Les pel·lícules com a recurs didàctic per explicar biologia i geologia a secundària

Màster Universitari de Formació del Professorat de Secundària Obligatòria i Batxillerat, Facultat d'Educació, Universitat de Barcelona, Curs: 2020-2021, Tutor: Francisco Javier Íñiguez Porras[cat] L’ensenyament de les ciències i el cinema són dues disciplines que poden unir-se i treballar molt bé de forma conjunta. Des de l’aparició del cinema al 1895 són moltes i molt diverses les aplicacions didàctiques que se li han donat a aquest. Entre elles, destaca l’ús de les pel·lícules de ciència ficció per explicar i/o aclarir certs conceptes de ciències que mostren un elevat grau de dificultat o comprensió. El present projecte mostra una proposta d’innovació adaptada als temps actuals que busca potenciar l’ús de les noves tecnologies per tal d’optimitzar l’aprenentatge significatiu en els joves de secundària. La realització del mencionat parteix de l’objectiu d’oferir una guia didàctica al docent, per tal de recolzar-se i transportar aquest recurs didàctic a l’aula. Fonamentalment, es basa en la descripció clara i ordenada de tot un llistat de pel·lícules que poden usar-se com a recurs didàctic per a explicar ‘Biologia i Geologia’ als alumnes de primer, tercer i quart curs de l’Educació Secundària Obligatòria. Tanmateix, s’inclou la programació completa de cada activitat, la temporització, els recursos que es requereixen i l’avaluació corresponent. S’espera que pugui esdevenir una proposta innovadora i interessant que pugui ser aplicada en les aules d’avui i d’un futur pròxim

Disseny i síntesi de noves quimioteques de potencials inhibidors d’entrada del VIH

El programa de la síndrome de la immunodeficiència adquirida (SIDA o sida) de les Nacions Unides va estimar a finals de 2008 que més de 33 milions de persones arreu del món vivien amb el virus de la immunodeficiència humana (VIH). En l’estudi de les dianes terapèutiques contra l’agent etiològic de la sida s’han validat com a tals els coreceptors CXCR4 i CCR5 d’unió i fusió del virus a la cèl•lula hoste. Actualment hi ha un inhibidor d’entrada i un de fusió per al tractament de la infecció per aquest retrovirus, tot i que cap d’ells inhibeix el coreceptor CXCR4. Això, unit a la capacitat del virus de desenvolupar resistència als fàrmacs actuals, fa necessària la cerca de noves famílies de compostos que hi facin front. El Grup d’Enginyeria Molecular (GEM) de l’IQS ha descrit prèviament una quimioteca combinatòria d’anàlegs de l’AMD3100, el cap de sèrie més actiu, formats per unitats estructurals polinitrogenades (que consisteixen en un heterocicle nitrogenat, un seguit de baules metilèniques i un grup amina primària terminal) unides a un espaiador p xililènic. La selecció d’aquesta quimioteca va dur a la identificació d’un nou candidat amb dos centres quirals amb activitat submicromolar contra el VIH. Aquest treball presenta diverses modificacions estructurals sobre ambdós caps de sèrie, en la cerca de nous inhibidors potencials del coreceptor d’entrada CXCR4. En primer lloc, per tal de rebaixar la basicitat de l’AMD3100, s’han substituït els seus anells ciclàmics per sistemes pirido[2,3 d]pirimidínics, en la síntesi dels quals es té molta experiència en el GEM. La baixa solubilitat en dissolvents comuns d’alguns dels compostos obtinguts es presenta com un greu inconvenient per al seu desenvolupament com a fàrmac. D’altra banda, tenint en compte el disseny racional descrit anteriorment al grup de recerca, s’amplia la quimioteca amb l’objectiu d’avaluar l’efecte de la distància entre àtoms de nitrogen i la presència de major impediment estèric entre l’espaiador aromàtic i el nitrogen que hi està directament unit. Tot i que no s’ha aconseguit millorar l’activitat del cap de sèrie, els compostos obtinguts presenten activitats prou satisfactòries. Igualment, s’obtenen els tres estereoisòmers del cap de sèrie amb activitat submicromolar i se n’avalua l’activitat antiviral per separat. Finalment, es duu a terme un disseny de novo de fàrmacs basat en l’estructura per buscar nous candidats que permetin obrir la porta a altres famílies de compostos amb activitat anti-VIH, a través de l’enumeració de la quimioteca virtual, la selecció i la posterior síntesi.El programa del síndrome de la inmunodeficiencia adquirida (SIDA o sida) de las Naciones Unidas estimó a finales de 2008 que más de 33 millones de personas en todo el mundo vivían con el virus de la inmunodeficiencia humana (VIH). En el estudio de las dianas terapéuticas contra el agente etiológico del sida se han validado como tales los correceptores CXCR4 y CCR5 de unión y fusión del virus a la célula huésped. Actualmente existe un inhibidor de entrada y uno de fusión para el tratamiento de la infección por este retrovirus, aunque ninguno de ellos inhibe el correceptor CXCR4. Ello, unido a la capacidad del virus de desarrollar resistencia a los fármacos actuales, hace necesaria la búsqueda de nuevas familias de compuestos que le hagan frente. El Grup d’Enginyeria Molecular (GEM) del IQS ha descrito previamente una quimioteca combinatoria de análogos del AMD3100, el candidato más activo, formados por unidades estructurales polinitrogenadas (que consisten en un heterociclo nitrogenado, una serie de eslabones metilénicos y un grupo amina primaria terminal) unidas a un espaciador p xililénico. La selección de esta quimioteca llevó a la identificación de un nuevo candidato con dos centros quirales con actividad submicromolar contra el VIH. Este trabajo presenta diversas modificaciones estructurales sobre ambos candidatos, en la búsqueda de nuevos inhibidores potenciales del correceptor de entrada CXCR4. En primer lugar, para rebajar la basicidad del AMD3100, se han substituido sus anillos ciclámicos por sistemas pirido[2,3 d]pirimidínicos, en la síntesis de los cuales se tiene mucha experiencia en el GEM. La baja solubilidad en disolventes comunes de algunos de los compuestos obtenidos se presenta como un grave inconveniente para su desarrollo como fármaco. Por otra parte, teniendo en cuenta el diseño racional descrito anteriormente en el grupo de investigación, se amplía la quimioteca con el objetivo de evaluar el efecto de la distancia entre átomos de nitrógeno y la presencia de mayor impedimento estérico entre el espaciador aromático y el nitrógeno que está directamente unido a él. Aunque no se ha conseguido mejorar la actividad de la estructura de referencia, los compuestos obtenidos presentan actividades satisfactorias. Asimismo, se obtienen los tres estereoisómeros del candidato con actividad submicromolar y se evalúa la actividad antiviral por separado. Finalmente, se lleva a cabo un diseño de novo de fármacos basado en la estructura para buscar nuevos candidatos que permitan abrir la puerta a otras familias de compuestos con actividad anti-VIH, a través de la enumeración de la quimioteca virtual, la selección y la posterior síntesis.The Joint United Nations Programme on Acquired Immunodeficiency Syndrome (AIDS) estimated in 2008 that more than 33 million people around the world lived with the human immunodeficiency virus (HIV). HIV cell fusion and entry coreceptors CXCR4 and CCR5 have been validated as targets for therapeutic intervention. Nowadays, there is one entry and one fusion inhibitor available for the treatment of this retrovirus infection, although none of them inhibits CXCR4 coreceptor. Due to this fact, added to the virus’ capacity of developing resistance to actual drugs, the search of new families of compounds facing up to these situations becomes necessary. The Grup d’Enginyeria Molecular (GEM) at IQS previously described a combinatorial library of analogues of the currently most active lead AMD3100, whose polinitrogenated building block consisted of a nitrogen-containing heterocycle, a saturated chain spacer and a terminal primary amine group, bonded to a p xylylene spacer. Library selection led to the identification of a new lead with two chiral centres and submicromolar activity against HIV. This work presents various structural modifications on both leads, looking for new potential CXCR4 inhibitors. First of all, in order to reduce basicity of AMD3100, cyclam rings were substituted by pyrido[2,3 d]pyrimidinic systems, whose synthesis has been widely studied at GEM. Low solubility in common solvents of some of the obtained compounds remains as a great inconvenience for their development as a drug. Furthermore, regarding the rational design previously described by the research group, the library has been expanded with the aim of evaluating the effect of the distance between nitrogen atoms and the steric effects between the linker and the nitrogen atom directly connected to it. Although biological activities do not improve the lead’s one, the obtained compounds present interesting activities. Moreover, the three stereoisomers of the lead compound with submicromolar activity have been synthesised and their activity has been evaluated separately. Finally, a de novo structure based drug design has been carried out looking for new hits allowing to identify new families of compounds with anti-HIV activity, by enumeration of the virtual library, selection of candidates and their synthesis

El tall de cua i ullals en garrins nounats

Treball presentat a l'assignatura de Deontologia i Veterinària Legal (21223

Multiscale modeling for complex chemical systems: Highlights about the Nobel Prize in Chemistry 2013

The Nobel Prize in Chemistry 2013 was awarded jointly to Martin Karplus, Michael Levitt and Arieh Warshel for the development of multiscale models for complex chemical systems. From the simplest approximation of molecular mechanics (MM) to quantum mechanics (QM), computational techniques allow simulating a great variety ofchemical systems. Combined QM/MM methodologies, however, are the best consensus for treating complex biological systems. Herein we review the theoretical basis of QM/MM methods and their applications during the last twenty years.

Deletions and duplications of the 22q11.2 region in spermatozoa from DiGeorge/velocardiofacial fathers

Altres ajuts: Universitat Autònoma de Barcelona CF-180034 i PIF/2012Background: DiGeorge/velocardiofacial syndrome (DGS/VCFS) is the most common deletion syndrome in humans. Low copy repeats flanking the 22q11.2 region confer a substrate for non-allelic homologous recombination (NAHR) events leading to rearrangements. This study sought to identify DGS/VCFS fathers with increased susceptibility to deletions and duplications at the 22q11.2 region in spermatozoa and to assess the particular contribution of intra-chromatid and/or inter-chromatid NAHR. Semen samples from nine DGS/VCFS fathers were analyzed by triple-color FISH using a probe combination that discriminated between normal, deleted and duplicated genotypes. Microsatellite analysis were performed in the parents and the affected children to determine the parental origin of the deleted chromosome 22. - Results: A significant increase in 22q11.2 deletions was observed in the sperm of two out of nine DGS/VCFS fathers (odds ratio 2.03-fold, P < 0.01), and in both cases the deletion in the offspring was transmitted by the father. Patients with significant increases in sperm anomalies presented a disturbed deletion:duplication 1:1 ratio (P < 0.01). - Conclusions: Altogether, results support that intra-chromatid NAHR is the mechanism responsible for the higher rate of sperm deletions, which is directly related to the transmission of the deleted chromosome 22 to offspring. Accordingly, the screening of sperm anomalies in the 22q11.2 region should be taken into account in the genetic counseling of DGS/VCFS families

Beneficial effect of a multistrain synbiotic prodefen® plus on the systemic and vascular alterations associated with metabolic syndrome in rats: The role of the neuronal nitric oxide synthase and protein kinase A

A high fat diet (HFD) intake is crucial for the development and progression of metabolic syndrome (MtS). Increasing evidence links gut dysbiosis with the metabolic and vascular alterations associated with MtS. Here we studied the use of a combination of various probiotic strains together with a prebiotic (synbiotic) in a commercially available Prodefen® Plus. MtS was induced by HFD (45%) in maleWistar rats. Half of the MtS animals received Prodefen® Plus for 4 weeks. At 12 weeks, we observed an increase in body weight, together with the presence of insulin resistance, liver steatosis, hypertriglyceridemia and hypertension in MtS rats. Prodefen® Plus supplementation did not a ect the body weight gain but ameliorated all the MtS-related symptoms. Moreover, the hypertension induced by HFD is caused by a diminished both nitric oxide (NO) functional role and release probably due to a diminished neuronal nitric oxide synthase (nNOS) activation by protein kinase A (PKA) pathway. Prodefen® Plus supplementation for 4 weeks recovered the NO function and release and the systolic blood pressure was returned to normotensive values as a result. Overall, supplementation with Prodefen® Plus could be considered an interesting non-pharmacological approach in MtS.This research was funded by Italfarmaco, S.A (L.O.U. 83; 0138/2018), CiberCV (Grant number: CB16/11/00286), the European Regional Development Grant (FEDER) (Comunidad de Madrid, Grant number B2017/BMD-3676), and R + D projects for young researchers, Universidad Autónoma de Madrid (Comunidad de Madrid (SI1-PJI-2019-00321). R.R.-D. received a fellowship from Juan de la Cierva Program (IJCI-2017-31399)

A blunted sympathetic function and an enhanced nitrergic activity contribute to reduce mesenteric resistance in hyperthyroidism

We aimed to determine whether an experimental model of hyperthyroidism could alter the function of sympathetic and nitrergic components of mesenteric innervation. For this purpose, male Wistar rats were divided into (1) control rats (CT) and (2) rats infused with L-Thyroxine (HT). Body weight gain and adipose tissue accumulation were lower in HT rats, while systolic blood pressure and citrate synthase activity in the soleus muscle were increased by HT. In segments from the superior mesenteric artery, the application of an electrical field stimulation (EFS) induced a vasoconstrictor response, which was lower in arteries from HT animals. The alpha-adrenoceptor antagonist phentolamine diminished EFS-induced vasoconstriction to a lower extent in HT arter-ies, while the purinergic receptor antagonist suramin reduced contractile response to EFS only in segments from CT. In line with this, noradrenaline release, tyrosine hydroxylase expression and activation and dopamine β hydroxylase expression were diminished in HT. The unspecific nitric oxide synthase (NOS) inhibitor L-NAME increased EFS-induced vasoconstriction more markedly in segments from HT rats. NO release was enhanced in HT, probably due to an enhancement in neuronal NOS activity, in which a hyperactivation of both PKC and PI3K-AKT signaling pathways might play a relevant role. In conclusion, perivascular mesenteric innervation might contribute to reduce the vascular resistance observed in hyperthyroidism.This research was funded by CiberCV (Grant number: CB16/11/00286), the European Regional Development Grant (FEDER) (Comunidad de Madrid, Grant number B2017/BMD-3676), Ministerio de Economía, Industria y Competitividad (SAF 2016-80905-P) and R + D projects for young researchers, Universidad Autónoma de Madrid (Comunidad de Madrid (SI1-PJI-2019-00321)

Environmental exposure to chlorpyrifos during gestation, APOE polymorphism and the risk on autistic-like behaviors

Autism spectrum disorder (ASD) encompasses several neurodevelopmental conditions characterized by communication and social impairment, as well as repetitive patterns of behavior. However, it can co-occur with other mental conditions such as anxiety. The massive use of chlorpyrifos (CPF) has been linked to the increased prevalence of developmental disorders. Likewise, ASD has also been closely linked to a wide variety of genetic factors. The aims of the present investigation are to study how gestational CPF exposure and APOE polymorphism affects communication skills, early development and mid-term anxiety-like behaviors, as well as, changes in gene expression related to the cholinergic system. C57BL/6J and humanized apoE3 and apoE4 homozygous mice were exposed to 0 or 1 mg/kg/day of CPF through the diet, from gestational day (GD) 12-18. In addition, a group of C57BL/6J females were injected subcutaneously with 300 mg/kg/day of valproic acid (VPA) on GD 12 and 13. This group was used as a positive control for studying some core and associated autism-like behaviors. Communication skills by means of ultrasonic vocalizations and physical/motor development were assessed during the preweaning period, whereas locomotor activity, anxiety-like behaviors and the gene expression of cholinergic elements were evaluated during adolescence. Our results showed that C57BL/6J mice prenatally exposed to CPF or VPA showed a decrease in body weight and a delay in eye opening. Communication and anxiety behavior were affected differently depending on treatment, while gene expression was altered by sex and treatment. In addition, none of the parameters evaluated in apoE transgenic mice exposed to CPF were affected, but there were differences between genotypes. Therefore, we suggest that prenatal CPF exposure and VPA produce divergent effects on communication and anxiety. Keywords: APOE genotype; Anxiety; Autism; Chlorpyrifos; Cholinergic system; Development; Ultrasonic vocalizations

Las aplicaciones móviles interactivas en el aula: análisis evolutivo de sus efectos en el aprendizaje e implicación del alumno y propuestas de mejora para la docencia

Depto. de MarketingDepto. de Ciencias de la Comunicación AplicadaFac. de Ciencias Económicas y EmpresarialesFac. de Ciencias de la InformaciónFALSEsubmitte

Impact of comorbidities on hospital mortality in patients with acute pancreatitis : a population-based study of 110,021 patients

The impact of pre-existing comorbidities on acute pancreatitis (AP) mortality is not clearly defined. Our study aims to determine the trend in AP hospital mortality and the role of comorbidities as a predictor of hospital mortality. We analyzed patients aged ≥ 18 years hospitalized with AP diagnosis between 2016 and 2019. The data have been extracted from the Spanish National Hospital Discharge Database of the Spanish Ministry of Health. We performed a univariate and multivariable analysis of the association of age, sex, and comorbidities with hospital mortality in patients with AP. The role of the Charlson and Elixhauser comorbidity indices as predictors of mortality was evaluated. A total of 110,021 patients diagnosed with AP were hospitalized during the analyzed period. Hospital mortality was 3.8%, with a progressive decrease observed in the years evaluated. In multivariable analysis, age ≥ 65 years (OR: 4.11, p 1.5 (OR: 2.03, p 1.5 (OR: 2.71, p < 0.001) comorbidity indices were also independently associated with mortality, and ROC curve analysis showed that they are useful for predicting hospital mortality. Advanced age, heart disease, renal disease, moderate-severe liver disease, peripheral vascular disease, and cerebrovascular disease before admission were independently associated with hospital mortality. The Charlson and Elixhauser comorbidity indices are useful for predicting hospital mortality in AP patients. The online version contains supplementary material available at 10.1186/s12876-023-02730-6