Proteomics of citrullination in cardiovascular disease

Citrullination is an enzymatic posttranslational modification (PTM), which has become a topic of recent research due to its involvement in various physiologic and pathologic processes. This review will focus primarily on the cardiovascular pathology associated to date with citrullination, including myocardial citrullination as well as the potential role of citrullination in atherosclerosis as a driver inflammation, especially in patients with rheumatoid arthritis (RA). There is extensive citrullination within normal and RA myocardium as well as the atherosclerotic plaque; and increased levels of antibodies to citrullinated proteins have been associated with increased cardiovascular burden in patients with RA. Given robust citrullination in both RA as well as non-RA patients, there also exists the potential for protein citrullination to contribute to cardiovascular pathology in the general population. However, to investigate this possibility will require development of improved biochemical and proteomic tools for the study of protein citrullination. The remainder of this review will discuss current and developing methodologies to study protein citrullination and discuss their applicability for the analysis of complex samples. The ability to identify and quantify citrullinated protein is a key to understanding the role of this PTM. Methodologies and limitations of current technology for the identification of citrullination are discussed.     

The effect of copper ions on interaction of UV radiation with methacrylic matrix – EPR study

The role of metal ions introduced to polymer matrix in the photochemical degradation of material is not fully understood. In this paper, we considered the effect of copper ions on the photochemical changes in Methafilcon A after UV-irradiation. The presence of methacrylic acid in the structure of Methafilcon A increases the loading capacity of these ions. In result, there is observed the production much more radicals after UV-irradiation than in pure matrix, without copper ions. When the time of UV-exposure increases, the EPR signal of trapped Cu(II) ions in the material decreases. This proves the transformation of Cu(II) to a diamagnetic state of stable Cu(I)-intermediates or copper oxides. Simultaneously, in the first 5-min of UV-irradiation there is observed a rapid increase in intensity of the radical signal, which disappears when the exposure time is extended. This mechanism of radical generating is quite different than for Methafilcon A matrix without copper ions.     

Pharmacological Profile and Molecular Modeling of Cyclic Opioid Analogues Incorporating Various Phenylalanine Derivatives

Peptide-based agonists of the μ opioid receptor (μOR) are promising therapeutic candidates for pain relief with reduced side effects compared to morphine. A deep understanding of μOR–ligand interactions is necessary for future design of peptide-based opioid analgesics. To explore the requirements of the μOR binding pocket, eight new analogues of our cyclic peptide Tyr-c[d -Lys−Phe−Phe−Asp]NH₂ displaying high μOR affinity were synthesized, in which Phe in either the third or fourth position was replaced by various derivatives of this amino acid (β³-Phe, homoPhe, β³-homoPhe and PhGly). The aim of this research was to examine the structural effects of such modifications on the bioactivity, and both experimental and theoretical methods were used. The binding of the cyclic analogues to all three OR types (μ, δ, κ) was assessed by radioligand competitive binding assay, and their functional activity was determined in a calcium mobilization assay. In order to provide structural hypotheses explaining the obtained experimental affinities, the complexes of the cyclic peptides with μOR were subjected to molecular modeling.     

The missing asymmetry in the Polish house price cycle: an analysis of the behaviour of house prices in 17 major cities

Journal of Housing and the Built Environment - This paper investigates the house price cycle in 17 major cities in Poland, analysing separately prices of newly constructed housing and prices in the...     

Chronic and Intermittent Hyperglycemia Modulates Expression of Key Molecules of PI3K/AKT Pathway in Differentiating Human Visceral Adipocytes

Background: Due to its prominence in the regulation of metabolism and inflammation, adipose tissue is a major target to investigate alterations in insulin action. This hormone activates PI3K/AKT pathway which is essential for glucose homeostasis, cell differentiation, and proliferation in insulin-sensitive tissues, like adipose tissue. The aim of this work was to evaluate the impact of chronic and intermittent high glucose on the expression of biomolecules of insulin signaling pathway during the differentiation and maturation of human visceral preadipocytes. Methods: Human visceral preadipocytes (HPA-V) cells were treated with high glucose (30 mM)during the proliferation and/or differentiation and/or maturation stage. The level of mRNA (by Real-Time PCR) and protein (by Elisa tests) expression of IRS1, PI3K, PTEN, AKT2, and GLUT4 was examined after each culture stage. Furthermore, we investigated whether miR-29a-3p, miR-143-3p, miR-152-3p, miR-186-5p, miR-370-3p, and miR-374b-5p may affect the expression of biomolecules of the insulin signaling pathway. Results: Both chronic and intermittent hyperglycemia affects insulin signaling in visceral pre/adipocytes by upregulation of analyzed PI3K/AKT pathway molecules. Both mRNA and protein expression level is more dependent on stage-specific events than the length of the period of high glucose exposure. What is more, miRs expression changes seem to be involved in PI3K/AKT expression regulation in response to hyperglycemic stimulation.     

Scanning electron microscopy and energy dispersive X-ray study of a recovered dental implant

A recovered dental implant has been studied for surface contamination using SEM and EDS microanalysis. The implant had been in place for 4 years in an adult male (age: 56 years), who had poor oral hygiene and was a smoker. Loosening had occurred, and the implant was removed accidentally during the taking of an impression. Using SEM, three distinct regions were identified, a clear one where the metal appeared shiny and unaffected, a discoloured one, where the surface appeared smooth and uncoated, and a region where there was a distinct deposit. All three regions gave elemental compositions of approximately 85% Ti, 12% Al, 3% V, which is a little richer in aluminium than the nominal overall composition of the usual alloy employed in implants. All three regions showed the presence of carbon, with the highest levels being associated with the surface deposit, and the lowest with the clear region. Oxygen was also present in substantial amounts, with most being found in the discoloured region. No nitrogen was detected, which suggests that the organic surface contamination is not due to interaction with proteins, despite their presence in saliva and crevicular fluid within the mouth.     

Chiral analysis of chloro intermediates of methylamphetamine by one-dimensional and multidimentional NMR and GC/MS

Impurity profiling and classification of abused drugs using chiral analytical techniques is of particular interest and importance because of the additional information obtained from this approach. When these methods are applied to the synthesis of illicitly used substances, they can supply valuable information about the conditions/chemicals used in the synthesis. We have applied GC and NMR methods to the study of intermediates found in methylamphetamine manufacture with the aim of linking the intermediates to the ephedrine/pseudoephedrine starting materials. Therefore, determination of the stereochemical makeup within samples of forensic interest is important giving further specific information to the analyst. This study investigates the stereochemical course of the Emde synthesis of methylamphetamine with particular focus on intermediate formation via the chlorination of ephedrine and pseudoephedrine enantiomers. The configurations of these chloro-phenethylamines were determined by 1D and 2D NMR analysis, and thereafter, the GC/MS analysis was carried out. We have shown here that chlorination of the ephedrine/pseudoephedrine compounds occurs via inversion (S(N)2) and retention (S(N)i) of configuration around the α carbon and mixture of diastereoisomers (chloroephedrine and chloropseudoephedrine) were formed, with the ratio of the resulting compounds dependent on the precursors used. The preparation and analytical properties of these intermediate standards provide data for laboratories interested in the stereochemical analysis of methylamphetamine intermediates such as forensic/law enforcement, and illustrate the value of using a combination of analytical methodology.     

一种被遗忘的城市主义

城市是文化物品;技术官僚制度下的城市设计体系(Urbanism),是一个来自19世纪欧洲的产物,尽管它已被中国广泛采用,却和中国的文化环境没有多大关联。中国有自己的城市设计传统,其中一种可以在中国南方的城市中找到,它为城市活动找到一种体量化的表达。文章认为,在这些地区可以找到更多适合中国的城市设计方法。     

Development of electronic textiles to support networks, communications, and medical applications in future U.S. military protective clothing systems.

The focus of this paper is on the development of textile-based wearable electronics that can be integrated into military protective clothing. A materials and manufacturing survey was conducted to determine the best performing and most durable materials to withstand the rigors of textile manufacturing and potential military use. Narrow woven technology was selected as one of the most promising textile manufacturing methods. A working wearable narrow fabric version of the Universal Serial Bus (USB), as well as a radiating conductor, were successfully developed and fabricated. A circular knit T-shirt with an integrated spiral bus was also developed. Military products developed include components of a personal area network providing data and power transport, and a body-borne antenna integrated into a load-bearing vest.