Human linker histones: interplay between phosphorylation and O-β-GlcNAc to mediate chromatin structural modifications

Eukaryotic chromatin is a combination of DNA and histone proteins. It is established fact that epigenetic mechanisms are associated with DNA and histones. Initial studies emphasize on core histones association with DNA, however later studies prove the importance of linker histone H1 epigenetic. There are many types of linker histone H1 found in mammals. These subtypes are cell specific and their amount in different types of cells varies as the cell functions. Many types of post-translational modifications which occur on different residues in each subtype of linker histone H1 induce conformational changes and allow the different subtypes of linker histone H1 to interact with chromatin at different stages during cell cycle which results in the regulation of transcription and gene expression. Proposed O-glycosylation of linker histone H1 promotes condensation of chromatin while phosphorylation of linker histone H1 is known to activate transcription and gene regulation by decondensation of chromatin. Interplay between phosphorylation and O-β-GlcNAc modification on Ser and Thr residues in each subtype of linker histone H1 in Homo sapiens during cell cycle may result in diverse functional regulation of proteins. This in silico study describes the potential phosphorylation, o-glycosylation and their possible interplay sites on conserved Ser/Thr residues in various subtypes of linker histone H1 in Homo sapiens

A numerical investigation of mathematical modelling in 3D hexagonal porous prism on oil recovery using nanoflooding

The use of nanomaterials as a means of recovering heavy and light oil from petroleum reservoirs has increased over the preceding twenty years. Most researchers have found that injecting a nanoparticle dispersion (nanofluids) has led to good results and increased the amount of oil that can be recovered. In this research, we aim to imitate the three-dimensional hexagonal prism in the existence of SiO2 and Al2O3 nanoparticles for better oil recovery. Porosity (0.1≤φ≤0.4), mass flow rate (0.05mL/min≤Q≤0.05ml/min), nanoparticle concentration (0.01≤ψ≤0.04), and the effect of relative permeability (kr) on oil and water saturation in the presence of gravity under different time durations are all investigated. The result obtained for the model is verified with existing experimental data. The results indicated that the infulence of nanoparticle volume fraction (VF) is significant in enhancing the oil recovery rate. It is also observed that at low porosity values the oil recovery is maximum. The maximum oil recovery is attained at low values of mass flow rate in the 3D hexagonal prism in the presence of silicon and aluminium nanoparticles It is also observed that the use of SiO2 gives a better oil recovery rate than Al2O3. It is also observed that maximum oil recovery is obtained at 99% at a flow rate of 0.05 mL/min in the presence of silicon injection

Association of promoter region A-1012G polymorphism (rs4516035) of vitamin-D receptor gene with coronary artery disease

Objective: To investigate the correlation of Adenine-1012-Guanine (rs4516035) promoter region polymorphism of vitamin-D receptor gene with serum levels of omentin-1, vitamin-D and vitamin-D receptor protein in patients with coronary artery disease. Method: The case-control study was conducted January to June 2020 at the cardiac unit of Civil hospital Karachi (CHK), and comprised coronary artery disease patients and controls. The tetra-primer amplification refractory mutation system polymerase chain reaction method was used to genotype Adenine-1210Guanine polymorphism in the vitamin D receptor gene.  Serum levels of omentin-1, vitamin-D, and vitamin-D receptor protein were measured in both the groups using an enzyme-linked immunosorbent assay. Data was analysed using SPSS 17. Results: Of the 1,000 subjects, there were 500(50%) cases; males 306(61.2%) and 194(38.8%) females with overall mean age of 51.08±9.55 years. The remaining 500(50%) were controls; 290(58%) males and 210(42%) females with overall mean age of 50.9±10.78 years. The mutant Guanine allele was more prevalent in controls 261(52.2%), and had a non-significant correlation with coronary artery disease (p=0.45).  Among the cases, the wild Adenine-Adenine genotype had a higher prevalence 402(80.4%) and had a significant correlation with coronary artery disease (p<0.001). The heterozygous genotype Adenine-Guanine was significantly more predominant among the controls 346(69.2%) compared to the cases 66(13.2) (p=0.002). Conclusion: Adenine-1012-Guanine polymorphism in the vitamin-D receptor gene was found to be a protective polymorphism for coronary artery disease in the recessive model. Key Words: Coronary artery disease, Omentin-1, Vitamin-D, Vitamin-D receptor

Analysis of drug-related problems identified by future pharmacists in medical wards of tertiary hospitals in the state of Pahang, Malaysia

Objective: Clinical attachments undertaken by pharmacy students in Malaysia are one of the important platforms in order to prepare future candidates for patient-centred pharmacy practice. The lack of data regarding the identification of Drug-related problems (DRPs) and the suggestion of relevant interventions by final year pharmacy students has directed the current research to describe pharmacy students’ abilities in identifying DRPs in their final year clinical placements. Methods: As a descriptive cross-sectional study, it involved the analysis of the clinical case reports of final year pharmacy students during their six-week clinical attachments between February and April 2017 across three different tertiary hospitals in the state of Pahang, Malaysia. A six-member team, who had received the required training by the study’s principal researcher, performed the data extraction from the clinical attachment reports. Results: A total of 385 clinical case reports, identified 880 DRPs. The two most common types of identified DRPs were the untreated condition (17.4 %), followed by inappropriate drug selection (16.3 %). Nearly 47.7 % of total detected DRPs were related to the indication and efficacy domains of therapy assessment. Additionally, there was a positive correlation found between the number of underlying diseases and the number of identified DRP, rs(372) = .14, p = .007. Conclusion: During the final year clinical attachments, the majority of the students were able to identify a considerable number of DRPs in the hospital setting under the supervision of their preceptors. The characterisation of the identified DRPs could be instrumental in refining the experiential clinical learning among future pharmacy practitioners

Serine 204 phosphorylation and O-β-GlcNAC interplay of IGFBP-6 as therapeutic indicator to regulate IGF-II functions in viral mediated hepatocellular carcinoma

Hepatocellular carcinoma is mainly associated with viral hepatitis B and C. Activation of cell growth stimulator IGF-II gene is observed in tumor formation especially in viral associated hepatocellular carcinoma. Elevated IGF-II levels are indicator of increased risk for cholangiocellular and hepatocellular carcinomas through over saturation of IGF-II binding capacities with IGF receptors leading to cellular dedifferentiation. In HCV, core protein is believed to trans-activate host IGF-II receptor through PKC pathway and the inhibition of tumor cell growth can be achieved by blocking IGF-II pathway either at transcriptional level or increasing its binding with IGFBPs (Insulin like growth factor proteins) at C-terminal, so that it is not available in free form. IGFBP-6 is a specific inhibitor of IGF-II actions. Affinity of IGFBPs with IGFs is controlled by post-translational modifications. Phosphorylation of IGFBPs inhibits IGFs action on target cells while O-glycosylation prevents binding of IGFBP-6 to glycosaminoglycans and cell membranes and resulting in a 10-fold higher affinity for IGF-II. O-glycosylation and phosphorylation operate the functional expression of cellular proteins, this switching on and off the protein expression is difficult to monitor in vivo. By using neural network based prediction methods, we propose that alternate O-β-GlcNAc modification and phosphorylation on Ser 204 control the binding of IGFBP-6 with IGF-II. This information may be used for developing new therapies by regulating IGFBP-6 assembly with IGF-II to minimize the risk of viral associated hepatocellular carcinoma. We can conclude that during HCV/HBV infection, O-β-GlcNAc of IGFBP-6 at Ser 204 diminish their binding with IGF-II, increase IGF-II cellular expression and promote cancer progression which can lead to hepatocellular carcinoma. Furthermore, this site can be used for developing new therapies to control the IGF-II actions during viral infection to minimize the risk of hepatocellular carcinoma

Serine 204 phosphorylation and O-<it>β</it>-GlcNAC interplay of IGFBP-6 as therapeutic indicator to regulate IGF-II functions in viral mediated hepatocellular carcinoma

Abstract Hepatocellular carcinoma is mainly associated with viral hepatitis B and C. Activation of cell growth stimulator IGF-II gene is observed in tumor formation especially in viral associated hepatocellular carcinoma. Elevated IGF-II levels are indicator of increased risk for cholangiocellular and hepatocellular carcinomas through over saturation of IGF-II binding capacities with IGF receptors leading to cellular dedifferentiation. In HCV, core protein is believed to trans-activate host IGF-II receptor through PKC pathway and the inhibition of tumor cell growth can be achieved by blocking IGF-II pathway either at transcriptional level or increasing its binding with IGFBPs (Insulin like growth factor proteins) at C-terminal, so that it is not available in free form. IGFBP-6 is a specific inhibitor of IGF-II actions. Affinity of IGFBPs with IGFs is controlled by post-translational modifications. Phosphorylation of IGFBPs inhibits IGFs action on target cells while O-glycosylation prevents binding of IGFBP-6 to glycosaminoglycans and cell membranes and resulting in a 10-fold higher affinity for IGF-II. O-glycosylation and phosphorylation operate the functional expression of cellular proteins, this switching on and off the protein expression is difficult to monitor in vivo. By using neural network based prediction methods, we propose that alternate O-β-GlcNAc modification and phosphorylation on Ser 204 control the binding of IGFBP-6 with IGF-II. This information may be used for developing new therapies by regulating IGFBP-6 assembly with IGF-II to minimize the risk of viral associated hepatocellular carcinoma. We can conclude that during HCV/HBV infection, O-β-GlcNAc of IGFBP-6 at Ser 204 diminish their binding with IGF-II, increase IGF-II cellular expression and promote cancer progression which can lead to hepatocellular carcinoma. Furthermore, this site can be used for developing new therapies to control the IGF-II actions during viral infection to minimize the risk of hepatocellular carcinoma.</p