Towards sustainable energy systems. The role of deregulated electricity markets

Durante los últimos 20 años los gobiernos de muchos países han empezado un proceso de liberalización de sectores clave como los de telecomunicaciones, transportes y energía. Tradicionalmente, estos sectores eran considerados monopolios naturales, pero a finales de los setenta los principios bases del modelo de monopolio fueron criticados por muchos economistas. El 19 de diciembre de 1996, la directiva europea 96/92/CE fue el comienzo de un proceso de reforma estructural de enormes dimensiones. La directiva introdujo una nueva tipología de mercado eléctrico europeo basada en la desregulación del sector. El siguiente trabajo, en la primera parte, trata de analizar la reforma del mercado eléctrico mediante un estudio y una crítica de las directivas europeas y del estado de progreso de los países europeos en la satisfacción de los requerimientos de la reforma. La segunda parte es una elucubración del autor sobre los resultados que la reforma puede lograr con respecto al desarrollo sostenible. El propósito del siguiente proyecto es encontrar una respuesta a la siguiente pregunta: “Are the deregulated energy markets suitable to facilitate a development towards sustainable energy systems?

Towards sustainable energy systems. The role of deregulated electricity markets

Durante los últimos 20 años los gobiernos de muchos países han empezado un proceso de liberalización de sectores clave como los de telecomunicaciones, transportes y energía. Tradicionalmente, estos sectores eran considerados monopolios naturales, pero a finales de los setenta los principios bases del modelo de monopolio fueron criticados por muchos economistas. El 19 de diciembre de 1996, la directiva europea 96/92/CE fue el comienzo de un proceso de reforma estructural de enormes dimensiones. La directiva introdujo una nueva tipología de mercado eléctrico europeo basada en la desregulación del sector. El siguiente trabajo, en la primera parte, trata de analizar la reforma del mercado eléctrico mediante un estudio y una crítica de las directivas europeas y del estado de progreso de los países europeos en la satisfacción de los requerimientos de la reforma. La segunda parte es una elucubración del autor sobre los resultados que la reforma puede lograr con respecto al desarrollo sostenible. El propósito del siguiente proyecto es encontrar una respuesta a la siguiente pregunta: “Are the deregulated energy markets suitable to facilitate a development towards sustainable energy systems?

A Rational Approach to Drug Repositioning in β-thalassemia: Induction of Fetal Hemoglobin by Established Drugs

Drug repositioning and the relevance of orphan drug designation for β-thalassemia is reviewed. Drug repositioning and similar terms ('drug repurposing', 'drug reprofiling', 'drug redirecting', 'drug rescue', 'drug re-tasking' and/or 'drug rediscovery') have gained great attention, especially in the field or rare diseases (RDs), and represent relevant novel drug development strategies to be considered together with the 'off-label' use of pharmaceutical products under clinical trial regimen. The most significant advantage of drug repositioning over traditional drug development is that the repositioned drug has already passed a significant number of short- and long-term toxicity tests, as well as it has already undergone pharmacokinetic and pharmacodynamic (PK/PD) studies. The established safety of repositioned drugs is known to significantly reduce the probability of project failure. Furthermore, development of repurposed drugs can shorten much of the time needed to bring a drug to market. Finally, patent filing of repurposed drugs is expected to catch the attention of pharmaceutical industries interested in the development of therapeutic protocols for RDs. Repurposed molecules that could be proposed as potential drugs for β-thalassemia, will be reported, with some of the most solid examples, including sirolimus (rapamycin) that recently has been tested in a pilot clinical trial

Cell phenotype changes and oxidative stress response in Vibrio spp. induced into viable but non-culturable (VBNC) state

Purpose: Aquatic bacteria of the genus Vibrio include animal and human pathogens. The occurrence of Vibrio-related diseases has been associated with the current climate change-driven increase of sea surface temperature. Vibrio spp. can enter into the viable but non-culturable (VBNC) state, as a consequence of starvation in seawater at low temperatures. In such physiological state, Vibrio cells are no longer culturable on standard media agar plates but can resuscitate if incubated at 30 °C prior to plating, retaining virulence. Since limited information is available on regards to this topic, in this work, we characterized the phenotypic changes of four Vibrio spp. strains (one laboratory strain and three environmental isolates) in cold seawater microcosms, investigating the relationship between resuscitation and a hydrogen peroxide-induced oxidative stress. Methods: Cell phenotypic changes and the effect of hydrogen peroxide and/or catalase addition to the medium were studied on VBNC and resuscitated cells by flow cytometry in microcosm experiments, paralleled by culturability experiments by plating. Results: The cells of all the Vibrio strains changed their phenotype upon the induction of the VBNC state resulting in cell dwarfing and decrease in DNA quantity, losing the ability to grow on solid media. These features were partially or totally reverted when the cells were treated for resuscitation. Hydrogen peroxide at concentrations as low as 0.007 mM prevented resuscitation and a prolonged exposure to hydrogen peroxide at concentrations far under those inhibiting the growth of log-phase cells permanently damaged VBNC cells, which could not be resuscitated. However, the potential of culturability of VBNC cells could be preserved, at least for a part of the population, by plating the cells in the presence of catalase. The study also showed that during the resuscitation process, the cells gradually increased their resistance to hydrogen peroxide. Conclusions: The timing and mode of induction of the VBNC state, as well as cell resuscitation and response to hydrogen peroxide, differed among Vibrio strains, indicating that induction and resuscitation from dormancy could vary in the context of species belonging to a single genus

Expression of γ-globin genes in β-thalassemia patients treated with sirolimus: results from a pilot clinical trial (Sirthalaclin)

Introduction: β-thalassemia is caused by autosomal mutations in the β-globin gene, which induce the absence or low-level synthesis of β-globin in erythroid cells. It is widely accepted that a high production of fetal hemoglobin (HbF) is beneficial for patients with β-thalassemia. Sirolimus, also known as rapamycin, is a lipophilic macrolide isolated from a strain of Streptomyces hygroscopicus that serves as a strong HbF inducer in vitro and in vivo. In this study, we report biochemical, molecular, and clinical results of a sirolimus-based NCT03877809 clinical trial (a personalized medicine approach for β-thalassemia transfusion-dependent patients: testing sirolimus in a first pilot clinical trial, Sirthalaclin). Methods: Accumulation of γ-globin mRNA was analyzed using reverse-transcription quantitative polymerase chain reaction (PCR), while the hemoglobin pattern was analyzed using high-performance liquid chromatography (HPLC). The immunophenotype was analyzed using a fluorescence-activated cell sorter (FACS), with antibodies against CD3, CD4, CD8, CD14, CD19, CD25 (for analysis of peripheral blood mononuclear cells), or CD71 and CD235a (for analysis of in vitro cultured erythroid precursors). Results: The results were obtained in eight patients with the β+/β+ and β+/β0 genotypes, who were treated with a starting dosage of 1 mg/day sirolimus for 24–48 weeks. The first finding of this study was that the expression of γ-globin mRNA increased in the blood and erythroid precursor cells isolated from β-thalassemia patients treated with low-dose sirolimus. This trial also led to the important finding that sirolimus influences erythropoiesis and reduces biochemical markers associated with ineffective erythropoiesis (excess free α-globin chains, bilirubin, soluble transferrin receptor, and ferritin). A decrease in the transfusion demand index was observed in most (7/8) of the patients. The drug was well tolerated, with minor effects on the immunophenotype, and an only side effect of frequently occurring stomatitis. Conclusion: The data obtained indicate that low doses of sirolimus modify hematopoiesis and induce increased expression of γ-globin genes in a subset of patients with β-thalassemia. Further clinical trials are warranted, possibly including testing of the drug in patients with less severe forms of the disease and exploring combination therapies. © The Author(s), 2022

Phenomics and Genomics Reveal Adaptation of Virgibacillus dokdonensis Strain 21D to Its Origin of Isolation, the Seawater-Brine Interface of the Mediterranean Sea Deep Hypersaline Anoxic Basin Discovery

The adaptation of sporeformers to extreme environmental conditions is frequently questioned due to their capacity to produce highly resistant endospores that are considered as resting contaminants, not representing populations adapted to the system. In this work, in order to gain a better understanding of bacterial adaptation to extreme habitats, we investigated the phenotypic and genomic characteristics of the halophile Virgibacillus sp. 21D isolated from the seawater-brine interface (SBI) of the MgCl2-saturated deep hypersaline anoxic basin Discovery located in the Eastern Mediterranean Sea. Vegetative cells of strain 21D showed the ability to grow in the presence of high concentrations of MgCl2, such as 14.28% corresponding to 1.5 M. Biolog phenotype MicroArray (PM) was adopted to investigate the strain phenotype, with reference to carbon energy utilization and osmotic tolerance. The strain was able to metabolize only 8.4% of 190 carbon sources provided in the PM1 and PM2 plates, mainly carbohydrates, in accordance with the low availability of nutrients in its habitat of origin. By using in silico DNA-DNA hybridization the analysis of strain 21D genome, assembled in one circular contig, revealed that the strain belongs to the species Virgibacillus dokdonensis. The genome presented compatible solute-based osmoadaptation traits, including genes encoding for osmotically activated glycine-betaine/carnitine/choline ABC transporters, as well as ectoine synthase enzymes. Osmoadaptation of the strain was then confirmed with phenotypic assays by using the osmolyte PM9 Biolog plate and growth experiments. Furthermore, the neutral isoelectric point of the reconstructed proteome suggested that the strain osmoadaptation was mainly mediated by compatible solutes. The presence of genes involved in iron acquisition and metabolism indicated that osmoadaptation was tailored to the iron-depleted saline waters of the Discovery SBI. Overall, both phenomics and genomics highlighted the potential capability of V. dokdonensis 21D vegetative cells to adapt to the environmental conditions in Discovery SBI

Towards sustainable energy systems. The role of deregulated electricity markets

Durante los últimos 20 años los gobiernos de muchos países han empezado un proceso de liberalización de sectores clave como los de telecomunicaciones, transportes y energía. Tradicionalmente, estos sectores eran considerados monopolios naturales, pero a finales de los setenta los principios bases del modelo de monopolio fueron criticados por muchos economistas. El 19 de diciembre de 1996, la directiva europea 96/92/CE fue el comienzo de un proceso de reforma estructural de enormes dimensiones. La directiva introdujo una nueva tipología de mercado eléctrico europeo basada en la desregulación del sector. El siguiente trabajo, en la primera parte, trata de analizar la reforma del mercado eléctrico mediante un estudio y una crítica de las directivas europeas y del estado de progreso de los países europeos en la satisfacción de los requerimientos de la reforma. La segunda parte es una elucubración del autor sobre los resultados que la reforma puede lograr con respecto al desarrollo sostenible. El propósito del siguiente proyecto es encontrar una respuesta a la siguiente pregunta: “Are the deregulated energy markets suitable to facilitate a development towards sustainable energy systems?