BINA

Carbocations play key roles in classical organic reactions and have also been implicated in several enzyme families. A hallmark of carbocation chemistry is multitudes of competing reaction pathways, and to be able to distinguish between pathways with quantum chemical calculations, it is necessary to approach chemical accuracy for relative energies between carbocations. Here, we present an extensive study of the performance of selected density functional theory (DFT) methods in describing the thermochemistry and kinetics of carbocations and their corresponding neutral alkenes both in the gas-phase and within a hybrid quantum mechanics-molecular mechanics (QM/MM) framework. The density functionals are benchmarked against accurate ab initio methods such as CBS-QB3 and DLPNO-CCSD(T). Based on the findings in the gas-phase calculations of carbocations and alkenes, the best functionals are …

This article has been corrected: The bioinformatics analysis of TCGA data in Figure 4 (panels A, B, C, I) was inadvertently conducted on LINC00116. We have reworked that analysis using the LINC01116 expression values so that it is aligned with the rest of the paper, which discusses LINC01116. The redrawn Figures 4A-C and 4I and edits to the associated paragraph in the text are shown below. Please note that similar trends are shown for LINC00116 and LINC01116 so the primary message of the paper is not affected. The authors declare that these corrections do not change the results or conclusions of this paper.Original article: Oncotarget. 2017; 8: 31785–31801. https://doi. org/10.18632/oncotarget. 15991

The development of precious group metal-free (PGM-free) catalysts for the oxygen reduction reaction is considered as the main thrust for the cost reduction of fuel cell technologies and their mass production. Within the PGM-free category, molecular catalysts offer an advantage over other heat-treated PGM-free catalysts owing to their well-defined structure, which enables further design of more active, selective, and durable catalysts. Even though non-heat-treated molecular catalysts with exceptional performance have been reported in the past, they were rarely tested in a fuel cell. Herein, we report on a molecular catalyst under alkaline conditions: fluorinated iron phthalocyanine (FeFPc) supported on cheap and commercially available high-surface area carbon─BP2000 (FeFPc@BP2000). It exhibits the highest activity ever reported for molecular catalysts under alkaline conditions in half-cells and fuel cells.

Carbon dots (CDs) and their doped counterparts including nitrogen-doped CDs (N@CDs) have been synthesized by bottom-up or top-down approaches from different precursors. The attractiveness of such emerging 2D‑carbon-based nanosized materials is attributed to their excellent biocompatibility, preparation, aqueous dispersibility, and functionality. The antimicrobial, optical, and electrochemical properties of CDs have been advocated for two important biotechnological applications: bacterial eradication and sensing/biosensing. CDs as well as N@CDs act as antimicrobial agents as their surfaces encompass functional hydroxyl, carboxyl, and amino groups that generate free radicals. As a new class of photoluminescent nanomaterials, CDs can be employed in diversified analytics. CDs with surface carboxyl or amino groups form nanocomposites with nanomaterials or be conjugated with biorecognition …

Electron paramagnetic resonance (EPR) spectroscopy has emerged as an ideal biophysical tool to study complex biological processes. EPR spectroscopy can follow minor conformational changes in various proteins as a function of ligand or protein binding or interactions with high resolution and sensitivity. Resolving cellular mechanisms, involving small ligand binding or metal ion transfer, is not trivial and cannot be studied using conventional biophysical tools. In recent years, our group has been using EPR spectroscopy to study the mechanism underlying copper ion transfer in eukaryotic and prokaryotic systems. This mini-review focuses on our achievements following copper metal coordination in the diamagnetic oxidation state, Cu(I), between biomolecules. We discuss the conformational changes induced in proteins upon Cu(I) binding, as well as the conformational changes induced in two proteins involved in Cu(I) transfer. We also consider how EPR spectroscopy, together with other biophysical and computational tools, can identify the Cu(I)-binding sites. This work describes the advantages of EPR spectroscopy for studying biological processes that involve small ligand binding and transfer between intracellular proteins.

Rapid and sensitive detection of human pathogens, such as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is an urgent and challenging task for clinical laboratories. Currently, the gold standard for SARS-CoV-2–specific RNA is based on quantitative RT-PCR (RT-qPCR), which relies on target amplification by Taq polymerase and uses a fluorescent resonance energy transfer–based hydrolysis probe. Although this method is accurate and specific, it is also time consuming. Here, a new molecular assay is described that combines a highly sensitive magnetic modulation biosensing (MMB) system, rapid thermal cycling, and a modified double-quenched hydrolysis probe. In vitro transcribed SARS-CoV-2 RNA targets spiked in PCR-grade water, were used to show that the calculated limit of detection of the MMB-based molecular assay was 1.6 copies per reaction. Testing 309 RNA extracts from …

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a transforming gammaherpesvirus. Like other herpesviruses, KSHV infection is for life long and there is no treatment that can cure patients from the virus. In addition, there is an urgent need to target viral genes to study their role during the infection cycle. The CRISPR-Cas9 technology offers a means to target viral genomes and thus may offer a novel strategy for viral cure as well as for better understanding of the infection process. We evaluated the suitability of this platform for the targeting of KSHV. We have used the recombinat KSHV BAC16 genome, which contains an expression cassette encoding hygromycin-resistance and a GFP marker gene. Three genes were targeted: gfp, which serves as a marker for infection; orf45 encoding a lytic viral protein; and orf73, encoding LANA which is crucial for latent infection. The fraction of cells expressing GFP, viral DNA levels and LANA expression were monitored and viral genomes were sequenced. We found that KSHV episomes can be targeted by CRISPR-Cas9. Interestingly, the quantity of KSHV DNA declined, even when target sites were not functionally important for latency. In addition, we show that antibiotic selection, used to maintain infection, interferes with the outcome of targeting. Our study provides insights into the use of this fundamental approach for the study and manipulation of KSHV. It provides guidelines for the targeting CRISPR-Cas9 to the viral genome and for outcomes interpretation.

To mitigate the associated challenges of instability and capacity improvement in Na3V2(PO4)2F3 (NVPF), rationally designed uniformly distributed hollow spherical NVPF and coating the surface of NVPF with ultrathin (≈2 nm) amorphous TiO2 by atomic layer deposition is demonstrated. The coating facilitates higher mobility of the ion through the cathode electrolyte interphase (CEI) and enables higher capacity during cycling. The TiO2@NVPF exhibit discharge capacity of >120 mAhg−1, even at 1C rates, and show lower irreversible capacity in the first cycle. Further, nearly 100% capacity retention after rate performance in high current densities and 99.9% coulombic efficiency after prolonged cycling in high current density is reported. The improved performance in TiO2@NVPF is ascribed to the passivation behavior of TiO2 coating which protects the surface of NVPF from volume expansion, significantly less …

Carbocations play key roles in classical organic reactions and have also been implicated in several enzyme families. A hallmark of carbocation chemistry is multitudes of competing reaction pathways, and to be able to distinguish between pathways with quantum chemical calculations, it is necessary to approach chemical accuracy for relative energies between carbocations. Here, we present an extensive study of the performance of selected density functional theory (DFT) methods in describing the thermochemistry and kinetics of carbocations and their corresponding neutral alkenes both in the gas-phase and within a hybrid quantum mechanics-molecular mechanics (QM/MM) framework. The density functionals are benchmarked against accurate ab initio methods such as CBS-QB3 and DLPNO-CCSD(T). Based on the findings in the gas-phase calculations of carbocations and alkenes, the best functionals are …

Catheter-associated urinary tract infections (CAUTIs), caused by biofilms, are the most frequent health-care associated infections. Novel antibiofilm coatings are needed to increase the urinary catheters' life-span, decrease the prevalence of CAUTIs and reduce the development of antimicrobial resistance. Herein, antibacterial zinc oxide nanoparticles (ZnO NPs) were decorated with a biofilm matrix-degrading enzyme amylase (AM) and simultaneously deposited onto silicone urinary catheters in a one-step sonochemical process. The obtained nano-enabled coatings inhibited the biofilm formation of Escherichia coli and Staphylococcus aureus by 80% and 60%, respectively, for up to 7 days in vitro in a model of catheterized bladder with recirculation of artificial urine due to the complementary mode of antibacterial and antibiofilm action provided by the NPs and the enzyme. Over this period, the coatings did not induce …

In their seminal paper, Caves and Schumaker presented a new formalism for quantum optics, intended to serve as a building block for describing two-photon processes, in terms of new, generalized qudratures. The important, revolutionary concept in their formalism was that it was fundamentally two-mode, i.e. the related observables could not be attributed to any single one of the comprising modes, but rather to a generalized complex quadrature that could only be attributed to both of them. Here, we propose a subtle, but fundamentally meaningful modification to their important work. Unlike the above proposal, we deliberately choose a frequency-agnostic definition of the two-mode quadrature, that we motivate on physical grounds. This simple modification has far-reaching implications to the formalism – the real and imaginary parts of the quadratures now coincide with the famous EPR variables, and our two-mode …

Base editors are dedicated engineered deaminases that enable directed conversion of specific bases in the genome or transcriptome in a precise and efficient manner, and hold promise for correcting pathogenic mutations. A major concern limiting application of this powerful approach is the issue of off-target edits. Several recent studies have shown substantial off-target RNA activity induced by base editors and demonstrated that off-target mutations may be suppressed by improved deaminases versions or optimized guide RNAs. Here, we describe a new class of off-target events that are invisible to the established methods for detection of genomic variations and were thus far overlooked. We show that nonspecific, seemingly stochastic, off-target events affect a large number of sites throughout the genome or the transcriptome, and account for the majority of off-target activity. We develop and employ a different …

We present a fluorescence fluctuation image correlation analysis method that can rapidly and simultaneously measure the diffusion coefficient, photoblinking rates, and fraction of diffusing particles of fluorescent molecules in cells. Unlike other image correlation techniques, we demonstrated that our method could be applied irrespective of a nonuniformly distributed, immobile blinking fluorophore population. This allows us to measure blinking and transport dynamics in complex cell morphologies, a benefit for a range of super-resolution fluorescence imaging approaches that rely on probe emission blinking. Furthermore, we showed that our technique could be applied without directly accounting for photobleaching. We successfully employed our technique on several simulations with realistic EMCCD noise and photobleaching models, as well as on Dronpa-C12-labeled β-actin in living NIH/3T3 and HeLa cells. We …

The development of precious group metal-free (PGM-free) catalysts for the oxygen reduction reaction is considered as the main thrust for the cost reduction of fuel cell technologies and their mass production. Within the PGM-free category, molecular catalysts offer an advantage over other heat-treated PGM-free catalysts owing to their well-defined structure, which enables further design of more active, selective, and durable catalysts. Even though non-heat-treated molecular catalysts with exceptional performance have been reported in the past, they were rarely tested in a fuel cell. Herein, we report on a molecular catalyst under alkaline conditions: fluorinated iron phthalocyanine (FeFPc) supported on cheap and commercially available high-surface area carbon─BP2000 (FeFPc@BP2000). It exhibits the highest activity ever reported for molecular catalysts under alkaline conditions in half-cells and fuel cells.

The oxygen reduction reaction (ORR) is a key process in anion exchange membrane fuel cells. The alkaline conditions should allow silver‐based cost‐efficient catalysts to replace platinum group metal materials. However, Ag electrochemical stability or lack of stability in alkaline medium is still to be demonstrated. Herein, Ag catalyst nanoparticles (NPs) are characterized by identical location transmission electron microscopy and X‐ray photoelectron spectroscopy after electrochemical cycling, revealing the losses of activity and surface. Herein, a facile method for enhancing the chemical stability of Ag catalysts in an alkaline environment by depositing a protective polydopamine (PDA) coating is reported. It is enhanced via crosslinking with polyethyleneimine (PEI), on the surface of Ag NPs. The enhanced electrochemical stability of Ag PDA–PEI nanocatalyst via the analysis of ORR polarization curves during …

In the parasite Trypanosoma brucei, the causative agent of human African sleeping sickness, all mRNAs are trans-spliced to generate a common 5′ exon derived from the spliced leader (SL) RNA. Perturbations of protein translocation across the endoplasmic reticulum (ER) induce the spliced leader RNA silencing (SLS) pathway. SLS activation is mediated by a serine-threonine kinase, PK3, which translocates from the cytosolic face of the ER to the nucleus, where it phosphorylates the TATA-binding protein TRF4, leading to the shutoff of SL RNA transcription, followed by induction of programmed cell death. Here, we demonstrate that SLS is also induced by depletion of the essential ER-resident chaperones BiP and calreticulin, ER oxidoreductin 1 (ERO1), and the Golgi complex-localized quiescin sulfhydryl oxidase (QSOX). Most strikingly, silencing of Rhomboid-like 1 (TIMRHOM1), involved in mitochondrial …

This work is part of ongoing and systematic investigations by our groups on the synthesis, electrochemical behavior, structural investigations, and computational modeling of the Ni-rich materials Li[NixCoyMnz]O2 (x+y+z=1; x≥0.8) for advanced lithium-ion batteries. This study focuses on the LiNi0.85Co0.10Mn0.05O2 (NCM85) material and its improvement upon doping with B3+ cations. The data demonstrate the substantial improvement of the doped electrodes in terms of cycling performance, lower voltage hysteresis and reduced self-discharge upon high temperature storage. The electronic structure of the undoped and B-doped material was modelled using density functional theory (DFT), which identified interstitial positions as the preferential location of the dopant. DFT models were also used to shed light on the influence of boron on surface segregation, surface stability, and oxygen binding energy in NCM85 …

In this introduction we provide an overview of the papers that were accepted for publication in the special issue on light detection and ranging (lidar). Four of the papers were published in JOSA A, and four were published in JOSA B. They represent different aspects of this important and fast-growing field while showing the relevant state-of-the-art achievements currently existing in the field of lidars in the world of science and engineering.