Search

Background Atherosclerosis is driven by synergistic interactions between pathological biomechanical and lipid metabolic factors. Long noncoding RNAs (LncRNAs) have been implicated in atherogenesis. The purpose of this study was to investigate the potential mechanism of lncRNA AI662270 on macrophage cholesterol transport in atherosclerosis. Methods Apolipoprotein E deficiency (ApoE−/−) mice were fed a high fat diet for 16 weeks to construct atherosclerotic model, and the mice were injected with recombinant lentivirus carrying AI662270 gene to overexpress AI662270. Macrophages were cleared by liposomal clondronate in vivo. Fundamental experiments and functional assays, hematoxylin and eosin staining, oil red O staining and others, were performed to evaluate the function of AI662270 on atherogenesis. Peritoneal macrophages were treated with oxidized low density lipoprotein (ox-LDL) to simulate in vitro model. Mechanism assays, RNA-interacting protein immunoprecipitation, RNA–protein pulldown and others, were performed to study the regulatory mechanism of AI662270 in macrophages. Results The novel AI662270 was mainly enriched in macrophages, but not in endothelial cells, smooth muscle cells and fibroblasts of mouse atherosclerotic lesions and was upregulated by ox-LDL. Overexpression of AI662270 resulted in lipid accumulation, larger atherosclerotic plaques and cardiac dysfunction in vivo. After macrophages were removed, the pro-atherogenic effect of AI662270 disappeared. Downregulation of AI662270 in macrophages protected against foam cell formation by potentiating cholesterol efflux and reducing intracellular total cholesterol. The opposite effect was observed in macrophage-specific AI662270-overexpressed cells in vitro. AI662270 bound to adenosine triphosphate-binding cassette transporter A1 (Abca1) responsible for regulating cholesterol efflux in macrophages. Forced expression of AI662270 in macrophages decreased Abca1 expression. The reverse occurred when expression of AI662270 was repressed. Conclusion These findings reveal an essential role for AI662270 in atherosclerosis progression by regulating cholesterol efflux from macrophages.

Despite of multiple systematic studies of schizophrenia based on proteomics, metabolomics, and genome-wide significant loci, reconstruction of underlying mechanism is still a challenging task. Combination of the advanced data for quantitative proteomics, metabolomics, and genome-wide association study (GWAS) can enhance the current fundamental knowledge about molecular pathogenesis of schizophrenia. In this study, we utilized quantitative proteomic and metabolomic assay, and high throughput genotyping for the GWAS study. We identified 20 differently expressed proteins that were validated on an independent cohort of patients with schizophrenia, including ALS, A1AG1, PEDF, VTDB, CERU, APOB, APOH, FASN, GPX3, etc. and almost half of them are new for schizophrenia. The metabolomic survey revealed 18 group-specific compounds, most of which were the part of transformation of tyrosine and steroids with the prevalence to androgens (androsterone sulfate, thyroliberin, thyroxine, dihydrotestosterone, androstenedione, cholesterol sulfate, metanephrine, dopaquinone, etc.). The GWAS assay mostly failed to reveal significantly associated loci therefore 52 loci with the smoothened p −5 were fractionally integrated into proteome-metabolome data. We integrated three omics layers and powered them by the quantitative analysis to propose a map of molecular events associated with schizophrenia psychopathology. The resulting interplay between different molecular layers emphasizes a strict implication of lipids transport, oxidative stress, imbalance in steroidogenesis and associated impartments of thyroid hormones as key interconnected nodes essential for understanding of how the regulation of distinct metabolic axis is achieved and what happens in the conditioned proteome and metabolome to produce a schizophrenia-specific pattern.

A formal probabilistic theory of the interconversions of atoms in the presence of three (NS = 3) spatial dimensions of their electronic structures, proposed in our earlier works, is extended to the general case NS ≥ 3, i.e., to include exotic variants with NS > 3, which are possible, for example, in field theory. As in these earlier works, the results of the present paper are actually also applicable to the case of an arbitrary system of identical objects that can be found in NS ≥ 3 states interconnected by probabilistic relations. Prospects for further development of the proposed theory are indicated.

This paper is a generalization of two of our preceding papers which considered, among other things, a version of the solution with a minimum and a maximum number of atoms in the spatial configurations 1+2+3. Some results of these works, pertaining to probabilistic transitions of atoms from one configuration to another, follow from the results of the given paper as a special case.

The paper studies the optical turbulence structure at the Large Solar Vacuum Telescope of the Baikal Astrophysical Observatory. Some results on the study of the wavefront distortions are given to expand the data archive. The possibilities of detecting layers with enhanced optical turbulence intensity in the atmosphere are discussed. The altitudes of the atmospheric turbulent layers within the boundary layer are estimated.

Cryo-FIB/SEM combined with cryo-ET has emerged from within the field of cryo-EM as the method for obtaining the highest resolution structural information of complex biological samples in-situ in native and non-native environments. However, challenges remain in conventional cryo-FIB/SEM workflows, including milling thick specimens that do not vitrify well, specimens with preferred orientation, low-throughput when milling small and/or low concentration specimens, and cellular specimens that distribute poorly across grid squares. Here we present a general approach we call the ‘Waffle Method’ which leverages high-pressure freezing to address these challenges. We illustrate the mitigation of these challenges by applying the Waffle Method and cryo-ET to reveal the macrostructure of the polar tube in microsporidian spores in multiple complementary orientations, which was previously not possible due to preferred orientation of the spores on the grid. We demonstrate the broadness of the Waffle Method by applying it to three additional cellular samples and a single particle sample using a variety of cryo-FIB-milling hardware, with both manual and automated approaches. We also present a unique and critical stress-relief gap designed specifically for waffled lamellae. Additionally, we describe applications of the Waffle Method which are currently being explored. We propose the Waffle Method as a way to achieve many of the advantages of cryo-liftout on the specimen grid while avoiding the long, challenging, and technically-demanding process required for cryo-liftout.

Crohn’s disease (CD) is associated with increased postoperative morbidity. Sarcopenia correlates with increased morbidity and mortality in various medical conditions. We assessed correlations of the lean body mass marker and psoas muscle area (PMA), with postoperative outcomes in CD patients undergoing gastrointestinal surgery. We included patients with CD who underwent gastrointestinal surgery between June 2009 and October 2018 and had CT/MRI scans within 8 weeks preoperatively. PMA was measured bilaterally on perioperative imaging. Of 121 patients, the mean age was 35.98 ± 15.07 years; 51.2% were male. The mean BMI was 21.56 ± 4 kg/m2. The mean PMA was 95.12 ± 263.2cm2. Patients with postoperative complications (N = 31, 26%) had significantly lower PMA compared with patients with a normal postoperative recovery (8.5 ± 2.26 cm2 vs. 9.85 ± 2.68 cm2, P = 0.02). A similar finding was noted comparing patients with anastomotic leaks to those without anastomotic leaks (7.48 ± 0.1 cm2 vs. 9.6 ± 2.51 cm2, P = 0.04). PMA correlated with the maximum degree of complications per patient, according to the Clavien-Dindo classification (Spearman’s coefficient = −0.26, P = 0.004). Patients with major postoperative complications (Clavien-Dindo ≥ 3) had lower mean PMA (8.12 ± 2.75 cm2 vs. 9.71 ± 2.57 cm2, P = 0.03). Associations were similar when stratifying by gender and operation urgency. On multivariate analysis, PMA (HR = 0.72/cm2, P = 0.02), operation urgency (HR = 3.84, P < 0.01), and higher white blood cell count (HR = 1.14, P = 0.02) were independent predictive factors for postoperative complications. PMA is an easily measured radiographic parameter associated with postoperative complications in patients with CD undergoing bowel resection.

Separation of pre-recorded messages (Interactive Voice Response, IVR) from live speech fragments in real-time plays a significant role in speech emotion recognition (SER) systems, unwanted calls filtering, automatic detection of answering machine responses, reduction of stored record sizes, voice mail spam filtration, etc. The problem complexity is that, unlike with silent, music, and noise fragments studied by the conventional voice activity recognition (VAD), IVR usually contains speech. Three classifiers for live speech fragments detection in phone call records are considered: based on the support vector machine (SVM), gradient boosting (XGBoost) and convolutional neural network (CNN). The Geneva Minimalistic Acoustic Parameter Set for XGBoost and SVM, and log-spectrograms and gammatonegrams for CNN were used for feature representation of audio fragments. Experiments with a dataset of phone calls demonstrate comparable quality (around 0.96 according to the F1-averaged measure) of the considered algorithms with CNN having a advantage (0.98).

Based on the experimentally established existence of atoms with spatially one- and two-dimensional electronic structures that can be paired with conventional three-dimensional atoms, a formal theoretical substantiation is proposed in favor of the possibility of simultaneous presence of all three types of atoms with spatial dimension DI = D1, D2, D3 . Despite the fundamental difference in the computational procedure, the results of the present study seem to be quite adequate being a significant addition to the results of previous V. V. Skobelev’s works. The conclusions of the work can be verified in experiments, though the principal feasibility of such experiments is not obvious. This last problem needs further substantiation and is not discussed in this work.

Polarization studies of the ZrB2–SiC–AlN compact ceramic material and thermal spray coatings of the same composition were conducted in a 3% NaCl solid solution to analyze their cathodic and anodic behavior. The compact ceramic material was produced by hot pressing, the plasma-sprayed coating 240 μm thick was deposited onto a C/C–SiC graphite substrate, and the detonation-sprayed coating 340 μm thick was applied to 12Kh18N9T stainless steel. The microstructure and phase composition of the compact sample and thermal spray coatings were examined. The microstructure was heterophase in all cases. The compact sample and plasma-sprayed coating contained SiC, AlN, and ZrB2 as the main phases, and the detonation-sprayed coating additionally had a small amount of nickel and zirconium oxide. Electron microprobe analysis showed that the plasma-sprayed coating had 20 wt.% oxygen; i.e., the coating contained oxide phases in the amount not revealed by X-rays. The compact ceramic sample showed exceptionally high resistance to electrochemical oxidation: electrochemical potential, Ecorr, at which corrosion current occurs is very high and constitutes +1.51 eV. For the detonation- and plasma-sprayed coatings, Ecorr = –0.25 and –0.05 eV, respectively. The great resistance of the compact ceramic material to electrochemical oxidation correlates with its resistance to high-temperature oxidation above 1700°C. This is due to the formation of an Al2O3–SiO2 mullite film on the surface. The lower resistance of the coatings to electrochemical oxidation compared to the compact material is associated with their increased porosity.

The objective of the present study was to evaluate hair essential and trace element levels and metabolic risk markers in overweight and obese subjects in relation to body mercury burden. According to 2 × 2 factorial design a total of 440 adults were distributed to four groups: (i) low-Hg normal-weight subjects (n = 114); (ii) high-Hg normal weight subjects (n = 113); (iii) low-Hg overweight (BMI > 25) subjects (n = 110); (iv) high-Hg overweight (BMI > 25) subjects (n = 110). Hg-exposed groups consisted of subjects characterized by frequent seafood consumption (> 4 times/week) subsequently evaluated by hair analysis (> 0.58 μg/g). Dietary-exposed subjects were characterized by a more than 3-fold higher hair Hg content irrespectively of body weight values. Both low-Hg and high-Hg overweight subjects were characterized by significantly higher ALT activity, as well as elevated serum glucose, LDL, and triglyceride levels as compared to the respective groups of normal weight subjects. High Hg body burden had a more significant effect on metabolic parameters in overweight and obese adults. Particularly, high-Hg overweight subjects were characterized by significantly higher serum creatinine and uric acid levels, as well as increased GGT and CK activity as compared to low-Hg overweight counterparts. In addition, hair Mg, Mn, and Sr content in high-Hg overweight subjects was significantly lower than that in low-Hg normal weight and overweight examinees. In turn, high Hg levels in overweight subjects were associated with significantly higher hair Se and Zn levels when compared to unexposed overweight adults. Generally, the obtained data demonstrate that increased hair Hg levels in overweight and obese subjects is associated with adverse metabolic profile. It is proposed that observed metabolic alterations may be at least partially mediated by Hg-associated disturbances in essential trace element and mineral metabolism.

DNA polymerase ζ (Polζ) belongs to the same B-family as high-fidelity replicative polymerases, yet is specialized for the extension reaction in translesion DNA synthesis (TLS). Despite its importance in TLS, the structure of Polζ is unknown. We present cryo-EM structures of the Saccharomyces cerevisiae Polζ holoenzyme in the act of DNA synthesis (3.1 A) and without DNA (4.1 A). Polζ displays a pentameric ring-like architecture, with catalytic Rev3, accessory Pol31‚ Pol32 and two Rev7 subunits forming an uninterrupted daisy chain of protein–protein interactions. We also uncover the features that impose high fidelity during the nucleotide-incorporation step and those that accommodate mismatches and lesions during the extension reaction. Collectively, we decrypt the molecular underpinnings of Polζ’s role in TLS and provide a framework for new cancer therapeutics. Cryo-EM structures of free and DNA-bound pol ζ holoenzyme from budding yeast reveal how this DNA polymerase ensures fidelity and facilitates lesion bypass during translesion DNA synthesis.

An approach to increasing the diagnostic accuracy of the ECG stress test for transient myocardial ischemia is considered. It is proposed to modify the decision rule by including an additional procedure for assessing the temporal dynamics of the equivalent cardiac generator in the ST-T segment. The results of evaluating the sensitivity and specificity of diagnosis in a group of subjects are presented.

A comparative analysis of the results of experimental investigations on determination of the conditions necessary and sufficient for the localization of ground, crown, and combined forest fires with the use of a barrier strip of moistened forest materials has been performed. The rational volumes of water used for the formation of such a strip in front of a forest fire and its sizes were determined. Different variants of localization of flame combustion and thermal decomposition of forest combustible materials depending on the action of an air flow (wind) on them were analyzed.

Extra-intestinal manifestations (EIM) are common in inflammatory bowel diseases (IBD) and may affect up to 40% of the patients during the course of the disease. Peripheral arthralgia (PA) is by far the most common EIM. To date, TNFα inhibitors are the most established treatment for EIMs in IBD. Infliximab (IFX) trough levels (TL) and anti-IFX antibodies (ATI) are correlated with multiple outcomes in IBD such as clinical response and remission, mucosal healing, fistular healing, and more. So far, a correlation between PA and IFX TL\ATI has not been evaluated. This retrospective study included IBD patients followed by the gastroenterology department of Sheba Medical Center. Patients with active PA at onset of IFX treatment were included. IFX TL and ATI were evaluated at week 6, 14, and 26 and correlated with PA persistence. Forty patients (37 Crohn’s and 3 ulcerative colitis) with IBD-related PA were included. The overall prevalence of PA was 55% (22/40), 42.5% (17/40), and 55% (22/40) after 6, 14, and 26 weeks, respectively. IFX trough drug levels were not associated with reported PA at week 6 [median, 11.8 μg/ml (IQR 6.6–15.5) vs 10.05 μg/ml (IQR 7.35–12.87), p = 0.56], week 14 [median, 4.7 μg/ml (IQR 2.3–7) vs 3.1 μg/ml (IQR 1.35–7.35), p = 0.55], and week 26 [median, 3 μg/ml (IQR 1.15–5.17) vs 3.4 μg/ml (IQR 0.13–6.75), p = 0.94]. Detectable ATI were significantly more prevalent in patients with PA than in patients without PA at week 26 [11/22 (50%) vs 3/18 (16.7%), p = 0.028]. In patients with IBD-related PA, ATI are associated with an increased risk of persistence of PA. No direct correlation was demonstrated between IFX TL and persistence of PA.

Results of experiments on determination of the temperature, velocity, and mechanical trajectory of fragments of forest combustible materials subjected to pyrolysis, flying away under the action of high-velocity air flow, are presented. The effect of flying of such fragments over a fire barrage was mainly investigated. The experiments were performed with conifer needles and leaves, representing typical combustible materials in ground forest fires. On the basis of the experimentally determined effect of inclination of a flame over a fire barrage formed of moistened forest materials, physical and mathematical models of flying of fragments of forest combustible materials subjected to pyrolysis upstream of such a fire barrage have been developed. With the use of these models, the characteristic length of the zone of flame combustion of a forest material, the height of the flame in this zone, and the geometric dimensions of the fire barrage necessary and sufficient for reliable localization of the flame combustion and thermal decomposition of forest combustible material were determined.

With more than 14,000 patients awaiting liver transplantation in the USA and a mortality rate of 20–25% on the wait list, a diligent pre-operative evaluation is crucial to ensure optimal risk assessment. Cardiac disease remains the leading cause of early mortality after liver transplantation. In this review, we discuss common cardiac comorbidities, frequently used testing modalities, and updated literature on cardiac evaluation in liver transplant candidates. Optimal cardiac evaluation, especially in the asymptomatic patient, remains controversial as shown by conflicting results in the literature. Non-invasive testing is associated with low sensitivity in this patient population; therefore, coronary angiography remains the standard for detecting CAD. There is general agreement that all liver transplant candidates have to undergo cardiac evaluation; however, universally accepted guidelines are currently not available. Often the choice of the cardiac evaluation modality has to be made on a case-by-case basis by a multidisciplinary transplant team based on the perceived risk of invasive studies when compared to perioperative cardiac events.

Results of experimental investigations on the suppression of the flame combustion and thermal decomposition of forest combustible materials by aerosol flows of a pure water and aqueous solutions are presented. The characteristics of some sprayers were determined and the densities of wetting of a fire hotbed, provided by them, were calculated. The times of extinguishing hotbeds of model crown and ground forest fi res were measured, and distributions of temperatures and heat flows in them were determined. It is shown that the efficiency of extinguishing a forest fire is mainly determined by the sizes of the aerosol droplets acting on it.

The paper demonstrates the prospects of spark plasma sintering (SPS) for the high-speed diffusion bonding of the high-strength ultrafine-grained (UFG) near-α Ti–5Al–2V alloy. The effect of increased diffusion bonding intensity in the UFG Ti alloys is discussed also. The bonding areas of the UFG near-α Ti–5Al–2V alloy obtained by SPS are featured by high density, strength, and corrosion resistance. The rate of bonding in the UFG alloys has been shown to depend on the heating rate non-monotonously (with a pronounced maximum). At the stage of continuous heating and isothermic holding, the bonding kinetics was found to be determined by the exponential creep rate, the intensity of which in the coarse-grained alloys is limited by the diffusion rate in the crystal lattice α-Ti. In the UFG alloy, the exponential creep processes associated with gliding and climb of dislocations, the activation energy of which corresponds to the diffusion activation energy in the lattice dislocation nuclei, may take place simultaneously with the grain boundary sliding and Coble creep, the activation energy of which corresponds to the grain boundary diffusion activation energy.

Printed documents protection problem against leakage is still one of the relevant. Existing security tools allow us to protect electronic text documents, however are ineffective in protecting their printed versions. This research presents the marking approach for text electronic documents invariant to the print-and-scan transformation. During marker embedding source text line spacing values are changing to the specified values within perceptual invisibility. The watermark extraction is carried out from the images containing text and based on normal Radon transform and Gaussian mixture model. This marking approach is robust to various image transformations and distortions. The accuracy of embedded information extraction was more than 0.98 for 200 DPI images and line spacing value change about 490 micrometers.