Editorial

Ars Pharmaceutica is a multidisciplinary scientific journal which focuses on all aspects of pharmaceutical science. It was the first journal of its type in Spain, and has been published by the Faculty of Pharmacy of the University of Granada every year for the past 51 years. During this time, it has evolved in the same way as most scientific journals, and is now no longer only printed in paper format, but is also available free of charge via the Internet. This means that more and more researchers from around the world can access the journal. And they have done so, as proven by the high number of website hits and researchers’ growing interest in having their work published in the journal. Another reason why the number of papers received over the last year has increased is that the journal now accepts papers in both Spanish and English. The journal is currently indexed in the following databases: Chemical Abstracts; ICYT (CSIC); EMBASE/Excerpta Médica; International Pharmaceutical Abstracts (IPA); Indice Bibliográfico Español en Ciencias de la Salud (IBECS); Biological Abstracts; and Life Sciences Collection. We are working to have the journal included in more databases in the future.The current issue, number 52, is the first of a new era, for which we, the editorial team at Ars Pharmaceutica, have set ourselves two priority objectives: to produce a top-quality journal, and to achieve maximum exposure amongst the scientific and pharmaceutical community.We have therefore designed and developed a new website. The different categories of papers suitable for publication have been clearly defined. An electronic submission system has been developed to make it easier for authors to submit their papers via our website. We now have more human and financial resources, and these have allowed us to produce the journal in electronic format, available free of charge to all the scientists and professionals who want to read it.In this new era for the journal, the publication and editorial guidelines will be adapted so that they come into line with international requirements for scientific publications. We would therefore like to remind authors to check that their papers meet the requirements stipulated in the Guide for authors before they submit them to us. Ars Pharmaceutica uses a peer review system so that each paper is reviewed by experts in the research focus of each study and the methodologies used.Our second aim is to increase the readership of Ars Pharmaceutica and encourage authors to submit their papers to the journal. To do this, we will make the publication available to public and private research bodies and scientific and professional associations. We would therefore like to take this opportunity to invite all authors to send their contributions to the different sections of the journal.We cannot sign off without thanking the people whose hard work made all of this possible back in the 1960s, Professors Cabo and Suñé. If it were not for their enthusiasm and determination to create and maintain this journal, with so little money and hardly any external help, we would not be here today, pouring all our renewed energy into what we believe could become a key tool for the dissemination of scientific knowledge in the field of pharmacy.Ars Pharmaceutica es una revista científica de carácter multidisciplinar, en el ámbito de las ciencias farmacéuticas en su sentido más amplio, pionera en España, editada por la Facultad de Farmacia de la Universidad de Granada durante los últimos 51 años de manera ininterrumpida. Durante este tiempo se ha ido adaptando a la evolución de la mayoría de las revistas científicas, en la que se ha pasado de su publicación en papel a convertirla en una revista electrónica de libre acceso. Esto ha supuesto una mayor accesibilidad de investigadores de todos los países a la publicación, lo que se ha podido comprobar por el número de visitas recibidas en la web, y un interés por publicar sus trabajos en ella. El hecho de aceptar trabajos en español o inglés indistintamente, también ha contribuido a aumentar el número de originales recibidos en el último año. Actualmente se encuentra indexada en las siguientes bases de datos: Chemicals Abstracts, ICYT (CSIC); EMBASE/Excerpta Médica; International Pharmaceutical Abstrac (IPA); Indice Bibliográfico Español en Ciencias de la Salud (IBECS); Biological Abstrac, Life Sciencies Collection, y es nuestra intención aumentar su presencia en otras bases.Este número 52 es el primero de una nueva etapa, en la cual los responsables de Ars Pharmacéutica nos hemos planteado como principales objetivos, conseguir la mejor calidad editorial posible y la máxima visibilidad en la comunidad científica relacionada con las áreas farmacéuticas.Para ello hemos diseñado y desarrollado una nueva página web. Se han establecido de forma clara las distintas categorías de trabajos que se pueden publicar. Para agilizar el envió de originales a través de la web se ha desarrollado un sistema electrónico de envío. Se han habilitado recursos humanos y económicos, que nos permiten ofrecer la revista en formato electrónico y de forma gratuita a todos los científicos y profesionales interesados.Esta nueva etapa supondrá también la adaptación de las normas de publicación y las normas editoriales a los requerimientos internacionales de publicaciones científicas. De ahí que se llame la atención a los autores a que antes de enviar un trabajo comprueben que cumple los requisitos que se incluyen en la guía de autor. Ars Pharmacéutica es una revista arbitrada que utiliza el sistema de revisión externa por expertos (peer-review), en el conocimiento de los objetos investigados y en las metodologías utilizadas en las investigaciones.Nuestro segundo objetivo es conseguir una difusión masiva de Ars Pharmaceutica y fomentar el interés por publicar en la misma, poniéndola a disposición de los organismos de investigación públicos y privados, sociedades científicas y profesionales. Por ello desde aquí invitamos a todos los autores a enviar sus aportaciones a las distintas secciones de la revista.No quisiéramos finalizar estas palabras sin tener un cariñoso recuerdo de los que fueron los artífices y promotores de esta revista, los profesores Cabo y Suñé. Su ilusión, tesón e interés en los años 60 del pasado siglo, por crear y mantener con bajo presupuesto y poca ayuda exterior esta revista, ha permitido que hoy sigamos con renovadas energías lo que consideramos puede ser un órgano de difusión del conocimiento científico en el ámbito farmacéutico

Recomendaciones nutricionales para los ancianos

En los últimos años, el rápido envejecimiento de la población está originando un gran número de estudios encaminadosa conocer en mayor profundidad este proceso, así como a identificar los factores de riesgo que puedenmodificarlo de forma negativa. Dentro de estos factores de riesgo hay que considerar la importancia que tiene unaalimentación adecuada en esta etapa de la vida. Sin embargo es difícil establecer unas recomendaciones nutricionalespara un grupo de población tan heterogéneo. En esta revisión, se recogen las recomendaciones nutricionales dadaspor distintos organismos para población mayor

Editorial

Ars Pharmaceutica es una revista científica de carácter multidisciplinar, en el ámbito de las ciencias farmacéuticas en su sentido más amplio, pionera en España, editada por la Facultad de Farmacia de la Universidad de Granada durante los últimos 51 años de manera ininterrumpida. Durante este tiempo se ha ido adaptando a la evolución de la mayoría de las revistas científicas, en la que se ha pasado de su publicación en papel a convertirla en una revista electrónica de libre acceso. Esto ha supuesto una mayor accesibilidad de investigadores de todos los países a la publicación, lo que se ha podido comprobar por el número de visitas recibidas en la web, y un interés por publicar sus trabajos en ella. El hecho de aceptar trabajos en español o inglés indistintamente, también ha contribuido a aumentar el número de originales recibidos en el último año. Actualmente se encuentra indexada en las siguientes bases de datos: Chemicals Abstracts, ICYT (CSIC); EMBASE/Excerpta Médica; International Pharmaceutical Abstrac (IPA); Indice Bibliográfico Español en Ciencias de la Salud (IBECS); Biological Abstrac, Life Sciencies Collection, y es nuestra intención aumentar su presencia en otras bases.Este número 52 es el primero de una nueva etapa, en la cual los responsables de Ars Pharmacéutica nos hemos planteado como principales objetivos, conseguir la mejor calidad editorial posible y la máxima visibilidad en la comunidad científica relacionada con las áreas farmacéuticas.Para ello hemos diseñado y desarrollado una nueva página web. Se han establecido de forma clara las distintas categorías de trabajos que se pueden publicar. Para agilizar el envió de originales a través de la web se ha desarrollado un sistema electrónico de envío. Se han habilitado recursos humanos y económicos, que nos permiten ofrecer la revista en formato electrónico y de forma gratuita a todos los científicos y profesionales interesados.Esta nueva etapa supondrá también la adaptación de las normas de publicación y las normas editoriales a los requerimientos internacionales de publicaciones científicas. De ahí que se llame la atención a los autores a que antes de enviar un trabajo comprueben que cumple los requisitos que se incluyen en la guía de autor. Ars Pharmacéutica es una revista arbitrada que utiliza el sistema de revisión externa por expertos (peer-review), en el conocimiento de los objetos investigados y en las metodologías utilizadas en las investigaciones.Nuestro segundo objetivo es conseguir una difusión masiva de Ars Pharmaceutica y fomentar el interés por publicar en la misma, poniéndola a disposición de los organismos de investigación públicos y privados, sociedades científicas y profesionales, por ello desde aquí invitamos a todos los autores a enviar sus aportaciones a las distintas secciones de la revista.No quisiéramos finalizar estas palabras sin tener un cariñoso recuerdo de los que fueron los artífices y promotores de esta revista, los profesores Cabo y Suñé. Su ilusión, tesón e interés en los años 60 del pasado siglo, por crear y mantener con bajo presupuesto y poca ayuda exterior esta revista, ha permitido que hoy sigamos con renovadas energías lo que consideramos puede ser un órgano de difusión del conocimiento científico en el ámbito farmacéutico. Ars Pharmaceutica is a multidisciplinary scientific journal which focuses on all aspects of pharmaceutical science. It was the first journal of its type in Spain, and has been published by the Faculty of Pharmacy of the University of Granada every year for the past 51 years. During this time, it has evolved in the same way as most scientific journals, and is now no longer only printed in paper format, but is also available free of charge via the Internet. This means that more and more researchers from around the world can access the journal. And they have done so, as proven by the high number of website hits and researchers’ growing interest in having their work published in the journal. Another reason why the number of papers received over the last year has increased is that the journal now accepts papers in both Spanish and English. The journal is currently indexed in the following databases: Chemical Abstracts; ICYT (CSIC); EMBASE/Excerpta Médica; International Pharmaceutical Abstracts (IPA); Indice Bibliográfico Español en Ciencias de la Salud (IBECS); Biological Abstracts; and Life Sciences Collection. We are working to have the journal included in more databases in the future.The current issue, number 52, is the first of a new era, for which we, the editorial team at Ars Pharmaceutica, have set ourselves two priority objectives: to produce a top-quality journal, and to achieve maximum exposure amongst the scientific and pharmaceutical community.We have therefore designed and developed a new website. The different categories of papers suitable for publication have been clearly defined. An electronic submission system has been developed to make it easier for authors to submit their papers via our website. We now have more human and financial resources, and these have allowed us to produce the journal in electronic format, available free of charge to all the scientists and professionals who want to read it.In this new era for the journal, the publication and editorial guidelines will be adapted so that they come into line with international requirements for scientific publications. We would therefore like to remind authors to check that their papers meet the requirements stipulated in the Guide for authors before they submit them to us. Ars Pharmaceutica uses a peer review system so that each paper is reviewed by experts in the research focus of each study and the methodologies used.Our second aim is to increase the readership of Ars Pharmaceutica and encourage authors to submit their papers to the journal. To do this, we will make the publication available to public and private research bodies and scientific and professional associations. We would therefore like to take this opportunity to invite all authors to send their contributions to the different sections of the journal.We cannot sign off without thanking the people whose hard work made all of this possible back in the 1960s, Professors Cabo and Suñé. If it were not for their enthusiasm and determination to create and maintain this journal, with so little money and hardly any external help, we would not be here today, pouring all our renewed energy into what we believe could become a key tool for the dissemination of scientific knowledge in the field of pharmacy

A Sox2–Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells

Increased cancer stem cell content during development of resistance to tamoxifen in breast cancer is driven by multiple signals, including Sox2-dependent activation of Wnt signalling. Here, we show that Sox2 increases and estrogen reduces the expression of the transcription factor Sox9. Gain and loss of function assays indicate that Sox9 is implicated in the maintenance of human breast luminal progenitor cells. CRISPR/Cas knockout of Sox9 reduces growth of tamoxifen-resistant breast tumours in vivo. Mechanistically, Sox9 acts downstream of Sox2 to control luminal progenitor cell content and is required for expression of the cancer stem cell marker ALDH1A3 and Wnt signalling activity. Sox9 is elevated in breast cancer patients after endocrine therapy failure. This new regulatory axis highlights the relevance of SOX family transcription factors as potential therapeutic targets in breast cancer

B-Chromosome Ribosomal DNA Is Functional in the Grasshopper Eyprepocnemis plorans

B-chromosomes are frequently argued to be genetically inert elements, but activity for some particular genes has been reported, especially for ribosomal RNA (rRNA) genes whose expression can easily be detected at the cytological level by the visualization of their phenotypic expression, i.e., the nucleolus. The B24 chromosome in the grasshopper Eyprepocnemis plorans frequently shows a nucleolus attached to it during meiotic prophase I. Here we show the presence of rRNA transcripts that unequivocally came from the B24 chromosome. To detect these transcripts, we designed primers specifically anchoring at the ITS-2 region, so that the reverse primer was complementary to the B chromosome DNA sequence including a differential adenine insertion being absent in the ITS2 of A chromosomes. PCR analysis carried out on genomic DNA showed amplification in B-carrying males but not in B-lacking ones. PCR analyses performed on complementary DNA showed amplification in about half of B-carrying males. Joint cytological and molecular analysis performed on 34 B-carrying males showed a close correspondence between the presence of B-specific transcripts and of nucleoli attached to the B chromosome. In addition, the molecular analysis revealed activity of the B chromosome rDNA in 10 out of the 13 B-carrying females analysed. Our results suggest that the nucleoli attached to B chromosomes are actively formed by expression of the rDNA carried by them, and not by recruitment of nucleolar materials formed in A chromosome nucleolar organizing regions. Therefore, B-chromosome rDNA in E. plorans is functional since it is actively transcribed to form the nucleolus attached to the B chromosome. This demonstrates that some heterochromatic B chromosomes can harbour functional genes.This study was supported by a grant from the Spanish Ministerio de Ciencia e Innovación (CGL2009-11917), and was partially performed by FEDER funds. M. Ruiz-Estévez was supported by a fellowship (FPU) from the Spanish Ministerio de Ciencia e Innovación

Evolutionary and phenotypic characterization of two spike mutations in European lineage 20E of SARS-CoV-2.

We have detected two mutations in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at amino acid positions 1163 and 1167 that appeared independently in multiple transmission clusters and different genetic backgrounds. Furthermore, both mutations appeared together in a cluster of 1,627 sequences belonging to clade 20E. This cluster is characterized by 12 additional single nucleotide polymorphisms but no deletions. The available structural information on the S protein in the pre- and postfusion conformations predicts that both mutations confer rigidity, which could potentially decrease viral fitness. Accordingly, we observed reduced infectivity of this spike genotype relative to the ancestral 20E sequence in vitro, and the levels of viral RNA in nasopharyngeal swabs were not significantly higher. Furthermore, the mutations did not impact thermal stability or antibody neutrali- zation by sera from vaccinated individuals but moderately reduce neutralization by convalescent-phase sera from the early stages of the pandemic. Despite multi- ple successful appearances of the two spike mutations during the first year of SARS-CoV-2 evolution, the genotype with both mutations was displaced upon the expansion of the 20I (Alpha) variant. The midterm fate of the genotype investi- gated was consistent with the lack of advantage observed in the clinical and ex- perimental data

Preferential Occupancy of R2 Retroelements on the B Chromosomes of the Grasshopper Eyprepocnemis plorans

R2 non-LTR retrotransposons exclusively insert into the 28S rRNA genes of their host, and are expressed by co-transcription with the rDNA unit. The grasshopper Eyprepocnemis plorans contains transcribed rDNA clusters on most of its A chromosomes, as well as non-transcribed rDNA clusters on the parasitic B chromosomes found in many populations. Here the structure of the E. plorans R2 element, its abundance relative to the number of rDNA units and its retrotransposition activity were determined. Animals screened from five populations contained on average over 12,000 rDNA units on their A chromosomes, but surprisingly only about 100 R2 elements. Monitoring the patterns of R2 insertions in individuals from these populations revealed only low levels of retrotransposition. The low rates of R2 insertion observed in E. plorans differ from the high levels of R2 insertion previously observed in insect species that have many fewer rDNA units. It is proposed that high levels of R2 are strongly selected against in E. plorans, because the rDNA transcription machinery in this species is unable to differentiate between R2-inserted and uninserted units. The B chromosomes of E. plorans contain an additional 7,000 to 15,000 rDNA units, but in contrast to the A chromosomes, from 150 to over 1,500 R2 elements. The higher concentration of R2 in the inactive B chromosomes rDNA clusters suggests these chromosomes can act as a sink for R2 insertions thus further reducing the level of insertions on the A chromosomes. These studies suggest an interesting evolutionary relationship between the parasitic B chromosomes and R2 elements.This study was supported by grants from the Spanish Ministerio de Ciencia y Tecnología (CGL2009-11917) and Plan Andaluz de Investigacion (CVI-6649), and was partially performed by FEDER funds and a grant from the National Institutes of Health (GM42790)

The APPswe/PS1A246E mutations in an astrocytic cell line leads to increased vulnerability to oxygen and glucose deprivation, Ca2+ dysregulation and mitochondrial abnormalities

Growing evidence suggests a close relationship between Alzheimer's Disease (AD) and cerebral hypoxia. Astrocytes play a key role in brain homeostasis and disease states, while some of the earliest changes in AD occur in astrocytes. We have therefore asked whether mutations associated with AD increase astrocyte vulnerability to ischemia. Two astroglioma cell lines derived from APPSWE /PS1A246E (APP, amyloid precursor protein; PS1, presenilin 1) transgenic mice and controls from normal mice were subjected to oxygen and glucose deprivation (OGD), an in vitro model of ischemia. Cell death was increased in the APPSWE /PS1A246E line compared to the control. Increasing extracellular calcium concentration ([Ca2+ ]) exacerbated cell death in the mutant but not in the control cells. In order to explore cellular Ca2+ homeostasis the cells were challenged with ATP or thapsigargin and [Ca2+ ] was measured by fluorescence microscopy. Changes in cytosolic Ca2+ concentration ([Ca2+ ]c ) were potentiated in the APPSWE /PS1A246E transgenic line. Mitochondrial function was also altered in the APPSWE /PS1A246E astroglioma cells; mitochondrial membrane potential and production of reactive oxygen species were increased while mitochondrial basal respiratory rate and ATP production were decreased compared to control astroglioma cells. These results suggest that AD mutations in astrocytes make them more sensitive to ischemia; Ca2+ dysregulation and mitochondrial dysfunction may contribute to this increased vulnerability. Our results also highlight the role of astrocyte dyshomeostasis in the pathophysiology of neurodegenerative brain disorders