Pathogenesis of numerous diseases is associated with the formation of amyloid fibrils. Extrinsic fluorescent dyes, including Thioflavin T (ThT), are used to follow the fibrillation kinetics. It has ...recently been reported that the so-called deep-blue autofluorescence (dbAF) is changing during the aggregation process. However, the origin of dbAF and the reasons for its change remain debatable. Here, the kinetics of fibril formation in model proteins were comprehensively analyzed using fluorescence lifetime and intensity of ThT, intrinsic fluorescence of proteinaceous fluorophores, and dbAF. For all systems, intensity enhancement of the dbAF band with similar spectral parameters (∼350 nm excitation; ∼450 nm emission) was observed. Although the time course of ThT lifetime (indicative of protofibrils formation) coincided with that of tyrosine residues in insulin, and the kinetic changes in the ThT fluorescence intensity (reflecting formation of mature fibrils) coincided with changes in ThT absorption spectrum, the dbAF band started to increase from the beginning of the incubation process without a lag-phase. Our mass-spectrometry data and model experiments suggested that dbAF could be at least partially related to oxidation of amino acids. This study scrutinizes the dbAF features in the context of the existing hypotheses about the origin of this spectral band.
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•Deep-blue autofluorescence (dbAF) changes during protein aggregation.•dbAF is indicative of the earliest stages of protein fibrillation.•dbAF starts to increase prior to changes in the ThT lifetime and intensity.•dbAF lifetime can be used as an indicator of protofibrils formation.•dbAF could be partially related to oxidation of amino acids.
Recently, a scheme based on the method of weak measurements to register the trajectories of photons passing through a nested Mach–Zehnder interferometer was proposed L. Vaidman, Phys. Rev. A
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, ...052104 (2013) and then realized A. Danan, D. Farfurnik, S. Bar-Ad, et al., Phys. Rev. Lett.
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, 240402 (2013). Interpreting the results of the experiment, the authors concluded that “the photons do not always follow continuous trajectories.” It is shown in this work that these results can be easily and clearly explained in terms of traditional classical electrodynamics or quantum mechanics implying the continuity of all possible paths of photons. Consequently, a new concept of disconnected trajectories proposed by the authors of work Phys. Rev. Lett.
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, 240402 (2013) is unnecessary.
Pain therapy has remained conceptually stagnant since the opioid crisis, which highlighted the dangers of treating pain with opioids. An alternative addiction-free strategy to conventional ...painkiller-based treatment is targeting receptors at the origin of the pain pathway, such as transient receptor potential (TRP) ion channels. Thus, a founding member of the vanilloid subfamily of TRP channels, TRPV1, represents one of the most sought-after pain therapy targets. The need for selective TRPV1 inhibitors extends beyond pain treatment, to other diseases associated with this channel, including psychiatric disorders. Here we report the cryo-electron microscopy structures of human TRPV1 in the apo state and in complex with the TRPV1-specific nanomolar-affinity analgesic antagonist SB-366791. SB-366791 binds to the vanilloid site and acts as an allosteric hTRPV1 inhibitor. SB-366791 binding site is supported by mutagenesis combined with electrophysiological recordings and can be further explored to design new drugs targeting TRPV1 in disease conditions.
Primary focal segmental glomerulosclerosis (FSGS), along with minimal change disease (MCD), are diseases with primary podocyte damage that are clinically manifested by the nephrotic syndrome. The ...pathogenesis of these podocytopathies is still unknown, and therefore, the search for biomarkers of these diseases is ongoing. Our aim was to determine of the proteomic profile of urine from patients with FSGS and MCD. Patients with a confirmed diagnosis of FSGS (n = 30) and MCD (n = 9) were recruited for the study. For a comprehensive assessment of the severity of FSGS a special index was introduced, which was calculated as follows: the first score was assigned depending on the level of eGFR, the second score—depending on the proteinuria level, the third score—resistance to steroid therapy. Patients with the sum of these scores of less than 3 were included in group 1, with 3 or more—in group 2. The urinary proteome was analyzed using liquid chromatography/mass spectrometry. The proteome profiles of patients with severe progressive FSGS from group 2, mild FSGS from group 1 and MCD were compared. Results of the label free analysis were validated using targeted LC-MS based on multiple reaction monitoring (MRM) with stable isotope labelled peptide standards (SIS) available for 47 of the 76 proteins identified as differentiating between at least one pair of groups. Quantitative MRM SIS validation measurements for these 47 proteins revealed 22 proteins with significant differences between at least one of the two group pairs and 14 proteins were validated for both comparisons. In addition, all of the 22 proteins validated by MRM SIS analysis showed the same direction of change as at the discovery stage with label-free LC-MS analysis, i.e., up or down regulation in MCD and FSGS1 against FSGS2. Patients from the FSGS group 2 showed a significantly different profile from both FSGS group 1 and MCD. Among the 47 significantly differentiating proteins, the most significant were apolipoprotein A-IV, hemopexin, vitronectin, gelsolin, components of the complement system (C4b, factors B and I), retinol- and vitamin D-binding proteins. Patients with mild form of FSGS and MCD showed lower levels of Cystatin C, gelsolin and complement factor I.
Flax (Linum usitatissimum L.) is grown for fiber and seed in many countries. Flax cultivars differ in the oil composition and, depending on the ratio of fatty acids, are used in pharmaceutical, food, ...or paint industries. It is known that genes of SAD (stearoyl-ACP desaturase) and FAD (fatty acid desaturase) families play a key role in the synthesis of fatty acids, and some alleles of these genes are associated with a certain composition of flax oil. However, data on genetic polymorphism of these genes are still insufficient.
On the basis of the collection of the Institute for Flax (Torzhok, Russia), we formed a representative set of 84 cultivars and lines reflecting the diversity of fatty acid composition of flax oil. An approach for the determination of full-length sequences of SAD1, SAD2, FAD2A, FAD2B, FAD3A, and FAD3B genes using the Illumina platform was developed and deep sequencing of the 6 genes in 84 flax samples was performed on MiSeq. The obtained high coverage (about 400x on average) enabled accurate assessment of polymorphisms in SAD1, SAD2, FAD2A, FAD2B, FAD3A, and FAD3B genes and evaluation of cultivar/line heterogeneity. The highest level of genetic diversity was observed for FAD3A and FAD3B genes - 91 and 62 polymorphisms respectively. Correlation analysis revealed associations between particular variants in SAD and FAD genes and predominantly those fatty acids whose conversion they catalyze: SAD - stearic and oleic acids, FAD2 - oleic and linoleic acids, FAD3 - linoleic and linolenic acids. All except one low-linolenic flax cultivars/lines contained both the substitution of tryptophan to stop codon in the FAD3A gene and histidine to tyrosine substitution in the FAD3B gene, while samples with only one of these polymorphisms had medium content of linolenic acid and cultivars/lines without them were high-linolenic.
Genetic polymorphism of SAD and FAD genes was evaluated in the collection of flax cultivars and lines with diverse oil composition, and associations between particular polymorphisms and the ratio of fatty acids were revealed. The achieved results are the basis for the development of marker-assisted selection and DNA-based certification of flax cultivars.
•Good quality solid Ar films have been condensed on Au surface.•Measured X-ray photoelectron and reflected-electron-energy loss spectra at 5 K, 20 K.•Electronic bandgap is ∼14 eV for the ...face-centered cubic and hexagonal Ar lattices.•The excitonic peak appears in energy loss spectra at ∼ 12 eV for both Ar lattices.•Solid Ar is convenient for implanting 229Th to study exotic 8.2 eV nuclear transition.
We have studied condensed solid argon films on a gold surface, measuring its reflected electron energy-loss spectra (REELS) and X-ray photoelectron spectra (XPS) at the temperatures 5 K and 20 K. We have also reproduced theoretically the REELS considering both face-centered cubic (FCC) and hexagonal close-packed (HCP) lattices of solid argon using density-functional theory (DFT), GW approximation, random-phase approximation (RPA) and the Bethe–Salpeter equation (BSE). In the calculations the local-field dielectric screening, quasiparticles, and excitonic effects have been taken into account. The excitonic peaks in the REELS appear at ∼12 eV whereas the calculated electronic bandgap amounts to 14.3–14.4 eV for both the FCC and HCP lattices. Our results show that a solid argon film is a wide-gap dielectric best suited for implanting Th and studying its low-lying nuclear transition in 229Th with the energy of 8.2 eV.
Time-reversal breaking and parity-conserving millistrong interactions, suggested in 1965, still remain a viable mechanism of CP-violation beyond the Standard Model. One of its possible manifestations ...is the T-odd asymmetry in the transmission of tensor-polarized deuterons through a vector-polarized hydrogen gas target. Upon the rotation of the deuteron polarization from the vertical direction into the ring plane, the T-odd asymmetries, odd against the reversal of the proton polarization in the target, will continuously oscillate with first or second harmonics of the spin precession frequency. The Fourier analysis of the oscillating T-odd asymmetries allows for an easy separation from background persistent in conventional experiments employing static vector and tensor polarizations.
In the study, the characteristics of the phase transition from a face-centered cubic crystal to a homogeneous phase in helium were calculated based on the correlation cell–cluster extension. A ...comparison of theoretical data with experimental data was conducted, and good agreement was obtained. The use of data on phase transitions in helium for estimating the thermodynamic characteristics of the phase transition in a quantum system of hard spheres is discussed.
Introduction
Oral health behavior is based on an acquired experience and cultural traditions. University education may smooth out cultural differences in oral health practice.
Objectives
Our goal is ...to study self-reported oral health attitudes and behavior of university students and the cultural basis for it.
Methods
We used the English version of the Hiroshima University Dental Behavioral Inventory to carry out an online survey of 136 university students of Morocco and Russia.
Results
Over half of the students (60.3%) do not feel anxious when visiting a dentist. Most of them take care of their gums (41.2%), teeth color (49.3%) and the degree of their cleanness (38.2%). The overwhelming majority of the students brush their each tooth very thoroughly (62.5%), they regularly examine their teeth in the mirror after brushing them (90.4%). They are well aware that tooth brushing alone cannot prevent a gum disease (63.2%), and they feel concerned about the possibility of having bad breath (73.6%). At the same time, over half of the students (61.7%) put off their visit to a dentist until they have a toothache, which is a negative behavioral factor. We did not reveal any gender or cultural differences between the students of the two countries, which can be regarded as a universalization factor of oral health behavior in young people who get higher education in universities.
Conclusions
The majority of the surveyed Russian and Moroccan university students have similar patterns of oral health attitudes and behavior. This assumption needs verification on a larger sample of students.
Disclosure
No significant relationships.
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