The polypeptide Syn67 interacts physically with human holocarboxylase synthetase, but is not a target for biotinylation

Holocarboxylase synthetase (HCS) catalyzes the binding of biotin to lysines in carboxylases and histones in two steps. First, HCS catalyzes the synthesis of biotinyl-5′-AMP; second, the biotinyl moiety is ligated to lysine residues. It has been proposed that step two is fairly promiscuous, and that protein biotinylation may occur in the absence of HCS as long as sufficient exogenous biotinyl-5′- AMP is provided. Here, we identified a novel polypeptide (Syn67) with a basic patch of lysines and arginines. Yeast-two-hybrid assays and limited proteolysis assays revealed that both N- and C-termini of HCS interact with Syn67. A potential target lysine in Syn67 was biotinylated by HCS only after arginine-to-glycine substitutions in Syn67 produced a histone-like peptide. We identified a Syn67 docking site near the active pocket of HCS by in silico modeling and site directed mutagenesis. Biotinylation of proteins by HCS is more specific than previously assumed

The polypeptide Syn67 interacts physically with human holocarboxylase synthetase, but is not a target for biotinylation

Holocarboxylase synthetase (HCS) catalyzes the binding of biotin to lysines in carboxylases and histones in two steps. First, HCS catalyzes the synthesis of biotinyl-5′-AMP; second, the biotinyl moiety is ligated to lysine residues. It has been proposed that step two is fairly promiscuous, and that protein biotinylation may occur in the absence of HCS as long as sufficient exogenous biotinyl-5′- AMP is provided. Here, we identified a novel polypeptide (Syn67) with a basic patch of lysines and arginines. Yeast-two-hybrid assays and limited proteolysis assays revealed that both N- and C-termini of HCS interact with Syn67. A potential target lysine in Syn67 was biotinylated by HCS only after arginine-to-glycine substitutions in Syn67 produced a histone-like peptide. We identified a Syn67 docking site near the active pocket of HCS by in silico modeling and site directed mutagenesis. Biotinylation of proteins by HCS is more specific than previously assumed

Holocarboxylasesynthetase interacts physically with euchromatic histone-lysine N-methyltransferase, linking histone biotinylation with methylation events

Holocarboxylasesynthetase (HCS) catalyzes the binding of the vitamin biotin to histonesH3 and H4, thereby creating rare histonebiotinylation marks in the epigenome. These marksco-localize with K9-methylated histone H3 (H3K9me), an abundant gene repression mark. The abundance of H3K9me marks in transcriptionally competent loci decreases when HCS is knocked down and when cells are depleted of biotin. Here we tested the hypothesis that the creation of H3K9me marks is at least partially explained by physical interactions between HCS and histone-lysine Nmethyltransferases. Using a novel in silico protocol, we predicted that HCS-interacting proteins contain a GGGG(K/R)G(I/M)R motif. Thismotif, with minor variations, is present in the histonelysine N-methyltransferase EHMT1. Physical interactions between HCS and the N-terminal, ankyrin, and SET domains in EHMT1 were confirmed using yeast-two-hybrid assays, limited proteolysis assays, and co-immunoprecipitation. The interactions were stronger between HCS and the N-terminus in EHMT1 compared with the ankyrin and SET domains, consistent with the localization of the HCS-binding motif in the EHMT1 N-terminus. HCS has the catalytic activity to biotinylate K161 within the binding motif in EHMT1. Mutation of K161 weakenedthe physical interaction between EHMT1 and HCS, but it is unknown whether this effect was caused by loss of biotinylation or loss of the motif. Importantly, HCS knockdown decreased the abundance of H3K9me marks in repeats, suggesting that HCS plays a role in creating histone methylation marks in these loci. We conclude that physical interactionsbetween HCS and EHMT1 mediate epigenomic synergies between biotinylation and methylation events

The Identification of DepB: An Enzyme Responsible for the Final Detoxification Step in the Deoxynivalenol Epimerization Pathway in Devosia mutans 17-2-E-8

Deoxynivalenol (DON) is one of the most common mycotoxins found in cereal grains and grains contaminated with DON can cause health issues for both humans and animals and result in severe economic losses. Currently there is no feasible method to remediate affected grains. The development of a biological method for detoxification is becoming increasingly more plausible with the discovery of microbes which can transform DON to a relatively non-toxic stereoisomer, 3-epi-DON. Although bacteria capable of detoxifying DON have been known for some time, it is only recently an enzyme responsible was identified. In Devosia mutans 17-2-E-8 (Devosia sp. 17-2-E-8) a two-step DON epimerization (Dep) pathway, designated as the Dep system, completes this reaction. DepA was recently identified as the enzyme responsible for the conversion of DON to 3-keto-DON, and in this report, DepB, a NADPH dependent dehydrogenase, is identified as the second and final step in the pathway. DepB readily catalyzes the reduction of 3-keto-DON to 3-epi-DON. DepB is shown to be moderately thermostable as it did not lose significant activity after a heat treatment at 55°C and it is amenable to lyophilization. DepB functions at a range of pH-values (5–9) and functions equally well in multiple common buffers. DepB is clearly a NADPH dependent enzyme as it utilizes it much more efficiently than NADH. The discovery of the final step in the Dep pathway may provide a means to finally mitigate the losses from DON contamination in cereal grains through an enzymatic detoxification system. The further development of this system will need to focus on the activity of the Dep enzymes under conditions mimicking industrially relevant conditions to test their functionality for use in areas such as corn milling, fuel ethanol fermentation or directly in animal feed

Public Knowledge, Attitudes, and Practice towards COVID-19 Pandemic in Saudi Arabia: A Web-Based Cross-Sectional Survey

(1) Background: COVID-19 has become a worldwide public health problem. No previous study has investigated factors associated with COVID-19 knowledge, attitude, and practice (KAP) after completely lifting the curfew in all Saudi Arabia regions and cities. Therefore, adequate knowledge, a positive attitude, and correct control of COVID-19 are essential to eradicate the disease. Hence, this study aims to assess factors associated with KAP of COVID-19; (2) Methods: This cross-sectional web-based survey was performed with the participation of 4305 individuals aged over 15 years living in Saudi Arabia from 11 to 19 August 2020. They were included using the snowball sampling method; (3) Results: Of the 4305 participants, 94.9% were Saudis, 60% females, and 45.4% were in the age group of 20–34 years, 61.7% married, and 49.3% from the Eastern Province of Saudi Arabia. Most of the participants demonstrated good KAP levels (89.6%, 87.2%, and 87.2%) towards the COVID-19 pandemic, respectively. In addition, most of the participants (85.8%) used the internet and social media as a source for COVID-19 information (4) Conclusions: The finding showed that most of the participants demonstrated good knowledge of COVID-19, positive attitudes, and demonstrated good practices for preventing the spread of disease infection

The Role of Histone H4 Biotinylation in the Structure of Nucleosomes

Background: Post-translational modifications of histones play important roles in regulating nucleosome structure and gene transcription. It has been shown that biotinylation of histone H4 at lysine-12 in histone H4 (K12Bio-H4) is associated with repression of a number of genes. We hypothesized that biotinylation modifies the physical structure of nucleosomes, and that biotin-induced conformational changes contribute to gene silencing associated with histone biotinylation. Methodology/Principal Findings: To test this hypothesis we used atomic force microscopy to directly analyze structures of nucleosomes formed with biotin-modified and non-modified H4. The analysis of the AFM images revealed a 13% increase in the length of DNA wrapped around the histone core in nucleosomes with biotinylated H4. This statistically significant (p,0.001) difference between native and biotinylated nucleosomes corresponds to adding approximately 20 bp to the classical 147 bp length of nucleosomal DNA. Conclusions/Significance: The increase in nucleosomal DNA length is predicted to stabilize the association of DNA with histones and therefore to prevent nucleosomes from unwrapping. This provides a mechanistic explanation for the gene silencing associated with K12Bio-H4. The proposed single-molecule AFM approach will be instrumental for studying the effects of various epigenetic modifications of nucleosomes, in addition to biotinylation

Higher ethical objective (Maqasid al-Shari'ah) augmented framework for Islamic banks : assessing the ethical performance and exploring its determinants.

This study utilises higher objectives postulated in Islamic moral economy or the maqasid al-Shari’ah theoretical framework’s novel approach in evaluating the ethical, social, environmental and financial performance of Islamic banks. Maqasid al-Shari’ah is interpreted as achieving social good as a consequence in addition to well-being and, hence, it goes beyond traditional (voluntary) social responsibility. This study also explores the major determinants that affect maqasid performance as expressed through disclosure analysis. By expanding the traditional maqasid al-Shari’ah,, we develop a comprehensive evaluation framework in the form of a maqasid index, which is subjected to a rigorous disclosure analysis. Furthermore, in identifying the main determinants of the maqasid disclosure performance, panel data analysis is used by including several key variables alongside political and socio-economic environment, ownership structures, and corporate and Shari’ah governance-related factors. The sample includes 33 full-fledged Islamic banks from 12 countries for the period of 2008–2016. The findings show that although during the nine-year period the disclosure of maqasid performance of the sampled Islamic banks has improved, this is still short of ‘best practices’. Through panel data analysis, this study finds that the Muslim population indicator, CEO duality, Shari’ah governance, and leverage variables positively impact the disclosure of maqasid performance. However, the effect of GDP, financial development and human development index of the country, its political and civil rights, institutional ownership, and a higher share of independent directors have an overall negative impact on the maqasid performance. The findings reported in this study identify complex and multi-faceted relations between external market realities, corporate and Shari’ah governance mechanisms, and maqasid performance

Diabetes mellitus and obesity among South Asians with ischemic stroke across three countries

Background: Diabetes mellitus and central obesity are more common among South Asian populations than among White British people. This study explores the differences in diabetes and obesity in South Asians with stroke living in the United Kingdom, India, and Qatar compared with White British stroke patients. Methods: The study included the UK, Indian, and Qatari arms of the ongoing large Bio-Repository of DNA in Stroke (BRAINS) international prospective hospital-based study for South Asian stroke. BRAINS includes 4580 South Asian and White British recruits from UK, Indian, and Qatar sites with first-ever ischemic stroke. Results: The study population comprises 1751 White British (WB) UK residents, 1165 British South Asians (BSA), 1096 South Asians in India (ISA), and 568 South Asians in Qatar (QSA). ISA, BSA, and QSA South Asians suffered from higher prevalence of diabetes compared with WB by 14.5% (ISA: 95% confidence interval (CI) = 18.6–33.0, p < 0.001), 31.7% (BSA: 95% CI = 35.1–50.2, p < 0.001), and 32.7% (QSA: 95% CI = 28.1–37.3, p < 0.001), respectively. Although WB had the highest prevalence of body mass index (BMI) above 27 kg/m2 compared with South Asian patients (37% vs 21%, p < 0.001), South Asian patients had a higher waist circumference than WB (94.8 cm vs 90.8 cm, p < 0.001). Adjusting for traditional stroke risk factors, ISA, BSA, and QSA continued to display an increased risk of diabetes compared with WB by 3.28 (95% CI: 2.53–4.25, p < 0.001), 3.61 (95% CI: 2.90–4.51, p < 0.001), and 5.24 (95% CI: 3.93–7.00, p < 0.001), respectively. Conclusion: South Asian ischemic stroke patients living in Britain and Qatar have a near 3.5-fold risk of diabetes compared with White British stroke patients. Their body composition may partly help explain that increased risk. These findings have important implications for public health policymakers in nations with large South Asian populations