Copper physiology in ruminants: trafficking of systemic copper, adaptations to variation in nutritional supply and thiomolybdate challenge

Ruminants are recognised to suffer from Cu-responsive disorders. Present understanding of Cu transport and metabolism is limited and inconsistent across vets and veterinary professionals. There has been much progress from the studies of the 1980s and early 1990s in cellular Cu transport and liver metabolism which has not been translated into agricultural practice. Cu metabolism operates in regulated pathways of Cu trafficking rather than in pools of Cu lability. Cu in the cell is chaperoned to enzyme production, retention within metallothionein or excretion via the Golgi into the blood. The hepatocyte differs in that Cu-containing caeruloplasmin can be synthesised to provide systemic Cu supply and excess Cu is excreted via bile. The aim of the present review is to improve understanding and highlight the relevant progress in relation to ruminants through the translation of newer findings from medicine and non-ruminant animal models into ruminants

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

The trace element and humoral immune response of lambs administered a zinc, cobalt and selenium soluble glass bolus

Zinc, cobalt and selenium are essential trace elements for ruminants and all have roles in immune function. The delivery of these elements to grazing livestock can be problematical. The aim of this trial is to determine the effect of the administration of an intraruminal soluble glass bolus to supply zinc, cobalt and selenium to growing lambs at pasture and to determine the effect on humoral immune response via the administration of a novel keyhole limpet haemacyanin (KLH) antigen. On days 0, 17 lambs each had a zinc (15.1% w/w), cobalt (0.52% w/w) and selenium (0.15% w/w) soluble glass bolus (∼33 g) administered (bolused), whilst the 17 lambs received no bolus (control). All of the lambs were grazed together throughout the trial. Trace element status (selenium—erythrocyte glutathione peroxidise activity; cobalt—serum vitamin B12 concentration; zinc—plasma zinc concentration) and live weights were assessed on days 0, 20, 42 and 63, with immunisation with KLH on day 34 and assessment of IgG response by direct ELISA on days 20, 42, 49, 63. Lambs were slaughtered when commercially fit on either day 86 or 121 and livers analysed for copper and zinc concentrations and boluses recovered from the bolus group to assess dissolution rates. The bolused lambs had significantly increased serum vitamin B12 concentrations (p<0.001) and erythrocyte glutathione peroxidase activities (p<0.001) on all post-bolusing samplings. The bolused lambs had higher plasma zinc concentrations on day 42 (p<0.05) and day 63 (p<0.01). The humoral immune response was enhanced with the bolused lambs having significantly greater anti-KLH IgG levels on day 42 (p<0.05) and day 63 (p<0.01), although the two groups had a similar maximal value at day 49. There was no significant effect of the bolus on live-weight or liver zinc concentrations. The average bolus dissolution rate of the recovered boluses was 326 mg glass/d (s.d.±30 mg/d) giving a mean daily release of 49.3 mg zinc, 1.7 mg cobalt and 0.5 mg selenium. The pasture mineral status was not assessed, but the bolus alone was able to fulfil recommended intake requirements for the elements. In conclusion, administration of a zinc, cobalt and selenium soluble glass bolus resulted in an increased antibody response and fulfilled the daily requirements for cobalt, selenium and zinc with an elevated status of these elements compared to unsupplemented controls grazing the same pasture

The effects of oral drenching with Co or vitamin B12, drenching frequency and Co via rumen bolus on plasma vitamin B12 concentration in weaned lambs

Weaned lambs (n = 88) were stratified by sex and body weight (BW) and allocated at random to 1 of 10 treatments for 12 weeks (consecutive 6-week periods), to evaluate the effects of supplementation with Co or vitamin B12 (B12) on the concentrations of B12 in blood plasma. The treatments were: no supplementation (Control); rumen bolus containing Co only (Bolus); and oral administration of a liquid solution (Drench) containing Co or B12 at intervals of 1, 2, 3 or 6 weeks. One bolus (expected Co release [by leaching] of 0.8 mg/day for 4 months) was administered to the bolus group at the initiation of the study (day 0). The lambs on the drench treatments received totals of 63 mg Co (as CoSO4·7H2O) or 34.5 mg B12 over each 6-week period; drench concentrations were 2.1 mg/ml and 2.3 mg/ml for Co and B12, respectively. The lambs were managed in a rotational-grazing system on predominately perennial ryegrass swards. Blood samples were collected weekly (immediately prior to treatment administration), starting on day 0, and plasma was analysed for B12 and Co. Lambs on the Co-drench treatments had higher B12 concentrations (P 0.05) from these treatments in the second period. Lambs on the Bolus treatment had a higher plasma B12 concentration than Control lambs over the first (P < 0.001) and second (P < 0.05) periods. It is concluded that drenching with Co is more effective than drenching with B12, in terms of the effect on plasma B12 concentration. Drenching with Co at intervals of 1 or 2 weeks was more effective than drenching at intervals of 3 or 6 weeks. While the bolus treatment was effective in increasing plasma B12 concentration compared to Control over weeks 1 to 12, the difference between these treatments declined significantly over time

Eight new T4.5-T7.5 dwarfs discovered in the UKIDSS large area survey data release 1

The definitive version is available at www.blackwell-synergy.com Copyright Blackwell Publishing DOI : 10.1111/j.1365-2966.2007.12023.xPeer reviewe