The Multi-Kinase Inhibitor EC-70124 Is a Promising Candidate for the Treatment of FLT3-ITD-Positive Acute Myeloid Leukemia

Simple Summary: Patients with AML harboring constitutively active mutations in the FLT3 receptor generally have a poor prognosis (FLT3-ITDMUT). Despite the fact that several FLT3 inhibitors have been developed, clinical responses are commonly partial or not durable, highlighting the need for new molecules targeting FLT3-ITDMUT. Here, we tested EC-70124, a hybrid indolocarbazole analog from the same chemical space as midostaurin (a well-known FLT3 inhibitor). Our in vitro and in vivo experiments showed that EC-70124 exerts a robust and specific antileukemia activity against FLT3- ITDMUT AML cells while sparing healthy hematopoietic cells. Collectively, EC-70124 is a promising and safe agent for the treatment of this aggressive type of AML.Funding: We thank CERCA/Generalitat de Catalunya and Fundació Josep Carreras-Obra Social la Caixa for institutional support. This research was funded by the Spanish Ministry of Economy and Competitiveness (RTC-2016-4603-1 in collaboration with Entrechem, PID2019-108160RBI00/ AEI/10.13039/501100011033), the Interreg V-A program (POCTEFA) 2014–2020 (grant PROTEOblood EFA360/19), Health Canada (H4080-144541) and Deutsche Josep Carreras Leukämie Stiftung in collaboration with I.J. to P.M. (15R/2021). P.M. and M.R.-O. also acknowledge the support from ISCIII-RICORS within the Next Generation EU program (plan de recuperación, transformación y resiliencia). Additional funding was provided by Consejería de Salud y Familia (PI-0119-2019) to RDG, the Health Institute Carlos III (FIS PI20/00822), Asociación Española Contra el Cáncer (PRYGN211192BUEN) and Ministerio de Ciencia e Innovacion (PLE2021-007518 and PI20/00822) to C.B. M.V. was supported by Juan de la Cierva fellowship (IJCI-2017-33172). B.L.-M. was supported by the Asociación Española Contra el Cáncer (INVES20011LÓPE) and Consejería de Salud y Familia (PEER-0028-2020).Supplementary Materials: The following are available online at https://www.mdpi.com/article/10 .3390/cancers14061593/s1, Figure S1: Uncropped blots.Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Patients with AML harboring a constitutively active internal tandem duplication mutation (ITDMUT) in the FMS-like kinase tyrosine kinase (FLT3) receptor generally have a poor prognosis. Several tyrosine kinase/FLT3 inhibitors have been developed and tested clinically, but very few (midostaurin and gilteritinib) have thus far been FDA/EMA-approved for patients with newly diagnosed or relapse/refractory FLT3-ITDMUT AML. Disappointingly, clinical responses are commonly partial or not durable, highlighting the need for new molecules targeting FLT3-ITDMUT AML. Here, we tested EC-70124, a hybrid indolocarbazole analog from the same chemical space as midostaurin with a potent and selective inhibitory effect on FLT3. In vitro, EC-70124 exerted a robust and specific antileukemia activity against FLT3-ITDMUT AML primary cells and cell lines with respect to cytotoxicity, CFU capacity, apoptosis and cell cycle while sparing healthy hematopoietic (stem/progenitor) cells. We also analyzed its efficacy in vivo as monotherapy using two different xenograft models: an aggressive and systemic model based on MOLM-13 cells and a patient-derived xenograft model. Orally disposable EC-70124 exerted a potent inhibitory effect on the growth of FLT3-ITDMUT AML cells, delaying disease progression and debulking the leukemia. Collectively, our findings show that EC-70124 is a promising and safe agent for the treatment of AML with FLT3-ITDMUT.Asociación Española Contra el Cáncer INVES20011LÓPE, PEER-0028-2020Consejería de Salud y Familia PI-0119-2019Generalitat de Catalunya and Fundació Josep CarrerasISCIII-RICORSJuan de la Cierva fellowship IJCI-2017-33172Ministerio de Ciencia e Innovacion PI20/00822, PLE2021-007518Interreg EFA360/19Centres de Recerca de CatalunyaHealth Canada H4080-144541Ministerio de Economía y Competitividad PID2019-108160RBI00/AEI/10.13039/501100011033, RTC-2016-4603-1Instituto de Salud Carlos III FIS PI20/00822José Carreras Leukämie-Stiftung 15R/202

Experiencia docente en la asignatura Genética Aplicada mediante el uso de TICs

El principal objetivo de esta comunicación es presentar la plataforma de docencia virtual que hemos diseñado para la asignatura Genética Aplicada, correspondiente a la Licenciatura de Biología de la Universidad de Jaén, y la experiencia docente que hemos tenido con la misma. Para analizar el uso y valoración que los alumnos hacen de la plataforma virtual de la asignatura, hemos llevado a cabo una encuesta anónima entre el alumnado. De esta encuesta se han obtenido una serie de conclusiones interesantes. En general, los alumnos valoran muy positivamente la organización y estructura que le hemos aplicado a la plataforma, siendo la valoración global bastante buena. Dentro de las pocas mejoras que demandan los alumnos, la posibilidad de foros y chats son las más requeridas

NG2 antigen is a therapeutic target for MLL-rearranged B-cell acute lymphoblastic leukemia

Altres ajuts: This work has been supported by the Asociación Española Contra el Cáncer (AECC), Beca FERO, and OM are supported by postdoctoral fellowships from the AECC scientific foundation and the Catalunya Government (Beatriu de Pinos, BP00048), respectively. PM also acknowledges the financial support from the Obra Social La Caixa-Fundaciò Josep Carreras and "Premio Miguelín".B cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer, with cure rates of ∼80%. MLL-rearranged (MLLr) B-ALL (MLLr-B-ALL) has, however, an unfavorable prognosis with common therapy refractoriness and early relapse, and therefore new therapeutic targets are needed for relapsed/refractory MLLr-B-ALL. MLLr leukemias are characterized by the specific expression of chondroitin sulfate proteoglycan-4, also known as neuron-glial antigen-2 (NG2). NG2 was recently shown involved in leukemia invasiveness and central nervous system infiltration in MLLr-B-ALL, and correlated with lower event-free survival (EFS). We here hypothesized that blocking NG2 may synergize with established induction therapy for B-ALL based on vincristine, glucocorticoids, and l-asparaginase (VxL). Using robust patient-derived xenograft (PDX) models, we found that NG2 is crucial for MLLr-B-ALL engraftment upon intravenous (i.v.) transplantation. In vivo blockade of NG2 using either chondroitinase-ABC or an anti-NG2-specific monoclonal antibody (MoAb) resulted in a significant mobilization of MLLr-B-ALL blasts from bone marrow (BM) to peripheral blood (PB) as demonstrated by cytometric and 3D confocal imaging analysis. When combined with either NG2 antagonist, VxL treatment achieved higher rates of complete remission, and consequently higher EFS and delayed time to relapse. Mechanistically, anti-NG2 MoAb induces neither antibody-dependent cell-mediated not complement-dependent cytotoxicity. NG2 blockade rather overrides BM stroma-mediated chemoprotection through PB mobilization of MLLr-B-ALL blasts, thus becoming more accessible to chemotherapy. We provide a proof of concept for NG2 as a therapeutic target for MLLr-B-ALL

Robustness of dead Cas9 activators in human pluripotent and mesenchymal stem cells

Human pluripotent stem cells (hPSCs) and mesenchymal stromal/stem cells (hMSCs) are clinically relevant sources for cellular therapies and for modeling human development and disease. Many stem cell-based applications rely on the ability to activate several endogenous genes simultaneously to modify cell fate. However, genetic intervention of these cells remains challenging. Several catalytically dead Cas9 (dCas9) proteins fused to distinct activation domains can modulate gene expression when directed to their regulatory regions by a specific single-guide RNA (sgRNA). In this study, we have compared the ability of the first-generation dCas9-VP64 activator and the second-generation systems, dCas9-SAM and dCas9-SunTag, to induce gene expression in hPSCs and hMSCs. Several stem cell lines were tested for single and multiplexed gene activation. When the activation of several genes was compared, all three systems induced specific and potent gene expression in both single and multiplexed settings, but the dCas9-SAM and dCas9-SunTag systems resulted in the highest and most consistent level of gene expression. Simultaneous targeting of the same gene with multiple sgRNAs did not result in additive levels of gene expression in hPSCs nor hMSCs. We demonstrate the robustness and specificity of second-generation dCas9 activators as tools to simultaneously activate several endogenous genes in clinically relevant human stem cells.We thank CERCA/Generalitat de Catalunya and Fundació Josep Carreras-Obra Social la Caixa for their institutional support. We thank Jose Luis Sardina (IJC, Barcelona) for technical assistance with the teratoma assays. Financial support for this work was obtained from the Catalunya Goverment (SGR330 and PERIS 2017-2019), the Spanish Ministry of Economy and Competitiveness (SAF2016-80481-R), the European Research Council (CoG-2014-646903), and the Fundación Leo Messi to P.M.; the Spanish Association against Cancer (AECC-CI-2015) and the Health Institute Carlos III (ISCIII/FEDER, PI17/01028) to C.B.; the Biotechnology and Biological Sciences Research Council (BBRSC) to L.M.F. and A.F.; and the Spanish National Research and Development Plan (ISCIII/FEDER, PI17/02303) and the AEI/MICIU EXPLORA Project (BIO2017-91272-EXP) to S.R.-P. P.M. is an investigator of the Spanish Cell Therapy Cooperative Network (TERCEL). R.T.-R. is supported by a postdoctoral fellowship from the Asociación Española Contra el Cáncer (AECC).S

Bone Marrow Clonogenic Myeloid Progenitors from NPM1-Mutated AML Patients Do Not Harbor the NPM1 Mutation: Implication for the Cell-Of-Origin of NPM1+ AML

The cell-of-origin of NPM1- and FLT3-mutated acute myeloid leukemia (AML) is still a matter of debate. Here, we combined in vitro clonogenic assays with targeted sequencing to gain further insights into the cell-of-origin of NPM1 and FLT3-ITD-mutated AML in diagnostic bone marrow (BM) from nine NPM1+/FLT3-ITD (+/-) AMLs. We reasoned that individually plucked colony forming units (CFUs) are clonal and reflect the progeny of a single stem/progenitor cell. NPM1 and FLT3-ITD mutations seen in the diagnostic blasts were found in only 2/95 and 1/57 individually plucked CFUs, suggesting that BM clonogenic myeloid progenitors in NPM1-mutated and NPM1/FLT3-ITD-mutated AML patients do not harbor such molecular lesions. This supports previous studies on NPM1 mutations as secondary mutations in AML, likely acquired in an expanded pool of committed myeloid progenitors, perhaps CD34-, in line with the CD34-/low phenotype of NPM1-mutated AMLs. This study has important implications on the cell-of-origin of NPM1+ AML, and reinforces that therapeutic targeting of either NPM1 or FLT3-ITD mutations might only have a transient clinical benefit in debulking the leukemia, but is unlikely to be curative since will not target the AML-initiating/preleukemic cells. The absence of NPM1 and FLT3-ITD mutations in normal clonogenic myeloid progenitors is in line with their absence in clonal hematopoiesis of indeterminate potential.We thank CERCA/Generalitat de Catalunya and Fundació Josep Carreras-Obra Social la Caixa for their institutional support. Financial support for this work was obtained from the Generalitat de Catalunya (SGR330) to P.M., the Spanish Ministry of Economy and Competitiveness (SAF2016-80481-R to P.M. and SAF2016-76758-R to I.V.), the Fundación Uno entre Cienmil, the Obra Social La Caixa (ID 100010434, under agreement LCF/PR/HR19/52160011), the Josep Carreras Foundation, the Leo Messi Foundation, and the Banco Santander Foundation to P.M.; and the Spanish Association against cancer (AECC-CI-2015) to C.B. E.A. acknowledges support form “Fundación Hay Esperanza”. P.M. is an investigator of the Spanish Cell Therapy cooperative network (TERCEL)

Detailed Characterization of Mesenchymal Stem/Stromal Cells from a Large Cohort of AML Patients Demonstrates a Definitive Link to Treatment Outcomes

Altres ajuts: Health Canada's Genomics Research and Development Initiative Phase VI (H4080-144541-2014-2019); Obra Social La Caixa-Fundació Josep Carreras and the Generalitat de Catalunya (SGR330); Asociación Española Contra el Cáncer (AECC-CI-2015)Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are key components of the hematopoietic niche thought to have a direct role in leukemia pathogenesis. BM-MSCs from patients with acute myeloid leukemia (AML) have been poorly characterized due to disease heterogeneity. We report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. Stable MSC cultures were successfully established and characterized from 40 of 46 AML patients irrespective of the risk subgroup. AML-derived BM-MSCs never harbored tumor-specific cytogenetic/molecular alterations present in blasts, but displayed higher clonogenic potential than healthy donor (HD)-derived BM-MSCs. Although HD- and AML-derived BM-MSCs equally provided chemoprotection to AML cells in vitro, AML-derived BM-MSCs were more immunosuppressive/anti-inflammatory, enhanced suppression of lymphocyte proliferation, and diminished secretion of pro-inflammatory cytokines. Multivariate analysis revealed that the level of interleukin-10 produced by AML-derived BM-MSCs as an independent prognostic factor negatively affected overall survival. Collectively our data show that AML-derived BM-MSCs are not tumor related, but display functional differences contributing to therapy resistance and disease evolution. In this article, Díaz de la Guardia and colleagues report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. BM-MSCs never harbored tumor-specific cytogenetic/molecular alterations present in blasts, and IL-10 produced by AML-derived BM-MSCs is an independent prognostic factor negatively impacting on overall survival

Saúde ambiental de parques espanhóis: Abordagem ao potencial alergénico dos espaços verdes urbanos

Urban parks are green infrastructure elements that should contribute to improving the quality of life and well-being of citizens. In this work there are presented the results of applying a new index to estimate the potential allergenicity of parks located in 20 Spanish cities. This index, which considers intrinsic biological and biometric parameters of existing plant species in parks, allows the allergenic risk thereof to be calculated on a scale ranging from 0 to 1, depending on whether to the park’s allergenicity is zero or has a high risk for the population. The parks selected for this study have different typologies, sizes, species richness and biodiversities, which has yielded highly variable index values. Almost half of the analysed parks have an index value higher than 0.30, a threshold considered having a moderate to high risk, and therefore, enough to cause allergy symptoms in the population. Conversely, most of the parks had an index value below this threshold, so that the risk of suffering allergies is low or very low. The formula also allows the species that most contribute to the resulting value for allergenicity to be known, which are those having an anemophilous strategy of pollination, extended periods of flowering, and a referenced high allergenicity. These requirements are met by all species of the Betulaceae, Cupressaceae and Moraceae families, and to a lesser extent by Oleaceae and Platanaceae. It can be concluded that the development of an index to estimate the allergenicity of urban green spaces constitutes a useful tool to minimize the impact of pollen allergy on the population.Los parques urbanos son elementos de la infraestructura verde que deben contribuir a mejorar la calidad de vida y el bienestar ciudadano. En este trabajo se presentan los resultados de la aplicación de un novedoso índice que estima la alergenicidad potencial de las zonas verdes urbanas. Este índice, que contempla parámetros biológicos y biométricos intrínsecos a las especies arbóreas existentes en los parques, genera un resultado cuyo valor está comprendido entre 0 y 1 según el potencial alergénico del parque sea nulo o de riesgo alto para la población. En una primera fase el índice se ha aplicado a parques de diferente tipología, diseño, tamaño, riqueza específica y biodiversidad ubicados en 20 ciudades españolas. Los resultados han mostrado que algunos de los parques estudiados registran un valor de índice superior a 0.30, umbral suficiente para causar síntomas de alergia a la población expuesta, y por tanto, de riesgo moderado o alto. Por el contrario, en la mayoría de los parques se obtuvo un valor inferior a este umbral. También es posible conocer cuáles son las especies que más contribuyen al valor resultante, que son aquellas con estrategia de polinización anemófila, periodos de oración extensos y alta alergenicidad referenciada. Estos requisitos los cumplen todas las especies de las familias Betuláceas, Cupresáceas y Moráceas, y en menor extensión, Oleáceas y Platanáceas. Puede concluirse que el desarrollo de un índice de estimación de alergenicidad de espacios verdes urbanos constituye una herramienta de utilidad para minimizar el impacto de la alergia polínica en la población.Os parques urbanos são elementos da infraestrutura verde que devem contribuir para a melhoria da qualidade de vida dos cidadãos. Neste trabalho apresentam-se os resultados da aplicação de um índice inovador, que permite estimar a alergenicidade potencial dos espaços verdes urbanos. Este índice, que inclui parâmetros biológicos e biométricos, intrínsecos às próprias espécies existentes nos parques, tem como resultado um valor numa escala entre 0 e 1, de acordo com o potencial alergénico do parque, caso este seja, respetivamente e nos seus extremos, nulo ou de máximo risco para as populações. O índice foi aplicado em parques de diferentes tipologias, desenho, tamanho, riqueza específica e biodiversidade, situados em 20 cidades espanholas. Os resultados demonstram que alguns dos parques estudados registam um valor de índice superior a 0.30, limite su ciente para causar sintomas de alergia na população exposta, e por tanto, risco moderado a alto. No entanto, a maioria dos parques apresenta um valor inferior a este limite. Também é possível conhecer quais as espécies que mais contribuem para o valor do índice, que correspondem aquelas com a estratégia de polinização anemófila, períodos de oração extensos e potencial alergénico referenciado. Estes requisitos são aplicáveis a todas as espécies das famílias Betuláceas, Cupressáceas e Moráceas, e em menor medida, Oleáceas e Platanáceas. Pode assim concluir-se que a aplicação de um índice de previsão dos níveis de alergenicidade dos espaços verdes urbanos constitui uma ferramenta útil para minimizar o impacto da alergia polínica sobre a população

Saúde ambiental de parques espanhóis: Abordagem ao potencial alergénico dos espaços verdes urbanos

Los parques urbanos son elementos de la infraestructura verde que deben contribuir a mejorar la calidad de vida y el bienestar ciudadano. En este trabajo se presentan los resultados de la aplicación de un novedoso índice que estima la alergenicidad potencial de las zonas verdes urbanas. Este índice, que contempla parámetros biológicos y biométricos intrínsecos a las especies arbóreas existentes en los parques, genera un resultado cuyo valor está comprendido entre 0 y 1 según el potencial alergénico del parque sea nulo o de riesgo alto para la población. En una primera fase el índice se ha aplicado a parques de diferente tipología, diseño, tamaño, riqueza específica y biodiversidad ubicados en 20 ciudades españolas. Los resultados han mostrado que algunos de los parques estudiados registran un valor de índice superior a 0,30, umbral suficiente para causar síntomas de alergia a la población expuesta, y por tanto, de riesgo moderado o alto. Por el contrario, en la mayoría de los parques se obtuvo un valor inferior a este umbral. También es posible conocer cuáles son las especies que más contribuyen al valor resultante, que son aquellas con estrategia de polinización anemófila, periodos de floración extensos y alta alergenicidad referenciada. Estos requisitos los cumplen todas las especies de las familias Betuláceas, Cupresáceas y Moráceas, y en menor extensión, Oleáceas y Platanáceas. Puede concluirse que el desarrollo de un índice de estimación de alergenicidad de espacios verdes urbanos constituye una herramienta de utilidad para minimizar el impacto de la alergia polínica en la población.Urban parks are green infrastructure elements that should contribute to improving the quality of life and well-being of citizens. In this work there are presented the results of applying a new index to estimate the potential allergenicity of parks located in 20 Spanish cities. This index, which considers intrinsic biological and biometric parameters of existing plant species in parks, allows the allergenic risk thereof to be calculated on a scale ranging from 0 to 1, depending on whether to the park’s allergenicity is zero or has a high risk for the population. The parks selected for this study have different typologies, sizes, species richness and biodiversities, which has yielded highly variable index values. Almost half of the analysed parks have an index value higher than 0.30, a threshold considered having a moderate to high risk, and therefore, enough to cause allergy symptoms in the population. Conversely, most of the parks had an index value below this threshold, so that the risk of suffering allergies is low or very low. The formula also allows the species that most contribute to the resulting value for allergenicity to be known, which are those having an anemophillous strategy of pollination, extended periods of flowering, and a referenced high allergenicity. These requirements are met by all species of the Betulaceae, Cupressaceae and Moraceae families, and to a lesser extent by Oleaceae and Platanaceae. It can be concluded that the development of an index to estimate the allergenicity of urban green spaces constitutes a useful tool to minimize the impact of pollen allergy on the population.Os parques urbanos são elementos da infraestrutura verde que devem contribuir para a melhoria da qualidade de vida dos cidadãos. Neste trabalho apresentam-se os resultados da aplicação de um índice inovador, que permite estimar a alergenicidade potencial dos espaços verdes urbanos. Este índice, que inclui parâmetros biológicos e biométricos, intrínsecos às próprias espécies existentes nos parques, tem como resultado um valor numa escala entre 0 e 1, de acordo com o potencial alergénico do parque, caso este seja, respetivamente e nos seus extremos, nulo ou de máximo risco para as populações. O índice foi aplicado em parques de diferentes tipologias, desenho, tamanho, riqueza específica e biodiversidade, situados em 20 cidades espanholas. Os resultados demonstram que alguns dos parques estudados registam um valor de índice superior a 0,30, limite suficiente para causar sintomas de alergia na população exposta, e por tanto, risco moderado a alto. No entanto, a maioria dos parques apresenta um valor inferior a este limite. Também é possível conhecer quais as espécies que mais contribuem para o valor do índice, que correspondem aquelas com a estratégia de polinização anemófila, períodos de floração extensos e potencial alergénico referenciado. Estes requisitos são aplicáveis a todas as espécies das famílias Betuláceas, Cupressáceas e Moráceas, e em menor medida, Oleáceas e Platanáceas. Pode assim concluir-se que a aplicação de um índice de previsão dos níveis de alergenicidade dos espaços verdes urbanos constitui uma ferramenta útil para minimizar o impacto da alergia polínica sobre a população.peerReviewe

Environmental health of Spanish parks: An approach to the allergenic potential of urban green spaces

Los parques urbanos son elementos de la infraestructura verde que deben contribuir a mejorar la calidad de vida y el bienestar ciudadano. En este trabajo se presentan los resultados de la aplicación de un novedoso índice que estima la alergenicidad potencial de las zonas verdes urbanas. Este índice, que contempla parámetros biológicos y biométricos intrínsecos a las especies arbóreas existentes en los parques, genera un resultado cuyo valor está comprendido entre 0 y 1 según el potencial alergénico del parque sea nulo o de riesgo alto para la población. En una primera fase el índice se ha aplicado a parques de diferente tipología, diseño, tamaño, riqueza específica y biodiversidad ubicados en 20 ciudades españolas. Los resultados han mostrado que algunos de los parques estudiados registran un valor de índice superior a 0,30, umbral suficiente para causar síntomas de alergia a la población expuesta, y por tanto, de riesgo moderado o alto. Por el contrario, en la mayoría de los parques se obtuvo un valor inferior a este umbral. También es posible conocer cuáles son las especies que más contribuyen al valor resultante, que son aquellas con estrategia de polinización anemófila, periodos de floración extensos y alta alergenicidad referenciada. Estos requisitos los cumplen todas las especies de las familias Betuláceas, Cupresáceas y Moráceas, y en menor extensión, Oleáceas y Platanáceas. Puede concluirse que el desarrollo de un índice de estimación de alergenicidad de espacios verdes urbanos constituye una herramienta de utilidad para minimizar el impacto de la alergia polínica en la población.Urban parks are green infrastructure elements that should contribute to improving the quality of life and well-being of citizens. In this work there are presented the results of applying a new index to estimate the potential allergenicity of parks located in 20 Spanish cities. This index, which considers intrinsic biological and biometric parameters of existing plant species in parks, allows the allergenic risk thereof to be calculated on a scale ranging from 0 to 1, depending on whether to the park’s allergenicity is zero or has a high risk for the population. The parks selected for this study have different typologies, sizes, species richness and biodiversities, which has yielded highly variable index values. Almost half of the analysed parks have an index value higher than 0.30, a threshold considered having a moderate to high risk, and therefore, enough to cause allergy symptoms in the population. Conversely, most of the parks had an index value below this threshold, so that the risk of suffering allergies is low or very low. The formula also allows the species that most contribute to the resulting value for allergenicity to be known, which are those having an anemophillous strategy of pollination, extended periods of flowering, and a referenced high allergenicity. These requirements are met by all species of the Betulaceae, Cupressaceae and Moraceae families, and to a lesser extent by Oleaceae and Platanaceae. It can be concluded that the development of an index to estimate the allergenicity of urban green spaces constitutes a useful tool to minimize the impact of pollen allergy on the population.Os parques urbanos são elementos da infraestrutura verde que devem contribuir para a melhoria da qualidade de vida dos cidadãos. Neste trabalho apresentam-se os resultados da aplicação de um índice inovador, que permite estimar a alergenicidade potencial dos espaços verdes urbanos. Este índice, que inclui parâmetros biológicos e biométricos, intrínsecos às próprias espécies existentes nos parques, tem como resultado um valor numa escala entre 0 e 1, de acordo com o potencial alergénico do parque, caso este seja, respetivamente e nos seus extremos, nulo ou de máximo risco para as populações. O índice foi aplicado em parques de diferentes tipologias, desenho, tamanho, riqueza específica e biodiversidade, situados em 20 cidades espanholas. Os resultados demonstram que alguns dos parques estudados registam um valor de índice superior a 0,30, limite suficiente para causar sintomas de alergia na população exposta, e por tanto, risco moderado a alto. No entanto, a maioria dos parques apresenta um valor inferior a este limite. Também é possível conhecer quais as espécies que mais contribuem para o valor do índice, que correspondem aquelas com a estratégia de polinização anemófila, períodos de floração extensos e potencial alergénico referenciado. Estes requisitos são aplicáveis a todas as espécies das famílias Betuláceas, Cupressáceas e Moráceas, e em menor medida, Oleáceas e Platanáceas. Pode assim concluir-se que a aplicação de um índice de previsão dos níveis de alergenicidade dos espaços verdes urbanos constitui uma ferramenta útil para minimizar o impacto da alergia polínica sobre a população.S

Innovamos, jugamos y aprendemos combinando conocimientos de diferentes áreas

El objetivo principal de este proyecto de innovación docente es elaborar nuevas herramientas docentes para la enseñanza de la Bioquímica y la Fisiología, así como facilitar su aprendizaje y la relación de los conocimientos adquiridos entre ambas asignaturas en diferentes Grados tanto del Campus de Melilla como del Campus de Granada. Para ello nos planteamos los siguientes objetivos específicos: 1. Identificar una historia para hilar el contenido de la asignatura de Bioquímica. 2. Crear ligas o torneos para retar a los alumnos en su aprendizaje con estos juegos. 3. Relacionar contenidos entre las asignaturas de Bioquímica y Fisiología. 4. Evaluar el material didáctico al final del semestre mediante cuestionarios para comprobar su evolución en el aprendizaje de los conocimientos adquiridos. Por otro lado, también pretendemos que los alumnos identifiquen los conocimientos y competencias adquiridos y la utilidad y aplicación de esas tareas y habilidades en el ámbito empresarial, como un primer paso para el autoconocimiento profesional y la búsqueda de empleo. La dinámica de juego empleada será la realización de un Escape Room Educativo Virtual. Para alcanzar el primer objetivo en clase, identificaremos una historia o juego de interés entre los alumnos de primero. Si existen varias, se elegirá la que sea propuesta por el mayor número de alumnos. Tras la presentación de la historia, crearemos una liga o torneo para retar a los alumnos entre ellos. En el caso de que haya algún alumno/a con necesidades especiales, se nombrar un alumno colaborador, el cual le facilitará su participación durante la realización del juego. Además, el contenido será evaluado de modo que todos los alumnos tengan acceso a él, esto es, aumento del tamaño de letra, grabación de voz en off en caso necesario, aumento en el tiempo de realización de la actividad, etc. Algunas de las preguntas introducidas en el juego permitirán la relación de contenidos entre las asignaturas de Bioquímica y Fisiología y su aplicabilidad en su futuro profesional. Por último, al finalizar la actividad se les pasará a los alumnos un cuestionario para evaluar su satisfacción con este proyecto de innovación docente. Dicho proyecto docente ha sido aplicado al final del semestre en los Grados de Enfermería, Fisioterapia y el Doble Grado en Educación Primaria y Ciencias de la Actividad Física y del Deporte del Campus de Melilla y en los Grado de Fisioterapia y el Grado en Ciencias de la Actividad Física y del Deporte del Campus de Granada en la Universidad de Granada.The main objective of this teaching innovation project is to develop new teaching tools for the teaching of Biochemistry and Physiology, as well as to facilitate their learning and the relationship of the knowledge acquired between both subjects in different Degrees in both Melilla and Granada Campus at the University of Granada. To this end, we set ourselves the following specific objectives: 1. Identify a story to string together the content of the Biochemistry subject. 2. Create leagues or tournaments to resume students in their learning with these games. 3. Relate content between the subjects of Biochemistry and Physiology. 4. Evaluate the didactic material at the end of the semester by means of questionnaires to verify its evolution in the learning of the acquired knowledge. On the other hand, we also intend that students identify the knowledge and skills acquired and the usefulness and application of these tasks and skills in the business field, as a first step for professional self-knowledge and job search. The game dynamics used will be the realization of a Virtual Educational Escape Room. To achieve the first objective in class, we will identify a story or game of interest among the first graders. If there are several, the one proposed by the largest number of students will be chosen. After the presentation of the story, we will create a league or tournament to take the students back to each other. In the event that there is a student with special needs, a collaborating student will be appointed, who will facilitate their participation during the game. In addition, the content will be evaluated so that all students have access to it, that is, increased font size, voiceover recording if necessary, increased time to complete the activity, etc. Some of the questions presented in the game will allow the content relationship between the subjects of Biochemistry and Physiology and its applicability in their professional future. Finally, at the end of the activity, students will be given a questionnaire to assess their satisfaction with this teaching innovation project. This teaching project has been applied at the end of the semester in the Degrees of Nursing, Physiotherapy and the Double Degree in Primary Education and Physical Activity and Sports Sciences of the Melilla Campus and in the Degrees of Physiotherapy and the Degree in Sciences of the Physical Activity and Sports of the Granada Campus at the University of Granada