Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis

The Golgi enzyme beta1,6 N-acetylglucosaminyltransferase V (Mgat5) is up-regulated in carcinomas and promotes the substitution of N-glycan with poly N-acetyllactosamine, the preferred ligand for galectin-3 (Gal-3). Here, we report that expression of Mgat5 sensitized mouse cells to multiple cytokines. Gal-3 cross-linked Mgat5-modified N-glycans on epidermal growth factor and transforming growth factor-beta receptors at the cell surface and delayed their removal by constitutive endocytosis. Mgat5 expression in mammary carcinoma was rate limiting for cytokine signaling and consequently for epithelial-mesenchymal transition, cell motility, and tumor metastasis. Mgat5 also promoted cytokine-mediated leukocyte signaling, phagocytosis, and extravasation in vivo. Thus, conditional regulation of N-glycan processing drives synchronous modification of cytokine receptors, which balances their surface retention against loss via endocytosis.     

Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of T cell immune responses whose mechanism of action is the subject of debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that CTLA-4 can capture its ligands from opposing cells by a process of trans-endocytosis. After removal, these costimulatory ligands are degraded inside CTLA-4-expressing cells, resulting in impaired costimulation via CD28. Acquisition of CD86 from antigen-presenting cells is stimulated by T cell receptor engagement and observed in vitro and in vivo. These data reveal a mechanism of immune regulation in which CTLA-4 acts as an effector molecule to inhibit CD28 costimulation by the cell-extrinsic depletion of ligands, accounting for many of the known features of the CD28-CTLA-4 system.     

The impact of boreal forest fire on climate warming

We report measurements and analysis of a boreal forest fire, integrating the effects of greenhouse gases, aerosols, black carbon deposition on snow and sea ice, and postfire changes in surface albedo. The net effect of all agents was to increase radiative forcing during the first year (34 +/- 31 Watts per square meter of burned area), but to decrease radiative forcing when averaged over an 80-year fire cycle (-2.3 +/- 2.2 Watts per square meter) because multidecadal increases in surface albedo had a larger impact than fire-emitted greenhouse gases. This result implies that future increases in boreal fire may not accelerate climate warming.     

A retrospective investigation of feline gastrointestinal parasites in western Canada

Between 1998 and 2008, feline fecal specimens were submitted to provincial veterinary diagnostic laboratories in Regina and Saskatoon, Saskatchewan, for sucrose centrifugation-flotation (n = 635), parasite identification (n = 17), and/or Giardia (n = 283) or Cryptosporidium (n = 266) commercial direct immunofluorescence assay (IFA). The most commonly detected parasites on flotation were Toxocara cati (4.7%), Isospora (3.8%), and taeniid eggs (Echinococcus or Taenia) (1.3%). Cats less than 2 years of age were twice as likely to have a positive parasite test as cats older than 2 years. Using IFA, Giardia was detected in 9.9% of samples, and Cryptosporidium in 2.3% of samples. Relative to IFA, flotation had sensitivity values of 39% and 50% for detection of Giardia and Cryptosporidium, respectively. Giardia and Isospora were detected in a higher proportion of samples in our study population than reported in the general cat population in western Canada. This study highlights the importance of sensitivity when interpreting diagnostic tests and provides information to guide region-specific recommendations for helminth parasite prevention and treatment.     

Effect of Restricted Pasture Access on Pasture Dry Matter Intake Rate,Dietary Energy Intake,and Fecal pH in Horses

Eight mature horses were used in a 4 × 4 Latin square design to determine the effect of restricted pasture access on dry matter intake rate (DMIR), energy intake, and fecal pH. Horses were randomly assigned to one of four groups (HGRPs), each containing two horses. HGRPs were randomly assigned to one of four treatments consisting of 3, 6, 9, or 24 hours of pasture access, for a period of 7 days. Treatments were switched every 7 days. The 3- and 6-hour groups were fed free choice mature grass hay while not grazing. Daily pasture dry matter intake (DMI) for each HGRP was estimated by calculating the difference between initial herbage mass of the grazing cell before grazing and residual herbage mass after 7 days of grazing. Total dry matter intake was the sum of pasture and hay DMI for the 3- and 6-hour treatments. Fecal pH was measured on day 7 of each period. Response variables were analyzed using analysis of variance for Latin square design. Restricting pasture access decreased mean pasture DMI (P = .02), pasture dietary energy (DE) (P = .02), and fecal pH (P < .001), but increased DMIR (P = .02). Mean total dry matter intake was not different (P = .16) among treatments. In conclusion, restricting pasture access accelerates pasture DMIR and decreases fecal pH, and although restricting pasture access decreases DE intake from pasture, it did not result in a decrease in total DE intake for horses having ad libitum access to hay.     

Sensory properties and aromatic composition of baked snacks containing brewer's spent grain

The incorporation of brewer's spent grain (BSG) into baked snacks (crispy-slices) was investigated in terms of nutritional, sensory and aromatic properties. Wheat flour was replaced with BSG at the levels of 10, 15 and 25%. Snacks containing 10% BSG exhibited high Crispiness index (Ci), low Crispiness work (Wc) and a high number of peaks during texture analysis, indicating that the crispiness of the samples was not negatively affected. However higher levels of BSG affected the texture and the crumb structure of snacks and the results were significantly different to the 100% wheat control. Addition of BSG altered the odour profile of the snacks as shown by the volatile profiles, however sensory results indicated that BSG-containing snacks at a level of 10% were highly acceptable and highlighted the possibility of using BSG as a baking ingredient in the formulation of enhanced fibre baked snacks.     

Domoic Acid Improves the Competitive Ability of Pseudo-nitzschia delicatissima against the Diatom Skeletonema marinoi

Because domoic acid, a neurotoxic secondary metabolite produced by marine diatoms in the genus Pseudo-nitzschia, is hypothesized to be part of a high affinity iron uptake system, we investigated whether domoic acid could improve the competitive ability of Pseudo-nitzschia delicatissima, and whether the availability of iron changed the outcome of competition experiments. We found that domoic acid had a slight negative effect on growth of the diatom Skeletonema marinoi when it was grown in monocultures. However, when S. marinoi was cultured with P. delicatissima the presence of domoic acid resulted in a reduction of S. marinoi cells by up to 38% and an increase in P. delicatissima cell numbers by up to 17% under iron replete conditions. Similar effects were not observed in low iron treatments. Domoic acid was not taken up by P. delicatissima cells. Overall, our results indicate that domoic acid can improve the competitive ability of Pseudo-nitzschia spp. and that iron is likely to be involved. This study provides an unusual example of indirect inhibition of competitor growth mediated by a secondary metabolite.