Elucidation of the primary structure of the lantibiotic epilancin K7 from Staphylococcus epidermidis K7. Cloning and characterisation of the epilancin-K7-encoding gene and NMR analysis of mature epilancin K7

Lantibiotics are bacteriocins that contain unusual amino acids such as lanthionines and α,β-didehydro residues generated by posttranslational modification of a ribosomally synthesized precursor protein. The structural gene encoding the novel lantibiotic epilancin K7 from Staphylococcus epidemzidis K7 was cloned and its nucleotide sequence was determined. The gene, which was named elkA, codes for a 55-residue preprotein, consisting of an N-terminal 24-residue leader peptide, and a C-terminal 31-residue propeptide which is posttranslationally modified and processed to yield mature epilancin K7. In common with the type-A lantibiotics nisin A and nisin Z, subtilin, epidermin, gallidermin and Pep5, pre-epilancin K7 has a so-called class-A1 leader peptide. Downstream and upstream of the elkA gene, the starts of two open-reading-frames, named elkP and elkT, were identified. The elkP and elkT genes presumably encode a leader peptidase and a translocator protein, respectively, which may be involved in the processing and export of epilancin K7. The amino acid sequence of the unmodified pro-epilancin K7, deduced from the elkA gene sequence, is in full agreement with the amino acid sequence of mature epilancin K7, determined previously by means of NMR spectroscopy. The first residue of mature epilancin K7 appears to be modified in a way that has not been described for any other lantibiotic so far. NMR experiments show that the elkA-encoded serine residue at position +1 of pro-epilancin K7 is modified to a 2-hydroxypropionyl residue in the mature protein.

Effects of light therapy on mood and insulin sensitivity in patients with type 2 diabetes and depression:Results from a randomized placebo-controlled trial

OBJECTIVE: Depression is common in patients with type 2 diabetes, and adversely affects quality of life and diabetes outcomes. We assessed whether light therapy, an antidepressant, improves mood and insulin sensitivity in patients with depression and type 2 diabetes. RESEARCH DESIGN AND METHODS: This randomized, double-blind, placebo-controlled trial included 83 patients with depression and type 2 diabetes. The intervention comprised 4 weeks of light therapy (10,000 lux) or placebo light therapy daily at home. Primary outcomes included depressive symptoms (Inventory of Depressive Symptomatology [IDS]) and insulin sensitivity (M-value derived from the results of a hyperinsulinemic-euglycemic clamp). Secondary outcomes were related psychological and glucometabolic measures. RESULTS: Intention-to-treat analysis showed that light therapy was not superior to placebo in reducing depressive symptoms (-3.9 IDS points [95% CI -9.0 to 1.2]; P = 0.248) and had no effect on insulin sensitivity (0.15 mg/kg*min [95% CI -0.41 to 0.70]; P = 0.608). Analyses incorporating only those participants who accurately adhered to the light therapy protocol (n = 51) provided similar results, but did suggest positive effects of light therapy on depression response rates (≥50% reduction in IDS points) (26% more response; P = 0.031). Prespecified analysis showed effect moderation by baseline insulin sensitivity (P = 0.009) and use of glucose-lowering medication (P = 0.023). Light therapy did not affect depressive symptoms in participants with higher insulin sensitivity or those who use only oral glucose lowering medication or none at all, but it did produce a relevant effect in participants with lower insulin sensitivity (-12.9 IDS points [95% CI -21.6 to -4.2]; P = 0.017) and a trend toward effectiveness in those using insulin (-12.2 IDS points [95% CI -21.3 to -3.1]; P = 0.094). Light therapy was well tolerated. CONCLUSIONS: Although this trial is essentially inconclusive, secondary analyses indicate that light therapy might be a promising treatment for depression among a subgroup of highly insulin-resistant individuals with type 2 diabetes

Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis

Aim Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a metaanalysis of all available prospective data. Methods This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien–Dindo Grades III–V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. Results This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery formalignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49–2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46–0.75, P < 0.001) compared to normal weight patients. Conclusions In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

10.1371/journal.pone.0139981PLoS ONE1010e013998