Effect of APOB polymorphism rs562338 (G/A) on serum proteome of coronary artery disease patients: a “proteogenomic” approach

In the current study, APOB (rs1052031) genotype-guided proteomic analysis was performed in a cohort of Pakistani population. A total of 700 study subjects, including Coronary Artery Disease (CAD) patients (n = 480) and healthy individuals (n = 220) as a control group were included in the study. Genotyping was carried out by using tetra primer-amplification refractory mutation system-based polymerase chain reaction (T-ARMS-PCR) whereas mass spectrometry (Orbitrap MS) was used for label free quantification of serum samples. Genotypic frequency of GG genotype was found to be 90.1%, while 6.4% was for GA genotype and 3.5% was for AA genotypes in CAD patients. In the control group, 87.2% healthy subjects were found to have GG genotype, 11.8% had GA genotype, and 0.9% were with AA genotypes. Significant (p = 0.007) difference was observed between genotypic frequencies in the patients and the control group. The rare allele AA was found to be strongly associated with the CAD [OR: 4 (1.9–16.7)], as compared to the control group in recessive genetic model (p = 0.04). Using label free proteomics, altered expression of 60 significant proteins was observed. Enrichment analysis of these protein showed higher number of up-regulated pathways, including phosphatidylcholine-sterol O-acyltransferase activator activity, cholesterol transfer activity, and sterol transfer activity in AA genotype of rs562338 (G>A) as compared to the wild type GG genotype. This study provides a deeper insight into CAD pathobiology with reference to proteogenomics, and proving this approach as a good platform for identifying the novel proteins and signaling pathways in relation to cardiovascular diseases.

THE EFFECT OF TRANSFER DISTANCE TO LOWER BACK TWISTING AND BENDING PATTERNS IN MANUAL TRANSFER TASK

Manual material handling (MMH) activities utilize human’s effort with minimal aid from mechanical devices. MMH is typically associated with poor lower back posture which can lead to lower back injury. The likelihood to develop musculoskeletal disorders (MSDs) increases when poor working posture exist in combination with repetition and/or forceful exertion. In manual transfer activity, the distance between lifting origin and destination could affect workers’ exposure on poor lower back working posture. An experimental study was conducted to investigate the effect of transfer distance to lower back twisting and bending pattern in manual transfer activity. Positional body joints data of 26 male subjects were captured using the combination of motion capture (MOCAP) system with MVN studio software. Calculated data were plotted against time to track subjects’ lower back twisting and bending behavior. In general, longer the transfer distance would result in smaller twisting angle but higher bending angle. Statistical analysis in this study suggests 0.75m to 1.00m as the optimum transfer distance to balance lower back twisting and bending exposure on workers. This study is envisioned to provide insights for practitioners to consider space requirements for MMH activity to minimize lower back twisting and bending, and consequently the development of MSDs.

Human CETP lacks lipopolysaccharide transfer activity, but worsens inflammation and sepsis outcomes in mice

Bacterial lipopolysaccharides (LPSs or endotoxins) can bind most proteins of the lipid transfer/LPS-binding protein (LT/LBP) family in host organisms. The LPS-bound LT/LBP proteins then trigger either an LPS-induced proinflammatory cascade or LPS binding to lipoproteins that are involved in endotoxin inactivation and detoxification. Cholesteryl ester transfer protein (CETP) is an LT/LBP member, but its impact on LPS metabolism and sepsis outcome is unclear. Here, we performed fluorescent LPS transfer assays to assess the ability of CETP to bind and transfer LPS. The effects of intravenous (iv) infusion of purified LPS or polymicrobial infection (cecal ligation and puncture [CLP]) were compared in transgenic mice expressing human CETP and wild-type mice naturally having no CETP activity. CETP displayed no LPS transfer activity in vitro, but it tended to reduce biliary excretion of LPS in vivo. The CETP expression in mice was associated with significantly lower basal plasma lipid levels and with higher mortality rates in both models of endotoxemia and sepsis. Furthermore, CETPTg plasma modified cytokine production of macrophages in vitro. In conclusion, despite having no direct LPS binding and transfer property, human CETP worsens sepsis outcomes in mice by altering the protective effects of plasma lipoproteins against endotoxemia, inflammation, and infection.

ISSUES OF CLASSIFYING TRANSFER RISKS IN THE TRANSFER ACTIVITIES OF A FOOTBALL CLUB

The commercial attractiveness of football, the introduction of financial “fair play” and the need to disclose financial statements are forcing professional football clubs to pay more and more attention to issues of financial stability, improving management efficiency, including the transfer activities of football clubs. The article deals with the issues of transfer activity of a professional football club and the risks arising from this, which can significantly affect the financial, sports and reputation components of the club’s activities. This topic is especially relevant in view of the current situation with the coronavirus pandemic in the world, since one of the areas of activity that has been significantly affected is the football industry. Many clubs, including Russian ones, were forced to cut players’ and employees’ salaries, which was associated with a huge loss of income; and this obviously reflected on the transfer activity as well as the activity in the 2020 summer transfer window. Therefore, the need to pay even more attention to the topic of risks when making transfers seems obvious. This article is devoted to formulating the concept of transfer risk and creating a classification of transfer risks and transfer market participants, as well as their characteristics in terms of attitudes towards the risks arising from the transition of a professional footballer from one club to another in relation to the Russian professional football club. The article proposes a classification of transfer risks and transfer market participants from the point of view of their attitude to risks, which makes it possible to assess the degree of probability and the type of possible transfer risks to improve the efficiency of the transfer activities of a professional Russian football club. The article concludes that the most dangerous from the point of view of transfer risk due to incorrect decision-making and assessment of the situation are the actions of the representative of the buying club and the body that makes the final decision on the transfer; the least risky are the actions of the scout department and the intermediary agent. The article also introduces the concept of a player’s full transfer value, which is associated with a tendency for the difference between the market and transfer values of players to increase.