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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.

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.

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.

Correction to: Scientific Reports https://doi.org/10.1038/s41598-018-33241-0, published online 05 October 2018

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.

Correction to: Scientific Reports https://doi.org/10.1038/s41598-018-33241-0, published online 05 October 2018

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.

Ca2+-activated ion channels shape membrane excitability in response to elevations in intracellular Ca2+. The most extensively studied Ca2+-sensitive ion channels are Ca2+-activated K+ channels, whereas the physiological importance of Ca2+-activated Cl- channels has been poorly studied. Here we show that a Ca2+-activated Cl- currents (CaCCs) modulate repetitive firing in mouse sympathetic ganglion cells. Electrophysiological recording of mouse sympathetic neurons in an in vitro preparation of the superior cervical ganglion (SCG) identifies neurons with two different firing patterns in response to long depolarizing current pulses (1 s). Neurons classified as phasic (Ph) made up 67% of the cell population whilst the remainders were tonic (T). When a high frequency train of spikes was induced by intracellular current injection, SCG sympathetic neurons reached an afterpotential mainly dependent on the ratio of activation of two Ca2+-dependent currents: the K+ [IK(Ca)] and CaCC. When the IK(Ca) was larger, an afterhyperpolarization was the predominant afterpotential but when the CaCC was larger, an afterdepolarization (ADP) was predominant. These afterpotentials can be observed after a single action potential (AP). Ph and T neurons had similar ADPs and hence, the CaCC does not seem to determine the firing pattern (Ph or T) of these neurons. However, inhibition of Ca2+-activated Cl- channels with anthracene-9′-carboxylic acid (9AC) selectively inhibits the ADP, reducing the firing frequency and the instantaneous frequency without affecting the characteristics of single- or first-spike firing of both Ph and T neurons. Furthermore, we found that the CaCC underlying the ADP was significantly larger in SCG neurons from males than from females. Furthermore, the CaCC ANO1/TMEM16A was more strongly expressed in male than in female SCGs. Blocking ADPs with 9AC did not modify synaptic transmission in either Ph or T neurons. We conclude that the CaCC responsible for ADPs increases r

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 tis elimination in the faeces, would be twice 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.

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.

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 tis elimination in the faeces, would be twice 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.

Ca2+-activated ion channels shape membrane excitability in response to elevations in intracellular Ca2+. The most extensively studied Ca2+-sensitive ion channels are Ca2+-activated K+ channels, whereas the physiological importance of Ca2+-activated Cl- channels has been poorly studied. Here we show that a Ca2+-activated Cl- currents (CaCCs) modulate repetitive firing in mouse sympathetic ganglion cells. Electrophysiological recording of mouse sympathetic neurons in an in vitro preparation of the superior cervical ganglion (SCG) identifies neurons with two different firing patterns in response to long depolarizing current pulses (1 s). Neurons classified as phasic (Ph) made up 67% of the cell population whilst the remainders were tonic (T). When a high frequency train of spikes was induced by intracellular current injection, SCG sympathetic neurons reached an afterpotential mainly dependent on the ratio of activation of two Ca2+-dependent currents: the K+ [IK(Ca)] and CaCC. When the IK(Ca) was larger, an afterhyperpolarization was the predominant afterpotential but when the CaCC was larger, an afterdepolarization (ADP) was predominant. These afterpotentials can be observed after a single action potential (AP). Ph and T neurons had similar ADPs and hence, the CaCC does not seem to determine the firing pattern (Ph or T) of these neurons. However, inhibition of Ca2+-activated Cl- channels with anthracene-9′-carboxylic acid (9AC) selectively inhibits the ADP, reducing the firing frequency and the instantaneous frequency without affecting the characteristics of single- or first-spike firing of both Ph and T neurons. Furthermore, we found that the CaCC underlying the ADP was significantly larger in SCG neurons from males than from females. Furthermore, the CaCC ANO1/TMEM16A was more strongly expressed in male than in female SCGs. Blocking ADPs with 9AC did not modify synaptic transmission in either Ph or T neurons. We conclude that the CaCC responsible for ADPs increases r

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.

Ivermectin is a veterinary pharmaceutical generally used to control the ecto- and endoparasites of livestock, but its use has resulted in adverse effects on coprophilous insects, causing population decline and biodiversity loss. There is currently no information regarding the direct effects of ivermectin on dung beetle physiology and behaviour. Here, based on electroantennography and spontaneous muscle force tests, we show sub-lethal disorders caused by ivermectin in sensory and locomotor systems of Scarabaeus cicatricosus, a key dung beetle species in Mediterranean ecosystems. Our findings show that ivermectin decreases the olfactory and locomotor capacity of dung beetles, preventing them from performing basic biological activities. These effects are observed at concentrations lower than those usually measured in the dung of treated livestock. Taking into account that ivermectin acts on both glutamate-gated and GABA-gated chloride ion channels of nerve and muscle cells, we predict that ivermectin’s effects at the physiological level could influence many members of the dung pat community. The results indicate that the decline of dung beetle populations could be related to the harmful effects of chemical contamination in the dung.

Durante el curso 2013-2014 se implementó en la asignatura de Fisiología Animal I, del Grado en Biología de la Universidad de Alicante, un entorno personal de aprendizaje (EPA), a partir de la herramienta Scliped. Esta herramienta permitió desarrollar una red social de contenidos seleccionados por el profesorado, como estrategia docente para poner a disposición del alumnado recursos de excelencia que faciliten su aprendizaje. La inversión de tiempo y dinero requerida fue sensiblemente inferior a la necesaria para el desarrollo de materiales específicos equivalentes. El alumnado tuvo a su disposición un tablero de 130 contenidos seleccionados, distribuidos en 34 colecciones. Al finalizar el curso escolar 2013-2014, el EPA había recibido un total de 60.794 visitas. La evaluación del uso y conformidad del alumnado con esta herramienta mostró que, si bien opinaban que su uso era innovador, no podría sustituir la labor del profesorado. El porcentaje de adhesión a la herramienta fue bajo, tan sólo el 16% del alumnado encuestado, sin embargo, este grupo declaró que el uso de Scliped era sencillo y atractivo, que los contenidos eran pertinentes y estaban bien organizados, y que les habían facilitado el estudio y la comprensión de la materia.

Ivermectin is a veterinary pharmaceutical generally used to control the ecto- and endoparasites of livestock, but its use has resulted in adverse effects on coprophilous insects, causing population decline and biodiversity loss. There is currently no information regarding the direct effects of ivermectin on dung beetle physiology and behaviour. Here, based on electroantennography and spontaneous muscle force tests, we show sub-lethal disorders caused by ivermectin in sensory and locomotor systems of Scarabaeus cicatricosus, a key dung beetle species in Mediterranean ecosystems. Our findings show that ivermectin decreases the olfactory and locomotor capacity of dung beetles, preventing them from performing basic biological activities. These effects are observed at concentrations lower than those usually measured in the dung of treated livestock. Taking into account that ivermectin acts on both glutamate-gated and GABA-gated chloride ion channels of nerve and muscle cells, we predict that ivermectin’s effects at the physiological level could influence many members of the dung pat community. The results indicate that the decline of dung beetle populations could be related to the harmful effects of chemical contamination in the dung.

Durante el curso 2013-2014 se implementó en la asignatura de Fisiología Animal I, del Grado en Biología de la Universidad de Alicante, un entorno personal de aprendizaje (EPA), a partir de la herramienta Scliped. Esta herramienta permitió desarrollar una red social de contenidos seleccionados por el profesorado, como estrategia docente para poner a disposición del alumnado recursos de excelencia que faciliten su aprendizaje. La inversión de tiempo y dinero requerida fue sensiblemente inferior a la necesaria para el desarrollo de materiales específicos equivalentes. El alumnado tuvo a su disposición un tablero de 130 contenidos seleccionados, distribuidos en 34 colecciones. Al finalizar el curso escolar 2013-2014, el EPA había recibido un total de 60.794 visitas. La evaluación del uso y conformidad del alumnado con esta herramienta mostró que, si bien opinaban que su uso era innovador, no podría sustituir la labor del profesorado. El porcentaje de adhesión a la herramienta fue bajo, tan sólo el 16% del alumnado encuestado, sin embargo, este grupo declaró que el uso de Scliped era sencillo y atractivo, que los contenidos eran pertinentes y estaban bien organizados, y que les habían facilitado el estudio y la comprensión de la materia.

Ivermectin is a veterinary pharmaceutical generally used to control the ecto- and endoparasites of livestock, but its use has resulted in adverse effects on coprophilous insects, causing population decline and biodiversity loss. There is currently no information regarding the direct effects of ivermectin on dung beetle physiology and behaviour. Here, based on electroantennography and spontaneous muscle force tests, we show sub-lethal disorders caused by ivermectin in sensory and locomotor systems of Scarabaeus cicatricosus, a key dung beetle species in Mediterranean ecosystems. Our findings show that ivermectin decreases the olfactory and locomotor capacity of dung beetles, preventing them from performing basic biological activities. These effects are observed at concentrations lower than those usually measured in the dung of treated livestock. Taking into account that ivermectin acts on both glutamate-gated and GABA-gated chloride ion channels of nerve and muscle cells, we predict that ivermectin € s effects at the physiological level could influence many members of the dung pat community. The results indicate that the decline of dung beetle populations could be related to the harmful effects of chemical contamination in the dung.