Human milk xanthine oxidase and neonatal salivary nucleotide precursors generate hydrogen peroxide; a novel pathway with potential role in regulating oral microflora

Background: Xanthine oxidase (XO) is a complex molybdeno-flavoprotein occurring with high activity in the milk fat globule membrane (MFGM) in all mammalian milk and is involved in the final stage of degradation of purine nucleotides. It catalyzes the sequential oxidation of hypoxanthine to xanthine and uric acid, accompanied by production of hydrogen peroxide and superoxide anion. Human saliva has been extensively described for its composition of proteins, electrolytes, cortisol, melatonin and some metabolites such as amino acids, but little is known about nucleotide metabolites. Method: Saliva was collected with swabs from babies; at full-term 1-4 days, 6-weeks, 6-months and 12-months. Unstimulated fasting (morning) saliva samples were collected directly from 77 adults. Breast milk was collected from 24 new mothers. Saliva was extracted from swabs and ultra-filtered. Nucleotide metabolites were analyzed by RP-HPLC with UV-photodiode array and ESI-MS/MS. XO activity was measured as peroxide production from hypoxanthine. Bacterial inhibition over time was assessed using CFU/mL or OD. Results: Median concentrations (μmol/L) of salivary nucleobases and nucleosides for neonates/6-weeks/6-months/12-months/adult respectively were: uracil 5.3/0.8/1.4/0.7/0.8, hypoxanthine 27/7.0/1.1/0.8/2.0, xanthine 19/7.0/2.0/2.0/2.0, adenosine 12/7.0/0.9/0.8/0.1, inosine 11/5.0/0.3/0.4/0.2, guanosine 7.0/6.0/0.5/0.4/0.1, uridine 12/0.8/0.3/0.9/0.4. Deoxynucleosides and dihydropyrimidines concentrations were essentially negligible. XO activity (Vmax:mean ± SD) in breast milk was 8.9 ± 6.2 μmol/min/L and endogenous peroxide was 27 ± 12 μmol/L; mixing breast milk with neonate saliva generated ~40 μmol/L peroxide,which inhibited Staphylococcus aureus. Conclusions: Salivary metabolites, particularly xanthine/hypoxanthine, are high in neonates, transitioning to low adult levels between 6-weeks to 6-months (p < 0.001). Peroxide occurs in breast milk and is boosted during suckling as an antibacterial system.

A short-term production scheduling methodology for open-pit mines

A multi-resource multi-stage scheduling methodology is developed to solve short-term open-pit mine production scheduling problems as a generic multi-resource multi-stage scheduling problem. It is modelled using essential characteristics of short-term mining production operations such as drilling, sampling, blasting and excavating under the capacity constraints of mining equipment at each processing stage. Based on an extended disjunctive graph model, a shifting-bottleneck-procedure algorithm is enhanced and applied to obtain feasible short-term open-pit mine production schedules and near-optimal solutions. The proposed methodology and its solution quality are verified and validated using a real mining case study.

Valuing the influence of underlying attitudes and the demand for organic milk in Japan

Subjective perceptions about a product affect consumer choice. Accordingly, acquiring the underlying demand characteristics that consumers find desirable is vital for firms planning future marketing strategies. However, the extent to which product-specific perceptions affect consumer choice is poorly understood. New agricultural standards for organic livestock were introduced in Japan in November 2005 and are expected to influence the market significantly. Choice modeling (CM) is used to explore how consumers evaluate the latent demands and conventional attributes (or tangible values) of organic milk. The results suggest that latent demands, along with socioeconomic characteristics and conventional attributes, provide strong incentives for consumers to move from the purchase of conventional milk to organic milk. The analysis indicates that latent demands reflecting the safeness of organic milk, the better taste of organic milk, the image of environmental friendliness in the production process, and the image of the health and comfort of the cows are important factors that influence consumers' purchasing decisions. However, each specific factor has a corresponding conventional tangible attribute that needs to be targeted in marketing strategy.