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Prof Trevor Marshall
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I will be Chairing the workshop on Medical Metagenomics at the Metagenomics 2007 conference, upcoming next week Conference 11-13 July 2007 at UCSD. The program can be found at
http://research.calit2.net/metagenomics/program2.php

My poster presentation will be "Bacterial capnine blocks transcription of human antimicrobial peptides"

Last year there was a live webcast, but even if there is one this year, I don't think the workshops will be included in that event. Keep an eye on this thread, and I will post the URL if any live feed is available.

Metagenomics is the understanding of communities by studying their (collective) genomes. Studying what we call the "pea soup" of pathogens, understanding that individual species are in a state of flux (due to horizontal DNA transfer) and therefore individual study is somewhat pointless...

I have already posted the links to last years' (2006) conference program, and some of the video presentations which are online, at an earlier topic here:
http://www.marshallprotocol.com/forum39/9391.html

The URL for the live 2007 webcast is http://rpvss.ucsd.edu:8080/ramgen/broadcast/live.rm

The PDF of the conference program is at URL http://metagenomics.calit2.net/files/Metagenomics2007Program_lowres.pdf

The conference starts tomorrow (Wednesday, and goes through to Friday.

Enjoy!

..Trevor..

Last edited on Tue Jul 10th, 2007 17:36 by Prof Trevor Marshall

Jim N
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Capnine immediately reminded me of taurine, because as it turns out, capnine is an alkyl derivative of taurine.  Have you considered an interaction between taurine and capnine transport and/or signalling, or whether capnine enters cells on the taurine transporter?

Prof Trevor Marshall
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Jim,
I understand you are new here, so we need to flash back in time a little. The key realization we made back in 2001 was that the pathogenic bacteria which cause Th1 disease are already living within the phagocytes. Thus there is no need for any transport mechanism through the cytoplasmic membrane. The pathogens, and any RNA they produce, are immediately available to the ribosomes, and to the nuclear receptors which transit the cytoplasm (most of the NHR type 1).

Secondly, the ligand binding pockets of these Nuclear Hormone Receptors generally only bind stably to larger molecules. There is significant movement of the protein configuration with time, there is oscillation of the enclosed water molecules, and indeed, other small biological molecules as well (please look at the dynamics video linked from the abstract above). Thus, in order to retain a high affinity for the receptor configuration, the ligand generally has to be much larger than taurine.

I haven't had time to compute taurine yet, and I would rather have hoped that you could present me with your own docking data so that I don't have to go to that effort myself. After finding a high affinity static configuration one must then check that the molecule is stable in the LBP. That is where the Molecular dynamics comes into play. You will note that the abstract linked from my message above emphasizes that a stable configuration is maintained by capnine during dynamic simulation. Small molecules tend to be too easily "bumped" by the water molecules moving around in the LBP, and lose any stability they may have seemed to exhibit in a static configuration.

I hope this helps.
Trevor

wrotek
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When i looked at these photographs of bacteria inside immune cells i had no idea that i have no idea how complex interactions between bacterial proteins and cell metabolism must be, untill i saw this movie.

Cells seem to be so small but from their dimensions It is an entire new world.

"The inner life of the Cell" artistic with nice music.


"The inner life of the Cell" full lenght with descriptions.
 


At time 3:36 to the end You can see ribosome protein synthesis, ribosomes which bacteria also have and need in order to survive inside immune cells, and which we block with antibiotics.

Dr Marshall said

The Ribosomes only make proteins. This is a lipid, and a highly processed lipid. Enzymatic activity is what creates it. That is why a full-genome search is futile - gene transcription analysis doesn't take into account the enzymatic actions. However, enzymes start as complex proteins, and so by blocking the ribosomes we block the ability of the bacteria to form capnine.
At 1:17 until the end, there is a nice GPCR receptor showed.


Better visualization of how ribosome works from inside i found here



This video presentations makes understanding much easier.

Good luck Dr Marshall with Yours presentation, i see new nice photrographs on poster :)

IngeD
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Thanks Wrotek. Beautiful and fascinating ! Inge.

wrotek
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Yes Inged, we are cool machines, aren't we :)

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Wrotek - great videos!  Thank you.  Do you have a motherlode of these somewhere? 

wrotek
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Hi John here is better quality version http://tinyurl.com/qjjrx

 I will look if there are better versions.


Here are some technical stuff how video was created http://www.studiodaily.com/main/technique/tprojects/6850.html

Last edited on Sat Jul 7th, 2007 08:59 by wrotek

Jim N
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I wasn't suggesting taurine binds to the VDR.  My proposal is that capnine may block taurine transport and/or signalling because it's a taurine derivative. 

Taurine is a player in cellular immunity.  See Schuller-Levis and Park for a review of taurine and immunity.  You may also want to look at Marcinkiewicz vis-a-vis Taurine-Cl and IL-2 production.  Also, Petrosian suggests taurine is a universal carrier for lipid soluble vitamins.  If that is true, cellular depletion of taurine might reduce Vit D availability.  This brings up the question: Is the concentration of Vit D reduced inside the cells by sarcoidosis even though the plasma concentration is increased?


Taurine and Taurine-Cl (chloramine) are actively concentrated in many cells types to 10's of millimolar.  So, even if you can show that capnine binds to the VDR, you can expect additional effects if it blocks the taurine transporter.

I don't know if this makes sense as a source for sarcoidosis.  You'll have to tell me that.  I'm going to spend some time over the next couple of weeks to look at taurine and immune modulation (both are subjects I'm studying, for other reasons).  I'll let you know if I come up with anything more substantial.


 


Prof Trevor Marshall
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Jim,
It sure sounds like you are terribly confused about the Th1 pathogenesis we have elucidated. Have you had a chance to watch my presentations on our "Science" DVD? They explain the basics pretty well, I think.

Don't get tied up in complexities. These are fundamentally simple diseases for someone like you to understand. But you will need to set aside many pragma, such as those you cited. They are just plain wrong. Totally on the wrong track.

..Trevor..

Frans
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Trevor, there's a question that has been on my mind for some time now, so here it goes.

We know that (a part of) the AMPs and Beta defensins are regulated by the VDR. Are there any other receptors that have been identified in regulating the other AMPs and beta defensins?

If so, are they susceptible to the high concentrations of capnine, 1,25D and 25D?

In other words: do the high levels of capnine, 1,25D and 25D in the cells also hamper the rest of innate immunity (through other receptors)?

Sincerely, Frans

Last edited on Sat Jul 7th, 2007 12:02 by Frans

Prof Trevor Marshall
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Frans,
This issue is covered in my latest paper, that I can't release yet, since it is in a print-publication (not a web-publication).

You will recall that I isolated a number of type 1 receptors as being affected by 1,25-D. If you look through Brahmachary, et al,  you will see they are all involved in generating antimicrobial peptides.

Brahmachary M, Schönbach C, Yang L, Huang E, Tan SL, Chowdhary R, Krishnan SP, Lin CY, Hume DA, Kai C, Kawai J, Carninci P, Hayashizaki Y, Bajic VB. 2007. Computational promoter analysis of mouse, rat and human antimicrobial peptide-coding genes. BMC Bioinformatics. 18;7 Suppl 5:S8.
http://www.biomedcentral.com/1471-2105/7/S5/S8

When the VDR is blocked by the bacteria, the hormone 1,25-D builds up to high levels in the body. The levels accumulating in the cytoplasm of infected phagocytes are high enough to allow it to affect expression of antimicrobial peptides by the alpha-Thyroid and Glucocorticoid receptors, and probably by the Androgen and Progesterone receptors too.

There is logic and beauty in the way the human immune system works. In the delicate balance of hormones which weave the tapestry of life :)
 

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Do you suspect that these immunosuppressive effects of elevated 1,25D are the reason that some folks with TH1 disease report that prior to the MP they felt better in the summer or when getting a lot of sunshine?

Also, is there a simple explanation for why the increased 1,25D levels from sun exposure affect us in so much more of a negative way when we are on the MP versus prior to starting treatment? 

Congratulations on the abstract for the conference and the paper for the journal and all the work that went into those.  I hate to think where we would all be without the MP.

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THE EFFECT OF SUNLIGHT/DAYLIGHT AND BRIGHT LIGHTS

Why are my symptoms more intense after exposure to light &/or Vit D?

Why do I feel better in the summer? And worse in the winter?

jrfoutin
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John and Wrotek,
More videos from the Harvard group. Eye candy + discussion of where analyzing proteins fit in the scheme of things. Also Extravasation. Different Myosins.--JRF

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Meg:

in this link: Why do I feel better in the summer? And worse in the winter?

is this statement:

Blocking Angiotensin II removes the final hindrances to your body's ability to kill these bacteria.

That can't be our current understanding, is it?  -john

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You are correct. That statement is outdated and the information will be updated. Dr. Marshall has written:

"As you know, we have shown that the ARBs, as a class, have a wide range of activity in the Nuclear Receptors, quite distinct from their intended target, the Angiotensin II receptor. The Nuclear Receptors are responsible for transcription of genes which are active in the immune system. Others have now confirmed my work on PPAR activity, and I have gone on to specifically show that benicar is a strong agonist of the VDR nuclear receptor, which is at the heart of innate immunity."

wrotek
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Angiotensin II receptors have no role in our recovery ?

Last edited on Sun Jul 8th, 2007 22:56 by wrotek

Prof Trevor Marshall
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Probably not. Angiotensin II receptors have a role in Nuclear-Factor-kappa-B signalling but it seems that will be disabled by other VDR-mediated pathways.
 

Prof Trevor Marshall
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The URL for the live webcast is http://rpvss.ucsd.edu:8080/ramgen/broadcast/live.rm

The PDF of the conference program is at URL http://metagenomics.calit2.net/files/Metagenomics2007Program_lowres.pdf

The conference starts tomorrow (Wednesday, and goes through to Friday.

Enjoy!

..Trevor..

wrotek
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I understand broadcasting will start between 2:00-2:40 PM, at the moment link does not work for me. Is not it 40 minutes very short period of time for 5 presentations ?
2:40 - 3:00 PM coffee brake is half time of it.

Last edited on Wed Jul 11th, 2007 07:36 by wrotek

DMiller
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Wrotek,

I believe the 5 presentations happen at the same time in different rooms.

wrotek
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Or maybe at the same time in one room.

Last edited on Wed Jul 11th, 2007 10:05 by wrotek

wrotek
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It is one hour to transmission, at 3  PM ? 

Last edited on Wed Jul 11th, 2007 13:07 by wrotek

Ruth Goold
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Hi Wrotek,

What program are you going to use to view the webcast?

Thanks,

Ruth

wrotek
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I will try real player and real alternative. Dr Marshall speaks  tomorrow.

Ruth Goold
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Thanks Wrotek. ;)  I've downloaded it.

Ruth

Prof Trevor Marshall
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Only one of the sessions will be streamed live, the others will be recorded for streaming later. I will try to take my own video, just in case, if I have time. :)

I recommend Dave Relman's talk today.. check it out.. the other highlight, where Peter shows bugs are more important than diet, will be in my workshop, so you may have to wait for the video...
 

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I've had problems accessing the stream. (Was lucky enough to get the explanation of the book in the goodie bag, but the majority of time I have tried linking in I get a failure message.) I'll be looking forward to the web page of recorded events if live is not possible from where I sit.

Thank you for your outstanding leadership and your efforts.--Janet

wrotek
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I just started viewing and it works :) LOL and i see Dr Marshall on audience in yellow shirt. Did anybody record Dr Marshall presentation, i guess i got confused with time zones again. 

Last edited on Thu Jul 12th, 2007 15:28 by wrotek

tickbite
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Metagenomics 2007 Proceedings Now Available in Streaming Video

http://research.calit2.net/metagenomics/videoarchive.php

~Greg

tickbite
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I get a "timed out" message in the video and cuts it off. How do I fix that?

thanks~G

Prof Trevor Marshall
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Haven't had time to look at it yet, Greg, sorry, pretty busy right now :(

jrfoutin
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It sort of streams. Sort of. I've had to reopen and reload to get through some of the videos.--JRF



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