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00:00:00
of course kind invitation and introduction to my work um today would like to give you brought a and
00:00:08
concise uh overview of overgrown oral viruses in particles
00:00:13
will come up to speed on on bars in general
00:00:16
i'm more voices um i still the human health challenge
00:00:21
oh they are games of the family because see very da
00:00:25
and they are simple non envelope viruses which means that
00:00:29
they are not uh carrying like ants on the services
00:00:33
and they contain a single stranded aren't eight genome
00:00:37
which is surrounded by cats it that is composed
00:00:40
mainly off one major cuts it proteins that we see one protein
00:00:44
it's accompanied by a smaller protein the b. g. two protein which has just standard i see uh functions
00:00:53
uh no viruses together with broader whatever says i'm out the most freak in
00:00:58
the courses of of i really didn't used a cute guy stands right is worldwide
00:01:04
and um this goes to for developing and developed countries
00:01:09
so the numbers given here um maybe not actual
00:01:13
but um it is estimated that how patients um
00:01:17
uh there are seven a point seven million in our industry lies countries and point five million
00:01:24
hospital laceration depend on trees and if he's nine million hospital associations
00:01:30
in developing countries with nearly two hundred thousand deaths per year worldwide
00:01:36
and among children we have uh and only about fifty thousand deaths
00:01:44
um
00:01:46
no one is um are again as a which comprises a six g. two groups uh
00:01:52
do you want to g. six and only the dinner groups want to win for a infect humans
00:02:00
the most predominance plane which correspond to make a infections is she to four
00:02:07
um and in recent years in two thousand fifteen
00:02:11
a new strain emerged which is due to seventeen um
00:02:18
a couple of other gina groups are infecting other
00:02:21
animals for example bits and and and mice and talks
00:02:25
and the simple reason why these of strains are more or less
00:02:30
specific for this p. c.'s is that we have now a real
00:02:34
functional uh animal model for studying human affection in an animal
00:02:41
uh the only animal which can uh serve as an
00:02:44
animal model is also because voiced expresses also a broad
00:02:49
and got group like structures similar to the human structures
00:02:52
and we can use this model in to some extent
00:02:56
um but not for studying infection it's just the
00:03:00
binding of of the virus to the gastrointestinal tract
00:03:10
well as i said the most prevail and strain currently still worldwide it's the g.
00:03:14
two four um strain in particular the the uh the strain which has
00:03:21
emerged first in in australia instead they uh in a two thousand and twelve
00:03:28
and uh during the year of two thousand fifteen in use train
00:03:32
emerged a t. g. to seventeen in particular in in china and japan
00:03:38
these two strains which apparently the most relevant strains in in europe that human infection um
00:03:46
show a characteristic h. distributions um g.
00:03:51
tool uh for but that is infecting laundry
00:03:55
younger children and elderly people whereas the g.
00:03:59
seventeen shows them more broader spreading yeah infection pattern
00:04:05
so it it's claimed that g. two seventeen um has gained high affinity uh for
00:04:11
carbohydrates and uh this may explain his
00:04:14
uh it's a a stronger spreading a efficiency
00:04:22
no one has to i'll start or initiate an infection needs to bind to and and a
00:04:29
pity you miss covered up by a high high like like cause related to like a proteins
00:04:37
on long typical example of these like uh proteins is amusing mark one or using one
00:04:43
uh which is inserted into little crafts um of repeated use else and um
00:04:50
presents oh hundreds of all linguistic rights are only and all because second rights and um
00:04:58
he's only only only the second let's start with the addition of a gal next to the um
00:05:04
i mean last it's irina training and these collect tolls i
00:05:08
mean residues can then be extended it to a core one structure
00:05:13
uh by additional forgot like toes and this one structure then can be for the elongated you to buy
00:05:19
additional study guess which which says that the stop signals of
00:05:23
these structures are dead and products which cannot be elongated anymore
00:05:28
um or um and branches interviews fighter use introduction of the
00:05:34
uh the group are crazy due at the position six altogether like
00:05:38
and this you can proceed use then extend it
00:05:41
to form support probably locked for someone type structures
00:05:45
which can carry at their ends um brought new structures which
00:05:52
contain few crews and uh down that can't get a chance
00:05:57
so these structures also found on those means since which
00:06:00
was actually it's on the gastrointestinal also in the store mark
00:06:04
you're confronted with ease membrane uh boundaries since uh which are
00:06:09
the target sites for the for the wireless and um we
00:06:13
see also secreted news in speech uh form uh this plastic jewels
00:06:19
uh on the surface of the p. c. yeah in prevent a
00:06:23
a direct contact of the viruses and bacteria of course and so they
00:06:29
also express the same structures principally although each meeting digits a creature for example the store mark
00:06:36
as a organ characteristic or like presentation so one of the here since
00:06:42
which is expressed in the in the store markets the mark five a. c.
00:06:46
um and the other one is secreted by did gusty glance this
00:06:51
system works six which shows a very characteristic a distinct like oscillation
00:07:01
um this financial just to give you an overview although the
00:07:06
uh structures which are relevant in the context of this presentation um
00:07:11
drive from either type one structure switches collectibles links to uh
00:07:16
to supplement recalls online or type two structures uh about the linkages
00:07:22
a four to the group calls on mine uh that like the dust constructors all drive from b. by use
00:07:28
of the secret to genie pen if you puzzle transfer
00:07:31
ace which introduces few close to the to positional the collectibles
00:07:35
all by the lewis a specific enzyme which introduces a few close to the sort term the uh goes online
00:07:43
um the structures which are relevant in the context of milk or it was like writes ah phone
00:07:48
models on the left hand side and this is why ostensible that what betty as any evidence on that
00:07:55
a formation of these type two structures which can also be formed um
00:08:02
uh_huh
00:08:05
let me go on um no we also gene for and ineffective uh based on actual compound
00:08:11
the initial compounds beef first thought of our human it all it was sec rights and
00:08:17
the last question that these can be effective competitors of violet season to a. p. c. m.
00:08:26
but the idea is quite simple viruses of multifunctional or
00:08:31
of multi valence electing so on its surface expresses
00:08:36
them multiple copies of the p. t. one protein
00:08:39
and the protruding domains of these p. p. one protein uh
00:08:44
are forming like to like to maine which is able to bind
00:08:48
uh carbohydrates and also on the other side on the t. v. and we have um
00:08:55
the multifunctional like a protein so that this interaction to over come to
00:09:01
it will be a challenge for motivated and short chain carbohydrates but he thought the
00:09:07
and we should have a look at the larger starts was uh expressing more than one few
00:09:13
quotes and uh and to use these larger
00:09:17
structures s. potentially course to integrate this binding process
00:09:25
um the the t. one protein structure is shown on the on the right inside is composed
00:09:31
of three domains the estimate which is a structural core domain and uh this is a bit and
00:09:39
additionally back to for the domains of people on the p. two
00:09:42
protruding domain speech form at the end this a carbohydrate binding a pocket
00:09:51
you are using the this p. u. v. t.
00:09:53
one protein which forms spontaneously to bars like particles
00:09:58
and on the other hand to the diameter of the uh the t. one t. two domains
00:10:04
other this time it was used in crystallography studies
00:10:08
and coke crystallography studies uh with a macaw linguistic rights
00:10:13
rest maybe a virus like particles used exclusively in solid things by means times um
00:10:25
well i'm the coca solicitation was performed with the service
00:10:30
off of me calling the second i see that you find
00:10:33
standard compounds or mixtures of undefined or the the second rights because we
00:10:38
that our initial idea was to see whether um complex
00:10:43
august second right six even the size of of uh
00:10:46
take a cigarettes for example could bind or to their
00:10:50
own liked him of some of them um p. domain
00:10:56
and could in display in the crystal being trapped and these crucial
00:11:01
could then be analysed by it takes way uh an ally says or
00:11:04
by monday most spectrometry so you could be could have been able to
00:11:09
identify joe structures speech were preferentially and trapped in these the progress that's
00:11:17
unfortunately these larger structures never uh i gave a crystal says
00:11:23
to be um had to give up this project and um
00:11:28
you could demonstrate for a couple of viruses bottles strains
00:11:32
of this case here for the two ten the vietnam strain
00:11:36
um that only smaller size or because sec
00:11:39
rights could be cool christa lust and um
00:11:44
here for example to focus the like tools and three for the like tools although they have structurally nothing to do with
00:11:49
with each other uh were able to uh pursue last within a this fall within the pocket
00:11:58
um
00:12:01
on the other hand other structures which have a special relationship to the to focus the like toes like
00:12:07
like the n. new focal parental discipline uh did not a coke rustle us
00:12:17
um the uh
00:12:20
the g. u. group uh g. tool for has evolved within forty years so
00:12:25
in a nineteen seventy four the washing it's p. c.s uh the the bottom constrain uh
00:12:31
which is shown here uh the strange shows as strong um binding to got to base functions
00:12:38
press the uh later evolved city strain front without
00:12:42
those shows diminished binding to a blog today which means
00:12:46
that within these forty years of evolution strain has already
00:12:51
uh changed dramatically and you you see the many uh
00:12:56
occasional changes which have occurred and which um effect in some way the
00:13:01
starter aspects of the binding pocket of the uh v. p. one protein
00:13:08
and uh
00:13:11
this results finally in the orientation or the in
00:13:16
in the different orientation of this loop like structure here
00:13:21
uh in particular um and um two different binding of the
00:13:25
of the two for was locked tolls shown here as an example
00:13:29
so already this these a few imitation changes here uh occurring during forty years
00:13:36
have dramatically changed uh the specificity uh of the binding proof
00:13:43
so the result of this potential changes that uh the dude
00:13:48
you're much strain from two thousand and filth binds much better
00:13:51
to block waged structures and less to broadway structures
00:13:59
also the new he uh much strain uh chief
00:14:02
to seventeen uh shows the unimportant imitation what's been compared
00:14:09
when compared with the first emergence in two thousand to a inside time in japan
00:14:16
and this imitation refers to the replacement of a violin
00:14:20
at four hundred and forty four to eight times in
00:14:24
i'm acting pockets are generally characterised by the phenomenon that they contain
00:14:29
very often a problematic uh that's i mean it's it's i change which are are hiding tons of
00:14:35
and we can speculate that this mutation here has
00:14:39
a made this so buying pocket much more sugar fake
00:14:50
now you can own i'm very interested in
00:14:54
finding a structures with the higher binding potency
00:14:59
uh to the virus like particular uh in the faction off
00:15:03
high mass um basically go second right speech but kindly provided
00:15:07
by claimants comes from the sun um you provided us forty two fractions of high
00:15:14
mostly pounds which we characterised by a two
00:15:18
to six a few goes residents per chain
00:15:24
um what our strategy was based on an area which is the um compost
00:15:30
off in new like the lip it's the right from what it was like rights
00:15:34
these all because the cats have reducing tammy and we can a couple to these germany or
00:15:40
i'm positive i thought on i mean and these new broccoli
00:15:43
bits out an embedded in into a little bit layer and exposed
00:15:48
that complied itching to take his face so busy making this
00:15:52
fashion the situation on it p. c. or service to some extent
00:15:58
and in in this model was which was developed by ten phase
00:16:01
e. in the late eighties um yes usually tried to the um
00:16:09
you showed that we can use this approach um i'm in in this case we
00:16:14
used on the less relevant strangely to ten which is more important in in austin infection
00:16:21
um and we could just demonstrates that one fraction of this complex uh
00:16:27
um i really was most potent and this is a fraction
00:16:31
of mythological segments you off large high mass middle because sex rights
00:16:41
no we did the same to the forty two factions do it um provided by claimants comes
00:16:48
um and the coach demonstrated that all factions
00:16:52
there are active most factions very inactive at all
00:16:55
uh but a couple showed some uh um significant a binding um activity
00:17:08
if
00:17:10
not to to get insight into the structural requirements
00:17:13
in case of the g. two for a binding
00:17:17
uh we use also couple of standard uh compounds like like two focal controls upon it that made you
00:17:22
ice a form and selected focal point those to the with a expressing themselves
00:17:28
and this clearly showed that um the virus like particles could bind to
00:17:34
both block group h. structures but not to the do we say
00:17:37
structure though they some a degree of specificity and this binding um
00:17:44
but um in contradiction to other reports in from other investigate
00:17:50
us uh there is no discrimination between h. one and h. two
00:17:55
um there were reports um form a research
00:17:59
just working in with a separation transfer difference
00:18:03
and then our could show that there is a strict
00:18:07
um discrimination of the virus particles between got older h.
00:18:12
one and h. two and also data from x. ray
00:18:15
analysis which set the same but actually in this uh
00:18:20
maybe moralistic shape uh experiment um these tiny differences in
00:18:27
affinities we're not or did not become visible at all
00:18:31
so the virus like particles does not discriminate between the structures
00:18:40
now the isolated them most the most potent
00:18:45
most binding active uh a sub factions of this
00:18:49
for some of these fractions and state most spectrometry analysis
00:18:54
and which demonstrate that these highly active fractions are
00:18:58
characterised by multiple a few causation up to four
00:19:03
a few calls is better here found in this tech are a sector i don't know nothing right
00:19:10
and uh we could also game structure uh information and the concern to them
00:19:17
type one and type two structures at the ten minutes of this uh branched a structure
00:19:29
but what we saw on the level of the new black related areas uh we could we could use that
00:19:34
a new sense isolated from um dusted use of individuals which had been defined
00:19:40
was respect to the louis since a creature that groups status you could show that um
00:19:47
the virus like particles bound preferentially to that always be structured
00:19:52
to uh uh in case of the lose negative uh material too
00:19:57
that group h. structures but not so much less to would we say
00:20:09
now tried to inhibits the binding off of these
00:20:13
files like particles uh with this series of um
00:20:17
may wanna go sec rights and we started with the uh to focus electrodes which can be uh
00:20:23
refer to as a reference and with a lot of you could kinda all this one
00:20:29
well both showed uh in addition as high concentration so in case of the looked if you put
00:20:35
pen to also one um which is actually you or should be theoretically one of the best binders
00:20:41
we found i see fifty values in the range of fifty million small are or even more
00:20:48
we now have a better data which are not presented here
00:20:52
uh and and i can tell you that all a high
00:20:57
hi i'm asked what it was like that's like like two
00:20:59
foot controls one and that in the respective new i so form
00:21:04
both have these lousy uh affinities obviously in the system
00:21:10
i'm not i'm too for 'cause we like toes and three for good zoo looked always
00:21:15
have i see fifty that fifty values in the range of fifteen to twenty five minimal or
00:21:26
so obviously these these mourn avail and a linguistic rights on less potent in the
00:21:33
a blocking off the bottle binding and this could be due
00:21:37
to the valence e. of the lectern on the one side
00:21:40
and the other agency of the audio sec rights um in case of they get up if you use so if it's
00:21:49
so the question is how can be compete with
00:21:51
these that this motivated uh components inside the system
00:21:58
and uh this is an artificial or approach so to say be
00:22:04
thought we use a scaffold like office cycled extreme and couple to this set aside
00:22:09
would explain should was arrested use simply by an s. it's reversion technology yeah and
00:22:18
the few pros was shown a by but relation announces but you see him is
00:22:23
to be linked exclusively to the six position of the group calls in this ring structure
00:22:29
and the ship was whistling i'll funk like physically on mostly
00:22:33
uh on the basis of and um are are under license
00:22:38
so we could isolate that he and a mono
00:22:41
to access substitute its derivatives input to test these
00:22:45
and the s. binding inhibitors and you could see that um the
00:22:51
degree with the increased ugly off of substitution the was it
00:22:56
um tremendous increase in efficiency of blocking
00:23:04
so obviously the bail in c. is the most important point and uh that you will
00:23:08
agree with me that the structures shown here have nothing to do with the block structures
00:23:14
uh in a or an on under the fumes so it's just a few goes
00:23:18
which is important and this few close ah should be presented in a motivated fashion
00:23:26
and this led us to the question whether there could be other compounds in h. uh
00:23:31
which could substitute for these uh a block
00:23:35
group a specific structures in the book and um
00:23:40
be found um these um for cons of widens
00:23:45
uh which are expressed in sorry in many um
00:23:50
mclean invertebrates and and the cell walls of many brown already in
00:23:56
particular in the full contests and to let me know the obvious
00:24:00
he's a white consultants rice by long the chains what do we have a
00:24:06
core can be either completely composed of a few goes only or it can be
00:24:13
a a repeating few clothes and got tools are you the one three or one falling to
00:24:19
here is a structural model of the full who's physicals foot wide and
00:24:24
which is cancerous by a high degree of salvation so every
00:24:27
second because of this structure it's you concentrated it's soft sulfate
00:24:33
so these uh widens on on for some time and um they have been shown to exert
00:24:40
a multitude of bile activities among others on to
00:24:43
call active and and and it from barbecue activity
00:24:46
on the two weren't in you know model battery
00:24:48
actually and so on and some others also antiviral activity
00:24:54
for example of the polio virus adding virus and against the h.
00:24:59
i. v. and subtle made a lot less and have the simplex parsons
00:25:04
but i have to say all these other effects have nothing to do with the
00:25:09
binding competition so the mechanism he is completely different and it's
00:25:14
totally dependent on a solicitation of the white and
00:25:23
now we have tested various forms of widen as a
00:25:27
competitor of the viral binding to guess stick news since
00:25:33
and you could demonstrate that it is highly effective um as a competitive either in the native form or in
00:25:39
a d. sulfate it and partially fragmented form so you
00:25:43
can see here the the masses of a partially fragmented uh
00:25:47
form which has been generated by um so what license
00:25:54
and you see a partial structural those on a good segue
00:25:57
right show here um which were highly active in the system
00:26:10
but interesting leave an e. um hum
00:26:14
tried to and trap you what it was like right generated from a four by then
00:26:20
i'm in a nickel crystal with the um t. domains of the virus
00:26:27
we could demonstrate that only she calls uh shows up in the binding pocket
00:26:33
so this is exactly what we had expected um there's a
00:26:37
strong effect but is effective nothing to do with the specificity
00:26:41
uh um it's just a few goes registering to so it's
00:26:45
a no affinity binding but the high i think d. t.
00:26:53
the slide just shows the concentration dependency of the
00:26:57
effects which should be seen in a competitive uh system
00:27:03
and this like maybe interesting because it demonstrates that a viral particles
00:27:09
ah uh able to survive in somebody it even at
00:27:14
lower page conditions as they are given in the stomach
00:27:17
so down to th two point five they are quite active uh actively binding to get sick nuisance
00:27:27
kentucky are testing a variety of different preparations off we're for quite in
00:27:32
from difference pieces of course which is not shown here on the slide
00:27:36
and a or b. or comparing the fuel stuff with the more to refine stop
00:27:41
because proof occasion means that the soul solvents have to be use that oxidation um
00:27:49
uh processes aren't portion or these things and all
00:27:52
these uh chemical treatments have influence on the activity
00:27:59
no
00:28:00
this is one of my last slide um we are currently trying
00:28:05
to establish or as a as a model for binding or a combination
00:28:10
of of the virus particles in the gastrointestinal tract of these animals
00:28:15
um he could demonstrate um that actually the
00:28:21
the strains g. one g. two four are accumulating
00:28:26
and the system but interesting the not the g. two
00:28:29
seventeen cover exactly strain although this has been claims
00:28:33
to have a higher affinity to i'm not like structures
00:28:38
but obviously the but like structures a wreck transfer this train on not expressed in or is that
00:28:48
um we have already initial data and in this model and the can
00:28:53
tell you that um there is um a certain degree of inhibition
00:28:58
exerted by two full 'cause it looked goals the mid august sec right
00:29:02
in this instance all principally this model can can work
00:29:08
um let me sum up what we have done the you have shown the that the binding
00:29:15
of g. q. for the keys to human classic new since it's a sugar dependent
00:29:22
um the most important issue in this event is the few goes in block
00:29:27
h. one and always be related to a human being calling the sec rights
00:29:33
however the affinity of this specific interaction or at least a parent infinity
00:29:38
it is quite low in the system because of the multi latency halfway into reckless
00:29:45
the i. c. fifty values on the range of twenty
00:29:48
to sixty million more modal for these um tested middling segments
00:29:53
um we have demonstrated the latency important of uh what importance of the
00:30:00
valence e. effect in an artificial few caused intimate uh with these compounds
00:30:06
and have demonstrated that uh put a few courses so like the four wide and and for quite
00:30:12
and you lived um the only go if you poses are potent inhibitor this off a viable binding
00:30:21
the salvation of full time does not play any role so the mechanism of this
00:30:26
uh i'm inhibition is completely different from other vital in addition
00:30:34
okay
00:30:36
i think you and i just would like to
00:30:39
mention might collaborate assault shorten endlessly models of from mannheim
00:30:44
who are are doing these uh voiced experiments land huntsman who is responsible for the um
00:30:52
i'm cool it's radical crystallography uh stephan yellow vinyl provided a couple of uh
00:30:59
um with all because like writes ten face he was involved in the initial
00:31:03
uh you can go directly but every human screens for providing the
00:31:08
uh the only goes across of high mass and start all this the
00:31:12
us from the university of cologne at for performance of any more work
00:31:17
thank you for your touch how thank you very much
00:31:24
this paper is no help for discussion yes and that
00:31:30
uh_huh uh i thank you very much for the presentation i remember yeah yeah um
00:31:38
she fifty years ago so ah m. r. and they study the m.
00:31:44
there's been didn't make ah whole binding on or wires i found that
00:31:49
that was not the solar below because i arrives the mold inhibitor factors were actually did
00:31:55
you like corporal dance and what they're having that was using ten miles last emanate alive right
00:32:01
what they have in common is the tandem repeats that our local selected you have a comment on the of course
00:32:10
exactly in line with what i said before so that like approaches
00:32:14
it politically the musings of the much better competitors because the on motivations
00:32:20
and um in particular mock one which is one of the most related nuisance in in human okay
00:32:27
big rubber membrane it's some most important uh glycol
00:32:31
protein it's also secreted it's it's also shift from that
00:32:34
membrane defined it in high amounts in induction also in in the way of them
00:32:40
built on a lot of structural work in the late eighties on on this
00:32:43
museum and actually this missing would be a better player in this is about
00:32:50
not the motivated sequence
00:32:53
well i was actually thinking
00:32:56
is the fact that they had handed p. that are also they have
00:33:01
them in different fine lines on the same program i think that's a
00:33:04
yeah my one has for example up to one of the twenty
00:33:08
repeats yeah definitely does it transmit peptide and despite that contains five
00:33:13
a theoretical hold like switched positions they are not all substituted best
00:33:18
most of them so you can end up with hundreds of the set
00:33:22
very complex very into jeez of course but my movies also the spot complex is
00:33:31
uh_huh
00:33:32
other questions that are that are just other quick calculation is that was twenty to
00:33:38
fifty million dollar right so that would be ten to fifteen grams earlier off holiday so
00:33:45
which is exactly what we haven't human so totally chemical exactly
00:33:49
the right told us that so if we think of human milk
00:33:52
not just being one individual component but having struck a protein satisfaction
00:33:57
with it's having some antibodies every all kinds of other defence mechanisms
00:34:02
i would argue that it's not one particular compound that has the the fact that the interplay
00:34:08
of all of them together so if you add these all because a great and maybe it's only
00:34:14
eh in the ten million dollar range that it's attractive or five maybe moderation so when far
00:34:19
away from the i. c. fifty but together with all the other components it might actually make sense
00:34:25
actually we have no and i'm the kind of test these compounds and
00:34:28
this so we have just these artificial systems and we need to stick to
00:34:32
these should yeah i think it's it's a good argument that milk is
00:34:36
not just the somewhat different components it's it's a it's an orchestra really off
00:34:41
of multiple different defence mechanisms that play together but not augmenting
00:34:45
totally against the idea that will because the courts could make
00:34:49
the race so for example to focus lock tools is
00:34:52
tolerated by no doubt person up to twenty grams per day
00:34:58
this is enough
00:35:06
more questions about the hamish yes but over
00:35:12
a a
00:35:14
i just was wondering whether so unique about the vice chair in the context
00:35:18
of us and do you she no no less infections in an easy animals also
00:35:27
no not um well or is there has one advantage what we know that those um
00:35:34
or or what is the speech or expecting or accumulating you know it's the agenda we also infections in humans
00:35:42
so this is known for a long time source to came initially to on might because this is the norm trait
00:35:52
press pick for example have other the strains so they have the g. d.'s restrains and the
00:35:59
doc savage constraints so conned conned use any of these because they are not infections in humans are
00:36:09
she noah's outbreaks on on on cruise ships for example
00:36:13
a lot so they they need any particular relationship to uh
00:36:19
two yeah this could be
00:36:29
any other questions
00:36:35
if you know the i suggest we take a coffee break we were ah
00:36:39
yeah admirably hourly not value has an

Conference Program

Milk Oligosaccharides - Structure and Function
Prof. Lars Bode, University of California San Diego, CA | USA
Sept. 25, 2019 · 8:05 a.m.
922 views
Effects of Milk Antibodies and other Proteins on the Commensal Flora
Vanessa Dunne-Castagna
Sept. 25, 2019 · 1:58 p.m.
630 views