Bacterial infection of implanted scaffolds may have fatal consequences and, in combination with the emergence of multidrug bacterial resistance, the development of advanced antibacterial biomaterials ...and constructs is of great interest. Since decades ago, metals and their ions had been used to minimize bacterial infection risk and, more recently, metal-based nanomaterials, with improved antimicrobial properties, have been advocated as a novel and tunable alternative. A comprehensive review is provided on how metal ions and ion nanoparticles have the potential to decrease or eliminate unwanted bacteria. Antibacterial mechanisms such as oxidative stress induction, ion release and disruption of biomolecules are currently well accepted. However, the exact antimicrobial mechanisms of the discussed metal compounds remain poorly understood. The combination of different metal ions and surface decorations of nanoparticles will lead to synergistic effects and improved microbial killing, and allow to mitigate potential side effects to the host. Starting with a general overview of antibacterial mechanisms, we subsequently focus on specific metal ions such as silver, zinc, copper, iron and gold, and outline their distinct modes of action. Finally, we discuss the use of these metal ions and nanoparticles in tissue engineering to prevent implant failure.
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•Distinct mechanisms concertedly contribute to the antibacterial effect of metal ions and nanoparticles in tissue engineering.•Metal-mediated antibacterial mechanisms include membrane disruption, ROS generation, and protein/DNA damage.•As different metals/nanoparticles prompt different antibacterial mechanisms, biomaterials may benefit from combinatorial use.•Application specific antibacterial biomaterials with controlled metal release rates are achievable by combining techniques.
Nuclear medicine is defined as the use of radionuclides for diagnostic and therapeutic applications. The imaging modalities positron emission tomography (PET) and single-photon emission computed ...tomography (SPECT) are based on γ-emissions of specific energies. The therapeutic technologies are based on β
-particle-, α-particle-, and Auger electron emitters. In oncology, PET and SPECT are used to detect cancer lesions, to determine dosimetry, and to monitor therapy effectiveness. In contrast, radiotherapy is designed to irreparably damage tumor cells in order to eradicate or control the disease's progression. Radiometals are being explored for the development of diagnostic and therapeutic radiopharmaceuticals. Strategies that combine both modalities (diagnostic and therapeutic), referred to as theranostics, are promising candidates for clinical applications. This review provides an overview of the basic concepts behind therapeutic and diagnostic radiopharmaceuticals and their significance in contemporary oncology. Select radiometals that significantly impact current and upcoming cancer treatment strategies are grouped as clinically suitable theranostics pairs. The most important physical and chemical properties are discussed. Standard production methods and current radionuclide availability are provided to indicate whether a cost-efficient use in a clinical routine is feasible. Recent preclinical and clinical developments and outline perspectives for the radiometals are highlighted in each section.
Since the 2008 economic recession, state intervention in the real estate sector has strengthened. This article explains how housing financialization was reignited in Spain following key policy ...reforms in 2013. We argue that Spanish authorities managed to strategically recreate a finance-friendly environment to attract global investors. They combined financial policies, other deregulatory reforms and neoliberal measures in a coordinated manner we call a policy package. Our analysis provides evidence of the legal and political arrangements at various state levels that effectively facilitated the reanimation of a new cycle of housing financialization which caused rising inflation in prices and distress in tenants' rights. This approach contributes to the understanding of how state-led actions foster a spatial fix to overcome financial crises by granting global speculative funds extraordinary benefits. In addition, we show how this process occurred with poor democratic accountability and was also confronted by various forms of social contestation.
Summary
The ability to edit plant genomes through gene targeting (GT) requires efficient methods to deliver both sequence‐specific nucleases (SSNs) and repair templates to plant cells. This is ...typically achieved using Agrobacterium T‐DNA, biolistics or by stably integrating nuclease‐encoding cassettes and repair templates into the plant genome. In dicotyledonous plants, such as Nicotinana tabacum (tobacco) and Solanum lycopersicum (tomato), greater than 10‐fold enhancements in GT frequencies have been achieved using DNA virus‐based replicons. These replicons transiently amplify to high copy numbers in plant cells to deliver abundant SSNs and repair templates to achieve targeted gene modification. In the present work, we developed a replicon‐based system for genome engineering of cereal crops using a deconstructed version of the wheat dwarf virus (WDV). In wheat cells, the replicons achieve a 110‐fold increase in expression of a reporter gene relative to non‐replicating controls. Furthermore, replicons carrying CRISPR/Cas9 nucleases and repair templates achieved GT at an endogenous ubiquitin locus at frequencies 12‐fold greater than non‐viral delivery methods. The use of a strong promoter to express Cas9 was critical to attain these high GT frequencies. We also demonstrate gene‐targeted integration by homologous recombination (HR) in all three of the homoeoalleles (A, B and D) of the hexaploid wheat genome, and we show that with the WDV replicons, multiplexed GT within the same wheat cell can be achieved at frequencies of ~1%. In conclusion, high frequencies of GT using WDV‐based DNA replicons will make it possible to edit complex cereal genomes without the need to integrate GT reagents into the genome.
Significance Statement
Efficient methods to deliver genome engineering reagents are needed if gene targeting is to become routine, especially in difficult to transform crop species such as cereals. Here we demonstrate that Wheat Dwarf Virus‐based DNA replicons can achieve 12‐fold higher frequencies of gene targeting, in all three genomes of hexaploid wheat, and demonstrate multiplexed gene targeting through integration of reporter constructs simultaneously at two endogenous loci. Therefore it will be possible to edit complex cereal genomes without the need to integrate gene targeting reagents into the genome.
Following Ziya Gökalp and Ali Shariati’s assertion that Protestantism arose due to the influence of Islam in Europe in the Middle Ages, this study discusses the different discourses elaborated by the ...Turkish and Iranian authors based on this idea. The controversies surrounding modernity, westernization, colonialism, and Islam were a constant in their writings, despite the different geographical and historical circumstances. This paper discusses the logic of Gökalp and Shariati’s claim that Protestantism was Islamized Christianity. The aim is to provide a detailed perspective on how this claim illuminates their broader thinking about civilization, culture, and religion.
The surface modifications of titanium dental implants play important roles in the enhancement of osseointegration. The objective of the present study was to test two different implant surface ...treatments on a rabbit model to investigate the osseointegration. The tested surfaces were: a) acid-etched surface with sandblasting treatment (SA) and b) an oxidized implant surface (OS). The roughness was measured by an interferometeric microscope with white light and the residual stress of the surfaces was measured with X-ray residual stress Bragg-Bentano diffraction. Six New Zealand white rabbits were used for the in vivo study. Implants with the two different surfaces (SA and OS) were inserted in the femoral bone. After 12 weeks of implantation, histological and histomorphometric analyses of the blocks containing the implants and the surrounding bone were performed. All the implants were correctly implanted and no signs of infection were observed. SA and OS surfaces were both surrounded by newly formed trabeculae. Histomorphometric analysis revealed that the bone-implant contact % (BIC) was higher around the SA implants (53.49 ± 8.46) than around the OS implants (50.94 ± 16.42), although there were no significant statistical differences among them. Both implant surfaces (SA and OS) demonstrated a good bone response with significant amounts of newly formed bone along the implant surface after 12 weeks of implantation. These results confirmed the importance of the topography and physico-chemical properties of dental implants in the osseointegration.
We report a new family of titanium–organic frameworks that enlarges the limited number of crystalline, porous materials available for this metal. They are chemically robust and can be prepared as ...single crystals at multi‐gram scale from multiple precursors. Their heterometallic structure enables engineering of their photoactivity by metal doping rather than by linker functionalization. Compared to other methodologies based on the post‐synthetic metallation of MOFs, our approach is well‐fitted for controlling the positioning of dopants at an atomic level to gain more precise control over the band‐gap and electronic properties of the porous solid. Changes in the band‐gap are also rationalized with computational modelling and experimentally confirmed by photocatalytic H2 production.
Metal doping in titanium MOFs: MUV‐10 are crystalline, porous titanium frameworks with excellent chemical stability in water. The presence of heterometallic clusters in the structure of the frameworks enables chemical engineering of the band‐gap by suitable doping with open shell metals rather than by linker functionalization. This observation is confirmed by computational modelling of the electronic structure of this family of solids.
Though generally considered insulating, recent progress on the discovery of conductive porous metal–organic frameworks (MOFs) offers new opportunities for their integration as electroactive ...components in electronic devices. Compared to classical semiconductors, these metal–organic hybrids combine the crystallinity of inorganic materials with easier chemical functionalization and processability. Still, future development depends on the ability to produce high‐quality films with fine control over their orientation, crystallinity, homogeneity, and thickness. Here self‐assembled monolayer substrate modification and bottom‐up techniques are used to produce preferentially oriented, ultrathin, conductive films of Cu‐CAT‐1. The approach permits to fabricate and study the electrical response of MOF‐based devices incorporating the thinnest MOF film reported thus far (10 nm thick).
Preferably oriented, ultrathin, semiconductive films of the metal–organic framework (MOF) Cu‐CAT‐1 are formed by using self‐assembled monolayer substrate modification and bottom‐up techniques. The approach enables fabrication and study of the electrical response of MOF‐based devices incorporating the thinnest MOF film reported thus far (10 nm thick).
In dentistry and orthopedics, it is well accepted that implant fixation is a major goal. However, an emerging concern is bacterial infection. Infection of metallic implants can be catastrophic and ...significantly reduce patient quality of life. Accordingly, in this work, we focus on multifunctional coatings to simultaneously address and mitigate both these problems. We have developed a tailor-made peptide-based chemical platform that integrates the well-known RGD cell adhesive sequence and the lactoferrin-derived LF1-11 antimicrobial peptide. The platform was covalently grafted on titanium via silanization and the functionalization process characterized by contact angle, XPS, and QCM-D. The presence of the platform statistically improved the adhesion, proliferation and mineralization of osteoblast-like cells compared to control surfaces. At the same time, colonization by representative bacterial strains was significantly reduced on the surfaces. Furthermore, the biological potency of the multifunctional platform was verified in a co-culture in vitro model. Our findings demonstrate that this multifunctional approach can be useful to functionalize biomaterials to both improve cell integration and reduce the risk of bacterial infection.
We explore the relation between fund performance and the assets managed by the fund's managers that are outside the fund. Controlling for fund size, we find a negative relation between performance ...and the size of fund managers’ outside holdings, the number of other funds managed by a fund's managers, and the number of distinct fund categories managed by a fund's managers. This effect is driven by holdings that do not overlap with those held within the fund, and the effect's economic magnitude, while less than that of fund size, is comparable to that of fund family size and twice that of turnover. Endogeneity is addressed using fund mergers and recursive demeaning. Results suggest that manager responsibilities outside a fund significantly impact performance and that limited attention plays a role.
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