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Plastic pollution breaks a planetary boundary threatening wildlife and humans through its physical and chemical effects. Of the latter, the release of endocrine disrupting chemicals (EDCs) has consequences on the prevalence of human diseases related to the endocrine system. Bisphenols (BPs) and phthalates are two groups of EDCs commonly found in plastics that migrate into the environment and make low-dose human exposure ubiquitous. Here we review epidemiological, animal, and cellular studies linking exposure to BPs and phthalates to altered glucose regulation, with emphasis on the role of pancreatic β-cells. Epidemiological studies indicate that exposure to BPs and phthalates is associated with diabetes mellitus. Studies in animal models indicate that treatment with doses within the range of human exposure decreases insulin sensitivity and glucose tolerance, induces dyslipidemia, and modifies functional β-cell mass and serum levels of insulin, leptin, and adiponectin. These studies reveal that disruption of β-cell physiology by EDCs plays a key role in impairing glucose homeostasis by altering the mechanisms used by β-cells to adapt to metabolic stress such as chronic nutrient excess. Studies at the cellular level demonstrate that BPs and phthalates modify the same biochemical pathways involved in adaptation to chronic excess fuel. These include changes in insulin biosynthesis and secretion, electrical activity, expression of key genes, and mitochondrial function. The data summarized here indicate that BPs and phthalates are important risk factors for diabetes mellitus and support a global effort to decrease plastic pollution and human exposure to EDCs. The author’s laboratories are supported by Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) grant PID2020-117294RB-I00 (AN and JM-P), Generalitat Valenciana PROMETEO II/2020/006 (AN), and European Union’s Horizon 2020 research and innovation programme under grant agreement GOLIATH No. 825489 (AN). This work was supported by the National Institutes of Health (R01 ES028879 and P30 ES027792 supporting RMS).

Humans are constantly exposed to many environmental pollutants, some of which have been largely acknowledged as key factors in the development of metabolic disorders such as diabetes and obesity. These chemicals have been classified as endocrine-disrupting chemicals (EDCs) and, more recently, since they can interfere with metabolic functions, they have been renamed as metabolism-disrupting chemicals (MDCs). MDCs are present in many consumer products, including food packaging, personal care products, plastic bottles and containers, and detergents. The scientific literature has ever-increasingly focused on insulin-releasing pancreatic β-cells as one of the main targets for MDCs. Evidence highlights that these substances may disrupt glucose homeostasis by altering pancreatic β-cell physiology. However, their potential impact on glucagon-secreting pancreatic α-cells remains poorly known despite the essential role that this cellular type plays in controlling glucose metabolism. In the present study, we have selected seven paradigmatic MDCs representing major toxic classes, including bisphenols, phthalates, perfluorinated compounds, metals, and pesticides. By using an in vitro cell-based model, the pancreatic α-cell line αTC1-9, we have explored the effects of these compounds on pancreatic α-cell viability, gene expression, and secretion. We found that cell viability was moderately affected after bisphenol-A (BPA), bisphenol-F (BPF), and perfluorooctanesulfonic acid (PFOS) exposure, although cytotoxicity was relatively low. In addition, all bisphenols, as well as di(2-ethylhexyl) phthalate (DEHP) and cadmium chloride (CdCl2), promoted a marked decreased on glucagon secretion, together with changes in the expression of glucagon and/or transcription factors involved in cell function and identity, such as Foxo1 and Arx. Overall, our results indicated that most of the selected chemicals studied caused functional alterations in pancreatic α-cells. Moreover, we revealed, for the first time, their direct effects on key molecular aspects of pancreatic α-cell biology. This study received funding from the European Union’s Horizon 2020 Research and Innovation programme under Grant agreement no. 825712 (OBERON) project and Generalitat Valenciana: PROMETEO/2020/006 grant. The author’s laboratory also holds grant PID2020-113112RB-I00 funded by MCIN/AEI/10.13039/501100011033. CIBERDEM is an initiative of the Instituto de Salud Carlos III.

Studies indicate that the pesticide malathion may have a role in diabetes. Herein, we determined the effects of different concentrations of malathion on survival, ultrastructure, and electrophysiologic islet cell parameters. Acutely, high concentrations of malathion (0.5 or 1 mM) increased cell death in rat islet cells, while low concentrations (0.1 mM) caused signs of cell damage in pancreatic α and β cells. Exposure of RINm5F cells to malathion for 24 or 48 h confirmed the reduction in β-cell viability at lower concentrations (0.001–100 µM). Chronic exposure of mouse pancreatic α and β cells to 3 nM of malathion led to increased voltage-gated K+ (Kv) currents in α-cells. Our findings show a time and concentration dependency for the malathion effect on the reduction of islet cell viability and indicate that pancreatic α cells are more sensitive to malathion effects on Kv currents and cell death. F.N.S and J.R.N.M received a scholarship from the Coordenaçao de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) – Finance Code 001. D.R.V. received a scholarship from Fundaçao Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (grant number 204.651/2021). A.R is funded by a CNPq research grant (grant number 304338/2020–3). IQ is funded by a grant of Generalitat Valenciana (PROMETEO/2020/006).

The prevalence of type 2 diabetes (T2D) and impaired glucose tolerance (IGT) increases with ageing. T2D generally results from progressive impairment of the pancreatic islets to adapt β-cell mass and function in the setting of insulin resistance and increased insulin demand. Several studies have shown an age-related decline in peripheral insulin sensitivity. However, a precise understanding of the pancreatic β-cell response in ageing is still lacking. In this review, we summarize the age-related alterations, adaptations and/or failures of β-cells at the molecular, morphological and functional levels in mouse and human. Age-associated alterations include processes such as β-cell proliferation, apoptosis and cell identity that can influence β-cell mass. Age-related changes also affect β-cell function at distinct steps including electrical activity, Ca2+ signaling and insulin secretion, among others. We will consider the potential impact of these alterations and those mediated by senescence pathways on β-cells and their implications in age-related T2D. Finally, given the great diversity of results in the field of β-cell ageing, we will discuss the sources of this heterogeneity. A better understanding of β-cell biology during ageing, particularly at older ages, will improve our insight into the contribution of β-cells to age-associated T2D and may boost new therapeutic strategies. This research was supported by grants from the Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación, Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III and Generalitat Valenciana: PID2020-117294RB-I00 and PROMETEO/2020/006 to AN, BFU2016-77125-R to IQ, PID2020-113112RB-I00 to PAM and PI19/00246 to EM. CIBERDEM is an initiative of the Instituto de Salud Carlos III.

17β-estradiol protects pancreatic β-cells from apoptosis via the estrogen receptors ERα, ERβ and GPER. Conversely, the endocrine disruptor bisphenol-A (BPA), which exerts multiple effects in this cell type via the same estrogen receptors, increased basal apoptosis. The molecular-initiated events that trigger these opposite actions have yet to be identified. We demonstrated that combined genetic downregulation and pharmacological blockade of each estrogen receptor increased apoptosis to a different extent. The increase in apoptosis induced by BPA was diminished by the pharmacological blockade or the genetic silencing of GPER, and it was partially reproduced by the GPER agonist G1. BPA and G1-induced apoptosis were abolished upon pharmacological inhibition, silencing of ERα and ERβ, or in dispersed islet cells from ERβ knockout (BERKO) mice. However, the ERα and ERβ agonists PPT and DPN, respectively, had no effect on beta cell viability. To exert their biological actions, ERα and ERβ form homodimers and heterodimers. Molecular dynamics simulations together with proximity ligand assays and coimmunoprecipitation experiments indicated that the interaction of BPA with ERα and ERβ as well as GPER activation by G1 decreased ERαβ heterodimers. We propose that ERαβ heterodimers play an antiapoptotic role in beta cells and that BPA- and G1-induced decreases in ERαβ heterodimers lead to beta cell apoptosis. Unveiling how different estrogenic chemicals affect the crosstalk among estrogen receptors should help to identify diabetogenic endocrine disruptors. This work was supported by Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) grants BPU2017-86579-R (AN), PID2020-117294RB-I00 (AN, JM-P), Generalitat Valenciana PROMETEO II/2020/006 (AN) and European Union’s Horizon 2020 research and innovation programme under grant agreement GOLIATH No. 825489 (AN). Author laboratories hold grants from Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación y Fondo Europeo de Desarrollo Regional (FEDER) RTI2018-096724-B-C21 (J-AE) and PID2020-117569RA-I00 (LM). PROMETEO/2016/006 (J-AE) and SEJI/2018/023 (LM) supported by Generalitat Valenciana, Spain. Robert A. Welch Foundation (grant E-0004) (J-AG). CIBERDEM is an initiative of the Instituto de Salud Carlos III.

La divulgación científico-técnica es una forma de comunicación que hace accesible el conocimiento a toda la sociedad. Entendiendo que la comunicación del conocimiento forma parte de las actividades propias de la Universidad, este proyecto nace con el objetivo de mostrar, a los y las estudiantes que cursan un grado o máster en la Universidad de Alicante, la importancia de la divulgación de conocimiento científico-técnico. Además, se pretende que el cómic pueda ser utilizado como elemento didáctico que favorezca el proceso de aprendizaje. Mediante un formato de concurso (“BioMedComic”), se animó a los/as estudiantes a participar en este proyecto. Además se creó una web específica donde se establecen las bases del concurso (https://web.ua.es/es/biomedcomic/). La valoración de los cómics la realizaron seis profesores/as de la Universidad de Alicante y dos investigadores/as externos a la universidad. Tras la finalización del proyecto podemos decir que pese a que el estudiantado mostró gran entusiasmo, la participación fue reducida. Cabe destacar que los participantes eran tanto estudiantes de diferentes grados como de máster y los cómics presentados al concurso obtuvieron puntuaciones elevadas según los criterios de valoración. Además, tres de los cómics participantes también se han presentado al certamen nacional de comics sobre fisiología “FisioCómic22”.

Aging is associated with a decline in peripheral insulin sensitivity and an increased risk of impaired glucose tolerance and type 2 diabetes. During conditions of reduced insulin sensitivity, pancreatic β-cells undergo adaptive responses to increase insulin secretion and maintain euglycemia. However, the existence and nature of β-cell adaptations and/or alterations during aging are still a matter of debate. In this study, we investigated the effects of aging on β-cell function from control (3-month-old) and aged (20-month-old) mice. Aged animals were further categorized in two groups: high insulin sensitive (aged-HIS) and low insulin sensitive (aged-LIS). Aged-LIS mice were hyperinsulinemic, glucose intolerant and displayed impaired glucose-stimulated insulin and C-peptide secretion, whereas aged-HIS animals showed characteristics in glucose homeostasis similar to controls. In isolated β-cells, we observed that glucose-induced inhibition of KATP channel activity was reduced with aging, particularly in the aged-LIS group. Glucose-induced islet NAD(P)H production was decreased in aged mice, suggesting impaired mitochondrial function. In contrast, voltage-gated Ca 2+ currents were higher in aged-LIS β-cells, and pancreatic islets of both aged groups displayed increased glucose-induced Ca 2+ signaling and augmented insulin secretion compared with controls. Morphological analysis of pancreas sections also revealed augmented β-cell mass with aging, especially in the aged-LIS group, as well as ultrastructural β-cell changes. Altogether, these findings indicate that aged mouse β-cells compensate for the aging-induced alterations in the stimulus-secretion coupling, particularly by adjusting their Ca 2+ influx to ensure insulin secretion. These results also suggest that decreased peripheral insulin sensitivity exacerbates the effects of aging on β-cells. This research was supported by grants from the Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación, Fondo Europeo de Desarrollo Regional (FEDER) and Generalitat Valenciana (BFU2017-86579-R and PROMETEO/2020/006 to AN and BFU2016-77125-R to IQ) and from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (grant No. 304388/2020-3 to AR) and the Programa Institucional de Internacionalização from the Coordenação de Aperfeiçoamento de pessoal de Nível Superior (CAPES). CIBERDEM is an initiative of the Instituto de Salud Carlos III.

17β-Estradiol mediates the sensitivity to pain and is involved in sex differences in nociception. The widespread environmental disrupting chemical bisphenol A (BPA) has estrogenic activity, but its implications in pain are mostly unknown. Here we show that treatment of male mice with BPA (50 µg/kg/day) during 8 days, decreases the latency to pain behavior in response to heat, suggesting increased pain sensitivity. We demonstrate that incubation of dissociated dorsal root ganglia (DRG) nociceptors with 1 nM BPA increases the frequency of action potential firing. SCN9A encodes the voltage-gated sodium channel Nav1.7, which is present in DRG nociceptors and is essential in pain signaling. Nav1.7 and other voltage-gated sodium channels in mouse DRG are considered threshold channels because they produce ramp currents, amplifying small depolarizations and enhancing electrical activity. BPA increased Nav-mediated ramp currents elicited with slow depolarizations. Experiments using pharmacological tools as well as DRG from ERβ−/− mice indicate that this BPA effect involves ERα and phosphoinositide 3-kinase. The mRNA expression and biophysical properties other than ramp currents of Nav channels, were unchanged by BPA. Our data suggest that BPA at environmentally relevant doses affects the ability to detect noxious stimuli and therefore should be considered when studying the etiology of pain conditions. The authors’ laboratories are funded by the Ministerio de Economía, Industria y Competitividad, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER), BFU2017-86579-R (A.N.) and Generalitat Valenciana, PROMETEOII/2015/016 (A.N.). CIBERDEM is an initiative of the Instituto de Salud Carlos III. J.-A. G. was supported by a fellowship from the A. Welch Foundation (Grant E-0004).

The voltage-gated potassium channel Kv1.3 plays an apparent dual physiological role by participating in activation and proliferation of leukocytes as well as promoting apoptosis in several types of tumor cells. Therefore, Kv1.3 is considered a potential pharmacological target for immunodeficiency and cancer. Different cellular locations of Kv1.3, at the plasma membrane or the mitochondria, could be responsible for such duality. While plasma membrane Kv1.3 facilitates proliferation, the mitochondrial channel modulates apoptotic signaling. Several molecular determinants of Kv1.3 drive the channel to the cell surface, but no information is available about its mitochondrial targeting. Caveolins, which are able to modulate cell survival, participate in the plasma membrane targeting of Kv1.3. The channel, via a caveolin-binding domain (CDB), associates with caveolin 1 (Cav1), which localizes Kv1.3 to lipid raft membrane microdomains. The aim of our study was to understand the role of such interactions not only for channel targeting but also for cell survival in mammalian cells. By using a caveolin association-deficient channel (Kv1.3 CDBless), we demonstrate here that while the Kv1.3–Cav1 interaction is responsible for the channel localization in the plasma membrane, a lack of such interaction accumulates Kv1.3 in the mitochondria. Kv1.3 CDBless severely affects mitochondrial physiology and cell survival, indicating that a functional link of Kv1.3 with Cav1 within the mitochondria modulates the pro-apoptotic effects of the channel. Therefore, the balance exerted by these two complementary mechanisms fine-tune the physiological role of Kv1.3 during cell survival or apoptosis. Our data highlight an unexpected role for the mitochondrial caveolin–Kv1.3 axis during cell survival and apoptosis. Supported by the Ministerio de Ciencia e Innovación (MICINN), Spain (BFU2017-87104-R and PID2020-112647RB-I00 to AF; CSD2008-00005 to AM), the Italian Association for Cancer Research (AIRC IG grant 20286 to IS), the Italian Ministry of University and Education (PRIN 20174TB8KW_004 to IS), the Italian Association for Multiple Sclerosis (to IS), and the European Regional Development Fund.

The human and mouse islet of Langerhans is an endocrine organ composed of five different cells types; insulin-secreting β-cells, glucagon-producing α-cells, somatostatin-producing δ-cells, pancreatic polypeptide-secreting PP cells and ɛ-cells that secretes ghrelin. The most important cells are the pancreatic β-cells that comprise around 45–50% of human islets and 75–80% in the mouse. Pancreatic β-cells secrete insulin at high glucose concentration, thereby finely regulating glycaemia by the hypoglycaemic effects of this hormone. Different ion channels are implicated in the stimulus-secretion coupling of insulin. An increase in the intracellular ATP concentration leads to closure KATP channels, depolarizing the cell and opening voltage-gated calcium channels. The increase of intracellular calcium concentration induced by calcium entry through voltage-gated calcium channels promotes insulin secretion. Here, we briefly describe the diversity of ion channels present in pancreatic β-cells and the different mechanisms that are responsible to induce insulin secretion in human and mouse cells. Moreover, we described the pathophysiology due to alterations in the physiology of the main ion channels present in pancreatic β-cell and its implication to predispose metabolic disorders as type 2 diabetes mellitus.

Bisphenol-S (BPS) and Bisphenol-F (BPF) are current Bisphenol-A (BPA) substitutes. Here we used pancreatic β-cells from wild type (WT) and estrogen receptor β (ERβ) knockout (BERKO) mice to investigate the effects of BPS and BPF on insulin secretion, and the expression and activity of ion channels involved in β-cell function. BPS or BPF rapidly increased insulin release and diminished ATP-sensitive K+ (KATP) channel activity. Similarly, 48 h treatment with BPS or BPF enhanced insulin release and decreased the expression of several ion channel subunits in β-cells from WT mice, yet no effects were observed in cells from BERKO mice. PaPE-1, a ligand designed to preferentially trigger extranuclear-initiated ER pathways, mimicked the effects of bisphenols, suggesting the involvement of extranuclear-initiated ERβ pathways. Molecular dynamics simulations indicated differences in ERβ ligand-binding domain dimer stabilization and solvation free energy among different bisphenols and PaPE-1. Our data suggest a mode of action involving ERβ whose activation alters three key cellular events in β-cell, namely ion channel expression and activity, and insulin release. These results may help to improve the hazard identification of bisphenols. This work was supported by BPU2017-86579-R (AN) and BFU2016-77125-R (IQ) and RTI2018-096724-B-C21 (JAE) supported by FEDER /Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación, Spain. PROMETEO/2020/006 (AN), PROMETEO/2016/006 (JAE) and SEJI/2018/023 (LM) supported by Generalitat Valenciana, Spain. J-AG was supported by the Robert A. Welch Foundation (E 0004), USA. CIBERDEM is an initiative of the Instituto de Salud Carlos III, Spain.

La evaluación de los aprendizajes en competencias transversales requiere la aplicación de metodologías que favorezcan las oportunidades para aprender. El principal propósito de este proyecto ha sido el desarrollo de procedimientos de evaluación colaborativos aplicables a la evaluación de acciones formativas grupales y de sus productos, en la asignatura Iniciación a la Investigación en Biología (Grado en Biología). Para ello hemos trabajado a lo largo de cinco ejes principales: i) desarrollar rúbricas digitales colaborativas para la evaluación de productos de actividades grupales; ii) aplicar las rúbricas a trabajos colaborativos de estudiantes; iii) elaboración de cuestionarios de evaluación de las rúbricas de evaluación de las actividades formativas por el alumnado; iv) administrar la encuesta de evaluación para valorar la percepción del alumnado sobre el proceso de evaluación del trabajo grupal; y v) analizar y valorar los resultados y proponer posibles propuestas de mejora. Mayoritariamente, los estudiantes han valorado muy positivamente la utilización del sistema de e-rúbricas para la evaluación de las entregas realizadas durante el curso, y se han mostrado útiles para la autoevaluación de sus competencias, así como para la autocorrección de errores y la valoración de los indicadores de evaluación.

En el ámbito educativo existen diferentes modalidades de evaluación. Durante el curso 2020/21, debido a la pandemia sanitaria, la evaluación universitaria tuvo que adaptarse transformándose, en muchos casos, de una evaluación presencial en el aula a una evaluación en línea (online). En el presente trabajo hemos querido averiguar si este cambio en el método de evaluación podría afectar al rendimiento académico del estudiantado. Para ello, analizamos y comparamos las calificaciones del alumnado de Anatomía tras la realización de los exámenes presenciales del curso 2019/2020 y de los exámenes online del curso 2020/21. Tras analizar los resultados obtenidos, observamos que las calificaciones correspondientes a los exámenes presenciales de 2019/20 fueron significativamente más bajas (p< 0,0001) que las obtenidas en los exámenes online de 2020-21. El 71,4 % del alumnado afirmó que les resultó más fácil la prueba evaluativa realizada en clase de manera presencial. Sin embargo, los resultados obtenidos tras este trabajo muestran que la calificación obtenida tras el examen presencial fue menor, a pesar de que la autopercepción de aprendizaje es mayor, si se compara con las calificaciones obtenidas tras el examen online de las mismas características.

Endocrine-disrupting chemicals (EDCs) are chemical substances that can interfere with the normal function of the endocrine system. EDCs are ubiquitous and can be found in a variety of consumer products such as food packaging materials, personal care and household products, plastic additives, and flame retardants. Over the last decade, the impact of EDCs on human health has been widely acknowledged as they have been associated with different endocrine diseases. Among them, a subset called metabolism-disrupting chemicals (MDCs) is able to promote metabolic changes that can lead to the development of metabolic disorders such as diabetes, obesity, hepatic steatosis, and metabolic syndrome, among others. Despite this, today, there are still no definitive and standardized in vitro tools to support the metabolic risk assessment of existing and emerging MDCs for regulatory purposes. Here, we evaluated the following two different pancreatic cell-based in vitro systems: the murine pancreatic β-cell line MIN6 as well as the human pancreatic β-cell line EndoC-βH1. Both were challenged with the following range of relevant concentrations of seven well-known EDCs: (bisphenol-A (BPA), bisphenol-S (BPS), bisphenol-F (BPF), perfluorooctanesulfonic acid (PFOS), di(2-ethylhexyl) phthalate (DEHP), cadmium chloride (CdCl2), and dichlorodiphenyldichloroethylene (DDE)). The screening revealed that most of the tested chemicals have detectable, deleterious effects on glucose-stimulated insulin release, insulin content, electrical activity, gene expression, and/or viability. Our data provide new molecular information on the direct effects of the selected chemicals on key aspects of pancreatic β-cell function, such as the stimulus-secretion coupling and ion channel activity. In addition, we found that, in general, the sensitivity and responses were comparable to those from other in vivo studies reported in the literature. Overall, our results suggest that both systems can serve as effective tools for the rapid screening of potential MDC effects on pancreatic β-cell physiology as well as for deciphering and better understanding the molecular mechanisms that underlie their action. This study received funding from the European Union’s Horizon 2020 Research and Innovation programme under Grant agreement no 825712 (OBERON) project. The author’s laboratory also holds grant PID2020-113112RB-I00 funded by MCIN/AEI/10.13039/501100011033. CIBERDEM is an initiative of the Instituto de Salud Carlos III.

Endocrine Disrupting Chemicals (EDCs), including bisphenol-A (BPA) do not act as traditional toxic chemicals inducing massive cell damage or death in an unspecific manner. EDCs can work upon binding to hormone receptors, acting as agonists, antagonists or modulators. Bisphenol-A displays estrogenic activity and, for many years it has been classified as a weak estrogen, based on the classic transcriptional action of estrogen receptors serving as transcription factors. However, during the last two decades our knowledge about estrogen signaling has advanced considerably. It is now accepted that estrogen receptors ERα and ERβ activate signaling pathways outside the nucleus which may or may not involve transcription. In addition, a new membrane estrogen receptor, GPER, has been proposed. Pharmacological and molecular evidence, along with results obtained in genetically modified mice, demonstrated that BPA, and its substitute BPS, are potent estrogens acting at nanomolar concentrations via extranuclear ERα, ERβ, and GPER. The different signaling pathways activated by BPA and BPS explain the well-known estrogenic effects of low doses of EDCs as well as non-monotonic dose-response relationships. These signaling pathways may help to explain the actions of EDCs with estrogenic activity in the etiology of different pathologies, including type-2 diabetes and obesity. The author laboratories are funded by the Ministerio de Economía y Competitividad (SAF2014-58335-P and BFU2013-42789-P) and Generalitat Valenciana (PROMETEOII/2015/016). CIBERDEM is an initiative of the Instituto de Salud Carlos III.

It is well established that oxidative stress and inflammation are common pathogenic features of retinal degenerative diseases. ITH12674 is a novel compound that induces the transcription factor Nrf2; in so doing, the molecule exhibits anti-inflammatory, and antioxidant properties, and affords neuroprotection in rat cortical neurons subjected to oxidative stress. We here tested the hypothesis that ITH12674 could slow the retinal degeneration that causes blindness in rd10 mice, a model of retinitis pigmentosa. Methods: Animals were intraperitoneally treated with 1 or 10 mg/Kg ITH12674 or placebo from P16 to P30. At P30, retinal functionality and visual acuity were analyzed by electroretinography and optomotor test. By immunohistochemistry we quantified the photoreceptor rows and analyzed their morphology and connectivity. Oxidative stress and inflammatory state was studied by Western blot, and microglia reactivity was monitored by flow cytometry. The blood−brain barrier permeation of ITH12674 was evaluated using a PAMPA-BBB assay. Results: In rd10 mice treated with 10 mg/Kg of the compound, the following changes were observed (with respect to placebo): (i) a decrease of vision loss with higher scotopic a- and b-waves; (ii) increased visual acuity; (iii) preservation of cone photoreceptors morphology, as well as their synaptic connectivity; (iv) reduced expression of TNF-α and NF-κB; (v) increased expression of p38 MAPK and Atg12-Atg5 complex; and (vi) decreased CD11c, MHC class II and CD169 positive cell populations. Conclusion: These data support the view that a Nrf2 inducer compound may arise as a new therapeutic strategy to combat retinal neurodegeneration. At present, we are chemically optimising compound ITH12674 with the focus on improving its neuroprotective potential in retinal neurodegenerative diseases, This work was supported by grants from Bayer (Grats4Targets), from the Spanish Ministry of Economy and Competitiveness (MINECO-FEDER BFU2015-67139-R), Spanish Ministry of Education (FPU14/03166, FPU13/03737 and FPU16/04114), Instituto de Salud Carlos III co-financed by the European Regional Development’s funds (FEDER) (RETICSFEDER RD16/0008/0016, Programa Miguel Servet II (CP16/00014) and research project (grant PI17/01700)), Asociación Retina Asturias, Fundación La Caixa, CaixaImpulse program (grant CI17-00048), Comunidad Autónoma de Madrid (grant B2017/BMD-3827), Generalitat Valenciana (PROMETEO/2016/158 and ACIF/2016/055) Generalitat Valenciana-FEDER IDIFEDER/2017/064

La asignatura Iniciación a la Investigación en Biología del Grado en Biología se desarrolla a partir de una experiencia de aprendizaje basada en un proyecto de investigación bibliográfica y bibliométrica. Se presentan los resultados de una serie de encuestas de autoevaluación y de satisfacción del alumnado sobre experiencias para mejorar la motivación (elección de tema de investigación) y participación, y sobre la herramienta de planificación del trabajo colaborativo. Los resultados indican los aspectos positivos y cierto margen de mejora en la percepción y conocimientos del alumnado sobre la organización y planificación del trabajo.

En la docencia universitaria, ha sido constatada la necesidad de una incorporación efectiva de la perspectiva de género. En la asignatura de Anatomía que impartimos en titulaciones de la rama de conocimiento de Ciencias de la Salud de la Universidad de Alicante, tras identificar ciertos sesgos y estereotipos transmisores de desigualdad, modificamos las guías docentes y rediseñamos los contenidos de la asignatura. Una vez realizadas dichas modificaciones nuestro objetivo ha sido evaluar, mediante un cuestionario anónimo, la percepción del alumnado respecto a la implementación de la perspectiva de género en nuestra asignatura. Asimismo, realizamos una colaboración con un instituto de la provincia de Alicante con el objetivo de evaluar, si la elección de itinerario/estudios/profesión en la etapa preuniversitaria mostraba sesgos de género. Los resultados obtenidos indicaron que los alumnos no percibieron ningún tipo de desigualdad de género en la asignatura de Anatomía y que consideran que es importante la inclusión de la perspectiva de género en ésta y otras asignaturas de su carrera. Sin embargo, la elección del futuro educacional por los alumnos preuniversitarios mostró un importante sesgo de género, subrayando la importancia de fomentar una educación inclusiva desde la perspectiva de género en etapas escolares y preuniversitarias. El presente trabajo contó con una ayuda del Programa de Redes-I3CE de investigación en docencia universitaria del Instituto de Ciencias de la Educación de la Universidad de Alicante (convocatoria 2019-20). Ref.K262

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Las necesidades educativas actuales han cambiado debido a la creciente complejidad de los contenidos y el acceso a la tecnología. La educación superior debería reflejar este cambio, olvidando los procesos de memorización y enseñando la capacidad para desarrollar un pensamiento crítico. Esto se puede trabajar en el aula con el método socrático. Acciones previas de nuestro grupo revelaron, mediante un cuestionario de autoevaluación, la satisfacción con esta metodología de una población de 89 estudiantes de primer año, sin conocimientos previos de la materia, en las prácticas de Fisiología, del área de Ciencias Sociales y Jurídicas. Pese a los buenos resultados de la metodología, en las aulas universitarias se utiliza principalmente la clase teórica magistral. En esta segunda fase, se utilizó el método socrático en una población de 58 estudiantes de tercer año, con amplios conocimientos de Fisiología, en las clases teóricas de Fisiología, del área de Ciencias y se evaluaron sus respuestas con el mismo cuestionario. En ambos grupos se observó que el alumnado se sentía cómodo con la metodología docente, que la preferían sobre las clases magistrales y que facilitaba la asimilación de conceptos y aprendizaje. No hubo diferencias estadísticamente significativas en ninguna de las respuestas de las diferentes poblaciones.

Este trabajo se propone mejorar la adquisición de competencias transversales del Módulo Básico del Grado en Biología, a través de una mejora en la experiencia docencia-aprendizaje de la asignatura Iniciación a la Investigación en Biología del alumnado que cursa primero del Grado en Biología. Para ello hemos realizado un diagnóstico de la situación centrándonos en cuatro objetivos principales: el análisis de la experiencia del alumnado en el trabajo grupal y el método de aprendizaje basado en proyectos a través del análisis de rúbricas; el análisis de la adquisición de competencias trasversales del Módulo Básico del Grado en Biología; el análisis de las preferencias del alumnado sobre la selección de temas de investigación; y la evaluación de los métodos de evaluación individual formativa de conocimientos en tiempo real en clases de teoría. Los resultados obtenidos nos permiten asegurar que la adopción progresiva de nuevas estrategias de docencia-aprendizaje basadas en la retroalimentación de la propia Red Docente está consiguiendo mejorar los resultados de adquisición de competencias transversales de los estudiantes.

Aims/hypothesis: Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical that has been associated with type 2 diabetes development. Low doses of BPA modify pancreatic beta cell function and induce insulin resistance; some of these effects are mediated via activation of oestrogen receptors α (ERα) and β (ERβ). Here we investigated whether low doses of BPA regulate the expression and function of ion channel subunits involved in beta cell function. Methods: Microarray gene profiling of isolated islets from vehicle- and BPA-treated (100 μg/kg per day for 4 days) mice was performed using Affymetrix GeneChip Mouse Genome 430.2 Array. Expression level analysis was performed using the normalisation method based on the processing algorithm ‘robust multi-array average’. Whole islets or dispersed islets from C57BL/6J or oestrogen receptor β (ERβ) knockout (Erβ) mice were treated with vehicle or BPA (1 nmol/l) for 48 h. Whole-cell patch-clamp recordings were used to measure Na and K currents. mRNA expression was evaluated by quantitative real-time PCR. Results: Microarray analysis showed that BPA modulated the expression of 1440 probe sets (1192 upregulated and 248 downregulated genes). Of these, more than 50 genes, including Scn9a, Kcnb2, Kcnma1 and Kcnip1, encoded important Na and K channel subunits. These findings were confirmed by quantitative RT-PCR in islets from C57BL/6J BPA-treated mice or whole islets treated ex vivo. Electrophysiological measurements showed a decrease in both Na and K currents in BPA-treated islets. The pharmacological profile indicated that BPA reduced currents mediated by voltage-activated K channels (K2.1/2.2 channels) and large-conductance Ca-activated K channels (K1.1 channels), which agrees with BPA’s effects on gene expression. Beta cells from ERβ mice did not present BPA-induced changes, suggesting that ERβ mediates BPA’s effects in pancreatic islets. Finally, BPA increased burst duration, reduced the amplitude of the action potential and enlarged the action potential half-width, leading to alteration in beta cell electrical activity. Conclusions/interpretation: Our data suggest that BPA modulates the expression and function of Na and K channels via ERβ in mouse pancreatic islets. Furthermore, BPA alters beta cell electrical activity. Altogether, these BPA-induced changes in beta cells might play a role in the diabetogenic action of BPA described in animal models., This work was supported by Ministerio de Economía y Competitividad, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) grants BPU2017-86579-R and SAF2014-58335-P (AN) and BFU2016-77125-R (IQ); Generalitat Valenciana PROMETEO II/2015/016 (AN); Grant for Networks of Excellence from MICINN ‘Nuclear Receptors in Cancer, Metabolism and Inflammation’ (NuRCaMeIn) (SAF2017-90604-REDT); Spanish Institute of Health Carlos III grants PI16/00259 (AH), PI17/02104 and RD16/0011/0034 (BS) co-financed by FEDER Funds. LM holds a Juan de la Cierva fellowship from the Ministry of Economy, Industry and Competitiveness (IJCI-2015-24482). CIBERDEM is an initiative of the Instituto de Salud Carlos III. J-AG was supported by the Robert A. Welch Foundation (E-0004).

Although there is growing evidence that cortistatin regulates several functions in different tissues, its role in the endocrine pancreas is not totally known. Here, we aim to study the effect of cortistatin on pancreatic beta-cells and glucose-stimulated insulin secretion (GSIS). Exposure of isolated mouse islets to cortistatin inhibited GSIS. This effect was prevented using a somatostatin receptor antagonist. Additionally, cortistatin hyperpolarized the membrane potential and reduced glucose-induced action potentials in isolated pancreatic beta-cells. Cortistatin did not modify ATP-dependent K+ (KATP) channel activity. In contrast, cortistatin increased the activity of a small conductance channel with characteristics of G protein-coupled inwardly rectifying K+ (GIRK) channels. The cortistatin effects on membrane potential and GSIS were largely reduced in the presence of a GIRK channel antagonist and by down-regulation of GIRK2 with small interfering RNA. Thus, cortistatin acts as an inhibitory signal for glucose-induced electrical activity and insulin secretion in the mouse pancreatic beta-cell. This work was supported by grants from the Ministerio de Economía, Industria y Competitividad (Spain), Agencia Estatal de Investigación (Spain) and Fondo Europeo de Desarrollo Regional (BFU2013-42789; BFU2017-86579-R; BFU2016-77125-R), Generalitat Valenciana (Spain, PROMETEOII/2015/016), CNPq (Brazil; 302261/2014-1; 306359/2017-0) and Junta de Andalucía (Spain; CTS-1406, BIO-0139). L.M. holds a Juan de la Cierva fellowship from the Ministry of Economy, Industry and Competitiveness (Spain; IJCI-2015-24482). CIBERDEM and CIBERobn are an initiative of the Instituto de Salud Carlos III (Spain).

© The Author(s) 2018., Among macrocyclic lactones (ML), ivermectin (IVM) and moxidectin (MOX) potentially affect all Ecdysozoan species, with dung beetles being particularly sensitive. The comparative effects of IVM and MOX on adult dung beetles were assessed for the first time to determine both the physiological sub-lethal symptoms and pre-lethal consequences. Inhibition of antennal response and ataxia were tested as two intuitive and ecologically relevant parameters by obtaining the lowest observed effect concentration (LOEC) values and interpolating other relevant toxicity thresholds derived from concentration-response curves (IC50, as the concentration of each ML where the antennal response is inhibited by half; and pLC50, as the quantity of ingested ML where partial paralysis was observed by half of treated individuals) from concentration-response curves. Both sub-lethal and pre-lethal symptoms obtained in this study coincided in that IVM was six times more toxic than MOX for adult dung beetles. Values of LOEC, IC50 and pLC50 obtained for IVM and MOX evaluated in an environmental context indicate that MOX, despite needing more time for its elimination in the faeces, would be half as harmful to dung beetles as IVM. This approach will be valuable to clarify the real impact of MLs on dung beetle health and to avoid the subsequent environmental consequences., Financial support was provided by the project CGL2015-68207-R of the Secretaría de Estado de Investigación–Ministerio de Economía y Competitividad.

Uno de los principales objetivos de los estudios superiores es el desarrollo de un pensamiento crítico entre el alumnado. El pensamiento crítico es un pensamiento de orden superior, más complejo y elaborado que la memorización y exposición de hechos. Una de las mejores estrategias para favorecer este pensamiento es el método socrático. Este método implica un diálogo entre el profesorado y el alumnado, donde el profesorado dirige la comunicación a través de preguntas provocadoras que incitan la discusión analítica, el planteamiento y desarrollo de hipótesis, y la defensa de las mismas. Se utilizó el método socrático en una población de 89 estudiantes de las prácticas de los estudios universitarios de Fisiología. Se evaluó la satisfacción del alumnado con esta metodología mediante un cuestionario formado por tres bloques de preguntas sobre: 1- La metodología docente: el alumnado se sentía cómodo y percibía que el profesorado animaba a la participación, aunque fuera con respuestas incorrectas, y se generaba un diálogo que facilitaba el razonamiento; 2- La percepción subjetiva: el alumnado las prefería sobre las clases magistrales, pues eran amenas e interesantes; y 3- El autoconcepto de aprendizaje: esta metodología facilitaba la asimilación de conceptos, la reflexión y el aprendizaje. En general, los resultados de la encuesta mostraron que el alumnado estaba satisfecho con el método socrático.

In regulatory toxicology, the dose-response relationship is a key element towards fulfilling safety assessments and satisfying regulatory authorities. Conventionally, the larger the dose, the greater the response, following the dogma “the dose makes the poison”. Many endocrine disrupting chemicals, including bisphenol-A (BPA), induce non-monotonic dose response (NMDR) relationships, which are unconventional and have tremendous implications in risk assessment. Although several molecular mechanisms have been proposed to explain NMDR relationships, they are largely undemonstrated. Using mouse pancreatic β-cells from wild-type and oestrogen receptor ERβ−/− mice, we found that exposure to increasing doses of BPA affected Ca2+ entry in an NMDR manner. Low doses decreased plasma membrane Ca2+ currents after downregulation of Cav2.3 ion channel expression, in a process involving ERβ. High doses decreased Ca2+ currents through an ERβ-mediated mechanism and simultaneously increased Ca2+ currents via oestrogen receptor ERα. The outcome of both molecular mechanisms explains the NMDR relationship between BPA and Ca2+ entry in β-cells. The author laboratories are funded by the Ministerio de Economía, Industria y Competitividad, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER), SAF2014-58335-P (AN) and BFU2013-42789-P (IQ) and Generalitat Valenciana, PROMETEOII/2015/016 (AN). CIBERDEM is an initiative of the Instituto de Salud Carlos III. J-A G was supported by the Robert A. Welch Foundation (E-0004).

En este trabajo se ha intentado recoger las acciones que se han llevado a cabo en la coordinación de la implantación del segundo curso del nuevo grado de Tecnologías de la Información para la Salud, grado con un marcado carácter multidisciplinar que condiciona la enseñanza de los contenidos. Entre estas acciones se han revisado las guías de cada asignatura participante en la red y se han realizado reuniones de seguimiento de la implantación de las asignaturas para detectar fortalezas y debilidades en el proceso docente. También se ha contado con la opinión de alumnos bien a través de encuestas bien directamente en conversaciones con los representantes del alumnado. Pretendemos que las conclusiones obtenidas tras el análisis de resultados se puedan aplicar el curso que viene y, de esta forma, avanzar en la implantación de la titulación con calidad y, especialmente, con el objetivo de formar egresados que satisfagan las necesidades de la sociedad.

Objective. While bile acids are important for the digestion process, they also act as signaling molecules in many tissues, including the endocrine pancreas, which expresses specific bile acid receptors that regulate several cell functions. In this study, we investigated the effects of the conjugated bile acid TUDCA on glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. Methods. Pancreatic islets were isolated from 90-day-old male mice. Insulin secretion was measured by radioimmunoassay, protein phosphorylation by western blot, Ca2 + signals by fluorescence microscopy and ATP-dependent K+ (KATP) channels by electrophysiology. Results. TUDCA dose-dependently increased GSIS in fresh islets at stimulatory glucose concentrations but remained without effect at low glucose levels. This effect was not associated with changes in glucose metabolism, Ca2 + signals or KATP channel activity; however, it was lost in the presence of a cAMP competitor or a PKA inhibitor. Additionally, PKA and CREB phosphorylation were observed after 1-hour incubation with TUDCA. The potentiation of GSIS was blunted by the Gα stimulatory, G protein subunit-specific inhibitor NF449 and mimicked by the specific TGR5 agonist INT-777, pointing to the involvement of the bile acid G protein-coupled receptor TGR5. Conclusion. Our data indicate that TUDCA potentiates GSIS through the cAMP/PKA pathway. This work was supported by grants from Fundacão de Amparo á Pesquisa do Estado de São Paulo (FAPESP 2013/01318-4), Conselho Nacional para o Desenvolvimento Científico e Tecnológico (CNPq 200030/2014-0), Instituto Nacional de Obesidade e Diabetes (CNPq/FAPESP) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). This study was also supported by grants from the Spanish Ministerio de Ciencia e Innovación (BFU2013-42789-P; BFU2011-28358). CIBERDEM is an initiative of the Instituto de Salud Carlos III.

Con objeto de ayudar a adquirir las competencias requeridas en diversas asignaturas relacionadas con la Farmacología que se imparten en distintos grados de la Universidad de Alicante, en los últimos años hemos planteado distintas experiencias en el aula para fomentar el trabajo colaborativo entre los estudiantes (resolución de casos mediante el uso de TIC, experiencias de docencia inversa y utilización de recursos web en el aula entre otras). Tras seis años de implementación de distintas actividades, nuestro objetivo es realizar un análisis crítico de las fortalezas y debilidades de las técnicas aplicadas, así como una reflexión de su utilidad real. Hemos comprobado que en el desarrollo de una misma actividad, la participación y el éxito de la misma varían enormemente de unos grupos a otros. Detectamos algunos factores que pueden estar implicados, como el número de estudiantes en el aula o el tiempo y la metodología empleados para realizar los controles de evaluación, pero otros factores resultan difíciles de identificar. La tipificación de estos factores resulta fundamental para conseguir mejorar estas actividades y que resulten realmente útiles en el proceso de enseñanza-aprendizaje.

Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) produced in huge quantities in the manufacture of polycarbonate plastics and epoxy resins. It is present in most humans in developed countries, acting as a xenoestrogen and it is considered an environmental risk factor associated to several diseases. Among the whole array of identified mechanisms by which BPA can interfere with physiological processes in living organisms, changes on ion channel activity is one of the most poorly understood. There is still little evidence about BPA regulation of ion channel expression and function. However, this information is key to understand how BPA disrupts excitable and non-excitable cells, including neurons, endocrine cells and muscle cells. This report is the result of a comprehensive literature review on the effects of BPA on ion channels. We conclude that there is evidence to say that these important molecules may be key end-points for EDCs acting as xenoestrogens. However, more research on channel-mediated BPA effects is needed. Particularly, mechanistic studies to unravel the pathophysiological actions of BPA on ion channels at environmentally relevant doses. The author laboratories are funded by the Ministerio de Economía y Competitividad (SAF2014-58335-P and BFU2013-42789-P) and Generalitat Valenciana (PROMETEOII/2015/016). CIBERDEM is an initiative of the Instituto de Salud Carlos III.

Las nuevas tecnologías de la información y las comunicaciones (NTICs) se han ido incorporando a las enseñanzas universitarias como un componente metodológico atractivo, tanto para los docentes como para el alumnado. En este sentido, en los últimos años han aparecido multitud de herramientas que permiten tanto la enseñanza como la presentación de contenidos científicos al amparo de estas NTICs. Algunos ejemplos de la multitud de oportunidades que la red ofrece hoy en día a los docentes son, cursos en abierto de prestigiosas universidades (MIT, Caltech, Cambridge…), webinars llevados a cabo por investigadores altamente especializados en muy diversas áreas, apps científicas, conferencias TED, etc. En el trabajo de investigación que aquí se presenta se han seleccionado, analizado y evaluado algunas de las citadas herramientas para la presentación/enseñanza de contenidos científicos en el ámbito de la docencia universitaria. Como objeto de estudio de la red de investigación en docencia universitaria que ha dado lugar a este trabajo se ha escogido el área de Ciencias Experimentales.

Las nuevas tecnologías de la información y las comunicaciones (NTICs) se han ido incorporando a las enseñanzas universitarias como un componente metodológico atractivo, tanto para los docentes como para el alumnado. En este sentido, en los últimos años han aparecido multitud de herramientas que permiten tanto la enseñanza como la presentación de contenidos científicos al amparo de estas NTICs. Algunos ejemplos de la multitud de oportunidades que la red ofrece hoy en día a los docentes son, cursos en abierto de prestigiosas universidades (MIT, Caltech, Cambridge…), webinars llevados a cabo por investigadores altamente especializados en muy diversas áreas, apps científicas, conferencias TED, etc. En el trabajo de investigación que aquí se presenta se han seleccionado, analizado y evaluado algunas de las citadas herramientas para la presentación/enseñanza de contenidos científicos en el ámbito de la docencia universitaria. Como objeto de estudio de la red de investigación en docencia universitaria que ha dado lugar a este trabajo se ha escogido el área de Ciencias Experimentales.

El proyecto innovador liderado por el Laboratorio de Nanotecnología Molecular del Dpto. Química Inorgánica de la UA persigue la creación y actualización de una plataforma a nivel internacional para la formación en nanotecnología y el análisis de su posible implantación en titulaciones universitarias afines. Dicho proyecto integra tres componentes: (i) el primer MOOC en nanotecnología en España (y en español), (ii) la Red de investigación en docencia universitaria NanoMOOC, ambos desarrollados en colaboración con el Dpto. Lenguajes y Sistemas de la UA y UniMOOC, y (iii) la Red Iberoamericana de nanotecnología. La combinación de los mismos está permitiendo alcanzar los objetivos propuestos, los cuales se pueden resumir en el desarrollo de un MOOC de calidad en nanotecnología, accesible a cualquier usuario dado su condición de MOOC y la disponibilidad de realizarlo en dos de las tres lenguas más habladas del mundo, inglés y español.

Las necesidades educativas actuales han cambiado debido a la creciente complejidad de los contenidos y a la tecnología. La educación superior debería reflejar este cambio, olvidando los procesos de memorización y enseñando la capacidad para desarrollar un pensamiento crítico. Esto se puede trabajar en el aula con el método socrático. Pese a los buenos resultados de la metodología socrática, en las aulas universitarias se utiliza principalmente la clase magistral. Se enseñó con la metodología socrática y magistral a dos poblaciones: una población de 89 estudiantes de primer año, sin conocimientos previos de la materia, en las prácticas de Fisiología, del área de las Ciencias Sociales y Jurídicas y una población de 58 estudiantes de tercer año, con amplios conocimientos de Fisiología, en las clases teóricas de Fisiología, del área de Ciencias. Se utilizó un cuestionario de autoevaluación para medir la satisfacción el método socrático. En ambos grupos se observó que el alumnado se sentía cómodo con la metodología docente, que la preferían sobre las clases magistrales y que facilitaba la asimilación de conceptos y aprendizaje. No hubo diferencias estadísticamente significativas en ninguna de las respuestas de las diferentes poblaciones.