The WD repeat scaffolding protein RACK1 can mediate integration of the insulin-like growth factor I receptor (IGF-IR) and integrin signaling in transformed cells. To address the mechanism of RACK1 function, we searched for regulatory proteins that associate with RACK1 in an IGF-I-dependent manner. The serine threonine phosphatase protein phosphatase 2A (PP2A) was found associated with RACK1 in serum-starved cells, and it dissociated immediately upon stimulation with IGF-I. This dissociation of PP2A from RACK1 and an IGF-I-mediated decrease in cellular PP2A activity did not occur in cells expressing either the serine 1248 or tyrosine 1250/1251 mutants of the IGF-IR that do not interact with RACK1. Recombinant RACK1 could bind to PP2A in vitro and restore phosphatase activity to PP2A from IGF-I-stimulated cells. Ligation of integrins with fibronectin or Matrigel was sufficient to facilitate IGF-I-mediated dissociation of PP2A from RACK1 and also to recruit ␤1 integrin as PP2A dissociated. By using TAT-fused N-terminal and C-terminal deletion mutants of RACK1, we determined that both PP2A and ␤1 integrin interact in the C terminus of RACK1 within WD repeats 4 to 7. This suggests that integrin ligation displaces PP2A from RACK1. MCF-7 cells overexpressing RACK1 exhibited enhanced motility, which could be reversed by the PP2A inhibitor okadaic acid. Small interfering RNA-mediated suppression of RACK1 also decreased the migratory capacity of DU145 cells. Taken together, our findings indicate that RACK1 enhances IGF-I-mediated cell migration through its ability to exclusively associate with either ␤1 integrin or PP2A in a complex at the IGF-IR.

The scaffolding protein receptor for activated C kinase (RACK1) has been proposed to mediate the integration of insulin-like growth factor I receptor (IGF-IR) and adhesion signaling. Here we investigated the mechanism of this integration of signaling, by using an IGF-IR mutant (

Accumulating evidence demonstrates that dietary supplementation with functional food ingredients play a role in systemic and brain health as well as in healthy ageing. Conversely, deficiencies in calcium and magnesium as a result of the increasing prevalence of a high fat/high sugar “Western diet” have been associated with health problems such as obesity, inflammatory bowel diseases, and cardiovascular diseases, as well as metabolic, immune, and psychiatric disorders. It is now recognized that modulating the diversity of gut microbiota, the population of intestinal bacteria, through dietary intervention can significantly impact upon gut health as well as systemic and brain health. In the current study, we show that supplementation with a seaweed and seawater-derived functional food ingredient rich in bioactive calcium and magnesium (0.1% supplementation) as well as 70 other trace elements, significantly enhanced the gut microbial diversity in adult male rats. Given the significant impact of gut microbiota on health, these results position this marine multi-mineral blend (MMB) as a promising digestive-health promoting functional food ingredient.

Growing pigs can display undesirable behaviours, reflecting or causing poor welfare. Addition of magnesium (Mg) to the diet could reduce these, as Mg supplementation has been associated with improved coping ability in response to stress. This study examined the effect of supplementation with a Mg-rich marine extract-based product (Supplement) on the behaviour, skin and tail lesion scores and salivary cortisol concentrations of growing pigs. At weaning (28 days), 448 piglets were assigned to either Control or Supplement (0.05%) diets in single-sex groups of 14. Four weeks later (c. 17 kg), pigs were blocked according to weight and back test scores. Seven piglets from each pen were mixed with seven from another pen of the same sex and dietary treatment to yield the following groups: control male, Supplement male, control female and Supplement female (n 5 4 of each). This marked the start of the 9-week experimental period. Instances of the following behaviours were recorded in each pen for 8 3 2 min periods 1 day/week: aggression (fight, head-knock and bite); harmful (tail-in-mouth, ear-chewing and belly-nosing); and sexual/ mounting behaviour. Four focal pigs were selected from each pen, and their behaviour was continuously recorded for 2 3 5 min periods on the same day. Saliva was collected once per week at 1000 h by allowing pigs to chew on a cotton bud for c. 1 min. Salivary cortisol was analysed in duplicate by an enzyme immunoassay. Skin and tail lesions were scored according to severity 1 day/week. There were fewer aggressive incidents in Supplement pens ( P , 0.01), and mounting behaviour (performed only by males) was almost three times lower in Supplement than in control pens ( P , 0.01). However, there was no effect of Supplement on the incidence of each of the harmful behaviours. Behaviour of the focal pigs showed no treatment effect on the duration or incidence of aggressive behaviour. However, Supplement pigs spent less time performing harmful behaviours compared with control pigs ( P , 0.001). Supplement had no effect on the occurrence or severity of tail-biting outbreaks or on tail lesion scores. However, Supplement females had lower skin lesion scores, in particular in the ears and shoulders ( P , 0.01). Finally, Supplement pigs had lower salivary cortisol concentrations ( P , 0.01). Mounting is a major welfare concern in uncastrated pigs, and therefore this represents an important welfare benefit of Supplement. Reduced salivary cortisol, in conjunction with reduced skin lesion scores in supplemented females, suggests that addition of a Mg-rich marine extract improved pig welfare in this system.

It is well established that neuroinflammation contributes to brain aging, and that cortical cells are particularly vulnerable. Lipopolysaccharide stimulates the release of the pro‐inflammatory cytokines, tumor necrosis factor‐alpha and interleukin‐1beta from glial cells which consequently induces an impairment in neuronal cell function. The food supplement, Aquamin, is a natural, multi‐mineral derived from the red algae Lithothamnion corallioides, rich in calcium, magnesium and 72 other trace minerals. The aim of this study was to evaluate the anti‐inflammatory potential of Aquamin in lipopolysaccharide‐stimulated, glial‐enriched primary cultures of rat cortex. It is reported that Aquamin prevented lipopolysaccharide‐induced secretion of tumor necrosis factor‐alpha and interleukin‐1beta from cortical glia. These data suggest that nutritional supplements such as Aquamin may play an important role in impeding the detrimental effects of excessive inflammation in the brain. Copyright © 2010 John Wiley & Sons, Ltd.