A new class of carbon 1D structures with symmetry of rod groups P61 and P31 – laterally-extended expanded nanohelicenes (NHs) with zigzag edge morphology – has been thoroughly investigated in the DFT ...framework. It is shown that these compounds can be divided into two groups, with each group having its distinct properties. The spiral ribbons of NHs of the first and second groups have odd and even numbers of carbon hexagons across, respectively. The first group members are semiconductors and their electronic band gap strongly depends on the uniaxial strain. Expanding the “shaft” (the inner hollow region in a NH spiral) results in a smooth decrease of the electronic band gap. If the outer edge of a NH includes fewer than seven hexagons, then the NH is diamagnetic. When the edge includes seven or more hexagons, antiferromagnetic ordering appears. The second group consists of NHs which are diamagnetic metals at equilibrium geometry that, however, undergo a phase transition to antiferromagnetic semiconductors under small (about 10%) elastic stretching. The difference between the electronic and magnetic properties of NHs in the first and second groups stems from the difference in their electronic structure and can be explained using group theory.
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A novel class of fluorescent dyes based on conformationally locked GFP chromophore is reported. These dyes are characterized by red‐shifted spectra, high fluorescence quantum yields and ...pH‐independence in physiological pH range. The intra‐ and intermolecular mechanisms of radiationless deactivation of ABDI‐BF2 fluorophore by selective structural locking of various conformational degrees of freedom were studied. A unique combination of solvatochromic and lipophilic properties together with “infinite” photostability (due to a dynamic exchange between free and bound dye) makes some of the novel dyes promising bioinspired tools for labeling cellular membranes, lipid drops and other organelles.
The green mile: The creation of ABDI‐BF2, a novel class of fluorescent dyes based on a conformationally locked GFP chromophore, is reported (see scheme). These dyes are characterized by red‐shifted spectra, high fluorescence quantum yields and pH‐independence in physiological pH range. A unique combination of solvatochromic and lipophilic properties together with “infinite” photostability makes some of the novel dyes promising bioinspired tools for cellular labeling.
The aim of the study was to assess inflammatory markers and clinical outcomes in adult patients admitted to hospital with mild-to-moderate COVID-19 and treated with a combination of standard-of-care ...(SOC) and targeted immunosuppressive therapy including anti-IL-17A (netakimab), anti-IL-6R (tocilizumab), or JAK1/JAK2 inhibitor (baricitinib) or with a standard-of-care therapy alone. The observational cohort study included 154 adults hospitalized between February and August, 2020 with RT-PCR-confirmed SARS-CoV-2 with National Early Warning Score2 (NEWS2) < 7 and C-reactive protein (CRP) levels less than or equal to 140 mg/L on the day of the start of the therapy or observation. Patients were divided into the following groups: I) 4 mg baricitinib, 1 or 2 times a day for an average of 5 days (n = 38); II) 120 mg netakimab, one dose (n = 48); III) 400 mg tocilizumab, one dose (n = 34), IV) SOC only: hydroxychloroquine, antiviral, antibacterial, anticoagulant, and dexamethasone (n = 34). CRP levels significantly decreased after 72 h in the tocilizumab (p = 1 x 10.sup.-5) and netakimab (p = 8 x 10.sup.-4) groups and remained low after 120 h. The effect was stronger with tocilizumab compared to other groups (p = 0.028). A significant decrease in lactate dehydrogenase (LDH) levels was observed 72 h after netakimab therapy (p = 0.029). NEWS2 scores significantly improved 72 h after tocilizumab (p = 6.8 x 10.sup.-5) and netakimab (p = 0.01) therapy, and 120 h after the start of tocilizumab (p = 8.6 x 10.sup.-5 ), netakimab (p = 0.001), or baricitinib (p = 4.6 x 10.sup.-4) therapy, but not in the SOC group. Blood neutrophil counts (p = 6.4 x 10.sup.-4) and neutrophil-to-lymphocyte ratios (p = 0.006) significantly increased 72 h after netakimab therapy and remained high after 120 h. The percentage of patients discharged 5-7 days after the start of therapy was higher in the tocilizumab (44.1%) and netakimab (41.7%) groups than in the baricitinib (31.6%) and SOC (23.5%) groups. Compared to SOC (3 of the 34; 8.8%), mortality was lower in netakimab (0 of the 48; 0%, RR = 0.1 (95% CI: 0.0054 to 1.91)), tocilizumab (0 of the 34; 0%, RR = 0.14 (95% CI: 0.0077 to 2.67)), and baricitinib (1 of the 38; 2.6%, RR = 0.3 (95% CI: 0.033 to 2.73)) groups. In hospitalized patients with mild-to-moderate COVID-19, the combination of SOC with anti-IL-17A or anti-IL-6R therapy were superior or comparable to the combination with JAK1/JAK2 inhibitor, and all three were superior to SOC alone. Whereas previous studies did not demonstrate significant benefit of anti-IL-17A therapy for severe COVID-19, our data suggest that such therapy could be a rational choice for mild-to-moderate disease, considering the generally high safety profile of IL-17A blockers. The significant increase in blood neutrophil count in the netakimab group may reflect efflux of neutrophils from inflamed tissues. We therefore hypothesize that neutrophil count and neutrophil-to-lymphocyte ratio could serve as markers of therapeutic efficiency for IL-17A-blocking antibodies in the context of active inflammation.
A number of photoactivatable GFP-like fluorescent proteins (PAFPs) have been reported whose fluorescence can be switched on or whose fluorescent state can be modified by relatively intense ...irradiation at a specific wavelength. The use of these proteins gives unique opportunities to photolabel and track fusion proteins in a living cell. Here, we provide a protocol for the primary visualization, photoactivation and tracking of two monomeric PAFPs recently developed in our lab. Both these proteins, PS-CFP2 and Dendra2, are fluorescent and can be visualized before photoactivation. Upon photoactivation, their excitation and emission spectra undergo a dramatic red shift. The brightness of their initial and photoconverted states, along with the high dynamic ranges of both proteins, make them an attractive tool for protein photolabeling. Excluding genetic constructs cloning, cell culturing and transfection, the whole protocol may take anywhere from 10 min to several hours, depending on motility of the protein being studied.
Deep profiling of antibody and T cell-receptor repertoires by means of high-throughput sequencing has become an attractive approach for adaptive immunity studies, but its power is substantially ...compromised by the accumulation of PCR and sequencing errors. Here we report MIGEC (molecular identifier groups-based error correction), a strategy for high-throughput sequencing data analysis. MIGEC allows for nearly absolute error correction while fully preserving the natural diversity of complex immune repertoires.
The properties of multi-walled MoS2 nanotubes have been investigated by the first principles calculations and by molecular mechanics (MM) simulations using a revised three-body force field. The ...density functional theory (DFT) calculations have been performed on single-, double- and triple-walled MoS2 nanotubes. The new version of the force field is able to reproduce the structure integrity of the MoS2 nanotubes at temperatures up to 700 K through the molecular dynamics simulations. Comparison of the results of first principles and MM simulations of the multi-walled nanotubes demonstrates satisfactory agreement. The results of DFT and MM simulations indicate that the difference between chirality indices of adjacent shells of a multi-walled nanotube is the main factor that determines a possibility of the nanotube to be synthesized. The structure of zigzag 12-walled nanotubes with chirality indices difference 12 and 13, simulated by MM method and using the proposed force field, is the most close to the structure of experimentally detected nanotubes.
•Quantum & molecular mechanics simulations of 1-3-walled NTs provide close results.•3-body force field enables to model a 12-walled NT with outer diameter of 230 Å•Simulations predict the MoS2 armchair multi-walled NTs have a facetted structure.•All modelled MoS2 zigzag multi-walled NTs have a cylindrical optimized structure.
Green fluorescent protein (GFP) and GFP-like proteins represent invaluable genetically encoded fluorescent probes. In the last few years a new class of photoactivatable fluorescent proteins (PAFPs) ...capable of pronounced light-induced spectral changes have been developed. Except for tetrameric KFP1 (ref. 4), all known PAFPs, including PA-GFP, Kaede, EosFP, PS-CFP, Dronpa, PA-mRFP1 and KikGR require light in the UV-violet spectral region for activation through one-photon excitation-such light can be phototoxic to some biological systems. Here, we report a monomeric PAFP, Dendra, derived from octocoral Dendronephthya sp. and capable of 1,000- to 4,500-fold photoconversion from green to red fluorescent states in response to either visible blue or UV-violet light. Dendra represents the first PAFP, which is simultaneously monomeric, efficiently matures at 37 °C, demonstrates high photostability of the activated state, and can be photoactivated by a common, marginally phototoxic, 488-nm laser line. We demonstrate the suitability of Dendra for protein labeling and tracking to quantitatively study dynamics of fibrillarin and vimentin in mammalian cells.
We present protein-PAINT - the implementation of the general principles of PAINT (Point Accumulation for Imaging in Nanoscale Topography) for live-cell protein labeling. Our method employs the ...specific binding of cell-permeable fluorogenic dyes to genetically encoded protein tags. We engineered three mutants of the bacterial lipocalin Blc that possess different affinities to a fluorogenic dye and exhibit a strong increase in fluorescence intensity upon binding. This allows for rapid labeling and washout of intracellular targets on a time scale from seconds to a few minutes. We demonstrate an order of magnitude higher photostability of the fluorescence signal in comparison with spectrally similar fluorescent proteins. Protein-PAINT ensures prolonged super-resolution fluorescence microscopy of living cells in both single molecule detection and stimulated emission depletion regimes.
The topological analysis of the electron density is first performed for a bulk InTe crystal using the density functional theory calculations. Several types of two‐center chemical interactions have ...been identified. Crystal orbital Hamilton population method is used to estimate the corresponding bond strength. As expected, the InTe chemical bonds in the –InTe2– ring chains turn out to be the strongest and have a noticeable covalent contribution. The InIn metallic bonds in linear –In– chains are much weaker. The results obtained reveal that the additional InTe bonds between the –In– and –InTe2– chains can be attributed to weak dative interactions. However, due to their multiplicity, these bonds can play an important role in the stability of the tetragonal InTe phase. The van der Waals interactions of neighboring –InTe2– chains also stabilize the crystal structure. Both Hirshfeld and Bader populations show that the effective charge of indium in the –InTe2– ring chain is noticeably greater than that in the –In– linear chain.
The results obtained reveal five types of bond critical points of electron density. Two types of InTe bonds and one type of InIn bonds ensure the stability of the tetragonal InTe phase. Two types of TeTe bonds refer to interactions associated with van der Waals forces. Nonequivalent In atoms have different Bader and Hirshfeld effective charges.
For deep imaging of animal tissues, the optical window favorable for light penetration is in near-infrared wavelengths, which requires proteins with emission spectra in the far-red wavelengths. Here ...we report a far-red fluorescent protein, named Katushka, which is seven- to tenfold brighter compared to the spectrally close HcRed or mPlum, and is characterized by fast maturation as well as a high pH-stability and photostability. These unique characteristics make Katushka the protein of choice for visualization in living tissues. We demonstrate superiority of Katushka for whole-body imaging by direct comparison with other red and far-red fluorescent proteins. We also describe a monomeric version of Katushka, named mKate, which is characterized by high brightness and photostability, and should be an excellent fluorescent label for protein tagging in the far-red part of the spectrum.
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