Reinvestigation of the O-antigens of Yersinia pseudotuberculosis: revision of the O2c and confirmation of the O3 antigen structures

Structures of the O-antigens of Yersinia pseudotuberculosis O2c and O3 were reinvestigated by NMR spectroscopy, including 2D (1)H,(1)H COSY, TOCSY, ROESY, (1)H,(13)C HSQC, and HMBC experiments. The following revised structure of the O2c tetrasaccharide repeating unit was established, which differs from the structure proposed earlier in the glycosylation pattern of the mannose residue at the branching point: where Abe stands for 3,6-dideoxy-d-xylo-hexose. The structure of the Y. pseudotuberculosis O3 antigen reported earlier was confirmed.     

A self-contained system for the field production of plant recombinant interleukin-10

The production of pharmaceutical proteins in plants is creating a broad spectrum of new high-value traits in traditional crop species. As the production of these recombinant proteins moves from bench to field scale, containment and the presence of unwanted secondary metabolites are significant practical issues. We have developed a hybrid male-sterile low-alkaloid tobacco (MSLA) production platform. Recombinant protein is produced in leaves that are harvested prior to flowering. If considered for direct in vivo mammalian use the low-alkaloid background genotype addresses concerns about nicotine, and male sterility further reduces the risk of gene leakage. We have applied this system to the production of human interleukin-10 (phIL-10), a contra-inflammatory cytokine with potential application in the treatment of inflammatory bowel disease and autoimmune diseases. Transgenic low-alkaloid tobacco lines properly assembled a biologically active phIL-10 homodimer. Hybrids made by crossing a single homozygous high-expressing phIL-10 line with a MSLA female were field tested in a high density production system and harvested after 30 days. Recombinant phIL-10 yields were found to be similar in the hybrids and the homozygous control. MSLA tobacco is a practical, self-contained system for the production of plant recombinant proteins.     

Isolation of Polymer-Degrading Bacteria and Characterization of the Hindgut Bacterial Community from the Detritus-Feeding Larvae of Tipula abdominalis (Diptera: Tipulidae)

The Tipula abdominalis larval hindgut microbial community presumably facilitates digestion of the lignocellulosic diet. The microbial community was investigated through characterization of bacterial isolates and analysis of 16S rRNA gene clone libraries. This initial study revealed novel bacteria and provides a framework for future studies of this symbiosis.     

Bacteriophages ofBacillus subtilis: Comparison of different isolation techniques and possible use for classification ofBacillus subtilis strains

When different techniques are used for the isolation of bacteriophages ofBacillus subtilis a number of different phages may be obtained. Furthermore defective phages are found in old cultures of all strains ofB. subtilis tested so far. The possible use of the phages and the defective phages for classifyingB. subtilis strains into a number of groups according to their susceptibility to different phages and according to the presence of certain defective phages in the cells is discussed.     

Pharmacometabolomic signature links simvastatin therapy and insulin resistance

Introduction

Statins, widely prescribed drugs for treatment of cardiovascular disease, inhibit the biosynthesis of low density lipoprotein cholesterol (LDL-C). Despite providing major benefits, sub populations of patients experience adverse effects, including muscle myopathy and development of type II diabetes mellitus (T2DM) that may result in premature discontinuation of treatment. There are no reliable biomarkers for predicting clinical side effects in vulnerable individuals. Pharmacometabolomics provides powerful tools for identifying global biochemical changes induced by statin treatment, providing insights about drug mechanism of action, development of side effects and basis of variation of response.

Objective

To determine whether statin-induced changes in intermediary metabolism correlated with statin-induced hyperglycemia and insulin resistance; to identify pre-drug treatment metabolites predictive of post-drug treatment increased diabetic risk.

Methods

Drug-naïve patients were treated with 40 mg/day simvastatin for 6 weeks in the Cholesterol and Pharmacogenetics (CAP) study; metabolomics by gas chromatography-time-of-flight mass-spectrometry (GC–TOF–MS) was performed on plasma pre and post treatment on 148 of the 944 participants.

Results

Six weeks of simvastatin treatment resulted in 6.9% of patients developing hyperglycemia and 25% developing changes consistent with development of pre-diabetes. Altered beta cell function was observed in 53% of patients following simvastatin therapy and insulin resistance was observed in 54% of patients. We identified initial signature of simvastatin-induced insulin resistance, including ethanolamine, hydroxylamine, hydroxycarbamate and isoleucine which, upon further replication and expansion, could be predictive biomarkers of individual susceptibility to simvastatin-induced new onset pre-type II diabetes mellitus. No patients were clinically diagnosed with T2DM.

Conclusion

Within this short 6 weeks study, some patients became hyperglycemic and/or insulin resistant. Diabetic markers were associated with decarboxylated small aminated metabolites as well as a branched chain amino acid directly linked to glucose metabolism and fatty acid biosynthesis. Pharmacometabolomics provides powerful tools for precision medicine by predicting development of drug adverse effects in sub populations of patients. Metabolic profiling prior to start of drug therapy may empower physicians with critical information when prescribing medication and determining prognosis.