Cardiovascular disease (CVD) represents one of the main causes of mortality worldwide and nearly a half of it is related to ischemic heart disease (IHD). The article represents a comprehensive study ...on the diagnostics of IHD through the targeted metabolomic profiling and machine learning techniques. A total of 112 subjects were enrolled in the study, consisting of 76 IHD patients and 36 non-CVD subjects. Metabolomic profiling was conducted, involving the quantitative analysis of 87 endogenous metabolites in plasma. A novel regression method of age-adjustment correction of metabolomics data was developed. We identified 36 significantly changed metabolites which included increased cystathionine and dimethylglycine and the decreased ADMA and arginine. Tryptophan catabolism pathways showed significant alterations with increased levels of serotonin, intermediates of the kynurenine pathway and decreased intermediates of indole pathway. Amino acid profiles indicated elevated branched-chain amino acids and increased amino acid ratios. Short-chain acylcarnitines were reduced, while long-chain acylcarnitines were elevated. Based on these metabolites data, machine learning algorithms: logistic regression, support vector machine, decision trees, random forest, and gradient boosting, were used for IHD diagnostic models. Random forest demonstrated the highest accuracy with an AUC of 0.98. The metabolites Norepinephrine; Xanthurenic acid; Anthranilic acid; Serotonin; C6-DC; C14-OH; C16; C16-OH; GSG; Phenylalanine and Methionine were found to be significant and may serve as a novel preliminary panel for IHD diagnostics. Further studies are needed to confirm these findings.
A high-coverage Neandertal genome from Chagyrskaya Cave Mafessoni, Fabrizio; Grote, Steffi; de Filippo, Cesare ...
Proceedings of the National Academy of Sciences - PNAS,
06/2020, Letnik:
117, Številka:
26
Journal Article
Recenzirano
Odprti dostop
We sequenced the genome of a Neandertal from Chagyrskaya Cave in the Altai Mountains, Russia, to 27-fold genomic coverage. We show that this Neandertal was a female and that she was more related to ...Neandertals in western Eurasia Prüfer et al., Science 358, 655–658 (2017); Hajdinjak et al., Nature 555, 652–656 (2018) than to Neandertals who lived earlier in Denisova Cave Prüfer et al., Nature 505, 43–49 (2014), which is located about 100 km away. About 12.9% of the Chagyrskaya genome is spanned by homozygous regions that are between 2.5 and 10 centiMorgans (cM) long. This is consistent with the fact that Siberian Neandertals lived in relatively isolated populations of less than 60 individuals. In contrast, a Neandertal from Europe, a Denisovan from the Altai Mountains, and ancient modern humans seem to have lived in populations of larger sizes. The availability of three Neandertal genomes of high quality allows a view of genetic features that were unique to Neandertals and that are likely to have been at high frequency among them. We find that genes highly expressed in the striatum in the basal ganglia of the brain carry more aminoacid- changing substitutions than genes expressed elsewhere in the brain, suggesting that the striatum may have evolved unique functions in Neandertals.
Cardiovascular pathologies maintain the leading position in mortality worldwide. Atherosclerosis is a chronic disease that can result in a variety of serious complications, such as myocardial ...infarction, stroke, and cardiovascular disease. Inflammation and lipid metabolism alterations play a crucial role in atherogenesis, but the details of relationships and causality of these fundamental processes remain not clear. The oxidation of LDL was considered the main atherogenic modification of LDL within the vascular wall for decades. However, recent investigations provided a growing body of evidence in support of the multiple LDL modification theory. It suggests that LDL particles undergo numerous modifications that change their size, density, and chemical properties within the blood flow and vascular wall. Oxidation is the last stage in this cascade resulting in the atherogenic properties. Moreover, recent investigations have discovered that oxLDL may have both anti-inflammatory and pro-inflammatory properties. Oxidized LDL can trigger inflammation through the activation of macrophages and other cells. After all, oxidized LDL is still a promising object for further investigations that have the potential to clarify the unknown parts of the atherogenic process. In this review, we discuss the role of oxLDL in atherosclerosis development on different levels.
This review presents the state-of-the-art of optical sensors for determination of biogenic amines (BAs) in food by publications covering about the last 10 years. Interest in the development of rapid ...and preferably on-site methods for quantification of BAs is based on their important role in implementation and regulation of various physiological processes. At the same time, BAs can develop in different kinds of food by fermentation processes or microbial activity or arise due to contamination, which induces toxicological risks and food poisoning and causes serious health issues. Therefore, various optical chemosensor systems have been devised that are easy to assemble and fast responding and low-cost analytical tools. If amenable to on-site analysis, they are an attractive alternative to existing instrumental analytical methods used for BA determination in food. Hence, also portable sensor systems or dipstick sensors are described based on various probes that typically enable signal readouts such as photometry, reflectometry, luminescence, surface-enhanced Raman spectroscopy, or ellipsometry. The quantification of BAs in real food samples and the design of the sensors are highlighted and the analytical figures of merit are compared. Future instrumental trends for BA sensing point to the use of cell phone–based fully automated optical evaluation and devices that could even comprise microfluidic micro total analysis systems.
•A universal representation of the specific surface energy was found.•A fracture criterion containing a LP is proposed.•The existence of a threshold value of the LP was established.
The authors of ...the article considered a fracture model with a linear parameter (LP) associated with the thickness of the physical cut and the interaction layer (IL) on its continuation. With a zero value of the LP, the fracture model takes a form of a mathematical cut. The initial state of the body corresponds to the initial free binding energy, which is assumed to be negative. By the means of thermomechanical analysis of the fracturing processes, the authors established universal representation of the surface energy, which is valid for both physical and mathematical cuts. In the case of a physical cut, the surface energy is expressed as a product of multiplication of the LP value by the change in the specific free binding energy of the IL. It is called the energy product (EP). Using the proposed formulation, the authors considered the effect of decreasing LP on the critical state of samples of finite dimensions.
We performed a genome-wide association study of non-Hispanic, white individuals with fibrotic idiopathic interstitial pneumonias (IIPs; n = 1,616) and controls (n = 4,683), with follow-up replication ...analyses in 876 cases and 1,890 controls. We confirmed association with TERT at 5p15, MUC5B at 11p15 and the 3q26 region near TERC, and we identified seven newly associated loci (Pmeta = 2.4 × 10(-8) to 1.1 × 10(-19)), including FAM13A (4q22), DSP (6p24), OBFC1 (10q24), ATP11A (13q34), DPP9 (19p13) and chromosomal regions 7q22 and 15q14-15. Our results suggest that genes involved in host defense, cell-cell adhesion and DNA repair contribute to risk of fibrotic IIPs.
Thermophysical properties of phytosterols Korshunov, A. O.; Markin, A. V.; Kushnir, S. R. ...
Journal of thermal analysis and calorimetry,
12/2022, Letnik:
147, Številka:
24
Journal Article
Recenzirano
In the present research, the thermophysical properties of phytosterols were investigated by thermogravimetry (TG) and differential scanning calorimetry (DSC) in the range of 300–800 K. As a result, ...the areas of their thermal stability were established. The thermodynamic characteristics of melting and crystallization have been determined. For one of the samples, the specific heat was studied in the range 260–570 K. Comparison of the present results with the data available in the literature was carried out. The dependence of thermophysical properties on the composition and nature of phytosterols has been concluded.
The motor cortex controls motor behaviors by generating movement-specific signals and transmitting them through spinal cord circuits and motoneurons to the muscles. Precise and well-coordinated ...muscle activation patterns are necessary for accurate movement execution. Therefore, the activity of cortical neurons should correlate with movement parameters. To investigate the specifics of such correlations among activities of the motor cortex, spinal cord network and muscles, we developed a model for neural control of goal-directed reaching movements that simulates the entire pathway from the motor cortex through spinal cord circuits to the muscles controlling arm movements. In this model, the arm consists of two joints (shoulder and elbow), whose movements are actuated by six muscles (4 single-joint and 2 double-joint flexors and extensors). The muscles provide afferent feedback to the spinal cord circuits. Cortical neurons are defined as cortical "controllers" that solve an inverse problem based on a proposed straight-line trajectory to a target position and a predefined bell-shaped velocity profile. Thus, the controller generates a motor program that produces a task-specific activation of low-level spinal circuits that in turn induce the muscle activation realizing the intended reaching movement. Using the model, we describe the mechanisms of correlation between cortical and motoneuronal activities and movement direction and other movement parameters. We show that the directional modulation of neuronal activity in the motor cortex and the spinal cord may result from direction-specific dynamics of muscle lengths. Our model suggests that directional modulation first emerges at the level of muscle forces, augments at the motoneuron level, and further increases at the level of the motor cortex due to the dependence of frictional forces in the joints, contractility of the muscles and afferent feedback on muscle lengths and/or velocities.
Genomic analyses of Neanderthals have previously provided insights into their population history and relationship to modern humans
, but the social organization of Neanderthal communities remains ...poorly understood. Here we present genetic data for 13 Neanderthals from two Middle Palaeolithic sites in the Altai Mountains of southern Siberia: 11 from Chagyrskaya Cave
and 2 from Okladnikov Cave
-making this one of the largest genetic studies of a Neanderthal population to date. We used hybridization capture to obtain genome-wide nuclear data, as well as mitochondrial and Y-chromosome sequences. Some Chagyrskaya individuals were closely related, including a father-daughter pair and a pair of second-degree relatives, indicating that at least some of the individuals lived at the same time. Up to one-third of these individuals' genomes had long segments of homozygosity, suggesting that the Chagyrskaya Neanderthals were part of a small community. In addition, the Y-chromosome diversity is an order of magnitude lower than the mitochondrial diversity, a pattern that we found is best explained by female migration between communities. Thus, the genetic data presented here provide a detailed documentation of the social organization of an isolated Neanderthal community at the easternmost extent of their known range.
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