Biochemical and kinetic characterisation of a novel xylooligosaccharide-upregulated GH43 β-d-xylosidase/α-l-arabinofuranosidase (BXA43) from the probiotic Bifidobacterium animalis subsp. lactis BB-12

The Bifidobacterium animalis subsp. lactis BB-12 gene BIF_00092, assigned to encode a β-d-xylosidase (BXA43) of glycoside hydrolase family 43 (GH43), was cloned with a C-terminal His-tag and expressed in Escherichia coli. BXA43 was purified to homogeneity from the cell lysate and found to be a dual-specificity exo-hydrolase active on para-nitrophenyl-β-d-xylopyranoside (pNPX), para-nitrophenyl-α-L-arabinofuranoside (pNPA), β-(1 → 4)-xylopyranosyl oligomers (XOS) of degree of polymerisation (DP) 2–4, and birchwood xylan. A phylogenetic tree of the 92 characterised GH43 enzymes displayed five distinct groups (I − V) showing specificity differences. BXA43 belonged to group IV and had an activity ratio for pNPA:pNPX of 1:25. BXA43 was stable below 40°C and at pH 4.0–8.0 and showed maximum activity at pH 5.5 and 50°C. K(m) and k(cat) for pNPX were 15.6 ± 4.2 mM and 60.6 ± 10.8 s(-1), respectively, and substrate inhibition became apparent above 18 mM pNPX. Similar kinetic parameters and catalytic efficiency values were reported for β-d-xylosidase (XynB3) from Geobacillus stearothermophilus T‒6 also belonging to group IV. The activity of BXA43 for xylooligosaccharides increased with the size and was 2.3 and 5.6 fold higher, respectively for xylobiose and xylotetraose compared to pNPX. BXA43 showed clearly metal inhibition for Zn(2+) and Ag(+), which is different to its close homologues. Multiple sequence alignment and homology modelling indicated that Arg(505)Tyr(506) present in BXA43 are probably important for binding to xylotetraose at subsite +3 and occur only in GH43 from the Bifidobacterium genus

Vidensbaseret indsats over for udsatte børn i dagtilbud – modelprogram: Statusrapport 1. Design og metode. VIDA-forskningsserien 2011:01

Denne statusrapport præsenterer for første gang projektet Vidensbaseret indsats over for udsatte børn i dagtilbud (VIDA-projektet). Projektet belyser overordnet spørgsmålet: Hvordan tager vi i dagtilbuddene bedst hånd om socialt udsatte børn?Det omfattende projekt er bestilt og finansieret af Socialministeriet og udviklet af forskere ved DPU, Aarhus Universitet. Projektet skal udvikle og afprøve samt dokumentere hvilke pædagogiske indsatser i dagtilbud, der kan sikre udsatte børn en bedre tilværelse

Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial.

Background Coronary artery bypass grafting (CABG) is the standard treatment for revascularization in patients with left main coronary artery (LMCA) disease, but use of percutaneous coronary intervention (PCI) for this indication is increasing. We compared PCI and CABG for treatment of LMCA disease. Methods Patients with LMCA disease were enrolled in 36 centers and randomized 1:1 to treatment with PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris or non-ST elevation myocardial infarction. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE) - a composite of all-cause mortality, non-procedural myocardial infarction, any repeat coronary revascularization and stroke. The primary outcome was test for non-inferiority of PCI to CABG after up to 5 years of follow-up. Results A total of 1201 patients were randomized. Kaplan-Meier five-year estimates of MACCE were 28.7% for PCI and 20.1% for CABG, HR 1.46 [95% confidence interval (CI), 1.10 to 1.95], exceeding the limit for non-inferiority and significant for superiority of CABG over PCI (p=0.0078). Comparing PCI to CABG, five-year estimates were 11.5% vs. 9.5% [HR 1.04 (95% CI, 0.65 to 1.67), p=0.86] for all-cause mortality; 6.9% vs. 1.9% [HR 2.9 (95% CI, 1.40 to 5.90), p=0.004] for non-procedural myocardial infarction; 16.2% vs. 10.4% [HR 1.5 (95% CI, 1.04 to 2.17), p=0.03] for any revascularization; and 4.9% vs 1.7% [HR 2.3 (95% CI, 0.92 to 5.48), p=0.07] for stroke. Conclusion CABG provided a clinical outcome superior to PCI for treatment of LMCA disease.</p

Breast Cancer

Breast cancer remains one of the leading causes of cancer morbidity and mortality. Despite significant advances in treatment of breast cancer a substantial proportion of women affected by this disease succumb to it. Survival of patients with advanced disease, chemoresistant tumors or a suboptimal response to endocrine therapy is significantly shortened. Hence, further understanding of disease pathogenesis is required to enhance the arsenal of approaches to cure this deadly ailment. Recent advances in biochemistry, molecular cell biology and cancer research highlighted the importance of dysregulation of protein synthesis, translation, in the development and progression of tumors. This dysregulation appears to take place at an early stage of translation, called translation initiation, that is a highly controlled and rate-limiting step of the protein synthesis. In this chapter we summarize decades of knowledge accumulated in regards to the role of translation and its regulation in the development and progression of breast cancer. We then extensively discuss applications of this knowledge in diagnosis and treatment of breast cancer.SCOPUS: ch.binfo:eu-repo/semantics/publishe