[Music] some questions from the audience I yep there's one already you guess how bitter it is stimulating the it shock protein expression to be to be honest I realized this literate data a long time ago so have no precise idea on on the doses no I could not tell you but so feeling I have now is that our number of responses to beauty right but are really those dependent but for a number of them they are not fully those dependent those dependent for a given set of range of concentration and when we could reach a plateau and in maybe in your talk we could see also at this for systemic effects on systemic effects is if I remember they could have a kind of inhibitory effect at I doses so this probably does not provide very clear pictures to the question of which those who use the application level etc but it's a complicated I think area it would depend on the function we want to to boost or the effect the final effect we would like to see here some questions using the the app here can we use expression of the intestinal alkaline phosphatase as a marker of inflammation and in fact if so well that what level of the gut we're in the gut gene expression is one thing personally as all the fashion biochemist I rely more on the activity of young time well that's the first thing the second thing is that as I told you this Ann's ami is produced I amounts in in the small in all along the small intestine who depend on species for pigs it's all along the small intestine for rats and rodents in general it's more in the upper part but and interestingly part of this enzyme and enzymes TVT are still found in stools or in feces okay and where our finger now two papers in humans showing that it could be a good indicator of inflammation of more discriminating between for example control versus diabetic or pre-diabetic patients okay okay so it might be a kind of marker of interest another question there is someone asked what is the recommendation how to increase intestine alkaline phosphatase or is there a rationality to do it that's one secondly how we would you do that yes so as a nutritionist after having reviewed all these biology of his ons I'm I looked at the nutritional factors that would answer the expression and or activity of this enzyme and in fact you can see my previous reviews that many nutritional factors that fathers who are very important for for animal production I would say for example calcium is a strong stimulant of Vuitton's on and in fact the ratio between calcium and phosphorus are important to optimize the the activity of the emblem and in fact the under control the intestinal absorption of calcium that's one thing and when at the bone level is the other form the bone either form of alkaline phosphatase that is also deeply involved in in the model modeling of the bone of the yes growth and Christian and disappearance are all these plasticity of the bone then of nutritional factors recently a finger two or three years ago a group from Boston showed that we all of us know that omega-3 fatty acids have strong anti-inflammatory effects and we showed in the appropriate transgenic mouse models that it would be the presence of incorporation of these omega-3 fatty acid into the internal Seidman brain that controls the expression of the join of intestinal alkaline phosphatase which would mean that at least part of these anti-inflammatory effects of Omega free fatty acid stem in the boost of intestinal alkaline phosphatase and there are plenty of examples other questions from the audience still kindness activity which can count action to not kind kinase phosphatase okay normally you have a to phosphorylation right you have your phosphorylation yes and this enzyme like an IP IP yes it's a tip phosphoric right yeah and I I just wondering how what's the specificity that's one question the other one is still like count action like a kinase activity which can put enough force for a back to not substrate to regulate the activity yeah what I remember from this story at least from a very earlier papers is that alkaline phosphatase is no not only for difference for relating but also for phosphorylating a number of molecules okay and when the specificity I don't think this enzyme has a very strong specificity but it's very active okay one question I was wondering because you have a lot of let's say toxic between brackets substances in the girl to you FLP ask you a lot of things that activate so like receptors especially in chickens is probably important because you always have got damage of mycotoxins you've always cookie do this one would it make sense to actually add enzymes that let's say break down these components it would it make sense to add enzymes like alkaline phosphatase that's what we're doing scientist and so won't adjust administer it in feet yes of course we are already examples I can tell you or to two of examples of us first ones are set up in experiments with rodents for example every time you add the exogenous interesting alkaline phosphatase most of the experiments have been done with the ones from the bovine small intestine because by the way bovines have got seven copies of this gene in the small intestine compared to one copy in carnivores for example and everytime you you you provide this enzyme either orally are systemically in the blood then you can either prevent negative effects of given treatment for example even high-fat diets you can prevent the development of metabolic syndrome and all these things but if you add this after the animals have got the the syndrome you can reverse it okay which really indicates it's a really potent enzyme and the other example is in humans that have been shown by groups medical groups in Iran that so following sepsis the first organ that I will say collapses is the kidney and they have been able to prevent kidney breakdown I would say that I'd miss doing bovine intestinal Italian phosphatase systemically in patients so when they move to because of the risk of contamination for animal products okay they produced of an engineered chimeric intestinal alkaline phosphatase with the active site of them being the intestinal isoform from humans and the crown part of the of the enzyme which provides stability facing for example digestive enzyme coming from a placenta because the placenta is not also specific isoform which is very resistant to any forms of degradation and now this I think this is has been start to be used in the clinical trials but have not seen recently papers coming from this now this is a story maybe I can add a third example a bit aside from this that it might make some Ling with other questions about alternatives to antibiotics for example we've been also a paper data work done in Belgium 20 years ago showing that the strength of Saccharomyces cerevisiae baladi does produce alkaline phosphatase that are really able to detoxify so the first for late LPS etc so this might be one example of enzyme coming from now the microorganism but can also help I was already wondering for years how enter always working sorry this is the intro Rd this is the yeast yes is it someone in for final question yes you talks about in order to maximize the phosphatase alkane enzyme the calcium phosphorus you are you referring to this ratio in Phaedo in a plasma no in in feed in feeding feed and are you talking about your channel total to social or digestive to be honest I have not the data in mind but if you look at my reviews we found the papers that were published on on this matter okay yes because now as you will now formally using features it might change if you are referring to torture to tortures of the duration yeah I understand okay thank you sorry that you will find I can have a look at me tell you okay thank you for a great presentation thank you thanks