The Creation of an Experimental Camp of Protohistory at the Iberian Settlement of Estinclells (Verdú, Urgell, Catalonia)

The site of Estinclells is an Iberian Culture settlement in the Municipality of Verdú, Urgell (Catalonia) dating from thethird century BC (See Figures 1 and 2). Archaeological work was carried out between 2002 and 2014 under the auspices of the Regional Museum of Urgell (Museu Comarcal de l’Urgell) and the Archaeology Section of the Centre d’Estudis Lacetans in the framework of the research project entitled, "Economy and Evolution of the Iberian population in the Corb, Ondara and Sió River Valleys: Excavation of the Iberian Settlement of Estinclells, Verdú

Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease

Alternative splicing of pre-mRNA contributes strongly to the diversity of cell- and tissue-specific protein expression patterns. Global transcriptome analyses have suggested that >90% of human multiexon genes are alternatively spliced. Alterations in the splicing process cause missplicing events that lead to genetic diseases and pathologies, including various neurological disorders, cancers, and muscular dystrophies. In recent decades, research has helped to elucidate the mechanisms regulating alternative splicing and, in some cases, to reveal how dysregulation of these mechanisms leads to disease. The resulting knowledge has enabled the design of novel therapeutic strategies for correction of splicing-derived pathologies. In this review, we focus primarily on therapeutic approaches targeting splicing, and we highlight nanotechnology-based gene delivery applications that address the challenges and barriers facing nucleic acid-based therapeutics.Fil: Suñé Pou, Marc. Universidad de Barcelona; EspañaFil: Limeres, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Moreno Castro, Cristina. Institute of Parasitology and Biomedicine “López-Neyra"; EspañaFil: Hernández Munain, Cristina. Institute of Parasitology and Biomedicine “López-Neyra"; EspañaFil: Suñé Negre, Josep M.. Universidad de Barcelona; EspañaFil: Cuestas, María Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Suñé, Carlos. Institute of Parasitology and Biomedicine “López-Neyra"; Españ

Modeling of leishmaniasis infection dynamics: novel application to the design of effective therapies

<p>Abstract</p> <p>Background</p> <p>The WHO considers leishmaniasis as one of the six most important tropical diseases worldwide. It is caused by parasites of the genus <it>Leishmania </it>that are passed on to humans and animals by the phlebotomine sandfly. Despite all of the research, there is still a lack of understanding on the metabolism of the parasite and the progression of the disease. In this study, a mathematical model of disease progression was developed based on experimental data of clinical symptoms, immunological responses, and parasite load for <it>Leishmania amazonensis </it>in <it>BALB/c </it>mice.</p> <p>Results</p> <p>Four biologically significant variables were chosen to develop a differential equation model based on the GMA power-law formalism. Parameters were determined to minimize error in the model dynamics and time series experimental data. Subsequently, the model robustness was tested and the model predictions were verified by comparing them with experimental observations made in different experimental conditions. The model obtained helps to quantify relationships between the selected variables, leads to a better understanding of disease progression, and aids in the identification of crucial points for introducing therapeutic methods.</p> <p>Conclusions</p> <p>Our model can be used to identify the biological factors that must be changed to minimize parasite load in the host body, and contributes to the design of effective therapies.</p

Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease

Alternative splicing of pre-mRNA contributes strongly to the diversity of cell- and tissue-specific protein expression patterns. Global transcriptome analyses have suggested that >90% of human multiexon genes are alternatively spliced. Alterations in the splicing process cause missplicing events that lead to genetic diseases and pathologies, including various neurological disorders, cancers, and muscular dystrophies. In recent decades, research has helped to elucidate the mechanisms regulating alternative splicing and, in some cases, to reveal how dysregulation of these mechanisms leads to disease. The resulting knowledge has enabled the design of novel therapeutic strategies for correction of splicing-derived pathologies. In this review, we focus primarily on therapeutic approaches targeting splicing, and we highlight nanotechnology-based gene delivery applications that address the challenges and barriers facing nucleic acid-based therapeutics

Targeting Splicing in the Treatment of Human Disease

The tightly regulated process of precursor messenger RNA (pre-mRNA) alternative splicing (AS) is a key mechanism in the regulation of gene expression. Defects in this regulatory process affect cellular functions and are the cause of many human diseases. Recent advances in our understanding of splicing regulation have led to the development of new tools for manipulating splicing for therapeutic purposes. Several tools, including antisense oligonucleotides and trans-splicing, have been developed to target and alter splicing to correct misregulated gene expression or to modulate transcript isoform levels. At present, deregulated AS is recognized as an important area for therapeutic intervention. Here, we summarize the major hallmarks of the splicing process, the clinical implications that arise from alterations in this process, and the current tools that can be used to deliver, target, and correct deficiencies of this key pre-mRNA processing event. Keywords: alternative splicing, precursor messenger RNA, therapy, genetic diseas

Development and characterization of an improved formulation of cholesteryl oleate-loaded cationic solid-lipid nanoparticles as an efficient non-viral gene delivery system

Nanoparticle-mediated plasmid delivery is considered a useful tool to introduce foreign DNA into the cells for the purpose of DNA vaccination and/or gene therapy. Cationic solid-lipid nanoparticles (cSLNs) are considered one of the most promising non-viral vectors for nucleic acid delivery. Based on the idea that the optimization of the components is required to improve transfection efficiency, the present study aimed to formulate and characterize cholesteryl oleate-containing solid-lipid nanoparticles (CO-SLNs) incorporating protamine (P) to condense DNA to produce P:DNA:CO-SLN complexes as non-viral vectors for gene delivery with reduced cytotoxicity and high cellular uptake efficiency. For this purpose, CO-SLNs were used to prepare DNA complexes with and without protamine as DNA condenser and nuclear transfer enhancer. The main physicochemical characteristics, binding capabilities, cytotoxicity and cellular uptake of these novel CO-SLNs were analyzed. Positively charged spherical P:DNA:CO-SLN complexes with a particle size ranging from 330.1 ± 14.8 nm to 347.0 ± 18.5 nm were obtained. Positive results were obtained in the DNase I protection assay with a protective effect of the genetic material and 100% loading efficiency was achieved at a P:DNA:CO-SLN ratio of 2:1:7. Transfection studies in human embryonic kidney (HEK293T) cells showed the versatility of adding protamine to efficiently transfect cells, widening the potential applications of CO-SLN-based vectors, since the incorporation of protamine induced almost a 200-fold increase in the transfection capacity of CO-SLNs without toxicity. These results indicate that CO-SLNs with protamine are a safe and effective platform for non-viral nucleic acid delivery.Fil: Limeres, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina. Universidad de Barcelona; EspañaFil: Suñé Pou, Marc. Consejo Superior de Investigaciones Científicas; España. Universidad de Barcelona; EspañaFil: Prieto Sanchez, Silvia. Consejo Superior de Investigaciones Científicas; EspañaFil: Moreno Castro, Cristina. Consejo Superior de Investigaciones Científicas; EspañaFil: Nusblat, Alejandro David. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Hernandez Munain, Cristina. Consejo Superior de Investigaciones Científicas; EspañaFil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Suñe, Carlos. Consejo Superior de Investigaciones Científicas; EspañaFil: Suñé nNegre, Josep M.. Universidad de Barcelona; EspañaFil: Cuestas, María Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin