Desagregando estadísticas de población

Debido a cuestiones de confidencialidad y a fin de evitar que cualquier persona concreta pueda ser identificada (de forma directa, o indirectamente en conexión con cualquier otra información publicada), las leyes de protección de datos de carácter personal, tanto nacionales como internacionales, obligan a que las estadísticas referidas a variables sociales, económicas y demográficas deban ser publicadas agregadas por unidades espaciales (BOE, 1999; OJEU 2013; USC 2002)

Modulation of Fas receptor proteins and dynamin during opiate addiction and induction of opiate withdrawal in rat brain

The Fas receptor is involved in the regulation of apoptosis but also can function as a non-apoptotic signal transducer. This study was mainly designed to quantitate Fas proteins in rat brain during heroin addiction and opiate withdrawal. In rat, mouse and human brains, and in SH-SY5Y cells, similar forms of Fas were immunodetected with different antibodies (i.e., 35kDa native Fas and 48- and 51-kDa glycosylated Fas). Acute (2h) treatments with the μ-opioid receptor agonists heroin (10mg/kg) and morphine (30mg/kg) increased the immunodensity of native Fas (124% and 36%) but not that of glycosylated Fas in the cerebral cortex. Chronic (5days) heroin (5-30mg/kg) and morphine (10-100mg/kg) were also associated with increased native Fas (76% and 45%) and with different expressions of glycosylated Fas. In heroin-dependent rats, opiate withdrawal (48h) resulted in a sustained increase in native Fas (107%) and in up-regulation of 51kDa glycosylated Fas (51%). Acute treatments with selective δ-receptor (SNC-80, 10mg/kg) or κ-receptor (U 50488-H, 10mg/kg) agonists did not alter the content of native or glycosylated Fas. Chronic pentazocine (10-80mg/kg, 5days), a mixed opiate drug and σ1 receptor agonist, decreased native (48%) and glycosylated (38-82%) Fas proteins. Similarly, the selective σ1 agonist (+)-SKF 10047 also decreased native Fas (37%) and the effect was blocked by the σ1 antagonist BD 1063. Brain dynamin was up-regulated by acute and/or chronic heroin (30-39%), morphine (47-85%), pentazocine (51%) and heroin withdrawal (74%). The main results indicate that chronic heroin/morphine treatment and heroin withdrawal are associated with up-regulation of 35kDa native Fas (and with different expressions of glycosylated Fas), and also with concomitant increases of dynamin in rat brai

Design strategies for positively charged endolysins: Insights into Artilysin development

Endolysins are bacteriophage-encoded enzymes that can specifically degrade the peptidoglycan layer of bacterial cell wall, making them an attractive tool for the development of novel antibacterial agents. The use of genetic engineering techniques for the production and modification of endolysins offers the opportunity to customize their properties and activity against specific bacterial targets, paving the way for the development of personalized therapies for bacterial infections. Gram-negative bacteria possess an outer membrane that can hinder the action of recombinantly produced endolysins. However, certain endolysins are capable of crossing the outer membrane by virtue of segments that share properties resembling those of cationic peptides. These regions increase the affinity of the endolysin towards the bacterial surface and assist in the permeabilization of the membrane. In order to improve the bactericidal effectiveness of endolysins, approaches have been implemented to increase their net charge, including the development of Artilysins containing positively charged amino acids at one end. At present, there are no specific guidelines outlining the steps for implementing these modifications. There is an ongoing debate surrounding the optimal location of positive charge, the need for a linker region, and the specific amino acid composition of peptides for modifying endolysins. The aim of this study is to provide clarity on these topics by analyzing and comparing the most effective modifications found in previous literature.The authors are indebted to Agencia Española de Investigación for the granted project (PID2019-107298RB-C21/AEI/10.13039/501100011033 to EGF and AA and PID2019-107298RB-C22/AEI/10.13039/501100011033 to NFM), to Marató de TV3 foundation (grant 201812-30-31-32-33) and to AGAUR for project 2021 SGR 01552. The authors are also indebted to the CERCA Program (Generalitat de Catalunya) and European Social Fund for supporting our research. JVCT is supported with a Margarita Salas grant for the training of young doctoral graduates (722713).info:eu-repo/semantics/publishedVersio

Design strategies for positively charged endolysins : Insights into Artilysin development

Altres ajuts: acords transformatius de la UABEndolysins are bacteriophage-encoded enzymes that can specifically degrade the peptidoglycan layer of bacterial cell wall, making them an attractive tool for the development of novel antibacterial agents. The use of genetic engineering techniques for the production and modification of endolysins offers the opportunity to customize their properties and activity against specific bacterial targets, paving the way for the development of personalized therapies for bacterial infections. Gram-negative bacteria possess an outer membrane that can hinder the action of recombinantly produced endolysins. However, certain endolysins are capable of crossing the outer membrane by virtue of segments that share properties resembling those of cationic peptides. These regions increase the affinity of the endolysin towards the bacterial surface and assist in the permeabilization of the membrane. In order to improve the bactericidal effectiveness of endolysins, approaches have been implemented to increase their net charge, including the development of Artilysins containing positively charged amino acids at one end. At present, there are no specific guidelines outlining the steps for implementing these modifications. There is an ongoing debate surrounding the optimal location of positive charge, the need for a linker region, and the specific amino acid composition of peptides for modifying endolysins. The aim of this study is to provide clarity on these topics by analyzing and comparing the most effective modifications found in previous literature

Side effects of chaperone gene co-expression in recombinant protein production

Insufficient availability of molecular chaperones is observed as a major bottleneck for proper protein folding in recombinant protein production. Therefore, co-production of selected sets of cell chaperones along with foreign polypeptides is a common approach to increase the yield of properly folded, recombinant proteins in bacterial cell factories. However, unbalanced amounts of folding modulators handling folding-reluctant protein species might instead trigger undesired proteolytic activities, detrimental regarding recombinant protein stability, quality and yield. This minireview summarizes the most recent observations of chaperone-linked negative side effects, mostly focusing on DnaK and GroEL sets, when using these proteins as folding assistant agents. These events are discussed in the context of the complexity of the cell quality network and the consequent intricacy of the physiological responses triggered by protein misfolding

Microbial factories for recombinant pharmaceuticals

Most of the hosts used to produce the 151 recombinant pharmaceuticals so far approved for human use by the Food and Drug Administration (FDA) and/or by the European Medicines Agency (EMEA) are microbial cells, either bacteria or yeast. This fact indicates that despite the diverse bottlenecks and obstacles that microbial systems pose to the efficient production of functional mammalian proteins, namely lack or unconventional post-translational modifications, proteolytic instability, poor solubility and activation of cell stress responses, among others, they represent convenient and powerful tools for recombinant protein production. The entering into the market of a progressively increasing number of protein drugs produced in non-microbial systems has not impaired the development of products obtained in microbial cells, proving the robustness of the microbial set of cellular systems (so far Escherichia coli and Saccharomyces cerevisae) developed for protein drug production. We summarize here the nature, properties and applications of all those pharmaceuticals and the relevant features of the current and potential producing hosts, in a comparative wa

Interplay between optical emission and magnetism in the van der Waals magnetic semiconductor CrSBr in the two-dimensional limit

The van der Waals semiconductor metamagnet CrSBr offers an ideal platform for studying the interplay between optical and magnetic properties in the two-dimensional limit. Here, we carried out an exhaustive optical characterization of this material by means of temperature- and magnetic-field-dependent photoluminescence (PL) on flakes of different thicknesses down to the monolayer. We found a characteristic emission peak that is quenched upon switching the ferromagnetic layers from an antiparallel to a parallel configuration and exhibits a temperature dependence different from that of the peaks commonly ascribed to excitons. The contribution of this peak to the PL is boosted around 30-40 K, coinciding with the hidden order magnetic transition temperature. Our findings reveal the connection between the optical and magnetic properties via the ionization of magnetic donor vacancies. This behavior enables a useful tool for the optical reading of the magnetic states in atomically thin layers of CrSBr and shows the potential of the design of 2D heterostructures with magnetic and excitonic properties

The Elasticity of a Random Variable as a Tool for Measuring and Assessing Risks

Elasticity is a very popular concept in economics and physics, recently exported and reinterpreted in the statistical field, where it has given form to the so-called elasticity function. This function has proved to be a very useful tool for quantifying and evaluating risks, with applications in disciplines as varied as public health and financial risk management. In this study, we consider the elasticity function in random terms, defining its probability distribution, which allows us to measure for each stochastic process the probability of finding elastic or inelastic situations (i.e., with elasticities greater or less than 1). This new tool, together with new results on the most notable points of the elasticity function covered in this research, offers a new approach to risk assessment, facilitating proactive risk management. The paper also includes other contributions of interest, such as new results that relate elasticity and inverse hazard functions, the derivation of the functional form of the cumulative distribution function of a probability model with constant elasticity and how the elasticities of functionally dependent variables are related. The interested reader can also find in the paper examples of how elasticity cumulative distribution functions are calculated, and an extensive list of probability models with their associated elasticity functions and distributions

Towards Protein-Based Viral Mimetics for Cancer Therapies

High resistance and recurrence rates, along with elevated drug clearance, compel the use of maximum tolerated drug doses in cancer therapy, resulting in high-grade toxicities and limited clinical applicability. Promoting active drug accumulation in tumor tissues would minimize such issues and improve therapeutic outcomes. A new class of therapeutic drugs suitable for the task has emerged based on the concept of virus-mimetic nanocarriers, or 'artificial viruses.' Among the spectrum of materials under exploration in nanocarrier research, proteins offer unparalleled structural and functional versatility for designing viruslike molecular vehicles. By exhibiting 'smart' functions and biomimetic traits, protein-based nanocarriers will be a step ahead of the conventional drug-protein conjugates already in the clinics in ensuring efficient delivery of passenger antitumor drugs