Seasonal variations for PCDD/Fs appeared to be related to changes in their sources (e.g. domestic heating, open burning) rather than to temperature per se. In contrast, environmental temperature dependent factors (e.g. increased partitioning into the gas phase) drove seasonal variations in dl-PCBs instead of seasonal changes in their sources. Regarding spatial patterns, significant greater levels of PCDD/Fs and dl-PCBs were generally found in cities compared to background areas, pointing out the role of densely populated areas as sources for these pollutants in Spain. As proven by our results, long-term monitoring activities are essential to assess and understand temporal behaviors for these POPs, as well as to evalu