(Re)discovering Vicki Penfold's linocuts

Vicki Penfold (Krakow 1918 - Tenerife 2013) was a Polish-born artist who arrived in the Canary Islands in the 1960s after a long pilgrimage to places as disparate as Kenya, Paris and Israel, among others. She also traveled to Austria to become a student of Oskar Kokoschka in his Salzburg studio. Her personal archive, recently donated to the Instituto de Estudios Hispánicos de Canarias (hereafter IEHC) on the island of Tenerife, preserves a wide variety of materials that are currently being inventoried and catalogued. This collection presents a huge potential for study and cross-sectional analysis to address the methodology of the artist and the materiality of his work. This article proposes an initial analysis of the various matrices, relating them to the pieces currently preserved and establishing relationships with the documentation contained in his personal archive. It also aims to highlight Vicki Penfold as a graphic artist, perhaps her most overlooked facet, but one that highlights her enormous sensitivity and versatility in working with a wide variety of techniques.Vicki Penfold (Cracovie 1918 - Tenerife 2013) était une artiste d'origine polonaise qui est arrivée aux îles Canaries dans les années soixante du siècle dernier après un long pèlerinage dans des lieux aussi disparates que le Kenya, Paris et Israël, entre autres. Elle s'est également rendue en Autriche pour devenir l'élève d'Oskar Kokoschka dans son atelier de Salzbourg. Ses archives personnelles, récemment données à l'Instituto de Estudios Hispánicos de Canarias (ci-après IEHC) sur l'île de Ténérife, conservent une grande variété de matériaux qui sont actuellement en cours d'inventaire et de catalogage. Cette collection présente un énorme potentiel d'étude et d'analyse transversale pour aborder la méthodologie de l'artiste et la matérialité de son travail. Cet article propose une première analyse des différentes matrices, en les mettant en relation avec les pièces actuellement conservées et en établissant des relations avec la documentation contenue dans ses archives personnelles. Il cherche également à mettre en valeur la figure de Vicki Penfold en tant qu'artiste graphique, peut-être sa facette la plus méconnue, mais qui met en évidence son énorme sensibilité et sa polyvalence à travailler avec une grande variété de techniques

Vitamin D deficiency as a potential risk factor for accelerated aging, impaired hippocampal neurogenesis and cognitive decline: a role for Wnt/β-catenin signaling

Vitamin D is an essential fat-soluble vitamin that participates in several homeostatic functions in mammalian organisms. Lower levels of vitamin D are produced in the older population, vitamin D deficiency being an accelerating factor for the progression of the aging process. In this review, we focus on the effect that vitamin D exerts in the aged brain paying special attention to the neurogenic process. Neurogenesis occurs in the adult brain in neurogenic regions, such as the dentate gyrus of the hippocampus (DG). This region generates new neurons that participate in cognitive tasks. The neurogenic rate in the DG is reduced in the aged brain because of a reduction in the number of neural stem cells (NSC). Homeostatic mechanisms controlled by the Wnt signaling pathway protect this pool of NSC from being depleted. We discuss in here the crosstalk between Wnt signaling and vitamin D, and hypothesize that hypovitaminosis might cause failure in the control of the neurogenic homeostatic mechanisms in the old brain leading to cognitive impairment. Understanding the relationship between vitamin D, neurogenesis and cognitive performance in the aged brain may facilitate prevention of cognitive decline and it can open a door into new therapeutic fields by perspectives in the elderly.Ministerio de Ciencia, Innovación y Universidades RTI2018-099908-B-C21FEDER-UCA18-1066

Phorbol Diesters and 12-Deoxy-16-hydroxyphorbol 13,16-Diesters Induce TGFα Release and Adult Mouse Neurogenesis

A small library of phorbol 12,13-diesters bearing low lipophilicity ester chains was prepared as potential neurogenic agents in the adult brain. They were also used in a targeted UHPLC–HRMS screening of the latex of Euphorbia resinifera. Two new 12-deoxy-16-hydroxyphorbol 13,16-diesters were isolated, and their structures were deduced using two-dimensional NMR spectroscopy and NOE experiments. The ability of natural and synthetic compounds to stimulate transforming growth factor alpha (TFGα) release, to increase neural progenitor cell proliferation, and to stimulate neurogenesis was evaluated. All compounds that facilitated TGFα release promoted neural progenitor cell proliferation. The presence of two acyloxy moieties on the tigliane skeleton led to higher levels of activity, which decreased when a free hydroxyl group was at C-12. Remarkably, the compound bearing isobutyryloxy groups was the most potent on the TGFα assay and at inducing neural progenitor cell proliferation in vitro, also leading to enhanced neurogenesis in vivo when administered intranasally to mice.Ministerio de Ciencia, Innovación y Universidades de España y fondos FEDER. RTI2018–099908-B-C21 y RTI2018–099908-B-C2

Evolution of Experimental Models in the Study of Glioblastoma: Toward Finding Efficient Treatments

Glioblastoma (GBM) is the most common form of brain tumor characterized by its resistance to conventional therapies, including temozolomide, the most widely used chemotherapeutic agent in the treatment of GBM. Within the tumor, the presence of glioma stem cells (GSC) seems to be the reason for drug resistance. The discovery of GSC has boosted the search for new experimental models to study GBM, which allow the development of new GBM treatments targeting these cells. In here, we describe different strategies currently in use to study GBM. Initial GBM investigations were focused in the development of xenograft assays. Thereafter, techniques advanced to dissociate tumor cells into single-cell suspensions, which generate aggregates referred to as neurospheres, thus facilitating their selective expansion. Concomitantly, the finding of genes involved in the initiation and progression of GBM tumors, led to the generation of mice models for the GBM. The latest advances have been the use of GBM organoids or 3D-bioprinted mini-brains. 3D bio-printing mimics tissue cytoarchitecture by combining different types of cells interacting with each other and with extracellular matrix components. These in vivo models faithfully replicate human diseases in which the effect of new drugs can easily be tested. Based on recent data from human glioblastoma, this review critically evaluates the different experimental models used in the study of GB, including cell cultures, mouse models, brain organoids, and 3D bioprinting focusing in the advantages and disadvantages of each approach to understand the mechanisms involved in the progression and treatment response of this devastating disease

Effects of classical PKC activation on hippocampal neurogenesis and cognitive performance: mechanism of action

Hippocampal neurogenesis has widely been linked to memory and learning performance. New neurons generated from neural stem cells (NSC) within the dentate gyrus of the hippocampus (DG) integrate in hippocampal circuitry participating in memory tasks. Several neurological and neuropsychiatric disorders show cognitive impairment together with a reduction in DG neurogenesis. Growth factors secreted within the DG promote neurogenesis. Protein kinases of the protein kinase C (PKC) family facilitate the release of several of these growth factors, highlighting the role of PKC isozymes as key target molecules for the development of drugs that induce hippocampal neurogenesis. PKC activating diterpenes have been shown to facilitate NSC proliferation in neurogenic niches when injected intracerebroventricularly. We show in here that long-term administration of diterpene ER272 promotes neurogenesis in the subventricular zone and in the DG of mice, affecting neuroblasts differentiation and neuronal maturation. A concomitant improvement in learning and spatial memory tasks performance can be observed. Insights into the mechanism of action reveal that this compound facilitates classical PKCα activation and promotes transforming growth factor alpha (TGFα) and, to a lesser extent, neuregulin release. Our results highlight the role of this molecule in the development of pharmacological drugs to treat neurological and neuropsychiatric disorders associated with memory loss and a deficient neurogenesis.Ministerio de Ciencia, Innovación y Universidades de España (MICINN) RTI-2018-099908-B-C21 y RTI-2018-099908-B-C22Ministerio de Ciencia, Innovación y Universidades de España y Fondos FEDER de la Unión Europea (MICINN/FEDER) BFU2016-75038RConsejería de Economía, Conocimiento, Empresas y Universidades de la Junta de Andalucía y Fondos FEDER. FEDER-UCA18-10664

Rescue of neurogenesis and age-associated cognitive decline in SAMP8 mouse: Role of transforming growth factor-alpha

Neuropathological aging is associated with memory impairment and cognitive decline, affecting several brain areas including the neurogenic niche of the dentate gyrus of the hippocampus (DG). In the healthy brain, homeostatic mechanisms regulate neurogenesis within the DG to facilitate the continuous generation of neurons from neural stem cells (NSC). Nevertheless, aging reduces the number of activated neural stem cells and diminishes the number of newly generated neurons. Strategies that promote neurogenesis in the DG may improve cognitive performance in the elderly resulting in the development of treatments to prevent the progression of neurological disorders in the aged population. Our work is aimed at discovering targeting molecules to be used in the design of pharmacological agents that prevent the neurological effects of brain aging. We study the effect of age on hippocampal neurogenesis using the SAMP8 mouse as a model of neuropathological aging. We show that in 6-month-old SAMP8 mice, episodic and spatial memory are impaired; concomitantly, the generation of neuroblasts and neurons is reduced and the generation of astrocytes is increased in this model. The novelty of our work resides in the fact that treatment of SAMP8 mice with a transforming growth factor-alpha (TGFα) targeting molecule prevents the observed defects, positively regulating neurogenesis and improving cognitive performance. This compound facilitates the release of TGFα in vitro and in vivo and activates signaling pathways initiated by this growth factor. We conclude that compounds of this kind that stimulate neurogenesis may be useful to counteract the neurological effects of pathological aging.19 página

Effects of classical PKC activation on hippocampal neurogenesis and cognitive performance: mechanism of action

Hippocampal neurogenesis has widely been linked to memory and learning performance. New neurons generated from neural stem cells (NSC) within the dentate gyrus of the hippocampus (DG) integrate in hippocampal circuitry participating in memory tasks. Several neurological and neuropsychiatric disorders show cognitive impairment together with a reduction in DG neurogenesis. Growth factors secreted within the DG promote neurogenesis. Protein kinases of the protein kinase C (PKC) family facilitate the release of several of these growth factors, highlighting the role of PKC isozymes as key target molecules for the development of drugs that induce hippocampal neurogenesis. PKC activating diterpenes have been shown to facilitate NSC proliferation in neurogenic niches when injected intracerebroventricularly. We show in here that long-term administration of diterpene ER272 promotes neurogenesis in the subventricular zone and in the DG of mice, affecting neuroblasts differentiation and neuronal maturation. A concomitant improvement in learning and spatial memory tasks performance can be observed. Insights into the mechanism of action reveal that this compound facilitates classical PKC alpha activation and promotes transforming growth factor alpha (TGF alpha) and, to a lesser extent, neuregulin release. Our results highlight the role of this molecule in the development of pharmacological drugs to treat neurological and neuropsychiatric disorders associated with memory loss and a deficient neurogenesis

Targeting Protein Kinase C in Glioblastoma Treatment

Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor and is associated with a poor prognosis. Despite the use of combined treatment approaches, recurrence is almost inevitable and survival longer than 14 or 15 months after diagnosis is low. It is therefore necessary to identify new therapeutic targets to fight GBM progression and recurrence. Some publications have pointed out the role of glioma stem cells (GSCs) as the origin of GBM. These cells, with characteristics of neural stem cells (NSC) present in physiological neurogenic niches, have been proposed as being responsible for the high resistance of GBM to current treatments such as temozolomide (TMZ). The protein Kinase C (PKC) family members play an essential role in transducing signals related with cell cycle entrance, differentiation and apoptosis in NSC and participate in distinct signaling cascades that determine NSC and GSC dynamics. Thus, PKC could be a suitable druggable target to treat recurrent GBM. Clinical trials have tested the efficacy of PKC beta inhibitors, and preclinical studies have focused on other PKC isozymes. Here, we discuss the idea that other PKC isozymes may also be involved in GBM progression and that the development of a new generation of effective drugs should consider the balance between the activation of different PKC subtypes

Estudio comparativo del tiempo de tránsito intestinal con marcadores radiopacos en pacientes seropositivos y seronegativos para la enfermedad de Chagas

La enfermedad de Chagas afecta el sistema digestivo en un 10 a 15% de los casos. En el período crónico, dentro de los megasíndromes digestivos, el megacolon es más frecuente en Argentina. Este estudio intentó determinar el tiempo de tránsito colorrectal en pacientes seropositivos y seronegativos para la enfermedad de Chagas y así efectuar una comparación entre los mismos y evaluar si existen diferencias significativas. Fueron incluidos pacientes seropositivos y seronegativos para la Enfermedad de Chagas, a los cuales se les realizó examen físico, electrocardiograma, ecocardiograma, RX de tórax y extracción de sangre para realizar diagnóstico serológico actual con Hemaglutinación indirecta, ELISA e Inmunofluorescencia. Para la determinación del tiempo de tránsito colónico se emplearon 24 marcadores radiopacos Sitzmarks administrados y al 5to. día se realizó RX simple de abdomen de pié. Se consideró anormal al encontrarse 5 o más radiomarcadores en la RX