Nanosafety : towards safer nanoparticles by design

Background: Nanosafety aims for a solution through the safer design (and re-design) of nanostructured materials, optimizing both performance and safety, by resolving which structural features lead to the desired properties and modifying them to avoid their detrimental effects without losing their desired nanoscale properties in the process. Starting with known toxic NPs, the final aim should be the re-design of such detrimental specific NP characteristics and to redefine the way they should be manipulated from the beginning to the end of their life cycle. Methods: The researchers reviewed literature in the area of novel nanosafety strategies addressing the "safe-by-design" paradigm. Results: The potential hazards of engineered NPs are not only determined by the physicochemical properties of the engineered NPs per se but also on the interactions of these NPs with immediate surrounding environments. The aim of promoting the timely and safe development of NPs cannot be achieved via traditional studies as they address one material at one time. The development of a safer design strategy of engineered NPs requires an understanding of both intrinsic (synthetic) properties together with their extrinsic responses to external stimuli. Conclusions: We have summarized recent developments of novel nanosafety strategies addressing the "safe-by-design" paradigm for optimizing both performance and safety, allowing the comparison of results of different studies and ultimately providing guidelines for the re-design of safer NPs. The resulting discussion is intended to provide guidelines for synthetic nanochemists on how to design NPs to be safe during their full life cycle while maintaining their parental desired properties

Molecular bases of spinal muscular atrophy: the survival motor neuron gene

L'atròfia muscular espinal (AME) és una malaltia neuromuscular autosòmica recessiva caracteritzada per Ia degeneració i Ia pèrdua de Ies motoneurones de Ia banya anterior de Ia medul·la espinal. Les manifestacions clíniques més característiques són una debilitat proximal simètrica i una atròfia muscular progressiva. La identificació del gen SMN1 com a gen determinant de I'AME obre noves alternatives per a I'estudi de Ia malaltia. En Ia majoria dels pacients es detecta I'absència del gen SMN1 (ja sigui per deleció o per conversió), però també se n'han identificat mutacions puntuals en un petit percentatge. L'absència del gen SMN1 s'associa a un ampli espectre de manifestacions clíniques, que van des de formes congènites de Ia malaltia fins a casos asimptomàtics. Diferents factors modificadors, com el nombre de còpies del gen SMN2 – el gen homòleg present tant en controls com en malalts – poden modificar el fenotip i a Ia vegada ser útils per investigar un tractament eficaç. Tot i que el gen SMN s'expressa en diferents poblacions neuronals, només Ies motoneurones són Ies responsables de Ies manifestacions de Ia malaltia. La proteïna SMN forma part d'un complex amb altres proteïnes que participen en Ia reacció d'empalmament i aquesta funció, essencial per a totes Ies cèl·lules, sembla ser crítica per a Ies neurones motores. Cal aprofundir en I'estudi dels mecanismes que condueixen a I'atròfia muscular espinal.Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration and loss of motor neurons of the anterior horn of the spinal cord. The clinical manifestations include proximal symmetric weakness and progressive muscle atrophy. The identification of the SMN1 gene as determinant of SMA has opened alternative ways of studying the disease. Absence of SMN1 (either by deletion or conversion) was detected in the majority of patients and subtle mutations were described in a minority. SMN1 absence was associated with a wide spectrum of manifestations, from congenital disease to asymptomatic cases. Modifier factors, such as the number of copies of SMN2, its homologous copy present in all patients, could influence the phenotype and help to find a treatment for the disease. The SMN gene is expressed in various neuronal populations, although only motor neurons are responsible for the manifestations of the disease. The SMN protein is part of a complex with various proteins involved in the splicing reaction. This apparently essential function of all cells is critical for motor neurons, and warrants further research to elucidate the mechanisms of disease

Sculpting Windows onto AuAg Hollow Cubic Nanocrystals

Using surfactants in the galvanic replacement reaction (GRR) offers a versatile approach to modulating hollow metal nanocrystal (NC) morphology and composition. Among the various surfactants available, quaternary ammonium cationic surfactants are commonly utilised. However, understanding how they precisely influence morphological features, such as the size and void distribution, is still limited. In this study, we aim to uncover how adding different surfactants-CTAB, CTAC, CTApTS, and PVP-can fine-tune the morphological characteristics of AuAg hollow NCs synthesised via GRR at room temperature. Our findings reveal that the halide counterion in the surfactant significantly controls void formation within the hollow structure. When halogenated surfactants, such as CTAB or CTAC, are employed, multichambered opened nanoboxes are formed. In contrast, with non-halogenated CTApTS, single-walled closed nanoboxes with irregularly thick walls form. Furthermore, when PVP, a polymer surfactant, is utilised, changes in concentration lead to the production of well-defined single-walled closed nanoboxes. These observations highlight the role of surfactants in tailoring the morphology of hollow NCs synthesised through GRR

Size-dependent protein-nanoparticle interactions in citrate-stabilized gold nanoparticles : the emergence of the protein corona

Surface modifications of highly monodisperse citrate-stabilized gold nanoparticles (AuNPs) with sizes ranging from 3.5 to 150 nm after their exposure to cell culture media supplemented with fetal bovine serum were studied and characterized by the combined use of UV-vis spectroscopy, dynamic light scattering, and zeta potential measurements. In all the tested AuNPs, a dynamic process of protein adsorption was observed, evolving toward the formation of an irreversible hard protein coating known as Protein Corona. Interestingly, the thickness and density of this protein coating were strongly dependent on the particle size, making it possible to identify different transition regimes as the size of the particles increased: (i) NP-protein complexes (or incomplete corona), (ii) the formation of a near-single dense protein corona layer, and (iii) the formation of a multilayer corona. In addition, the different temporal patterns in the evolution of the protein coating came about more quickly for small particles than for the larger ones, further revealing the significant role that size plays in the kinetics of this process. Since the biological identity of the NPs is ultimately determined by the protein corona and different NP-biological interactions take place at different time scales, these results are relevant to biological and toxicological studies

Modeling the Optical Responses of Noble Metal Nanoparticles Subjected to Physicochemical Transformations in Physiological Environments : Aggregation, Dissolution and Oxidation

Herein, we study how optical properties of colloidal dispersions of noble metal nanoparticles (Au and Ag) are affected by processes such as aggregation and oxidative dissolution. The optical contributions of these processes to the extinction spectra in the UV-vis region are often overlapped, making difficult its interpretation. In this regard, modeling the UV-vis spectra (in particular absorbance curve, peaks position, intensity and full width at half maximum-FWHM) of each process separately offers a powerful tool to identify the transformation of NPs under relevant and complex scenarios, such as in biological media. The proper identification of these transformations is crucial to understand the biological effects of the NPs

Estudio económico y contable de la compañía general de tabacos de Filipinas: 1881-1922

El objetivo de este trabajo es estudiar la contabilidad de la empresa Compañía General de Tabacos de Filipinas a partir de la documentación depositada en el Arxiu Nacional de Catalunya (Archivo Nacional de Cataluña). El estudio tiene un horizonte temporal de cuarenta años, desde el momento de la fundación, 1881, hasta el año 1922. En una primera parte se estudian las actividades y evolución de la empresa, en concreto, como fue diversificando sus actividades y los problemas que esto le ocasionó. Especial mención merece la expansión que disfrutó durante la Primera Guerra Mundial y que marcará el acontecer futuro. En la segunda parte hay un estudio detallado de las partidas que formaron parte del balance de situación y de la cuenta de gestión. También aquí se detecta cómo de forma paralela a los negocios, las necesidades informativas fueron crecientes. Remarcar que aun cuando la empresa muestra un grado importante de sofisticación en la teneduría de libros tanto por el detalle de información proporcionada como por el tratamiento de la misma, la utilización abusiva de ciertas partidas, como Valores pendientes, no permite obtener una visión demasiado nítida de la evolución de los negocios. Se puede concluir a partir de este trabajo que la contabilidad de la compañía, además de cumplir con los requisitos legales que se establecían, permitía tomar decisiones sobre las diferentes actividades a la vez que muestra un alto grado de elaboración en una época sin ayudas tecnológicas. Hace falta decir, además, que dada la distancia geográfica entre los centros de explotación y la administración, el control que se ejercía sobre estos estaba fundamentado en la información administrativa y contable que se realizaba

La importancia de las actuaciones municipales en la garantía del derecho a la vivienda. Entre el urbanismo y la colaboración público-privada

Objectives: Examine the diverse actions, including urban planning and public-private collaboration, that Barcelona City Council has implemented to guarantee the right to access to adequate and decent housing. Methodology: Descriptive work. Results: Although, in the Spanish legal system, competence in housing matters corresponds exclusively to the Autonomous Communities, the City Councils have a basic and fundamental role in the management and promotion of the right to housing. For example, Barcelona City Council has promoted different mechanisms such as land reservation on consolidated urban land or cohousing. Conclusions: The Public Administration needs to implement a global policy to increase the supply of public housing. This policy must be characterized, especially, by strong and stable economic investment, by the configuration of a clear and secure legal framework and by the implementation of collaboration measures between the different Administrations and between the Administration and the private sector.Objetivos: analizar las distintas actuaciones, tanto urbanísticas como en materia de colaboración público-privada, que ha llevado a cabo el Ayuntamiento de Barcelona para garantizar el derecho de acceso a una vivienda digna y adecuada. Metodología: trabajo descriptivo. Resultados: a pesar de que en el ordenamiento jurídico español la competencia en materia de vivienda corresponde en exclusiva a las comunidades autónomas, los ayuntamientos tienen un papel básico y fundamental en la gestión y la promoción del derecho a la vivienda. Por ejemplo, el Ayuntamiento de Barcelona ha impulsado distintos mecanismos como la reserva de suelo en suelo urbano consolidado o la covivienda. Conclusiones: la Administración pública tiene la necesidad de implantar una política de actuación global para incrementar el parque público de vivienda. Esta política debe caracterizarse, especialmente, por una fuerte y estable inversión económica, por la configuración de un marco jurídico claro y seguro y por la implantación de medidas de colaboración entre las distintas Administraciones y entre la Administración y el sector privado

Temporal changes in the expression and distribution of adhesion molecules during liver development and regeneration

We have compared by immunocytochemistry and immunoblotting the expression and distribution of adhesion molecules participating in cell-matrix and cell-cell interactions during embryonic development and regeneration of rat liver. Fibronectin and the fibronectin receptor, integrin alpha 5 beta 1, were distributed pericellularly and expressed at a steady level during development from the 16th day of gestation and in neonate and adult liver. AGp110, a nonintegrin fibronectin receptor was first detected on the 17th day of gestation in a similar, nonpolarized distribution on parenchymal cell surfaces. At that stage of development haemopoiesis is at a peak in rat liver and fibronectin and receptors alpha 5 beta 1 and AGp110 were prominent on the surface of blood cell precursors. During the last 2 d of gestation (20th and 21st day) hepatocytes assembled around lumina. AGp110 was initially depolarized on the surface of these acinar cells but then confined to the lumen and to newly-formed bile canaliculi. At birth, a marked increase occurred in the canalicular expression of AGp110 and in the branching of the canalicular network. Simultaneously, there was enhanced expression of ZO-1, a protein component of tight junctions. On the second day postpartum, presence of AGp110 and of protein constituents of desmosomes and intermediate junctions, DGI and E-cadherin, respectively, was notably enhanced in cellular fractions insoluble in nonionic detergents, presumably signifying linkage of AGp110 with the cytoskeleton and assembly of desmosomal and intermediate junctions. During liver regeneration after partial hepatectomy, AGp110 remained confined to apical surfaces, indicating a preservation of basic polarity in parenchymal cells. A decrease in the extent and continuity of the canalicular network occurred in proliferating parenchyma, starting 24 h after resection in areas close to the terminal afferent blood supply of portal veins and spreading to the rest of the liver within the next 24 h. Distinct acinar structures, similar to the ones in prenatal liver, appeared at 72 h after hepatectomy. Restoration of the normal branching of the biliary tree commenced at 72 h. At 7 d postoperatively acinar formation declined and one-cell-thick hepatic plates, as in normal liver, were observed

The development of highly dense highly protected surfactant ionizable lipid RNA loaded nanoparticles

The long quest for efficient drug administration has been looking for a universal carrier that can precisely transport traditional drugs, new genomic and proteic therapeutic agents. Today, researchers have found conditions to overcome the two main drug delivery dilemmas. On the one side, the versatility of the vehicle to efficiently load, protect and transport the drug and then release it at the target place. On the other hand, the questions related to the degree of PEGylation which are needed to avoid nanoparticle (NP) aggregation and opsonization while preventing cellular uptake. The development of different kinds of lipidic drug delivery vehicles and particles has resulted in the development of ionizable lipid nanoparticles (iLNPs), which can overcome most of the typical drug delivery problems. Proof of their success is the late approval and massive administration as the prophylactic vaccine for SARS-CoV-2. These ILNPs are built by electrostatic aggregation of surfactants, the therapeutic agent, and lipids that self-segregate from an aqueous solution, forming nanoparticles stabilized with lipid polymers, such as PEG. These vehicles overcome previous limitations such as low loading and high toxicity, likely thanks to low charge at the working pH and reduced size, and their entry into the cells via endocytosis rather than membrane perforation or fusion, always associated with higher toxicity. We herein revise their primary features, synthetic methods to prepare and characterize them, pharmacokinetic (administration, distribution, metabolization and excretion) aspects, and biodistribution and fate. Owing to their advantages, iLNPs are potential drug delivery systems to improve the management of various diseases and widely available for clinical use