Anti-CLU polyclonal antibody [Biotin]

Supplying dietary zinc in excess of traditional requirements has clear impacts on the gut epithelium, but little research has explored whether similar impacts on the mammary epithelium may occur. Our objective was to determine the effects of supplemental Zn sources, in excess of minimal requirements, on markers of mammary epithelial integrity in blood and in milk as well as the heat stability of milk in mid-lactation cows. Twelve multiparous Holstein cows (132 +/- 21days in milk and 51 +/- 3kg/day milk) were blocked according to milk yield and enrolled in a replicated 3x3 Latin square experiment. Experimental periods were 21days, with 17days allowed for diet adaptation and 4days for sampling. Treatment sequences were randomly assigned to animals and treatments were as follows: (1) 0.97g Zn/day provided as ZnSO4 (34.5mg supplemental Zn/kg diet DM; 30-ZS), (2) 1.64g Zn/day provided as ZnSO4 (56.5mg supplemental Zn/kg diet DM; 60-ZS), and (3) 0.55g Zn/day provided as ZnSO4 plus 1.13g Zn/day provided as a zinc-methionine complex (58.2mg supplemental Zn/kg diet DM; 60-ZM). Treatments were administered once daily as an oral bolus containing all supplemental trace minerals. Rumen-bypass methionine was also included in the 30-ZS and 60-ZS boluses to provide metabolizable methionine equivalent to that provided in 60-ZM rations. Milk samples were assessed for electrolytes, somatic cell transcript abundance of genes related to zinc metabolism, and heat coagulation time. Whole blood samples were analyzed for Na and K concentrations, and plasma samples were analyzed for lactose concentration. Cows fed 60-ZS or 60-ZM had greater zinc intake compared to 30-ZS. Dry matter intake and milk fat content tended to be greater in 60-ZS and 60-ZM cows compared to 30-ZS. Somatic cell linear score was similar among treatments. Treatments neither affected markers of mammary epithelial integrity in blood nor in milk of cows, including plasma concentration of lactose, milk concentrations of Na+ and K+, and SLC30A2 and CLU transcript abundance. Treatments had no effect on milk N fractions or heat coagulation time. This study provided no evidence that supplemental Zn above the established requirements can improve blood-milk epithelial barrier or heat stability of milk in healthy mid-lactation dairy cows.

Dry eye is a common disorder caused by inadequate hydration of the ocular surface that results in disruption of barrier function. The homeostatic protein clusterin (CLU) is prominent at fluid-tissue interfaces throughout the body. CLU levels are reduced at the ocular surface in human inflammatory disorders that manifest as severe dry eye, as well as in a preclinical mouse model for desiccating stress that mimics dry eye. Using this mouse model, we show here that CLU prevents and ameliorates ocular surface barrier disruption by a remarkable sealing mechanism dependent on attainment of a critical all-or-none concentration. When the CLU level drops below the critical all-or-none threshold, the barrier becomes vulnerable to desiccating stress. CLU binds selectively to the ocular surface subjected to desiccating stress in vivo, and in vitro to the galectin LGALS3, a key barrier component. Positioned in this way, CLU not only physically seals the ocular surface barrier, but it also protects the barrier cells and prevents further damage to barrier structure. These findings define a fundamentally new mechanism for ocular surface protection and suggest CLU as a biotherapeutic for dry eye.