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Using mice deficient in hepatic cytochrome P-450 oxidoreductase (POR), which disables the liver cytochrome P-450 system, we examined the metabolism and biological response of the anticarcinogenic flavonoid, quercetin. Profiling circulating metabolites revealed similar profiles over 72 h in wild-type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that two- to threefold more genes responded significantly to quercetin in WT compared with KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling, and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism was predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase 1 detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. metabolite; microarray; nutrigenomics; flavonoid; global error assessment; pathway; systems biology; bioavailability

Bovine milk protein fractions that enable modification of the protein composition and amino acid profile of infant formulas to mimic those of human milk have recently become available. To determine the effects on protein quality and mineral bioavailability of replacing casein by [beta]-casein and of whey protein isolate by [alpha]-lactalbumin, 4 groups of growing rats were fed for 3 wk diets containing 10% protein as 1) casein (control); 2) [beta]-casein; 3) casein:whey (40:60); or 4) [beta]-casein: [alpha]-lactalbumin (40:60). Protein quality, determined as protein efficiency ratio (PER), net protein utilization (NPU), biological value (BV) and protein digestibility (PD), as well as body weight gain, were higher (P < 0.05) with consumption of the whey-adapted diets [casein:whey (40:60); [beta]-casein: [alpha]-lactalbumin (40:60)] compared with the casein diets (casein; [beta]-casein); however, there were no differences between the 2 casein diets or between the 2 whey-adapted diets. Apparent absorption of minerals (Ca, P, Fe, Zn) from the whey-adapted diets was higher than that from the casein diets (P < 0.05); but again, no differences were observed when casein or whey protein isolate were replaced by [beta]-casein or [alpha]-lactalbumin, respectively. Thus, substitution of casein by [beta]-casein or of whey protein isolate by [alpha]-lactalbumin does not affect protein quality or mineral bioavailability as determined in growing rats. KEY WORDS: * protein quality * mineral balance * [beta]-casein * [alpha]-lactalbumin

Examples of chemical defenses and their influence on predator-prey interactions abound in the terrestrial and marine benthic ecological literature. In contrast, considerably less is known about the role of chemical defenses in marine planktonic systems. In this study, we examined the potential for the phytoplankton-produced compound dimethylsulfoniopropionate (DMSP) and its cleavage products dimethyl sulfide (DMS) and acrylate to act as chemical defenses in seawater. Although added DMS and acrylate had no effect on protist grazers, added DMSP reduced grazing on the coccolithophorid Emiliania huxleyi by all four tested species (dinoflagellates Amphidinium longum, Gymnodinium sp., and Oxyrrhis marina and ciliate Coxliella sp.). A. longum and Gymnodinium were highly sensitive to 20-[micro]mol [L.sup.-1] concentrations of DMSP, nearly ceasing to feed, whereas O. marina and Coxliella showed only minor reductions in grazing activity. Grazing suppression in A. longum was DMSP concentration-dependent over the range 0.05 to 1,000 [micro]mol [L.sup.-1] and was also inhibited by added glycine betaine, a structural analog of DMSP. DMSP reduced A. longum grazing by similar amounts on five different algal species, some of which do not produce DMSP on their own. Thus, the efficacy of DMSP as a grazing deterrent appears to depend on grazer species, but not on algal strain or species. Because DMSP does not seem to be toxic, we hypothesize that DMSP and related compounds act as signals for the presence of potentially harmful algal cells. Should such sublethal chemical defense interactions be widespread in nature, they could be important in regulating the composition and biomass of phytoplankton communities.

A 62-year-old man presented to the emergency department with 5 weeks of worsening lower abdominal pain associated with watery diarrhoea, vomiting and 10% loss of body weight. He had recently experienced night blindness. There was no history of foreign travel. His past medical history included hypertension, sickle cell trait and type 2 diabetes well controlled on metformin. He had not been prescribed any recent steroids and denied significant alcohol intake. On examination, he had a tachycardia at 110 bpm and was afebrile and normotensive. He was malnourished with pedal pitting oedema extending to both knees. His abdomen was soft but distended and diffusely tender. Blood tests showed a serum albumin of 12 g/L. Stool samples were negative. HIV testing was negative, and immunoglobulin levels were normal. CT of the abdomen showed thickened, hyperenhancing jejunal loops with diffuse mesenteric inflammatory fat stranding and enlarged mesenteric lymph nodes. Colonoscopy was unremarkable. Enteroscopy showed granular oedematous mucosa and extensive, deep ulcerations. Jejunal biopsies were obtained. Microscopy samples were negative for tuberculosis (TB) culture. Histology revealed inflamed and ulcerated small bowel mucosa with plump endothelial cells with the appearance below. There were no granulomata (figures 1 and 2). Figure 1Endoscopic examination of the jejunum. Figure 2Plump endothelial cells seen on microscopy., Question: What is the differential diagnosis?, Competing Interests: Competing interests: None declared.