28 April 2009

Swine fever, Star Anise, Dr. Jim Salinger

Swine fever, Star Anise

Rumour has it that Tamiflu isnt much chop, even for swine flu.

The global supply of shikimic acid is met primarily through the fruits of the Chinese star anise tree that contains up to five per cent of the acid. But the tree yields seeds only after six years of ... the raw material used to produce oseltamivir, Tamiflu

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I was pondering a Sci-Fi script where a saint heals by touch.
The saint produces active virus particles which infect the sick person
The virus finds B Memory cells, enters and finds the V-regions of the antibody,
splices in a good sequence.
This cure is rapid, faster than the 10 days requires for Somatic Hypermutation, the normal fine tuning of B Cells
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John 9:11

Having said this, he spit on the ground, made some mud with the saliva, and put it on the man's eyes. "Go," he told him, "wash in the Pool of Siloam" (this word means Sent). So the man went and washed, and came home seeing. John 9:6-7 (NIV)

"It is not because of his sins or his parents' sins. This happened so that the power of God could be seen in his life." Then Jesus knelt down, spit on the ground, and stirred up some mud. He took the mud and put it on the blind man's eyes. He told him, "Now, go wash yourself in the pool of Siloam." The man went and washed the mud from his eyes and when he came back, he could see!
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Whats needed now is a 20 second $1 virus recognition kit
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Somatic Hypermutation
as evolution
needs memory
so DNA is the text, the palimpsest
RNA is too labile.
B Memory cells lurk for a lifetime? however long is that?


Discretion Valour Recognition Memory
handshake
Immunology has it all.
Self Not-self
Horror Autotoxicus

The body erects multiple layers of defence against self attack
As soon as multi-cellular, metazoan, existence was posited, defence became essential.
Defence against that defence was the next requirement.

"Hypermutation studied in vitro using a bacterial mutator strain
Improved Affinity studied by site-directed-mutagenesis in the hypervariable region"

Need about 5 recognition sticky spots to snag a big protein


Antibodies
not intended to be anti the body, indeed, the reverse, evolved to be anti the not-body, the rest of the world, the AntiGens.
The V for Variable region is assembled from selecting from chunks of DNA strung out along a few megabases on Chromosome 14
we have enough chunks to make 5 million Antibodies. In actuality rather fewer are made.

This is why we mate
To give up our body, finely honed by 500 million years of metazoan creeping, leaping
I will give up half my fine designerless design
To receive your set of cassettes of possible reactions to tiny indications of the other in my progenies humours

I share with my carefully chosen, loyal, glowing healthily con-specific, so that our descendants will know well how to discern difference.
This is what Species means. A club to share information against invisible attackers.

Racism is the fear of contagion from the other group.
Mexicans would have done well to be more racist against Spaniards.

The V assembly, hidden in the bone, was revealed by Tomogawa's lab in 1978.


The antibodies are attached to the exterior of the B-Cells
The recognition site, the patch whereby we grasp danger,
around 20 x 40 Angstroms - maybe 15 x 30
Defined by 360 DNA base pairs, 12o Amino Acids
But only recognises 4-6sugars or 6-8 Amino Acids
A small fragment of the world diffuses to tiny pads, blindly sticking in the groove.

The antibodies can float away, alone or in pentamers, where they coat invaders, block toxins.
Oponization , wonderful word, where foreigners are coated, slimed, so that they will be eaten, phagocytosed, invaginated.
fragmented, destroyed. Small sequences are then presented on the exterior, cupped in MHC buds.
MHC varies in a similar manner to the V region, but not as widely, nor with the fine tuning of Hypermutation.
The chunks that MHC presents are small sequences of polymers.

Some sneaky pathogens love to be eaten.
HIV is Oponized by Complement 3b, no immune recognition, so that its picked up by APCs and passed on to T cells.
If youre gonna endocytose, eat a virus, make sure you digest it.
Just why is that 3b floating about anyway? Inflammation? take an Aspirin?

Note that the Bcell antibodies recognise patterns that may not be sequences.
The Antibody to a globular protein may recognise Amino acids that far apart in the polymer sequence
but appear close together on the surface of the globule.

Some antibodies to myoglobin recognise it so tightly that they squeeze the heme right out of it, leaving a white precipitate

Each B cell has a single variety of Antibody.
It may eat whatever it recognises, then present a fragment via MHC on its surface.
Note this fragment will generally be different from the Antigen which the Antibody recognises.

The MHC is presented to a TCell CD4+ helper, which recognises it
(how? surely it sees the other side? more study on T cells required...)
The Helper T then gives permission, encouragement, to the B Cell, which proceeds to multiply many orders of magnitude,
To produce much Antibody, and to become 'Memory' cells which wait for years for the next epidemic.

This double antigen recognition is said to be part of Horror Autotoxicus
the body must not attack itself.
I havnt got my head around why double is good.
Immunology is a huge field ...
pnas

Hypermutation
back to the GC Germinal Centre
There may be GC in Tonsils lymph nodes... the text books jump to the Spleen
probably because most work is done on mice, and a mouse spleen is about as small as you need.

Mutation at 10-3 vs normal 10-10 per base pairs per generation

Anyway this evolution, random mutations, done by altering a C and repairing it with error-prone enzymes.
is then examined. BCells are ordered to die unless they are useful.
Rescued by FDC and Tcell CD40
Cognate helpers (another fine phrase)
FDCs present antigens to the B cell.
If its evil, the B Cell is allowed to live.

This raises the central question... How does the FDC know evil (non-self)?
how knowing is cognate?
Also, how does an FDC cell "Present" something huge, like a globular protein?
Or what about something really huge like a worm?

Seems there are ways for B cells to go it alone, without T Cell/FDC permission.
So metazoans survive, albiet in a cloud of auto-immune diseases.
You either got worms, or Asthma.






Dr. Jim Salinger, Nobel Prize winning Scientist fired from Govt institute
It seems that glaciers are a state secret?
This is a bad look, an international Bush level of monstrous idiotic injustice, if Dr. Jim's crimes amount to chatting about ice.


4:00AM Saturday Apr 25, 2009
By Mathew Dearnaley
Dr. Jim Salinger says he can't understand why he has lost his job. Photo / Brett Phibbs
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Leading Government scientist Jim Salinger, an international pioneer in climate change research, has been sacked for what he says is talking out of turn to news organisations.
Dr Salinger, 62, says he was summarily dismissed from the National Institute of Water and Atmospheric Research (Niwa) at 4pm on Thursday, and given three and a half hours to clear out his Auckland office.
He told the Weekend Herald he received no formal written warnings leading to his dismissal, which followed a 27-year career as a Government scientist, and no criticism of his work.
Dr Salinger claims the information he provided included calling television weatherman Jim Hickey from Greymouth last week to let him know the rivers were in flood.
His work helped an international group of scientists to which he belongs, the Intergovernmental Panel on Climate Change, share the Nobel Peace Prize in 2007 with former United States Vice-President Al Gore.
Dr Salinger, whose postgraduate studies in 1975 produced what later came to be regarded as a watershed paper on climate change at a time when the concept was resisted by most scientists, is also a Companion of the Royal Society and heads the World Commission for Agricultural Meteorology.
is sacking was condemned last night by Green Party co-leader Jeanette Fitzsimons, who feared it would harm New Zealand's reputation in the world science community and would make all Government scientists nervous about their jobs.
"New Zealand is on a slippery slope when trying to provide Kiwis with a greater understanding of our climate is a sackable offence," she said.
Other than confirming that Dr Salinger no longer worked for it, Niwa would make no comment on what it called a confidential employment matter.
Dr Salinger, who has instructed an employment lawyer to fight his dismissal, said he could not understand why he had been sacked so abruptly.
"It's not as though I was doing bad science," he said.
He said that of three instances cited against him of talking to media organisations without proper approval, two involved Television New Zealand, with which Niwa had a contract under his management to provide weather information.
In one of those cases, he said he gained clearance from Niwa's national communication manager for a reporter to join a snow-line survey flight, only to be told afterwards that he should have sought approval from someone e

nzherald
stuff


For those who would silence science, I give you the Galileo finger
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