Residue packing in globular and intrinsically disordered proteins

Intrinsically disordered proteins (IDPs)/regions do not have well‐defined secondary and tertiary structures, however, they are functional and it is critical to gain a deep understanding of their residue packing. The shape distributions methodology, which is usually utilized in pattern recognition, clustering, and classification studies in computer science, may be adopted to study the residue packing of the proteins. In this study, shape distributions of the globular proteins and IDPs were obtained to shed light on the residue packing of their structures. The shape feature that was used is the sphericity of tetrahedra obtained by Delaunay Tessellation of points of Cα coordinates. Then the sphericity probability distributions were compared by using Principal Component Analysis. This computational structural study shows that the set of IDPs constitute a more diverse set than the set of globular proteins in terms of the geometrical properties of their network structures.     

Substrate specificity of homogeneous monkeypox virus uracil-DNA glycosylase

Weak or nonexistent smallpox immunity in today's human population raises concerns about the possibility of natural or provoked genetic modifications leading to re-emergence of variola virus and other poxviruses. Thus, the development of new antiviral strategies aimed at poxvirus infections in humans is a high priority. The DNA repair protein uracil-DNA glycosylase (UNG) is one of the viral enzymes important for poxvirus pathogenesis. Consequently, the inhibition of UNG is a rational therapeutic strategy for infections with poxviruses. Monkeypox virus, which occurs naturally in Africa, can cause a smallpox-like disease in humans. Here, the monkeypox virus UNG (mpUNG) is characterized and compared to vaccinia virus UNG (vUNG) and human UNG (hUNG). The mpUNG protein excises uracil preferentially from single-stranded DNA. Furthermore, mpUNG prefers the U.G pair over the U.A pair and does not excise oxidized bases. Both mpUNG and vUNG viral proteins are strongly inhibited by physiological concentrations of NaCl and MgCl2. Although the two viral DNA repair enzymes have similar substrate specificities, the kcat/KM values of mpUNG are higher than those of vUNG. The mpUNG protein was strongly inhibited by 5-azauracil and to a lesser extent by 4(6)-aminouracil and 5-halogenated uracil analogues, whereas uracil had no effect. To develop antiviral drugs toward mpUNG, we also validated a repair assay using the molecular beacons containing multiple uracil residues. Potential targets and strategies for combating pathogenic orthopoxviruses, including smallpox, are discussed.     

Synthesis of regioselectively substituted cellulose derivatives and applications in chiral chromatography

Various cellulose-2,3-bis-arylcarbamate-6-O-arylesters and cellulose-2,3-bis-arylester-6-O-arylcarbamates, designed to test the possible combined effects of the known tris-arylcarbamate and tris-arylester classes, were synthesized with high regioselectivity at O-C(6), and their use as CSP s in liquid chromatography for enantiomeric separations was investigated. The separations obtained with the synthesized CSP s were compared to the separations achieved on a self-packed reference column, consisting of cellulose-tris-(3,5-dimethylphenyl-carbamate) as CSP standard. Among the synthesized, regioselectively substituted cellulose derivatives, 2,3-bis-O-(3,5-dimethylphenylcarbamate)-6-O-benzoate-cellulose and 2,3-bis-O-(benzoate)-6-O-(3,5-dichlorophenylcarbamate)-cellulose gave the best CSP s for the separation of the test racemates. CSP s from regioselectively substituted cellulose derivatives seem to exhibit higher selectivities than cellulose-tris-(3,5-dimethylphenylcarbamate) for certain classes of racemic compounds. Chirality 10:294–306, 1998. © 1998 Wiley-Liss, Inc.     

Antimicrobial defence and persistent infection in insects revisited

Insects show long-lasting antimicrobial immune responses that follow the initial fast-acting cellular processes. These immune responses are discussed to provide a form of phrophylaxis and/or to serve as a safety measure against persisting infections. The duration and components of such long-lasting responses have rarely been studied in detail, a necessary prerequisite to understand their adaptive value. Here, we present a 21 day proteomic time course of the mealworm beetle Tenebrio molitor immune-challenged with heat-killed Staphylococcus aureus. The most upregulated peptides are antimicrobial peptides (AMPs), many of which are still highly abundant 21 days after infection. The identified AMPs included toll and imd-mediated AMPs, a significant number of which have no known function against S. aureus or other Gram-positive bacteria. The proteome reflects the selective arena for bacterial infections. The results also corroborate the notion of synergistic interactions in vivo that are difficult to model in vitro.This article is part of the themed issue ‘Evolutionary ecology of arthropod antimicrobial peptides’.     

Different Profile of mRNA Expression in Sinoatrial Node from Streptozotocin-Induced Diabetic Rat

BackgroundExperiments in isolated perfused heart have shown that heart rate is lower and sinoatrial node (SAN) action potential duration is longer in streptozotocin (STZ)–induced diabetic rat compared to controls. In sino-atrial preparations the pacemaker cycle length and sino-atrial conduction time are prolonged in STZ heart. To further clarify the molecular basis of electrical disturbances in the diabetic heart the profile of mRNA encoding a wide variety of proteins associated with the generation and transmission of electrical activity has been evaluated in the SAN of STZ-induced diabetic rat heart.Conclusions/SignificanceCollectively, this study has demonstrated differences in the profile of mRNA encoding a variety of proteins that are associated with the generation, conduction and regulation of electrical signals in the SAN of STZ-induced diabetic rat heart. Data from this study will provide a basis for a substantial range of future studies to investigate whether these changes in mRNA translate into changes in electrophysiological function.     

The protective effects of caffeic acid phenethyl ester (CAPE) against liver damage induced by cigarette smoke inhalation in rats

The aim of this study was to investigate the histological and biochemical changes in liver of rats exposed to cigarette smoke and effects of caffeic acid phenetyl ester (CAPE) on these changes. For this purpose, 21 male Wistar rats were divided into three groups. Animals in Group I were used as control. Rats in Group II were exposed to cigarette smoke and rats in Group III were exposed to cigarette smoke and injected daily with CAPE. At the end of the 60-days experimental period, all rats were killed by decapitation and blood samples were obtained. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin levels and hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px ), malondialdehyde (MDA) contents were determined. Following routine histological procedures, liver tissue specimens were examined under a light microscope. The levels of ALT, AST, total bilirubin, SOD, GSH-Px and MDA were significantly increased in rats exposed to cigarette smoke compared with those of the controls. Light microscopic examination of liver specimens from rats exposed to cigarette smoke revealed mononuclear cell infiltration and that some of the hepatocytes had a hyperchromatic nucleus and enlarged sinusoids. The rats which were treated with CAPE along with cigarettes had partially attenuated histological changes associated with cigarette exposure. In conclusion, the damage inflicted by cigarette in the rat liver can be partially prevented by CAPE administration.     

25-hydroxyvitamin D (25-OHD) levels in Turkish geriatric population: A nationwide study

BackgroundAcross the world, 25-hydroxyvitamin D (25-OHD) deficiency is a major health problem associated with many chronic diseases in the geriatric population. Prior to this study, there were no data regarding 25-OHD levels among individuals over the age of 65 in Turkey. The aim of this study was to assess 25-OHD levels and seasonal variations in these values among people over the age of 65 in Turkey.MethodsThis study included vitamin D measurements taken in 2016, 2017, and 2018 from the Turkish population over the age of 65. The age, gender, and seasonal average data of the study population were defined. The study data were obtained from the database of the Ministry of Health, and a Kolmogorov-Smirnov test was used to assess the distribution of the data. Medians and interquartile ranges (IQRs) were calculated for all categories, as the data were nonparametric.ResultsThe number of vitamin D measurements taken from the geriatric individuals included in this study was 305,329 for 2016, 576,452 for 2017, and 752,837 for 2018. The medians and IQRs of the 25-OHD levels in this population were 16 μg/L (IQR 7.45-24.55 μg/L) for 2016, 16.1 μg/L (IQR 7.8-24.4 μg/L) for 2017, and 16.4 μg/L (IQR 8.95-23.85 μg/L) for 2018.ConclusionsWhile the 25-OHD levels of older men tended to increase during the period of seasonal sunlight in Turkey, this variability was observed in elderly women. This suggests that older women tend to live more sedentary lives and have insufficient sun exposure. Overall, the median 25-OHD levels of individuals over the age of 65 tended to decrease each year.