Evidence of Skyrmion-Tube Mediated Magnetization Reversal in Modulated Nanowires

Magnetic nanowires, conceived as individual building blocks for spintronic devices, constitute a well-suited model to design and study magnetization reversal processes, or to tackle fundamental questions, such as the presence of topologically protected magnetization textures under particular conditions. Recently, a skyrmion-tube mediated magnetization reversal process was theoretically reported in diameter modulated cylindrical nanowires. In these nanowires, a vortex nucleates at the end of the segments with larger diameter and propagates, resulting in a first switching of the nanowire core magnetization at small fields. In this work, we show experimental evidence of the so-called Bloch skyrmion-tubes, using advanced Magnetic Force Microscopy modes to image the magnetization reversal process of FeCoCu diameter modulated nanowires. By monitoring the magnetic state of the nanowire during applied field sweeping, a detected drop of magnetic signal at a given critical field unveils the presence of a skyrmion-tube, due to mutually compensating stray field components. That evidences the presence of a skyrmion-tube as an intermediate stage during the magnetization reversal, whose presence is related to the geometrical dimensions of the cylindrical segments

Exploring structure–activity relationships in photodynamic therapy anticancer agents based on Ir(III)-COUPY conjugates

Photodynamic therapy holds great promise as a non-invasive anticancer tool against drug-resistant cancers. However, highly effective, non-toxic, and reliable photosensitizers with operability under hypoxic conditions remain to be developed. Herein, we took the advantageous properties of COUPY fluorophores and cyclometalated Ir(III) complexes to develop novel PDT agents based on Ir(III)-COUPY conjugates with the aim of exploring structure–activity relationships. The structural modifications carried out within the coumarin scaffold had a strong impact on the photophysical properties and cellular uptake of the conjugates. All Ir(III)-COUPY conjugates exhibited high phototoxicity under green light irradiation, which was attributed to the photogeneration of ROS, while remaining non-toxic in the dark. Among them, two hit conjugates showed excellent phototherapeutic indexes in cisplatin-resistant A2780cis cancer cells, both in normoxia and in hypoxia, suggesting that photoactive therapy approaches based on the conjugation of far-red/NIR-emitting COUPY dyes and transition metal complexes could effectively tackle in vitro acquired resistance to cisplatin

Somatostatin subtype-2 receptor-targeted metal-based anticancer complexes

Conjugates of a dicarba analogue of octreotide, a potent somatostatin agonist whose receptors are overexpressed on tumor cells, with [PtCl 2(dap)] (dap = 1-(carboxylic acid)-1,2-diaminoethane) (3), [(η 6-bip)Os(4-CO 2-pico)Cl] (bip = biphenyl, pico = picolinate) (4), [(η 6-p-cym)RuCl(dap)] + (p-cym = p-cymene) (5), and [(η 6-p-cym)RuCl(imidazole-CO 2H)(PPh 3)] + (6), were synthesized by using a solid-phase approach. Conjugates 3-5 readily underwent hydrolysis and DNA binding, whereas conjugate 6 was inert to ligand substitution. NMR spectroscopy and molecular dynamics calculations showed that conjugate formation does not perturb the overall peptide structure. Only 6 exhibited antiproliferative activity in human tumor cells (IC 50 = 63 ± 2 μ in MCF-7 cells and IC 50 = 26 ± 3 μ in DU-145 cells) with active participation of somatostatin receptors in cellular uptake. Similar cytotoxic activity was found in a normal cell line (IC 50 = 45 ± 2.6 μ in CHO cells), which can be attributed to a similar level of expression of somatostatin subtype-2 receptor. These studies provide new insights into the effect of receptor-binding peptide conjugation on the activity of metal-based anticancer drugs, and demonstrate the potential of such hybrid compounds to target tumor cells specifically. © 2012 American Chemical Society

Domain Wall Propagation and Pinning Induced by Current Pulses in Cylindrical Modulated Nanowires

The future developments of three-dimensional magnetic nanotechnology require the control of domain wall dynamics by means of current pulses. While this has been extensively studied in planar magnetic strips (planar nanowires), few reports exist in cylindrical geometry, where Bloch point domain walls are expected to have intriguing properties. Here we report this investigation in cylindrical magnetic Ni nanowires with geometrical notches. Experimental work based on synchrotron X-ray magnetic circular dichroism (XMCD) combined with photoemission electron microscopy (PEEM) indicates that large current densities induce domain wall nucleation while smaller currents move domain walls preferably against the current direction. In the region where no pinning centers are present we found domain wall velocity of about 1 km/s. The domain wall motion along current was also detected in the vicinity of the notch region. Pinning of domain walls has been observed not only at geometrical constrictions but also outside of them. Thermal modelling indicates that large current densities temporarily raise the temperature in the nanowire above the Curie temperature leading to nucleation of domain walls during the system cooling. Micromagnetic modelling with spin-torque effect shows that for intermediate current densities Bloch point domain walls with chirality parallel to the Oersted field propagate antiparallel to the current direction. In other cases, domain walls can be bounced from the notches and/or get pinned outside their positions. We thus find that current is not only responsible for the domain wall propagation but is also a source of pinning due to the Oersted field action

Image processing tools for the validation of CryoEM maps

The number of maps deposited in public databases (Electron Microscopy Data Bank, EMDB) determined by cryo-electron microscopy has quickly grown in recent years. With this rapid growth, it is critical to guarantee their quality. So far, map validation has primarily focused on the agreement between maps and models. From the image processing perspective, the validation has been mostly restricted to using two halfmapsand the measurement of their internal consistency. In this article, we suggest that map validation can be taken much further from the point of view of image processing if 2D classes, particles, angles, coordinates, defoci, and micrographs are also provided. We present a progressive validation scheme that qualifies a result validation status from 0 to 5 and offers three optional qualifiers (A, W, and O) that can be added. The simplest validation state is 0, while the most complete would be 5AWO. This scheme has been implemented in a website https://biocomp.cnb.csic.es/EMValidationService/ to which reconstructed maps and their ESI can be uploaded.We are thankful to Philip Baldwin, Dmitry Lyumkis, and Gabriel Lander for making their validation methods available (4.h and A.c). Javier Vargas and Jordi Burguet would like to thank the Spanish Ministry of Science and Innovation for financial support through the call 2019 Proyectos de I+D+i – RTI Tipo A (PID2019- 108850RA-I00) and Arrate Muñoz Barrutia, PID2019-109820RB-I00, MCIN/AEI/ 10.13039/501100011033/, cofinanced by European Regional Development Fund (ERDF), “A way of making Europe.”. The authors acknowledge the economic support from MICIN of the Instruct Image Processing Center (I2PC) as part of the Spanish participation in Instruct-ERIC, the European Strategic Infrastructure Project (ESFRI) in the area of Structural Biology, Grant PID2019-104757RB-I00 funded by MCIN/AEI/10.13039/501100011033/ and “ERDF A way of making Europe”, by the European Union and Grant PRE2020 - 093527 funded by MCIN/ AEI/ 10.13039/501100011033 and by “ESF Investing in your future”. We also acknowledge support from “Comunidad Autónoma de Madrid” through Grant: S2017/BMD-3817, Instituto de Salud Carlos III (project IMPaCT-Data, exp. IMP/ 00019), co-funded by the European Union, European Regional Development Fund (ERDF, “A way to make Europe”), and European Union (EU) and Horizon 2020 through grants: EOSC Life (INFRAEOSC-04-2018, Proposal: 824087), High- ResCells (ERC – 2018 – SyG, Proposal: 810057), IMpaCT (WIDESPREAD-03-2018 – Proposal: 857203), EOSC – Synergy (EINFRA-EOSC-5, Proposal: 857647), iNEXTDiscovery (Proposal: 871037), EnLaCES (H2020-MSCA-IF-2020, Proposal: 101024130)

Conjugation of a Ru(II) Arene Complex to Neomycin or to Guanidinoneomycin Leads to Compounds with Differential Cytotoxicities and Accumulation between Cancer and Normal Cells

A straightforward methodology for the synthesis of conjugates between a cytotoxic organometallic ruthenium(II) complex and amino- and guanidinoglycosides, as potential RNA-targeted anticancer compounds, is described. Under microwave irradiation, the imidazole ligand incorporated on the aminoglycoside moiety (neamine or neomycin) was found to replace one triphenylphosphine ligand from the ruthenium precursor [(η6-p-cym)RuCl(PPh3)2]+, allowing the assembly of the target conjugates. The guanidinylated analogue was easily prepared from the neomycin-ruthenium conjugate by reaction with N,N′-di-Boc-N″-triflylguanidine, a powerful guanidinylating reagent that was compatible with the integrity of the metal complex. All conjugates were purified by semipreparative high-performance liquid chromatography (HPLC) and characterized by electrospray ionization (ESI) and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and NMR spectroscopy. The cytotoxicity of the compounds was tested in MCF-7 (breast) and DU-145 (prostate) human cancer cells, as well as in the normal HEK293 (Human Embryonic Kidney) cell line, revealing a dependence on the nature of the glycoside moiety and the type of cell (cancer or healthy). Indeed, the neomycin-ruthenium conjugate (2) displayed moderate antiproliferative activity in both cancer cell lines (IC50 ≈ 80 μM), whereas the neamine conjugate (4) was inactive (IC50 ≈ 200 μM). However, the guanidinylated analogue of the neomycin-ruthenium conjugate (3) required much lower concentrations than the parent conjugate for equal effect (IC50 = 7.17 μM in DU-145 and IC50 = 11.33 μM in MCF-7). Although the same ranking in antiproliferative activity was found in the nontumorigenic cell line (3 2 > 4), IC50 values indicate that aminoglycoside-containing conjugates are about 2-fold more cytotoxic in normal cells (e.g., IC50 = 49.4 μM for 2) than in cancer cells, whereas an opposite tendency was found with the guanidinylated conjugate, since its cytotoxicity in the normal cell line (IC50 = 12.75 μM for 3) was similar or even lower than that found in MCF-7 and DU-145 cancer cell lines, respectively. Cell uptake studies performed by ICP-MS with conjugates 2 and 3 revealed that guanidinylation of the neomycin moiety had a positive effect on accumulation (about 3-fold higher in DU-145 and 4-fold higher in HEK293), which correlates well with the higher antiproliferative activity of 3. Interestingly, despite the slightly higher accumulation in the normal cell than in the cancer cell line (about 1.4-fold), guanidinoneomycin-ruthenium conjugate (3) was more cytotoxic to cancer cells (about 1.8-fold), whereas the opposite tendency applied for neomycin-ruthenium conjugate (2). Such differences in cytotoxic activity and cellular accumulation between cancer and normal cells open the way to the creation of more selective, less toxic anticancer metallodrugs by conjugating cytotoxic metal-based complexes such as ruthenium(II) arene derivatives to guanidinoglycosides

Poetics/Poelitics of materiality in latin american digital poetry

Este artículo propone leer la poesía digital latinoamericana en vinculación con el acontecimiento poético-político que emerge cuando se considera su materialidad. Dar visibilidad a la materialidad habilita limitar la naturalización de los sentidos que vienen asociados a la cultura digital hegemónica contemporánea. Esto se logra desde procedimientos que ponen de relieve tanto los diversos niveles de materialidad inherentes a cada evento artístico literario digital —materialidad textual de superficie, materialidad relacional de las interfaces tanto de software como de hardware, materialidad del código— como los modos convencionales de ser con y hacer sentido de los entramados técnicos digitales que organizan nuestra vida cotidiana.This paper aims to read Latin American digital poetry in regards to the poetic-political event that emerges whenever its materiality is considered. To make materiality visible enables one to restrict the naturalization of meanings associate with contemporary hegemonic digital culture. This is accomplished through artistic procedures that emphasize, on the one hand, the multiple levels of materiality inherent to digital literary works— surface/textual materiality, software and hardware interface relational materiality, code materiality—and, on the other hand, the conventional ways to interact with and build meaning within the digital space that organize everyday life.Fil: Kozak, Claudia. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones "Gino Germani". Estudios Culturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Tres de Febrero; Argentin

Advances on the biosynthesis of pyridine rings

Numerous studies have investigated the biosynthesis of pyridine heterocycles derived from nicotinic acid. However, metabolic pathways generating pyridine heterocycles in nature remain uninvestigated. Here, we summarize recent contributions conducted in the last decade on the biosynthetic pathways of non-derivate from nicotinic acid pyridine rings and discuss their implication on the study of natural products with pyridine structures