Characterization of the meningococcal DNA glycosylase Fpg involved in base excision repair

<p>Abstract</p> <p>Background</p> <p><it>Neisseria meningitidis</it>, the causative agent of meningococcal disease, is exposed to high levels of reactive oxygen species inside its exclusive human host. The DNA glycosylase Fpg of the base excision repair pathway (BER) is a central player in the correction of oxidative DNA damage. This study aimed at characterizing the meningococcal Fpg and its role in DNA repair.</p> <p>Results</p> <p>The deduced <it>N. meningitidis </it>Fpg amino acid sequence was highly homologous to other Fpg orthologues, with particularly high conservation of functional domains. As for most <it>N. meningitidis </it>DNA repair genes, the <it>fpg </it>gene contained a DNA uptake sequence mediating efficient transformation of DNA. The recombinant <it>N. meningitidis </it>Fpg protein was over-expressed, purified to homogeneity and assessed for enzymatic activity. <it>N. meningitidis </it>Fpg was found to remove 2,6-diamino-4-hydroxy-5-formamidopyrimidine (faPy) lesions and 7,8-dihydro-8-oxo-2'-deoxyguanosine (8oxoG) opposite of C, T and G and to a lesser extent opposite of A. Moreover, the <it>N. meningitidis fpg </it>single mutant was only slightly affected in terms of an increase in the frequency of phase variation as compared to a mismatch repair mutant.</p> <p>Conclusion</p> <p>Collectively, these findings show that meningococcal Fpg functions are similar to those of prototype Fpg orthologues in other bacterial species.</p

Assessment of dietary intake of nicotinic acid and nicotinamide in relation to tolerable upper intake levels. Opinion of the Panel on Nutrition, Dietetic Products, Novel Food and Allergy of the Norwegian Scientific Committee for Food Safety. VKM report 2017:27

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has,at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the intake of niacin in the Norwegian population. NFSA has also requested that VKM conduct scenario calculations to illustrate the consequences of establishing separate maximum limits for nicotinic acid(1, 4, 8 or 10 mg/day)and nicotinamide (100, 500, 700 or 900mg/day)in food supplements, by assessing these scenarios against existing tolerable upper intake levels (ULs).The current maximum limit for niacin added to food supplements is 32mg/day, including nicotinic acid, nicotinamide and inositol hexanicotinate.publishedVersio

Combined cognitive and vocational interventions after mild to moderate traumatic brain injury: study protocol for a randomized controlled trial

Background A considerable proportion of patients with mild to moderate traumatic brain injury (TBI) experience long-lasting somatic, cognitive, and emotional symptoms that may hamper their capacity to return to work (RTW). Although several studies have described medical, psychological, and work-related factors that predict RTW after TBI, well-controlled intervention studies regarding RTW are scarce. Furthermore, there has traditionally been weak collaboration among health-related rehabilitation services, the labor and welfare sector, and workplaces. Methods/design This study protocol describes an innovative randomized controlled trial in which we will explore the effect of combining manualized cognitive rehabilitation (Compensatory Cognitive Training [CCT]) and supported employment (SE) on RTW and related outcomes for patients with mild to moderate TBI in real-life competitive work settings. The study will be carried out in the southeastern region of Norway and thereby be performed within the Norwegian welfare system. Patients aged 18–60 years with mild to moderate TBI who are employed in a minimum 50% position at the time of injury and sick-listed 50% or more for postconcussive symptoms 2 months postinjury will be included in the study. A comprehensive assessment of neurocognitive function, self-reported symptoms, emotional distress, coping style, and quality of life will be performed at baseline, immediately after CCT (3 months after inclusion), following the end of SE (6 months after inclusion), and 12 months following study inclusion. The primary outcome measures are the proportion of participants who have returned to work at 12-month follow-up and length of time until RTW, in addition to work stability as well as work productivity over the first year following the intervention. Secondary outcomes include changes in self-reported symptoms, emotional and cognitive function, and quality of life. Additionally, a qualitative RTW process evaluation focused on organizational challenges at the workplace will be performed. Discussion The proposed study will combine cognitive and vocational rehabilitation and explore the efficacy of increased cross-sectoral collaboration between specialized health care services and the labor and welfare system. If the intervention proves effective, the project will describe the cost-effectiveness and utility of the program and thereby provide important information for policy makers. In addition, knowledge about the RTW process for persons with TBI and their workplaces will be provided. Trial registration ClinicalTrials.gov, NCT03092713. Registered on 10 March 2017

Structural and mutational characterization of the catalytic A-module of the mannuronan C-5-epimerase AlgE4 from Azotobacter vinelandii

Alginate is a family of linear copolymers of (1→4)-linked β-d-mannuronic acid and its C-5 epimer α-l-guluronic acid. The polymer is first produced as polymannuronic acid and the guluronic acid residues are then introduced at the polymer level by mannuronan C-5-epimerases. The structure of the catalytic A-module of the Azotobacter vinelandii mannuronan C-5-epimerase AlgE4 has been determined by x-ray crystallography at 2.1-Å resolution. AlgE4A folds into a right-handed parallel β-helix structure originally found in pectate lyase C and subsequently in several polysaccharide lyases and hydrolases. The β-helix is composed of four parallel β-sheets, comprising 12 complete turns, and has an amphipathic α-helix near the N terminus. The catalytic site is positioned in a positively charged cleft formed by loops extending from the surface encompassing Asp(152), an amino acid previously shown to be important for the reaction. Site-directed mutagenesis further implicates Tyr(149), His(154), and Asp(178) as being essential for activity. Tyr(149) probably acts as the proton acceptor, whereas His(154) is the proton donor in the epimerization reaction

Assessment of zinc intake in relation to tolerable upper intake Levels. Opinion of the Panel on Nutrition, Dietetic Products, Novel Food and Allergy of the Norwegian Scientific Committee for Food Safety

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Assessment of vitamin B6 intake in relation to tolerable upper intake Levels. Opinion of the Panel on Nutrition, Dietetic Products, Novel Food and Allergy of the Norwegian Scientific Committee for Food Safety

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Assessment of iron intake in relation to tolerable upper intake Levels. Opinion of the Panel on Nutrition, Dietetic Products, Novel Food and Allergy of the Norwegian Scientific Committee for Food Safety

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Assessment of copper intake in relation to tolerable upper intake Levels. Opinion of the Panel on Nutrition, Dietetic Products, Novel Food and Allergy of the Norwegian Scientific Committee for Food Safety. VKM Report 2017:19

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Assessment of selenium intake in relation to tolerable upper intake levels. Opinion of the Panel on Nutrition, Dietetic Products, Novel Food and Allergy of the Norwegian Scientific Committee for Food Safety. VKM Report 2017:20

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