Nitrogen transactions along the digestive tract of lambs concurrently infected with Trichostrongylus colubriformis and Ostertagia circumcincta

Twelve lambs, paired on the basis of live weight, were cannulated in the abomasum, in the proximal jejunum approximately 4 m distal to the pylorus and in the terminal ileum. Six were infected with 3000 Trichostrongylus colubriformis and 3000 Ostertagia circumcincta larvae each day for 18 weeks and the remainder were pair-fed to individual infected lambs. All animals were offered ryegrass (Lolium perenne)–white clover (Trifolium repens) pasture, cut daily. Dry matter (DM) intake, live weight, faecal egg concentration, plasma pepsinogen and plasma protein concentrations were measured weekly. During weeks 7 and 17 after commencement of infection, the flow of digesta along the gastrointestinal tract was measured together with enteric plasma loss and true digestion and absorption of ¹²⁵I-labelled albumin in the small intestine. DM intake was depressed by parasitism, being 1331, (se 70), 423 (se 32) and 529 (se 52) g/d during weeks 3, 7 and 17 respectively. The flow of nitrogen at the proximal jejunum and in faeces was increased by parasitism during week 7 and at the abomasum and ileum during week 17. Plasma protein-N loss (g/d) into the gastrointestinal tract was 0.68 (se 0.091) and 1.97 (se 0.139) during week 7, and 0.85 (se0.158) and 1.96 (se 0.396) during week 17, in control and infected sheep respectively. True digestion and absorption of albumin in the proximal small intestine, the site of infection, was very low (mean 0.08) and was not affected by parasitism. Between the abomasum and terminal ileum absorption of albumin was high (mean 0.87) and again was not affected by parasitism. It was calculated that of the total increase in endogenous protein passing from the ileum tract as a result of infection, plasma protein comprised only a small percentage (10–36%). The major proportion of digestion and absorption of protein occurred in the distal small intestine beyond the site of infection and was not affected by infection

NRF2 regulates HER1 signaling pathway to modulate the sensitivity of ovarian cancer cells to lapatinib and erlotinib

NF-E2-related factor 2 (NRF2) regulates the transcription of a battery of metabolic and cytoprotective genes. NRF2 and epidermal growth factor receptors (EGFRs/HERs) are regulators of cellular proliferation and determinants of cancer initiation and progression. NRF2 and HERs confer cancers with resistance to several therapeutic agents. Nevertheless, there is limited understanding of the regulation of HER expression and activation and the link between NRF2 and HER signalling pathways. We show that NRF2 regulates both basal and inducible expression of HER1, as treatment of ovarian cancer cells (PEO1, OVCAR3, and SKOV3) with NRF2 activator tBHQ inducing HER1, while inhibition of NRF2 by siRNA knockdown or with retinoid represses HER1. Furthermore, treatment of cells with tBHQ increased total and phosphorylated NRF2, HER1, and AKT levels and compromised the cytotoxic effect of lapatinib or erlotinib. Treatment with siRNA or retinoid antagonised the effect of tBHQ on NRF2 and HER1 levels and enhanced the sensitivity of ovarian cancer cells to lapatinib or erlotinib. Pharmacological or genetic inhibition of NRF2 and/or treatment with lapatinib or erlotinib elevated cellular ROS and depleted glutathione. This extends the understanding of NRF2 and its regulation of HER family receptors and opens a strategic target for improving cancer therapy

Syracosphaera azureaplaneta sp. nov. and revision of Syracosphaera corolla Lecal, 1966

Here we show that the extant coccolithophore Syracosphaera corolla Lecal, 1966 comprises two consistently different non-intergrading morphotypes characterised respectively by exothecal coccoliths with wide and narrow central-areas. These are interpreted as separate species and so a new species is described, S. azureaplaneta, and a revised description is given for S. corolla

A frotarsius chatrathi, first tarsiiform primate (? Tarsiidae) from Africa

Tarsiiform primates have long been regarded as a Laurasian group, with an extensive fossil record in the Eocene of North America and EuropeI and two important but less well-known records from Asia

Paleoproductivity, ventilation, and organic carbon burial in the Santa Barbara Basin (ODP Site 893, off California) since the last glacial

Biogenic burial rates and coccolith assemblage data were generated for the past 16 ka at ODP Site 893 in the Santa Barbara Basin, off California, to determine if dysoxic events in the basin were related to changes in marine productivity. Coccolith abundance data show that changes in surface water conditions did indeed change in concert with oxygen levels at the sea floor. However, organic carbon burial rates varied independently, indicating that oxygenation of the water column is related mainly to intermediate water ventilation. A strong correlation of organic carbon burial rates with lithogenic, and to a lesser extent with carbonate and opal accumulation rates confirms recent conclusions that the export of organic carbon from the sea surface is largely controlled by the presence of ballast minerals

Sonogashira diversification of unprotected halotryptophans, halotryptophan containing tripeptides; and generation of a new to nature bromo-natural product and its diversification in water

The blending together of synthetic chemistry with natural product biosynthesis represents a potentially powerful approach to synthesis; to enable this, further synthetic tools and methodologies are needed. To this end, we have explored the first Sonogashira cross-coupling to halotryptophans in water. Broad reaction scope is demonstrated and we have explored the limits of the scope of the reaction. We have demonstrated this methodology to work excellently in the modification of model tripeptides. Furthermore, through precursor directed biosynthesis, we have generated for the first time a new to nature brominated natural product bromo-cystargamide, and demonstrated the applicability of our reaction conditions to modify this novel metabolite