BINA

Copper is a trace element vital to many cellular functions. Yet its abnormal levels are toxic to cells, provoking a variety of severe diseases. The high affinity Copper Transporter 1 (CTR1), being the main in-cell copper (Cu(I)) entry route, tightly regulates its cellular uptake via a still elusive mechanism. Here, all-atoms simulations unlock the molecular terms of Cu(I) transport in eukaryotes disclosing that the two Methionine triads, forming the selectivity filter, play an unprecedented dual role both enabling selective Cu(I) transport and regulating its uptake-rate thanks to an intimate coupling between the conformational plasticity of their bulky side chains and the number of bound Cu(I) ions. Namely, the Met residues act as a gate reducing the Cu(I) import-rate when two ions simultaneously bind to CTR1. This may represent an elegant autoregulatory mechanism through which CTR1 protects the cells from excessively high, and hence toxic, in-cell Cu(I) levels. Overall, these outcomes resolve fundamental questions in CTR1 biology and open new windows of opportunity to tackle diseases associated with an imbalanced copper uptake.

The functionality of a nanoscale silicon-based optoelectronic modulator is deeply analyzed while it appears that two competing processes, thermal and photonic, are occurring at the same time, and are preventing the optimization of the electro-optics coupling. While an incident illumination-beam first process is translated into photons, generating pairs of electrons–holes, a second process of thermal generation, creating phonons enables a loss of energy. Complementary studies, combining strong analytical models and numerical simulations, enabled to better understand this competition between photonic and thermal activities, in order to optimize the modulator. Moreover, in order to prevent unnecessary heating effects and to present a proposed solution, a picosecond pulsed laser is suggested and demonstrated as the ultimate solution so no energy will be wasted in heat, and still the photonic energy will be fully …

This review discusses, in brief, the various synthetic methods of two widely-used nanofillers; phyllosilicate and graphene. Both are 2D fillers introduced into hydrogel matrices to achieve mechanical robustness and water uptake behavior. Both the fillers are inserted by physical and chemical gelation methods where most of the chemical gelation, i.e., covalent approaches, results in better physical properties compared to their physical gels. Physical gels occur due to supramolecular assembly, van der Waals interactions, electrostatic interactions, hydrophobic associations, and H-bonding. For chemical gelation, in situ radical triggered gelation mostly occurs.

Near-infrared (NIR) fluorescence lifetime imaging (FLI) provides a unique contrast mechanism to monitor biological parameters and molecular events in vivo. Single-photon avalanche photodiode (SPAD) cameras have been recently demonstrated in FLI microscopy (FLIM) applications, but their suitability for in vivo macroscopic FLI (MFLI) in deep tissues remains to be demonstrated. Herein, we report in vivo NIR MFLI measurement with SwissSPAD2, a large time-gated SPAD camera. We first benchmark its performance in well-controlled in vitro experiments, ranging from monitoring environmental effects on fluorescence lifetime, to quantifying Förster Resonant Energy Transfer (FRET) between dyes. Next, we use it for in vivo studies of target-drug engagement in live and intact tumor xenografts using FRET. Information obtained with SwissSPAD2 was successfully compared to that obtained with a gated-ICCD camera, using two different approaches. Our results demonstrate that SPAD cameras offer a powerful technology for in vivo preclinical applications in the NIR window.

The sluggish kinetics of the anodic oxygen evolution reaction (OER) limit the overall efficiency of green hydrogen production. The proposed strategy to overcome this is to replace OER with other kinetically favorable anodic reactions like urea oxidation reaction (UOR). Herein, we develop an organometallic synthesis of nickel nitride nanoparticles supported on carbon (Ni3N–C) as the catalyst for both UOR and hydrogen evolution reaction (HER). A precious group metal-free electrolyzer based on Ni3N–C catalyst (as both anode and cathode) is implemented for the first time, and the urea electrolyzer cell has a 200 mV lower overpotential compared to that of the water electrolyzer.

Transition-metal dichalcogenides (TMDCs) are unique layered materials with exotic properties. So, examining their structures holds tremendous importance. 2H-MoSe2 (analogous to MoS2; Gr. 6 TMDC) is a crucial optoelectronic material studied extensively using Raman spectroscopy. In this regard, low-frequency Raman (LFR) spectroscopy can probe this material’s structure as it reveals distinct vibration modes. Here, we focus on understanding the microstructural evolution of different 2H-MoSe2 morphologies and their layers using LFR scattering. We grew phase-pure 2H-MoSe2 (with variable microstructures) directly on a Mo foil using a two-furnace ambient-pressure chemical vapor deposition (CVD) system by carefully controlling the process parameters. We analyzed the layers of exfoliated flakes after ultrasonication and drop-cast 2H-MoSe2 of different layer thicknesses by choosing different concentrations of …

T and B cell repertoires constitute the foundation of adaptive immunity. Adaptive immune receptor repertoire sequencing (AIRR-seq) is a common approach to study immune system dynamics. Understanding the genetic factors influencing the composition and dynamics of these repertoires is of major scientific and clinical importance. The chromosomal loci encoding for the variable regions of T and B cell receptors (TCRs and BCRs, respectively) are challenging to decipher due to repetitive elements and undocumented structural variants. To confront this challenge, AIRR-seq-based methods have been developed recently for B cells, enabling genotype and haplotype inference and discovery of undocumented alleles. Applying these methods to AIRR-seq data reveals a plethora of undocumented genomic variations. However, this approach relies on complete coverage of the receptors9 variable regions, and most T cell studies sequence only a small fraction of the variable region. Here, we adapted BCR inference methods to full and partial TCR sequences, and identified 38 undocumented polymorphisms in TRBV, 15 of them were also observed in genomic data assemblies. Further, we identified 31 undocumented 59 UTR sequences. A subset of these inferences was also observed using independent genomic approaches. We found the two documented TRBD2 alleles to be equally abundant in the population, and show that the single nucleotide that differentiates them is strongly associated with dramatic changes in the expressed repertoire. Our findings expand the knowledge of genomic variation in the TRB (T Cell Receptor Beta) locus and …

We report on stabilization of Li–S cells with different types of composite sulfur cathodes using ethereal LiTFSI/LiNO 3/DOL/DME electrolyte solutions containing a-priori 0.1 M Li 2 S 8. These electrolyte solutions enable an improved cycling behavior for Li–S cells compared to Li 2 S 8-free electrolyte solutions, thanks to the presence of LiS x species from the beginning of operation. We show that Li anodes cycled in Li∣ S cells with solutions containing Li 2 S 8 possess flatter and more uniform surface, higher dimensions of the surface structures in average and, as a result, a lower surface area. This surface morphology ensures a low rate of parasitic surface reactions of the electrolyte components on the Li anodes' surface, slower depletion of the electrolyte solution in the cells and stabilization of the cells cycling. Besides, the presence of Li 2 S 8 maintains a better integrity of composite sulfur/carbon/PVdF cathodes …

The loss of energy homeostasis seen during aging, is causally linked to multiple age-related pathologies. The AMP-activated protein kinase (AMPK) directly senses cellular energy levels, which are reflected in the ratio between AMP:ATP. However, the genetic regulation of vertebrate aging by the AMPK pathway remains poorly understood. Here, we manipulate ATP production by mutating APRT, a key enzyme in AMP biosynthesis, and extend vertebrate lifespan in a male-specific manner. Using a multi-omics approach, we demonstrate that the APRT mutation restores metabolic plasticity, and identify a distinct transcriptional signature linking mitochondria with the sex-related differences in longevity. Accordingly, APRT mutant cells display a reduction in mitochondrial functions and ATP levels, and an increase in AMPK activity, resembling a persistent state of energy starvation. In-vivo, a fasting-like response was observed exclusively in male mutants, including resistance to a high-fat diet. Finally, intermittent fasting eliminated the longevity benefits mediated by the APRT mutation in males. Together, these data identify AMP biosynthesis as a sex-specific mediator of vertebrate longevity and metabolic health.

Transition-metal dichalcogenides (TMDCs) are unique layered materials with exotic properties. So, examining their structures holds tremendous importance. 2H-MoSe2 (analogous to MoS2; Gr. 6 TMDC) is a crucial optoelectronic material studied extensively using Raman spectroscopy. In this regard, low-frequency Raman (LFR) spectroscopy can probe this material’s structure as it reveals distinct vibration modes. Here, we focus on understanding the microstructural evolution of different 2H-MoSe2 morphologies and their layers using LFR scattering. We grew phase-pure 2H-MoSe2 (with variable microstructures) directly on a Mo foil using a two-furnace ambient-pressure chemical vapor deposition (CVD) system by carefully controlling the process parameters. We analyzed the layers of exfoliated flakes after ultrasonication and drop-cast 2H-MoSe2 of different layer thicknesses by choosing different concentrations of …

The global energy demand is expected to rise continuously in the foreseeable future, and this demand cannot be fulfilled with fossil fuels if the ambitious goals for global reduction in greenhouse gas emissions are to be met. 1, 2 Therefore, it is necessary to switch to energy production from sustainable energy sources such as solar and wind. 3, 4 These sources suffer from intermittent production, producing a surplus of energy at certain hours and seasons and little to none at others. Hence, large energy storage solutions are necessary in order to store the excess energy in peak times and compensate at the lowand down-times. 4, 5One of the most promising energy storage solutions today is chemical, in the form of hydrogen, which can be used with fuel cells to generate electricity or burned to generate heat, as well as being used in the chemical industry for various applications. 5 It can be easily produced with various …

Quantum tunneling (QT) is not an effect often considered in chemistry, and rightfully so. However, in many cases it is significant, and in some cases it is even considerable. In this chapter we will describe the basic tenets of QT with a focus on catalysis, followed by some of the most important tools to study and compute them. The chapter goes on to address the title of the chapter by discussing several clear cases of QT for hydrogen-based reactions in organometallic, enzymatic, astrochemical, and organic systems. The insights highlighted in the chapter showcase the importance of QT in specific catalyzed reactions and help uncover the instances that are worth of attention.

Similarly to other transition metal sulfides, nickel sulfide nanocrystals can be potentially used for functional device applications. However, controlling morphology and stoichiometry to target specific applications is a synthesis challenge. In this work we developed a rapid, one-step, chemical vapor deposition synthesis of nickel sulfide dendritic nanostructures with fractal geometry. Microtome-EDS compositional analysis of the mature crystal indicates a trend of decreasing sulfur and increasing nickel concentration towards the tip of the mature crystals. Following thorough investigation of these nanocrystals at different stages of their nucleation and growth by means of XRD, HR-SEM, HR-TEM, and Raman spectroscopy, we suggest possible kinetic mechanisms for the crystal formation and development. This work contributes to the understanding of growth mechanisms of dendritic structures with complex morphology.

Pharmaceutical nanoparticles (NPs) carrying molecular payloads are used for medical purposes such as diagnosis and medical treatment. Currently, the research process of discovering a new applicative candidate for efficient clinical treatment is a time- and resource- consuming process due to the uncertainty of how NP behaves which requires a large number of experiments to study the properties of NPs-based drugs for clinical usage. In silico experiments are known to be powerful tools for studying biological and clinical systems and evaluating a drug9s efficiency, which can significantly reduce the number of in vivo experiments required. To this extent, in this study, we present a novel spatio-temporal pharmacokinetics-pharmacodynamics (PKPD) model of NPs based drugs. The proposed model takes into consideration the blood flow in the cardiovascular system as well as PKPD dynamics taking place during the drug9s flow and in the target sites. We show that the proposed model has a better fidelity compared to previous models on five in vivo experiments with 13 different NPs, done on mice.

RNA guided nucleases are regarded as the future genome editing technologies. As such, they need to meet strong safety margins. Two major challenges in incorporating CRISPR technologies into the clinical world are off-target activity and editing efficiency. The common way to tackle such issues is to measure the binding and cleavage kinetics of the CRISPR enzyme. This can be challenging since, for example, DNA is not released from the CAS9 protein post cleavage. Here a promising new microfluidic approach to characterizing Enzymatic Interaction and Function of CRISPR complexes on a microfluidic platform (EnzyMIF) is presented. The method can rapidly detect the kd, koff, km and kcat for various RNA guided nucleases. In this work, two single guide RNAs with significantly different in-cell cleavage efficiency, RAG2 and RAG1, are used as proof-of-concept. The EnzyMIF assay results provide biochemical …

Identifying and investigating protein–DNA interactions, which play significant roles in many biological processes, is essential for basic and clinical research. Current techniques for identification of protein–DNA interactions are laborious, time-consuming, and suffer from nonspecific binding and limited sensitivity. To overcome these challenges and assess protein–DNA interactions, we use a magnetic modulation biosensing (MMB) system. In MMB, one of the interacting elements (protein or DNA) is immobilized to magnetic beads, and the other is coupled to a fluorescent molecule. Thus, the link between the magnetic bead and the fluorescent molecule is established only when binding occurs, enabling detection of the protein–DNA interaction. Using magnetic forces, the beads are concentrated and manipulated in a periodic motion in and out of a laser beam, producing a detectable oscillating signal. Using MMB, we …

Chemical element mapping is an imaging tool that provides essential information about composite materials, and it is crucial for a broad range of fields ranging from fundamental science to numerous applications. Methods that exploit x-ray fluorescence are very advantageous and are widely used, but require focusing of the input beam and raster scanning of the sample. Thus, the methods are slow and exhibit limited resolution due to focusing challenges. Here, we demonstrate an x-ray fluorescence method based on computational ghost imaging that overcomes those limitations since it does not require focusing and show that when it is combined with compressed sensing the total measurement time can be significantly reduced. Our method opens the possibility to significantly enhance the resolution of chemical element maps and to extend the applicability of x-ray fluorescence inspection to new fields where the …