Structural and spectroscopic characterisation of a heme peroxidase from sorghum

A cationic class III peroxidase from Sorghum bicolor was purified to homogeneity. The enzyme contains a high-spin heme, as evidenced by UV-visible spectroscopy and EPR. Steady state oxidation of guaiacol was demonstrated and the enzyme was shown to have higher activity in the presence of calcium ions. A Fe(III)/Fe(II) reduction potential of -266 mV vs NHE was determined. Stopped-flow experiments with H2O2 showed formation of a typical peroxidase Compound I species, which converts to Compound II in the presence of calcium. A crystal structure of the enzyme is reported, the first for a sorghum peroxidase. The structure reveals an active site that is analogous to those for other class I heme peroxidase, and a substrate binding site (assigned as arising from binding of indole-3-acetic acid) at the γ-heme edge. Metal binding sites are observed in the structure on the distal (assigned as a Na(+) ion) and proximal (assigned as a Ca(2+)) sides of the heme, which is consistent with the Ca(2+)-dependence of the steady state and pre-steady state kinetics. It is probably the case that the structural integrity (and, thus, the catalytic activity) of the sorghum enzyme is dependent on metal ion incorporation at these positions

The preservation and conservation of library materials: the case of federal university of technology library, and Imo State Iniversity Library Owerri, Owerri, Imo State

It is important to know the methods adopted by libraries to preserve and conserve their numerous materials. As a result of this, the libraries of the Federal University of Technology, Owerri and Imo State University Owerri, Imo State were used for the study. A survey method was adopted in conducting the research and questionnaire administration also employed to obtain data from 209 respondents who returned questionnaire selected for the study. This was followed by analyzing the data obtained by using simple percentages and graphical analysis. Our findings revealed that the management of the libraries studied were not doing enough in conserving and preserving their numerous collections against the deteriorative agents for many reasons, suggestion and recommendations were therefore proffered on the best way to manage these library materials

Assessment of supply chain management in Nigerian construction industry for effective project delivery in Imo State, Nigeria

This paper on assessment of supply Chain Management (SCM) in Effective Project Delivery in the Nigerian Construction Industry in Imo state focused on identifying the challenges of construction supply chain management (CSCM) for effective project delivery in Imo state and also to identify the CSCM practiced in curtailing challenges in the construction industry in Imo state. A survey questionnaire was distributed to ninety five (95) construction stakeholders in Imo state both in the private and public sector of the construction industry. Sixty (60) were successfully retrieved and analyzed using statistical package for social sciences. Average mean scores (AMS) and relative important index (RII) was used for analyzing the raw data obtained from the field. The findings reveal that inadequate investment in information technology (I.T), ineffective communication and diverse objective were ranked highest whereas unfair risk allocation and poor understanding of SCM were ranked lowest among the challenges facing the construction industry. More so, the relative important index ranges from 0.82 for trust-based relationship, information flow and strong financial flow respectively (being the first on the list) to 0.69 for Human Resource supply chain which is the least on the list involving common construction supply chain management practices in curtailing challenges in the construction industry. The study recommends that construction stakeholders should embrace CSCM which is a key focus area in the current scenario of global competitive market. Also, professional bodies such as COREN, NSE and others should endeavour to enlighten construction stakeholders more on the numerous benefits which accrue to effective application CSCM via workshops, seminar and conference

DETERMINING STUDENTS’ ATTRIBUTES AND UTILIZATION OF INFORMATION RESOURCES IN ACADEMIC LIBRARIES IN IMO STATE, NIGERIA.

In this paper, we carry out a research on determining students’ attributes and utilization of information resources in academic libraries in Imo State. The study focused on four (4) Universities in Imo State with a sample of one hundred and twenty (120) respondents. The sample was drawn using a simple random sampling technique through questionnaires. The answer to the research questions were arrived at using the descriptive analysis while the hypotheses were tested using t-test. Our findings showed thus: That students ‘study in the library and balance their study time with recreation to avoid conflicts, these determine the students’ utilization of library resources in the Universities in Imo; That students find it fascinating to learn new information was why they come to the library; they come to the library to explore new ideas and when they learn something new, they like to find out more, that is why they visit the library. That the extent of students’ utilization of library resources is determined by students use of computer facilities provided to access electronic resources in the library, students use of the internet facilities provided by the library to have access to information resources for their assignment, etc. There was significant relationship between students’ study habit and the utilization of library resources in universities, that students’ intellectual curiosity significantly affects the utilization of library resources and finally, the students’ information literacy skill significantly affects the utilisation of library resources

The immunogenicity of fractional intradermal doses of the inactivated poliovirus vaccine is associated with the size of the intradermal fluid bleb

The immunogenicity of fractional (1/5th, 0.1mL) intradermal doses of the inactivated poliovirus vaccine (ID fIPV) is positively correlated with the size of the intradermal fluid bleb. Training of vaccinators for campaign and routine ID fIPV administration should focus on generating an 8 to 10mm bleb with each injection

The Clinically Used Iron Chelator Deferasirox Is an Inhibitor of Epigenetic JumonjiC Domain-Containing Histone Demethylases

Fe(II)- and 2-oxoglutarate (2OG)-dependent JumonjiC domain-containing histone demethylases (JmjC KDMs) are epigenetic eraser enzymes involved in the regulation of gene expression and are emerging drug targets in oncology. We screened a set of clinically used iron chelators and report that they potently inhibit JMJD2A (KDM4A) in vitro. Mode of action investigations revealed that one compound, deferasirox, is a bona fide active site-binding inhibitor as shown by kinetic and spectroscopic studies. Synthesis of derivatives with improved cell permeability resulted in significant upregulation of histone trimethylation and potent cancer cell growth inhibition. Deferasirox was also found to similarly inhibit human 2OG-dependent hypoxia inducible factor prolyl hydroxylase activity. Therapeutic effects of clinically used deferasirox may thus involve transcriptional regulation through 2OG oxygenase inhibition. Deferasirox may provide a useful starting point for the development of novel anticancer drugs targeting 2OG oxygenases and a valuable tool compound for investigations of KDM function.<br /

The clinically used iron chelator deferasirox is an inhibitor of epigenetic jumonjiC domain-containing histone demethylases

Fe(II)- and 2-oxoglutarate (2OG)-dependent JumonjiC domain-containing histone demethylases (JmjC KDMs) are epigenetic eraser enzymes involved in the regulation of gene expression and are emerging drug targets in oncology. We screened a set of clinically used iron chelators and report that they potently inhibit JMJD2A (KDM4A) in vitro. Mode of action investigations revealed that one compound, deferasirox, is a bona fide active site-binding inhibitor as shown by kinetic and spectroscopic studies. Synthesis of derivatives with improved cell permeability resulted in significant upregulation of histone trimethylation and potent cancer cell growth inhibition. Deferasirox was also found to similarly inhibit human 2OG-dependent hypoxia inducible factor prolyl hydroxylase activity. Therapeutic effects of clinically used deferasirox may thus involve transcriptional regulation through 2OG oxygenase inhibition. Deferasirox might provide a useful starting point for the development of novel anticancer drugs targeting 2OG oxygenases and a valuable tool compound for investigations of KDM function

The clinically used iron chelator deferasirox is an inhibitor of epigenetic jumonjiC domain-containing histone demethylases

Fe(II)- and 2-oxoglutarate (2OG)-dependent JumonjiC domain-containing histone demethylases (JmjC KDMs) are epigenetic eraser enzymes involved in the regulation of gene expression and are emerging drug targets in oncology. We screened a set of clinically used iron chelators and report that they potently inhibit JMJD2A (KDM4A) in vitro. Mode of action investigations revealed that one compound, deferasirox, is a bona fide active site-binding inhibitor as shown by kinetic and spectroscopic studies. Synthesis of derivatives with improved cell permeability resulted in significant upregulation of histone trimethylation and potent cancer cell growth inhibition. Deferasirox was also found to similarly inhibit human 2OG-dependent hypoxia inducible factor prolyl hydroxylase activity. Therapeutic effects of clinically used deferasirox may thus involve transcriptional regulation through 2OG oxygenase inhibition. Deferasirox might provide a useful starting point for the development of novel anticancer drugs targeting 2OG oxygenases and a valuable tool compound for investigations of KDM function

Midregional proatrial naturetic peptide (MRproANP) and copeptin (COPAVP) as predictors of all-cause mortality in recently diagnosed mild to moderate COPD—results from COSYCONET

Abstract Background MRproANP and COPAVP are prognostic markers for mortality in chronic obstructive pulmonary disease (COPD). Furthermore, these biomarkers predict mortality due to cardiovascular diseases, which are important prognostically determining comorbidities in patients with COPD. However, less is known about these biomarkers in recently diagnosed mild to moderate COPD. Therefore, we analyzed these biomarkers as potential predictors of mortality in recently diagnosed mild to moderate COPD. Methods The blood biomarkers considered were copeptin (COPAVP), midregional adrenomedullin (MRproADM), midregional proatrial naturetic peptide (MRproANP), and fibrinogen. Analyses were performed in patients with stable “recently diagnosed mild to moderate COPD” defined by GOLD grades 0–2 and diagnosis of COPD ≤ 5 years prior to inclusion into the COSYCONET cohort (COPD and Systemic Consequences—Comorbidities Network), using Cox regression analysis with stepwise adjustment for multiple COPD characteristics, comorbidities, troponin and NT-proBNP. Results 655 patients with recently diagnosed mild to moderate COPD were included. In the initial regression model, 43 of 655 patients died during the 6-year follow-up, in the final model 27 of 487. Regression analyses with adjustment for confounders identified COPAVP and MRproANP as statistically robust biomarkers (p < 0.05 each) of all-cause mortality, while MRproADM and fibrinogen were not. The fourth quartile of MRproANP (97 pmol/L) was associated with a hazard ratio of 4.5 (95%CI: 1.6; 12.8), and the fourth quartile of COPAVP (9.2 pmol/L) with 3.0 (1.1; 8.0). The results for MRproANP were confirmed in the total cohort of grade 0–4 (n = 1470 finally). Conclusion In patients with recently diagnosed mild to moderate COPD, elevated values of COPVP and in particular MRproANP were robust, independent biomarkers for all-cause mortality risk after adjustment for multiple other factors. This suggests that these markers might be considered in the risk assessment of early COPD