BINA

Millions of adenosines are deaminated throughout the transcriptome by ADAR1 and/or ADAR2 at varying levels, raising the question of what are the determinants guiding substrate specificity and how these differ between the two enzymes. We monitor how secondary structure modulates ADAR2 vs ADAR1 substrate selectivity, on the basis of systematic probing of thousands of synthetic sequences transfected into cell lines expressing exclusively ADAR1 or ADAR2. Both enzymes induce symmetric, strand-specific editing, yet with distinct offsets with respect to structural disruptions: −26 nt for ADAR2 and −35 nt for ADAR1. We unravel the basis for these differences in offsets through mutants, domain-swaps, and ADAR homologs, and find it to be encoded by the differential RNA binding domain (RBD) architecture. Finally, we demonstrate that this offset-enhanced editing can allow an improved design of ADAR2 …

Given the current status of coronavirus disease 2019 (COVID-19) as a global pandemic, it is of high priority to gain a deeper understanding of the disease's development and how the virus impacts its host. Adenosine (A)-to-Inosine (I) RNA editing is a post-transcriptional modification, catalyzed by the ADAR family of enzymes, that can be considered part of the inherent cellular defense mechanism as it affects the innate immune response in a complex manner. It was previously reported that various viruses could interact with the host's ADAR enzymes, resulting in epigenetic changes both to the virus and the host. Here, we analyze RNA-seq of nasopharyngeal swab specimens as well as whole-blood samples of COVID-19 infected individuals and show a significant elevation in the global RNA editing activity in COVID-19 compared to healthy controls. We also detect specific coding sites that exhibit higher editing …

Highly localized photodynamic therapy (PDT) is achieved by biolistic delivery of photosensitizer-loaded porous silicon microparticles directly into solid tumors, as demonstrated by Orit Shefi, Ester Segal, and co-workers in article 2300877. PDT irradiation following the uptake of the released photosensitizer payload induce substantial inhibition of tumor growth in vivo, opening new possibilities for an improved clinical PDT treatment.

Imaging speed and spatial resolution are key factors in optical diffraction tomography (ODT), while they are mutually exclusive in 3D refractive index imaging. This paper presents a multi-harmonic structured illumination-based optical diffraction tomography (MHSI-ODT) to acquire 3D refractive index (RI) maps of transparent samples. MHSI-ODT utilizes a digital micromirror device (DMD) to generate structured illumination containing multiple harmonics. For each structured illumination orientation, four spherical spectral crowns are solved from five phase-shifted holograms, meaning that the acquisition of each spectral crown costs 1.25 raw images. Compared to conventional SI-ODT, which retrieves two spectral crowns from three phase-shifted raw images, MHSI-ODT enhances the imaging speed by 16.7% in 3D RI imaging. Meanwhile, MHSI-ODT exploits both the 1st-order and the 2nd-order harmonics; therefore, it …

Given the current status of coronavirus disease 2019 (COVID-19) as a global pandemic, it is of high priority to gain a deeper understanding of the disease's development and how the virus impacts its host. Adenosine (A)-to-Inosine (I) RNA editing is a post-transcriptional modification, catalyzed by the ADAR family of enzymes, that can be considered part of the inherent cellular defense mechanism as it affects the innate immune response in a complex manner. It was previously reported that various viruses could interact with the host's ADAR enzymes, resulting in epigenetic changes both to the virus and the host. Here, we analyze RNA-seq of nasopharyngeal swab specimens as well as whole-blood samples of COVID-19 infected individuals and show a significant elevation in the global RNA editing activity in COVID-19 compared to healthy controls. We also detect specific coding sites that exhibit higher editing …

Atopic dermatitis (AD) is associated with dysregulated type 1 interferon (IFN)–mediated responses, in parallel with the dominant type 2 inflammation. However, the pathophysiology of this dysregulation is largely unknown. Adenosine-to-inosine (A-to-I) RNA editing plays a critical role in immune regulation by preventing double-stranded (ds) RNA recognition by MDA5 and IFN activation. We studied global A-to-I editing in AD in order to elucidate the role played by altered editing in the pathophysiology of this disease.Analysis of three RNA sequencing (RNA-seq) datasets of AD skin samples revealed reduced levels of A-to-I RNA editing in AD. This reduction was seen globally throughout Alu repeats, as well as in coding genes and in specific pre-mRNA loci expected to create long dsRNA, the main substrate of MDA5 leading to type I IFN activation. Consistently, IFN signature genes (ISG) were upregulated. In contrast …

Base editing (BE) techniques offer efficient means to modify specific nucleotides in the genome. While current research mainly focuses on applying BE for treating genetic diseases caused by single-nucleotide variants (SNVs), its potential in cancer is worth exploring, as many tumors arise from an accumulation of various mutations. BE techniques primarily consist of a fusion between a Cas nuclease and a deaminase (Cas-BE), that enables A-to-G or C-to-T edits. This allows for the correction of G>A and T>C SNVs at the DNA or RNA level. Additionally, BE can correct C>T and A>G SNVs at the DNA level through the cellular DNA repair response. Precise targeting is aimed by a programmed guide RNA (gRNA), which engages in Watson-Crick base pairing with the desired region. However, a remaining concern is gRNA binding to additional locations in the genome, leading to unintended off-target edits. An …

The exploration of cathode and anode materials that enable reversible storage of mono and multivalent cations has driven extensive research on organic compounds. In this regard, polyimide (PI)‐based electrodes have emerged as a promising avenue for the development of post‐lithium energy storage systems. This review article provides a comprehensive summary of the syntheses, characterizations, and applications of PI compounds as electrode materials capable of hosting a wide range of cations. Furthermore, the review also delves into the advancements in PI based solid state batteries, PI‐based separators, current collectors, and their effectiveness as polymeric binders. By highlighting the key findings in these areas, this review aims at contributing to the understanding and advancement of PI‐based structures paving the way for the next generation of energy storage systems.

X ray fluorescence ghost imaging (XRF-GI) was recently demonstrated for x ray lab sources. It has the potential to reduce the acquisition time and deposited dose by choosing their trade-off with a spatial resolution while alleviating the focusing constraints of the probing beam. Here, we demonstrate the realization of synchrotron-based XRF-GI: we present both an adapted experimental setup and its corresponding required computational technique to process the data. This extends the above-mentioned potential advantages of GI to synchrotron XRF imaging. In addition, it enables new strategies to improve resilience against drifts at all scales and the study of previously inaccessible samples, such as liquids.

The ability to control neuronal mobility and organization is of great importance in developing neuronal interfaces and novel therapeutic approaches. An emerging promising method is the manipulation of neuronal cells from afar via magnetic forces. Nevertheless, using magnetic iron oxide nanoparticles as internal actuators may lead to biotoxicity, adverse influence on intracellular processes, and thus requires prerequisite considerations for therapeutic approaches. Magnetizing the cells via the incorporation of magnetic particles that can be applied extracellularly is advantageous. Herein, we have developed a magnetic system based on streptavidin–biotin interaction to decorate cellular membrane with magnetic elements. In this model, superparamagnetic microparticles, coated with streptavidin, were specifically bound to biotinylated PC12 cells. We demonstrated that cell movement can be directed remotely by the forces produced by pre-designed magnetic fields. First, using time lapse imaging, we analyzed the kinetics of cell migration towards the higher flux zone. Next, to form organized networks of cells we designed and fabricated micro-patterned magnetic devices. The fabricated devices were composed of a variety of ferromagnetic shapes, sputter-deposited onto glass substrates. Cells that were conjugated to the magnetic particles were plated atop the micro-patterned substrates, attracted to the magnetic actuators and became fixed onto the magnetic patterns. In all, our study presents a novel system based on a well-known molecular technology combined with nanotechnology that may well lead to the expansion of implantable magnetic …

The European Cooperation in Science and Technology (COST) is an intergovernmental organization dedicated to funding and coordinating scientific and technological research in Europe, fostering collaboration among researchers and institutions across countries. Recently, COST Action funded the "Genome Editing to treat Human Diseases" (GenE-HumDi) network, uniting various stakeholders such as pharmaceutical companies, academic institutions, regulatory agencies, biotech firms, and patient advocacy groups. GenE-HumDi's primary objective is to expedite the application of genome editing for therapeutic purposes in treating human diseases. To achieve this goal, GenE-HumDi is organized in several working groups, each focusing on specific aspects. These groups aim to enhance genome editing technologies, assess delivery systems, address safety concerns, promote clinical translation, and develop …

Iron–nitrogen–carbon (FeNC) catalysts are a viable alternative to platinum, but still lack the necessary performance. Now, pyrolysis under forming gas is found as a path to boosting their site density, activity and durability.

The process of aging refers to physiological changes that occur to an organism as time progresses and involves changes to DNA, proteins, metabolism, cells, and organs. Like the rest of the cells in the body, gametes age, and it is well established that there is a decline in reproductive capabilities in females and males with aging. One of the major pathways known to be involved in aging is epigenetic changes. The epigenome is the multitude of chemical modifications performed on DNA and chromatin that affect the ability of chromatin to be transcribed. In this review, we explore the effects of aging on female and male gametes with a focus on the epigenetic changes that occur in gametes throughout aging. Quality decline in oocytes occurs at a relatively early age. Epigenetic changes constitute an important part of oocyte aging. DNA methylation is reduced with age, along with reduced expression of DNA …

The state‐of‐the‐art Platinum group metal (PGM)‐free oxygen reduction reaction (ORR) catalysts have been synthesized using the pyrolysis of iron, nitrogen, and carbon precursors, and result in highly active ORR catalysts, but their undefined structure limits their further development. Since the inspiration for these catalysts came from well‐defined structures of transition metal complexes, it is important to understand the various parameters that govern the reaction potential, selectivity, and the stability with well‐defined catalysts and try to extrapolate them to the pyrolyzed catalysts. In this chapter, we give an overview of the parameters that influence the catalysis of ORR with well‐defined ORR catalysts. These can later be used to further enhance the performance of the state‐of‐the‐art PGM‐free ORR catalysts.

The ability to control neuronal mobility and organization is of great importance in developing neuronal interfaces and novel therapeutic approaches. An emerging promising method is the manipulation of neuronal cells from afar via magnetic forces. Nevertheless, using magnetic iron oxide nanoparticles as internal actuators may lead to biotoxicity, adverse influence on intracellular processes, and thus requires prerequisite considerations for therapeutic approaches. Magnetizing the cells via the incorporation of magnetic particles that can be applied extracellularly is advantageous. Herein, we have developed a magnetic system based on streptavidin–biotin interaction to decorate cellular membrane with magnetic elements. In this model, superparamagnetic microparticles, coated with streptavidin, were specifically bound to biotinylated PC12 cells. We demonstrated that cell movement can be directed remotely by the forces produced by pre-designed magnetic fields. First, using time lapse imaging, we analyzed the kinetics of cell migration towards the higher flux zone. Next, to form organized networks of cells we designed and fabricated micro-patterned magnetic devices. The fabricated devices were composed of a variety of ferromagnetic shapes, sputter-deposited onto glass substrates. Cells that were conjugated to the magnetic particles were plated atop the micro-patterned substrates, attracted to the magnetic actuators and became fixed onto the magnetic patterns. In all, our study presents a novel system based on a well-known molecular technology combined with nanotechnology that may well lead to the expansion of implantable magnetic …

The seawater electrolysis is an economically favorable approach for water splitting application because seawater is one of the plentiful abundant natural resources on our earth. In water splitting pathway, the anodic half-cell reaction from seawater stills a challenging task due to anodic corrosion and the competitive chloride oxidation process. In the current study, we prepared flower-shaped porous nanorods of iron doped cobalt nickel layered double hydroxide supported on nickel foam (Fe0.05 CoNi LDH/NF), which require very less oxygen evolution reaction (OER) overpotential in 1M KOH (212mV) and alkaline seawater (287mV) to deliver 10 mAcm−2 current density and exhibited remarkable 14h durability. At the same time, post treated sample reveals the better OER activity after chronopotentiometry analysis, because of superior conductivity and corrosion-resistance of the electrocatalyst. The doping of Fe cation …

Imaging speed and spatial resolution are key factors in optical diffraction tomography (ODT), while they are mutually exclusive in 3D refractive index imaging. This paper presents a multi-harmonic structured illumination-based optical diffraction tomography (MHSI-ODT) to acquire 3D refractive index (RI) maps of transparent samples. MHSI-ODT utilizes a digital micromirror device (DMD) to generate structured illumination containing multiple harmonics. For each structured illumination orientation, four spherical spectral crowns are solved from five phase-shifted holograms, meaning that the acquisition of each spectral crown costs 1.25 raw images. Compared to conventional SI-ODT, which retrieves two spectral crowns from three phase-shifted raw images, MHSI-ODT enhances the imaging speed by 16.7% in 3D RI imaging. Meanwhile, MHSI-ODT exploits both the 1st-order and the 2nd-order harmonics; therefore, it …

Natural killer (NK) cells are a vital component of cancer immune surveillance. They provide a rapid and potent immune response, including direct cytotoxicity and mobilization of the immune system, without the need for antigen processing and presentation. NK cells may also be better tolerated than T cell therapy approaches and are susceptible to various gene manipulations. Therefore, NK cells have become the focus of extensive translational research. Gamida Cell’s nicotinamide (NAM) platform for cultured NK cells provides an opportunity to enhance the therapeutic potential of NK cells. CD38 is an ectoenzyme ubiquitously expressed on the surface of various hematologic cells, including multiple myeloma (MM). It has been selected as a lead target for numerous monoclonal therapeutic antibodies against MM. Monoclonal antibodies target CD38, resulting in the lysis of MM plasma cells through various antibody-mediated mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis, significantly improving the outcomes of patients with relapsed or refractory MM. However, this therapeutic strategy has inherent limitations, such as the anti-CD38-induced depletion of CD38-expressing NK cells, thus hindering ADCC. We have developed genetically engineered NK cells tailored to treat MM, in which CD38 was knocked-out using CRISPR-Cas9 technology and an enhanced chimeric antigen receptor (CAR) targeting CD38 was introduced using mRNA electroporation. This combined genetic approach allows for an improved cytotoxic activity directed against …

Surface characterization is essential for understanding chemical and electrochemical transformations occurring on surfaces or at interfaces. Battery electrode aging processes, biofilm growth, crystallization, and transport/signaling across cellular membranes are only a few examples of such phenomena. This special issue delves into applied electrochemistry and nonlinear optical techniques applicable to surface characterization.

In article number 2200029, Vasily Astratov and colleagues representing 27 research teams worldwide created a roadmap on label-free super-resolution imaging. Its scope spans from diffraction-limited interference detection techniques to methods allowing to overcome classical diffraction limit without using fluorescent markers, which are based on information science; structured illumination; near-field, nonlinear, and transformation optics; and advanced superlens designs. Cover images are provided by Aydogan Ozcan and Nikolay Zheludev participating in this Roadmap.