Trans-Splicing Improvement by the Combined Application of Antisense Strategies

Spliceosome-mediated RNA trans-splicing has become an emergent tool for the repair of mutated pre-mRNAs in the treatment of genetic diseases. RNA trans-splicing molecules (RTMs) are designed to induce a specific trans-splicing reaction via a binding domain for a respective target pre-mRNA region. A previously established reporter-based screening system allows us to analyze the impact of various factors on the RTM trans-splicing efficiency in vitro. Using this system, we are further able to investigate the potential of antisense RNAs (AS RNAs), presuming to improve the trans-splicing efficiency of a selected RTM, specific for intron 102 of COL7A1. Mutations in the COL7A1 gene underlie the dystrophic subtype of the skin blistering disease epidermolysis bullosa (DEB). We have shown that co-transfections of the RTM and a selected AS RNA, interfering with competitive splicing elements on a COL7A1-minigene (COL7A1-MG), lead to a significant increase of the RNA trans-splicing efficiency. Thereby, accurate trans-splicing between the RTM and the COL7A1-MG is represented by the restoration of full-length green fluorescent protein GFP on mRNA and protein level. This mechanism can be crucial for the improvement of an RTM-mediated correction, especially in cases where a high trans-splicing efficiency is required.     

Social media in conflicts and crises

ABSTRACT

The growing importance of social media in conflicts and crises is accompanied by an ever-increasing research interest in the crisis informatics field in order to identify potential benefits and develop measures against the technology’s abuse. This special issue sets out to give an overview of current research on the use of social media in conflicts and crises. In doing so, it focuses on both good and malicious aspects of social media and includes a variety of papers of conceptual, theoretical and empirical nature. In six sections, the special issue presents an overview of the field, analytical methods, technical challenges, current advancements and the accepted papers before concluding. Specific topics range from cyber deception over information trustworthiness to mining and near-real-time processing of social media data.     

Structural properties of nanocomposites based on resole-type phenol-formaldehyde oligomers and detonation nanodiamonds

Using the methods of infrared spectroscopy (IRS) and X-ray photoelectron spectroscopy (XPS), it was shown that short-term high-energy machining of detonation nanodiamonds (DND) leads to structural changes in the crystal structure and functional composition of the surface layer on particles. The possibility of spontaneous formation for stable colloidal systems with a narrow size distribution of mechanically activated DND in phenol-formaldehyde oligomers (PFO) was established. By molecular spectroscopy it was revealed that π → π* interactions of the aromatic rings of PFO are caused by orientational phenomena as a result of hydrogen bonds between an activated DND surface and functional groups of PFO. The effect of DND concentration on the curing reaction parameters ofpsgr the phenol-formaldehyde oligomer was determined by differential scanning calorimetry (DSC). The concentration effect of mechanically activated nanodiamonds on the physical and mechanical characteristics of a composite material based on phenol-formaldehyde binder and polyamide paper (Nomex) was studied. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48582.     

Intervertebral Disc Regeneration Injection of a Cell-Loaded Collagen Hydrogel in a Sheep Model

Degenerated intervertebral discs (IVDs) were treated with autologous adipose-derived stem cells (ASC) loaded into an injectable collagen scaffold in a sheep model to investigate the implant’s therapeutic potential regarding the progression of degeneration of previously damaged discs. In this study, 18 merino sheep were subjected to a 3-step minimally invasive injury and treatment model, which consisted of surgically induced disc degeneration, treatment of IVDs with an ASC-loaded collagen hydrogel 6 weeks post-operatively, and assessment of the implant’s influence on degenerative tissue changes after 6 and 12 months of grazing. Autologous ASCs were extracted from subcutaneous adipose tissue and cultivated in vitro. At the end of the experiment, disc heights were determined by µ-CT measurements and morphological tissue changes were histologically examined.Histological investigations show that, after treatment with the ASC-loaded collagen hydrogel implant, degeneration-specific features were observed less frequently. Quantitative studies of the degree of degeneration did not demonstrate a significant influence on potential tissue regeneration with treatment. Regarding disc height analysis, at both 6 and 12 months after treatment with the ASC-loaded collagen hydrogel implant a stabilization of the disc height can be seen. A complete restoration of the intervertebral disc heights however could not be achieved.The reported injection procedure describes in a preclinical model a translational therapeutic approach for degenerative disc diseases based on adipose-derived stem cells in a collagen hydrogel scaffold. Further investigations are planned with the use of a different injectable scaffold material using the same test model.     

EGFR-Binding Peptides: From Computational Design towards Tumor-Targeting of Adeno-Associated Virus Capsids

The epidermal growth factor receptor (EGFR) plays a central role in the progression of many solid tumors. We used this validated target to analyze the de novo design of EGFR-binding peptides and their application for the delivery of complex payloads via rational design of a viral vector. Peptides were computationally designed to interact with the EGFR dimerization interface. Two new peptides and a reference (EDA peptide) were chemically synthesized, and their binding ability characterized. Presentation of these peptides in each of the 60 capsid proteins of recombinant adeno-associated viruses (rAAV) via a genetic based loop insertion enabled targeting of EGFR overexpressing tumor cell lines. Furthermore, tissue distribution and tumor xenograft specificity were analyzed with systemic injection in chicken egg chorioallantoic membrane (CAM) assays. Complex correlations between the targeting of the synthetic peptides and the viral vectors to cells and in ovo were observed. Overall, these data demonstrate the potential of computational design in combination with rational capsid modification for viral vector targeting opening new avenues for viral vector delivery and specifically suicide gene therapy.     

Entwicklung eines Transformationsmodells – Modularisierung schrittweise gedacht

For some years now, the process industry has been meeting the challenges of the markets with modular production and logistics concepts. This article presents this development process in the form of a four-stage transformation model. It is shown that the path towards modular production environments can be taken step by step. The motto is “evolution instead of revolution”. First, an overview of the state of the art of modularized production and logistics systems is given. Based on this, the article describes and classifies the four different stages of modularization.     

Exploring Implicit and Explicit Geometrical Structure of Data for Deep Embedded Clustering

Neural Processing Letters - Clustering is an essential data analysis technique and has been studied extensively over the last decades. Previous studies have shown that data representation and data...     

Bi3+ as an enhancer for down- and upconversion luminescence in ternary vanadate structures

A series of dual-mode nanomaterials based on Ba₂LaV₃O₁₁:Yb³⁺, Er³⁺, Bi³⁺, with different bismuth content were synthesized using the hydrothermal method. Various analytical methods, such as x-ray diffraction (XRD) with additional detailed Rietveld analysis, transmission electron microscopy (TEM), inductively coupled plasma mass spectroscopy (ICP-MS) and laser spectroscopy have confirmed that with increasing Bi³⁺ content, phase purity, optical absorption and luminescence intensity significantly increased. Moreover, a slight luminescence color tunability was observed along with the gradual introduction of bismuth into the host structure since, among the others, the local crystal field around emitting Er³⁺ ions was changing. The use of ultraviolet and near-infrared excitation wavelengths allowed to obtain a dual mode luminescence, which extended the emission range and demonstrated the possibility of using the studied materials, e.g. in solar cells.