Silver nanoparticles: applications and toxic risks to human health and environment

Se estima que de todos los nanomateriales utilizados en productos para el consumo, las nanopartículas de plata (AgNPs) son las que tienen un mayor grado de comercialización. Se utilizan en electrónica, ropa, pinturas, cosméticos, bactericidas, biofungicidas, aplicaciones biomédicas, en la industria médico-farmaceútica y alimentaria. Por ello, se hace tremendamente necesario que los productos fabricados con nanopartículas así como sus aplicaciones sean seguros tanto para la salud de las personas como del medio ambiente. Algunos estudios han mostrado que la toxicidad intrínseca de las AgNPs depende de una serie de factores como son el tamaño, la forma, el área superficial, la carga superficial, la solubilidad y el estado de aglomeración. Asimismo, numerosas investigaciones in vitro indican que las AgNPs son tóxicas para las células de mamífero. Además, consecuencias inflamatorias, oxidativas y genotóxicas están asociadas con la exposición de AgNPs. Este artículo muestra una visión global de las principales aplicaciones de las AgNPs, sus vías de exposición, sus efectos tóxicos y los mecanismos de toxicidad implicados.It is estimated that of all the nanomaterials used in consumer products, silver nanoparticles (AgNPs) currently have the highest degree of commercialization. They are used in electronics, clothing, paints, cosmetic, bactericides, bio-fungicides, biomedical applications, in the medical-pharmaceutical industry and food industry. Therefore, it is extremely necessary that products made with nanoparticles as well as their applications are safe for the health and the environment. Some studies have shown that the intrinsic toxicity of AgNPs depend on a range of factors such as, size, shape, surface area, surface charge, solubility and state of agglomeration. In addition, a number of in vitro studies indicate that AgNPs are toxic to mammalian cells. Furthermore, inflammatory, oxidative and genotoxic consequences are associated with AgNPs exposure. This paper shows a global view of the main applications of AgNPs, their routes of exposure, toxic effects and toxicity mechanisms involved

N-nitrosopiperidina y N-nitrosodibutilamina (II): relevancia en la carcinógenesis química y genotoxicidad

La N-nitrosopiperidina (NPIP) y la N-nitrosodibutilamina (NDBA) han sido clasificadas como posibles carcinógenos en humanos. La NPIP causa tumores en esófago, y también en cavidad nasal, hígado y estómago, mientras que la NDBA es carcinógeno de vejiga urinaria. Ambas N-nitrosaminas son consideradas carcinógenos genotóxicos indirectos puesto que necesitan una bioactivación para generar metabolitos que reaccionen con el DNA. La principal lesión al DNA inducida por las N-nitrosaminas es el daño alquilativo. En el caso de la NDBA, la posición de alquilación es en el O6 de la guanina, formando la O6 butilguanina y la O6-4-hidroxibutilguanina. Sin embargo, esta N-nitrosamina alquila preferentemente proteínas. Por otra parte, la bioactivación de la NPIP genera metabolitos que reaccionan con el N2 de la guanina in vitro, aunque se desconocen sus efectos in vivo. Además, durante la activación metabólica pueden también producirse especies reactivas del oxígeno (EROs) y del nitrógeno (ERNs). Las lesiones oxidativas y nitrativas más comunes son la 8- hidroxideoxiguanosina (8 OHdG) y la 8-nitroguanina, respectivamente, que producen mutaciones y conducen a la carcinogénesis.N-nitrosopiperidine (NPIP) and N-nitrosodibutylamine (NDBA) have been classified as possibly carcinogenic to humans. NPIP causes tumours in oesophagus, and also in nasal cavity, liver and stomach, whereas NDBA is a bladder carcinogen. Both N-nitrosamines are considered indirect genotoxic carcinogens since they need a bioactivation to generate metabolites that react with DNA. The main DNA lesion induced by N nitrosamines is the alkylative damage. In the case of NDBA, the alkylation position is in O6 of guanine, forming O6 butylguanine and O6-4-hydroxybutylguanine. However, this N-nitrosamine alkylates proteins preferably. On the other hand, NPIP bioactivation generates metabolites that react with N2 of guanine in vitro, although its in vivo effects are unknown. Moreover, during metabolic activation reactive oxygen species (ROS) and nitrogen species (RNS) can be also produced. The most common oxidative and nitrative lesions are 8-hydroxydeoxyguanosine (8-OhdG) and 8-nitroguanine, respectively, that produce mutations and lead to carcinogenesis

N-nitrosopiperidina y N-nitrosodibutilamina (I): formación, exposición humana y metabolismo

Los vegetales, el agua de bebida y los productos cárnicos son las principales fuentes de exposición de nitratos en humanos. La toxicidad de estos compuestos es resultado de su conversión en nitritos que actúan como agentes nitrosantes en la formación de las Nnitrosaminas. Las N-nitrosaminas son uno de los grupos de agentes carcinogénicos más estudiados y existe una gran preocupación debido a su presencia en nuestra vida diaria. Sin embargo, son muy escasos los estudios realizados con dos N-nitrosaminas, la Nnitrosopiperidina (NPIP) y la N-nitrosodibutilamina (NDBA). La NPIP se encuentra en productos cárnicos que incluyan especias en la formulación de sus mezclas y la NDBA en productos cárnicos envasados en goma y en chupetes y tetinas para biberones. Además, la NPIP y la NDBA son compuestos genotóxicos indirectos que necesitan una activación metabólica para dañar el DNA y ejercer su efecto carcinogénico. Este proceso es llevado a cabo por el citocromo P450, en concreto, por las isoformas enzimáticas CYP 2A6 y el CYP 1A1, respectivamente.Vegetables, drinking water and meat products are the main sources of exposure to nitrates in humans. The toxicity of these compounds is usually the result of the conversion of nitrates into nitrites, which act as nitrosating agents in the N-nitrosamine formation. N-nitrosamines are one of the most studied carcinogenic group and great concern exists due to its presence in our daily life. However, the performed studies with two N-nitrosamines, N-nitrosopiperidine (NPIP) and N-nitrosodibutylamine (NDBA), are very limited. NPIP is found in meat products with spices in their formulation and NDBA in meat products packed in rubber nettings and in pacifiers and nipples. Moreover, NPIP and NDBA are indirect genotoxic compounds that need a metabolic activation to damage DNA and exert their carcinogenic effect. This process is carried out by cytochrome P450, in particular, by enzymatic isoforms CYP 2A6 y el CYP 1A1, respectively

Submesoscale Kinematic Properties in Summer and Winter Surface Flows in the Northern Gulf of Mexico

Statistical properties of near-surface horizontal velocity gradients are obtained from four drifter experiments conducted in the Gulf of Mexico during Summer 2012 and Winter 2016. The data density provided by the near-simultaneous deployments of 90-326 surface drifters in each allows direct, drifter-based estimates of the scale dependence of velocity gradients at separation scales ranging from 200 m to 5 km. The robustness of these estimates, derived from uniquley sampled, nearly equilateral triplets, is confirmed by comparisons with estimates produced from larger drifter clusters, and with estimates based on concurrent Eulerian X-band radar observations. The winter launches were deployed above a ∼80 m deep mixed layer, one in a region with nearly homogeneous horizontal density structure, the other in a region of strong surface density gradients associated with filaments of fresh Mississippi River water. The summer launches occurred in a shallow (10m) mixed layer, one launched across a mesoscale frontal jet separating regions of horizontally homogeneous density and the other, similar to the corresponding winter launch, also in a region filamented by shallow lenses of cold, fresh water. Seasonal differences are observed, with larger velocity fluctuations and greater variance in divergence and vorticity, especially at the smallest scales, in winter. Differences between same-season launches are, however, as large as seasonal differences. In both seasons, observations sampling regions directly impacted by fresh water fluxes show strongly skewed vorticity distributions, with cyclonic vorticity dominating strain. For the other launches, one in each season, strain dominated minimally skewed vorticity

Effect of Sr, Mg and Fe substitution on the physico-chemical and biological properties of Si Ca P multilayer scaffolds

In this work, a new combination of ceramic materials is proposed for bone tissue engi neering applications. Multilayer scaffolds consisting of a core composed mainly of calcium pyrophosphate and external coatings of silica and calcium doped with Fe3+, Sr2+ and Mg2+ were prepared. To study the influence of the arrangement of dopant ions in the external coatings, two different scaffolds were developed: scaffolds 3J consisting of a single exter nal coating with 9mol% of Fe3+, Sr2+ and Mg2+ ions; and scaffolds 3S comprising three external coatings, each containing 3mol% of Fe3+, Sr2+ and Mg2+ ions. Scaffolds were physico chemically characterized and evaluated for in vitro bioactivity and cellular response in the presence of MG-63 cells. The results showed that the core scaffold displayed no in vitro bioac tivity or good cellular response, but served as a support for the external coatings given its mechanical resistance. The cell viability of scaffolds 3J and 3S increased more than 100% in relation to the core, and also improved cell proliferation and adhesion resulting in a dense layer of cells that covered the scaffolds’ entire surface. The arrangement of ions in the external coatings did not influence the cellular response, but determined the bioactivity rateNayarit A. Mata was funded by a grant from the Generalitat Valenciana with reference GRISOLIAP/2018/037 and pre-doctoral mobility co-financed by the European Social Fund and the Generalitat Valenciana with reference BEFPI/2021/056. TThis publication is part of the Grant PID2020- 116693RB-C21 funded by MCIN/AEI/10.13039/501100011033

Submesoscale dispersion in the vicinity of the Deepwater Horizon spill

Reliable forecasts for the dispersion of oceanic contamination are important for coastal ecosystems, society and the economy as evidenced by the Deepwater Horizon oil spill in the Gulf of Mexico in 2010 and the Fukushima nuclear plant incident in the Pacific Ocean in 2011. Accurate prediction of pollutant pathways and concentrations at the ocean surface requires understanding ocean dynamics over a broad range of spatial scales. Fundamental questions concerning the structure of the velocity field at the submesoscales (100 meters to tens of kilometers, hours to days) remain unresolved due to a lack of synoptic measurements at these scales. \textcolor{black} {Using high-frequency position data provided by the near-simultaneous release of hundreds of accurately tracked surface drifters, we study the structure of submesoscale surface velocity fluctuations in the Northern Gulf Mexico. Observed two-point statistics confirm the accuracy of classic turbulence scaling laws at 200m$-$50km scales and clearly indicate that dispersion at the submesoscales is \textit{local}, driven predominantly by energetic submesoscale fluctuations.} The results demonstrate the feasibility and utility of deploying large clusters of drifting instruments to provide synoptic observations of spatial variability of the ocean surface velocity field. Our findings allow quantification of the submesoscale-driven dispersion missing in current operational circulation models and satellite altimeter-derived velocity fields.Comment: 9 pages, 6 figure

Non-immunoglobulin scaffold proteins: Precision tools for studying protein-protein interactions in cancer

Cancer is frequently characterised by dysregulation of the cellular signalling processes that govern proliferation, survival and attachment. Understanding such dysregulation continues to present a challenge given the importance of protein-protein interactions in intracellular processes. Exploring this protein-protein interactome requires novel tools capable of discriminating between highly homologous proteins, individual domains and post-translational modifications. This review examines the potential of scaffold-based binding proteins to fulfil these requirements. It also explores protein-protein interactions in the context of intracellular signalling pathways and cancer, and demonstrates the uses of scaffold proteins as functional moderators, biosensors and imaging reagents. This review also highlights the timeliness and potential to develop international consortia to develop and validate highly specific “proteome” scaffold-based binding protein reagents with the ultimate aim of developing screening tools for studying the interactome

Ocean convergence and the dispersion of flotsam

Floating oil, plastics, and marine organisms are continually redistributed by ocean surface currents. Prediction of their resulting distribution on the surface is a fundamental, long-standing, and practically important problem. The dominant paradigm is dispersion within the dynamical context of a nondivergent flow: objects initially close together will on average spread apart but the area of surface patches of material does not change. Although this paradigm is likely valid at mesoscales, larger than 100 km in horizontal scale, recent theoretical studies of submesoscales (less than ∼10 km) predict strong surface convergences and downwelling associated with horizontal density fronts and cyclonic vortices. Here we show that such structures can dramatically concentrate floating material. More than half of an array of ∼200 surface drifters covering ∼20 × 20 km2 converged into a 60 × 60 m region within a week, a factor of more than 105 decrease in area, before slowly dispersing. As predicted, the convergence occurred at density fronts and with cyclonic vorticity. A zipperlike structure may play an important role. Cyclonic vorticity and vertical velocity reached 0.001 s−1 and 0.01 ms−1, respectively, which is much larger than usually inferred. This suggests a paradigm in which nearby objects form submesoscale clusters, and these clusters then spread apart. Together, these effects set both the overall extent and the finescale texture of a patch of floating material. Material concentrated at submesoscale convergences can create unique communities of organisms, amplify impacts of toxic material, and create opportunities to more efficiently recover such material

Ocean convergence and the dispersion of flotsam

Floating oil, plastics, and marine organisms are continually redistributed by ocean surface currents. Prediction of their resulting distribution on the surface is a fundamental, long-standing, and practically important problem. The dominant paradigm is dispersion within the dynamical context of a nondivergent flow: objects initially close together will on average spread apart but the area of surface patches of material does not change. Although this paradigm is likely valid at mesoscales, larger than 100 km in horizontal scale, recent theoretical studies of submesoscales (less than ∼10 km) predict strong surface convergences and downwelling associated with horizontal density fronts and cyclonic vortices. Here we show that such structures can dramatically concentrate floating material. More than half of an array of ∼200 surface drifters covering ∼20 × 20 km2 converged into a 60 × 60 m region within a week, a factor of more than 105 decrease in area, before slowly dispersing. As predicted, the convergence occurred at density fronts and with cyclonic vorticity. A zipperlike structure may play an important role. Cyclonic vorticity and vertical velocity reached 0.001 s−1 and 0.01 ms−1, respectively, which is much larger than usually inferred. This suggests a paradigm in which nearby objects form submesoscale clusters, and these clusters then spread apart. Together, these effects set both the overall extent and the finescale texture of a patch of floating material. Material concentrated at submesoscale convergences can create unique communities of organisms, amplify impacts of toxic material, and create opportunities to more efficiently recover such material

Selection of the silicon sensor thickness for the Phase-2 upgrade of the CMS Outer Tracker

During the operation of the CMS experiment at the High-Luminosity LHC the silicon sensors of the Phase-2 Outer Tracker will be exposed to radiation levels that could potentially deteriorate their performance. Previous studies had determined that planar float zone silicon with n-doped strips on a p-doped substrate was preferred over p-doped strips on an n-doped substrate. The last step in evaluating the optimal design for the mass production of about 200 m$^{2}$ of silicon sensors was to compare sensors of baseline thickness (about 300 μm) to thinned sensors (about 240 μm), which promised several benefits at high radiation levels because of the higher electric fields at the same bias voltage. This study provides a direct comparison of these two thicknesses in terms of sensor characteristics as well as charge collection and hit efficiency for fluences up to 1.5 × 10$^{15}$ n$_{eq}$/cm$^{2}$. The measurement results demonstrate that sensors with about 300 μm thickness will ensure excellent tracking performance even at the highest considered fluence levels expected for the Phase-2 Outer Tracker