Unveiling interactions between DNA and cytotoxic 2-arylpiperidinyl-1,4-naphthoquinone derivatives: A combined electrochemical and computational study

Indexación: Scopus.Three 2-arylpiperidinyl-1,4-naphthoquinone derivatives were synthesized and evaluated in vitro to determine their cytotoxicity on cancer and normal cell lines. In order to establish their possible action mechanism, the electrochemical behaviour of these quinones was examined using cyclic voltammetry (CV) as technique by using a three-electrode setup: a glassy carbon, Ag/AgCl (in 3 M KCl), and platinum wire as working, reference, and counter electrodes, respectively. Kinetic studies were done to determine the control of the reduction reaction and the number of transferred electrons in the process. Furthermore, the addition of dsDNA to the quinone solutions allowed for the observation of an interaction between each quinone and dsDNA as the current-peaks became lower in presence of dsDNA. Otherwise, motivated to support the aforementioned results, electronic structure calculations at the TPSS-D3/6-31+G(d,p) level of theory were carried out in order to find the most favourable noncovalently bonded complexes between quinones and DNA. Noncovalent complexes formed between DNA and 2-arylpiperidinyl-1,4-naphthoquinones and stabilized by π-stacking interactions along with the well-known hydrogen-bonded complexes were found, with the former being more stable than the latter. These results suggest that the intercalation of these quinone derivatives in DNA is the most likely action mechanism. © 2018 King Saud Universityhttps://www.sciencedirect.com/science/article/pii/S1878535218300893?via%3Dihu

High-precision analysis of binary stars with planets. I. Searching for condensation temperature trends in the HD 106515 system

We explore the probable chemical signature of planet formation in the remarkable binary system HD 106515. The A star hosts a massive long-period planet with 9 MJup detected by radial velocity. We also refine stellar and planetary parameters by using non-solar-scaled opacities when modeling the stars. Methods. We carried out a simultaneous determination of stellar parameters and abundances, by applying for the first time non-solar-scaled opacities in this binary system, in order to reach the highest possible precision. Results. The stars A and B in the binary system HD 106515 do not seem to be depleted in refractory elements, which is different when comparing the Sun with solar-twins. Then, the terrestrial planet formation would have been less efficient in the stars of this binary system. Together with HD 80606/7, this is the second binary system which does not seem to present a (terrestrial) signature of planet formation, and hosting both systems an eccentric giant planet. This is in agreement with numerical simulations, where the early dynamical evolution of eccentric giant planets clear out most of the possible terrestrial planets in the inner zone. We refined the stellar mass, radius and age for both stars and found a notable difference of 78% in R compared to previous works. We also refined the planet mass to mp sini = 9.08 +/- 0.20 MJup, which differs by 6% compared with literature. In addition, we showed that the non-solar-scaled solution is not compatible with the classical solar-scaled method, and some abundance differences are comparable to NLTE or GCE effects specially when using the Sun as reference. Then, we encourage the use of non-solar-scaled opacities in high-precision studies such as the detection of Tc trends.[abridged]Comment: 9 pages, 10 figures, A&A accepted. arXiv admin note: text overlap with arXiv:1507.0812

Thermal stability of microstructural and optical modifications induced in sapphire by ultrafast laser filamentation

We report on the thermal stability of both structural and optical micromodifications created by ultrafast laser written filaments in sapphire crystals. By using the Cr3+ traces as optical probes, we have concluded that the filaments are constituted by both reversible and nonreversible defects with very different spatial locations. The strain field measured from the analysis of R lines has been found to be erased at the same time when the reversible centers are recombined (∼1100 °C). This fact seems to indicate that these defects act as pinning centers for the induced stress. Furthermore, we have found that the waveguide generated in the proximity of the filament disappear for annealing temperatures above 1100 °C. This clearly supports the assumption that waveguiding is produced by the strain stress induced refractive index increment based on the dominant electronic polarizability enhancement. © 2010 American Institute of Physics

Absorption efficiency of gold nanorods determined by quantum dot fluorescence thermometry

In this work quantum dot fluorescence thermometry, in combination with double-beam confocal microscopy, has been applied to determine the thermal loading of gold nanorods when subjected to an optical excitation at the longitudinal surface plasmon resonance. The absorbing/heating efficiency of low (≈3) aspect ratio gold nanorods has been experimentally determined to be close to 100%, in excellent agreement with theoretical simulations of the extinction, absorption, and scattering spectra based on the discrete dipole approximation

Upconverting nanorockers for intracellular viscosity measurements during chemotherapy

Funding: Ministerio de Economía y Competitividad de España (MAT2016-75362-C3-1-R and MAT2017-83111R); Instituto de Salud Carlos III (PI16/ 00812); Comunidad Autónoma de Madrid (B2017/BMD-3867RENIMCM), and co-financed by the European Structural funds and also by COST action CM1403; Comunidad de Madrid predoctorate contracts and from the Spanish national project FIS2017-86007-C3-1-P (R.D-B and R.P.P).Chemicals capable of producing structural and chemical changes on cells are used to treat diseases (e.g., cancer). Further development and optimization of chemotherapies require thorough knowledge of the effect of the chemical on the cellular structure and dynamics. This involves studying, in a noninvasive way, the properties of individual cells after drug administration. Intracellular viscosity is affected by chemical treatments and it can be reliably used to monitor chemotherapies at the cellular level. Here, cancer cell monitoring during chemotherapeutic treatments is demonstrated using intracellular allocated upconverting nanorockers. A simple analysis of the polarized visible emission of a single particle provides a real-time readout of its rocking dynamics that are directly correlated to the cytoplasmic viscosity. Numerical simulations and immunodetection are used to correlate the measured intracellular viscosity alterations to the changes produced in the cytoskeleton of cancer cells by anticancer drugs (colchicine and Taxol). This study evidences the possibility of monitoring cellular properties under an external chemical stimulus for the study and development of new treatments. Moreover, it provides the biomedical community with new tools to study intracellular dynamics and cell functioning.PostprintPeer reviewe

Bias in Intracellular Luminescence Thermometry: The Case of the Green Fluorescent Protein

Measurement of intracellular temperature in a fast, accurate, reliable, and remote manner is crucial for the understanding of cellular processes. Nanothermometers based on the green fluorescence protein (GFP) are of special interest because intracellular temperature readouts can be obtained from the analysis of the polarization state of its luminescence. Despite the good results provided by GFP thermometers, the reliability of their intracellular thermal readouts is still a question of debate. Here, light is shed on this issue by introducing cell activity as a relevant bias mechanism that prevents the use of GFP for reliable intranuclear thermal measurements. Experimental evidence that this lack of reliability can affect not only GFP but also other widely used thermometers such as semiconductor nanocrystals is provided. It is discussed how differences observed between calibration curves obtained in presence and absence of cell activity can inform about the presence of bias. The presented results and discussion are aimed to warn the community working in intracellular thermometry and encourage authors to approach the issue in a conscious manner. The performance and reliability of the chosen intracellular thermometers must be judiciously assessed. This is the only way intracellular thermometry can progress and deliver indisputable resultsThis work was financed by the Spanish Ministerio de Innovación y Ciencias under Project Nos. RTI2018-101050-J-I00, NANONERV PID2019- 106211RB-I00, and EIN2020-112419. Additional funding was provided by the European Union Horizon 2020 FETOpen project NanoTBTech (Grant No. 801305). P.R.-S. is grateful for a Juan de la Cierva – Incorporación scholarship (Grant No. IJC2019-041915-I). A.E. is grateful to Retos Projects Program of the Spanish Ministry of Science, Innovation, and Universities, the Spanish State Research Agency, co-funded by the European Regional Development Fund (A.E. is an EMBO Young Investigator). S.T. is grateful to AECC (Spanish Association Against Cancer) IDEAS21989THOM

SNOM characterization of a potential low cost thin gold coated micro-structured grating using a commercial CD substrate

In this work near-field optical measurements of a corrugated grating coated with a 30 nm thick gold film are presented. The grating was made using the polycarbonate corrugated substrate of a commercially available recordable CD as template. This has been proved to be a versatile and low cost technique in producing large 1.6 μm period gratings. The study was carried out using a Scanning Near-Field Optical Microscope (SNOM) working in both collection and reflection modes at two different wavelengths, 532 nm and 633 nm. The results illustrate that the intensity patterns of near-field images are strongly polarization-dependent, even showing different periodicity of the localized fields for orthogonal polarization states. When electric field of the light is polarized parallel to the grooves, the periodicity of the SNOM images is coincident with the grating period, whereas when the light is polarized perpendicular to the grooves the SNOM pattern shows a periodicity twice that of the corresponding topography of the grating. Numerical simulations of the SNOM data based on a two-dimensional Finite Difference Time-Domain (2D-FDTD) model have been realized. The results of the simulations are in good agreement with the experimental data, emphasizing the need of performing numerical simulation for the correct interpretation of SNOM data

KELT-17: a chemically peculiar Am star and a hot-Jupiter planet

Context. The detection of planets orbiting chemically peculiar stars is very scarcely known in the literature. Aims. To determine the detailed chemical composition of the remarkable planet host star KELT-17. This object hosts a hot-Jupiter planet with 1.31 MJup detected by transits, being one of the more massive and rapidly rotating planet hosts to date. We aimed to derive a complete chemical pattern for this star, in order to compare it with those of chemically peculiar stars. Methods. We carried out a detailed abundance determination in the planet host star KELT-17 via spectral synthesis. Stellar parameters were estimated iteratively by fitting Balmer line profiles and imposing the Fe ionization balance, using the program SYNTHE together with plane-parallel ATLAS12 model atmospheres. Specific opacities for an arbitrary composition and microturbulence velocity vmicro were calculated through the Opacity Sampling (OS) method. The abundances were determined iteratively by fitting synthetic spectra to metallic lines of 16 different chemical species using the program SYNTHE. The complete chemical pattern of KELT-17 was compared to the recently published average pattern of Am stars. We estimated the stellar radius by two methods: a) comparing the synthetic spectral energy distribution with the available photometric data and the Gaia parallax, and b) using a Bayesian estimation of stellar parameters using stellar isochrones. Results. We found overabundances of Ti, Cr, Mn, Fe, Ni, Zn, Sr, Y, Zr, and Ba, together with subsolar values of Ca and Sc. Notably, the chemical pattern agrees with those recently published of Am stars, being then KELT-17 the first exoplanet host whose complete chemical pattern is unambiguously identified with this class. The stellar radius derived by two different methods agrees to each other and with those previously obtained in the literature.Comment: 5 pages, 8 figures, 2 tables, A&A accepte

Elemental abundances differences in the massive planet-hosting wide binary HD 196067-68

It has been suggested that small chemical anomalies observed in planet-hosting wide binary systems could be due to planet signatures, where the role of the planetary mass is still unknown. We search for a possible planet signature by analyzing the Tc trends in the remarkable binary system HD196067-HD196068. At the moment, only HD196067 is known to host a planet which is near the brown dwarf regime. We take advantage of the strong physical similarity between both stars, which is crucial to achieving the highest possible precision in stellar parameters and elemental chemical abundances. This system gives us a unique opportunity to explore if a possible depletion of refractories in a binary system could be inhibited by the presence of a massive planet. We performed a line-by-line chemical differential study, employing the non-solar-scaled opacities, in order to reach the highest precision in the calculations. After differentially comparing both stars, HD196067 displays a clear deficiency in refractory elements in the Tc plane, a lower iron content (0.051 dex) and also a lower Li I content (0.14 dex) than its companion. In addition, the differential abundances reveal a Tc trend. These targets represent the first cases of an abundance difference around a binary system hosting a super-Jupiter. Although we explored several scenarios to explain the chemical anomalies, none of them can be entirely ruled out. Additional monitoring of the system as well as studies of larger sample of wide binary systems hosting massive planets, are needed to better understand the chemical abundance trend observed in HD196067-68.Comment: 9 pages, six figures, three table

The value of early and comprehensive diagnoses in a human fetus with hydrocephalus and progressive obliteration of the aqueduct of Sylvius: Case Report

BACKGROUND: Mutant rodent models have highlighted the importance of the ventricular ependymal cells and the subcommissural organ (a brain gland secreting glycoproteins into the cerebrospinal fluid) in the development of fetal onset hydrocephalus. Evidence indicates that communicating and non-communicating hydrocephalus can be two sequential phases of a single pathological phenomenon triggered by ependymal disruption and/or abnormal function of the subcommissural organ. We have hypothesized that a similar phenomenon may occur in human cases with fetal onset hydrocephalus. CASE PRESENTATION: We report here on a case of human fetal communicating hydrocephalus with no central nervous system abnormalities other than stenosis of the aqueduct of Sylvius (SA) that became non-communicating hydrocephalus during the first postnatal week due to obliteration of the cerebral aqueduct. The case was followed closely by a team of basic and clinic investigators allowing an early diagnosis and prediction of the evolving pathophysiology. This information prompted neurosurgeons to perform a third ventriculostomy at postnatal day 14. The fetus was monitored by ultrasound, computerized axial tomography and magnetic resonance imaging (MRI). After birth, the follow up was by MRI, electroencephalography and neurological and neurocognitive assessments. Cerebrospinal fluid (CSF) collected at surgery showed abnormalities in the subcommissural organ proteins and the membrane proteins L1-neural cell adhesion molecule and aquaporin-4. The neurological and neurocognitive assessments at 3 and 6 years of age showed neurological impairments (epilepsy and cognitive deficits). CONCLUSIONS: (1) In a hydrocephalic fetus, a stenosed SA can become obliterated at perinatal stages. (2) In the case reported, a close follow up of a communicating hydrocephalus detected in utero allowed a prompt postnatal surgery aiming to avoid as much brain damage as possible. (3) The clinical and pathological evolution of this patient supports the possibility that the progressive stenosis of the SA initiated during the embryonic period may have resulted from ependymal disruption of the cerebral aqueduct and dysfunction of the subcommissural organ. The analysis of subcommissural organ glycoproteins present in the CSF may be a valuable diagnostic tool for the pathogenesis of congenital hydrocephalus