Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma.

Multiple myeloma (MM), an incurable plasma cell malignancy, requires localisation within the bone marrow. This microenvironment facilitates crucial interactions between the cancer cells and stromal cell types that permit the tumour to survive and proliferate. There is increasing evidence that the bone marrow mesenchymal stem cell (BMMSC) is stably altered in patients with MM-a phenotype also postulated to exist in patients with monoclonal gammopathy of undetermined significance (MGUS) a benign condition that precedes MM. In this study, we describe a mechanism by which increased expression of peptidyl arginine deiminase 2 (PADI2) by BMMSCs in patients with MGUS and MM directly alters malignant plasma cell phenotype. We identify PADI2 as one of the most highly upregulated transcripts in BMMSCs from both MGUS and MM patients, and that through its enzymatic deimination of histone H3 arginine 26, PADI2 activity directly induces the upregulation of interleukin-6 expression. This leads to the acquisition of resistance to the chemotherapeutic agent, bortezomib, by malignant plasma cells. We therefore describe a novel mechanism by which BMMSC dysfunction in patients with MGUS and MM directly leads to pro-malignancy signalling through the citrullination of histone H3R26.

Fatty acid and triglyceride composition of milk fat from lactating Holstein cows in response to supplemental canola oil.

The objective was to determine the influence of dietary lipid on total and sn-2 fatty acid composition and triglyceride structure of milk fat in lactating Holstein cows. Five primiparous Holstein cows surgically fitted with ruminal and duodenal cannulas were used in a 4 x 5 incomplete Latin square. All cows received a basal diet. Treatments consisted of a basal diet with no supplemental canola oil (control), basal diet with canola oil added to the concentrate portion of the diet to provide 1.6% fat, basal diet with 330 g of canola oil infused directly into the rumen, and basal diet with 330 g of canola oil infused directly into the abomasum. Canola oil treatments decreased palmitic acid and increased oleic acid content of milk fat compared with the control. Stearate was higher when canola oil was rumen available compared with control and abomasal infusion. Abomasal infusion increased linoleic and linoleic acids in milk fat compared with the other treatments. The sn-2 fatty acid composition reflected total fatty acid composition. All canola oil treatments reduced palmitic acid and increased oleic acid content at the sn-2 position. Changes in sn-2 composition reflect specificity of the acyl transferases and substrate concentration. Triglyceride composition reported as carbon number was altered by canola oil. Triglycerides in carbon number C50, C52, and C54 were increased while C32, C34, and C36 were decreased.

Ash content of detergent fibers in feeds, digesta, and feces and its relevance in fiber digestibility calculations.

The influence of insoluble ash in diet, digesta, and fecal samples was evaluated. Ash-free values of neutral detergent fiber (NDF) and acid detergent fiber (ADF) for feed, digesta, and fecal samples were compared with uncorrected values of NDF and ADF in two digestibility experiments. Six feed samples were selected at random along with four duodenal and two fecal samples; the latter two were a part of two digestion studies. The silica composition of feed samples was low with the exception of oat hay and rice straw. Ash-free values of NDF and ADF for digesta and fecal samples were lower than uncorrected values of NDF and ADF, and silica accounted for the majority of the differences. The use of ash-free values of NDF and ADF in both digestibility experiments with dairy cows resulted in more realistic digestibility estimates and reduced the amount of variability associated with the calculation of the digestibility of NDF and ADF in the rumen and total digestive tract. The source of the insoluble ash was not identified but could have come from individual feedstuffs or the consumption of sand. Sample contamination by silica and other ash components may influence NDF and ADF composition if the fiber residues are not ashed prior to calculation of NDF and ADF.