Ermitas de la Sierra Morena cordobesa

Análisis de las ermitas cordobesas de Sierra Morena en función del paisaje, los valores arquitectónicos y como contenedoras de bienes muebles.Las ermitas constituyen uno de los bienes inmuebles de naturaleza religiosa con un intenso calado social. De los procesos de inventario realizados en la provincia de Córdoba en la década de los noventa del siglo pasado se ha obtenido una serie de rasgos y características, muchos comunes a la tipología, de la comarca de Sierra Morena, basados en la relación con el territorio, la organización del espacio arquitectónico y los bienes muebles que lo ocupan

Recensiones [Revista de Historia Económica Año II Primavera-Verano 1984 n. 2 pp. 185-208]

Lester K. Little. Pobreza voluntaria y economía de beneficio en ¡a Europa medieval (Miguel Ángel Ladero Quesada).-- Fermín Rey Velasco. Historia económica y social de Extremadura a finales del Antiguo Régimen (Enrique Llopis Agelan).-- D. R. Ringrose. Madrid and the Spanish Economy, 1360-1850 (Agustín González Enciso).-- J. Romero González. Propiedad agraria y sociedad rural en la España mediterránea. Los casos valenciano y castellano en los siglos XIX y XX (Ramón Garrabou).-- Karl Dietrich Bracher. Controversias de historia contemporánea sobre fascismo, totalitarismo y democracia (Mercedes Cabrera).-- Banco De España. Actas del Primer Congreso sobre Archivos Económicos de Entidades Privadas (Pablo Martín Aceña).-- Francisca Alexandre Tena. Catálogo de la Biblioteca y Archivo del Instituto Valenciano de Economía (Teresa Tortella).-- Manuel Garzón Pareja. La Hacienda de Carlos II (Joaquín del Moral Ruiz)Publicad

Small Molecules as Dream Modulators: New Avenues for the Search of Drugs for Neurodegenerative Diseases

Trabajo presentado en el 9th drug Design and Medicinal Chemistry, celebrado en Berlín (Alemania) del 05 al 06 de mayo de 2015.Altered neuronal calcium homeostasis and early compensatory changes in transcriptional programs are common features of many neurodegenerative pathologies including Alzheimer¿s disease, Down syndrome and Huntington¿s disease. DREAM (Downstream Regulatory Element Antagonist Modulator), also known as calsenilin or KChIP-3 (potassium channel interacting protein-3), is a multifunctional calcium binding protein that controls the expression level and/or the activity of several proteins related to calcium homeostasis, neuronal excitability and neuronal survival. This protein is widely expressed in the brain and, depending on the cell type and physiological conditions, shows multiple subcellular localizations, in the nucleus, cytosol or cell membrane. The interest in DREAM is based on its key role in the regulation of intracellular calcium levels. As a calcium-dependent transcriptional repressor, DREAM is a master regulator of activity-dependent gene expression and controls genes important for calcium homeostasis such as the sodium/calcium exchanger-3 (NCX3), IP3R and L-type calcium channels. As an auxiliary protein in the plasma membrane, DREAM interacts with and regulates the gating of Kv4 potassium channels, L- and T-type voltage-dependent calcium channels and NMDA receptors. These findings suggest that DREAM could be a novel and versatile target for therapeutic intervention in neurodegeneration and that molecules able to bind to DREAM and block its physiological functions could be candidates for drugs to treat neurodegenerative diseases. Moreover, up to now, only two DREAM-binding molecules have been identified. In this communication we report the rational design and the synthesis of novel DREAM-binding molecules and their effects on the modulation of DREAM/protein interactions

Adsorción del colorante azul directo 2 sobre borra de café en una columna de lecho fijo a escala de laboratorio

La contaminación del agua con colorantes sintéticos, resultado de las actividades industriales, es un problema latente en la sociedad. Su presencia, aun en concentraciones muy bajas, influye drásticamente en los procesos de fotosíntesis, porque impide la penetración de la luz, afectando la vida acuática e, incluso, la salud humana. La adsorción con carbón activado es una de las técnicas más empleadas para remover el color de los efluentes, pero sus altos costos han dirigido la atención de los investigadores hacia el estudio de materiales adsorbentes provenientes, principalmente, de la agroindustria. Este artículo presenta un estudio sobre la remoción del colorante azul directo 2 en disolución acuosa sobre borra de café sin tratar y modificada a 30±1°C, en una columna empacada. Se realizó la caracterización fisicoquímica de los adsorbentes, que incluye la evaluación de las propiedades de textura, mediante isotermas de adsorción, con N2 a 77K, la identificación y cuantificación de grupos funcionales orgánicos, con FTIR y el método de Boemh. El estudio en columna evaluó el efecto de la altura del lecho del adsorbente (Z = 3 y 6cm), el flujo volumétrico (Qv= 2 y 4cm3min-1) y la concentración inicial (Co = 8 y 14mgdm-3), sobre el tiempo de ruptura y la capacidad de adsorción. Los datos experimentales de las curvas de ruptura se ajustaron al modelo BDST (Bed Depth Service Time). Los resultados muestran que el rendimiento de la columna mejora con el incremento de Z y la disminución de Qv y Co, siendo la concentración inicial, el factor con mayor significancia

Neutral and ionic platinum compounds containing a cyclometalated chiral primary amine: Synthesis, antitumor activity, DNA interaction and topoisomerase I - cathepsin B inhibition

The synthesis and preliminary biological evaluation of neutral and cationic platinum derivatives of chiral 1-(1-naphthyl)ethylamine are reported, namely cycloplatinated neutral complexes [PtCl{(R or S)-NH(2)CH(CH(3))C(10)H(6)}(L)] [L = SOMe(2) ( 1-R or 1-S ), L = PPh(3) (2-R or 2-S), L = P(4-FC(6)H(4))(3) (3-R), L = P(CH(2))(3)N(3)(CH(2))(3) (4-R)], cycloplatinated cationic complexes [Pt{(R)-NH(2)CH(CH(3))C(10)H(6)}{L}]Cl [L = Ph(2)PCH(2)CH(2)PPh(2) (5-R), L = (C(6)F(5))(2)PCH(2)CH(2)P(C(6)F(5))(2) (6-R)] and the Pt(ii) coordination compound trans-[PtCl(2){(R)-NH(2)CH(CH(3))C(10)H(6)}(2)] (7-R). The X-ray molecular structure of 7-R is reported. The cytotoxic activity against a panel of human adenocarcinoma cell lines (A-549 lung, MDA-MB-231 and MCF-7 breast, and HCT-116 colon), cell cycle arrest and apoptosis, DNA interaction, topoisomerase I and cathepsin B inhibition, and Pt cell uptake of the studied compounds are presented. Remarkable cytotoxicity was observed for most of the synthesized Pt(ii) compounds regardless of (i) the absolute configuration R or S, and (ii) the coordinated/cyclometallated (neutral or cationic) nature of the complexes. The most potent compound 2-R (IC(50) = 270 nM) showed a 148-fold increase in potency with regard to cisplatin in HCT-116 colon cancer cells. Preliminary biological results point out to different biomolecular targets for the investigated compounds. Neutral cyclometallated complexes 1-R and 2-R, modify the DNA migration as cisplatin, cationic platinacycle 5-R was able to inhibit topoisomerase I-promoted DNA supercoiling, and Pt(ii) coordination compound 7-R turned out to be the most potent inhibitor of cathepsin B. Induction of G-1 phase ( 2-R and 5-R ), and S and G-2 phases (6-R) arrests are related to the antiproliferative activity of some representative compounds upon A-549 cells. Induction of apoptosis is also observed for 2-R and 6-R

A GIS-supported Multidisciplinary Database for the Management of UNESCO Global Geoparks: the Courel Mountains Geopark (Spain)

[Abstract] The management of a UNESCO Global Geopark (UGGp) requires a vast wealth of miscellaneous scientific knowledge that can be successfully organised using a Geographical Information System (GIS). This paper presents a pragmatic GIS database to assist in the suitable governance of the Courel Mountains UGGp (2017) in Northwest Spain. The database is structured in 66 coverages compiled from public sources and previous works or produced through traditional mapping (combining fieldwork and photointerpretation) and GIS tools. The acquired data was later homogenised and validated by a multidisciplinary team and archived in independent coverages. Forty thematic maps illustrate the broad range of cartographic information included in the GIS database. Among them, 25 basic maps provide an overview of the UGGp and 15 new maps focus on crosscutting and technical issues. All maps illustrate the huge potential of GIS to create new resources combining coverages and adapting the legend according to their purpose and audience. The database facilitates the suitable publishing of consistent outputs (e.g., brochures, books, panels, webpages, web serves), as well as the elaboration of technical data to assist the park management. The database furnishes information on the design of education actions, touristic routes, activities and Geopark facilities. The GIS database is also a supportive tool for scientific research and provides the necessary knowledge to conduct geoconservation actions based on land use, geological hazards and the occurrence of natural and cultural heritages. Altogether, the GIS database constitutes a powerful instrument for policy-making, facilitating the identification and evaluation of alternative strategy plans.This work was developed in the framework of the Scientific Program of the Courel Mountains UGGp with the cooperation of tourism agents (A.M. Arza and A. López), roofing slate quarries (Pizarras de Villarbacú, Pizarras de Quiroga) and local people (M. Reinosa, G. Díaz, O. Álvarez). We are deeply grateful to J.R. Martínez Catalán (Universidad de Salamanca), A. Pérez-Alberti and J. Guitián (both from Universidade de Santiago de Compostela), J.R. Gutiérrez-Marco (ICOG, Universidad Complutense de Madrid/CSIC), J. Vegas (IGME-CSIC), L. González-Menéndez (IGME-CSIC), J.M. García Queijeiro (Universidade de Vigo), L. Santos and A. Grandal-D’Anglade (both from Universidade da Coruña) for their assistance supplying information involved in the database. We thank also E. de Boer for proofreading the article. DB is grant holder of Plan Andaluz de Investigación, Desarrollo e Innovación 2021, funded by Junta de Andalucí

Stroma-Mediated Resistance to S63845 and Venetoclax through MCL-1 and BCL-2 Expression Changes Induced by miR-193b-3p and miR-21-5p Dysregulation in Multiple Myeloma.

BH3-mimetics targeting anti-apoptotic proteins such as MCL-1 (S63845) or BCL-2 (venetoclax) are currently being evaluated as effective therapies for the treatment of multiple myeloma (MM). Interleukin 6, produced by mesenchymal stromal cells (MSCs), has been shown to modify the expression of anti-apoptotic proteins and their interaction with the pro-apoptotic BIM protein in MM cells. In this study, we assess the efficacy of S63845 and venetoclax in MM cells in direct co-culture with MSCs derived from MM patients (pMSCs) to identify additional mechanisms involved in the stroma-induced resistance to these agents. MicroRNAs miR-193b-3p and miR-21-5p emerged among the top deregulated miRNAs in myeloma cells when directly co-cultured with pMSCs, and we show their contribution to changes in MCL-1 and BCL-2 protein expression and in the activity of S63845 and venetoclax. Additionally, direct contact with pMSCs under S63845 and/or venetoclax treatment modifies myeloma cell dependence on different BCL-2 family anti-apoptotic proteins in relation to BIM, making myeloma cells more dependent on the non-targeted anti-apoptotic protein or BCL-XL. Finally, we show a potent effect of the combination of S63845 and venetoclax even in the presence of pMSCs, which supports this combinatorial approach for the treatment of MM

La sensibilización precoz hacia la muerte en la adquisición de competencias actitudinales en estudiantes de Medicina: fase clínica

Memoria ID-0205. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2016-2017

Functional Connectivity Disruption in Subjective Cognitive Decline and Mild Cognitive Impairment: A Common Pattern of Alterations

Functional connectivity (FC) alterations represent a key feature in Alzheimer's Disease (AD) and provide a useful tool to characterize and predict the course of the disease. Those alterations have been also described in Mild Cognitive Impairment (MCI), a prodromal stage of AD. There is a growing interest in detecting AD pathology in the brain in the very early stages of the disorder. Subjective Cognitive Decline (SCD) could represent a preclinical asymptomatic stage of AD but very little is known about this population. In the present work we assessed whether FC disruptions are already present in this stage, and if they share any spatial distribution properties with MCI alterations (a condition known to be highly related to AD). To this end, we measured electromagnetic spontaneous activity with MEG in 39 healthy control elders, 41 elders with SCD and 51 MCI patients. The results showed FC alterations in both SCD and MCI compared to the healthy control group. Interestingly, both groups exhibited a very similar spatial pattern of altered links: a hyper-synchronized anterior network and a posterior network characterized by a decrease in FC. This decrease was more pronounced in the MCI group. These results highlight that elders with SCD present FC alterations. More importantly, those disruptions affected AD typically related areas and showed great overlap with the alterations exhibited by MCI patients. These results support the consideration of SCD as a preclinical stage of AD and may indicate that FC alterations appear very early in the course of the disease