BINA

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 …

Forward Brillouin scattering fiber sensors can detect and analyze media outside the cladding of standard fibers, where guided light does not reach. Nearly all such sensors reported to-date have relied on the radially symmetric guided acoustic modes of the fiber. Wave motion in these modes is strictly dilatational. However, forward Brillouin scattering also takes place through torsional–radial guided acoustic modes of the fiber. Torsional–radial modes exhibit more complex tensor characteristics, and they consist of both dilatational and shear wave contributions. In this work, we show that forward Brillouin sensing through torsional–radial acoustic modes is qualitatively different from processes based on the radial ones. While dilatational wave components may dissipate toward liquids outside the fiber cladding, shear waves do not. Consequently, the effect of outside liquids varies among torsional–radial modes. Those …

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 …

Recent studies have underscored the pivotal role of adenosine-to-inosine RNA editing, catalyzed by ADAR1, in suppressing innate immune interferon responses triggered by cellular double-stranded RNA (dsRNA). However, the specific ADAR1 editing targets crucial for this regulatory function remain elusive. We review analyses of transcriptome-wide ADAR1 editing patterns and their evolutionary dynamics, which offer valuable insights into this unresolved query. The growing appreciation of the significance of immunogenic dsRNAs and their editing in inflammatory and autoimmune diseases and cancer calls for a more comprehensive understanding of dsRNA immunogenicity, which may promote our understanding of these diseases and open doors to therapeutic avenues.

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 …

This work presents an original method based on the variance properties of the microwave absorption spectrum of an ensemble of nitrogen vacancy centers in diamond. The spectrum is measured optically. A compact and simple device is designed to optimize the photon collection. We conduct a quantitative comparison of the ensemble's optical signal in both the visible and near infrared range. Using the enhanced signal-to-noise ratio achieved through the device geometry we perform real-time DC magnetometry at moderate light and microwave powers. Under these conditions, the amplitude of a DC magnetic field can be extracted from the variance of the microwave absorption spectrum in a fast and reproducible manner, without the burden of complex fitting techniques.

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.

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.

Tissue-integrated micro-electronic devices for neural stimulation hold great potential in restoring the functionality of degenerated organs, specifically, retinal prostheses, which are aimed at vision restoration. The fabrication process of 3D polymer-metal devices with high resolution and a high aspect-ratio (AR) is very complex and faces many challenges that impair its functionality. Here we describe the optimization of the fabrication process of a bio-functionalized 3D high-resolution 1mm circular subretinal implant composed of SU-8 polymer integrated with dense gold microelectrodes (23μm pitch) passivated with 3D micro-well-like structures (20μm diameter, 3μm resolution). The main challenges were overcome by step-by-step planning and optimization while utilizing a two-step bi-layer lift-off process; bio-functionalization was carried out by N2 plasma treatment and the addition of a bio-adhesion molecule. In-vitro and in-vivo investigations, including SEM and FIB cross section examinations, revealed a good structural design, as well as a good long-term integration of the device in the rat sub-retinal space and cell migration into the wells. Moreover, the feasibility of subretinal neural stimulation using the fabricated device was demonstrated in-vitro by electrical activation of rat’s retina. The reported process and optimization steps described here in detail can aid in designing and fabricating retinal prosthetic devices or similar neural implants.

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.

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.

Maintaining protein homeostasis is critical for cellular function, as disruptions can result in accumulation of misfolded proteins associated with various diseases. RNA editing, particularly deamination by base-editing enzymes like ADAR, can modify the transcriptome, potentially influencing amino acid sequences and protein diversity. We hypothesize that irregular RNA editing, leading to a more complex proteome, may generate defective proteins, triggering cellular toxicity. Using an editing-naïve yeast system expressing a robust ADAR enzyme, we demonstrated that extensive RNA editing results in non-synonymous protein changes, correlated with increased protein ubiquitination and reliance on quality control pathways. This suggests that extensive editing in yeast produces abnormal proteins prone to misfolding and degradation. While mouse and human genomes are well-adapted to the ADAR enzymes, introduction of base editors into human cells is found to increase activity in proteotoxic-stress-related pathways due to off-target editing. Signs of proteotoxic stress are also observed in human samples exhibiting elevated activity of endogenous ADARs. These findings emphasize the detrimental impact of dysregulated RNA editing on protein balance and suggest a potential role for aberrant editing in disease onset and progression.

This paper revisits the geometric foundations of electromagnetic theory, by studying Faraday's concept of field lines. We introduce "covariant electromagnetic field lines," a novel construct that extends traditional field line concepts to a covariant framework. Our work includes the derivation of a closed-form formula for the field line curvature in proximity to a moving electric charge, showcasing the curvature is always non-singular, including nearby a point charge. Our geometric framework leads to a geometric derivation of the Lorentz force equation and its first-order corrections, circumventing the challenges of self-force singularities and providing insights into the problem of radiation-reaction. This study not only provides a fresh geometric perspective on electromagnetic field lines but also opens avenues for future research in fields like quantum electrodynamics, gravitational field theory, and beyond.

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 …

We report tunable random lasing in 2D and 1D solid-state polymer-based dye-doped random lasers. In 2D configuration, we show that the laser emission can be red-shifted by either decreasing scatterer density or increasing pump area. In 1D system, we demonstrate temperature-controlled spectral tunability of a partially-pumped single-wavelength random laser.

Owing to high energy density and economic viability, rechargeable Mg-ion batteries (MIB) are considered as alternative to lithium-ion batteries. However, beside chevrel phase, none of conventional inorganic cathode materials demonstrate reversible intercalation/deintercalation of Mg+2 ions in anhydrous electrolyte system. The lack of high voltage and high-capacity cathode frustrates the realization of MIB. Previous studies indicated that vanadium pentoxide (V2O5) has potential to reversibly insert\extract Mg ions. However, many attempts to utilize V2O5 demonstrated limited electrochemical response, due to hindered Mg ion mobility in solid. Herein, we demonstrated a tailored approach to synthesize uniformly dispersed spherical V2O5 homogeneously coated with 2D VS2 through a facile in-situ chemical method and study the electrochemical activity in 0.2 M Mg(TFSI)2 + MgCl2 in DME electrolyte system and …

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.

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 …