Engineering conductive protein films through nanoscale self-assembly and gold nanoparticles doping

Protein-based materials are usually considered as insulators, although conductivity has been recently shown in proteins. This fact opens the door to develop new biocompatible conductive materials. While there are emerging efforts in this area, there is an open challenge related to the limited conductivity of protein-based systems. This work shows a novel approach to tune the charge transport properties of protein-based materials by using electron-dense AuNPs. Two strategies are combined in a unique way to generate the conductive solid films: (1) the controlled self-assembly of a protein building block; (2) the templating of AuNPs by the engineered building block. This bottom-up approach allows controlling the structure of the films and the distribution of the AuNPs within, leading to enhanced conductivity. This work illustrates a promising strategy for the development of effective hybrid protein-based bioelectrical materialsThis work was partially supported by the European Research Council ERC-CoG-648071-ProNANO, ERC-PoC-841063-NIMM, Agencia Estatal de Investigación, Spain (PID2019- 111649RB-I00; and MAT2017-88693-R), and the Basque Government (Elkartek KK-2017/00008), E.L-M thanks the Spanish Ministry of Science and Innovation for the FPI grant (BES-2017-079646). This work was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency – Grant No. MDM-2017-0720 (CIC biomaGUNE) and SEV-2016-0686 (IMDEA Nanociencia

Expression of osteoprotegerin and its ligands, RANKL and TRAIL, in rheumatoid arthritis

Osteoprotegerin (OPG), receptor activator of nuclear factor-?B ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been involved in rheumatoid arthritis (RA) pathophysiology. In this study, we assessed messenger RNA (mRNA) expression of these molecules by qPCR in peripheral blood from 26 patients with RA (12 of them with ischemic heart disease -IHD) and 10 healthy controls. Correlation coefficients between OPG, RANKL and TRAIL expression levels in RA patients and their clinical and demographic characteristics were also evaluated. Whereas OPG and OPG/TRAIL ratio expression were significantly increased in RA patients compared to controls (fold change?=?1.79, p?=?0.013 and 2.07, p?=?0.030, respectively), RANKL/OPG ratio was significantly decreased (fold change?=?0.50, p?=?0.020). No significant differences were found between patients and controls in RANKL and TRAIL expression. Interestingly, TRAIL expression was significantly higher in RA patients with IHD compared to those without IHD (fold change?=?1.46, p?=?0.033). Moreover, biologic disease-modifying antirheumatic drugs (DMARDs) significantly decreased RANKL expression in RA patients (p?=?0.016). Our study supports an important role of OPG and TRAIL in RA. Furthermore, it highlights an effect of biologic DMARDs in the modulation of RANKL

Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs

Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell's proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.Comment: review article, 29 pages, 7 figure

10 Myr evolution of sedimentation rates in a deep marine to non-marine foreland basin system: Tectonic and sedimentary controls (Eocene, Tremp–Jaca Basin, Southern Pyrenees, NE Spain)

The propagation of the deformation front in foreland systems is typically accompanied by the incorporation of parts of the basin into wedge-top piggy-back basins, this process is likely producing considerable changes to sedimentation rates (SR). Here we investigate the spatial-temporal evolution of SR for the Tremp–Jaca Basin in the Southern Pyrenees during its evolution from a wedge-top, foreredeep, forebulge configuration to a wedge-top stage. SR were controlled by a series of tectonic structures that influenced subsidence distribution and modified the sediment dispersal patterns. We compare the decompacted SR calculated from 12 magnetostratigraphic sections located throughout the Tremp–Jaca Basin represent the full range of depositional environment and times. While the derived long-term SR range between 9.0 and 84.5 cm/kyr, compiled data at the scale of magnetozones (0.1–2.5 Myr) yield SR that range from 3.0 to 170 cm/kyr. From this analysis, three main types of depocenter are recognized: a regional depocenter in the foredeep depozone; depocenters related to both regional subsidence and salt tectonics in the wedge-top depozone; and a depocenter related to clastic shelf building showing transgressive and regressive trends with graded and non-graded episodes. From the evolution of SR we distinguish two stages. The Lutetian Stage (from 49.1–41.2 Ma) portrays a compartmentalized basin characterized by variable SR in dominantly underfilled accommodation areas. The markedly different advance of the deformation front between the Central and Western Pyrenees resulted in a complex distribution of the foreland depozones during this stage. The Bartonian–Priabonian Stage (41.2–36.9 Ma) represents the integration of the whole basin into the wedge-top, showing a generalized reduction of SR in a mostly overfilled relatively uniform basin. The stacking of basement units in the hinterland during the whole period produced unusually high SR in the wedge-top depozoneAgència de Gestió d'Ajuts Universitaris i de Recerca, Grant/Award Number: 2017SGR596; Secretaría de Estado de Investigación, Desarrollo e Innovación, Grant/Award Number: BES-2015-073302 and CGL2014-55900-P; Swiss National Science Foundation, Grant/Award Number: 200020_18201

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

The role of a functional variant of TYK2 in vasculitides and infections

Objective The TYK2 gene encodes a tyrosin kinase which is involved in multiple immune functions. A functional variant of this gene has been identified to play a protective role in multiple autoimmune diseases. The goal of this study was to evaluate the involvement of this variant of TYK2 in vasculitides [giant cell arteritis (GCA), ANCA-associated vasculitis (AAV) and IgA vasculitis (IgAV)] and viral infections [hepatitis C virus (HCV) and human immunodeficiency virus type I (HIV-1)]. Methods The study sample was composed of 13,745 European individuals. The genotyping was performed by Immunochip and TaqMan 5’allele discrimination assays and the allele frequencies were compared using PLINK. Results Although the results obtained did not reach the genome-wide level of significance, p-values at nominal significance were observed, suggesting that the TYK2 variant provides protection against two vasculitides: GCA (p=5.94E-3; OR (95%CI) = 0.56 (0.37–0.85) and AAV (p=6.79E-3; OR (95%CI) = 0.65 (0.47–0.89). However, this variant was not found to be associated with IgAV. No evidence was gained that the TYK2 variant confers susceptibility to HCV and HIV-1 infection. Conclusion This is the first study to propose the association between the TYK2 and both GCA and AAV. Our findings also suggest that TYK2 does not play a relevant role in IgAV or in susceptibility to HCV and HVI-1